Anthrax edema toxin disrupts distinct steps in Rab11-dependent junctional transport.

PubMed

Guichard, Annabel; Jain, Prashant; Moayeri, Mahtab; Schwartz, Ruth; Chin, Stephen; Zhu, Lin; Cruz-Moreno, Beatriz; Liu, Janet Z; Aguilar, Bernice; Hollands, Andrew; Leppla, Stephen H; Nizet, Victor; Bier, Ethan

2017-09-01

Various bacterial toxins circumvent host defenses through overproduction of cAMP. In a previous study, we showed that edema factor (EF), an adenylate cyclase from Bacillus anthracis, disrupts endocytic recycling mediated by the small GTPase Rab11. As a result, cargo proteins such as cadherins fail to reach inter-cellular junctions. In the present study, we provide further mechanistic dissection of Rab11 inhibition by EF using a combination of Drosophila and mammalian systems. EF blocks Rab11 trafficking after the GTP-loading step, preventing a constitutively active form of Rab11 from delivering cargo vesicles to the plasma membrane. Both of the primary cAMP effector pathways -PKA and Epac/Rap1- contribute to inhibition of Rab11-mediated trafficking, but act at distinct steps of the delivery process. PKA acts early, preventing Rab11 from associating with its effectors Rip11 and Sec15. In contrast, Epac functions subsequently via the small GTPase Rap1 to block fusion of recycling endosomes with the plasma membrane, and appears to be the primary effector of EF toxicity in this process. Similarly, experiments conducted in mammalian systems reveal that Epac, but not PKA, mediates the activity of EF both in cell culture and in vivo. The small GTPase Arf6, which initiates endocytic retrieval of cell adhesion components, also contributes to junctional homeostasis by counteracting Rab11-dependent delivery of cargo proteins at sites of cell-cell contact. These studies have potentially significant practical implications, since chemical inhibition of either Arf6 or Epac blocks the effect of EF in cell culture and in vivo, opening new potential therapeutic avenues for treating symptoms caused by cAMP-inducing toxins or related barrier-disrupting pathologies.

Neutralization of B. anthracis toxins during ex vivo phagocytosis.

PubMed

Tarasenko, Olga; Scott, Ashley; Jones, April; Soderberg, Lee; Alusta, Pierre

2013-07-01

Glycoconjugates (GCs) are recognized as stimulation and signaling agents, affecting cell adhesion, activation, and growth of living organisms. Among GC targets, macrophages are considered ideal since they play a central role in inflammation and immune responses against foreign agents. In this context, we studied the effects of highly selective GCs in neutralizing toxin factors produced by B. anthracis during phagocytosis using murine macrophages. The effects of GCs were studied under three conditions: A) prior to, B) during, and C) following exposure of macrophages to B. anthracis individual toxin (protective antigen [PA], edema factor [EF], lethal factor [LF] or toxin complexes (PA-EF-LF, PA-EF, and PA-LF). We employed ex vivo phagocytosis and post-phagocytosis analysis including direct microscopic observation of macrophage viability, and macrophage activation. Our results demonstrated that macrophages are more prone to adhere to GC-altered PA-EF-LF, PA-EF, and PA-LF toxin complexes. This adhesion results in a higher phagocytosis rate and toxin complex neutralization during phagocytosis. In addition, GCs enhance macrophage viability, activate macrophages, and stimulate nitric oxide (NO) production. The present study may be helpful in identifying GC ligands with toxin-neutralizing and/or immunomodulating properties. In addition, our study could suggest GCs as new targets for existing vaccines and the prospective development of vaccines and immunomodulators used to combat the effects of B. anthracis.

Bacillus anthracis-derived edema toxin (ET) counter-regulates movement of neutrophils and macromolecules through the endothelial paracellular pathway.

PubMed

Nguyen, Chinh; Feng, Chiguang; Zhan, Min; Cross, Alan S; Goldblum, Simeon E

2012-01-09

A common finding amongst patients with inhalational anthrax is a paucity of polymorphonuclear leukocytes (PMNs) in infected tissues in the face of abundant circulating PMNs. A major virulence determinant of anthrax is edema toxin (ET), which is formed by the combination of two proteins produced by the organism, edema factor (EF), which is an adenyl cyclase, and protective antigen (PA). Since cAMP, a product of adenyl cyclase, is known to enhance endothelial barrier integrity, we asked whether ET might decrease extravasation of PMNs into tissues through closure of the paracellular pathway through which PMNs traverse. Pretreatment of human microvascular endothelial cell(EC)s of the lung (HMVEC-L) with ET decreased interleukin (IL)-8-driven transendothelial migration (TEM) of PMNs with a maximal reduction of nearly 60%. This effect required the presence of both EF and PA. Conversely, ET did not diminish PMN chemotaxis in an EC-free system. Pretreatment of subconfluent HMVEC-Ls decreased transendothelial 14 C-albumin flux by ~ 50% compared to medium controls. Coadministration of ET with either tumor necrosis factor-α or bacterial lipopolysaccharide, each at 100 ng/mL, attenuated the increase of transendothelial 14 C-albumin flux caused by either agent alone. The inhibitory effect of ET on TEM paralleled increases in protein kinase A (PKA) activity, but could not be blocked by inhibition of PKA with either H-89 or KT-5720. Finally, we were unable to replicate the ET effect with either forskolin or 3-isobutyl-1-methylxanthine, two agents known to increase cAMP. We conclude that ET decreases IL-8-driven TEM of PMNs across HMVEC-L monolayers independent of cAMP/PKA activity.

Heart failure with preserved ejection fraction and systolic dysfunction in the community.

PubMed

Moutinho, Marco Aurélio Esposito; Colucci, Flávio Augusto; Alcoforado, Veronica; Tavares, Leandro Reis; Rachid, Mauricio Bastos Freitas; Rosa, Maria Luisa Garcia; Ribeiro, Mário Luiz; Abdalah, Rosemery; Garcia, Juliana Lago; Mesquita, Evandro Tinoco

2008-02-01

In developed countries, heart failure with preserved ejection fraction (HFpEF) is more prevalent than heart failure with reduced ejection fraction (HFrEF) in the community. However, it has not been completely established if this fact is also observed within our community. To determine the most prevalent form of heart failure (HFpEF or HFrEF) and whether the prevalence of HFpEF is higher in the community. This is a cross-sectional study conducted with patients clinically diagnosed with HF who were seen in community-based health care centers from January to December 2005. Echodopplercardiograms were performed for all patients. The form of HF was stratified according to the presence of abnormalities and the shortening fraction observed on the echodopplercardiogram. The study evaluated 170 patients (61.0 +/- 13.3 years of age), most of them women and elderly. HFpEF was the more prevalent form of HF (64.2%, p<0.001), affecting mostly elderly women (62%, p = 0.07), whereas the opposite condition, HFrEF, was observed mostly in elderly men (63.6%, p = 0.07). Patients with no HF represented one-third of the cases (27.6%). HFrEF patients had more lower-limb edema, coronary disease, diabetes, chronic renal failure, higher Boston scores and hospital readmissions. Use of alcoholic beverages and smoking were also more common among HFrEF patients. HFpEF is the most prevalent form of HF in the community especially among elderly women, whereas HFrEF affects mostly elderly men and is associated with greater clinical severity, main risk factors and no changes in lifestyle. Despite the signs and symptoms of HF, this condition was not confirmed for one-third of the cases.

Transcriptional Profiling of Human Peripheral Blood Mononuclear Cells Exposed to Bacillus anthracis in vitro

DTIC Science & Technology

2013-03-11

are derived from the combination of three polypeptides, namely the Protective antigen (PA, 83 kDa), the edema factor (EF, 89 kDa), and the lethal...p38MAPK-dependent pathways. The T-cell receptors and CD3-mediated antigenic recognition processes are possibly restrained, and the expression of CD79...NY), using a VersArray microarrayer ( Bio -Rad, CA). Arrays were post- processed using UV-cross linking at 1200 mJ/cm2, followed by baking for 4 hrs

[Screening of full human anthrax lethal factor neutralizing antibody in transgenic mice].

PubMed

Wang, Xiaolin; Chi, Xiangyang; Liu, Ju; Liu, Weicen; Liu, Shuling; Qiu, Shunfang; Wen, Zhonghua; Fan, Pengfei; Liu, Kun; Song, Xiaohong; Fu, Ling; Zhang, Jun; Yu, Changming

2016-11-25

Anthrax is a highly lethal infectious disease caused by the spore-forming bacterium Bacillus anthracis. The major virulence factor of B. anthracis consists of protective antigen (PA), lethal factor (LF) and edema factor (EF). PA binds with LF to form lethal toxin (LT), and PA binds with EF to form edema toxin (ET). Antibiotics is hard to work in advanced anthrax infections, because injuries and deaths of the infected are mainly caused by lethal toxin (LT). Thus, the therapeutic neutralizing antibody is the most effective treatment of anthrax. Currently most of the anthrax toxin antibodies are monoclonal antibodies (MAbs) for PA and US FDA has approved ABTHRAX humanized PA monoclonal antibody for the treatment of inhalational anthrax. Once B. anthracis was artificially reconstructed or PA had mutations within recognized neutralization epitopes, anti-PA MAbs would no longer be effective. Therefore, anti-LF MAbs is an important supplement for anthrax treatment. Most of the anti-LF antibodies are murine or chimeric antibodies. By contrast, fully human MAbs can avoid the high immunogenicity of murine antibodies. First, we used LF to immunize the transgenic mice and used fluorescent cell sorting to get antigen-specific memory B cells from transgenic mice spleen lymphocytes. By single cell PCR method, we quickly found two strains of anti-LF MAbs with binding activity, 1D7 and 2B9. Transiently transfected Expi 293F cells to obtain MAbs protein after purification. Both 1D7 and 2B9 efficiently neutralized LT in vitro, and had good synergistic effect when mixed with anti-PA MAbs. In summary, combining the advantages of transgenic mice, fluorescent cell sorting and single-cell PCR methods, this study shows new ideas and methods for the rapid screening of fully human monoclonal antibodies.

Mechanism of reactant and product dissociation from the anthrax edema factor: a locally enhanced sampling and steered molecular dynamics study.

PubMed

Martínez, Leandro; Malliavin, Thérèse E; Blondel, Arnaud

2011-05-01

The anthrax edema factor is a toxin overproducing damaging levels of cyclic adenosine monophosphate (cAMP) and pyrophosphate (PPi) from ATP. Here, mechanisms of dissociation of ATP and products (cAMP, PPi) from the active site are studied using locally enhanced sampling (LES) and steered molecular dynamics simulations. Various substrate conformations and ionic binding modes found in crystallographic structures are considered. LES simulations show that PPi and cAMP dissociate through different solvent accessible channels, while ATP dissociation requires significant active site exposure to solvent. The ionic content of the active site directly affects the dissociation of ATP and products. Only one ion dissociates along with ATP in the two-Mg(2+) binding site, suggesting that the other ion binds EF prior to ATP association. Dissociation of reaction products cAMP and PPi is impaired by direct electrostatic interactions between products and Mg(2+) ions. This provides an explanation for the inhibitory effect of high Mg(2+) concentrations on EF enzymatic activity. Breaking of electrostatic interactions is dependent on a competitive binding of water molecules to the ions, and thus on the solvent accessibility of the active site. Consequently, product dissociation seems to be a two-step process. First, ligands are progressively solvated while preserving the most important electrostatic interactions, in a process that is dependent on the flexibility of the active site. Second, breakage of the electrostatic bonds follows, and ligands diffuse into solvent. In agreement with this mechanism, product protonation facilitates dissociation.

Biomarkers in Acutely Decompensated Heart Failure with Preserved or Reduced Ejection Fraction

PubMed Central

Bishu, Kalkidan; Deswal, Anita; Chen, Horng H.; LeWinter, Martin M.; Lewis, Gregory D.; Semigran, Marc J.; Borlaug, Barry A.; McNulty, Steven; Hernandez, Adrian F.; Braunwald, Eugene; Redfield, Margaret M.

2013-01-01

Background Acute decompensated heart failure (ADHF) occurs with preserved (HFpEF, EF≥50%) or reduced (HFrEF, EF<50%) ejection fraction. Natriuretic peptide (NP) levels are lower in HFpEF than HFrEF. We hypothesized that lower NP levels in HFpEF may be associated with other differences in biomarkers; specifically, renin-angiotensin-aldosterone system (RAAS) activation, oxidative stress and a biomarker that reflects collagen synthesis. Methods In this pre-specified ancillary analysis of ADHF patients enrolled in the Diuretic Optimization Strategies Evaluation (DOSE) study, clinical features and NT-proBNP, cystatin C, plasma renin activity (PRA), aldosterone, oxidative stress (uric acid) and procollagen type III N-terminal peptide (PIIINP) were compared in HFpEF and HFrEF at enrollment and 60 day follow-up. Results Compared to HFrEF (n=219), HFpEF (n=81) patients were older, heavier, more commonly female, less treated with RAAS antagonists, but with similar NYHA class, jugular venous pressure and edema severity. NT-proBNP was lower and systolic blood pressure (BP) and cystatin C were higher in HFpEF. Despite higher systolic BP and less RAAS antagonist use in HFpEF, PRA and aldosterone levels were similar in HFpEF and HFrEF as were uric acid and PIIINP levels. Changes in biomarker levels from enrollment to 60 days were similar between HFrEF (n=149) and HFpEF (n=50). Conclusion Lower NP levels in decompensated HFpEF occur in association with similar ADHF severity, more impaired vascular and renal function but similar elevation of biomarkers that reflect RAAS activation, oxidative stress and collagen synthesis as in HFrEF. PMID:23137508

The Protective Antigen Component of Anthrax Toxin Forms Functional Octameric Complexes

PubMed Central

Kintzer, Alexander F.; Thoren, Katie L.; Sterling, Harry J.; Dong, Ken C.; Feld, Geoffrey K.; Tang, Iok I.; Zhang, Teri T.; Williams, Evan R.; Berger, James M.; Krantz, Bryan A.

2009-01-01

The assembly of bacterial toxins and virulence factors is critical to their function, but the regulation of assembly during infection has not been studied. We begin to address this question using anthrax toxin as a model. The protective antigen (PA) component of the toxin assembles into ring-shaped homooligomers that bind the two other enzyme components of the toxin, lethal factor (LF) and edema factor (EF), to form toxic complexes. To disrupt the host, these toxic complexes are endocytosed, such that the PA oligomer forms a membrane-spanning channel that LF and EF translocate through to enter the cytosol. We show using single-channel electrophysiology that PA channels contain two populations of conductance states, which correspond with two different PA pre-channel oligomers observed by electron microscopy—the well-described heptamer and a novel octamer. Mass spectrometry demonstrates that the PA octamer binds four LFs, and assembly routes leading to the octamer are populated with even-numbered, dimeric and tetrameric, PA intermediates. Both heptameric and octameric PA complexes can translocate LF and EF with similar rates and efficiencies. Here we also report a 3.2-Å crystal structure of the PA octamer. The octamer comprises ∼20−30% of the oligomers on cells, but outside of the cell, the octamer is more stable than the heptamer under physiological pH. Thus the PA octamer is a physiological, stable, and active assembly state capable of forming lethal toxins that may withstand the hostile conditions encountered in the bloodstream. This assembly mechanism may provide a novel means to control cytotoxicity. PMID:19627991

Nitric oxide production contributes to Bacillus anthracis edema toxin-associated arterial hypotension and lethality: ex vivo and in vivo studies in the rat

PubMed Central

Li, Yan; Cui, Xizhong; Xu, Wanying; Ohanjanian, Lernik; Sampath-Kumar, Hanish; Suffredini, Dante; Moayeri, Mahtab; Leppla, Stephen; Fitz, Yvonne

2016-01-01

We showed previously that Bacillus anthracis edema toxin (ET), comprised of protective antigen (PA) and edema factor (EF), inhibits phenylephrine (PE)-induced contraction in rat aortic rings and these effects are diminished in endothelial-denuded rings. Therefore, employing rat aortic ring and in vivo models, we tested the hypothesis that nitric oxide (NO) contributes to ET's arterial effects. Compared with rings challenged with PA alone, ET (PA + EF) reduced PE-stimulated maximal contractile force (MCF) and increased the PE concentration producing 50% MCF (EC50) (P < 0.0001). Compared with placebo, l-nitro-arginine methyl-ester (l-NAME), an NO synthase (NOS) inhibitor, reduced ET's effects on MCF and EC50 in patterns that approached or were significant (P = 0.06 and 0.03, respectively). In animals challenged with 24-h ET infusions, l-NAME (0.5 or 1.0 mg·kg−1·h−1) coadministration increased survival to 17 of 28 animals (60.7%) compared with 4 of 27 (14.8%) given placebo (P = 0.01). Animals receiving l-NAME but no ET all survived. Compared with PBS challenge, ET increased NO levels at 24 h and l-NAME decreased these increases (P < 0.0001). ET infusion decreased mean arterial blood pressure (MAP) in placebo and l-NAME-treated animals (P < 0.0001) but l-NAME reduced decreases in MAP with ET from 9 to 24 h (P = 0.03 for the time interaction). S-methyl-l-thiocitrulline, a selective neuronal NOS inhibitor, had effects in rings and, at a high dose in vivo models, comparable to l-NAME, whereas N′-[3-(aminomethyl)benzyl]-acetimidamide, a selective inducible NOS inhibitor, did not. NO production contributes to ET's arterial relaxant, hypotensive, and lethal effects in the rat. PMID:27448553

Protective activity and immunogenicity of two recombinant anthrax vaccines for veterinary use.

PubMed

Fasanella, A; Tonello, F; Garofolo, G; Muraro, L; Carattoli, A; Adone, R; Montecucco, C

2008-10-23

In this study, the efficacy of two experimental vaccines against Bacillus anthracis toxinaemia was evaluated in the rabbit model. A recombinant Protective Antigen (rPA) mutant and a trivalent vaccine (TV) composed by the rPA, a inactive mutant of Lethal Factor (mLF-Y728A; E735A) and a inactive mutant of Edema Factor (mEF-K346R), both emulsified with mineral oils, were evaluated for their immunogenicity and protective activity in New Zealand white rabbits. Rabbits vaccinated subcutaneously with rPA and TV rapidly produced high level of anti-PA, anti-LF and anti-EF antibodies, which were still present 6 months later. In the efficacy test, these vaccines protected 100% of rabbits challenged with B. anthracis virulent strain 0843 one week after the vaccination. Moreover, all animals vaccinated twice with rPA and TV, resisted B. anthracis infection 6 months later. Our data indicate that rPA and TV could be good vaccine candidates for inducing protection against B. anthracis infection in target animal host. They could successfully be used in an emergency with simultaneous long-acting antibiotics to halt incubating infections or during an anthrax epidemic.

Novel Yersinia Pestis Toxin that Resembles Bacillus Anthracis Edema Factor: Study of Activity and Structural Modeling

DOE Office of Scientific and Technical Information (OSTI.GOV)

Motin, V; Garcia, E; Barsky, D

2003-02-05

The goal of this project was to begin both experimental and computational studies of the novel plague toxin to establish its biological properties and create its 3D-model. The project was divided into two parts. (1) Experimental--This part was devoted to determine distribution of the genes encoding novel plague toxin among different isolates of Y.pestis. If the EF-like activity is important for Y.pestis pathogenicity, it is anticipated that all highly virulent strains will contain the toxin genes. Also, they proposed to initiate research to investigate the functionality of the novel Y.pestis toxin that they hypothesize is likely to significantly contribute tomore » the virulence of this dangerous microbe. this research design consisted of amplification, cloning and expression in E.coli the toxin genes followed by affinity purification of the recombinant protein that can be further used for testing of enzymatic activity. (2) Computational--The structural modeling of the putative EF of Y.pestis was based on multiple sequence alignments, secondary structure predictions, and comparison with 3D models of the EF of B. anthracis. The x-ray structure of the last has been recently published [Nature. 2002. 415(Jan):396-402]. The final model was selected after detailed analysis to determine if the structure is consistent with the biological function.« less

High-sensitivity MALDI-TOF MS quantification of anthrax lethal toxin for diagnostics and evaluation of medical countermeasures.

PubMed

Boyer, Anne E; Gallegos-Candela, Maribel; Quinn, Conrad P; Woolfitt, Adrian R; Brumlow, Judith O; Isbell, Katherine; Hoffmaster, Alex R; Lins, Renato C; Barr, John R

2015-04-01

Inhalation anthrax has a rapid progression and high fatality rate. Pathology and death from inhalation of Bacillus anthracis spores are attributed to the actions of secreted protein toxins. Protective antigen (PA) binds and imports the catalytic component lethal factor (LF), a zinc endoprotease, and edema factor (EF), an adenylyl cyclase, into susceptible cells. PA-LF is termed lethal toxin (LTx) and PA-EF, edema toxin. As the universal transporter for both toxins, PA is an important target for vaccination and immunotherapeutic intervention. However, its quantification has been limited to methods of relatively low analytic sensitivity. Quantification of LTx may be more clinically relevant than LF or PA alone because LTx is the toxic form that acts on cells. A method was developed for LTx-specific quantification in plasma using anti-PA IgG magnetic immunoprecipitation of PA and quantification of LF activity that co-purified with PA. The method was fast (<4 h total time to detection), sensitive at 0.033 ng/mL LTx in plasma for the fast analysis (0.0075 ng/mL LTx in plasma for an 18 h reaction), precise (6.3-9.9% coefficient of variation), and accurate (0.1-12.7%error; n ≥ 25). Diagnostic sensitivity was 100% (n = 27 animal/clinical cases). Diagnostic specificity was 100% (n = 141). LTx was detected post-antibiotic treatment in 6/6 treated rhesus macaques and 3/3 clinical cases of inhalation anthrax and as long as 8 days post-treatment. Over the course of infection in two rhesus macaques, LTx was first detected at 0.101 and 0.237 ng/mL at 36 h post-exposure and increased to 1147 and 12,107 ng/mL in late-stage anthrax. This demonstrated the importance of LTx as a diagnostic and therapeutic target. This method provides a sensitive, accurate tool for anthrax toxin detection and evaluation of PA-directed therapeutics.

Anthrax biosensor, protective antigen ion channel asymmetric blockade.

PubMed

Halverson, Kelly M; Panchal, Rekha G; Nguyen, Tam L; Gussio, Rick; Little, Stephen F; Misakian, Martin; Bavari, Sina; Kasianowicz, John J

2005-10-07

The significant threat posed by biological agents (e.g. anthrax, tetanus, botulinum, and diphtheria toxins) (Inglesby, T. V., O'Toole, T., Henderson, D. A., Bartlett, J. G., Ascher, M. S., Eitzen, E., Friedlander, A. M., Gerberding, J., Hauer, J., Hughes, J., McDade, J., Osterholm, M. T., Parker, G., Perl, T. M., Russell, P. K., and Tonat, K. (2002) J. Am. Med. Assoc. 287, 2236-2252) requires innovative technologies and approaches to understand the mechanisms of toxin action and to develop better therapies. Anthrax toxins are formed from three proteins secreted by fully virulent Bacillus anthracis, protective antigen (PA, 83 kDa), lethal factor (LF, 90 kDa), and edema factor (EF, 89 kDa). Here we present electrophysiological measurements demonstrating that full-length LF and EF convert the current-voltage relationship of the heptameric PA63 ion channel from slightly nonlinear to highly rectifying and diode-like at pH 6.6. This effect provides a novel method for characterizing functional toxin interactions. The method confirms that a previously well characterized PA63 monoclonal antibody, which neutralizes anthrax lethal toxin in animals in vivo and in vitro, prevents the binding of LF to the PA63 pore. The technique can also detect the presence of anthrax lethal toxin complex from plasma of infected animals. The latter two results suggest the potential application of PA63 nanopore-based biosensors in anthrax therapeutics and diagnostics.

Anthrax Toxin

DTIC Science & Technology

1984-10-26

focused initially on EF because it seemed possible that this component, like cholera toxin, might cause edema in skin through elevation of cellular cAMP...behavior differed from that seen in cells exposed to cholera toxin, where cellular cAMP levels remain elevated upon toxin removal. Studies in CHO cell...LF, the rat bioassay is not likely to be an appropriate system for studying the cellular and molecular mechanisms of action of LF. Therefore, a survey

Risk Factors for Incident Hospitalized Heart Failure With Preserved Versus Reduced Ejection Fraction in a Multiracial Cohort of Postmenopausal Women.

PubMed

Eaton, Charles B; Pettinger, Mary; Rossouw, Jacques; Martin, Lisa Warsinger; Foraker, Randi; Quddus, Abdullah; Liu, Simin; Wampler, Nina S; Hank Wu, Wen-Chih; Manson, JoAnn E; Margolis, Karen; Johnson, Karen C; Allison, Matthew; Corbie-Smith, Giselle; Rosamond, Wayne; Breathett, Khadijah; Klein, Liviu

2016-10-01

Heart failure is an important and growing public health problem in women. Risk factors for incident hospitalized heart failure with preserved ejection fraction (HFpEF) compared with heart failure with reduced ejection fraction (HFrEF) in women and differences by race/ethnicity are not well characterized. We prospectively evaluated the risk factors for incident hospitalized HFpEF and HFrEF in a multiracial cohort of 42 170 postmenopausal women followed up for a mean of 13.2 years. Cox regression models with time-dependent covariate adjustment were used to define risk factors for HFpEF and HFrEF. Differences by race/ethnicity about incidence rates, baseline risk factors, and their population-attributable risk percentage were analyzed. Risk factors for both HFpEF and HFrEF were as follows: older age, white race, diabetes mellitus, cigarette smoking, and hypertension. Obesity, history of coronary heart disease (other than myocardial infarction), anemia, atrial fibrillation, and more than one comorbidity were associated with HFpEF but not with HFrEF. History of myocardial infarction was associated with HFrEF but not with HFpEF. Obesity was found to be a more potent risk factor for African American women compared with white women for HFpEF (P for interaction=0.007). For HFpEF, the population-attributable risk percentage was greatest for hypertension (40.9%) followed by obesity (25.8%), with the highest population-attributable risk percentage found in African Americans for these risk factors. In this multiracial cohort of postmenopausal women, obesity stands out as a significant risk factor for HFpEF, with the strongest association in African American women. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00000611. © 2016 American Heart Association, Inc.

Purification and properties of the heterogeneous subunits of elongation factor EF-1 from Guerin epithelioma cells.

PubMed

Marcinkiewicz, C; Gajko, A; Gałasiński, W

1991-01-01

Elongation factor EF-1 from Guerin epithelioma was separated into two subunit forms EF-1A and EF-1B by chromatography in the presence of 25% glycerol, successively on CM-Sephadex and DEAE-Sephadex. It was shown that EF-1A is a thermolabile, single polypeptide which catalyses the binding of aminoacyl-tRNA to ribosomes, similarly as eukaryotic EF-1 alpha or prokaryotic EF-Tu. EF-1B was characterized as a complex composed of at least two polypeptides. One of them is EF-1A, the other EF-1C, which stimulates EF-1A activity and protects this elongation factor from thermal inactivation.

Interaction of apicoplast-encoded elongation factor (EF) EF-Tu with nuclear-encoded EF-Ts mediates translation in the Plasmodiumfalciparum plastid.

PubMed

Biswas, Subir; Lim, Erin E; Gupta, Ankit; Saqib, Uzma; Mir, Snober S; Siddiqi, Mohammad Imran; Ralph, Stuart A; Habib, Saman

2011-03-01

Protein translation in the plastid (apicoplast) of Plasmodium spp. is of immense interest as a target for potential anti-malarial drugs. However, the molecular data on apicoplast translation needed for optimisation and development of novel inhibitors is lacking. We report characterisation of two key translation elongation factors in Plasmodium falciparum, apicoplast-encoded elongation factor PfEF-Tu and nuclear-encoded PfEF-Ts. Recombinant PfEF-Tu hydrolysed GTP and interacted with its presumed nuclear-encoded partner PfEF-Ts. The EF-Tu inhibitor kirromycin affected PfEF-Tu activity in vitro, indicating that apicoplast EF-Tu is indeed the target of this drug. The predicted PfEF-Ts leader sequence targeted GFP to the apicoplast, confirming that PfEF-Ts functions in this organelle. Recombinant PfEF-Ts mediated nucleotide exchange on PfEF-Tu and homology modeling of the PfEF-Tu:PfEF-Ts complex revealed PfEF-Ts-induced structural alterations that would expedite GDP release from PfEF-Tu. Our results establish functional interaction between two apicoplast translation factors encoded by genes residing in different cellular compartments and highlight the significance of their sequence/structural differences from bacterial elongation factors in relation to inhibitor activity. These data provide an experimental system to study the effects of novel inhibitors targeting PfEF-Tu and PfEF-Tu.PfEF-Ts interaction. Our finding that apicoplast EF-Tu possesses chaperone-related disulphide reductase activity also provides a rationale for retention of the tufA gene on the plastid genome. Copyright © 2010 Australian Society for Parasitology Inc. All rights reserved.

Elongation factor Ts directly facilitates the formation and disassembly of the Escherichia coli elongation factor Tu·GTP·aminoacyl-tRNA ternary complex.

PubMed

Burnett, Benjamin J; Altman, Roger B; Ferrao, Ryan; Alejo, Jose L; Kaur, Navdep; Kanji, Joshua; Blanchard, Scott C

2013-05-10

Aminoacyl-tRNA (aa-tRNA) enters the ribosome in a ternary complex with the G-protein elongation factor Tu (EF-Tu) and GTP. EF-Tu·GTP·aa-tRNA ternary complex formation and decay rates are accelerated in the presence of the nucleotide exchange factor elongation factor Ts (EF-Ts). EF-Ts directly facilitates the formation and disassociation of ternary complex. This system demonstrates a novel function of EF-Ts. Aminoacyl-tRNA enters the translating ribosome in a ternary complex with elongation factor Tu (EF-Tu) and GTP. Here, we describe bulk steady state and pre-steady state fluorescence methods that enabled us to quantitatively explore the kinetic features of Escherichia coli ternary complex formation and decay. The data obtained suggest that both processes are controlled by a nucleotide-dependent, rate-determining conformational change in EF-Tu. Unexpectedly, we found that this conformational change is accelerated by elongation factor Ts (EF-Ts), the guanosine nucleotide exchange factor for EF-Tu. Notably, EF-Ts attenuates the affinity of EF-Tu for GTP and destabilizes ternary complex in the presence of non-hydrolyzable GTP analogs. These results suggest that EF-Ts serves an unanticipated role in the cell of actively regulating the abundance and stability of ternary complex in a manner that contributes to rapid and faithful protein synthesis.

Structural outline of the detailed mechanism for elongation factor Ts-mediated guanine nucleotide exchange on elongation factor Tu.

PubMed

Thirup, Søren S; Van, Lan Bich; Nielsen, Tine K; Knudsen, Charlotte R

2015-07-01

Translation elongation factor EF-Tu belongs to the superfamily of guanine-nucleotide binding proteins, which play key cellular roles as regulatory switches. All G-proteins require activation via exchange of GDP for GTP to carry out their respective tasks. Often, guanine-nucleotide exchange factors are essential to this process. During translation, EF-Tu:GTP transports aminoacylated tRNA to the ribosome. GTP is hydrolyzed during this process, and subsequent reactivation of EF-Tu is catalyzed by EF-Ts. The reaction path of guanine-nucleotide exchange is structurally poorly defined for EF-Tu and EF-Ts. We have determined the crystal structures of the following reaction intermediates: two structures of EF-Tu:GDP:EF-Ts (2.2 and 1.8Å resolution), EF-Tu:PO4:EF-Ts (1.9Å resolution), EF-Tu:GDPNP:EF-Ts (2.2Å resolution) and EF-Tu:GDPNP:pulvomycin:Mg(2+):EF-Ts (3.5Å resolution). These structures provide snapshots throughout the entire exchange reaction and suggest a mechanism for the release of EF-Tu in its GTP conformation. An inferred sequence of events during the exchange reaction is presented. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Do executive functions explain the covariance between internalizing and externalizing behaviors?

PubMed

Hatoum, Alexander S; Rhee, Soo Hyun; Corley, Robin P; Hewitt, John K; Friedman, Naomi P

2017-11-16

This study examined whether executive functions (EFs) might be common features of internalizing and externalizing behavior problems across development. We examined relations between three EF latent variables (a common EF factor and factors specific to updating working memory and shifting sets), constructed from nine laboratory tasks administered at age 17, to latent growth intercept (capturing stability) and slope (capturing change) factors of teacher- and parent-reported internalizing and externalizing behaviors in 885 individual twins aged 7 to 16 years. We then estimated the proportion of intercept-intercept and slope-slope correlations predicted by EF as well as the association between EFs and a common psychopathology factor (P factor) estimated from all 9 years of internalizing and externalizing measures. Common EF was negatively associated with the intercepts of teacher-rated internalizing and externalizing behavior in males, and explained 32% of their covariance; in the P factor model, common EF was associated with the P factor in males. Shifting-specific was positively associated with the externalizing slope across sex. EFs did not explain covariation between parent-rated behaviors. These results suggest that EFs are associated with stable problem behavior variation, explain small proportions of covariance, and are a risk factor that that may depend on gender.

Heat tolerance and expression of protein synthesis elongation factors, EF-Tu and EF-1a, in spring wheat

USDA-ARS?s Scientific Manuscript database

Protein elongation factors, EF-Tu and EF-1a, have been implicated in cell response to heat stress. In spring wheat, EF-Tu displays chaperone activity and reduces thermal aggregation of Rubisco activase. Similarly, in mammalian cells, EF-1a displays chaperone-like activity and regulates the expressio...

Characterisation of Translation Elongation Factor eEF1B Subunit Expression in Mammalian Cells and Tissues and Co-Localisation with eEF1A2

PubMed Central

Janikiewicz, Justyna; Doig, Jennifer; Abbott, Catherine M.

2014-01-01

Translation elongation is the stage of protein synthesis in which the translation factor eEF1A plays a pivotal role that is dependent on GTP exchange. In vertebrates, eEF1A can exist as two separately encoded tissue-specific isoforms, eEF1A1, which is almost ubiquitously expressed, and eEF1A2, which is confined to neurons and muscle. The GTP exchange factor for eEF1A1 is a complex called eEF1B made up of subunits eEF1Bα, eEF1Bδ and eEF1Bγ. Previous studies have cast doubt on the ability of eEF1B to interact with eEF1A2, suggesting that this isoform might use a different GTP exchange factor. We show that eEF1B subunits are all widely expressed to varying degrees in different cell lines and tissues, and at different stages of development. We show that ablation of any of the subunits in human cell lines has a small but significant impact on cell viability and cycling. Finally, we show that both eEF1A1 and eEF1A2 colocalise with all eEF1B subunits, in such close proximity that they are highly likely to be in a complex. PMID:25436608

Quantitative Determination of Lethal Toxin Proteins in Culture Supernatant of Human Live Anthrax Vaccine Bacillus anthracis A16R.

PubMed

Zai, Xiaodong; Zhang, Jun; Liu, Ju; Liu, Jie; Li, Liangliang; Yin, Ying; Fu, Ling; Xu, Junjie; Chen, Wei

2016-02-25

Bacillus anthracis (B. anthracis) is the etiological agent of anthrax affecting both humans and animals. Anthrax toxin (AT) plays a major role in pathogenesis. It includes lethal toxin (LT) and edema toxin (ET), which are formed by the combination of protective antigen (PA) and lethal factor (LF) or edema factor (EF), respectively. The currently used human anthrax vaccine in China utilizes live-attenuated B. anthracis spores (A16R; pXO1+, pXO2-) that produce anthrax toxin but cannot produce the capsule. Anthrax toxins, especially LT, have key effects on both the immunogenicity and toxicity of human anthrax vaccines. Thus, determining quantities and biological activities of LT proteins expressed by the A16R strain is meaningful. Here, we explored LT expression patterns of the A16R strain in culture conditions using another vaccine strain Sterne as a control. We developed a sandwich ELISA and cytotoxicity-based method for quantitative detection of PA and LF. Expression and degradation of LT proteins were observed in culture supernatants over time. Additionally, LT proteins expressed by the A16R and Sterne strains were found to be monomeric and showed cytotoxic activity, which may be the main reason for side effects of live anthrax vaccines. Our work facilitates the characterization of anthrax vaccines components and establishment of a quality control standard for vaccine production which may ultimately help to ensure the efficacy and safety of the human anthrax vaccine A16R.

Pathogenesis of Brain Edema and Investigation into Anti-Edema Drugs

PubMed Central

Michinaga, Shotaro; Koyama, Yutaka

2015-01-01

Brain edema is a potentially fatal pathological state that occurs after brain injuries such as stroke and head trauma. In the edematous brain, excess accumulation of extracellular fluid results in elevation of intracranial pressure, leading to impaired nerve function. Despite the seriousness of brain edema, only symptomatic treatments to remove edema fluid are currently available. Thus, the development of novel anti-edema drugs is required. The pathogenesis of brain edema is classified as vasogenic or cytotoxic edema. Vasogenic edema is defined as extracellular accumulation of fluid resulting from disruption of the blood-brain barrier (BBB) and extravasations of serum proteins, while cytotoxic edema is characterized by cell swelling caused by intracellular accumulation of fluid. Various experimental animal models are often used to investigate mechanisms underlying brain edema. Many soluble factors and functional molecules have been confirmed to induce BBB disruption or cell swelling and drugs targeted to these factors are expected to have anti-edema effects. In this review, we discuss the mechanisms and involvement of factors that induce brain edema formation, and the possibility of anti-edema drugs targeting them. PMID:25941935

The real factor for polypeptide elongation in Dictyostelium cells is EF-2B, not EF-2A

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yoshino, Tomoko; Maeda, Yasuo; Amagai, Aiko

2007-08-03

Polypeptide elongation factor 2 (EF-2) plays an essential role in protein synthesis and is believed to be indispensable for cell proliferation. Recently, it has been demonstrated that there are two kinds of EF-2 (EF-2A and EF-2B with 76.6% of sequence identity at the amino acid level) in Dictyostelium discoideum. Although the knockout of EF-2A slightly impaired cytokinesis, EF-2A null cells exhibited almost normal protein synthesis and cell growth, suggesting that there is another molecule capable of compensating for EF-2 function. Since EF-2B is the most likely candidate, we examined its function using ef-2b knockdown cells prepared by the RNAi method.more » Our results strongly suggest that EF-2B is required for protein synthesis and cell proliferation, functioning as the real EF-2. Interestingly, the expressions of ef-2a and ef-2b mRNAs during development are reversely regulated, and the ef-2b expression is greatly augmented in ef-2a null cells.« less

Elongation Factor Ts Directly Facilitates the Formation and Disassembly of the Escherichia coli Elongation Factor Tu·GTP·Aminoacyl-tRNA Ternary Complex*

PubMed Central

Burnett, Benjamin J.; Altman, Roger B.; Ferrao, Ryan; Alejo, Jose L.; Kaur, Navdep; Kanji, Joshua; Blanchard, Scott C.

2013-01-01

Aminoacyl-tRNA enters the translating ribosome in a ternary complex with elongation factor Tu (EF-Tu) and GTP. Here, we describe bulk steady state and pre-steady state fluorescence methods that enabled us to quantitatively explore the kinetic features of Escherichia coli ternary complex formation and decay. The data obtained suggest that both processes are controlled by a nucleotide-dependent, rate-determining conformational change in EF-Tu. Unexpectedly, we found that this conformational change is accelerated by elongation factor Ts (EF-Ts), the guanosine nucleotide exchange factor for EF-Tu. Notably, EF-Ts attenuates the affinity of EF-Tu for GTP and destabilizes ternary complex in the presence of non-hydrolyzable GTP analogs. These results suggest that EF-Ts serves an unanticipated role in the cell of actively regulating the abundance and stability of ternary complex in a manner that contributes to rapid and faithful protein synthesis. PMID:23539628

Role of the α clamp in the protein translocation mechanism of anthrax toxin

PubMed Central

Brown, Michael J.; Thoren, Katie L.; Krantz, Bryan A.

2015-01-01

Membrane-embedded molecular machines are utilized to move water-soluble proteins across these barriers. Anthrax toxin forms one such machine through the self-assembly of its three component proteins—protective antigen (PA), lethal factor (LF), and edema factor (EF). Upon endocytosis into host cells, acidification of the endosome induces PA to form a membrane-inserted channel, which unfolds LF and EF and translocates them into the host cytosol. Translocation is driven by the proton motive force, comprised of the chemical potential, the proton-gradient (ΔpH), and the membrane potential (ΔΨ). A crystal structure of the lethal toxin core complex revealed an “α clamp” structure that binds to substrate helices nonspecifically. Here we test the hypothesis that through the recognition of unfolding helical structure the α clamp can accelerate the rate of translocation. We produced a synthetic PA mutant in which an α helix was crosslinked into the α clamp to block its function. This synthetic construct impairs translocation by raising a yet uncharacterized translocation barrier shown to be much less force dependent than the known unfolding barrier. We also report that the α clamp more stably binds substrates that can form helices than those, such as polyproline, that cannot. Hence the α clamp recognizes substrates by a general shape-complementarity mechanism. Substrates that are incapable of forming compact secondary structure (due to the introduction of a polyproline track) are severely deficient for translocation. Therefore, the α clamp and its recognition of helical structure in the translocating substrate play key roles in the molecular mechanism of protein translocation. PMID:26344833

Electrostatic Ratchet in the Protective Antigen Channel Promotes Anthrax Toxin Translocation*

PubMed Central

Wynia-Smith, Sarah L.; Brown, Michael J.; Chirichella, Gina; Kemalyan, Gigi; Krantz, Bryan A.

2012-01-01

Central to the power-stroke and Brownian-ratchet mechanisms of protein translocation is the process through which nonequilibrium fluctuations are rectified or ratcheted by the molecular motor to transport substrate proteins along a specific axis. We investigated the ratchet mechanism using anthrax toxin as a model. Anthrax toxin is a tripartite toxin comprised of the protective antigen (PA) component, a homooligomeric transmembrane translocase, which translocates two other enzyme components, lethal factor (LF) and edema factor (EF), into the cytosol of the host cell under the proton motive force (PMF). The PA-binding domains of LF and EF (LFN and EFN) possess identical folds and similar solution stabilities; however, EFN translocates ∼10–200-fold slower than LFN, depending on the electrical potential (Δψ) and chemical potential (ΔpH) compositions of the PMF. From an analysis of LFN/EFN chimera proteins, we identified two 10-residue cassettes comprised of charged sequence that were responsible for the impaired translocation kinetics of EFN. These cassettes have nonspecific electrostatic requirements: one surprisingly prefers acidic residues when driven by either a Δψ or a ΔpH; the second requires basic residues only when driven by a Δψ. Through modeling and experiment, we identified a charged surface in the PA channel responsible for charge selectivity. The charged surface latches the substrate and promotes PMF-driven transport. We propose an electrostatic ratchet in the channel, comprised of opposing rings of charged residues, enforces directionality by interacting with charged cassettes in the substrate, thereby generating forces sufficient to drive unfolding. PMID:23115233

Quantitative Determination of Lethal Toxin Proteins in Culture Supernatant of Human Live Anthrax Vaccine Bacillus anthracis A16R

PubMed Central

Zai, Xiaodong; Zhang, Jun; Liu, Ju; Liu, Jie; Li, Liangliang; Yin, Ying; Fu, Ling; Xu, Junjie; Chen, Wei

2016-01-01

Bacillus anthracis (B. anthracis) is the etiological agent of anthrax affecting both humans and animals. Anthrax toxin (AT) plays a major role in pathogenesis. It includes lethal toxin (LT) and edema toxin (ET), which are formed by the combination of protective antigen (PA) and lethal factor (LF) or edema factor (EF), respectively. The currently used human anthrax vaccine in China utilizes live-attenuated B. anthracis spores (A16R; pXO1+, pXO2−) that produce anthrax toxin but cannot produce the capsule. Anthrax toxins, especially LT, have key effects on both the immunogenicity and toxicity of human anthrax vaccines. Thus, determining quantities and biological activities of LT proteins expressed by the A16R strain is meaningful. Here, we explored LT expression patterns of the A16R strain in culture conditions using another vaccine strain Sterne as a control. We developed a sandwich ELISA and cytotoxicity-based method for quantitative detection of PA and LF. Expression and degradation of LT proteins were observed in culture supernatants over time. Additionally, LT proteins expressed by the A16R and Sterne strains were found to be monomeric and showed cytotoxic activity, which may be the main reason for side effects of live anthrax vaccines. Our work facilitates the characterization of anthrax vaccines components and establishment of a quality control standard for vaccine production which may ultimately help to ensure the efficacy and safety of the human anthrax vaccine A16R. PMID:26927174

The C-terminal Helix of Pseudomonas aeruginosa Elongation Factor Ts Tunes EF-Tu Dynamics to Modulate Nucleotide Exchange.

PubMed

De Laurentiis, Evelina Ines; Mercier, Evan; Wieden, Hans-Joachim

2016-10-28

Little is known about the conservation of critical kinetic parameters and the mechanistic strategies of elongation factor (EF) Ts-catalyzed nucleotide exchange in EF-Tu in bacteria and particularly in clinically relevant pathogens. EF-Tu from the clinically relevant pathogen Pseudomonas aeruginosa shares over 84% sequence identity with the corresponding elongation factor from Escherichia coli Interestingly, the functionally closely linked EF-Ts only shares 55% sequence identity. To identify any differences in the nucleotide binding properties, as well as in the EF-Ts-mediated nucleotide exchange reaction, we performed a comparative rapid kinetics and mutagenesis analysis of the nucleotide exchange mechanism for both the E. coli and P. aeruginosa systems, identifying helix 13 of EF-Ts as a previously unnoticed regulatory element in the nucleotide exchange mechanism with species-specific elements. Our findings support the base side-first entry of the nucleotide into the binding pocket of the EF-Tu·EF-Ts binary complex, followed by displacement of helix 13 and rapid binding of the phosphate side of the nucleotide, ultimately leading to the release of EF-Ts. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Similarity and diversity of translational GTPase factors EF-G, EF4, and BipA: From structure to function.

PubMed

Ero, Rya; Kumar, Veerendra; Chen, Yun; Gao, Yong-Gui

2016-12-01

EF-G, EF4, and BipA are members of the translation factor family of GTPases with a common ribosome binding mode and GTPase activation mechanism. However, topological variations of shared as well as unique domains ensure different roles played by these proteins during translation. Recent X-ray crystallography and cryo-electron microscopy studies have revealed the structural basis for the involvement of EF-G domain IV in securing the movement of tRNAs and mRNA during translocation as well as revealing how the unique C-terminal domains of EF4 and BipA interact with the ribosome and tRNAs contributing to the regulation of translation under certain conditions. EF-G, EF-4, and BipA are intriguing examples of structural variations on a common theme that results in diverse behavior and function. Structural studies of translational GTPase factors have been greatly facilitated by the use of antibiotics, which have revealed their mechanism of action.

Ribosomal elongation factor 4 promotes cell death associated with lethal stress.

PubMed

Li, Liping; Hong, Yuzhi; Luan, Gan; Mosel, Michael; Malik, Muhammad; Drlica, Karl; Zhao, Xilin

2014-12-09

Ribosomal elongation factor 4 (EF4) is highly conserved among bacteria, mitochondria, and chloroplasts. However, the EF4-encoding gene, lepA, is nonessential and its deficiency shows no growth or fitness defect. In purified systems, EF4 back-translocates stalled, posttranslational ribosomes for efficient protein synthesis; consequently, EF4 has a protective role during moderate stress. We were surprised to find that EF4 also has a detrimental role during severe stress: deletion of lepA increased Escherichia coli survival following treatment with several antimicrobials. EF4 contributed to stress-mediated lethality through reactive oxygen species (ROS) because (i) the protective effect of a ΔlepA mutation against lethal antimicrobials was eliminated by anaerobic growth or by agents that block hydroxyl radical accumulation and (ii) the ΔlepA mutation decreased ROS levels stimulated by antimicrobial stress. Epistasis experiments showed that EF4 functions in the same genetic pathway as the MazF toxin, a stress response factor implicated in ROS-mediated cell death. The detrimental action of EF4 required transfer-messenger RNA (tmRNA, which tags truncated proteins for degradation and is known to be inhibited by EF4) and the ClpP protease. Inhibition of a protective, tmRNA/ClpP-mediated degradative activity would allow truncated proteins to indirectly perturb the respiratory chain and thereby provide a potential link between EF4 and ROS. The connection among EF4, MazF, tmRNA, and ROS expands a pathway leading from harsh stress to bacterial self-destruction. The destructive aspect of EF4 plus the protective properties described previously make EF4 a bifunctional factor in a stress response that promotes survival or death, depending on the severity of stress. Translation elongation factor 4 (EF4) is one of the most conserved proteins in nature, but it is dispensable. Lack of strong phenotypes for its genetic knockout has made EF4 an enigma. Recent biochemical work has demonstrated that mild stress may stall ribosomes and that EF4 can reposition stalled ribosomes to resume proper translation. Thus, EF4 protects cells from moderate stress. Here we report that EF4 is paradoxically harmful during severe stress, such as that caused by antimicrobial treatment. EF4 acts in a pathway that leads to excessive accumulation of reactive oxygen species (ROS), thereby participating in a bacterial self-destruction that occurs when cells cannot effectively repair stress-mediated damage. Thus, EF4 has two opposing functions-at low-to-moderate levels of stress, the protein is protective by allowing stress-paused translation to resume; at high-levels of stress, EF4 helps bacteria self-destruct. These data support the existence of a bacterial live-or-die response to stress. Copyright © 2014 Li et al.

Energy Factor Analysis for Gas Heat Pump Water Heaters

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gluesenkamp, Kyle R

2016-01-01

Gas heat pump water heaters (HPWHs) can improve water heating efficiency with zero GWP and zero ODP working fluids. The energy factor (EF) of a gas HPWH is sensitive to several factors. In this work, expressions are derived for EF of gas HPWHs, as a function of heat pump cycle COP, tank heat losses, burner efficiency, electrical draw, and effectiveness of supplemental heat exchangers. The expressions are used to investigate the sensitivity of EF to each parameter. EF is evaluated on a site energy basis (as used by the US DOE for rating water heater EF), and a primary energy-basismore » energy factor (PEF) is also defined and included. Typical ranges of values for the six parameters are given. For gas HPWHs, using typical ranges for component performance, EF will be 59 80% of the heat pump cycle thermal COP (for example, a COP of 1.60 may result in an EF of 0.94 1.28). Most of the reduction in COP is due to burner efficiency and tank heat losses. Gas-fired HPWHs are theoretically be capable of an EF of up to 1.7 (PEF of 1.6); while an EF of 1.1 1.3 (PEF of 1.0 1.1) is expected from an early market entry.« less

Study of phosphorylation of translation elongation factor 2 (EF-2) from wheat germ.

PubMed

Smailov, S K; Lee, A V; Iskakov, B K

1993-04-26

Phosphorylation of elongation factor 2 (EF-2) by specific Ca2+/calmodulin-dependent kinase is considered as a possible mechanism of regulation of protein biosynthesis in animal cells at the level of polypeptide chain elongation. In this report we show that wheat germ EF-2 can be intensively phosphorylated by the rabbit reticulocyte EF-2 kinase. Phosphorylation results in inhibition of the activity of plant EF-2 in poly(U)-dependent cell-free translation system. Thus, the activity of EF-2 in plant cells can be potentially regulated by phosphorylation. However, we could not detect endogenous EF-2 kinase activity in wheat germ either in vitro or in vivo. Furthermore, EF-2 kinase activity is not displayed in different organs of wheat and other higher plants.

Kirromycin, an Inhibitor of Protein Biosynthesis that Acts on Elongation Factor Tu

PubMed Central

Wolf, Heinz; Chinali, Gianni; Parmeggiani, Andrea

1974-01-01

Kirromycin, a new inhibitor of protein synthesis, is shown to interfere with the peptide transfer reaction by acting on elongation factor Tu (EF-Tu). All the reactions associated with this elongation factor are affected. Formation of the EF-Tu·GTP complex is strongly stimulated. Peptide bond formation is prevented only when Phe-tRNAPhe is bound enzymatically to ribosomes, presumably because GTP hydrolysis associated with enzymatic binding of Phe-tRNAPhe is not followed by release of EF-Tu·GDP from the ribosome. This antibiotic also enables EF-Tu to catalyze the binding of Phe-tRNAPhe to the poly(U)·ribosome complex even in the absence of GTP. EF-Tu activity in the GTPase reaction is dramatically affected by kirromycin: GTP hydrolysis, which normally requires ribosomes and aminoacyl-tRNA, takes place with the elongation factor alone. This GTPase shows the same Km for GTP as the one dependent on Phe-tRNAPhe and ribosomes in the absence of the antibiotic. Ribosomes and Phe-tRNAPhe, but not tRNAPhe or Ac-Phe-tRNAPhe, stimulate the kirromycin-induced EF-Tu GTPase. These results indicate that the catalytic center of EF-Tu GTPase that is dependent upon aminoacyl-tRNA and ribosomes is primarily located on the elongation factor. In conclusion, kirromycin can substitute for GTP, aminoacyl-tRNA, or ribosomes in various reactions involving EF-Tu, apparently by affecting the allosteric controls between the sites on the EF-Tu molecule interacting with these components. PMID:4373734

Phosphorylation of eukaryotic elongation factor 2 (eEF2) by cyclin A-cyclin-dependent kinase 2 regulates its inhibition by eEF2 kinase.

PubMed

Hizli, Asli A; Chi, Yong; Swanger, Jherek; Carter, John H; Liao, Yi; Welcker, Markus; Ryazanov, Alexey G; Clurman, Bruce E

2013-02-01

Protein synthesis is highly regulated via both initiation and elongation. One mechanism that inhibits elongation is phosphorylation of eukaryotic elongation factor 2 (eEF2) on threonine 56 (T56) by eEF2 kinase (eEF2K). T56 phosphorylation inactivates eEF2 and is the only known normal eEF2 functional modification. In contrast, eEF2K undergoes extensive regulatory phosphorylations that allow diverse pathways to impact elongation. We describe a new mode of eEF2 regulation and show that its phosphorylation by cyclin A-cyclin-dependent kinase 2 (CDK2) on a novel site, serine 595 (S595), directly regulates T56 phosphorylation by eEF2K. S595 phosphorylation varies during the cell cycle and is required for efficient T56 phosphorylation in vivo. Importantly, S595 phosphorylation by cyclin A-CDK2 directly stimulates eEF2 T56 phosphorylation by eEF2K in vitro, and we suggest that S595 phosphorylation facilitates T56 phosphorylation by recruiting eEF2K to eEF2. S595 phosphorylation is thus the first known eEF2 modification that regulates its inhibition by eEF2K and provides a novel mechanism linking the cell cycle machinery to translational control. Because all known eEF2 regulation is exerted via eEF2K, S595 phosphorylation may globally couple the cell cycle machinery to regulatory pathways that impact eEF2K activity.

Phosphorylation of Eukaryotic Elongation Factor 2 (eEF2) by Cyclin A–Cyclin-Dependent Kinase 2 Regulates Its Inhibition by eEF2 Kinase

PubMed Central

Hizli, Asli A.; Chi, Yong; Swanger, Jherek; Carter, John H.; Liao, Yi; Welcker, Markus; Ryazanov, Alexey G.

2013-01-01

Protein synthesis is highly regulated via both initiation and elongation. One mechanism that inhibits elongation is phosphorylation of eukaryotic elongation factor 2 (eEF2) on threonine 56 (T56) by eEF2 kinase (eEF2K). T56 phosphorylation inactivates eEF2 and is the only known normal eEF2 functional modification. In contrast, eEF2K undergoes extensive regulatory phosphorylations that allow diverse pathways to impact elongation. We describe a new mode of eEF2 regulation and show that its phosphorylation by cyclin A–cyclin-dependent kinase 2 (CDK2) on a novel site, serine 595 (S595), directly regulates T56 phosphorylation by eEF2K. S595 phosphorylation varies during the cell cycle and is required for efficient T56 phosphorylation in vivo. Importantly, S595 phosphorylation by cyclin A-CDK2 directly stimulates eEF2 T56 phosphorylation by eEF2K in vitro, and we suggest that S595 phosphorylation facilitates T56 phosphorylation by recruiting eEF2K to eEF2. S595 phosphorylation is thus the first known eEF2 modification that regulates its inhibition by eEF2K and provides a novel mechanism linking the cell cycle machinery to translational control. Because all known eEF2 regulation is exerted via eEF2K, S595 phosphorylation may globally couple the cell cycle machinery to regulatory pathways that impact eEF2K activity. PMID:23184662

Mammalian translation elongation factor eEF1A2: X-ray structure and new features of GDP/GTP exchange mechanism in higher eukaryotes

PubMed Central

Crepin, Thibaut; Shalak, Vyacheslav F.; Yaremchuk, Anna D.; Vlasenko, Dmytro O.; McCarthy, Andrew; Negrutskii, Boris S.; Tukalo, Michail A.; El'skaya, Anna V.

2014-01-01

Eukaryotic elongation factor eEF1A transits between the GTP- and GDP-bound conformations during the ribosomal polypeptide chain elongation. eEF1A*GTP establishes a complex with the aminoacyl-tRNA in the A site of the 80S ribosome. Correct codon–anticodon recognition triggers GTP hydrolysis, with subsequent dissociation of eEF1A*GDP from the ribosome. The structures of both the ‘GTP’- and ‘GDP’-bound conformations of eEF1A are unknown. Thus, the eEF1A-related ribosomal mechanisms were anticipated only by analogy with the bacterial homolog EF-Tu. Here, we report the first crystal structure of the mammalian eEF1A2*GDP complex which indicates major differences in the organization of the nucleotide-binding domain and intramolecular movements of eEF1A compared to EF-Tu. Our results explain the nucleotide exchange mechanism in the mammalian eEF1A and suggest that the first step of eEF1A*GDP dissociation from the 80S ribosome is the rotation of the nucleotide-binding domain observed after GTP hydrolysis. PMID:25326326

Direct evidence of an elongation factor-Tu/Ts·GTP·Aminoacyl-tRNA quaternary complex.

PubMed

Burnett, Benjamin J; Altman, Roger B; Ferguson, Angelica; Wasserman, Michael R; Zhou, Zhou; Blanchard, Scott C

2014-08-22

During protein synthesis, elongation factor-Tu (EF-Tu) bound to GTP chaperones the entry of aminoacyl-tRNA (aa-tRNA) into actively translating ribosomes. In so doing, EF-Tu increases the rate and fidelity of the translation mechanism. Recent evidence suggests that EF-Ts, the guanosine nucleotide exchange factor for EF-Tu, directly accelerates both the formation and dissociation of the EF-Tu-GTP-Phe-tRNA(Phe) ternary complex (Burnett, B. J., Altman, R. B., Ferrao, R., Alejo, J. L., Kaur, N., Kanji, J., and Blanchard, S. C. (2013) J. Biol. Chem. 288, 13917-13928). A central feature of this model is the existence of a quaternary complex of EF-Tu/Ts·GTP·aa-tRNA(aa). Here, through comparative investigations of phenylalanyl, methionyl, and arginyl ternary complexes, and the development of a strategy to monitor their formation and decay using fluorescence resonance energy transfer, we reveal the generality of this newly described EF-Ts function and the first direct evidence of the transient quaternary complex species. These findings suggest that EF-Ts may regulate ternary complex abundance in the cell through mechanisms that are distinct from its guanosine nucleotide exchange factor functions. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Influence of fuel mass load, oxygen supply and burning rate on emission factor and size distribution of carbonaceous particulate matter from indoor corn straw burning.

PubMed

Shen, Guofeng; Xue, Miao; Wei, Siye; Chen, Yuanchen; Wang, Bin; Wang, Rong; Shen, Huizhong; Li, Wei; Zhang, Yanyan; Huang, Ye; Chen, Han; Wei, Wen; Zhao, Qiuyue; Li, Bin; Wu, Haisuo; Tao, Shu

2013-03-01

The uncertainty in emission estimation is strongly associated with the variation in emission factor (EF), which could be influenced by a variety of factors such as fuel properties, stove type, fire management and even methods used in measurements. The impacts of these factors are complicated and often interact with each other. Controlled burning experiments were conducted to investigate the influences of fuel mass load, air supply and burning rate on the emissions and size distributions of carbonaceous particulate matter (PM) from indoor corn straw burning in a cooking stove. The results showed that the EFs of PM (EF(PM)), organic carbon (EFoc) and elemental carbon (EF(EC)) were independent of the fuel mass load. The differences among them under different burning rates or air supply amounts were also found to be insignificant (p > 0.05) in the tested circumstances. PM from the indoor corn straw burning was dominated by fine PM with diameter less than 2.1 microm, contributing 86.4% +/- 3.9% of the total. The size distribution of PM was influenced by the burning rate and air supply conditions. On average, EF(PM), EF(OC) and EF(EC) for corn straw burned in a residential cooking stove were (3.84 +/- 1.02), (0.846 +/- 0.895) and (0.391 +/- 0.350) g/kg, respectively. EF(PM), EF(OC) and EF(EC) were found to be positively correlated with each other (p < 0.05), but they were not significantly correlated with the EF of co-emitted CO, suggesting that special attention should be paid to the use of CO as a surrogate for other incomplete combustion pollutants.

21 CFR 172.860 - Fatty acids.

Code of Federal Regulations, 2011 CFR

2011-04-01

.... (2) It is free of chick-edema factor: (i) As evidenced during the bioassay method for determining the chick-edema factor as prescribed in paragraph (c)(2) of this section; or (ii) As evidenced by the... the bioassay method prescribed in paragraph (c)(2) of this section for determining chick-edema factor...

21 CFR 172.860 - Fatty acids.

Code of Federal Regulations, 2010 CFR

2010-04-01

.... (2) It is free of chick-edema factor: (i) As evidenced during the bioassay method for determining the chick-edema factor as prescribed in paragraph (c)(2) of this section; or (ii) As evidenced by the... the bioassay method prescribed in paragraph (c)(2) of this section for determining chick-edema factor...

Revisiting the Concept of Targeting Only Bacillus anthracis Toxins as a Treatment for Anthrax.

PubMed

Glinert, Itai; Bar-David, Elad; Sittner, Assa; Weiss, Shay; Schlomovitz, Josef; Ben-Shmuel, Amir; Mechaly, Adva; Altboum, Zeev; Kobiler, David; Levy, Haim

2016-08-01

Protective antigen (PA)-based vaccines are effective in preventing the development of fatal anthrax disease both in humans and in relevant animal models. The Bacillus anthracis toxins lethal toxin (lethal factor [LF] plus PA) and edema toxin (edema factor [EF] plus PA) are essential for the establishment of the infection, as inactivation of these toxins results in attenuation of the pathogen. Since the toxins reach high toxemia levels at the bacteremic stages of the disease, the CDC's recommendations include combining antibiotic treatment with antitoxin (anti-PA) immunotherapy. We demonstrate here that while treatment with a highly potent neutralizing monoclonal antibody was highly efficient as postexposure prophylaxis treatment, it failed to protect rabbits with any detectable bacteremia (≥10 CFU/ml). In addition, we show that while PA vaccination was effective against a subcutaneous spore challenge, it failed to protect rabbits against systemic challenges (intravenous injection of vegetative bacteria) with the wild-type Vollum strain or a toxin-deficient mutant. To test the possibility that additional proteins, which are secreted by the bacteria under pathogenicity-stimulating conditions in vitro, may contribute to the vaccine's potency, we immunized rabbits with a secreted protein fraction from a toxin-null mutant. The antiserum raised against the secreted fraction reacts with the bacteria in an immunofluorescence assay. Immunization with the secreted protein fraction did not protect the rabbits against a systemic challenge with the fully pathogenic bacteria. Full protection was obtained only by a combined vaccination with PA and the secreted protein fraction. Therefore, these results indicate that an effective antiserum treatment in advanced stages of anthrax must include toxin-neutralizing antibodies in combination with antibodies against bacterial cell targets. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Investigation of a panel of monoclonal antibodies and polyclonal sera against anthrax toxins resulted in identification of an anti-lethal factor antibody with disease-enhancing characteristics.

PubMed

Kulshreshtha, Parul; Tiwari, Ashutosh; Priyanka; Joon, Shikha; Sinha, Subrata; Bhatnagar, Rakesh

2015-12-01

Hybridomas were created using spleen of mice that were actively immunized with rLFn (recombinant N-terminal domain of lethal factor). Later on, separate group of mice were immunized with rLFn to obtain a polyclonal control for passive immunization studies of monoclonal antibodies. This led to the identification of one cohort of rLFn-immnized mice that harboured disease-enhancing polyclonal antibodies. At the same time, the monoclonal antibodies secreted by all the hybridomas were being tested. Two hybridomas secreted monoclonal antibodies (H10 and H8) that were cross-reactive with EF (edema factor) and LF (lethal factor), while the other two hybridomas secreted LF-specific antibodies (H7 and H11). Single chain variable fragment (LETscFv) was derived from H10 hybridoma. H11 was found to have disease-enhancing property. Combination of H11 with protective monoclonal antibodies (H8 and H10) reduced its disease enhancing nature. This in vitro abrogation of disease-enhancement provides the proof of concept that in polyclonal sera the disease enhancing character of a fraction of antibodies is overshadowed by the protective nature of the rest of the antibodies generated on active immunization. Copyright © 2015. Published by Elsevier Ltd.

Bacterial translation elongation factor EF-Tu interacts and colocalizes with actin-like MreB protein.

PubMed

Defeu Soufo, Hervé Joël; Reimold, Christian; Linne, Uwe; Knust, Tobias; Gescher, Johannes; Graumann, Peter L

2010-02-16

We show that translation initiation factor EF-Tu plays a second important role in cell shape maintenance in the bacterium Bacillus subtilis. EF-Tu localizes in a helical pattern underneath the cell membrane and colocalizes with MreB, an actin-like cytoskeletal element setting up rod cell shape. The localization of MreB and of EF-Tu is interdependent, but in contrast to the dynamic MreB filaments, EF-Tu structures are more static and may serve as tracks for MreB filaments. In agreement with this idea, EF-Tu and MreB interact in vivo and in vitro. Lowering of the EF-Tu levels had a minor effect on translation but a strong effect on cell shape and on the localization of MreB, and blocking of the function of EF-Tu in translation did not interfere with the localization of MreB, showing that, directly or indirectly, EF-Tu affects the cytoskeletal MreB structure and thus serves two important functions in a bacterium.

Polysaccharides from Arctium lappa L.: Chemical structure and biological activity.

PubMed

Carlotto, Juliane; de Souza, Lauro M; Baggio, Cristiane H; Werner, Maria Fernanda de P; Maria-Ferreira, Daniele; Sassaki, Guilherme L; Iacomini, Marcello; Cipriani, Thales R

2016-10-01

The plant Arctium lappa L. is popularly used to relieve symptoms of inflammatory disorders. A crude polysaccharide fraction (SAA) resulting of aqueous extraction of A. lappa leaves showed a dose dependent anti-edematogenic activity on carrageenan-induced paw edema, which persisted for up to 48h. Sequential fractionation by ultrafiltration at 50kDa and 30kDa cut-off membranes yielded three fractions, namely RF50, RF30, and EF30. All these maintained the anti-edematogenic effect, but RF30 showed a more potent action, inhibiting 57% of the paw edema at a dose of 4.9mg/kg. The polysaccharide RF30 contained galacturonic acid, galactose, arabinose, rhamnose, glucose, and mannose in a 7:4:2:1:2:1 ratio and had a Mw of 91,000g/mol. Methylation analysis and NMR spectroscopy indicated that RF30 is mainly constituted by a type I rhamnogalacturonan branched by side chains of types I and II arabinogalactans, and arabinan. Copyright © 2016 Elsevier B.V. All rights reserved.

The effects of deterioration and technological levels on pollutant emission factors for gasoline light-duty trucks.

PubMed

Zhang, Qingyu; Fan, Juwang; Yang, Weidong; Chen, Bixin; Zhang, Lijuan; Liu, Jiaoyu; Wang, Jingling; Zhou, Chunyao; Chen, Xuan

2017-07-01

Vehicle deterioration and technological change influence emission factors (EFs). In this study, the impacts of vehicle deterioration and emission standards on EFs of regulated pollutants (carbon monoxide [CO], hydrocarbon [HC], and nitrogen oxides [NO x ]) for gasoline light-duty trucks (LDTs) were investigated according to the inspection and maintenance (I/M) data using a chassis dynamometer method. Pollutant EFs for LDTs markedly varied with accumulated mileages and emission standards, and the trends of EFs are associated with accumulated mileages. In addition, the study also found that in most cases, the median EFs of CO, HC, and NO x are higher than those of basic EFs in the International Vehicle Emissions (IVE) model; therefore, the present study provides correction factors for the IVE model relative to the corresponding emission standards and mileages. Currently, vehicle emissions are great contributors to air pollution in cities, especially in developing countries. Emission factors play a key role in creating emission inventory and estimating emissions. Deterioration represented by vehicle age and accumulated mileage and changes of emission standards markedly influence emission factors. In addition, the results provide collection factors for implication in the IVE model in the region levels.

Strong Genetic Overlap Between Executive Functions and Intelligence

PubMed Central

Engelhardt, Laura E.; Mann, Frank D.; Briley, Daniel A.; Church, Jessica A.; Harden, K. Paige; Tucker-Drob, Elliot M.

2016-01-01

Executive functions (EFs) are cognitive processes that control, monitor, and coordinate more basic cognitive processes. EFs play instrumental roles in models of complex reasoning, learning, and decision-making, and individual differences in EFs have been consistently linked with individual differences in intelligence. By middle childhood, genetic factors account for a moderate proportion of the variance in intelligence, and these effects increase in magnitude through adolescence. Genetic influences on EFs are very high, even in middle childhood, but the extent to which these genetic influences overlap with those on intelligence is unclear. We examined genetic and environmental overlap between EFs and intelligence in a racially and socioeconomically diverse sample of 811 twins ages 7-15 years (M = 10.91, SD = 1.74) from the Texas Twin Project. A general EF factor representing variance common to inhibition, switching, working memory, and updating domains accounted for substantial proportions of variance in intelligence, primarily via a genetic pathway. General EF continued to have a strong, genetically-mediated association with intelligence even after controlling for processing speed. Residual variation in general intelligence was influenced only by shared and nonshared environmental factors, and there remained no genetic variance in general intelligence that was unique of EF. Genetic variance independent of EF did remain, however, in a more specific perceptual reasoning ability. These results provide evidence that genetic influences on general intelligence are highly overlapping with those on EF. PMID:27359131

RECURRENT STROKE IN THE WARFARIN VERSUS ASPIRIN IN REDUCED EJECTION FRACTION (WARCEF) TRIAL

PubMed Central

Pullicino, Patrick M.; Qian, Min; Sacco, Ralph L.; Freudenberger, Ron; Graham, Susan; Teerlink, John R.; Mann, Douglas; Di Tullio, Marco R.; Ponikowski, Piotr; Lok, Dirk J.; Anker, Stefan D.; Lip, Gregory Y.H.; Estol, Conrado J.; Levin, Bruce; Mohr, J.P.; Thompson, John L. P.; Homma, Shunichi

2014-01-01

Background and Purpose WARCEF randomized 2305 patients in sinus rhythm with ejection fraction (EF) ≤35% to warfarin (INR 2.0–3.5) or aspirin 325 mg. Warfarin reduced the incident ischemic stroke (IIS) hazard rate by 48% over aspirin in a secondary analysis. The IIS rate in heart failure (HF) is too low to warrant routine anticoagulation but epidemiologic studies show that prior stroke increases the stroke risk in HF. We here explore IIS rates in WARCEF patients with and without baseline stroke to look for risk factors for IIS and determine if a subgroup with an IIS rate high enough to give a clinically relevant stroke risk reduction can be identified. Methods We compared potential stroke risk factors between patients with baseline stroke and those without using the exact conditional score test for Poisson variables. We looked for risk factors for IIS, by comparing IIS rates between different risk factors. For EF we tried cutoff points of 10%, 15% and 20%. 15% was used as it was the highest EF that was associated with a significant increase in IIS rate. IIS and EF strata were balanced as to warfarin/aspirin assignment by the stratified randomized design. A multiple Poisson regression examined the simultaneous effects of all risk factors on IIS rate. IIS rates per hundred patient years (/100PY) were calculated in patient groups with significant risk factors. Missing values were assigned the modal value. Results Twenty of 248 (8.1%) patients with baseline stroke and 64 of 2048 (3.1%) without had IIS. IIS rate in patients with baseline stroke (2.37/100PY) was greater than patients without (0.89/100PY)(rate ratio 2.68, p<0.001). Fourteen of 219 (6.4%) patients with ejection fraction (EF)<15% and 70 of 2079 (3.4%) with EF ≥15% had IIS. In the multiple regression analysis stroke at baseline (p<0.001) and EF<15% vs. ≥15% (p=.005) remained significant predictors of IIS. IIS rate was 2.04/100PY in patients with EF<15% and 0.95/100PY in patients with EF ≥15% (p=0.009). IIS rate in patients with baseline stroke and reduced EF was 5.88/100PY with EF<15% decreasing to 2.62/100PY with EF<30%. Conclusions In a WARCEF exploratory analysis, prior stroke and EF<15% were risk factors for IIS. Further research is needed to determine if a clinically relevant stroke risk reduction is obtainable with warfarin in HF patients with prior stroke and reduced EF. PMID:25300706

[Biotoxic effects of aqueous humour-a unifying pathogenetic theory, based on certain hypothetic biotoxic factors in aqueus (author's transl)].

PubMed

Worst, J G

1975-09-01

A hypothesis is proposed attributing a number of biotoxic effects to aqueous humor (ABC equals Aqueous Biotoxic Complex). Under normal anatomical and physiological conditions aqueous humour is contained in the anterior and posterior chamber reservoir and the ABC effects remain silent because the boundaries of the aqueous humour reservoir are resistant to these biotoxic factors. These factors are biochemically undefined but fall in the category of collagenolysins and anti-vascular enzymes (Prostaglandins?). Outside the normal reservoir these biotoxic effects result in a specific pathology such as corneal edema, subconjunctival edema, lens fiber edema, macular edema, papilledema and chorioidal edema.

Isolation and properties of the subunit form EF-1C of elongation factor 1 from Guerin epithelioma cells.

PubMed

Marcinkiewicz, C; Gałasiński, W

1993-01-01

EF-1C is a component of the aggregate EF-1B, consisting of the subunit forms EF-1A.EF-1C; it was isolated by dissociation of this aggregate in the presence of GTP. The subunit form EF-1C stimulates binding of aminoacyl-tRNA to ribosomes, catalysed by EF-1A, similarly as EF-1 beta gamma which stimulates the activity of EF-1 in other eukaryotic cells. EF-1C in the presence of 6 M urea was separated into two polypeptides. Polypeptide of molecular mass 32,000 Da is responsible for regeneration of the EF-1A.GTP active complex. Thermal sensitivity of EF-1A was much higher than that of EF-1B, thus a protective role of EF-1C in the EF-1A.EF-1C complex is suggested.

Mammalian translation elongation factor eEF1A2: X-ray structure and new features of GDP/GTP exchange mechanism in higher eukaryotes.

PubMed

Crepin, Thibaut; Shalak, Vyacheslav F; Yaremchuk, Anna D; Vlasenko, Dmytro O; McCarthy, Andrew; Negrutskii, Boris S; Tukalo, Michail A; El'skaya, Anna V

2014-11-10

Eukaryotic elongation factor eEF1A transits between the GTP- and GDP-bound conformations during the ribosomal polypeptide chain elongation. eEF1A*GTP establishes a complex with the aminoacyl-tRNA in the A site of the 80S ribosome. Correct codon-anticodon recognition triggers GTP hydrolysis, with subsequent dissociation of eEF1A*GDP from the ribosome. The structures of both the 'GTP'- and 'GDP'-bound conformations of eEF1A are unknown. Thus, the eEF1A-related ribosomal mechanisms were anticipated only by analogy with the bacterial homolog EF-Tu. Here, we report the first crystal structure of the mammalian eEF1A2*GDP complex which indicates major differences in the organization of the nucleotide-binding domain and intramolecular movements of eEF1A compared to EF-Tu. Our results explain the nucleotide exchange mechanism in the mammalian eEF1A and suggest that the first step of eEF1A*GDP dissociation from the 80S ribosome is the rotation of the nucleotide-binding domain observed after GTP hydrolysis. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

The Potyviral P3 Protein Targets Eukaryotic Elongation Factor 1A to Promote the Unfolded Protein Response and Viral Pathogenesis1[OPEN

PubMed Central

Shine, M.B.; Cui, Xiaoyan; Chen, Xin; Ma, Na; Kachroo, Pradeep; Zhi, Haijan; Kachroo, Aardra

2016-01-01

The biochemical function of the potyviral P3 protein is not known, although it is known to regulate virus replication, movement, and pathogenesis. We show that P3, the putative virulence determinant of soybean mosaic virus (SMV), targets a component of the translation elongation complex in soybean. Eukaryotic elongation factor 1A (eEF1A), a well-known host factor in viral pathogenesis, is essential for SMV virulence and the associated unfolded protein response (UPR). Silencing GmEF1A inhibits accumulation of SMV and another ER-associated virus in soybean. Conversely, endoplasmic reticulum (ER) stress-inducing chemicals promote SMV accumulation in wild-type, but not GmEF1A-knockdown, plants. Knockdown of genes encoding the eEF1B isoform, which is important for eEF1A function in translation elongation, has similar effects on UPR and SMV resistance, suggesting a link to translation elongation. P3 and GmEF1A promote each other’s nuclear localization, similar to the nuclear-cytoplasmic transport of eEF1A by the Human immunodeficiency virus 1 Nef protein. Our results suggest that P3 targets host elongation factors resulting in UPR, which in turn facilitates SMV replication and place eEF1A upstream of BiP in the ER stress response during pathogen infection. PMID:27356973

Developmental Trajectories in Toddlers’ Self-restraint Predict Individual Differences in Executive Functions 14 Years Later: A Behavioral Genetic Analysis

PubMed Central

Friedman, Naomi P.; Miyake, Akira; Robinson, JoAnn L.; Hewitt, John K.

2011-01-01

We examined whether self-restraint in early childhood predicted individual differences in three executive functions (EFs; inhibiting prepotent responses, updating working memory, and shifting task sets) in late adolescence in a sample of ~950 twins. At ages 14, 20, 24, and 36 months, the children were shown an attractive toy and told not to touch it for 30 seconds. Latency to touch the toy increased with age, and latent class growth modeling distinguished two groups of children that differed in their latencies to touch the toy at all 4 time points. Using confirmatory factor analysis, the three EFs (measured with latent variables at age 17 years) were decomposed into a Common EF factor (isomorphic to response inhibition ability) and two factors specific to updating and shifting, respectively. Less restrained children had significantly lower scores on the Common EF factor, equivalent scores on the Updating-specific factor, and higher scores on the Shifting-specific factor than the more restrained children. The less restrained group also had lower IQ scores, but this effect was entirely mediated by the EF components. Twin models indicated that the associations were primarily genetic in origin for the Common EF variable but split between genetics and nonshared environment for the Shifting-specific variable. These results suggest a biological relation between individual differences in self-restraint and EFs, one that begins early in life and persists into late adolescence. PMID:21668099

Strong genetic overlap between executive functions and intelligence.

PubMed

Engelhardt, Laura E; Mann, Frank D; Briley, Daniel A; Church, Jessica A; Harden, K Paige; Tucker-Drob, Elliot M

2016-09-01

Executive functions (EFs) are cognitive processes that control, monitor, and coordinate more basic cognitive processes. EFs play instrumental roles in models of complex reasoning, learning, and decision making, and individual differences in EFs have been consistently linked with individual differences in intelligence. By middle childhood, genetic factors account for a moderate proportion of the variance in intelligence, and these effects increase in magnitude through adolescence. Genetic influences on EFs are very high, even in middle childhood, but the extent to which these genetic influences overlap with those on intelligence is unclear. We examined genetic and environmental overlap between EFs and intelligence in a racially and socioeconomically diverse sample of 811 twins ages 7 to 15 years (M = 10.91, SD = 1.74) from the Texas Twin Project. A general EF factor representing variance common to inhibition, switching, working memory, and updating domains accounted for substantial proportions of variance in intelligence, primarily via a genetic pathway. General EF continued to have a strong, genetically mediated association with intelligence even after controlling for processing speed. Residual variation in general intelligence was influenced only by shared and nonshared environmental factors, and there remained no genetic variance in general intelligence that was unique of EF. Genetic variance independent of EF did remain, however, in a more specific perceptual reasoning ability. These results provide evidence that genetic influences on general intelligence are highly overlapping with those on EF. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Purification and Characterization of Tagless Recombinant Human Elongation Factor 2 Kinase (eEF-2K) Expressed in Escherichia coli

PubMed Central

Abramczyk, Olga; Tavares, Clint D. J.; Devkota, Ashwini K.; Ryazanov, Alexey G.; Turk, Benjamin E.; Riggs, Austen F.; Ozpolat, Bulent; Dalby, Kevin N.

2012-01-01

The eukaryotic elongation factor 2 kinase (eEF-2K) modulates the rate of protein synthesis by impeding the elongation phase of translation by inactivating the eukaryotic elongation factor 2 (eEF-2) via phosphorylation. eEF-2K is known to be activated by calcium and calmodulin, whereas the mTOR and MAPK pathways are suggested to negatively regulate kinase activity. Despite its pivotal role in translation regulation and potential role in tumor survival, the structure, function and regulation of eEF-2K have not been described in detail. This deficiency may result from the difficulty of obtaining the recombinant kinase in a form suitable for biochemical analysis. Here we report the purification and characterization of recombinant human eEF-2K expressed in the Escherichia coli strain Rosetta-gami 2(DE3). Successive chromatography steps utilizing Ni-NTA affinity, anion-exchange and gel filtration columns accomplished purification. Cleavage of the thioredoxin-His6-tag from the N-terminus of the expressed kinase with TEV protease yielded 9 mg of recombinant (G-D-I)-eEF-2K per liter of culture. Light scattering shows that eEF-2K is a monomer of ~ 85 kDa. In vitro kinetic analysis confirmed that recombinant human eEF-2K is able to phosphorylate wheat germ eEF-2 with kinetic parameters comparable to the mammalian enzyme. PMID:21605678

Molecular Mechanism for the Control of Eukaryotic Elongation Factor 2 Kinase by pH: Role in Cancer Cell Survival

PubMed Central

Xie, Jianling; Mikolajek, Halina; Pigott, Craig R.; Hooper, Kelly J.; Mellows, Toby; Moore, Claire E.; Mohammed, Hafeez; Werner, Jörn M.; Thomas, Gareth J.

2015-01-01

Acidification of the extracellular and/or intracellular environment is involved in many aspects of cell physiology and pathology. Eukaryotic elongation factor 2 kinase (eEF2K) is a Ca2+/calmodulin-dependent kinase that regulates translation elongation by phosphorylating and inhibiting eEF2. Here we show that extracellular acidosis elicits activation of eEF2K in vivo, leading to enhanced phosphorylation of eEF2. We identify five histidine residues in eEF2K that are crucial for the activation of eEF2K during acidosis. Three of them (H80, H87, and H94) are in its calmodulin-binding site, and their protonation appears to enhance the ability of calmodulin to activate eEF2K. The other two histidines (H227 and H230) lie in the catalytic domain of eEF2K. We also identify His108 in calmodulin as essential for activation of eEF2K. Acidification of cancer cell microenvironments is a hallmark of malignant solid tumors. Knocking down eEF2K in cancer cells attenuated the decrease in global protein synthesis when cells were cultured at acidic pH. Importantly, activation of eEF2K is linked to cancer cell survival under acidic conditions. Inhibition of eEF2K promotes cancer cell death under acidosis. PMID:25776553

Structural basis for the binding of didemnins to human elongation factor eEF1A and rationale for the potent antitumor activity of these marine natural products.

PubMed

Marco, Esther; Martín-Santamaría, Sonsoles; Cuevas, Carmen; Gago, Federico

2004-08-26

Didemnins and tamandarins are closely related marine natural products with potent inhibitory effects on protein synthesis and cell viability. On the basis of available biochemical and structural evidence and results from molecular dynamics simulations, a model is proposed that accounts for the strong and selective binding of these compounds to human elongation factor eEF1A in the presence of GTP. We suggest that the p-methoxyphenyl ring of these cyclic depsipeptides is inserted into the same pocket in eEF1A that normally lodges either the 3' terminal adenine of aminoacylated tRNA, as inferred from two prokaryotic EF-Tu.GTP.tRNA complexes, or the aromatic side chain of Phe/Tyr-163 from the nucleotide exchange factor eEF1Balpha, as observed in several X-ray crystal structures of a yeast eEF1A:eEF1Balpha complex. This pocket, which has a strong hydrophobic character, is formed by two protruding loops on the surface of eEF1A domain 2. Further stabilization of the bound depsipeptide is brought about by additional crucial interactions involving eEF1A domain 1 in such a way that the molecule fits snugly at the interface between these two domains. In the GDP-bound form of eEF1A, this binding site exists only as two separate halves, which accounts for the much greater affinity of didemnins for the GTP-bound form of this elongation factor. This binding mode is entirely different from those seen in the complexes of the homologous prokaryotic EF-Tu with kirromycin-type antibiotics or the cyclic thiazolyl peptide antibiotic GE2270A. Interestingly, the set of interactions used by didemnins to bind to eEF1A is also distinct from that used by eEF1Balpha or eEF1Bbeta, thus establishing a competition for binding to a common site that goes beyond simple molecular mimicry. The model presented here is consistent with both available biochemical evidence and known structure-activity relationships for these two classes of natural compounds and synthetic analogues and provides fertile ground for future research.

The eukaryotic translation elongation factor eEF1A2 induces neoplastic properties and mediates tumorigenic effects of ZNF217 in precursor cells of human ovarian carcinomas

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sun, Yu; Wong, Nicholas; Guan, Yinghui

2008-04-25

Ovarian epithelial carcinomas (OEC) frequently exhibit amplifications at the 20q13 locus which is the site of several oncogenes, including the eukaryotic elongation factor EEF1A2 and the transcription factor ZNF217. We reported previously that overexpressed ZNF217 induces neoplastic characteristics in precursor cells of OEC. Unexpectedly, ZNF217, which is a transcriptional repressor, enhanced expression of eEF1A2. In this study, array comparative genomic hybridization, single nucleotide polymorphism and Affymetrix analysis of ZNF217-overexpressing cell lines confirmed consistently increased expression of eEF1A2 but not of other oncogenes, and revealed early changes in EEF1A2 gene copy numbers and increased expression at crisis during immortalization. We definedmore » the influence of eEF1A2 overexpression on immortalized ovarian surface epithelial cells, and investigated interrelationships between effects of ZNF217 and eEF1A2 on cellular phenotypes. Lentivirally induced eEF1A2 overexpression caused delayed crisis, apoptosis resistance and increases in serum-independence, saturation densities, and anchorage independence. siRNA to eEF1A2 reversed apoptosis resistance and reduced anchorage independence in eEF1A2-overexpressing lines. Remarkably, siRNA to eEF1A2 was equally efficient in inhibiting both anchorage independence and resistance to apoptosis conferred by ZNF217 overexpression. Our data define neoplastic properties that are caused by eEF1A2 in nontumorigenic ovarian cancer precursor cells, and suggest that eEF1A2 plays a role in mediating ZNF217-induced neoplastic progression.« less

Inhibition of IκB Kinase-Nuclear Factor-κB Signaling Pathway by 3,5-Bis(2-flurobenzylidene)piperidin-4-one (EF24), a Novel Monoketone Analog of Curcumin*

PubMed Central

Kasinski, Andrea L.; Du, Yuhong; Thomas, Shala L.; Zhao, Jing; Sun, Shi-Yong; Khuri, Fadlo R.; Wang, Cun-Yu; Shoji, Mamoru; Sun, Aiming; Snyder, James P.; Liotta, Dennis; Fu, Haian

2009-01-01

The nuclear factor-κB (NF-κB) signaling pathway has been targeted for therapeutic applications in a variety of human diseases, includuing cancer. Many naturally occurring substances, including curcumin, have been investigated for their actions on the NF-κB pathway because of their significant therapeutic potential and safety profile. A synthetic monoketone compound termed 3,5-bis(2-flurobenzylidene)piperidin-4-one (EF24) was developed from curcumin and exhibited potent anticancer activity. Here, we report a mechanism by which EF24 potently suppresses the NF-κB signaling pathway through direct action on IκB kinase (IKK). We demonstrate that 1) EF24 induces death of lung, breast, ovarian, and cervical cancer cells, with a potency about 10 times higher than that of curcumin; 2) EF24 rapidly blocks the nuclear translocation of NF-κB, with an IC50 value of 1.3 μM compared with curcumin, with an IC50 value of 13 μM; 3) EF24 effectively inhibits tumor necrosis factor (TNF)-α-induced IκB phosphorylation and degradation, suggesting a role of this compound in targeting IKK; and 4) EF24 indeed directly inhibits the catalytic activity of IKK in an in vitro-reconstituted system. Our study identifies IKK as an effective target for EF24 and provides a molecular explanation for a superior activity of EF24 over curcumin. The effective inhibition of TNF-α-induced NF-κB signaling by EF24 extends the therapeutic application of EF24 to other NF-κB-dependent diseases, including inflammatory diseases such as rheumatoid arthritis. PMID:18577686

Inhibition of IkappaB kinase-nuclear factor-kappaB signaling pathway by 3,5-bis(2-flurobenzylidene)piperidin-4-one (EF24), a novel monoketone analog of curcumin.

PubMed

Kasinski, Andrea L; Du, Yuhong; Thomas, Shala L; Zhao, Jing; Sun, Shi-Yong; Khuri, Fadlo R; Wang, Cun-Yu; Shoji, Mamoru; Sun, Aiming; Snyder, James P; Liotta, Dennis; Fu, Haian

2008-09-01

The nuclear factor-kappaB (NF-kappaB) signaling pathway has been targeted for therapeutic applications in a variety of human diseases, includuing cancer. Many naturally occurring substances, including curcumin, have been investigated for their actions on the NF-kappaB pathway because of their significant therapeutic potential and safety profile. A synthetic monoketone compound termed 3,5-bis(2-flurobenzylidene)piperidin-4-one (EF24) was developed from curcumin and exhibited potent anticancer activity. Here, we report a mechanism by which EF24 potently suppresses the NF-kappaB signaling pathway through direct action on IkappaB kinase (IKK). We demonstrate that 1) EF24 induces death of lung, breast, ovarian, and cervical cancer cells, with a potency about 10 times higher than that of curcumin; 2) EF24 rapidly blocks the nuclear translocation of NF-kappaB, with an IC(50) value of 1.3 microM compared with curcumin, with an IC(50) value of 13 microM; 3) EF24 effectively inhibits tumor necrosis factor (TNF)-alpha-induced IkappaB phosphorylation and degradation, suggesting a role of this compound in targeting IKK; and 4) EF24 indeed directly inhibits the catalytic activity of IKK in an in vitro-reconstituted system. Our study identifies IKK as an effective target for EF24 and provides a molecular explanation for a superior activity of EF24 over curcumin. The effective inhibition of TNF-alpha-induced NF-kappaB signaling by EF24 extends the therapeutic application of EF24 to other NF-kappaB-dependent diseases, including inflammatory diseases such as rheumatoid arthritis.

Measuring Executive Function in Early Childhood: A Case for Formative Measurement

PubMed Central

Willoughby, Michael T.; Blair, Clancy B.

2015-01-01

This study tested whether individual executive function (EF) tasks were better characterized as formative (causal) or reflective (effect) indicators of the latent construct of EF. EF data that were collected as part of the Family Life Project (FLP), a prospective longitudinal study of families who were recruited at the birth of a new child (N = 1292), when children were 3, 4, and 5 years old. Vanishing tetrad tests were used to test the relative fit of models in which EF tasks were used as either formative or reflective indicators of the latent construct of EF in the prediction of intellectual ability (at age 3), attention deficit/hyperactivity disorder symptoms (at ages 3–5 years), and academic achievement (at kindergarten). Results consistently indicated that EF tasks were better represented as formative indicators of the latent construct of EF. Next, individual tasks were combined to form an overall measure of EF ability in ways generally consistent with formative (i.e., creating a composite mean score) and reflective (i.e., creating an EF factor score) measurement. The test-retest reliability and developmental trajectories of EF differed substantially, depending on which overall measure of EF ability was used. In general, the across-time stability of EF was markedly higher, perhaps implausibly high, when represented as a factor score versus composite score. Results are discussed with respect to the ways in which the statistical representation of EF tasks can exert a large impact on inferences regarding the developmental causes, course, and consequences of EF. More generally, these results exemplify how some psychological constructs may not conform to conventional measurement wisdom. PMID:26121388

Peptide probes reveal a hydrophobic steric ratchet in the anthrax toxin protective antigen translocase

PubMed Central

Colby, Jennifer M.; Krantz, Bryan A.

2015-01-01

Anthrax toxin is a tripartite virulence factor produced by Bacillus anthracis during infection. Under acidic endosomal pH conditions, the toxin's protective antigen (PA) component forms a transmembrane channel in host cells. The PA channel then translocates its two enzyme components, lethal factor (LF) and edema factor (EF), into the host cytosol under the proton motive force (PMF). Protein translocation under a PMF is catalyzed by a series of nonspecific polypeptide binding sites, called clamps. A 10-residue guest/host peptide model system, KKKKKXXSXX, was used to functionally probe polypeptide-clamp interactions within wild-type PA channels. The guest residues were Thr, Ala, Leu, Phe, Tyr, and Trp. In steady-state translocation experiments, the channel blocked most tightly with peptides that had increasing amounts of nonpolar surface area. Cooperative peptide binding was observed in the Trp-containing peptide sequence but not the other tested sequences. Trp substitutions into a flexible, uncharged linker between LF amino-terminal domain and diphtheria toxin A chain expedited translocation. Therefore, peptide clamp sites in translocase channels can sense large steric features (like tryptophan) in peptides; and while these steric interactions may make a peptide translocate poorly, in the context of folded domains they can make the protein translocate more rapidly presumably via a hydrophobic steric ratchet mechanism. PMID:26363343

Study protocol, randomized controlled trial: reducing symptom burden in patients with heart failure with preserved ejection fraction using ubiquinol and/or D-ribose.

PubMed

Pierce, Janet D; Mahoney, Diane E; Hiebert, John B; Thimmesch, Amanda R; Diaz, Francisco J; Smith, Carol; Shen, Qiuhua; Mudaranthakam, Dinesh Pal; Clancy, Richard L

2018-04-02

Heart failure (HF), the leading cause of morbidity and mortality in the US, affects 6.6 million adults with an estimated additional 3 million people by 2030. More than 50% of HF patients have heart failure with preserved left ventricular ejection fraction (HFpEF). These patients have impaired cardiac muscle relaxation and diastolic filling, which investigators have associated with cellular energetic impairment. Patients with HFpEF experience symptoms of: (1) fatigue; (2) shortness of breath; and (3) swelling (edema) of the lower extremities. However, current HF guidelines offer no effective treatment to address these underlying pathophysiologic mechanisms. Thus, we propose a biobehavioral symptom science study using ubiquinol and D-ribose (therapeutic interventions) to target mitochondrial bioenergetics to reduce the complex symptoms experienced by patients with HFpEF. Using a randomized, double-blind, placebo-controlled design, the overall objective is to determine if administering ubiquinol and/or D-ribose to HFpEF patients for 12 weeks would decrease the severity of their complex symptoms and improve their cardiac function. The measures used to assess patients' perceptions of their health status and level of vigor (energy) will be the Kansas City Cardiomyopathy Questionnaire (KCCQ) and Vigor subscale of the Profile of Mood States. The 6-min walk test will be used to test exercise tolerance. Left ventricular diastolic function will be assessed using innovative advanced echocardiography software called speckle tracking. We will measure B-type natriuretic peptides (secreted from ventricles in HF) and lactate/ATP ratio (measure of cellular energetics). Ubiquinol (active form of Coenzyme Q10) and D-ribose are two potential treatments that can positively affect cellular energetic impairment, the major underlying mechanism of HFpEF. Ubiquinol, the reduced form of CoQ10, is more effective in adults over the age of 50. In patients with HFpEF, mitochondrial deficiency of ubiquinol results in decreased adenosine triphosphate (ATP) synthesis and reduced scavenging of reactive oxygen species. D-ribose is a substrate required for ATP synthesis and when administered has been shown to improve impaired myocardial bioenergetics. Therefore, if the biological underpinning of deficient mitochondrial ATP in HFpEF is not addressed, patients will suffer major symptoms including lack of energy, fatigue, exertional dyspnea, and exercise intolerance. ClinicalTrials.gov Identifier: NCT03133793 ; Data of Registration: April 28, 2017.

The role of arterial hypertension in development heart failure with preserved ejection fraction: just a risk factor or something more?

PubMed

Tadic, Marijana; Cuspidi, Cesare; Frydas, Athanasios; Grassi, Guido

2018-04-04

Heart failure with preserved ejection fraction (HFpEF) is an entity that still raises many questions. The agreement about definition, pathophysiology, and therapeutic approach is still missing. Arterial hypertension is present in majority of patients with HFpEF, and it is still not clear if it represent a risk factor or "sine qua non" condition for HFpEF development. The underlying mechanisms of hypertension and HFpEF involve the same biohumoral systems: renin-angiotensin-aldosterone, sympathetic nervous system, and oxidative stress. However, not all hypertensive patients have HFpEF. The predisposition of some hypertensive patients to develop HFpEF needs to be resolved. Large randomized controlled trials did not prove the usefulness of renin-angiotensin-aldosterone inhibitors, diuretics, calcium channel blockers, and beta-blockers in HFpEF patients. The majority of studies did not succeed to demonstrate the reduction of cardiovascular and all-cause mortality in HFpEF individuals. One of the major limitations in these investigations was the inconsistency of HFpEF definition, which mainly refers to left ventricular ejection fraction (LVEF) cut-off that ranged from 40 to 50% in different studies. This review article provides the available data about pathophysiology and mechanisms that connect hypertension and HFpEF, investigations and therapy used in both conditions.

Translation Control of Swarming Proficiency in Bacillus subtilis by 5-Amino-pentanolylated Elongation Factor P.

PubMed

Rajkovic, Andrei; Hummels, Katherine R; Witzky, Anne; Erickson, Sarah; Gafken, Philip R; Whitelegge, Julian P; Faull, Kym F; Kearns, Daniel B; Ibba, Michael

2016-05-20

Elongation factor P (EF-P) accelerates diprolyl synthesis and requires a posttranslational modification to maintain proteostasis. Two phylogenetically distinct EF-P modification pathways have been described and are encoded in the majority of Gram-negative bacteria, but neither is present in Gram-positive bacteria. Prior work suggested that the EF-P-encoding gene (efp) primarily supports Bacillus subtilis swarming differentiation, whereas EF-P in Gram-negative bacteria has a more global housekeeping role, prompting our investigation to determine whether EF-P is modified and how it impacts gene expression in motile cells. We identified a 5-aminopentanol moiety attached to Lys(32) of B. subtilis EF-P that is required for swarming motility. A fluorescent in vivo B. subtilis reporter system identified peptide motifs whose efficient synthesis was most dependent on 5-aminopentanol EF-P. Examination of the B. subtilis genome sequence showed that these EF-P-dependent peptide motifs were represented in flagellar genes. Taken together, these data show that, in B. subtilis, a previously uncharacterized posttranslational modification of EF-P can modulate the synthesis of specific diprolyl motifs present in proteins required for swarming motility. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Eukaryotic polypeptide elongation system and its sensitivity to the inhibitory substances of plant origin.

PubMed

Gałasiński, W

1996-05-01

The structural and functional characteristics of the elongation system (ribosomes and elongation factors) are presented. The immunochemical and diagnostic meaning of the ribosome investigations is considered. Evidence of the participation of ribosomes in the first step of protein glycosylation is presented. The heterogeneous elongation factor eEF-1, isolated from Guerin epithelioma, can be separated into three fractions: one of them functionally corresponds to EF-1 alpha, the second on to EF-1 beta gamma, and the third is an unidentified, active aggregate named EF-1B, which contains the subunit forms EF-1 alpha and EF-1 beta gamma, and other polypeptides showing protein kinase activity. The aggregate EF-1B can be autophosphorylated, while the subunit forms EF-1 alpha and EF-1 beta gamma can neither become autophosphorylated nor phosphorylate other polypeptides. The subunit form EF-beta gamma consists from two polypeptides of 32 and 51 kDa, corresponding to other eukaryotic beta and gamma polypeptides, respectively. EF-1 beta gamma is thermostable and protects against thermal inactivation of EF-1 alpha in the EF-1 alpha-EF-1 beta gamma complex. Pure eEF-2 preparations isolated from normal and neoplastic tissues show different structural features. The existence of eEF-2 in multiple forms, differing in molecular mass, have been found. The eEF-2 with molecular weight of about 100 kDa can be phosphorylated, while eEF-2 of about 65 kDa was not phosphorylated by protein kinase eEF-2. The phosphorylated eEF-2 lost its activity, and this effect was reversed by dephosphorylation. The eEF-2 (65 kDa) was isolated from the active polyribosomes, and it may directly participate in the translocation step of the peptide elongation. It was noted that the components of elongation system can be inhibited, in separate steps, by the substances isolated from various sources of plant origin. Alkaloids emetine and cepheline, cardiac remedy digoxin, saponin glycoside, and its aglycon directly inactivated ribosomes. Quercetin inhibited eEF-1 activity by directly influencing its subunit form EF-1 alpha. eEF-2 was shown to be a target site of the inhibitory action of the glycoside isolated from Melissa officinalis leaves.

Including the spatial variability of metal speciation in the effect factor in life cycle impact assessment: Limits of the equilibrium partitioning method.

PubMed

Tromson, Clara; Bulle, Cécile; Deschênes, Louise

2017-03-01

In life cycle assessment (LCA), the potential terrestrial ecotoxicity effect of metals, calculated as the effect factor (EF), is usually extrapolated from aquatic ecotoxicological data using the equilibrium partitioning method (EqP) as it is more readily available than terrestrial data. However, when following the AMI recommendations (i.e. with at least enough species that represents three different phyla), there are not enough terrestrial data for which soil properties or metal speciation during ecotoxicological testing are specified to account for the influence of soil property variations on metal speciation when using this approach. Alternatively, the TBLM (Terrestrial Biotic Ligand Model) has been used to determine an EF that accounts for speciation, but is not available for metals; hence it cannot be consistently applied to metals in an LCA context. This paper proposes an approach to include metal speciation by regionalizing the EqP method for Cu, Ni and Zn with a geochemical speciation model (the Windermere Humic Aqueous Model 7.0), for 5213 soils selected from the Harmonized World Soil Database. Results obtained by this approach (EF EqP regionalized ) are compared to the EFs calculated with the conventional EqP method, to the EFs based on available terrestrial data and to the EFs calculated with the TBLM (EF TBLM regionalized ) when available. The spatial variability contribution of the EF to the overall spatial variability of the characterization factor (CF) has been analyzed. It was found that the EFs EqP regionalized show a significant spatial variability. The EFs calculated with the two non-regionalized methods (EqP and terrestrial data) fall within the range of the EFs EqP regionalized . The EFs TBLM regionalized cover a larger range of values than the EFs EqP regionalized but the two methods are not correlated. This paper highlights the importance of including speciation into the terrestrial EF and shows that using the regionalized EqP approach is not an acceptable proxy for terrestrial ecotoxicological data even if it can be applied to all metals. Copyright © 2016. Published by Elsevier B.V.

Interaction of Leptospira Elongation Factor Tu with Plasminogen and Complement Factor H: A Metabolic Leptospiral Protein with Moonlighting Activities

PubMed Central

Abe, Cecília M.; Monaris, Denize; Morais, Zenaide M.; Souza, Gisele O.; Vasconcellos, Sílvio A.; Isaac, Lourdes; Abreu, Patrícia A. E.; Barbosa, Angela S.

2013-01-01

The elongation factor Tu (EF-Tu), an abundant bacterial protein involved in protein synthesis, has been shown to display moonlighting activities. Known to perform more than one function at different times or in different places, it is found in several subcellular locations in a single organism, and may serve as a virulence factor in a range of important human pathogens. Here we demonstrate that Leptospira EF-Tu is surface-exposed and performs additional roles as a cell-surface receptor for host plasma proteins. It binds plasminogen in a dose-dependent manner, and lysine residues are critical for this interaction. Bound plasminogen is converted to active plasmin, which, in turn, is able to cleave the natural substrates C3b and fibrinogen. Leptospira EF-Tu also acquires the complement regulator Factor H (FH). FH bound to immobilized EF-Tu displays cofactor activity, mediating C3b degradation by Factor I (FI). In this manner, EF-Tu may contribute to leptospiral tissue invasion and complement inactivation. To our knowledge, this is the first description of a leptospiral protein exhibiting moonlighting activities. PMID:24312361

Isolation and characterization of elongation factor EF-2 from Guerin tumour.

PubMed

Jabłonowska, K; Kopacz-Jodczyk, T; Niedźwiecka, J; Gałasiński, W

1983-01-01

A homogeneous preparation of EF-2 from Guerin tumour cells was obtained. Its Mr (68 000), pI (6.5), optimum pH (7.0) and amino acid composition are very close to those of rat liver elongation factor. EF-2 from Guerin tumour cells is active in the heterologous liver - tumour system, although half as effective as in the homologous system.

The Association between Parenting Behavior and Executive Functioning in Children and Young Adolescents

PubMed Central

Sosic-Vasic, Zrinka; Kröner, Julia; Schneider, Sibylle; Vasic, Nenad; Spitzer, Manfred; Streb, Judith

2017-01-01

Executive functioning (EF) is associated with various aspects of school achievement and cognitive development in children and adolescents. There has been substantial research investigating associations between EF and other factors in young children, such as support processes and parenting, but less research has been conducted about external factors relating to EF in older children and adolescents. Therefore, the present study investigates one possible factor that could correlate with EF in school-age children and adolescents: parenting behavior. The cross-sectional study design gathered data from 169 children in primary schools, middle-schools, and Gymnasien, and their corresponding parents. All children underwent a standardized task to measure EF, the computer-based Erikson Flanker task, which evaluates EF as a function of error rates and response time. A self-report questionnaire was used to assess parenting behavior. Multilevel analysis was implemented to test the effects of parenting behavior on EF in school-age children. The results show significant associations between various parenting behaviors and children's EF: High scores on parental involvement or parental responsibility are associated with low error rates on the Erikson Flanker task, whereas high parental scores on inconsistent discipline are associated with high error rates. These correlations between parenting behavior and EF remained significant despite controlling for child age, maternal education, family income, and baseline performance (i.e., congruent trials on the Erikson Flanker task). No associations were found between parental behavior and reaction time on the Erikson Flanker task. These results indicate the important association between parenting behaviors and EF skills in school-age children, and foster the necessity to inform parents about ways in which they can optimally support their children's cognitive development. PMID:28424644

Executive Functions and Attachment Relationships in Children With ADHD: Links to Externalizing/Internalizing Problems, Social Skills, and Negative Mood Regulation.

PubMed

Al-Yagon, Michal; Forte, Dovrat; Avrahami, Lital

2017-09-01

Theoretical models suggest multiple underlying pathways for ADHD and multiple risk factors' co-occurrence as impairing this population's affective, interpersonal, and behavioral adjustment. After comparing groups' executive functioning (EF) difficulties and attachment security with each parent, this study primarily aimed to examine four risk factors (ADHD, child-father attachment, child-mother attachment, EF) as possibly explaining children's socioemotional/behavioral measures (externalizing/internalizing behavior, social skills, negative mood regulation). Participants were 100 children in Grades 5-6 (ages 11-12 years; M=11.45 years, SD=.50): 50 with formally diagnosed ADHD, and 50 with typical development (TD). Instruments were children's self-report measures and teachers' evaluation. Significant group differences emerged on all EF measures and attachment relationships, and most socioemotional/behavioral measures. Findings demonstrated the significant contribution of children's ADHD, parental attachments, and, partially, EF difficulties in explaining children's socioemotional/behavioral adjustment. Children with ADHD, compared to children with TD, reported significantly larger EF deficits and a significantly higher incidence of insecure attachment to the father as well as a lower sense of trust and closeness to the mother. Outcomes highlighted the role of children's four risk factors (ADHD, child-father attachment, child-mother attachment, EF) in explaining their socioemotional/behavioral adjustment. The EF deficits contributed only to intrapersonal maladjustment.

In-Plume Emission Test Stand 2: emission factors for 10- to 100-kW U.S. military generators.

PubMed

Zhu, Dongzi; Nussbaum, Nicholas J; Kuhns, Hampden D; Chang, M-C Oliver; Sodeman, David; Uppapalli, Sebastian; Moosmüller, Hans; Chow, Judith C; Watson, John G

2009-12-01

Although emissions of air pollutants from some military tactical equipment are not subject to the emissions standards, local communities near military bases must conform to the National Ambient Air Quality Standards. Military diesel generators are widely used in training. A portable in-plume system was used to measure fuel-based emission factors (EFs) for particulate matter (PM), carbon monoxide (CO), nitrogen oxides (NOx), and hydrocarbons (HCs) for 30-, 60-, and 100-kW generators at five load levels and for cold starts. It was found that EFs depend on multiple parameters including engine size, engine load, unit age, and total running hours. The average CO EF of generators tested was 5% lower, and the average NOx EF was 63% lower than AP-42 estimates; average PM EF was 80% less than the AP-42 estimates. A 2002 model-year 60-kW engine produced 25% less PM than a 1995 engine of the same family with similar running hours. CO EFs decrease with increasing engine load, NOx EFs increase up to mid-loads and decrease slightly at high loads, PM EFs increase with loads for 30- and 60-kW engines. CO and PM have higher EFs and NOx has a lower EF during cold starts than during hot-stabilized operation. PM chemical source profiles were also examined.

Executive Dysfunction Among Children With Reading Comprehension Deficits

PubMed Central

Locascio, Gianna; Mahone, E. Mark; Eason, Sarah H.; Cutting, Laurie E.

2010-01-01

Emerging research supports the contribution of executive function (EF) to reading comprehension; however, a unique pattern has not been established for children who demonstrate comprehension difficulties despite average word recognition ability (specific reading comprehension deficit; S-RCD). To identify particular EF components on which children with S-RCD struggle, a range of EF skills was compared among 86 children, ages 10 to 14, grouped by word reading and comprehension abilities: 24 average readers, 44 with word recognition deficits (WRD), and 18 S-RCD. An exploratory principal components analysis of EF tests identified three latent factors, used in subsequent group comparisons: Planning/Spatial Working Memory, Verbal Working Memory, and Response Inhibition. The WRD group exhibited deficits (relative to controls) on Verbal Working Memory and Inhibition factors; S-RCD children performed more poorly than controls on the Planning factor. Further analyses suggested the WRD group’s poor performance on EF factors was a by-product of core deficits linked to WRD (after controlling for phonological processing, this group no longer showed EF deficits). In contrast, the S-RCD group’s poor performance on the planning component remained significant after controlling for phonological processing. Findings suggest reading comprehension difficulties are linked to executive dysfunction; in particular, poor strategic planning/organizing may lead to reading comprehension problems. PMID:20375294

Executive dysfunction among children with reading comprehension deficits.

PubMed

Locascio, Gianna; Mahone, E Mark; Eason, Sarah H; Cutting, Laurie E

2010-01-01

Emerging research supports the contribution of executive function (EF) to reading comprehension; however, a unique pattern has not been established for children who demonstrate comprehension difficulties despite average word recognition ability (specific reading comprehension deficit; S-RCD). To identify particular EF components on which children with S-RCD struggle, a range of EF skills was compared among 86 children, ages 10 to 14, grouped by word reading and comprehension abilities: 24 average readers, 44 with word recognition deficits (WRD), and 18 S-RCD. An exploratory principal components analysis of EF tests identified three latent factors, used in subsequent group comparisons: Planning/ Spatial Working Memory, Verbal Working Memory, and Response Inhibition. The WRD group exhibited deficits (relative to controls) on Verbal Working Memory and Inhibition factors; S-RCD children performed more poorly than controls on the Planning factor. Further analyses suggested the WRD group's poor performance on EF factors was a by-product of core deficits linked to WRD (after controlling for phonological processing, this group no longer showed EF deficits). In contrast, the S-RCD group's poor performance on the planning component remained significant after controlling for phonological processing. Findings suggest reading comprehension difficulties are linked to executive dysfunction; in particular, poor strategic planning/organizing may lead to reading comprehension problems.

The translation elongation factor eEF1A1 couples transcription to translation during heat shock response

PubMed Central

Vera, Maria; Pani, Bibhusita; Griffiths, Lowri A; Muchardt, Christian; Abbott, Catherine M; Singer, Robert H; Nudler, Evgeny

2014-01-01

Translation elongation factor eEF1A has a well-defined role in protein synthesis. In this study, we demonstrate a new role for eEF1A: it participates in the entire process of the heat shock response (HSR) in mammalian cells from transcription through translation. Upon stress, isoform 1 of eEF1A rapidly activates transcription of HSP70 by recruiting the master regulator HSF1 to its promoter. eEF1A1 then associates with elongating RNA polymerase II and the 3′UTR of HSP70 mRNA, stabilizing it and facilitating its transport from the nucleus to active ribosomes. eEF1A1-depleted cells exhibit severely impaired HSR and compromised thermotolerance. In contrast, tissue-specific isoform 2 of eEF1A does not support HSR. By adjusting transcriptional yield to translational needs, eEF1A1 renders HSR rapid, robust, and highly selective; thus, representing an attractive therapeutic target for numerous conditions associated with disrupted protein homeostasis, ranging from neurodegeneration to cancer. DOI: http://dx.doi.org/10.7554/eLife.03164.001 PMID:25233275

Idiopathic remitting seronegative symmetrical synovitis with pitting edema syndrome associated with bilateral pleural and pericardial effusions: a case report.

PubMed

Yanamoto, Shozaburo; Fukae, Jiro; Fukiyama, Yurie; Fujioka, Shinsuke; Ouma, Shinji; Tsuboi, Yoshio

2016-07-20

Remitting seronegative symmetrical synovitis with pitting edema syndrome is characterized by symmetrical synovitis with pitting edema in the dorsum of the hands or feet. Most cases of remitting seronegative symmetrical synovitis with pitting edema syndrome are idiopathic, but some are secondary to malignancy, autoimmune disease, or neurodegenerative disorders. Pleural and pericardial effusions are unusual complications in idiopathic remitting seronegative symmetrical synovitis with pitting edema syndrome. A 74-year-old Japanese woman presented to our hospital with arthralgia and pitting edema in her feet. She had pain in multiple joints, peripheral edema, and a markedly elevated erythrocyte sedimentation rate. Enhanced computed tomography and laboratory data showed no evidence of malignancy. These findings suggested that she had idiopathic remitting seronegative symmetrical synovitis with pitting edema syndrome. She also developed respiratory distress because of bilateral pleural and pericardial effusions. Laboratory data showed that serum vascular endothelial growth factor and interleukin-6 were significantly elevated. After administration of steroids, her pleural and pericardial effusions decreased and finally disappeared. Furthermore, vascular endothelial growth factor and interleukin-6 decreased when the pleural and pericardial effusions disappeared. Here we report the case of a patient with idiopathic remitting seronegative symmetrical synovitis with pitting edema syndrome associated with life-threatening complications, including bilateral pleural and pericardial effusions during the course of the illness, which led to respiratory failure and atrial fibrillation. Elevated vascular endothelial growth factor and interleukin-6 may be associated with the cause of pleural and pericardial effusions in idiopathic remitting seronegative symmetrical synovitis with pitting edema syndrome.

Purification and characterization of the protein kinase eEF-2 isolated from rat liver cells.

PubMed

Gajko, A; Gałasiński, W; Gindzieński, A

1994-01-01

The elongation factor 2 (eEF-2) protein kinase was isolated from rat liver cells, purified and partly characterized. It was found that the enzyme exists in an inactive form in the homogenate of rat liver. The active fraction of kinase eEF-2 was obtained after removal of the inhibitory substance by hydroxyapatite column chromatography. The purified enzyme is an electrophoretically homogeneous protein with relative molecular mass of approximately 90,000 and isoelectric point, pI = 5.9. The enzyme specifically phosphorylates the elongation factor eEF-2 in the presence of calmodulin and Ca2+.

Phosphorylation decelerates conformational dynamics in bacterial translation elongation factors

PubMed Central

Talavera, Ariel; Hendrix, Jelle; Versées, Wim; Jurėnas, Dukas; Van Nerom, Katleen; Vandenberk, Niels; Singh, Ranjan Kumar; Konijnenberg, Albert; De Gieter, Steven; Castro-Roa, Daniel; Barth, Anders; De Greve, Henri; Sobott, Frank; Hofkens, Johan; Zenkin, Nikolay; Loris, Remy; Garcia-Pino, Abel

2018-01-01

Bacterial protein synthesis is intricately connected to metabolic rate. One of the ways in which bacteria respond to environmental stress is through posttranslational modifications of translation factors. Translation elongation factor Tu (EF-Tu) is methylated and phosphorylated in response to nutrient starvation upon entering stationary phase, and its phosphorylation is a crucial step in the pathway toward sporulation. We analyze how phosphorylation leads to inactivation of Escherichia coli EF-Tu. We provide structural and biophysical evidence that phosphorylation of EF-Tu at T382 acts as an efficient switch that turns off protein synthesis by decoupling nucleotide binding from the EF-Tu conformational cycle. Direct modifications of the EF-Tu switch I region or modifications in other regions stabilizing the β-hairpin state of switch I result in an effective allosteric trap that restricts the normal dynamics of EF-Tu and enables the evasion of the control exerted by nucleotides on G proteins. These results highlight stabilization of a phosphorylation-induced conformational trap as an essential mechanism for phosphoregulation of bacterial translation and metabolism. We propose that this mechanism may lead to the multisite phosphorylation state observed during dormancy and stationary phase. PMID:29546243

EF24 suppresses maturation and inflammatory response in dendritic cells.

PubMed

Vilekar, Prachi; Awasthi, Shanjana; Natarajan, Aravindan; Anant, Shrikant; Awasthi, Vibhudutta

2012-07-01

Synthetic curcuminoid EF24 was studied for its effect on the maturation and inflammatory response in murine bone marrow derived immortalized JAWS II dendritic cells (DCs). EF24 reduced the expression of LPS-induced MHC class II, CD80 and CD86 molecules. It also abrogated the appearance of dendrites, a typical characteristic of mature DCs. These effects were accompanied by the inhibition of LPS-induced activation of transcription factor nuclear factor kappa-light-chain enhancer of activated B cells (NF-κB). Simultaneous reduction of pro-inflammatory cytokines [tumor necrosis factor (TNF)-α, IL-6] both at the mRNA and secreted levels was also observed. To investigate the dependency of LPS effects on MyD88 adaptor protein, we transfected JAWS II DCs with dominant negative MyD88 plasmid construct (MyD88-DN). EF24 reduced NF-κB activity and TNF-α secretion in a MyD88-dependent manner. These results suggest that EF24 modulates DCs by suppressing their maturation and reducing the secretion of inflammatory cytokines. Further, it appears that EF24 acts at or upstream of MyD88 in the LPS-TLR4/MyD88/NF-κB pathway.

EF24 suppresses maturation and inflammatory response in dendritic cells

PubMed Central

Vilekar, Prachi; Natarajan, Aravindan; Anant, Shrikant

2012-01-01

Synthetic curcuminoid EF24 was studied for its effect on the maturation and inflammatory response in murine bone marrow derived immortalized JAWS II dendritic cells (DCs). EF24 reduced the expression of LPS-induced MHC class II, CD80 and CD86 molecules. It also abrogated the appearance of dendrites, a typical characteristic of mature DCs. These effects were accompanied by the inhibition of LPS-induced activation of transcription factor nuclear factor kappa-light-chain enhancer of activated B cells (NF-κB). Simultaneous reduction of pro-inflammatory cytokines [tumor necrosis factor (TNF)-α, IL-6] both at the mRNA and secreted levels was also observed. To investigate the dependency of LPS effects on MyD88 adaptor protein, we transfected JAWS II DCs with dominant negative MyD88 plasmid construct (MyD88-DN). EF24 reduced NF-κB activity and TNF-α secretion in a MyD88-dependent manner. These results suggest that EF24 modulates DCs by suppressing their maturation and reducing the secretion of inflammatory cytokines. Further, it appears that EF24 acts at or upstream of MyD88 in the LPS-TLR4/MyD88/NF-κB pathway. PMID:22378503

Interaction of plant chimeric calcium/calmodulin-dependent protein kinase with a homolog of eukaryotic elongation factor-1alpha

NASA Technical Reports Server (NTRS)

Wang, W.; Poovaiah, B. W.

1999-01-01

A chimeric Ca2+/calmodulin-dependent protein kinase (CCaMK) was previously cloned and characterized in this laboratory. To investigate the biological functions of CCaMK, the yeast two-hybrid system was used to isolate genes encoding proteins that interact with CCaMK. One of the cDNA clones obtained from the screening (LlEF-1alpha1) has high similarity with the eukaryotic elongation factor-1alpha (EF-1alpha). CCaMK phosphorylated LlEF-1alpha1 in a Ca2+/calmodulin-dependent manner. The phosphorylation site for CCaMK (Thr-257) was identified by site-directed mutagenesis. Interestingly, Thr-257 is located in the putative tRNA-binding region of LlEF-1alpha1. An isoform of Ca2+-dependent protein kinase (CDPK) phosphorylated multiple sites of LlEF-1alpha1 in a Ca2+-dependent but calmodulin-independent manner. Unlike CDPK, CCaMK phosphorylated only one site, and this site is different from CDPK phosphorylation sites. This suggests that the phosphorylation of EF-1alpha by these two kinases may have different functional significance. Although the phosphorylation of LlEF-1alpha1 by CCaMK is Ca2+/calmodulin-dependent, in vitro binding assays revealed that CCaMK binds to LlEF-1alpha1 in a Ca2+-independent manner. This was further substantiated by coimmunoprecipitation of CCaMK and EF-1alpha using the protein extract from lily anthers. Dissociation of CCaMK from EF-1alpha by Ca2+ and phosphorylation of EF-1alpha by CCaMK in a Ca2+/calmodulin-dependent manner suggests that these interactions may play a role in regulating the biological functions of EF-1alpha.

Effect of isothermal dilution on emission factors of organic carbon and n-alkanes in the particle and gas phases of diesel exhaust

NASA Astrophysics Data System (ADS)

Fujitani, Yuji; Saitoh, Katsumi; Fushimi, Akihiro; Takahashi, Katsuyuki; Hasegawa, Shuich; Tanabe, Kiyoshi; Kobayashi, Shinji; Furuyama, Akiko; Hirano, Seishiro; Takami, Akinori

2012-11-01

To investigate the effect of isothermal dilution (30 °C) on emission factors (EFs) of semivolatile and nonvolatile compounds of heavy-duty diesel exhaust, we measured EFs for particulate matter (PM), organic carbon (OC), and elemental carbon (EC) in the particle phase, and EFs for n-alkanes in both the particle phase and the gas phase of exhaust produced under high-idle engine operating conditions at dilution ratios (DRs) ranging from 8 to 1027. The EC EFs did not vary with DR, whereas the OC EFs in the particle phase determined at DR = 1027 were 13% of the EFs determined at DR = 8, owing to evaporation of organic compounds. Using partitioning theory and n-alkane EFs measured at DR = 14 and 238, we calculated the distributions of compounds between the particle and gas phases at DR = 1760, which corresponds to the DR for tailpipe emissions as they move from the tailpipe to the roadside atmosphere. The gas-phase EF of a compound with a vapor pressure of 10-7 Pa was 0.01 μg kg-1-fuel at DR = 14, and this value is 1/330 the value derived at DR = 1760. Our results suggest that the EFs of high-volatility compounds in the particle phase will be overestimated and that the EFs of low-volatility compounds in the gas phase will be underestimated if the estimates are derived from data obtained at the low DRs and they are applied to the real world. Therefore, extrapolation from EFs derived at low DR values to EFs at atmospherically relevant DRs will be a source of error in predictions of the concentrations of particulate matter and gas-phase precursors to secondary organic aerosols in air quality models.

Trastuzumab-induced cardiotoxicity and its risk factors in real-world setting of breast cancer patients.

PubMed

Moilanen, Tiina; Jokimäki, Anna; Tenhunen, Olli; Koivunen, Jussi P

2018-06-05

Cardiotoxicity is the most important side effect of trastuzumab treatment. Heart function monitoring is recommended during the treatment which has led to growing use of resources. The aim of this retrospective study was to determine the frequency and timing of trastuzumab cardiotoxicity and its risk factors in real-world setting. Single institute, retrospective collection of data on HER2+ breast cancer patients (n = 246) was carried out through a pharmacy search for patients who had received trastuzumab in 2006-2014. Clinical and pathological factors, treatment history, EF measurements, cardiac medications, cardiovascular disease history, cardiac symptoms, and survival data were collected from patient records. 32 patients (13%) had EF decline ≥ 10%, eleven (4.5%) had EF decline ≥ 20% within 1 year after trastuzumab initiation, and trastuzumab was discontinued due to suspected cardiotoxicity in six patients (2.4%). 49 patients (19.9%) experienced symptoms related to cardiotoxicity during therapy, which accumulated among those with EF drop. Underlying cardiovascular diseases and multiple (≥ 2) cardiac medications were related to EF drop (≥ 20%) and trastuzumab discontinuation. Majority of EF drops (≥ 10%) and trastuzumab discontinuations were seen within 6months of trastuzumab initiation and recovery of EF drop to < 10% of the baseline was seen in most cases (62.5%). There was no statistically significant difference in the survival of patients according to EF drop. Trastuzumab cardiotoxicity seems to accumulate among patients with underlying cardiac conditions. EF monitoring could be targeted to risk groups without compromising of the cardiac health or survival of HER2-positive breast cancer patients.

Measuring executive function in Indian mothers and their 4-year-old daughters.

PubMed

von Suchodoletz, Antje; Slot, Pauline L; Shroff, Delshad M

2017-03-01

Executive function (EF), including cognitive flexibility, attention shifting, and inhibitory control, has been linked to a range of outcomes across the lifespan, such as school readiness and academic functioning, job performance, health, and social-emotional well-being. Yet, research investigating links between parent EF and child EF is still limited. This is partly due to challenges in measuring the same EF abilities in parents and their children. The current study investigated the applicability of a computer-based battery of various EF tasks for use with both mothers and children. The battery included the following EF tasks: Dimensional Change Card Sort, Hearts and Flowers, and Fish Flanker. Participants were 80 Indian mothers and their 4-year-old daughters. EF was measured with regard to accuracy scores, response time, and inverse efficiency (IE) scores of the most complex blocks of each task. Scoring patterns indicated that children's task performance appeared to be determined by their ability to recognize the cue indicating which task to perform at any given trial and to inhibit an incorrect response. In contrast, mothers' performance appeared to be determined by response time, that is, their ability to be quick in giving the correct response. However, for both children and mothers, IE scores best captured individual differences in EF performance between participants. Furthermore, confirmatory factor analyses found that, for both children and mothers, all EF measures loaded on a latent factor, suggesting that the measures shared common variance in EF. There appeared to be no significant association between mothers' and children's EF scores, controlling for several background variables. Directions for further research include examining the applicability of the EF task battery to reliably describe developmental trajectories of EF abilities over time, and further examining variability in the parent-child EF association across the lifespan. © 2017 The Institute of Psychology, Chinese Academy of Sciences and John Wiley & Sons Australia, Ltd.

The effects of EF-Ts and bismuth on EF-Tu in Helicobacter pylori: implications for an elegant timing for the introduction of EF-Ts in the elongation and EF-Tu as a potential drug target.

PubMed

Wang, Dongxian; Luo, Benping; Shan, Weiran; Hao, Mingcong; Sun, Xuesong; Ge, Ruiguang

2013-06-01

Helicobacter pylori is a common human pathogen responsible for various gastric diseases. Bismuth can effectively inhibit the growth of this bacterium and is commonly recommended for the treatment of the related diseases. Translation elongation factors EF-Tu and EF-Ts are two important components of the protein translation system. EF-Ts has inhibitory effects on the GTPase activity of EF-Tu and enhances GDP release, a hint that careful timing for the introduction of EF-Ts in the elongation should be accomplished to prevent the complete inhibition of the elongation process. Bismuth inhibits the chaperone activity of EF-Tu, and has opposite effects on the elongation activity: inhibitory effects on the intrinsic GTPase activity and stimulation of GDP release. The present work deepens our understanding of the bacterial elongation process as mediated by EF-Tu and EF-Ts and extends our knowledge about the inhibitory effects of bismuth-based drugs against Helicobacter pylori.

Ratings of Everyday Executive Functioning (REEF): A parent-report measure of preschoolers' executive functioning skills.

PubMed

Nilsen, Elizabeth S; Huyder, Vanessa; McAuley, Tara; Liebermann, Dana

2017-01-01

Executive functioning (EF) facilitates the development of academic, cognitive, and social-emotional skills and deficits in EF are implicated in a broad range of child psychopathologies. Although EF has clear implications for early development, the few questionnaires that assess EF in preschoolers tend to ask parents for global judgments of executive dysfunction and thus do not cover the full range of EF within the preschool age group. Here we present a new measure of preschoolers' EF-the Ratings of Everyday Executive Functioning (REEF)-that capitalizes on parents' observations of their preschoolers' (i.e., 3- to 5-year-olds) behavior in specific, everyday contexts. Over 4 studies, items comprising the REEF were refined and the measure's reliability and validity were evaluated. Factor analysis of the REEF yielded 1 factor, with items showing strong internal reliability. More important, children's scores on the REEF related to both laboratory measures of EF and another parent-report EF questionnaire. Moreover, reflecting divergent validity, the REEF was more strongly related to measures of EF as opposed to measures of affective styles. The REEF also captured differences in children's executive skills across the preschool years, and norms at 6-month intervals are reported. In summary, the REEF is a new parent-report measure that provides researchers with an efficient, valid, and reliable means of assessing preschoolers' executive functioning. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Assembly of Q{beta} viral RNA polymerase with host translational elongation factors EF-Tu and -Ts.

PubMed

Takeshita, Daijiro; Tomita, Kozo

2010-09-07

Replication and transcription of viral RNA genomes rely on host-donated proteins. Qbeta virus infects Escherichia coli and replicates and transcribes its own genomic RNA by Qbeta replicase. Qbeta replicase requires the virus-encoded RNA-dependent RNA polymerase (beta-subunit), and the host-donated translational elongation factors EF-Tu and -Ts, as active core subunits for its RNA polymerization activity. Here, we present the crystal structure of the core Qbeta replicase, comprising the beta-subunit, EF-Tu and -Ts. The beta-subunit has a right-handed structure, and the EF-Tu:Ts binary complex maintains the structure of the catalytic core crevasse of the beta-subunit through hydrophobic interactions, between the finger and thumb domains of the beta-subunit and domain-2 of EF-Tu and the coiled-coil motif of EF-Ts, respectively. These hydrophobic interactions are required for the expression and assembly of the Qbeta replicase complex. Thus, EF-Tu and -Ts have chaperone-like functions in the maintenance of the structure of the active Qbeta replicase. Modeling of the template RNA and the growing RNA in the catalytic site of the Qbeta replicase structure also suggests that structural changes of the RNAs and EF-Tu:Ts should accompany processive RNA polymerization and that EF-Tu:Ts in the Qbeta replicase could function to modulate the RNA folding and structure.

Inhibition of the NF-κB signaling pathway by the curcumin analog, 3,5-Bis(2-pyridinylmethylidene)-4-piperidone (EF31): anti-inflammatory and anti-cancer properties

PubMed Central

Olivera, Anlys; Moore, Terry W.; Hu, Fang; Brown, Andrew P.; Sun, Aiming; Liotta, Dennis C.; Snyder, James P.; Yoon, Younghyoun; Shim, Hyunsuk; Marcus, Adam I.; Miller, Andrew H.; Pace, Thaddeus W. W.

2012-01-01

Nuclear factor kappa B (NF-κB) is a key signaling molecule in the elaboration of the inflammatory response. Data indicate that curcumin, a natural ingredient of the curry spice turmeric, acts as a NF-κB inhibitor and exhibits both anti-inflammatory and anti-cancer properties. Curcumin analogues with enhanced activity on the NF-κB and other inflammatory signaling pathways have been developed including the synthetic monoketone compound termed 3,5-Bis(2-fluorobenzylidene)-4-piperidone (EF24). 3,5-Bis(2-pyridinylmethylidene)-4-piperidone (EF31) is a structurally-related curcumin analogue whose potency for NF-κB inhibition has yet to be determined. To examine the activity of EF31 compared to EF24 and curcumin, mouse RAW264.7 macrophages were treated with EF31, EF24, curcumin (1–100µM) or vehicle (DMSO 1%) for 1 hour. NF-κB pathway activity was assessed following treatment with lipopolysaccharide (LPS) (1µg/mL). EF31 (IC50 ~5µM) exhibited significantly more potent inhibition of LPS-induced NF-κB DNA binding compared to both EF24 (IC50~35µM) and curcumin (IC50 >50µM). In addition, EF31 exhibited significantly greater inhibition of NF-κB nuclear translocation as well as the induction of downstream inflammatory mediators including pro-inflammatory cytokine mRNA and protein (tumor necrosis factor-α, interleukin-1β, and interleukin-6). Regarding the mechanism of these effects on NF-κB activity, EF31 (IC50~1.92µM) exhibited significantly greater inhibition of IκB kinase β compared to EF24 (IC50~131µM). Finally, EF31 demonstrated potent toxicity in NF-κB-dependent cancer cell lines while having minimal and reversible toxicity in RAW264.7 macrophages. These data indicate that EF31 is a more potent inhibitor of NF-κB activity than either EF24 or curcumin while exhibiting both anti-inflammatory and anticancer activities. Thus, EF31 represents a promising curcumin analogue for further therapeutic development. PMID:22197802

Inhibition of the NF-κB signaling pathway by the curcumin analog, 3,5-Bis(2-pyridinylmethylidene)-4-piperidone (EF31): anti-inflammatory and anti-cancer properties.

PubMed

Olivera, Anlys; Moore, Terry W; Hu, Fang; Brown, Andrew P; Sun, Aiming; Liotta, Dennis C; Snyder, James P; Yoon, Younghyoun; Shim, Hyunsuk; Marcus, Adam I; Miller, Andrew H; Pace, Thaddeus W W

2012-02-01

Nuclear factor kappa B (NF-κB) is a key signaling molecule in the elaboration of the inflammatory response. Data indicate that curcumin, a natural ingredient of the curry spice turmeric, acts as a NF-κB inhibitor and exhibits both anti-inflammatory and anti-cancer properties. Curcumin analogs with enhanced activity on NF-κB and other inflammatory signaling pathways have been developed including the synthetic monoketone compound 3,5-Bis(2-fluorobenzylidene)-4-piperidone (EF24). 3,5-Bis(2-pyridinylmethylidene)-4-piperidone (EF31) is a structurally-related curcumin analog whose potency for NF-κB inhibition has yet to be determined. To examine the activity of EF31 compared to EF24 and curcumin, mouse RAW264.7 macrophages were treated with EF31, EF24, curcumin (1-100 μM) or vehicle (DMSO 1%) for 1h. NF-κB pathway activity was assessed following treatment with lipopolysaccharide (LPS) (1 μg/mL). EF31 (IC(50)~5 μM) exhibited significantly more potent inhibition of LPS-induced NF-κB DNA binding compared to both EF24 (IC(50)~35 μM) and curcumin (IC(50) >50 μM). In addition, EF31 exhibited greater inhibition of NF-κB nuclear translocation as well as the induction of downstream inflammatory mediators including pro-inflammatory cytokine mRNA and protein (tumor necrosis factor-α, interleukin-1β, and interleukin-6). Regarding the mechanism of these effects on NF-κB, EF31 (IC(50)~1.92 μM) exhibited significantly greater inhibition of IκB kinase β compared to EF24 (IC(50)~131 μM). Finally, EF31 demonstrated potent toxicity in NF-κB-dependent cancer cell lines while having minimal and reversible toxicity in RAW264.7 macrophages. These data indicate that EF31 is a more potent inhibitor of NF-κB activity than either EF24 or curcumin while exhibiting both anti-inflammatory and anticancer activities. Thus, EF31 represents a promising curcumin analog for further therapeutic development. Copyright © 2011 Elsevier B.V. All rights reserved.

Self-limiting Atypical Antipsychotics-induced Edema: Clinical Cases and Systematic Review

PubMed Central

Umar, Musa Usman; Abdullahi, Aminu Taura

2016-01-01

A number of atypical antipsychotics have been associated with peripheral edema. The exact cause is not known. We report two cases of olanzapine-induced edema and a brief review of atypical antipsychotic-induced edema, possible risk factors, etiology, and clinical features. The recommendation is given on different methods of managing this side effect. PMID:27335511

Self-limiting Atypical Antipsychotics-induced Edema: Clinical Cases and Systematic Review.

PubMed

Umar, Musa Usman; Abdullahi, Aminu Taura

2016-01-01

A number of atypical antipsychotics have been associated with peripheral edema. The exact cause is not known. We report two cases of olanzapine-induced edema and a brief review of atypical antipsychotic-induced edema, possible risk factors, etiology, and clinical features. The recommendation is given on different methods of managing this side effect.

Multiformity of elongation factor eEF-2 isolated from rat liver cells.

PubMed

Gajko, A; Gałasiński, W; Gindzieński, A

1994-07-29

Two fractions of eEF-2 (M(r) approx. 100,000 and M(r) approx. 65,000) were isolated from post-ribosomal supernatant of the rat liver cells. Only eEF-2, with mol. weight of about 100,000 Da, can be phosphorylated, but only eEF-2, with mol. weight of about 65,000 Da, was isolated from the active polyribosomes. The existence of two eEF-2 forms with different properties in the rat liver cells is striking and uncovers new aspects for the cellular function of this protein.

Elongation factor Tu resistant to kirromycin in an Esherichia coli mutant altered in both tuf genes

PubMed Central

Fischer, Eckhard; Wolf, Heinz; Hantke, Klaus; Parmeggiani, Andrea

1977-01-01

A mutant of Escherichia coli is described that displays kirromycin resistance in a cell-free system by virtue of an altered elongation factor Tu (EF-Tu). In poly(U)-directed poly(Phe) synthesis the kirromycin resistance of the crystallized enzyme ranged between a factor of 80 and 700, depending on temperature. Similarly, kirromycin-induced EF-Tu GTPase activity uncoupled from ribosomes and aminoacyl-tRNA required correspondingly higher concentrations of the antibiotic. Resistance of EF-Tu to kirromycin is a consequence of a modified enzyme structure as indicated by its altered fingerprint pattern. P1 transduction experiments showed that the kirromycin-resistant EF-Tu is coded by an altered tufB gene (tufB1). The known existence of two genes coding for EF-Tu would interfere with the recognition of a mutant altered in only one of those genes, if the mutation were recessive. Because kirromycin blocks EF-Tu release from the ribosome, kirromycin sensitivity is dominant, as shown by the failure of a mixed EF-Tu population to express resistance in vitro. Therefore, phenotypic expression of kirromycin resistance in vivo appears to be only possible if the EF-Tu mutant lacks an active tufA gene, a property likely to be inherited from the parental D22 strain. The observations that introduction of a tufA+ region makes the resistant strain sensitive to the antibiotic and that transduction of tufB1 into a recipient other than E. coli D22 yields kirromycin-sensitive progeny support these conclusions. Images PMID:337296

Adenoviral Expression of a Bispecific VHH-Based Neutralizing Agent That Targets Protective Antigen Provides Prophylactic Protection from Anthrax in Mice.

PubMed

Moayeri, Mahtab; Tremblay, Jacqueline M; Debatis, Michelle; Dmitriev, Igor P; Kashentseva, Elena A; Yeh, Anthony J; Cheung, Gordon Y C; Curiel, David T; Leppla, Stephen; Shoemaker, Charles B

2016-01-06

Bacillus anthracis, the causative agent of anthrax, secretes three polypeptides, which form the bipartite lethal and edema toxins (LT and ET, respectively). The common component in these toxins, protective antigen (PA), is responsible for binding to cellular receptors and translocating the lethal factor (LF) and edema factor (EF) enzymatic moieties to the cytosol. Antibodies against PA protect against anthrax. We previously isolated toxin-neutralizing variable domains of camelid heavy-chain-only antibodies (VHHs) and demonstrated their in vivo efficacy. In this work, gene therapy with an adenoviral (Ad) vector (Ad/VNA2-PA) (VNA, VHH-based neutralizing agents) promoting the expression of a bispecific VHH-based neutralizing agent (VNA2-PA), consisting of two linked VHHs targeting different PA-neutralizing epitopes, was tested in two inbred mouse strains, BALB/cJ and C57BL/6J, and found to protect mice against anthrax toxin challenge and anthrax spore infection. Two weeks after a single treatment with Ad/VNA2-PA, serum VNA2-PA levels remained above 1 μg/ml, with some as high as 10 mg/ml. The levels were 10- to 100-fold higher and persisted longer in C57BL/6J than in BALB/cJ mice. Mice were challenged with a lethal dose of LT or spores at various times after Ad/VNA2-PA administration. The majority of BALB/cJ mice having serum VNA2-PA levels of >0.1 μg/ml survived LT challenge, and 9 of 10 C57BL/6J mice with serum levels of >1 μg/ml survived spore challenge. Our findings demonstrate the potential for genetic delivery of VNAs as an effective method for providing prophylactic protection from anthrax. We also extend prior findings of mouse strain-based differences in transgene expression and persistence by adenoviral vectors. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Review and analysis of global agricultural N₂O emissions relevant to the UK.

PubMed

Buckingham, S; Anthony, S; Bellamy, P H; Cardenas, L M; Higgins, S; McGeough, K; Topp, C F E

2014-07-15

As part of a UK government funded research project to update the UK N2O inventory methodology, a systematic review of published nitrous oxide (N2O) emission factors was carried out of non-UK research, for future comparison and synthesis with the UK measurement based evidence base. The aim of the study is to assess how the UK IPCC default emission factor for N2O emissions derived from synthetic or organic fertiliser inputs (EF1) compares to international values reported in published literature. The availability of data for comparing and/or refining the UK IPCC default value and the possibility of analysing sufficient auxiliary data to propose a Tier 2 EF1 reporting strategy is evaluated. The review demonstrated a lack of consistency in reporting error bounds for fertiliser-derived EFs and N2O flux data with 8% and 44% of publications reporting EF and N2O flux error bounds respectively. There was also poor description of environmental (climate and soil) and experimental design auxiliary data. This is likely to be due to differences in study objectives, however potential improvements to soil parameter reporting are proposed. The review demonstrates that emission factors for agricultural-derived N2O emissions ranged -0.34% to 37% showing high variation compared to the UK Tier 1 IPCC EF1 default values of 1.25% (IPCC 1996) and 1% (IPPC 2006). However, the majority (83%) of EFs reported for UK-relevant soils fell within the UK IPCC EF1 uncertainty range of 0.03% to 3%. Residual maximum likelihood (REML) analysis of the data collated in the review showed that the type and rate of fertiliser N applied and soil type were significant factors influencing EFs reported. Country of emission, the length of the measurement period, the number of splits, the crop type, pH and SOC did not have a significant impact on N2O emissions. A subset of publications where sufficient data was reported for meta-analysis to be conducted was identified. Meta-analysis of effect sizes of 41 treatments demonstrated that the application of fertiliser has a significant effect on N2O emissions in comparison to control plots and that emission factors were significantly different to zero. However no significant relationships between the quantity of fertiliser applied and the effect size of the amount of N2O emitted from fertilised plots compared to control plots were found. Annual addition of fertiliser of 35 to 557 kg N/ha gave a mean increase in emissions of 2.02 ± 0.28 g N2O/ha/day compared to control treatments (p<0.01). Emission factors were significantly different from zero, with a mean emission factor estimated directly from the meta analysis of 0.17 ± 0.02%. This is lower than the IPCC 2006 Tier 1 EF1 value of 1% but falling within the uncertainty bound for the IPCC 2006 Tier 1 EF1 (0.03% to 3%). As only a small number of papers were viable for meta analysis to be conducted due to lack of reporting of the key controlling factors, the estimates of EF in this paper cannot include the true variability under conditions similar to the UK. Review-derived EFs of 0.34% to 37% and mean EF from meta-analysis of 0.17 ± 0.02% highlight variability in reporting EFs depending on the method applied and sample size. A protocol of systematic reporting of N2O emissions and key auxiliary parameters in publications across disciplines is proposed. If adopted this would strengthen the community to inform IPCC Tier 2 reporting development and reduce the uncertainty surrounding reported UK N2O emissions. Copyright © 2014 Elsevier B.V. All rights reserved.

On-road measurements of NMVOCs and NOx: Determination of light-duty vehicles emission factors from tunnel studies in Brussels city center

NASA Astrophysics Data System (ADS)

Ait-Helal, W.; Beeldens, A.; Boonen, E.; Borbon, A.; Boréave, A.; Cazaunau, M.; Chen, H.; Daële, V.; Dupart, Y.; Gaimoz, C.; Gallus, M.; George, C.; Grand, N.; Grosselin, B.; Herrmann, H.; Ifang, S.; Kurtenbach, R.; Maille, M.; Marjanovic, I.; Mellouki, A.; Miet, K.; Mothes, F.; Poulain, L.; Rabe, R.; Zapf, P.; Kleffmann, J.; Doussin, J.-F.

2015-12-01

Emission factors (EFs) of pollutants emitted by light-duty vehicles (LDV) were investigated in the Leopold II tunnel in Brussels city center (Belgium), in September 2011 and in January 2013, respectively. Two sampling sites were housing the instruments for the measurements of a large range of air pollutants, including non-methane volatile organic compounds (NMVOCs), nitrogen oxides (NOx) and carbon dioxide (CO2). The NMVOCs and NOx traffic EFs for LDV were determined from their correlation with CO2 using a single point analysis method. The emission factor of NOx is (544 ± 199) mg vehicle-1 km-1; NMVOCs emission factors vary from (0.26 ± 0.09) mg vehicle-1 km-1 for cis-but-2-ene to (8.11 ± 2.71) mg vehicle-1 km-1 for toluene. Good agreement is observed between the EFs determined in the Leopold II tunnel and the most recent EFs determined in another European roadway tunnel in 2004, with only a slight decrease of the EFs during the last decade. An historical perspective is provided and the observed trend in the NMVOCs emission factors reflect changes in the car fleet composition, the fuels and/or the engine technology that have occurred within the last three decades in Europe.

Review of ammonia emission factors for United States animal agriculture

NASA Astrophysics Data System (ADS)

Faulkner, W. B.; Shaw, B. W.

Ammonia emissions from agricultural industries are a significant source of atmospheric reactive nitrogen, which can lead to negative environmental consequences such as ecosystem change and formation of fine particulate. While a number of emission factors (EFs) have been proposed for developing ammonia emissions inventories for the US, most are based on European research with little discussion of their applicability to US production systems. Recently developed ammonia EFs from literature for animal feeding operations (AFOs), including production facilities for beef and dairy cattle, swine, and poultry, are presented. Tentative EFs for US animal agriculture are suggested until further research can be conducted. Currently, there is a dearth of EFs developed specifically for agricultural production practices in the US.

Hemorrhagic shock-induced cerebral bioenergetic imbalance is corrected by pharmacologic treatment with EF24 in a rat model.

PubMed

Rao, Geeta; Xie, Jun; Hedrick, Andria; Awasthi, Vibhudutta

2015-12-01

Maintenance of cerebral viability and function is an important goal of critical care in victims of injury due to ischemia and hypovolemia. As part of the multiple organ dysfunction syndrome, the brain function after trauma is influenced by the systemic inflammatory response. We investigated the effect of EF24, an anti-inflammatory bis-chalcone, on cerebral bioenergetics in a rat model of 45% hemorrhagic shock. The rats were treated with EF24 (0.4 mg/kg) or EF24 with an artificial oxygen carrier liposome-encapsulated hemoglobin (LEH). The volume of LEH administered was equal to the shed blood. The brain was collected after 6 h of shock for biochemical assays. EF24 treatment showed significant recovery of ATP, phosphocreatine, and NAD/NADH ratio. It also increased citrate synthase activity and cytochrome c oxidase subunit IV expression which were reduced in shock brain. Furthermore, it reduced the shock-induced accumulation of pyruvate and pyruvate dehydrogenase kinase-1 expression, suggesting that EF24 treatment improves cerebral energetics by restoring perturbed pyruvate metabolism in the mitochondria. These effects of EF24 were associated with reduced poly(ADP-ribose) polymerase cleavage and a significant improvement in the levels of nerve growth factor and brain-derived neurotrophic factor in shock brain. Co-administration of LEH with EF24 was only marginally more effective as compared to the treatment with EF24 alone. These results show that EF24 treatment sets up a pro-survival phenotype in shock by resurrecting cerebral bioenergetics. Since EF24 was effective in the absence of accompanying fluid resuscitation, it has potential utility as a pre-hospital pharmacotherapy in shock due to accidental blood loss. Copyright © 2015 Elsevier Ltd. All rights reserved.

Greater impact of acute high-intensity interval exercise on post-exercise executive function compared to moderate-intensity continuous exercise.

PubMed

Tsukamoto, Hayato; Suga, Tadashi; Takenaka, Saki; Tanaka, Daichi; Takeuchi, Tatsuya; Hamaoka, Takafumi; Isaka, Tadao; Hashimoto, Takeshi

2016-03-01

Aerobic moderate-intensity continuous exercise (MCE) can improve executive function (EF) acutely, potentially through the activation of both physiological and psychological factors. Recently, high-intensity interval exercise (HIIE) has been reported to be more beneficial for physical adaptation than MCE. Factors for EF improvement can potentially be more enhanced by HIIE than by MCE; but the effects of HIIE on EF remain unknown. Therefore, we aimed to examine to what extent HIIE impacts post-exercise EF immediately after exercise and during post-exercise recovery, compared with traditional MCE. Twelve healthy male subjects performed cycle ergometer exercise based on either HIIE or MCE protocols in a randomized and counterbalanced order. The HIIE protocol consisted of four 4-min bouts at 90% of peak VO2 with 3-min active recovery at 60% of peak VO2. A volume-matched MCE protocol was applied at 60% of peak VO2. To evaluate EF, a color-words Stroop task was performed pre- and post-exercise. Improvement in EF immediately after exercise was the same for the HIIE and MCE protocols. However, the improvement of EF by HIIE was sustained during 30 min of post-exercise recovery, during which MCE returned to the pre-exercise level. The EF response in the post-exercise recovery was associated with changes in physiological and psychological responses. The present findings showed that HIIE and MCE were capable of improving EF. Moreover, HIIE could prolong improvement in EF during post-exercise recovery. For the first time, we suggest that HIIE may be more effective strategy than MCE for improving EF. Copyright © 2015 Elsevier Inc. All rights reserved.

Relationship between soluble microbial products (SMP) and effluent organic matter (EfOM): characterized by fluorescence excitation emission matrix coupled with parallel factor analysis.

PubMed

Yu, Huarong; Qu, Fangshu; Sun, Lianpeng; Liang, Heng; Han, Zhengshuang; Chang, Haiqing; Shao, Senlin; Li, Guibai

2015-02-01

Effluent organic matter (EfOM) originating from wastewater treatment plant (WWTP) is of significant concern, as it not only influences the discharge quality of WWTP but also exerts a significant effect on the efficiency of the downstream advanced treatment facilities. Soluble microbial products (SMP) is a major part of EfOM. In order to further understand the relationship between soluble microbial products (SMP) and EfOM, and in turn, to propose measures for EfOM control, the formation of SMP and EfOM in identical activated sludge sequencing batch reactors (SBR) with different feed water was investigated using fluorescence excitation and emission spectroscopy matrix coupled with parallel factor analysis (EEM-PARAFAC) as well as other organic matter quantification tools. Results showed that EfOM contained not only SMP but also a considerable amount of allochthonous organic matter that derived not merely from natural organic matter (NOM). Four components in EfOM/SMP were identified by EEM-PARAFAC. Tyrosine-like substances in EfOM (Component 3, λex/em=270/316 nm) were mainly originated from utilization associated products (UAP) of SMP. Tryptophan-like substances (Component 2, λex/em=280/336 nm) as well as fulvic-like and humic-like substances in EfOM (Component 1, λex/em=240(290)/392 nm and Component 4, λex/em=260(365)/444 nm) were majorly derived from the refractory substances introduced along with the influent, among which Component 2 was stemmed from sources other than NOM. As solid retention time (SRT) increased, Component 2 and polysaccharides in SMP/EfOM decreased, while Component 4 in SMP increased. Copyright © 2014 Elsevier Ltd. All rights reserved.

Hemorrhagic shock-induced cerebral bioenergetic imbalance is corrected by pharmacologic treatment with EF24 in a rat model

PubMed Central

Rao, Geeta; Xie, Jun; Hedrick, Andria; Awasthi, Vibhudutta

2015-01-01

Maintenance of cerebral viability and function is an important goal of critical care in victims of injury due to ischemia and hypovolemia. As part of the multiple organ dysfunction syndrome, the brain function after trauma is influenced by systemic inflammatory response. We investigated the effect of EF24, an anti-inflammatory bis-chalcone, on cerebral bioenergetics in a rat model of 45% hemorrhagic shock. The rats were treated with EF24 (0.4 mg/kg) or EF24 with an artificial oxygen carrier liposome-encapsulated hemoglobin (LEH). The volume of LEH administered was equal to the shed blood. The brain was collected after 6 h of shock for biochemical assays. EF24 treatment showed significant recovery of ATP, phosphocreatine, and NAD/NADH ratio. It also increased citrate synthase activity and cytochrome c oxidase subunit IV expression which were reduced in shock brain. Furthermore, it reduced the shock-induced accumulation of pyruvate and pyruvate dehydrogenase kinase-1 expression, suggesting that EF24 treatment improves cerebral energetics by restoring perturbed pyruvate metabolism in the mitochondria. These effects of EF24 were associated with reduced poly(ADP-ribose) polymerase cleavage and a significant improvement in the levels of nerve growth factor and brain-derived neurotrophic factor in shock brain. Co-administration of LEH with EF24 was only marginally more effective as compared to the treatment with EF24 alone. These results show that EF24 treatment sets up a pro-survival phenotype in shock by resurrecting cerebral bioenergetics. Since EF24 was effective in the absence of accompanying fluid resuscitation, it has potential utility as a pre-hospital pharmacotherapy in shock due to accidental blood loss. PMID:26232641

The Drosophila mitochondrial translation elongation factor G1 contains a nuclear localization signal and inhibits growth and DPP signaling.

PubMed

Trivigno, Catherine; Haerry, Theodor E

2011-02-25

Mutations in the human mitochondrial elongation factor G1 (EF-G1) are recessive lethal and cause death shortly after birth. We have isolated mutations in iconoclast (ico), which encodes the highly conserved Drosophila orthologue of EF-G1. We find that EF-G1 is essential during fly development, but its function is not required in every tissue. In contrast to null mutations, missense mutations exhibit stronger, possibly neomorphic phenotypes that lead to premature death during embryogenesis. Our experiments show that EF-G1 contains a secondary C-terminal nuclear localization signal. Expression of missense mutant forms of EF-G1 can accumulate in the nucleus and cause growth and patterning defects and animal lethality. We find that transgenes that encode mutant human EF-G1 proteins can rescue ico mutants, indicating that the underlying problem of the human disease is not just the loss of enzymatic activity. Our results are consistent with a model where EF-G1 acts as a retrograde signal from mitochondria to the nucleus to slow down cell proliferation if mitochondrial energy output is low.

The Drosophila Mitochondrial Translation Elongation Factor G1 Contains a Nuclear Localization Signal and Inhibits Growth and DPP Signaling

PubMed Central

Trivigno, Catherine; Haerry, Theodor E.

2011-01-01

Mutations in the human mitochondrial elongation factor G1 (EF-G1) are recessive lethal and cause death shortly after birth. We have isolated mutations in iconoclast (ico), which encodes the highly conserved Drosophila orthologue of EF-G1. We find that EF-G1 is essential during fly development, but its function is not required in every tissue. In contrast to null mutations, missense mutations exhibit stronger, possibly neomorphic phenotypes that lead to premature death during embryogenesis. Our experiments show that EF-G1 contains a secondary C-terminal nuclear localization signal. Expression of missense mutant forms of EF-G1 can accumulate in the nucleus and cause growth and patterning defects and animal lethality. We find that transgenes that encode mutant human EF-G1 proteins can rescue ico mutants, indicating that the underlying problem of the human disease is not just the loss of enzymatic activity. Our results are consistent with a model where EF-G1 acts as a retrograde signal from mitochondria to the nucleus to slow down cell proliferation if mitochondrial energy output is low. PMID:21364917

Tensor Factorization for Precision Medicine in Heart Failure with Preserved Ejection Fraction

PubMed Central

Luo, Yuan; Ahmad, Faraz S.; Shah, Sanjiv J.

2017-01-01

Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous clinical syndrome that may benefit from improved subtyping in order to better characterize its pathophysiology and to develop novel targeted therapies. The United States Precision Medicine Initiative comes amid the rapid growth in quantity and modality of clinical data for HFpEF patients ranging from deep phenotypic to trans-omic data. Tensor factorization, a form of machine learning, allows for the integration of multiple data modalities to derive clinically relevant HFpEF subtypes that may have significant differences in underlying pathophysiology and differential response to therapies. Tensor factorization also allows for better interpretability by supporting dimensionality reduction and identifying latent groups of data for meaningful summarization of both features and disease outcomes. In this narrative review, we analyze the modest literature on the application of tensor factorization to related biomedical fields including genotyping and phenotyping. Based on the cited work including work of our own, we suggest multiple tensor factorization formulations capable of integrating the deep phenotypic and trans-omic modalities of data for HFpEF, or accounting for interactions between genetic variants at different -omic hierarchies. We encourage extensive experimental studies to tackle challenges in applying tensor factorization for precision medicine in HFpEF, including effectively incorporating existing medical knowledge, properly accounting for uncertainty, and efficiently enforcing sparsity for better interpretability. PMID:28116551

Associations between and development of cool and hot executive functions across early childhood.

PubMed

O'Toole, Sarah; Monks, Claire P; Tsermentseli, Stella

2018-03-01

This study explored the development of cool and hot EF skills across early childhood. Children 4.5- to 5.5-years-old (N = 80) completed performance-based assessments of cool EF (inhibition and working memory), hot EF (affective decision-making and delay of gratification) at three time points across 12 months. Cool EF task performance was consistently correlated with early childhood, but hot EF task performance was not. Performance on cool EF tasks showed significant improvements over early childhood, but performance on hot EF tasks did not. During early childhood performance on delay of gratification and affective decision-making tasks may therefore be unrelated and show limited sensitivity to improvement. Statement of contribution What is already known about cool and hot EF An EF model has been proposed that distinguishes between cool-cognitive and hot-affective skills. Findings regarding whether cool and hot EF are distinct in early childhood are mixed. Hot EF skills, compared to cool EF abilities, are thought to develop more gradually. What the present study adds to understanding of cool and hot EF Performance on cool EF tasks and hot delay of gratification were associated in early childhood. Performance on hot EF tasks was not related, meaning they do not tap the same underlying factor. Age related gains in hot EF were not found, but 5-year-olds had better hot EF than 4-year-olds. © 2017 The British Psychological Society.

Determination of car on-road black carbon and particle number emission factors and comparison between mobile and stationary measurements

NASA Astrophysics Data System (ADS)

Ježek, I.; Drinovec, L.; Ferrero, L.; Carriero, M.; Močnik, G.

2015-01-01

We have used two methods for measuring emission factors (EFs) in real driving conditions on five cars in a controlled environment: the stationary method, where the investigated vehicle drives by the stationary measurement platform and the composition of the plume is measured, and the chasing method, where a mobile measurement platform drives behind the investigated vehicle. We measured EFs of black carbon and particle number concentration. The stationary method was tested for repeatability at different speeds and on a slope. The chasing method was tested on a test track and compared to the portable emission measurement system. We further developed the data processing algorithm for both methods, trying to improve consistency, determine the plume duration, limit the background influence and facilitate automatic processing of measurements. The comparison of emission factors determined by the two methods showed good agreement. EFs of a single car measured with either method have a specific distribution with a characteristic value and a long tail of super emissions. Measuring EFs at different speeds or slopes did not significantly influence the EFs of different cars; hence, we propose a new description of vehicle emissions that is not related to kinematic or engine parameters, and we rather describe the vehicle EF with a characteristic value and a super emission tail.

Traffic emission factors of ultrafine particles: effects from ambient air.

PubMed

Janhäll, Sara; Molnar, Peter; Hallquist, Mattias

2012-09-01

Ultrafine particles have a significant detrimental effect on both human health and climate. In order to abate this problem, it is necessary to identify the sources of ultrafine particles. A parameterisation method is presented for estimating the levels of traffic-emitted ultrafine particles in terms of variables describing the ambient conditions. The method is versatile and could easily be applied to similar datasets in other environments. The data used were collected during a four-week period in February 2005, in Gothenburg, as part of the Göte-2005 campaign. The specific variables tested were temperature (T), relative humidity (RH), carbon monoxide concentration (CO), and the concentration of particles up to 10 μm diameter (PM(10)); all indicators are of importance for aerosol processes such as coagulation and gas-particle partitioning. These variables were selected because of their direct effect on aerosol processes (T and RH) or as proxies for aerosol surface area (CO and PM(10)) and because of their availability in local monitoring programmes, increasing the usability of the parameterization. Emission factors are presented for 10-100 nm particles (ultrafine particles; EF(ufp)), for 10-40 nm particles (EF(10-40)), and for 40-100 nm particles (EF(40-100)). For EF(40-100) no effect of ambient conditions was found. The emission factor equations are calculated based on an emission factor for NO(x) of 1 g km(-1), thus the particle emission factors are easily expressed in units of particles per gram of NO(x) emitted. For 10-100 nm particles the emission factor is EF(ufp) = 1.8 × 10(15) × (1 - 0.095 × CO - 3.2 × 10(-3) × T) particles km(-1). Alternative equations for the EFs in terms of T and PM(10) concentration are also presented.

The pretranslocation ribosome is targeted by GTP-bound EF-G in partially activated form

PubMed Central

Hauryliuk, Vasili; Mitkevich, Vladimir A.; Eliseeva, Natalia A.; Petrushanko, Irina Yu.; Ehrenberg, Måns; Makarov, Alexander A.

2008-01-01

Translocation of the tRNA·mRNA complex through the bacterial ribosome is driven by the multidomain guanosine triphosphatase elongation factor G (EF-G). We have used isothermal titration calorimetry to characterize the binding of GDP and GTP to free EF-G at 4°C, 20°C, and 37°C. The binding affinity of EF-G is higher to GDP than to GTP at 4°C, but lower at 37°C. The binding enthalpy and entropy change little with temperature in the case of GDP binding but change greatly in the case of GTP binding. These observations are compatible with a large decrease in the solvent-accessible hydrophobic surface area of EF-G on GTP, but not GDP, binding. The explanation we propose is the locking of the switch 1 and switch 2 peptide loops in the G domain of EF-G to the γ-phosphate of GTP. From these data, in conjunction with previously reported structural data on guanine nucleotide-bound EF-G, we suggest that EF-G enters the pretranslocation ribosome as an “activity chimera,” with the G domain activated by the presence of GTP but the overall factor conformation in the inactive form typical of a GDP-bound multidomain guanosine triphosphatase. We propose that the active overall conformation of EF-G is attained only in complex with the ribosome in its “ratcheted state,” with hybrid tRNA binding sites. PMID:18836081

Edema: a silent but important factor.

PubMed

Villeco, June P

2012-01-01

Edema is a normal response to injury. Even the smallest injury is associated with some inflammation, and initial edema is part of the normal inflammatory process. However, edema becomes a concern when it persists beyond the inflammatory phase. Once we have progressed into the rebuilding, or fibroplastic phase of healing, edema will delay healing and contribute to complications such as pain and stiffness. Early prevention and management to prevent this progression are therefore critical. This article discusses edema in relation to stages of healing and presents the research behind techniques available to the clinician to manage localized extracellular upper extremity edema in the patient with an intact lymphatic system. Copyright © 2012 Hanley & Belfus. Published by Elsevier Inc. All rights reserved.

Surgical versus non-surgical approach in primary desmoid-type fibromatosis patients: A nationwide prospective cohort from the French Sarcoma Group.

PubMed

Penel, Nicolas; Le Cesne, Axel; Bonvalot, Sylvie; Giraud, Antoine; Bompas, Emmanuelle; Rios, Maria; Salas, Sébastien; Isambert, Nicolas; Boudou-Rouquette, Pascaline; Honore, Charles; Italiano, Antoine; Ray-Coquard, Isabelle; Piperno-Neumann, Sophie; Gouin, François; Bertucci, François; Ryckewaert, Thomas; Kurtz, Jean-Emmanuel; Ducimetiere, Françoise; Coindre, Jean-Michel; Blay, Jean-Yves

2017-09-01

The outcome of desmoid-type fibromatosis (DTF) is unpredictable. Currently, a wait-and-see approach tends to replace large en bloc resection as the first therapeutic approach. Nevertheless, there are no validated factors to guide the treatment choice. We conducted a prospective study of 771 confirmed cases of DTF. We analysed event-free survival (EFS) based on the occurrence of relapse after surgery, progressive disease during the wait-and-see approach, or change in therapeutic strategy. Identification of prognostic factors was performed using classical methods (log-rank test and Cox model). Overall, the 2-year EFS was 56%; this value did not differ between patients undergoing an operation and those managed by the wait-and-see approach (53% versus 58%, p = 0.415). In univariate analysis, two prognostic factors significantly influenced the outcome: the nature of diagnostic sampling (p = 0.466) and primary location (p = 0.0001). The 2-year EFS was only 32% after open biopsy. The 2-year EFS was 66% for favourable locations (abdominal wall, intra-abdominal, breast, digestive viscera and lower limb) and 41% for unfavourable locations. Among patients with favourable locations, the 2-year EFS was similar in patients treated by both surgery (70%) and the wait-and-see approach (63%; p = 0.413). Among patients with unfavourable locations, the 2-year EFS was significantly enhanced in patients initially managed with the wait-and-see approach (52%) compared with those who underwent initial surgery (25%; p = 0.001). The location of DTF is a major prognostic factor for EFS. If these findings are confirmed by independent analysis, personalised management of DTF must consider this easily obtained parameter. Copyright © 2017 Elsevier Ltd. All rights reserved.

HFpEF and HFrEF Display Different Phenotypes as Assessed by IGF-1 and IGFBP-1.

PubMed

Faxén, Ulrika Ljung; Hage, Camilla; Benson, Lina; Zabarovskaja, Stanislava; Andreasson, Anna; Donal, Erwan; Daubert, Jean-Claude; Linde, Cecilia; Brismar, Kerstin; Lund, Lars H

2017-04-01

Anabolic drive is impaired in heart failure with reduced ejection fraction (HFrEF) but insufficiently studied in heart failure with preserved ejection fraction (HFpEF). Insulin-like growth factor 1 (IGF-1) mediates growth hormone effects and IGF binding protein 1 (IGFBP-1) regulates IGF-1 activity. We tested the hypothesis that HFpEF and HFrEF are similar with regard to IGF-1 and IGFBP-1. In patients with HFpEF (n = 79), HFrEF (n = 85), and controls (n = 136), we analyzed serum IGF-1 and IGFBP-1 concentrations, correlations, and associations with outcome. Age-standardized scores of IGF-1 were higher in HFpEF, median arbitrary units (interquartile range); 1.21 (0.57-1.96) vs HFrEF, 0.09 (-1.40-1.62), and controls, 0.22 (-0.47-0.96), P overall <.001. IGFBP-1 was increased in HFpEF, 48 (28-79), and HFrEF, 65 (29-101), vs controls, 27(14-35) µg/L, P overall <.001. These patterns persisted after adjusting for metabolic and HF severity confounders. IGF-1 was associated with outcomes in HFrEF, hazard ratio per natural logarithmic increase in IGF-1 SD score 0.51 (95% confidence interval 0.32-0.82, P = .005), but not significantly in HFpEF. IGFBP-1 was not associated with outcomes in either HFpEF nor HFrEF. HFpEF and HFrEF phenotypes were similar with regard to increased IGFBP-1 concentrations but differed regarding IGF-1 levels and prognostic role. HFrEF and HFpEF may display different impairment in anabolic drive. Copyright © 2016 Elsevier Inc. All rights reserved.

The Role of the Y-Located TSPY Gene in Prostatic Oncogenesis

DTIC Science & Technology

2007-02-01

to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data ...from CIS to invasive germ cell tumors [7, 31]. To validate the microarray data , we had selected 4 up-regulated (RGC32, PDGFC, WNT5A and CCND2) and 4...on selection medium ( data not shown). eEF1A1 is one of two isoforms (eEF1A1 and eEF1A2) of translation elongation factor alpha (eEF1A). eEF1A1 is

Characterizing executive functioning in older special populations: from cognitively elite to cognitively impaired.

PubMed

de Frias, Cindy M; Dixon, Roger A; Strauss, Esther

2009-11-01

The authors examined the structure and invariance of executive functions (EF) across (a) a continuum of cognitive status in 3 groups of older adults (cognitively elite [CE], cognitively normal [CN], and cognitively impaired [CI]) and (b) a 3-year longitudinal interval. Using latent variable analyses (LISREL 8.80), the authors tested 3-factor models ("Inhibition": Hayling [Burgess & Shallice, 1997], Stroop [Regard, 1981]; "Shifting": Brixton [Burgess & Shallice, 1997], Color Trails [D'Elia et al., 1996]; and "Updating": Reading and Computational Span [Salthouse & Babcock, 1991]) and 1-factor models within each group. Participants (initial N = 570; 53-90 years) were from the Victoria Longitudinal Study (Sample 3, Waves 1 and 2). Cross-sectionally, the authors observed a 3-factor EF structure especially for the CE group and 1-factor solutions for all 3 groups. Longitudinally, temporal invariance was supported for the 3-factor model (CE and CN groups) and the 1-factor model (CI and CN groups). Subgroups with higher cognitive status and greater 3-year stability performed better on EF factors than corresponding groups with lower cognitive status and less stability. Studies of EF structure, performance, dedifferentiation, and dysfunction will benefit from considering initial cognitive status and longitudinal stability.

In Vivo and In Vitro Suppression of Hepatocellular Carcinoma by EF24, a Curcumin Analog

PubMed Central

Wang, Luoluo; Tian, Lantian; Song, Ruipeng; Han, Tianwen; Pan, Shangha; Liu, Lianxin

2012-01-01

The synthetic compound 3,5-bis(2-flurobenzylidene)piperidin-4-one (EF24) is a potent analog of curcumin that exhibits enhanced biological activity and bioavailability without increasing toxicity. EF24 exerts antitumor activity by arresting the cell cycle and inducing apoptosis, suppressing many types of cancer cells in vitro. The antiproliferative and antiangiogenic properties of EF24 provide theoretical support for its development and application to liver cancers. We investigated the in vitro and in vivo activities of EF24 on liver cancer to better understand its therapeutic effects and mechanisms. EF24 induced significant apoptosis and G2/M-phase cell cycle arrest in mouse liver cancer cell lines, Hepa1-6 and H22. The expression levels of G2/M cell cycle regulating factors, cyclin B1 and Cdc2, were significantly decreased, pp53, p53, and p21 were significantly increased in EF24-treated cells. In addition, EF24 treatment significantly reduced Bcl-2 concomitant with an increase in Bax, enhanced the release of cytochrome c from the mitochondria into the cytosol, resulting in an upregulation of cleaved-caspase-3, which promoted poly (ADP-ribose) polymerase cleavage. EF24-treated cells also displayed decreases in phosphorylated Akt, phosphorylated extracellular signal-regulated kinase and vascular endothelial growth factor. Our in vitro protein expression data were confirmed in vivo using a subcutaneous hepatocellular carcinoma (HCC) tumor model. This mouse HCC model confirmed that total body weight was unchanged following EF24 treatment, although tumor weight was significantly decreased. Using an orthotopic HCC model, EF24 significantly reduced the liver/body weight ratio and relative tumor areas compared to the control group. In situ detection of apoptotic cells and quantification of Ki-67, a biomarker of cell proliferation, all indicated significant tumor suppression with EF24 treatment. These results suggest that EF24 exhibits anti-tumor activity on liver cancer cells via mitochondria-dependent apoptosis and inducing cell cycle arrest coupled with antiangiogenesis. The demonstrated activities of EF24 support its further evaluation as a treatment for human liver cancers. PMID:23118928

In vivo and in vitro suppression of hepatocellular carcinoma by EF24, a curcumin analog.

PubMed

Liu, Haitao; Liang, Yingjian; Wang, Luoluo; Tian, Lantian; Song, Ruipeng; Han, Tianwen; Pan, Shangha; Liu, Lianxin

2012-01-01

The synthetic compound 3,5-bis(2-flurobenzylidene)piperidin-4-one (EF24) is a potent analog of curcumin that exhibits enhanced biological activity and bioavailability without increasing toxicity. EF24 exerts antitumor activity by arresting the cell cycle and inducing apoptosis, suppressing many types of cancer cells in vitro. The antiproliferative and antiangiogenic properties of EF24 provide theoretical support for its development and application to liver cancers. We investigated the in vitro and in vivo activities of EF24 on liver cancer to better understand its therapeutic effects and mechanisms. EF24 induced significant apoptosis and G2/M-phase cell cycle arrest in mouse liver cancer cell lines, Hepa1-6 and H22. The expression levels of G2/M cell cycle regulating factors, cyclin B1 and Cdc2, were significantly decreased, pp53, p53, and p21 were significantly increased in EF24-treated cells. In addition, EF24 treatment significantly reduced Bcl-2 concomitant with an increase in Bax, enhanced the release of cytochrome c from the mitochondria into the cytosol, resulting in an upregulation of cleaved-caspase-3, which promoted poly (ADP-ribose) polymerase cleavage. EF24-treated cells also displayed decreases in phosphorylated Akt, phosphorylated extracellular signal-regulated kinase and vascular endothelial growth factor. Our in vitro protein expression data were confirmed in vivo using a subcutaneous hepatocellular carcinoma (HCC) tumor model. This mouse HCC model confirmed that total body weight was unchanged following EF24 treatment, although tumor weight was significantly decreased. Using an orthotopic HCC model, EF24 significantly reduced the liver/body weight ratio and relative tumor areas compared to the control group. In situ detection of apoptotic cells and quantification of Ki-67, a biomarker of cell proliferation, all indicated significant tumor suppression with EF24 treatment. These results suggest that EF24 exhibits anti-tumor activity on liver cancer cells via mitochondria-dependent apoptosis and inducing cell cycle arrest coupled with antiangiogenesis. The demonstrated activities of EF24 support its further evaluation as a treatment for human liver cancers.

Computer Systems Acquisition Metrics Handbook. Volume II. Quality Factor Modules.

DTIC Science & Technology

1982-05-01

are unable to evil .mte) IPAW BrY: APFD If: i Ef-24 EFFICICYe: EfPDF.l L C1E PHASE: Sota S): PRELINARY DESIGN EfP. 1 EfDC. 2 = StSM NAM:. I. CUM...unable to evaluate) Iv. D6PB=’S C3#rm: PWAPM BY:______ APFD N _______ Po-30 MACHM NDE WM4 MEASE SO= Go&e:. PoII4LS LIM P E PHAiSE: SJRMCs): IMPLEME

A structural equation modeling of executive functions, IQ and mathematical skills in primary students: Differential effects on number production, mental calculus and arithmetical problems.

PubMed

Arán Filippetti, Vanessa; Richaud, María Cristina

2017-10-01

Though the relationship between executive functions (EFs) and mathematical skills has been well documented, little is known about how both EFs and IQ differentially support diverse math domains in primary students. Inconsistency of results may be due to the statistical techniques employed, specifically, if the analysis is conducted with observed variables, i.e., regression analysis, or at the latent level, i.e., structural equation modeling (SEM). The current study explores the contribution of both EFs and IQ in mathematics through an SEM approach. A total of 118 8- to 12-year-olds were administered measures of EFs, crystallized (Gc) and fluid (Gf) intelligence, and math abilities (i.e., number production, mental calculus and arithmetical problem-solving). Confirmatory factor analysis (CFA) offered support for the three-factor solution of EFs: (1) working memory (WM), (2) shifting, and (3) inhibition. Regarding the relationship among EFs, IQ and math abilities, the results of the SEM analysis showed that (i) WM and age predict number production and mental calculus, and (ii) shifting and sex predict arithmetical problem-solving. In all of the SEM models, EFs partially or totally mediated the relationship between IQ, age and math achievement. These results suggest that EFs differentially supports math abilities in primary-school children and is a more significant predictor of math achievement than IQ level.

Effector region of the translation elongation factor EF-Tu.GTP complex stabilizes an orthoester acid intermediate structure of aminoacyl-tRNA in a ternary complex.

PubMed Central

Förster, C; Limmer, S; Zeidler, W; Sprinzl, M

1994-01-01

tRNA(Val) from Escherichia coli was aminoacylated with [1-13C]valine and its complex with Thermus thermophilus elongation factor EF-Tu.GTP was analyzed by 13C NMR spectroscopy. The results suggest that the aminoacyl residue of the valyl-tRNA in ternary complex with bacterial EF-Tu and GTP is not attached to tRNA by a regular ester bond to either a 2'- or 3'-hydroxyl group; instead, an intermediate orthoester acid structure with covalent linkage to both vicinal hydroxyls of the terminal adenosine-76 is formed. Mutation of arginine-59 located in the effector region of EF-Tu, a conserved residue in protein elongation factors and the alpha subunits of heterotrimeric guanine nucleotide-binding regulatory proteins (G proteins), abolishes the stabilization of the orthoester acid structure of aminoacyl-tRNA. PMID:8183898

Pharmacologic Suppression of Inflammation by a Diphenyldifluoroketone, EF24, in a Rat Model of Fixed-Volume Hemorrhage Improves Survival

PubMed Central

Yadav, Vivek R.; Sahoo, Kaustuv; Roberts, Pamela R.

2013-01-01

An exaggerated release of proinflammatory cytokines and accompanying inflammation contributes to the development of multiple organ failure after hemorrhagic shock. Here, we tested the nuclear factor (NF) κ-light-chain-enhancer of activated B cell (NF-κB)–mediated transcriptional control of inflammatory pathways as a target in the management of hemorrhage-induced inflammation. We performed a study in a rat model of fixed-volume hemorrhage to investigate the anti-inflammatory effects of the diphenyldifluoroketone EF24 [3,5-bis(2-fluorobenzylidene)piperidin-4-one], an NF-κB inhibitor, in lung tissue. EF24 treatment (0.4 mg/kg) significantly prevented the upregulation of inflammatory biomarkers in rats subjected to 50% hemorrhage and preserved the pulmonary histology in hemorrhaged rats. The lung tissue from treated rats showed marked suppression of the hemorrhage-mediated induction of Toll-like receptor 4, phospho-p65 NF-κB, inducible nitric-oxide synthase, heme oxygenase–1, and cyclooxygenase-2 (COX-2). The hemorrhage-induced COX-2 activity was also significantly inhibited by the EF24 treatment. At the same time, EF24 induced nuclear factor (erythroid-derived 2)-like 2–mediated protective mechanisms against oxidative stress. EF24 also reduced hemorrhage-induced lung myeloperoxidase activity. The plasma levels of proinflammatory tumor necrosis factor-α, interleukin (IL)-6, IL-1α, and IL-1β were lower in EF24-treated rats than in untreated rats. Moreover, there was a significant reduction in the pulmonary expression of high-mobility group B1 protein. These biochemical effects were accompanied by a significant improvement in the survival of rats administered with EF24 as compared with the rats receiving vehicle control (P < 0.05). Overall, the results suggest that EF24 attenuates hemorrhage-induced inflammation and could serve as a salutary anti-inflammatory agent in resuscitation strategies. PMID:23995597

Culture-specific links between maternal executive function, parenting, and preschool children's executive function in South Korea.

PubMed

Lee, Min Kyung; Baker, Sara; Whitebread, David

2018-06-01

Research on the relationships between parental factors and children's executive function (EF) has been conducted mainly in Western cultures. This study provides the first empirical test, in a non-Western context, of how maternal EF and parenting behaviours relate to child EF. South Korean mothers and their preschool children (N = 95 dyads) completed EF tasks. Two aspects of parental scaffolding were observed during a puzzle task: contingency (i.e., adjusting among levels of scaffolding according to the child's ongoing evidence of understanding) and intrusiveness (i.e., directive, mother-centred interactions). Maternal EF and maternal contingency each accounted for unique variance in child EF, above and beyond child age, child language and maternal education. Maternal intrusiveness, however, was not significantly related to child EF. Additionally, no mediating role of parenting was found in the maternal and child EF link. However, child language was found to partially mediate the link between maternal contingency and child EF. These results complement prior findings by revealing distinctive patterns in the link between maternal EF, parenting behaviours, and child EF in the Korean context. © 2018 The British Psychological Society.

Use of early remedial services in children with transposition of the great arteries.

PubMed

Calderon, Johanna; Bonnet, Damien; Pinabiaux, Charlotte; Jambaqué, Isabelle; Angeard, Nathalie

2013-10-01

To characterize the prevalence of use of early remedial services and its associated demographic, medical, and cognitive factors in children aged 4-6 years with corrected transposition of the great arteries (TGA). This was a prospective study of neurocognitive outcomes after TGA. Children underwent formal neuropsychological testing including general intelligence and a comprehensive battery of executive functions (EF) including motor and interference control, short-term memory, and working memory as well as cognitive flexibility. Parental reports on the children's behavior and EF were also evaluated. Demographic factors and preoperative, intraoperative, and postoperative factors as well as cognitive factors were examined according to the current use of remediation. Forty-five patients (67% male) and their parents participated in this study. Twenty-four (53%) patients were receiving remedial services. Male sex, a postnatal diagnosis of TGA, and a longer postoperative intensive care unit stay were significantly associated with use of remediation. Children receiving remediation had lower EF scores, had more severe EF deficits as observed by formal testing, and were rated as having more behavioral daily life difficulties. However, in the group without remediation, 13 children (43%) also displayed EF deficits rated as moderate to severe. Demographic and medical factors could help identify children at higher risk for neurocognitive delays. Evaluation of executive functioning from an early age may influence referral for remediation. Copyright © 2013 Mosby, Inc. All rights reserved.

Targeting tissue factor-expressing tumor angiogenesis and tumors with EF24 conjugated to factor VIIa.

PubMed

Shoji, Mamoru; Sun, Aiming; Kisiel, Walter; Lu, Yang J; Shim, Hyunsuk; McCarey, Bernard E; Nichols, Christopher; Parker, Ernest T; Pohl, Jan; Mosley, Cara A; Alizadeh, Aaron R; Liotta, Dennis C; Snyder, James P

2008-04-01

Tissue factor (TF) is aberrantly expressed on tumor vascular endothelial cells (VECs) and on cancer cells in many malignant tumors, but not on normal VECs, making it a promising target for cancer therapy. As a transmembrane receptor for coagulation factor VIIa (fVIIa), TF forms a high-affinity complex with its cognate ligand, which is subsequently internalized through receptor-mediated endocytosis. Accordingly, we developed a method for selectively delivering EF24, a potent synthetic curcumin analog, to TF-expressing tumor vasculature and tumors using fVIIa as a drug carrier. EF24 was chemically conjugated to fVIIa through a tripeptide-chloromethyl ketone. After binding to TF-expressing targets by fVIIa, EF24 will be endocytosed along with the drug carrier and will exert its cytotoxicity. Our results showed that the conjugate inhibits vascular endothelial growth factor-induced angiogenesis in a rabbit cornea model and in a Matrigel model in athymic nude mice. The conjugate-induced apoptosis in tumor cells and significantly reduced tumor size in human breast cancer xenografts in athymic nude mice as compared with the unconjugated EF24. By conjugating potent drugs to fVIIa, this targeted drug delivery system has the potential to enhance therapeutic efficacy, while reducing toxic side effects. It may also prove to be useful for treating drug-resistant tumors and micro-metastases in addition to primary tumors.

Effects of Exergame Play on EF in Children and Adolescents at a Summer Camp for Low Income Youth

PubMed Central

Flynn, Rachel M.; Richert, Rebekah A.; Staiano, Amanda E.; Wartella, Ellen; Calvert, Sandra L.

2014-01-01

Past research has suggested exergame play improves adolescents’ executive function (EF) skills. EF change in 70 African American and Hispanic/Latino 10- to 16-year-olds participating in an inner-city summer camp was assessed following five 30-minute exergame play sessions. Children’s EF scores improved from pre- to posttest, and factors related to this change were examined. The number of exergame sessions the participants attended predicted posttest scores. In addition, level of achievement during game play was related to EF scores. Finally, the children’s level of enjoyment was not related to EF; however, frustration and boredom during game play were negatively related to EF. The findings are discussed in terms of their implications for the relationship between exergame play and cognitive benefits for adolescent players. PMID:25328562

Effects of Exergame Play on EF in Children and Adolescents at a Summer Camp for Low Income Youth.

PubMed

Flynn, Rachel M; Richert, Rebekah A; Staiano, Amanda E; Wartella, Ellen; Calvert, Sandra L

2014-01-01

Past research has suggested exergame play improves adolescents' executive function (EF) skills. EF change in 70 African American and Hispanic/Latino 10- to 16-year-olds participating in an inner-city summer camp was assessed following five 30-minute exergame play sessions. Children's EF scores improved from pre- to posttest, and factors related to this change were examined. The number of exergame sessions the participants attended predicted posttest scores. In addition, level of achievement during game play was related to EF scores. Finally, the children's level of enjoyment was not related to EF; however, frustration and boredom during game play were negatively related to EF. The findings are discussed in terms of their implications for the relationship between exergame play and cognitive benefits for adolescent players.

Emission factors of air pollutants from CNG-gasoline bi-fuel vehicles: Part II. CO, HC and NOx.

PubMed

Huang, Xiaoyan; Wang, Yang; Xing, Zhenyu; Du, Ke

2016-09-15

The estimation of emission factors (EFs) is the basis of accurate emission inventory. However, the EFs of air pollutants for motor vehicles vary under different operating conditions, which will cause uncertainty in developing emission inventory. Natural gas (NG), considered as a "cleaner" fuel than gasoline, is increasingly being used to reduce combustion emissions. However, information is scarce about how much emission reduction can be achieved by motor vehicles burning NG (NGVs) under real road driving conditions, which is necessary for evaluating the environmental benefits for NGVs. Here, online, in situ measurements of the emissions from nine bi-fuel vehicles were conducted under different operating conditions on the real road. A comparative study was performed for the EFs of black carbon (BC), carbon monoxide (CO), hydrocarbons (HCs) and nitrogen oxides (NOx) for each operating condition when the vehicles using gasoline and compressed NG (CNG) as fuel. BC EFs were reported in part I. The part II in this paper series reports the influence of operating conditions and fuel types on the EFs of CO, HC and NOx. Fuel-based EFs of CO showed good correlations with speed when burning CNG and gasoline. The correlation between fuel-based HC EFs and speed was relatively weak whether burning CNG or gasoline. The fuel-based NOx EFs moderately correlated with speed when burning CNG, but weakly correlated with gasoline. As for HC, the mileage-based EFs of gasoline vehicles are 2.39-12.59 times higher than those of CNG vehicles. The mileage-based NOx EFs of CNG vehicles are slightly higher than those of gasoline vehicles. These results would facilitate a detailed analysis of the environmental benefits for replacing gasoline with CNG in light duty vehicles. Copyright © 2016 Elsevier B.V. All rights reserved.

A new Leukemia Prognostic Scoring System for refractory/relapsed adult acute myelogeneous leukaemia patients: a GOELAMS study.

PubMed

Chevallier, P; Labopin, M; Turlure, P; Prebet, T; Pigneux, A; Hunault, M; Filanovsky, K; Cornillet-Lefebvre, P; Luquet, I; Lode, L; Richebourg, S; Blanchet, O; Gachard, N; Vey, N; Ifrah, N; Milpied, N; Harousseau, J-L; Bene, M-C; Mohty, M; Delaunay, J

2011-06-01

A simplified prognostic score is presented based on the multivariate analysis of 138 refractory/relapsed acute myeloid leukaemia (AML) patients (median age 55 years, range: 19-70) receiving a combination of intensive chemotherapy+Gemtuzumab as salvage regimen. Overall, 2-year event-free survival (EFS) and overall survival (OS) were 29±4% and 36±4%, respectively. Disease status (relapse <12 months, including refractory patients), FLT3-ITD-positive status and high-risk cytogenetics were the three strongest independent adverse prognostic factors for OS and EFS in this series. We then defined three subgroups with striking different outcomes at 2 years: no adverse factor (favourable, N=36): OS 58%, EFS 45%; one adverse factor (intermediate, N=54): OS 37%, EFS 31%; two or three adverse factors (poor, N=43): OS 12%, EFS 12% (P<10(-4), P=0.001). This new simplified Leukemia Prognostic Scoring System was then validated on an independent cohort of 111 refractory/relapsed AML patients. This new simplified prognostic score, using three clinical and biological parameters routinely applied, allow to discriminate around two third of the patients who should benefit from a salvage intensive regimen in the setting of refractory/relapsed AML patients. The other one third of the patients should receive investigational therapy.

The Role of Protein Elongation Factor eEF1A2 in Breast Cancer

DTIC Science & Technology

2006-09-01

serve as regulators of multiple signaling pathways (15-18). PIs are composed of an inositol ring covalently bound to a lipid phosphatidic acid ...mouse model of aristolochic acid nephropathy, and human kidney-proximal tubule cells. Satisfyingly, one of these targets is Dishevelled 2 (DVL2...Rho signaling proteins together. The two human eEF1A isoforms (eEF1A2 and eEF1A2) are very similar proteins (92% amino acid identity). The two

Development of methane emission factors for enteric fermentation in cattle from Benin using IPCC Tier 2 methodology.

PubMed

Kouazounde, J B; Gbenou, J D; Babatounde, S; Srivastava, N; Eggleston, S H; Antwi, C; Baah, J; McAllister, T A

2015-03-01

The objective of this study was to develop emission factors (EF) for methane (CH4) emissions from enteric fermentation in cattle native to Benin. Information on livestock characteristics and diet practices specific to the Benin cattle population were gathered from a variety of sources and used to estimate EF according to Tier 2 methodology of the 2006 Intergovernmental Panel on Climate Change (IPCC) Guidelines for National Greenhouse Gas Inventories. Most cattle from Benin are Bos taurus represented by Borgou, Somba and Lagune breeds. They are mainly multi-purpose, being used for production of meat, milk, hides and draft power and grazed in open pastures and crop lands comprising tropical forages and crops. Estimated enteric CH4 EFs varied among cattle breeds and subcategory owing to differences in proportions of gross energy intake expended to meet maintenance, production and activity. EFs ranged from 15.0 to 43.6, 16.9 to 46.3 and 24.7 to 64.9 kg CH4/head per year for subcategories of Lagune, Somba and Borgou cattle, respectively. Average EFs for cattle breeds were 24.8, 29.5 and 40.2 kg CH4/head per year for Lagune, Somba and Borgou cattle, respectively. The national EF for cattle from Benin was 39.5 kg CH4/head per year. This estimated EF was 27.4% higher than the default EF suggested by IPCC for African cattle with the exception of dairy cattle. The outcome of the study underscores the importance of obtaining country-specific EF to estimate global enteric CH4 emissions.

In Situ Tropical Peatland Fire Emission Factors and Their Variability, as Determined by Field Measurements in Peninsula Malaysia

NASA Astrophysics Data System (ADS)

Smith, T. E. L.; Evers, S.; Yule, C. M.; Gan, J. Y.

2018-01-01

Fires in tropical peatlands account for >25% of estimated total greenhouse gas emissions from deforestation and degradation. Despite significant global and regional impacts, our understanding of specific gaseous fire emission factors (EFs) from tropical peat burning is limited to a handful of studies. Furthermore, there is substantial variability in EFs between sampled fires and/or studies. For example, methane EFs vary by 91% between studies. Here we present new fire EFs for the tropical peatland ecosystem; the first EFs measured for Malaysian peatlands, and only the second comprehensive study of EFs in this crucial environment. During August 2015 (under El Niño conditions) and July 2016, we embarked on field campaigns to measure gaseous emissions at multiple peatland fires burning on deforested land in Southeast Pahang (2015) and oil palm plantations in North Selangor (2016), Peninsula Malaysia. Gaseous emissions were measured using open-path Fourier transform infrared spectroscopy. The IR spectra were used to retrieve mole fractions of 12 different gases present within the smoke (including carbon dioxide and methane), and these measurements used to calculate EFs. Peat samples were taken at each burn site for physicochemical analysis and to explore possible relationships between specific physicochemical properties and fire EFs. Here we present the first evidence to indicate that substrate bulk density affects methane fire EFs reported here. This novel explanation of interplume, within-biome variability, should be considered by those undertaking greenhouse gas accounting and haze forecasting in this region and is of importance to peatland management, particularly with respect to artificial compaction.

Chronic ethanol feeding causes depression of mitochondrial elongation factor Tu in the rat liver: implications for the mitochondrial ribosome.

PubMed

Weiser, Brian; Gonye, Gregory; Sykora, Peter; Crumm, Sara; Cahill, Alan

2011-05-01

Chronic ethanol feeding is known to negatively impact hepatic energy metabolism. Previous studies have indicated that the underlying lesion responsible for this may lie at the level of the mitoribosome. The aim of this study was to characterize the structure of the hepatic mitoribosome in alcoholic male rats and their isocalorically paired controls. Our experiments revealed that chronic ethanol feeding resulted in a significant depletion of both structural (death-associated protein 3) and functional [elongation factor thermo unstable (EF-Tu)] mitoribosomal proteins. In addition, significant increases were found in nucleotide elongation factor thermo stable (EF-Ts) and structural mitochondrial ribosomal protein L12 (MRPL12). The increase in MRPL12 was found to correlate with an increase in the levels of the 39S large mitoribosomal subunit. These changes were accompanied by decreased levels of nuclear- and mitochondrially encoded respiratory subunits, decreased amounts of intact respiratory complexes, decreased hepatic ATP levels, and depressed mitochondrial translation. Mathematical modeling of ethanol-mediated changes in EF-Tu and EF-Ts using prederived kinetic data predicted that the ethanol-mediated decrease in EF-Tu levels could completely account for the impaired mitochondrial protein synthesis. In conclusion, chronic ethanol feeding results in a depletion of mitochondrial EF-Tu levels within the liver that is mathematically predicted to be responsible for the impaired mitochondrial protein synthesis seen in alcoholic animals.

Lopinavir Impairs Protein Synthesis and Induces eEF2 Phosphorylation via the Activation of AMP-Activated Protein Kinase

PubMed Central

Hong-Brown, Ly Q.; Brown, C. Randell; Huber, Danuta S.; Lang, Charles H.

2008-01-01

HIV anti-retroviral drugs decrease protein synthesis, although the underlying regulatory mechanisms of this process are not fully established. Therefore, we investigated the effects of the HIV protease inhibitor lopinavir (LPV) on protein metabolism. We also characterized the mechanisms that mediate the effects of this drug on elongation factor-2 (eEF2), a key component of the translational machinery. Treatment of C2C12 myocytes with LPV produced a dose-dependent inhibitory effect on protein synthesis. This effect was observed at 15 min and was maintained for at least 4 h. Mechanistically, LPV increased the phosphorylation of eEF2 and thereby decreased the activity of this protein. Increased phosphorylation of eEF2 was associated with increased activity of its upstream regulators AMP-activated protein kinase (AMPK) and eEF2 kinase (eEF2K). Both AMPK and eEF2K directly phosphorylated eEF2 in an in vitro kinase assay suggesting two distinct paths lead to eEF2 phosphorylation. To verify this connection, myocytes were treated with the AMPK inhibitor compound C. Compound C blocked eEF2K and eEF2 phosphorylation, demonstrating that LPV affects eEF2 activity via an AMPK-eEF2K dependent pathway. In contrast, incubation of myocytes with rottlerin suppressed eEF2K, but not eEF2 phosphorylation, suggesting that eEF2 can be regulated independent of eEF2K. Finally, LPV did not affect PP2A activity when either eEF2 or peptide was used as the substrate. Collectively, these results indicate that LPV decreases protein synthesis, at least in part, via inhibition of eEF2. This appears regulated by AMPK which can act directly on eEF2 or indirectly via the action of eEF2K. PMID:18712774

Remote Monitoring in Heart Failure: the Current State.

PubMed

Mohan, Rajeev C; Heywood, J Thomas; Small, Roy S

2017-03-01

The treatment of congestive heart failure is an expensive undertaking with much of this cost occurring as a result of hospitalization. It is not surprising that many remote monitoring strategies have been developed to help patients maintain clinical stability by avoiding congestion. Most of these have failed. It seems very unlikely that these failures were the result of any one underlying false assumption but rather from the fact that heart failure is a progressive, deadly disease and that human behavior is hard to modify. One lesson that does stand out from the myriad of methods to detect congestion is that surrogates of congestion, such as weight and impedance, are not reliable or actionable enough to influence outcomes. Too many factors influence these surrogates to successfully and confidently use them to affect HF hospitalization. Surrogates are often attractive because they can be inexpensively measured and followed. They are, however, indirect estimations of congestion, and due to the lack specificity, the time and expense expended affecting the surrogate do not provide enough benefit to warrant its use. We know that high filling pressures cause transudation of fluid into tissues and that pulmonary edema and peripheral edema drive patients to seek medical assistance. Direct measurement of these filling pressures appears to be the sole remote monitoring modality that shows a benefit in altering the course of the disease in these patients. Congestive heart failure is such a serious problem and the consequences of hospitalization so onerous in terms of patient well-being and costs to society that actual hemodynamic monitoring, despite its costs, is beneficial in carefully selected high-risk patients. Those patients who benefit are ones with a prior hospitalization and ongoing New York Heart Association (NYHA) class III symptoms. Patients with NYHA class I and II symptoms do not require hemodynamic monitoring because they largely have normal hemodynamics. Those with NYHA class IV symptoms do not benefit because their hemodynamics are so deranged that they cannot be substantially altered except by mechanical circulatory support or heart transplantation. Finally, hemodynamic monitoring offers substantial hope to those patients with normal ejection fraction (EF) heart failure, a large group for whom medical therapy has largely been a failure. These patients have not benefited from the neurohormonal revolution that improved the lives of their brothers and sisters with reduced ejection fractions. Hemodynamic stabilization improves the condition of both but more so of the normal EF cohort. This is an important observation that will help us design future trials for the 50% of heart failure patients with normal systolic function.

The effect of phosphorylation of the EF-2 isolated from rat liver cells on protein biosynthesis in vitro.

PubMed

Gajko, A; Sredzińska, K; Marcinkiewicz, C; Gałasiński, W

1991-01-01

The activity of EF-2 was distinctly decreased after phosphorylation catalysed by a partly purified calmodulin and Ca2+ dependent protein kinase III. At the same time 32P from [gamma-32P]ATP was incorporated into EF-2 molecule. After dephosphorylation of EF-2 catalysed by alkaline phosphatase the activity of this factor was increased. This suggests that the phosphorylation-dephosphorylation of EF-2 is the regulatory process in the elongation step of the translation. Preliminary purification of the kinase III from rat liver resulted in 8-fold purified enzyme with a recovery of 60%.

Site of ADP-ribosylation and the RNA-binding site are situated in different domains of the elongation factor EF-2

DOE Office of Scientific and Technical Information (OSTI.GOV)

Davydova, E.K.

1987-01-01

One of the proteins participating in the process of elongation of polypeptide chains - elongation factor 2 (EF-2) - can be ADP-ribosylated at a unique amino acid residue - diphthamide. Since the ADP-ribosylation of EF-2 at dipthamide leads to a loss of affinity of the factor for RNA while the presence of RNA inhibits the ADP-ribosylation reaction, it seemed probable to the authors that diphthamide participated directly in the binding of EF-2 to DNA. The experiments presented in this article showed that this was not the case: diphthamide and the RNA-binding site are situated on different domains of EF-2. Thus,more » ADP-ribosylation of factor EF-2 in one domain leads to a loss of the ability to bind to RNA in the other. The authors investigated the mutual arrangement of diphthamide and the RNA-binding site on the EF-2 molecule by preparing a factor from rabbit reticulocytes and subjecting it to proteolytic digestion with elastase. The factor was incubated with elastase for 15 min at 37/sup 0/C at an enzyme:substrate ratio of 1:100 in buffer solution containing 20 mM Tris-HCl, pH 7.6, 10 mM KCl, 1 mM MgCl/sub 2/, and 2 mM dithiothreitol. The reaction was stopped by adding para-methylsulfonyl fluoride to 50 micro-M. The authors obtained a preparation as a result of proteolysis and applied it on a column with RNA-Sepharose and separated into two fractions: RNA-binding and without affinity for RNA. The initial preparation and its fractions were subjected to exhaustive ADP-ribosylation in the presence of diphtheria toxin and (U-/sup 14/C) nicotinaide adenine dinucleotide ((/sup 14/C)NAD) (296 mCi/mmole). The samples were analyzed electrophoretically in a polyacrylamide gel gradient in the presence of sodium dodecyl sulfate. For the detection of (/sup 14/C) ADP-ribosylated components, the gels were dried and exposed with RM-V x-ray film.« less

Executive Function and Magnitude Skills in Preschool Children

PubMed Central

Prager, Emily O.; Sera, Maria D.; Carlson, Stephanie M.

2016-01-01

Executive Function (EF) has been highlighted as a potentially important factor for mathematical understanding. The relation has been well established in school-aged children but has been less explored at younger ages. The current study investigated the relation between EF and mathematics in preschool aged children. Participants were 142 typically developing 3- and 4-year-olds. Controlling for verbal ability, a significant positive correlation was found between EF and general math abilities in this age group. Importantly, we further examined this relation causally by varying the EF load on a magnitude comparison task. Results suggested a developmental pattern wherein 3-year-olds’ performance on the magnitude comparison task was worst when EF was taxed the most. Conversely, 4-year-olds performed well on the magnitude task despite varying EF demands, suggesting that EF might play a critical role in the development of math concepts. PMID:27082019

Heart Failure with Preserved Ejection Fraction: Molecular Pathways of the Aging Myocardium

PubMed Central

Loffredo, Francesco S.; Nikolova, Andriana P.; Pancoast, James R.; Lee, Richard T.

2014-01-01

Age-related diastolic dysfunction is a major factor in the epidemic of heart failure. In patients hospitalized with heart failure, diastolic heart failure is now as common as systolic heart failure. We now have many successful treatments for HFrEF, while specific treatment options for HFpEF patients remain elusive. The lack of treatments for HFpEF reflects our very incomplete understanding of this constellation of diseases. There are many pathophysiological factors in HFpEF, but aging appears to play an important role. Here we propose that aging of the myocardium is itself a specific pathophysiological process. New insights into the aging heart, including hormonal controls and specific molecular pathways such as microRNAs, are pointing to myocardial aging as a potentially reversible process. While the overall process of aging remains mysterious, understanding the molecular pathways of myocardial aging has never been more important. Unraveling these pathways could lead to new therapies for the enormous and growing problem of HFpEF. PMID:24951760

Structure of a novel antibacterial toxin that exploits elongation factor Tu to cleave specific transfer RNAs

DOE PAGES

Michalska, Karolina; Gucinski, Grant C.; Garza-Sanchez, Fernando; ...

2017-08-11

Contact-dependent growth inhibition (CDI) is a mechanism of inter-cellular competition in which Gram-negative bacteria exchange polymorphic toxins using type V secretion systems. Here, we present structures of the CDI toxin from Escherichia coli NC101 in ternary complex with its cognate immunity protein and elongation factor Tu (EF-Tu). The toxin binds exclusively to domain 2 of EF-Tu, partially overlapping the site that interacts with the 3'-end of aminoacyl-tRNA (aa-tRNA). The toxin exerts a unique ribonuclease activity that cleaves the single-stranded 3'-end from tRNAs that contain guanine discriminator nucleotides. EF-Tu is required to support this tRNase activity in vitro, suggesting the toxinmore » specifically cleaves substrate in the context of GTP·EF-Tu·aa-tRNA complexes. However, superimposition of the toxin domain onto previously solved GTP·EF-Tu·aa-tRNA structures reveals potential steric clashes with both aa-tRNA and the switch I region of EF-Tu. Further, the toxin induces conformational changes in EF-Tu, displacing a β-hairpin loop that forms a critical salt-bridge contact with the 3'-terminal adenylate of aa-tRNA. Altogether, these observations suggest that the toxin remodels GTP·EF-Tu·aa-tRNA complexes to free the 3'-end of aa-tRNA for entry into the nuclease active site.« less

Structure of a novel antibacterial toxin that exploits elongation factor Tu to cleave specific transfer RNAs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Michalska, Karolina; Gucinski, Grant C.; Garza-Sanchez, Fernando

Contact-dependent growth inhibition (CDI) is a mechanism of inter-cellular competition in which Gram-negative bacteria exchange polymorphic toxins using type V secretion systems. Here, we present structures of the CDI toxin from Escherichia coli NC101 in ternary complex with its cognate immunity protein and elongation factor Tu (EF-Tu). The toxin binds exclusively to domain 2 of EF-Tu, partially overlapping the site that interacts with the 3'-end of aminoacyl-tRNA (aa-tRNA). The toxin exerts a unique ribonuclease activity that cleaves the single-stranded 3'-end from tRNAs that contain guanine discriminator nucleotides. EF-Tu is required to support this tRNase activity in vitro, suggesting the toxinmore » specifically cleaves substrate in the context of GTP·EF-Tu·aa-tRNA complexes. However, superimposition of the toxin domain onto previously solved GTP·EF-Tu·aa-tRNA structures reveals potential steric clashes with both aa-tRNA and the switch I region of EF-Tu. Further, the toxin induces conformational changes in EF-Tu, displacing a β-hairpin loop that forms a critical salt-bridge contact with the 3'-terminal adenylate of aa-tRNA. Altogether, these observations suggest that the toxin remodels GTP·EF-Tu·aa-tRNA complexes to free the 3'-end of aa-tRNA for entry into the nuclease active site.« less

Cloning and characterization of EF-Tu and EF-Ts from Pseudomonas aeruginosa.

PubMed

Palmer, Stephanie O; Rangel, Edna Y; Montalvo, Alberto E; Tran, Alexis T; Ferguson, Kate C; Bullard, James M

2013-01-01

We have cloned genes encoding elongation factors EF-Tu and EF-Ts from Pseudomonas aeruginosa and expressed and purified the proteins to greater than 95% homogeneity. Sequence analysis indicated that P. aeruginosa EF-Tu and EF-Ts are 84% and 55% identical to E. coli counterparts, respectively. P. aeruginosa EF-Tu was active when assayed in GDP exchange assays. Kinetic parameters for the interaction of EF-Tu with GDP in the absence of EF-Ts were observed to be K M = 33 μM, k cat (obs) = 0.003 s(-1), and the specificity constant k cat (obs)/K M was 0.1 × 10(-3) s(-1) μM(-1). In the presence of EF-Ts, these values were shifted to K M = 2 μM, k cat (obs) = 0.005 s(-1), and the specificity constant k(cat)(obs)/K M was 2.5 × 10(-3) s(-1) μM(-1). The equilibrium dissociation constants governing the binding of EF-Tu to GDP (K GDP) were 30-75 nM and to GTP (K GTP) were 125-200 nM. EF-Ts stimulated the exchange of GDP by EF-Tu 10-fold. P. aeruginosa EF-Tu was active in forming a ternary complex with GTP and aminoacylated tRNA and was functional in poly(U)-dependent binding of Phe-tRNA(Phe) at the A-site of P. aeruginosa ribosomes. P. aeruginosa EF-Tu was active in poly(U)-programmed polyphenylalanine protein synthesis system composed of all P. aeruginosa components.

EF-1 alpha is a target site for an inhibitory effect of quercetin in the peptide elongation process.

PubMed

Marcinkiewicz, C; Gałasiński, W; Gindzieński, A

1995-01-01

The effect of quercetin (3,3',4',5,7-pentahydroxyflavone) on the polypeptide elongation system isolated from rat liver cells, was investigated. Quercetin inhibited [14C]leucine incorporation into proteins in vitro and the inhibitory effect is being directed towards the elongation factor eEF-1, but not to eEF-2 and ribosomes. Quercetin was found to form a complex with EF-1 alpha, which was inactive in GTP-dependent binding to ribosomes. It can be suggested that quercetin can block the total or the part of the domain of EF-1 alpha structure that is responsible for formation of the ternary complex EF-1 alpha-GTP-[14C]Phe-tRNA and therefore preventing formation of the quaternary complex with ribosomes.

Culture-Specific Links between Maternal Executive Function, Parenting, and Preschool Children's Executive Function in South Korea

ERIC Educational Resources Information Center

Lee, Min Kyung; Baker, Sara; Whitebread, David

2018-01-01

Background: Research on the relationships between parental factors and children's executive function (EF) has been conducted mainly in Western cultures. Aim: This study provides the first empirical test, in a non-Western context, of how maternal EF and parenting behaviours relate to child EF. Sample South Korean mothers and their preschool…

Catching Fish and Avoiding Sharks: Investigating Factors That Influence Developmentally Appropriate Measurement of Preschoolers' Inhibitory Control

ERIC Educational Resources Information Center

Howard, Steven J.; Okely, Anthony D.

2015-01-01

Although researchers agree that the first 5 years of life are critical for children's developing executive functions (EFs), further advances are hindered by a lack of consensus on the design and selection of developmentally appropriate EF tasks for young children. Given this debate, well-established adult measures of EF routinely have been adapted…

Energetics of Glutathione Binding to Human Eukaryotic Elongation Factor 1 Gamma: Isothermal Titration Calorimetry and Molecular Dynamics Studies.

PubMed

Tshabalala, Thabiso N; Tomescu, Mihai-Silviu; Prior, Allan; Balakrishnan, Vijayakumar; Sayed, Yasien; Dirr, Heini W; Achilonu, Ikechukwu

2016-12-01

The energetics of ligand binding to human eukaryotic elongation factor 1 gamma (heEF1γ) was investigated using reduced glutathione (GSH), oxidised glutathione (GSSG), glutathione sulfonate and S-hexylglutathione as ligands. The experiments were conducted using isothermal titration calorimetry, and the findings were supported using computational studies. The data show that the binding of these ligands to heEF1γ is enthalpically favourable and entropically driven (except for the binding of GSSG). The full length heEF1γ binds GSSG with lower affinity (K d  = 115 μM), with more hydrogen-bond contacts (ΔH = -73.8 kJ/mol) and unfavourable entropy (-TΔS = 51.7 kJ/mol) compared to the glutathione transferase-like N-terminus domain of heEF1γ, which did not show preference to any specific ligand. Computational free binding energy calculations from the 10 ligand poses show that GSSG and GSH consistently bind heEF1γ, and that both ligands bind at the same site with a folded bioactive conformation. This study reveals the possibility that heEF1γ is a glutathione-binding protein.

Identification and cloning of two immunogenic C. perfringens proteins, elongation factor Tu (EF-Tu) and pyruvate:ferredoxin oxidoreductase (PFO) of Clostridium perfringens

USDA-ARS?s Scientific Manuscript database

Clostridium related poultry diseases such as necrotic enteritis (NE) and gangrenous dermatitis (GD) cause substantial economic losses on a global scale. Two antigenic C. perfringens proteins, elongation factor Tu (EF-Tu) and pyruvate:ferredoxin oxidoreductase (PFO), were identified by reaction with...

Interpreting the paleo-redox record: Mn enrichment factors

NASA Astrophysics Data System (ADS)

Chun, C. O.; Delaney, M. L.

2006-12-01

Redox-sensitive metal enrichment factors (EF), have the ability to describe the redox chemistry of the overlying water and marine sediments at time of burial. Manganese (Mn) precipitates as Mn-rich oxyhydroxides in oxic environments, leading to sedimentary EF > 1 calculated relative to average continental crust as the presumed detrital source. Mn EF can also occur from source changes that are unrelated to redox changes. We compared bulk sediment digestions to sample splits treated with a reductive cleaning step prior to sediment digestion, to test whether the Mn EF are from oxyhydroxides. We measured sedimentary Mn EF for the past 30 m.y. for a Nazca Ridge site in the southeast Pacific (ODP Site 1237). The site is marked by a pronounced color change at 162 mcd, within an interval dominated by calcareous-rich lithology, prompting questions of source versus paleo-redox changes. Mn EF were measured across the Paleocene-Eocene Thermal Maximum (PETM) at three sites on Walvis Ridge in the southeast Atlantic (ODP Sites 1262, 1266, and 1263). The PETM global warming event leads to questions of redox changes. At Nazca Ridge Mn EF range from 10-70 prior to the change with decrease to crustal averages after the boundary. After two reductive cleanings on sediments exhibiting Mn EF >1, Mn EF were at crustal averages. Mn EF prior to the color change are oxyhydroxides and not a major input of detrital material. We suggest the color change represents a paleo-redox boundary, more oxygenated depositional setting prior to the change and more reducing depositional setting afterwards. Walvis Ridge PETM sections exhibit Mn EF values ranging between 4 and 12 prior to the warming, values at crustal averages during the warming, return to pre-event values in the recovery period. After the reductive cleaning procedure the deep (1262) and intermediate (1266) sites with Mn EF >1 before and after the warming event reduced to crustal averages with no change to Mn EF during the event. Bottom waters at those two sites were most likely oxygenated prior to the event, reducing at the onset of the warming, and returned to pre-event conditions in the recovery. Future studies of Mn EF as a paleo-redox indicator should include the reductive cleaning procedure to verify Mn-oxyhydroxides.

Time trend of polycyclic aromatic hydrocarbon emission factors from motor vehicles

NASA Astrophysics Data System (ADS)

Tao, Shu; Shen, Huizhong; Wang, Rong; Sun, Kang

2010-05-01

Motor vehicle is an important emission source of polycyclic aromatic hydrocarbons (PAHs) and this is particularly true in urban areas. Motor vehicle emission factors (EFs) for individual PAH compound reported in the literature varied for 4 to 5 orders of magnitude, leading to high uncertainty in emission estimation. In this study, the major factors affecting EFs were investigated and characterized by regression models. Based on the model developed, a motor vehicle PAH emission inventory at country level was developed. It was found that country and model year are the most important factors affecting EFs for PAHs. The influence of the two factors can be quantified by a single parameter of per capita gross domestic production (purchasing power parity), which was used as the independent variables of the regression models. The models developed using randomly selected 80% of measurements and tested with the remained data accounted for 28 to 48% of the variations in EFs for PAHs measured in 16 countries over 50 years. The regression coefficients of the EF prediction models were molecular weight dependent. Motor vehicle emission of PAHs from individual countries in the world in 1985, 1995, 2005, 2015, and 2025 were calculated and the global emission of total PAHs were 470, 390, and 430 Gg in 1985, 1995, and 2005 and will be 290 and 130 Gg in 2015 and 2025, respectively. The emission is currently passing its peak and will decrease due to significant decrease in China and other developing countries.

Spatially distributed modeling of soil organic carbon across China with improved accuracy

NASA Astrophysics Data System (ADS)

Li, Qi-quan; Zhang, Hao; Jiang, Xin-ye; Luo, Youlin; Wang, Chang-quan; Yue, Tian-xiang; Li, Bing; Gao, Xue-song

2017-06-01

There is a need for more detailed spatial information on soil organic carbon (SOC) for the accurate estimation of SOC stock and earth system models. As it is effective to use environmental factors as auxiliary variables to improve the prediction accuracy of spatially distributed modeling, a combined method (HASM_EF) was developed to predict the spatial pattern of SOC across China using high accuracy surface modeling (HASM), artificial neural network (ANN), and principal component analysis (PCA) to introduce land uses, soil types, climatic factors, topographic attributes, and vegetation cover as predictors. The performance of HASM_EF was compared with ordinary kriging (OK), OK, and HASM combined, respectively, with land uses and soil types (OK_LS and HASM_LS), and regression kriging combined with land uses and soil types (RK_LS). Results showed that HASM_EF obtained the lowest prediction errors and the ratio of performance to deviation (RPD) presented the relative improvements of 89.91%, 63.77%, 55.86%, and 42.14%, respectively, compared to the other four methods. Furthermore, HASM_EF generated more details and more realistic spatial information on SOC. The improved performance of HASM_EF can be attributed to the introduction of more environmental factors, to explicit consideration of the multicollinearity of selected factors and the spatial nonstationarity and nonlinearity of relationships between SOC and selected factors, and to the performance of HASM and ANN. This method may play a useful tool in providing more precise spatial information on soil parameters for global modeling across large areas.

Nephrotic syndrome complicated by idiopathic central diabetes insipidus.

PubMed

Konomoto, Takao; Tanaka, Etsuko; Imamura, Hideaki; Orita, Mayuko; Sawada, Hirotake; Nunoi, Hiroyuki

2014-05-01

There is ongoing discussion regarding the mechanisms underlying edema formation in nephrotic syndrome (NS). Many studies published in the last decade reported that primary renal sodium retention was a major factor in edema formation. However, many of the factors influencing edema formation in NS remain unclear, including the role of arginine vasopressin (AVP). We report a 12-year-old boy with steroid-dependent NS complicated by idiopathic central diabetes insipidus (CDI). He did not develop edema during his first relapse of NS after developing CDI, despite having hypoalbuminemia. He had polydipsia, polyuria, low urine osmolality, and a low serum arginine AVP level. His fractional excretion of sodium was only slightly low. Endocrinological testing and magnetic resonance imaging revealed idiopathic CDI. After starting desmopressin therapy, he developed edema when his NS relapsed. This is the first known reported case of NS in a patient with CDI. The findings suggest that appropriate AVP secretion in response to an increase in serum osmolality caused by renal sodium retention is necessary for excess extracellular fluid accumulation in NS. Further investigation is needed to more fully understand the role of AVP in edema formation in NS.

Improved fermentation performance in an expanded ectopic fermentation system inoculated with thermophilic bacteria.

PubMed

Guo, Hui; Zhu, Changxiong; Geng, Bing; Liu, Xue; Ye, Jing; Tian, Yunlong; Peng, Xiawei

2015-12-01

Previous research showed that ectopic fermentation system (EFS) inoculated with thermophilic bacteria is an excellent alternative for cow wastewater treatment. In this study, the effects of thermophilic bacterial consortium on the efficiency and quality of the fermentation process in EFS were evaluated by measuring physicochemical and environmental factors and the changes in organic matter composition. In parallel, the microbial communities correlated with fermentation performance were identified. Inoculation of EFS with thermophilic bacterial consortium led to higher temperatures, increased wastewater requirements for continuous fermentation, and improved quality of the litters in terms of physicochemical factors, security test, functional group analysis, and bacterial community composition. The relationship between the transformation of organic component and the dominant bacteria species indicated that environmental factors contributed to strain growth, which subsequently promoted the fermentation process. The results highlight the great potential of EFS model for wide application in cow wastewater treatment and re-utilization as bio-fertilizer. Copyright © 2015 Elsevier Ltd. All rights reserved.

Synthetic curcumin analog EF31 inhibits the growth of head and neck squamous cell carcinoma xenografts

PubMed Central

Zhu, Shijun; Moore, Terry W.; Lin, Xiaoqian; Morii, Nao; Mancini, Alessandra; Howard, Randy B.; Culver, Deborah; Arrendale, Richard F.; Reddy, Prabhakar; Evers, Taylor J.; Zhang, Hongzheng; Sica, Gabriel; Chen, Zhuo G.; Sun, Aiming; Fu, Haian; Khuri, Fadlo R.; Shin, Dong M.; Snyder, James P.; Shoji, Mamoru

2013-01-01

Objectives are to examine the efficacy of new synthetic curcumin analogs EF31 in head and neck squamous cell carcinoma in vitro and in vivo, and study their pharmacokinetic and toxicologic effects in vivo. The synthesis of EF31 was described for the first time. Solubility of EF24, EF31 was compared using nephelometric analysis. Human head and neck squamous cell carcinoma Tu212 xenograft tumors were established in athymic nude mice and treated with EF31 i.p. once daily five days a week for about 5 – 6 weeks. The long term effect of EF31 on the NF-κB signaling system in the tumors was examined by Western blot analysis. EF31 at 25 mg/kg, i.p. inhibited tumor growth almost completely. Solubility of EF24 and EF31 are <10, 13 μg/mL or <32, 47 μM, respectively. The serum chemistry profiles of treated mice were within the limits of normal, it revealed a linear increase of Cmax. EF31 decreased the level of phosphorylation of NF-κB p65. In conclusion, the novel synthetic curcumin analogs EF31 is efficacious in inhibiting the growth of Tu212 xenograft tumors and may be useful for treating head and neck squamous cell carcinoma. The long term EF31 treatment inhibited NF-kB p65 phosphorylation in xenografts, implicating downregulation of cancer promoting transcription factors such as angiogenesis and metastasis. PMID:22532032

Synthetic curcumin analog EF31 inhibits the growth of head and neck squamous cell carcinoma xenografts.

PubMed

Zhu, Shijun; Moore, Terry W; Lin, Xiaoqian; Morii, Nao; Mancini, Alessandra; Howard, Randy B; Culver, Deborah; Arrendale, Richard F; Reddy, Prabhakar; Evers, Taylor J; Zhang, Hongzheng; Sica, Gabriel; Chen, Zhuo G; Sun, Aiming; Fu, Haian; Khuri, Fadlo R; Shin, Dong M; Snyder, James P; Shoji, Mamoru

2012-06-01

Objectives are to examine the efficacy, pharmacokinetics, and toxicology of a synthetic curcumin analog EF31 in head and neck squamous cell carcinoma. The synthesis of EF31 was described for the first time. Solubility of EF24 and EF31 was compared using nephelometric analysis. Human head and neck squamous cell carcinoma Tu212 xenograft tumors were established in athymic nude mice and treated with EF31 i.p. once daily five days a week for about 5-6 weeks. The long term effect of EF31 on the NF-κB signaling system in the tumors was examined by Western blot analysis. EF31 at 25 mg kg(-1), i.p. inhibited tumor growth almost completely. Solubilities of EF24 and EF31 are <10 and 13 μg mL(-1) or <32 and 47 μM, respectively. The serum chemistry profiles of treated mice were within the limits of normal, they revealed a linear increase of C(max). EF31 decreased the level of phosphorylation of NF-κB p65. In conclusion, the novel synthetic curcumin analog EF31 is efficacious in inhibiting the growth of Tu212 xenograft tumors and may be useful for treating head and neck squamous cell carcinoma. The long term EF31 treatment inhibited NF-κB p65 phosphorylation in xenografts, implicating downregulation of cancer promoting transcription factors such as angiogenesis and metastasis.

Mortality associated with heart failure with preserved vs. reduced ejection fraction in a prospective international multi-ethnic cohort study.

PubMed

Lam, Carolyn S P; Gamble, Greg D; Ling, Lieng H; Sim, David; Leong, Kui Toh Gerard; Yeo, Poh Shuan Daniel; Ong, Hean Yee; Jaufeerally, Fazlur; Ng, Tze P; Cameron, Vicky A; Poppe, Katrina; Lund, Mayanna; Devlin, Gerry; Troughton, Richard; Richards, A Mark; Doughty, Robert N

2018-05-21

Whether prevalence and mortality of patients with heart failure with preserved or mid-range (40-49%) ejection fraction (HFpEF and HFmREF) are similar to those of heart failure with reduced ejection fraction (HFrEF), as reported in some epidemiologic studies, remains highly controversial. We determined and compared characteristics and outcomes for patients with HFpEF, HFmREF, and HFrEF in a prospective, international, multi-ethnic population. Prospective multi-centre longitudinal study in New Zealand (NZ) and Singapore. Patients with HF were assessed at baseline and followed over 2 years. The primary outcome was death from any cause. Secondary outcome was death and HF hospitalization. Cox proportional hazards models were used to compare outcomes for patients with HFpEF, HFmrEF, and HFrEF. Of 2039 patients enrolled, 28% had HFpEF, 13% HFmrEF, and 59% HFrEF. Compared with HFrEF, patients with HFpEF were older (62 vs. 72 years), more commonly female (17% vs. 48%), and more likely to have a history of hypertension (61% vs. 78%) but less likely to have coronary artery disease (55% vs. 41%). During 2 years of follow-up, 343 (17%) patients died. Adjusting for age, sex, and clinical risk factors, patients with HFpEF had a lower risk of death compared with those with HFrEF (hazard ratio 0.62, 95% confidence interval 0.46-0.85). Plasma (NT-proBNP) was similarly related to mortality in both HFpEF, HFmrEF, and HFrEF independent of the co-variates listed and of ejection fraction. Results were similar for the composite endpoint of death or HF and were consistent between Singapore and NZ. These prospective multinational data showed that the prevalence of HFpEF within the HF population was lower than HFrEF. Death rate was comparable in HFpEF and HFmrEF and lower than in HFrEF. Plasma levels of NT-proBNP were independently and similarly predictive of death in the three HF phenotypes. Australian New Zealand Clinical Trial Registry (ACTRN12610000374066).

Anomalous coagulation factors in non-arteritic anterior ischemic optic neuropathy with central retinal vein occlusion: A case report.

PubMed

Kim, Ji Hong; Kang, Min Ho; Seong, Mincheol; Cho, Heeyoon; Shin, Yong Un

2018-04-01

Non-arteritic anterior ischemic optic neuropathy (NAION) is characterized by sudden, painless visual loss and optic disc edema. NAION occurs mainly in the presence of cardiovascular disease and hypercoagulability, mainly in patients over 50 years of age. We experienced a case of NAION associated with central retinal vein occlusion (CRVO) in a young man with no underlying disease. A 46-year-old man was referred to our clinic following a sudden loss of vision in his right eye. The patient exhibited no underlying disease and reported no ongoing medication. Significant visual loss and visual disturbance of the right eye were observed. The pupil of the right eye was enlarged and an afferent pupillary defect was observed. On fundus examination, retinal hemorrhage was observed in the peripheral retina; macular edema was observed in optical coherence tomography analysis. However, optic disc edema was not evident. No abnormal findings were found in routine blood tests for hypercoagulability. After 3 days of steroid intravenous injection, macular edema disappeared and visual acuity was improved, but optic disc edema began to appear. One week later, optic disc edema was evident and visual acuity was significantly reduced; thus, the patient was diagnosed with NAION. In fluorescein angiography, peripheral retinal ischemia was observed, suggesting that CRVO was complicated. Blood tests, including analysis of coagulation factors, were performed again, showing that coagulation factors IX and XI were increased. Anomalous coagulation factors in non-arteritic anterior ischemic optic neuropathy with central retinal vein occlusion. Systemic steroids were administered. One month later, optic disc edema and retinal hemorrhage gradually diminished and eventually disappeared; however, visual acuity did not recover. In young patients without underlying disease, cases of NAION require careful screening for coagulation disorders. Even if there is no abnormality in the test for routine coagulation status, it may be necessary to confirm a coagulation defect through an additional coagulation factor assay.

The independent and interacting effects of hedonic hunger and executive function on binge eating

PubMed Central

Manasse, Stephanie M.; Espel, Hallie M.; Forman, Evan M.; Ruocco, Anthony C.; Juarascio, Adrienne S.; Butryn, Meghan L.; Zhang, Fengqing; Lowe, Michael R.

2015-01-01

Poor executive function (EF; pre-frontal cognitive control processes governing goal-directed behavior) and elevated hedonic hunger (i.e., preoccupation with palatable foods in the absence of physiological hunger) are theoretical risk and maintenance factors for binge eating (BE) distinct from general obesity. Recent theoretical models posit that dysregulated behavior such as BE may result from a combination of elevated appetitive drive (e.g., hedonic hunger) and decreased EF (e.g., inhibitory control and delayed discounting). The present study sought to test this model in distinguishing BE from general obesity by examining the independent and interactive associations of EF and hedonic hunger with BE group status (i.e., odds of categorization in BE group versus non-BE group). Treatment-seeking overweight and obese women with BE (n = 31) and without BE (OW group; n = 43) were assessed on measures of hedonic hunger and EF (inhibitory control and delay discounting). Elevated hedonic hunger increased the likelihood of categorization in the BE group, regardless of EF. When hedonic hunger was low, poor EF increased the likelihood of categorization in the BE group. Results indicate that the interplay of increased appetitive drives and decreased cognitive function may distinguish BE from overweight/obesity. Future longitudinal investigations of the combinatory effect of hedonic hunger and EF in increasing risk for developing BE are warranted, and may inform future treatment development to target these factors. PMID:25613129

Does Executive Functioning (EF) Predict Depression in Clinic-Referred Adults?: EF Tests vs. Rating Scales

PubMed Central

Knouse, Laura E.; Barkley, Russell A.; Murphy, Kevin R.

2012-01-01

Background Deficits in executive functioning (EF) are implicated in neurobiological and cognitive-processing theories of depression. EF deficits are also associated with Attention-deficit/hyperactivity disorder (ADHD) in adults, who are also at increased risk for depressive disorders. Given debate about the ecological validity of laboratory measures of EF, we investigated the relationship between depression diagnoses and symptoms and EF as measured by both rating scales and tests in a sample of adults referred for evaluation of adult ADHD. Method Data from two groups of adults recruited from an ADHD specialty clinic were analyzed together: Adults diagnosed with ADHD (N=146) and a clinical control group of adults referred for adult ADHD assessment but not diagnosed with the disorder ADHD (N=97). EF was assessed using a rating scale of EF deficits in daily life and a battery of tests tapping various EF constructs. Depression was assessed using current and lifetime SCID diagnoses (major depression, dysthymia) and self-report symptom ratings. Results EF as assessed via rating scale predicted depression across measures even when controlling for current anxiety and impairment. Self-Management to Time and Self-Organization and Problem-Solving showed the most robust relationships. EF tests were weakly and inconsistently related to depression measures. Limitations Prospective studies are needed to rigorously evaluate EF problems as true risk factors for depressive onset. Conclusions EF problems in everyday life were important predictors of depression. Researchers and clinicians should consistently assess for the ADHD-depression comorbidity. Clinicians should consider incorporating strategies to address EF deficits when treating people with depression. PMID:22858220

Elongation factor-2 kinase regulates TG2/β1 integrin/Src/uPAR pathway and epithelial–mesenchymal transition mediating pancreatic cancer cells invasion

PubMed Central

Ashour, Ahmed A; Gurbuz, Nilgun; Alpay, Sultan Neslihan; Abdel-Aziz, Abdel-Aziz H; Mansour, Ahmed M; Huo, Longfei; Ozpolat, Bulent

2014-01-01

Pancreatic ductal adenocarcinoma is one of the lethal cancers with extensive local tumour invasion, metastasis, early systemic dissemination and poorest prognosis. Thus, understanding the mechanisms regulating invasion/metastasis and epithelial–mesenchymal transition (EMT), is the key for developing effective therapeutic strategies for pancreatic cancer (PaCa). Eukaryotic elongation factor-2 kinase (eEF-2K) is an atypical kinase that we found to be highly up-regulated in PaCa cells. However, its role in PaCa invasion/progression remains unknown. Here, we investigated the role of eEF-2K in cellular invasion, and we found that down-regulation of eEF-2K, by siRNA or rottlerin, displays impairment of PaCa cells invasion/migration, with significant decreases in the expression of tissue transglutaminase (TG2), the multifunctional enzyme implicated in regulation of cell attachment, motility and survival. These events were associated with reductions in β1 integrin/uPAR/MMP-2 expressions as well as decrease in Src activity. Furthermore, inhibition of eEF-2K/TG2 axis suppresses the EMT, as demonstrated by the modulation of the zinc finger transcription factors, ZEB1/Snail, and the tight junction proteins, claudins. Importantly, while eEF-2K silencing recapitulates the rottlerin-induced inhibition of invasion and correlated events, eEF-2K overexpression, by lentivirus-based expression system, suppresses such rottlerin effects and potentiates PaCa cells invasion/migration capability. Collectively, our results show, for the first time, that eEF-2K is involved in regulation of the invasive phenotype of PaCa cells through promoting a new signalling pathway, which is mediated by TG2/β1 integrin/Src/uPAR/MMP-2, and the induction of EMT biomarkers which enhance cancer cell motility and metastatic potential. Thus, eEF-2K could represent a novel potential therapeutic target in pancreatic cancer. PMID:25215932

Palliative Care Edema: Patient Population, Causal Factors, and Types of Edema Referred to a Specialist Palliative Care Edema Service.

PubMed

Real, Shirley; Cobbe, Sinead; Slattery, Sinead

2016-07-01

Edema in palliative care patients is a common symptom, however, the research base for all aspects of its care is extremely poor. To evaluate a specialist palliative care edema service in order to report on the patient population referred, the types of edema encountered, and the causes of edema. Prior to study, three different edema types were described for evaluation: lymphedema, nonlymphatic edema, and a combination of the two. Retrospective chart evaluation was completed from August 2013 through January 2014. Patients with edema assessed by the specialist palliative care physiotherapy edema service. Sixty-three cases were included, comprising 10.5% of all new palliative care referrals during the study period. Ninety-two percent (n = 58) had a diagnosis of cancer and 57% (n = 36) were female. Age ranged from 45-97 years. The most common edema type was a mixed edema (46%, n = 29), followed by lymphedema (27%, n = 18) and nonlymphatic edema (16%, n = 10). Lymphorrhea occurred in 9.5% of cases. The most common reasons for edema, based on clinical opinion, were blocked lymphatics (33%) and dependency from immobility (27%). The most common site for edema was in the lower limbs (89%, n = 56). The time lapse from the last treatment to death ranged from 1-225 days. Having a mixed edema type or lymphorrhea was a relatively poor prognostic sign. This is the first study to describe in detail the occurrence of edema in palliative care patients. Edema may be present for many months prior to death making the search for effective treatments imperative.

The role of allergy in the etiology of Reinke's edema on vocal folds.

PubMed

Kravos, Alenka; Zupevc, Avgust; Cizmarevic, Bogdan; Hocevar-Boltezar, Irena

2010-05-01

To identify the role of allergy in the occurrence of Reinke's edema on vocal folds. This was a prospective study in patients with Reinke's edema on vocal folds (n = 80) and a control group of patients without Reinke's edema (n = 80). All the patients were examined by the same ENT specialist at an ENT outpatient center in the period 2001-2003. The control group comprised 80 successive patients from the same clinic who were willing to cooperate in the study and were not already being treated for allergic disease by any specialist other than an ENT specialist. Patients from both groups were examined by rigid laryngoscope, skin prick allergic testing (type I allergy) and laboratory determination of serum thyroid-stimulating hormone level. The prevalence of allergy was not significantly different between the two groups: 20.0% in the patients with Reinke's edema and 23.8% in the control group (P = 0.576). No significant difference was detected in the prevalence of allergy when comparing patients with recurrent Reinke's edema after previous surgical treatment (n = 10) with patients with a first occurrence (n = 70) (P = 1.000). However, we found significantly more type I allergy in the patients with Reinke's edema and chronic hyperplastic rhinitis than in the patients with Reinke's edema without chronic hyperplastic rhinitis. All other risk factors (reflux of gastric content to the larynx, vocal abuse or misuse, unfavorable microclimate conditions at work, thyroid diseases) appeared significantly more often in the group with Reinke's edema on vocal folds than in the control group. Type I allergy is not a crucial factor in the pathogenesis of Reinke's edema on vocal folds or in recurrence of the disease after surgical treatment.

Electric Field Exposure Improves Subjective Symptoms Related to Sleeplessness in College Students: A Pilot Study of Electric Field Therapy for Sleep Disorder

PubMed Central

Ohtsuki, Takashi; Nabeta, Tomoyuki; Nakanishi, Hiromoto; Kawahata, Hirohisa; Ogihara, Toshio; Morishita, Ryuichi; Aoki, Motokuni

2017-01-01

Background: Sleep disorder is a common health problem in modern days. Estab-lishment of safe, non-invasive, convenient and effective treatment is anticipated in the field of complementary and alternative medicine. Objective: We designed a protocol for a randomized controlled trial to investigate the effect of Electric Field (EF) exposure on sleep disorder. Methods: Nineteen college students with sleep disorder, defined as a score of 8 or higher on the Pitzburg Sleep Quality Index, were divided into two groups; EF intervention and sham treatment. EF exposure (50-Hz, 18 kV) was performed for 30 minutes a day for five con-secutive days. Subjective parameters were obtained by an OSA sleep inventory MA version consisting of five factors, and objective parameters were measured using a sleep-scan. Results: Significant improvement in scores of three factors (sleepiness on rising, refreshing and sleep length) was observed after 5 days of EF exposure intervention, as compared to both before intervention and after 5 days of sham treatment. Moreover, improvement rati-os for these three factors were significantly higher in the EF group than in the sham treat-ment group. Analysis of the sleep-scan demonstrated a high improvement ratio for duration of nocturnal awakening in the EF group. Conclusion: The beneficial effect of electric field therapy on sleep disorder in college stu-dents is considered to be beyond a placebo effect. This study raises the therapeutic possibil-ity of electric field exposure.

A Delphi study on environmental factors that impact work and social life participation of individuals with multiple sclerosis in Austria and Switzerland.

PubMed

Prodinger, Birgit; Weise, Andrea P; Shaw, Lynn; Stamm, Tanja A

2010-01-01

This study aimed to gain knowledge about environmental factors (EFs) that impact work and social life participation of people with multiple sclerosis (MS) in Austria and Switzerland to extend the knowledge of participation and to identify key areas for measuring participation. A three-round Delphi study was conducted defining patients as experts. In the 1st round, qualitative data was gathered through questionnaires, analyzed with content analysis, and factors were assigned to EFs as classified in the ICF. In the 2nd and 3rd round, experts judged EFs according to its relevance to obtain consensus (cut-off 75%). Categories were ranked on a scale from mostly important to important. One hundred and twelve Austrian and 109 Swiss experts were recruited. The content analysis revealed 768 EFs. The study resulted in a list of 176 consensus factors for Austria and 177 Switzerland. Five categories revealed to be highly important, 12 moderately important, 6 fairly important, and 10 important. This study indicates that participation in work or social life is influenced by physical, social, attitudinal, and policy factors. Consensus factors afford insights into areas for consideration in the development of participation outcome measurements and support a comprehensive and inclusive rehabilitation approach.

[RS3PE associated with tuberculosis].

PubMed

Nicolás-Sánchez, F J; Rozadilla Sacanell, J R; Gort Oromí, A M; Torres Cortada, G; Soler Rosell, T; Sarrat-Nuevo, R M; Nicolás-Sánchez, M E; Cabau-Rubies, J

2007-10-01

The remitting seronegative symmetrical synovitis with pitting edema of the elderly patient with edema and fovea (RS3PE), characterizes for the appearance of one polyarthritis symmetrical with fovea in the back of the hands, and negative reumatoideal factor. The association to tuberculosis had not been described before. One presents the case of a 89-year-old patient who consulted for anorexia of month and a half of evolution accompanied of edema in hands and feet, with negative reumatoideal factor. He was presenting a pulmonary infiltrated, which microbiological study revealed the infection for Mycobacterium tuberculosis.

Early Executive Function at Age Two Predicts Emergent Mathematics and Literacy at Age Five

PubMed Central

Mulder, Hanna; Verhagen, Josje; Van der Ven, Sanne H. G.; Slot, Pauline L.; Leseman, Paul P. M.

2017-01-01

Previous work has shown that individual differences in executive function (EF) are predictive of academic skills in preschoolers, kindergartners, and older children. Across studies, EF is a stronger predictor of emergent mathematics than literacy. However, research on EF in children below age three is scarce, and it is currently unknown whether EF, as assessed in toddlerhood, predicts emergent academic skills a few years later. This longitudinal study investigates whether early EF, assessed at two years, predicts (emergent) academic skills, at five years. It examines, furthermore, whether early EF is a significantly stronger predictor of emergent mathematics than of emergent literacy, as has been found in previous work on older children. A sample of 552 children was assessed on various EF and EF-precursor tasks at two years. At age five, these children performed several emergent mathematics and literacy tasks. Structural Equation Modeling was used to investigate the relationships between early EF and academic skills, modeled as latent factors. Results showed that early EF at age two was a significant and relatively strong predictor of both emergent mathematics and literacy at age five, after controlling for receptive vocabulary, parental education, and home language. Predictive relations were significantly stronger for mathematics than literacy, but only when a verbal short-term memory measure was left out as an indicator to the latent early EF construct. These findings show that individual differences in emergent academic skills just prior to entry into the formal education system can be traced back to individual differences in early EF in toddlerhood. In addition, these results highlight the importance of task selection when assessing early EF as a predictor of later outcomes, and call for further studies to elucidate the mechanisms through which individual differences in early EF and precursors to EF come about. PMID:29075209

Early Executive Function at Age Two Predicts Emergent Mathematics and Literacy at Age Five.

PubMed

Mulder, Hanna; Verhagen, Josje; Van der Ven, Sanne H G; Slot, Pauline L; Leseman, Paul P M

2017-01-01

Previous work has shown that individual differences in executive function (EF) are predictive of academic skills in preschoolers, kindergartners, and older children. Across studies, EF is a stronger predictor of emergent mathematics than literacy. However, research on EF in children below age three is scarce, and it is currently unknown whether EF, as assessed in toddlerhood, predicts emergent academic skills a few years later. This longitudinal study investigates whether early EF, assessed at two years, predicts (emergent) academic skills, at five years. It examines, furthermore, whether early EF is a significantly stronger predictor of emergent mathematics than of emergent literacy, as has been found in previous work on older children. A sample of 552 children was assessed on various EF and EF-precursor tasks at two years. At age five, these children performed several emergent mathematics and literacy tasks. Structural Equation Modeling was used to investigate the relationships between early EF and academic skills, modeled as latent factors. Results showed that early EF at age two was a significant and relatively strong predictor of both emergent mathematics and literacy at age five, after controlling for receptive vocabulary, parental education, and home language. Predictive relations were significantly stronger for mathematics than literacy, but only when a verbal short-term memory measure was left out as an indicator to the latent early EF construct. These findings show that individual differences in emergent academic skills just prior to entry into the formal education system can be traced back to individual differences in early EF in toddlerhood. In addition, these results highlight the importance of task selection when assessing early EF as a predictor of later outcomes, and call for further studies to elucidate the mechanisms through which individual differences in early EF and precursors to EF come about.

On the indiscriminate use of imported emission factors in environmental impact assessment: A case study in Chile

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bernal, María Fernanda; Oyarzún, Jorge; Oyarzún, Ricardo, E-mail: royarzun@userena.cl

Environmental Impact Assessment (EIA) aims to determine if the environmental effect of an activity or project complies with standards and regulations. A primary component of the environment to evaluate is air and the effect that various activities can have on its quality. To this end, emission factors (EFs), which are empirical coefficients or mathematical relationships, are normally used. The present research critically analyzes the implications and consequences of using imported EFs in environmental impact studies (EISs), taking as case of study the situation in Chile. Among the main results, the widespread use of EFs in EISs in the country andmore » the lack of assessments of their actual applicability stand out. In addition, the official guidelines related to emissions estimation that are used for EIA in the country mostly include EFs derived elsewhere, without considering the recommendations or restrictions that the original sources indicate for their use. Finally, the broad use of default values defined for the Metropolitan Region in Central Chile, is highly questionable for a country that extends north-south along more than 35° of latitude, with wide variability in climate, traffic conditions, population, soil types, etc. Finally, it is very likely that situations similar to those observed in the present work occurs in other countries with young environmental impact assessment systems, and therefore, that the results herein presented should be of general interest and relevance. - Highlights: • Emission factors are widely used in environmental impact assessment in Chile. • There is a lack of a proper understanding of the limitations of EFs for EIA. • Imported emission factors use requires caution and full understanding. • Misuse of foreign EFs may have serious environmental and economic consequences.« less

Proteomic analysis of trichloroethylene-induced alterations in expression, distribution, and interactions of SET/TAF-Iα and two SET/TAF-Iα-binding proteins, eEF1A1 and eEF1A2, in hepatic L-02 cells.

PubMed

Hong, Wen-Xu; Yang, Liang; Chen, Moutong; Yang, Xifei; Ren, Xiaohu; Fang, Shisong; Ye, Jinbo; Huang, Haiyan; Peng, Chaoqiong; Zhou, Li; Huang, Xinfeng; Yang, Fan; Wu, Desheng; Zhuang, Zhixiong; Liu, Jianjun

2012-09-01

Emerging evidence indicates that trichloroethylene (TCE) exposure causes severe hepatotoxicity. However, the mechanisms of TCE hepatotoxicity remain unclear. Recently, we reported that TCE exposure up-regulated the expression of the oncoprotein SET/TAF-Iα and SET knockdown attenuated TCE-induced cytotoxicity in hepatic L-02 cells. To decipher the function of SET/TAF-Iα and its contributions to TCE-induced hepatotoxicity, we employed a proteomic analysis of SET/TAF-Iα with tandem affinity purification to identify SET/TAF-Iα-binding proteins. We identified 42 novel Gene Ontology co-annotated SET/TAF-Iα-binding proteins. The identifications of two of these proteins (eEF1A1, elongation factor 1-alpha 1; eEF1A2, elongation factor 1-alpha 2) were confirmed by Western blot analysis and co-immunoprecipitation (Co-IP). Furthermore, we analyzed the effects of TCE on the expression, distribution and interactions of eEF1A1, eEF1A2 and SET in L-02 cells. Western blot analysis reveals a significant up-regulation of eEF1A1, eEF1A2 and two isoforms of SET, and immunocytochemical analysis reveals that eEF1A1 and SET is redistributed by TCE. SET is redistributed from the nucleus to the cytoplasm, while eFE1A1 is translocated from the cytoplasm to the nucleus. Moreover, we find by Co-IP that TCE exposure significantly increases the interaction of SET with eEF1A2. Our data not only provide insights into the physiological functions of SET/TAF-Iα and complement the SET interaction networks, but also demonstrate that TCE exposure induces alterations in the expression, distribution and interactions of SET and its binding partners. These alterations may constitute the mechanisms of TCE cytotoxicity. Copyright © 2012 Elsevier Inc. All rights reserved.

Multiple anticancer activities of EF24, a novel curcumin analog, on human ovarian carcinoma cells.

PubMed

Tan, Xin; Sidell, Neil; Mancini, Alessandra; Huang, Ruo-Pan; Shenming Wang; Horowitz, Ira R; Liotta, Dennis C; Taylor, Robert N; Wieser, Friedrich

2010-10-01

Curcumin, a component of turmeric, has been reported to exhibit potential antitumor activities. This study assessed the effects of a novel synthetic curcumin analog, EF24, on proliferation, apoptosis, and vascular endothelial growth factor (VEGF) regulation in platinum-sensitive (IGROV1) and platinum-resistant (SK-OV-3) human ovarian cancer cells. EF24 time- and dose-dependently suppressed the growth of both cell lines and synergized with cisplatin to induce apoptosis. Although treatment with EF24 had no significant effect on VEGF messenger RNA (mRNA) expression,VEGF protein secretion into conditioned media was dose-dependently reduced with EF24 demonstrating ∼8-fold greater potency than curcumin (P < .05). EF24 significantly inhibited hydrogen peroxide (H(2)O(2))-induced VEGF expression, as did the phenolic antioxidant tert-butylhydroquinone (t-BHQ). EF24 upregulated cellular antioxidant responses as observed by the suppression of reactive oxygen species (ROS) generation and activation of antioxidant response element (ARE)-dependent gene transcription. Given its high potency, EF24 is an excellent lead candidate for further development as an adjuvant therapeutic agent in preclinical models of ovarian cancer.

A prospective study on MRI findings and prognostic factors in athletes with MTSS.

PubMed

Moen, M H; Schmikli, S L; Weir, A; Steeneken, V; Stapper, G; de Slegte, R; Tol, J L; Backx, F J G

2014-02-01

In medial tibial stress syndrome (MTSS) bone marrow and periosteal edema of the tibia on the magnetic resonance imaging (MRI) is frequently reported. The relationship between these MRI findings and recovery has not been previously studied. This prospective study describes MRI findings of 52 athletes with MTSS. Baseline characteristics were recorded and recovery was related to these parameters and MRI findings to examine for prognostic factors. Results showed that 43.5% of the symptomatic legs showed bone marrow or periosteal edema. Absence of periosteal and bone marrow edema on MRI was associated with longer recovery (P = 0.033 and P = 0.013). A clinical scoring system for sports activity (SARS score) was significantly higher in the presence of bone marrow edema (P = 0.027). When clinical scoring systems (SARS score and the Lower Extremity Functional Scale) were combined in a model, time to recovery could be predicted substantially (explaining 54% of variance, P = 0.006). In conclusion, in athletes with MTSS, bone marrow or periosteal edema is seen on MRI in 43,5% of the symptomatic legs. Furthermore, periosteal and bone marrow edema on MRI and clinical scoring systems are prognostic factors. Future studies should focus on MRI findings in symptomatic MTSS and compare these with a matched control group. © 2012 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Duplication of Drosophila melanogaster mitochondrial EF-Tu: pre-adaptation to T-arm truncation and exclusion of bulky aminoacyl residues.

PubMed

Sato, Aya; Suematsu, Takuma; Aihara, Koh-Ki; Kita, Kiyoshi; Suzuki, Tsutomu; Watanabe, Kimitsuna; Ohtsuki, Takashi; Watanabe, Yoh-Ichi

2017-03-07

Translation elongation factor Tu (EF-Tu) delivers aminoacyl-tRNA (aa-tRNA) to ribosomes in protein synthesis. EF-Tu generally recognizes aminoacyl moieties and acceptor- and T-stems of aa-tRNAs. However, nematode mitochondrial (mt) tRNAs frequently lack all or part of the T-arm that is recognized by canonical EF-Tu. We previously reported that two distinct EF-Tu species, EF-Tu1 and EF-Tu2, respectively, recognize mt tRNAs lacking T-arms and D-arms in the mitochondria of the chromadorean nematode Caenorhabditis elegans C. elegans EF-Tu2 specifically recognizes the seryl moiety of serylated D-armless tRNAs. Mitochondria of the enoplean nematode Trichinella possess three structural types of tRNAs: T-armless tRNAs, D-armless tRNAs, and cloverleaf tRNAs with a short T-arm. Trichinella mt EF-Tu1 binds to all three types and EF-Tu2 binds only to D-armless Ser-tRNAs, showing an evolutionary intermediate state from canonical EF-Tu to chromadorean nematode (e.g. C. elegans ) EF-Tu species. We report here that two EF-Tu species also participate in Drosophila melanogaster mitochondria. Both D. melanogaster EF-Tu1 and EF-Tu2 bound to cloverleaf and D-armless tRNAs. D. melanogaster EF-Tu1 has the ability to recognize T-armless tRNAs that do not evidently exist in D. melanogaster mitochondria, but do exist in related arthropod species. In addition, D. melanogaster EF-Tu2 preferentially bound to aa-tRNAs carrying small amino acids, but not to aa-tRNAs carrying bulky amino acids. These results suggest that the Drosophila mt translation system could be another intermediate state between the canonical and nematode mitochondria-type translation systems. © 2017 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

A Complex Distribution of Elongation Family GTPases EF1A and EFL in Basal Alveolate Lineages

PubMed Central

Mikhailov, Kirill V.; Janouškovec, Jan; Tikhonenkov, Denis V.; Mirzaeva, Gulnara S.; Diakin, Andrei Yu.; Simdyanov, Timur G.; Mylnikov, Alexander P.; Keeling, Patrick J.; Aleoshin, Vladimir V.

2014-01-01

Translation elongation factor-1 alpha (EF1A) and the related GTPase EF-like (EFL) are two proteins with a complex mutually exclusive distribution across the tree of eukaryotes. Recent surveys revealed that the distribution of the two GTPases in even closely related taxa is frequently at odds with their phylogenetic relationships. Here, we investigate the distribution of EF1A and EFL in the alveolate supergroup. Alveolates comprise three major lineages: ciliates and apicomplexans encode EF1A, whereas dinoflagellates encode EFL. We searched transcriptome databases for seven early-diverging alveolate taxa that do not belong to any of these groups: colpodellids, chromerids, and colponemids. Current data suggest all seven are expected to encode EF1A, but we find three genera encode EFL: Colpodella, Voromonas, and the photosynthetic Chromera. Comparing this distribution with the phylogeny of alveolates suggests that EF1A and EFL evolution in alveolates cannot be explained by a simple horizontal gene transfer event or lineage sorting. PMID:25179686

Emulsifier of Arthrobacter RAG-1: specificity of hydrocarbon substrate.

PubMed Central

Rosenberg, E; Perry, A; Gibson, D T; Gutnick, D L

1979-01-01

The purified extracellular emulsifying factor produced by Arthrobacter RAG-1 (EF-RAG) emulsified light petroleum oil, diesel oil, and a variety of crude oils and gas oils. Although kerosine and gasoline were emulsified poorly by EF-RAG, they were converted into good substrates for emulsification by addition of aromatic compounds, such as 2-methylnaphthalene. Neither aromatic nor aliphatic fractions of crude oil were emulsified by EF-RAG; however, mixtures containing both fractions were emulsified. Pure aliphatic or aromatic hydrocarbons were emulsified poorly by EF-RAG. Binary mixtures containing an aliphatic and an aromatic hydrocarbon, however, were excellent substrates for EF-RAG-induced emulsification. Of a variety of alkylcyclohexane and alkylbenzene derivatives tested, only hexyl- or heptylbenzene and octyl- or decylcyclohexane were effectively emulsified by EF-RAG. These data indicate that for EF-RAG to induce emulsification of hydrocarbons in water, the hydrocarbon substrate must contain both aliphatic and cyclic components. With binary mixtures of methylnaphthalene and hexadecane, maximum emulsion was obtained with 25% hexadecane. PMID:453821

eEF2K/eEF2 Pathway Controls the Excitation/Inhibition Balance and Susceptibility to Epileptic Seizures

PubMed Central

Heise, Christopher; Taha, Elham; Murru, Luca; Ponzoni, Luisa; Cattaneo, Angela; Guarnieri, Fabrizia C.; Montani, Caterina; Mossa, Adele; Vezzoli, Elena; Ippolito, Giulio; Zapata, Jonathan; Barrera, Iliana; Ryazanov, Alexey G.; Cook, James; Poe, Michael; Stephen, Michael Rajesh; Kopanitsa, Maksym; Benfante, Roberta; Rusconi, Francesco; Braida, Daniela; Francolini, Maura; Proud, Christopher G.; Valtorta, Flavia; Passafaro, Maria; Sala, Mariaelvina; Bachi, Angela; Verpelli, Chiara; Rosenblum, Kobi; Sala, Carlo

2017-01-01

Abstract Alterations in the balance of inhibitory and excitatory synaptic transmission have been implicated in the pathogenesis of neurological disorders such as epilepsy. Eukaryotic elongation factor 2 kinase (eEF2K) is a highly regulated, ubiquitous kinase involved in the control of protein translation. Here, we show that eEF2K activity negatively regulates GABAergic synaptic transmission. Indeed, loss of eEF2K increases GABAergic synaptic transmission by upregulating the presynaptic protein Synapsin 2b and α5-containing GABAA receptors and thus interferes with the excitation/inhibition balance. This cellular phenotype is accompanied by an increased resistance to epilepsy and an impairment of only a specific hippocampal-dependent fear conditioning. From a clinical perspective, our results identify eEF2K as a potential novel target for antiepileptic drugs, since pharmacological and genetic inhibition of eEF2K can revert the epileptic phenotype in a mouse model of human epilepsy. PMID:27005990

Flt1/VEGFR1 heterozygosity causes transient embryonic edema.

PubMed

Otowa, Yasunori; Moriwaki, Kazumasa; Sano, Keigo; Shirakabe, Masanori; Yonemura, Shigenobu; Shibuya, Masabumi; Rossant, Janet; Suda, Toshio; Kakeji, Yoshihiro; Hirashima, Masanori

2016-06-02

Vascular endothelial growth factor-A is a major player in vascular development and a potent vascular permeability factor under physiological and pathological conditions by binding to a decoy receptor Flt1 and its primary receptor Flk1. In this study, we show that Flt1 heterozygous (Flt1(+/-)) mouse embryos grow up to adult without life-threatening abnormalities but exhibit a transient embryonic edema around the nuchal and back regions, which is reminiscent of increased nuchal translucency in human fetuses. Vascular permeability is enhanced and an intricate infolding of the plasma membrane and huge vesicle-like structures are seen in Flt1(+/-) capillary endothelial cells. Flk1 tyrosine phosphorylation is elevated in Flt1(+/-) embryos, but Flk1 heterozygosity does not suppress embryonic edema caused by Flt1 heterozygosity. When Flt1 mutants are crossed with Aspp1(-/-) mice which exhibit a transient embryonic edema with delayed formation and dysfunction of lymphatic vessels, only 5.7% of Flt1(+/-); Aspp1(-/-) mice survive, compared to expected ratio (25%). Our results demonstrate that Flt1 heterozygosity causes a transient embryonic edema and can be a risk factor for embryonic lethality in combination with other mutations causing non-lethal vascular phenotype.

Are emissions of black carbon from gasoline vehicles overestimated? Real-time, in situ measurement of black carbon emission factors.

PubMed

Wang, Yang; Xing, Zhenyu; Zhao, Shuhui; Zheng, Mei; Mu, Chao; Du, Ke

2016-03-15

Accurately quantifying black carbon (BC) emission factors (EFs) is a prerequisite for estimation of BC emission inventory. BC EFs determined by measuring BC at the roadside or chasing a vehicle on-road may introduce large uncertainty for low emission vehicles. In this study, BC concentrations were measured inside the tailpipe of gasoline vehicles with different engine sizes under different driving modes to determine the respective EFs. BC EFs ranged from 0.005-7.14 mg/kg-fuel under the speeds of 20-70 km/h, 0.05-28.95 mg/kg-fuel under the accelerations of 0.5-1.5m/s(2). Although the water vapor in the sampling stream could result in an average of 12% negative bias, the BC EFs are significantly lower than the published results obtained with roadside or chasing vehicle measurement. It is suggested to conduct measurement at the tailpipe of gasoline vehicles instead of in the atmosphere behind the vehicles to reduce the uncertainty from fluctuation in ambient BC concentration. Copyright © 2015 Elsevier B.V. All rights reserved.

Lethal factor is not required for Bacillus anthracis virulence in guinea pigs and rabbits.

PubMed

Levy, Haim; Weiss, Shay; Altboum, Zeev; Schlomovitz, Josef; Rothschild, Nili; Blachinsky, Eran; Kobiler, David

2011-11-01

The major virulence factor of Bacillus anthracis is the tripartite anthrax toxin, comprising the protective antigen (PA), lethal factor (LF) and edema factor (EF). The LF of B. anthracis is a metalloprotease that has been shown to play an important role in pathogenicity. Deletion of this gene (lef) in the Sterne strain was reported to dramatically reduce the pathogenicity of this strain in mice, and was reported to be as dramatic as the deletion of PA. We evaluated the effect on pathogenicity of the lef deletion in the fully virulent Vollum strain in guinea pigs and NZW rabbits by either subcutaneous injection or intranasal instillation. In guinea pigs, no major differences between the mutant strain and the wild type could be detected in the LD(50) or mean time to death values. On the other hand, the lef deletion caused death of 50-70% of all rabbits infected with the mutant spores at doses equivalent or higher than the wild type LD(50). The surviving rabbits, which were infected with spore doses higher than the wild type LD(50), developed a protective immune response that conferred resistance to challenge with the wild type strain. These findings may indicate that the mutant lacking the LF is capable of host colonization which causes death in 50-70% of the animals and a protective immune response in the others. These results indicate that unlike the data obtained in mice, the LF mutation does not abolish B. anthracis pathogenicity. Copyright © 2011 Elsevier Ltd. All rights reserved.

Electrical control of cell polarization in the fission yeast Schizosaccharomyces pombe.

PubMed

Minc, Nicolas; Chang, Fred

2010-04-27

Electric signals surround tissues and cells and have been proposed to participate in directing cell polarity in processes such as development, wound healing, and host invasion [1, 2]. The application of exogenous electric fields (EFs) can direct cell polarization in cell types ranging from bacteria and fungi to neurons and neutrophils [3-7]. The mechanisms by which EFs modulate cell polarity, however, remain poorly understood. Here we introduce the fission yeast Schizosaccharomyces pombe as a model organism to elucidate the mechanisms underlying this process. In these rod-shaped cells, an exogenous EF reorients cell growth in a direction orthogonal to the field, producing cells with a bent morphology. A candidate genetic screen identifies conserved factors involved in this process: an integral membrane proton ATPase pma1p that regulates intracellular pH, the small GTPase cdc42p, and the formin for3p that assembles actin cables. Interestingly, mutants in these genes still respond to the EF but orient in a different direction, toward the anode. In addition, EFs also cause electrophoretic movement of cell wall synthase complex proteins toward the anode. These data suggest molecular models for how the EF reorients cell polarization by modulating intracellular pH and steering cell polarity factors in multiple directions. Copyright © 2010 Elsevier Ltd. All rights reserved.

Design, synthesis, and biological evaluation of novel EF24 and EF31 analogs as potential IκB kinase β inhibitors for the treatment of pancreatic cancer.

PubMed

Xie, Xuemeng; Tu, Jinfu; You, Heyi; Hu, Bingren

2017-01-01

Given the important role that inhibitory kappa B (IκB) kinase β (IKKβ) plays in pancreatic cancer (PC) development and progression, inhibitors targeting IKKβ are believed to be increasingly popular as novel anti-PC therapies. Two synthetic molecules, named EF24 and EF31 , exhibited favorable potential in terms of inhibition of both IKKβ activity and PC cell proliferation. Aiming to enhance their cellular efficacy and to analyze their structure-activity relationship, four series of EF24 and EF31 analogs were designed and synthesized. Through kinase activity and vitality screening of cancer cells, D6 displayed excellent inhibition of both IKKβ activity and PC cell proliferation. Additionally, multiple biological evaluations showed that D6 was directly bound to IKKβ and significantly suppressed the activation of the IKKβ/nuclear factor κB pathway induced by tumor necrosis factor-α, as well as effectively inducing cancer cell apoptosis. Moreover, molecular docking and molecular dynamics simulation analysis indicated that the dominant force between D6 and IKKβ comprised hydrophobic interactions. In conclusion, D6 may be a promising therapeutic agent for PC treatment and it also provides a structural lead for the design of novel IKKβ inhibitors.

Design, synthesis, and biological evaluation of novel EF24 and EF31 analogs as potential IκB kinase β inhibitors for the treatment of pancreatic cancer

PubMed Central

Xie, Xuemeng; Tu, Jinfu; You, Heyi; Hu, Bingren

2017-01-01

Given the important role that inhibitory kappa B (IκB) kinase β (IKKβ) plays in pancreatic cancer (PC) development and progression, inhibitors targeting IKKβ are believed to be increasingly popular as novel anti-PC therapies. Two synthetic molecules, named EF24 and EF31, exhibited favorable potential in terms of inhibition of both IKKβ activity and PC cell proliferation. Aiming to enhance their cellular efficacy and to analyze their structure–activity relationship, four series of EF24 and EF31 analogs were designed and synthesized. Through kinase activity and vitality screening of cancer cells, D6 displayed excellent inhibition of both IKKβ activity and PC cell proliferation. Additionally, multiple biological evaluations showed that D6 was directly bound to IKKβ and significantly suppressed the activation of the IKKβ/nuclear factor κB pathway induced by tumor necrosis factor-α, as well as effectively inducing cancer cell apoptosis. Moreover, molecular docking and molecular dynamics simulation analysis indicated that the dominant force between D6 and IKKβ comprised hydrophobic interactions. In conclusion, D6 may be a promising therapeutic agent for PC treatment and it also provides a structural lead for the design of novel IKKβ inhibitors. PMID:28553074

Mechanism and influencing factors on critical pulse width of oil-immersed polymer insulators under short pulses

NASA Astrophysics Data System (ADS)

Zhao, Liang; Su, Jian Cang; Li, Rui; Zeng, Bo; Cheng, Jie; Zheng, Lei; Yu, Bin Xiong; Wu, Xiao Long; Zhang, Xi Bo; Pan, Ya Feng

2015-04-01

The critical pulse width (τc) is a pulse width at which the surface flashover threshold (Ef) is equal to the bulk breakdown threshold (EBD) for liquid-polymer composite insulation systems, which is discovered by Zhao et al. [Annual Report Conference on Electrical Insulation and Dielectric Phenomena (IEEE Dielectrics and Electrical Insulation Society, Shenzhen, China, 2013), Vol. 2, pp. 854-857]. In this paper, the mechanism of τc is interpreted in perspective of the threshold and the time delay (td) of surface flashover and bulk breakdown, respectively. It is found that two changes appear as the pulse width decreases which are responsible for the existence of τc: (1) EBD is lower than Ef; (2) td of bulk breakdown is shorter than td of surface flashover. In addition, factors which have influences on τc are investigated, such as the dielectric type, the insulation length, the dielectric thickness, the dielectrics configuration, the pulse number, and the liquid purity. These influences of factors are generalized as three types if τc is expected to increase: (1) factors causing EBD to decrease, such as increasing the pulse number or employing a dielectric of lower EBD; (2) factors causing Ef to increase, such as complicating the insulator's configuration or increasing the liquid purity; (3) factors causing EBD and Ef to increase together, but Ef increases faster than EBD, such as decreasing the dielectric thickness or the insulation length. With the data in references, all the three cases are verified experimentally. In the end, a general method based on τc for solid insulation design is presented and the significance of τc on solid insulation design and on solid demolition are discussed.

Reductions in emissions of carbonaceous particulate matter and polycyclic aromatic hydrocarbons from combustion of biomass pellets in comparison with raw fuel burning.

PubMed

Shen, Guofeng; Tao, Shu; Wei, Siye; Zhang, Yanyan; Wang, Rong; Wang, Bin; Li, Wei; Shen, Huizhong; Huang, Ye; Chen, Yuanchen; Chen, Han; Yang, Yifeng; Wang, Wei; Wei, Wen; Wang, Xilong; Liu, Wenxing; Wang, Xuejun; Masse Simonich, Staci L y

2012-06-05

Biomass pellets are emerging as a cleaner alternative to traditional biomass fuels. The potential benefits of using biomass pellets include improving energy utilization efficiency and reducing emissions of air pollutants. To assess the environmental, climate, and health significance of replacing traditional fuels with biomass pellets, it is critical to measure the emission factors (EFs) of various pollutants from pellet burning. However, only a few field measurements have been conducted on the emissions of carbon monoxide (CO), particulate matter (PM), and polycyclic aromatic hydrocarbons (PAHs) from the combustion of pellets. In this study, pine wood and corn straw pellets were burned in a pellet burner (2.6 kW), and the EFs of CO, organic carbon, elemental carbon, PM, and PAHs (EF(CO), EF(OC), EF(EC), EF(PM), and EF(PAH)) were determined. The average EF(CO), EF(OC), EF(EC), and EF(PM) were 1520 ± 1170, 8.68 ± 11.4, 11.2 ± 8.7, and 188 ± 87 mg/MJ for corn straw pellets and 266 ± 137, 5.74 ± 7.17, 2.02 ± 1.57, and 71.0 ± 54.0 mg/MJ for pine wood pellets, respectively. Total carbonaceous carbon constituted 8 to 14% of the PM mass emitted. The measured values of EF(PAH) for the two pellets were 1.02 ± 0.64 and 0.506 ± 0.360 mg/MJ, respectively. The secondary side air supply in the pellet burner did not change the EFs of most pollutants significantly (p > 0.05). The only exceptions were EF(OC) and EF(PM) for pine wood pellets because of reduced combustion temperatures with the increased air supply. In comparison with EFs for the raw pine wood and corn straw, EF(CO), EF(OC), EF(EC), and EF(PM) for pellets were significantly lower than those for raw fuels (p < 0.05). However, the differences in EF(PAH) were not significant (p > 0.05). Based on the measured EFs and thermal efficiencies, it was estimated that 95, 98, 98, 88, and 71% reductions in the total emissions of CO, OC, EC, PM, and PAHs could be achieved by replacing the raw biomass fuels combusted in traditional cooking stoves with pellets burned in modern pellet burners.

Combustion efficiency and emission factors for wildfire-season fires in mixed conifer forests of the northern Rocky Mountains, US

Treesearch

S. P. Urbanski

2013-01-01

In the US, wildfires and prescribed burning present significant challenges to air regulatory agencies attempting to achieve and maintain compliance with air quality regulations. Fire emission factors (EF) are essential input for the emission models used to develop wildland fire emission inventories. Most previous studies quantifying wildland fire EF of temperate...

The independent and interacting effects of hedonic hunger and executive function on binge eating.

PubMed

Manasse, Stephanie M; Espel, Hallie M; Forman, Evan M; Ruocco, Anthony C; Juarascio, Adrienne S; Butryn, Meghan L; Zhang, Fengqing; Lowe, Michael R

2015-06-01

Poor executive function (EF; pre-frontal cognitive control processes governing goal-directed behavior) and elevated hedonic hunger (i.e., preoccupation with palatable foods in the absence of physiological hunger) are theoretical risk and maintenance factors for binge eating (BE) distinct from general obesity. Recent theoretical models posit that dysregulated behavior such as BE may result from a combination of elevated appetitive drive (e.g., hedonic hunger) and decreased EF (e.g., inhibitory control and delayed discounting). The present study sought to test this model in distinguishing BE from general obesity by examining the independent and interactive associations of EF and hedonic hunger with BE group status (i.e., odds of categorization in BE group versus non-BE group). Treatment-seeking overweight and obese women with BE (n = 31) and without BE (OW group; n = 43) were assessed on measures of hedonic hunger and EF (inhibitory control and delay discounting). Elevated hedonic hunger increased the likelihood of categorization in the BE group, regardless of EF. When hedonic hunger was low, poor EF increased the likelihood of categorization in the BE group. Results indicate that the interplay of increased appetitive drives and decreased cognitive function may distinguish BE from overweight/obesity. Future longitudinal investigations of the combinatory effect of hedonic hunger and EF in increasing risk for developing BE are warranted, and may inform future treatment development to target these factors. Copyright © 2015 Elsevier Ltd. All rights reserved.

The Influence of the Toxin/Antitoxin mazEF on Growth and Survival of Listeria monocytogenes under Stress.

PubMed

Curtis, Thomas D; Takeuchi, Ippei; Gram, Lone; Knudsen, Gitte M

2017-01-13

A major factor in the resilience of Listeria monocytogenes is the alternative sigma factor B (σ B ). Type II Toxin/Antitoxin (TA) systems are also known to have a role in the bacterial stress response upon activation via the ClpP or Lon proteases. Directly upstream of the σ B operon in L. monocytogenes is the TA system mazEF , which can cleave mRNA at UACMU sites. In this study, we showed that the mazEF TA locus does not affect the level of persister formation during treatment with antibiotics in lethal doses, but exerts different effects according to the sub-inhibitory stress added. Growth of a Δ mazEF mutant was enhanced relative to the wildtype in the presence of sub-inhibitory norfloxacin and at 42 °C, but was decreased when challenged with ampicillin and gentamicin. In contrast to studies in Staphylococcus aureus , we found that the mazEF locus did not affect transcription of genes within the σ B operon, but MazEF effected the expression of the σ B -dependent genes opuCA and lmo0880 , with a 0.22 and 0.05 fold change, respectively, compared to the wildtype under sub-inhibitory norfloxacin conditions. How exactly this system operates remains an open question, however, our data indicates it is not analogous to the system of S. aureus , suggesting a novel mode of action for MazEF in L. monocytogenes.

Direct Nitrous Oxide Emissions From Tropical And Sub-Tropical Agricultural Systems - A Review And Modelling Of Emission Factors.

PubMed

Albanito, Fabrizio; Lebender, Ulrike; Cornulier, Thomas; Sapkota, Tek B; Brentrup, Frank; Stirling, Clare; Hillier, Jon

2017-03-10

There has been much debate about the uncertainties associated with the estimation of direct and indirect agricultural nitrous oxide (N 2 O) emissions in developing countries and in particular from tropical regions. In this study, we report an up-to-date review of the information published in peer-review journals on direct N 2 O emissions from agricultural systems in tropical and sub-tropical regions. We statistically analyze net-N 2 O-N emissions to estimate tropic-specific annual N 2 O emission factors (N 2 O-EFs) using a Generalized Additive Mixed Model (GAMM) which allowed the effects of multiple covariates to be modelled as linear or smooth non-linear continuous functions. Overall the mean N 2 O-EF was 1.2% for the tropics and sub-tropics, thus within the uncertainty range of IPCC-EF. On a regional basis, mean N 2 O-EFs were 1.4% for Africa, 1.1%, for Asia, 0.9% for Australia and 1.3% for Central &South America. Our annual N 2 O-EFs, estimated for a range of fertiliser rates using the available data, do not support recent studies hypothesising non-linear increase N 2 O-EFs as a function of applied N. Our findings highlight that in reporting annual N 2 O emissions and estimating N 2 O-EFs, particular attention should be paid in modelling the effect of study length on response of N 2 O.

Direct Nitrous Oxide Emissions From Tropical And Sub-Tropical Agricultural Systems - A Review And Modelling Of Emission Factors

PubMed Central

Albanito, Fabrizio; Lebender, Ulrike; Cornulier, Thomas; Sapkota, Tek B.; Brentrup, Frank; Stirling, Clare; Hillier, Jon

2017-01-01

There has been much debate about the uncertainties associated with the estimation of direct and indirect agricultural nitrous oxide (N2O) emissions in developing countries and in particular from tropical regions. In this study, we report an up-to-date review of the information published in peer-review journals on direct N2O emissions from agricultural systems in tropical and sub-tropical regions. We statistically analyze net-N2O-N emissions to estimate tropic-specific annual N2O emission factors (N2O-EFs) using a Generalized Additive Mixed Model (GAMM) which allowed the effects of multiple covariates to be modelled as linear or smooth non-linear continuous functions. Overall the mean N2O-EF was 1.2% for the tropics and sub-tropics, thus within the uncertainty range of IPCC-EF. On a regional basis, mean N2O-EFs were 1.4% for Africa, 1.1%, for Asia, 0.9% for Australia and 1.3% for Central & South America. Our annual N2O-EFs, estimated for a range of fertiliser rates using the available data, do not support recent studies hypothesising non-linear increase N2O-EFs as a function of applied N. Our findings highlight that in reporting annual N2O emissions and estimating N2O-EFs, particular attention should be paid in modelling the effect of study length on response of N2O. PMID:28281637

Mutations in Elongation Factor Ef-1α Affect the Frequency of Frameshifting and Amino Acid Misincorporation in Saccharomyces Cerevisiae

PubMed Central

Sandbaken, M. G.; Culbertson, M. R.

1988-01-01

A mutational analysis of the eukaryotic elongation factor EF-1α indicates that this protein functions to limit the frequency of errors during genetic code translation. We found that both amino acid misincorporation and reading frame errors are controlled by EF-1α. In order to examine the function of this protein, the TEF2 gene, which encodes EF-1α in Saccharomyces cerevisiae, was mutagenized in vitro with hydroxylamine. Sixteen independent TEF2 alleles were isolated by their ability to suppress frameshift mutations. DNA sequence analysis identified eight different sites in the EF-1α protein that elevate the frequency of mistranslation when mutated. These sites are located in two different regions of the protein. Amino acid substitutions located in or near the GTP-binding and hydrolysis domain of the protein cause suppression of frameshift and nonsense mutations. These mutations may effect mistranslation by altering the binding or hydrolysis of GTP. Amino acid substitutions located adjacent to a putative aminoacyl-tRNA binding region also suppress frameshift and nonsense mutations. These mutations may alter the binding of aminoacyl-tRNA by EF-1α. The identification of frameshift and nonsense suppressor mutations in EF-1α indicates a role for this protein in limiting amino acid misincorporation and reading frame errors. We suggest that these types of errors are controlled by a common mechanism or closely related mechanisms. PMID:3066688

Direct Nitrous Oxide Emissions From Tropical And Sub-Tropical Agricultural Systems - A Review And Modelling Of Emission Factors

NASA Astrophysics Data System (ADS)

Albanito, Fabrizio; Lebender, Ulrike; Cornulier, Thomas; Sapkota, Tek B.; Brentrup, Frank; Stirling, Clare; Hillier, Jon

2017-03-01

There has been much debate about the uncertainties associated with the estimation of direct and indirect agricultural nitrous oxide (N2O) emissions in developing countries and in particular from tropical regions. In this study, we report an up-to-date review of the information published in peer-review journals on direct N2O emissions from agricultural systems in tropical and sub-tropical regions. We statistically analyze net-N2O-N emissions to estimate tropic-specific annual N2O emission factors (N2O-EFs) using a Generalized Additive Mixed Model (GAMM) which allowed the effects of multiple covariates to be modelled as linear or smooth non-linear continuous functions. Overall the mean N2O-EF was 1.2% for the tropics and sub-tropics, thus within the uncertainty range of IPCC-EF. On a regional basis, mean N2O-EFs were 1.4% for Africa, 1.1%, for Asia, 0.9% for Australia and 1.3% for Central & South America. Our annual N2O-EFs, estimated for a range of fertiliser rates using the available data, do not support recent studies hypothesising non-linear increase N2O-EFs as a function of applied N. Our findings highlight that in reporting annual N2O emissions and estimating N2O-EFs, particular attention should be paid in modelling the effect of study length on response of N2O.

Structure of the Acinetobacter baumannii Dithiol Oxidase DsbA Bound to Elongation Factor EF-Tu Reveals a Novel Protein Interaction Site

PubMed Central

Premkumar, Lakshmanane; Kurth, Fabian; Duprez, Wilko; Grøftehauge, Morten K.; King, Gordon J.; Halili, Maria A.; Heras, Begoña; Martin, Jennifer L.

2014-01-01

The multidrug resistant bacterium Acinetobacter baumannii is a significant cause of nosocomial infection. Biofilm formation, that requires both disulfide bond forming and chaperone-usher pathways, is a major virulence trait in this bacterium. Our biochemical characterizations show that the periplasmic A. baumannii DsbA (AbDsbA) enzyme has an oxidizing redox potential and dithiol oxidase activity. We found an unexpected non-covalent interaction between AbDsbA and the highly conserved prokaryotic elongation factor, EF-Tu. EF-Tu is a cytoplasmic protein but has been localized extracellularly in many bacterial pathogens. The crystal structure of this complex revealed that the EF-Tu switch I region binds to the non-catalytic surface of AbDsbA. Although the physiological and pathological significance of a DsbA/EF-Tu association is unknown, peptides derived from the EF-Tu switch I region bound to AbDsbA with submicromolar affinity. We also identified a seven-residue DsbB-derived peptide that bound to AbDsbA with low micromolar affinity. Further characterization confirmed that the EF-Tu- and DsbB-derived peptides bind at two distinct sites. These data point to the possibility that the non-catalytic surface of DsbA is a potential substrate or regulatory protein interaction site. The two peptides identified in this work together with the newly characterized interaction site provide a novel starting point for inhibitor design targeting AbDsbA. PMID:24860094

Methylation of eukaryotic elongation factor 2 induced by basic fibroblast growth factor via mitogen-activated protein kinase.

PubMed

Jung, Gyung Ah; Shin, Bong Shik; Jang, Yeon Sue; Sohn, Jae Bum; Woo, Seon Rang; Kim, Jung Eun; Choi, Go; Lee, Kyung Mi; Min, Bon Hong; Lee, Kee Ho; Park, Gil Hong

2011-10-31

Protein arginine methylation is important for a variety of cellular processes including transcriptional regulation, mRNA splicing, DNA repair, nuclear/cytoplasmic shuttling and various signal transduction pathways. However, the role of arginine methylation in protein biosynthesis and the extracellular signals that control arginine methylation are not fully understood. Basic fibroblast growth factor (bFGF) has been identified as a potent stimulator of myofibroblast dedifferentiation into fibroblasts. We demonstrated that symmetric arginine dimethylation of eukaryotic elongation factor 2 (eEF2) is induced by bFGF without the change in the expression level of eEF2 in mouse embryo fibroblast NIH3T3 cells. The eEF2 methylation is preceded by ras-raf-mitogen-activated protein kinase kinase (MEK)-extracellular signal-regulated kinase (ERK1/2)- p21Cip/WAF1 activation, and suppressed by the mitogenactivated protein kinase (MAPK) inhibitor PD98059 and p21Cip/WAF1 short interfering RNA (siRNA). We determined that protein arginine methyltransferase 7 (PRMT7) is responsible for the methylation, and that PRMT5 acts as a coordinator. Collectively, we demonstrated that eEF2, a key factor involved in protein translational elongation is symmetrically arginine-methylated in a reversible manner, being regulated by bFGF through MAPK signaling pathway.

Methylation of eukaryotic elongation factor 2 induced by basic fibroblast growth factor via mitogen-activated protein kinase

PubMed Central

Jung, Gyung Ah; Shin, Bong Shik; Jang, Yeon Sue; Sohn, Jae Bum; Woo, Seon Rang; Kim, Jung Eun; Choi, Go; Lee, Kyung-Mi; Min, Bon Hong

2011-01-01

Protein arginine methylation is important for a variety of cellular processes including transcriptional regulation, mRNA splicing, DNA repair, nuclear/cytoplasmic shuttling and various signal transduction pathways. However, the role of arginine methylation in protein biosynthesis and the extracellular signals that control arginine methylation are not fully understood. Basic fibroblast growth factor (bFGF) has been identified as a potent stimulator of myofibroblast dedifferentiation into fibroblasts. We demonstrated that symmetric arginine dimethylation of eukaryotic elongation factor 2 (eEF2) is induced by bFGF without the change in the expression level of eEF2 in mouse embryo fibroblast NIH3T3 cells. The eEF2 methylation is preceded by ras-raf-mitogen-activated protein kinase kinase (MEK)-extracellular signal-regulated kinase (ERK1/2)-p21Cip/WAF1 activation, and suppressed by the mitogen-activated protein kinase (MAPK) inhibitor PD98059 and p21Cip/WAF1 short interfering RNA (siRNA). We determined that protein arginine methyltransferase 7 (PRMT7) is responsible for the methylation, and that PRMT5 acts as a coordinator. Collectively, we demonstrated that eEF2, a key factor involved in protein translational elongation is symmetrically arginine-methylated in a reversible manner, being regulated by bFGF through MAPK signaling pathway. PMID:21778808

Deconstructing racial differences: the effects of quality of education and cerebrovascular risk factors.

PubMed

Carvalho, Janessa O; Tommet, Doug; Crane, Paul K; Thomas, Michael L; Claxton, Amy; Habeck, Christian; Manly, Jennifer J; Romero, Heather R

2015-07-01

To evaluate the effects of vascular conditions and education quality on cognition over time in White and African American (AA) older adults. We investigated cross-sectional and longitudinal racial differences in executive functioning (EF) and memory composites among Whites (n = 461) and AAs (n = 118) enrolled in a cohort study. We examined whether cerebrovascular risk factors and Shipley Vocabulary scores (a proxy for education quality) accounted for racial differences. On average, AAs had lower quality of education and more cerebrovascular risk factors including hypertension, diabetes, and obesity. AAs had lower mean EF and memory at baseline, but there were no group differences in rates of decline. Cross-sectional racial differences in EF and memory persisted after controlling for vascular disease, but disappeared when controlling for Shipley Vocabulary. Quality of education appears to be more important than cerebrovascular risk factors in explaining cross-sectional differences in memory and EF performance between White and AA older adults. Further investigation is needed regarding the relative contribution of education quality and cerebrovascular risk factors to cognitive decline among ethnically/racially diverse older adults. © The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Treatment of periorbital edema with human corticotropin-releasing factor after blepharoplasty.

PubMed

Schendel, S A; Stephanides, M

1996-03-01

This prospective study of 32 patients was undertaken to ev evaluate the formation of postoperative periorbital edema after administration of human corticotropin-releasing factor (hCRF). Human corticotropin-releasing factor has strong antiedematous properties as a result of direct action on blood vessels independent of endocrine function and has been shown to have a positive effect on vascular permeability in animal studies independent of corticosteroid effects. Human corticotropin-releasing factor was administered intravenously preoperatively to patients undergoing blepharoplasty in doses of 2, 4, and 8 mu g/kg body weight as a randomized, double-blind, placebo-controlled study. The periorbital edema was measured by the use of a three-dimensional laser scanner to determine facial and eyelid volume changes as specified times postoperatively. Human corticotropin-releasing factor was well tolerated when administered intravenously over a ten-minute period to healthy patients undergoing blepharoplasty. Mild transitory flushing and hypotension were the most common adverse events. Transient decreases in systolic and diastolic blood pressure and increases in heart rate occurred at hCRF doses greater than 2 mu g/kg and were most prominent at 8 mu g/kg. The 8 mu g/kg hCRF dose also showed a trend toward less postoperative edema but this was not statistically significant at the p<0.05 level. Human corticotropin-releasing factor appears to be safe for intravenous use in patients undergoing blepharoplasty; however, its efficacy in reducing postoperative edema as a single preoperative administration was not conclusively demonstrated in this study. Further research with a larger study population and other dosing regimens is indicated.

Efficient determination of vehicle emission factors by fuel use category using on-road measurements: downward trends on Los Angeles freight corridor I-710

PubMed Central

Hudda, N.; Fruin, S.; Delfino, R. J.; Sioutas, C.

2013-01-01

To evaluate the success of vehicle emissions regulations, trends in both fleet-wide average emissions as well as high-emitter emissions are needed, but it is challenging to capture the full spread of vehicle emission factors (EFs) with chassis dynamometer or tunnel studies, and remote sensing studies cannot evaluate particulate compounds. We developed an alternative method that links real-time on-road pollutant measurements from a mobile platform with real-time traffic data, and allows efficient calculation of both the average and the spread of EFs for light-duty gasoline-powered vehicles (LDG) and heavy-duty diesel-powered vehicles (HDD). This is the first study in California to report EFs under a full range of real-world driving conditions on multiple freeways. Fleet average LDG EFs were in agreement with most recent studies and an order of magnitude lower than observed HDD EFs. HDD EFs reflected the relatively rapid decreases in diesel emissions that have recently occurred in Los Angeles/California, and on I-710, a primary route used for goods movement and a focus of additional truck fleet turnover incentives, HDD EFs were often lower than on other freeways. When freeway emission rates (ER) were quantified as the product of EF and vehicle miles traveled (VMT) per time per mile of freeway, despite a twoto three-fold difference in HDD fractions between freeways, ERs were found to be generally similar in magnitude. Higher LDG VMT on low HDD fraction freeways largely offset the difference. Therefore, the conventional assumption that free ways with the highest HDD fractions are significantly worse sources of total emissions in Los Angeles may no longer be true. PMID:24244208

Efficient determination of vehicle emission factors by fuel use category using on-road measurements: downward trends on Los Angeles freight corridor I-710.

PubMed

Hudda, N; Fruin, S; Delfino, R J; Sioutas, C

2013-01-11

To evaluate the success of vehicle emissions regulations, trends in both fleet-wide average emissions as well as high-emitter emissions are needed, but it is challenging to capture the full spread of vehicle emission factors (EFs) with chassis dynamometer or tunnel studies, and remote sensing studies cannot evaluate particulate compounds. We developed an alternative method that links real-time on-road pollutant measurements from a mobile platform with real-time traffic data, and allows efficient calculation of both the average and the spread of EFs for light-duty gasoline-powered vehicles (LDG) and heavy-duty diesel-powered vehicles (HDD). This is the first study in California to report EFs under a full range of real-world driving conditions on multiple freeways. Fleet average LDG EFs were in agreement with most recent studies and an order of magnitude lower than observed HDD EFs. HDD EFs reflected the relatively rapid decreases in diesel emissions that have recently occurred in Los Angeles/California, and on I-710, a primary route used for goods movement and a focus of additional truck fleet turnover incentives, HDD EFs were often lower than on other freeways. When freeway emission rates (ER) were quantified as the product of EF and vehicle miles traveled (VMT) per time per mile of freeway, despite a twoto three-fold difference in HDD fractions between freeways, ERs were found to be generally similar in magnitude. Higher LDG VMT on low HDD fraction freeways largely offset the difference. Therefore, the conventional assumption that free ways with the highest HDD fractions are significantly worse sources of total emissions in Los Angeles may no longer be true.

Disaggregated N2O emission factors in China based on cropping parameters create a robust approach to the IPCC Tier 2 methodology

PubMed Central

Shepherd, Anita; Yan, Xiaoyuan; Nayak, Dali; Newbold, Jamie; Moran, Dominic; Dhanoa, Mewa Singh; Goulding, Keith; Smith, Pete; Cardenas, Laura M.

2015-01-01

China accounts for a third of global nitrogen fertilizer consumption. Under an International Panel on Climate Change (IPCC) Tier 2 assessment, emission factors (EFs) are developed for the major crop types using country-specific data. IPCC advises a separate calculation for the direct nitrous oxide (N2O) emissions of rice cultivation from that of cropland and the consideration of the water regime used for irrigation. In this paper we combine these requirements in two independent analyses, using different data quality acceptance thresholds, to determine the influential parameters on emissions with which to disaggregate and create N2O EFs. Across China, the N2O EF for lowland horticulture was slightly higher (between 0.74% and 1.26% of fertilizer applied) than that for upland crops (values ranging between 0.40% and 1.54%), and significantly higher than for rice (values ranging between 0.29% and 0.66% on temporarily drained soils, and between 0.15% and 0.37% on un-drained soils). Higher EFs for rice were associated with longer periods of drained soil and the use of compound fertilizer; lower emissions were associated with the use of urea or acid soils. Higher EFs for upland crops were associated with clay soil, compound fertilizer or maize crops; lower EFs were associated with sandy soil and the use of urea. Variation in emissions for lowland vegetable crops was closely associated with crop type. The two independent analyses in this study produced consistent disaggregated N2O EFs for rice and mixed crops, showing that the use of influential cropping parameters can produce robust EFs for China. PMID:26865831

Emission Factors, Size Distributions and Emission Inventories of Carbonaceous Particulate Matter from Residential Wood Combustion in Rural China

PubMed Central

Shen, Guofeng; Wei, Siye; Wei, Wen; Zhang, Yanyan; Min, Yujia; Wang, Bin; Wang, Rong; Li, Wei; Shen, Huizhong; Huang, Ye; Huang, Ye; Yang, Yifeng; Wang, Wei; Wang, Xilong; Wang, Xuejun; Tao, Shu

2012-01-01

Published emission factors (EFs) often vary significantly, leading to high uncertainties in emission estimations. There are few reliable EFs from field measurements of residential wood combustion in China. In this study, 17 wood fuels and one bamboo were combusted in a typical residential stove in rural China to measure realistic EFs of particulate matter (PM), organic carbon (OC) and elemental carbon (EC), as well as to investigate the influence of fuel properties and combustion conditions on the EFs. Measured EFs of PM, OC, and EC (EFPM, EFOC, and EFEC, respectively) were in the range of 0.38~6.4, 0.024~3.0 and 0.039~3.9 g/kg (dry basis), with means and standard derivation of 2.2±1.2, 0.62±0.64 and 0.83±0.69 g/kg, respectively. Shrubby biomass combustion produced higher EFs than tree woods, and both species had lower EFs than those of indoor crop residue burning (p<0.05). Significant correlations between EFPM, EFOC and EFEC were expected. By using a nine-stage cascade impactor, it was shown that size distributions of PM emitted from tree biomass combustions were unimodal with peaks at a diameter less than 0.4 µm (PM0.4), much finer than the PM from indoor crop residue burning. Approximately 79.4% of the total PM from tree wood combustion was PM with a diameter less than 2.1µm (PM2.1). PM size distributions for shrubby biomasses were slightly different from those for tree fuels. Based on the measured EFs, total emissions of PM, OC, and EC from residential wood combustion in rural China in 2007 were estimated at about 303, 75.7, and 92.0 Gg. PMID:22380753

Disaggregated N2O emission factors in China based on cropping parameters create a robust approach to the IPCC Tier 2 methodology

NASA Astrophysics Data System (ADS)

Shepherd, Anita; Yan, Xiaoyuan; Nayak, Dali; Newbold, Jamie; Moran, Dominic; Dhanoa, Mewa Singh; Goulding, Keith; Smith, Pete; Cardenas, Laura M.

2015-12-01

China accounts for a third of global nitrogen fertilizer consumption. Under an International Panel on Climate Change (IPCC) Tier 2 assessment, emission factors (EFs) are developed for the major crop types using country-specific data. IPCC advises a separate calculation for the direct nitrous oxide (N2O) emissions of rice cultivation from that of cropland and the consideration of the water regime used for irrigation. In this paper we combine these requirements in two independent analyses, using different data quality acceptance thresholds, to determine the influential parameters on emissions with which to disaggregate and create N2O EFs. Across China, the N2O EF for lowland horticulture was slightly higher (between 0.74% and 1.26% of fertilizer applied) than that for upland crops (values ranging between 0.40% and 1.54%), and significantly higher than for rice (values ranging between 0.29% and 0.66% on temporarily drained soils, and between 0.15% and 0.37% on un-drained soils). Higher EFs for rice were associated with longer periods of drained soil and the use of compound fertilizer; lower emissions were associated with the use of urea or acid soils. Higher EFs for upland crops were associated with clay soil, compound fertilizer or maize crops; lower EFs were associated with sandy soil and the use of urea. Variation in emissions for lowland vegetable crops was closely associated with crop type. The two independent analyses in this study produced consistent disaggregated N2O EFs for rice and mixed crops, showing that the use of influential cropping parameters can produce robust EFs for China.

Elongation Factor 1 alpha interacts with phospho-Akt in breast cancer cells and regulates their proliferation, survival and motility.

PubMed

Pecorari, Luisa; Marin, Oriano; Silvestri, Chiara; Candini, Olivia; Rossi, Elena; Guerzoni, Clara; Cattelani, Sara; Mariani, Samanta A; Corradini, Francesca; Ferrari-Amorotti, Giovanna; Cortesi, Laura; Bussolari, Rita; Raschellà, Giuseppe; Federico, Massimo R; Calabretta, Bruno

2009-08-03

Akt/PKB is a serine/threonine kinase that has attracted much attention because of its central role in regulating cell proliferation, survival, motility and angiogenesis. Activation of Akt in breast cancer portends aggressive tumour behaviour, resistance to hormone-, chemo-, and radiotherapy-induced apoptosis and it is correlated with decreased overall survival. Recent studies have identified novel tumor-specific substrates of Akt that may provide new diagnostic and prognostic markers and serve as therapeutic targets. This study was undertaken to identify pAkt-interacting proteins and to assess their biological roles in breast cancer cells. We confirmed that one of the pAkt interacting proteins is the Elongation Factor EF1alpha. EF1alpha contains a putative Akt phosphorylation site, but is not phosphorylated by pAkt1 or pAkt2, suggesting that it may function as a modulator of pAkt activity. Indeed, downregulation of EF1alpha expression by siRNAs led to markedly decreased expression of pAkt1 and to less extent of pAkt2 and was associated with reduced proliferation, survival and invasion of HCC1937 cells. Proliferation and survival was further reduced by combining EF1alpha siRNAs with specific pAkt inhibitors whereas EF1alpha downregulation slightly attenuated the decreased invasion induced by Akt inhibitors. We show here that EF1alpha is a pAkt-interacting protein which regulates pAkt levels. Since EF1alpha is often overexpressed in breast cancer, the consequences of EF1alpha increased levels for proliferation, survival and invasion will likely depend on the relative concentration of Akt1 and Akt2.

Relations Between Self-reported Executive Functioning and Speech Perception Skills in Adult Cochlear Implant Users.

PubMed

Moberly, Aaron C; Patel, Tirth R; Castellanos, Irina

2018-02-01

As a result of their hearing loss, adults with cochlear implants (CIs) would self-report poorer executive functioning (EF) skills than normal-hearing (NH) peers, and these EF skills would be associated with performance on speech recognition tasks. EF refers to a group of high order neurocognitive skills responsible for behavioral and emotional regulation during goal-directed activity, and EF has been found to be poorer in children with CIs than their NH age-matched peers. Moreover, there is increasing evidence that neurocognitive skills, including some EF skills, contribute to the ability to recognize speech through a CI. Thirty postlingually deafened adults with CIs and 42 age-matched NH adults were enrolled. Participants and their spouses or significant others (informants) completed well-validated self-reports or informant-reports of EF, the Behavior Rating Inventory of Executive Function - Adult (BRIEF-A). CI users' speech recognition skills were assessed in quiet using several measures of sentence recognition. NH peers were tested for recognition of noise-vocoded versions of the same speech stimuli. CI users self-reported difficulty on EF tasks of shifting and task monitoring. In CI users, measures of speech recognition correlated with several self-reported EF skills. The present findings provide further evidence that neurocognitive factors, including specific EF skills, may decline in association with hearing loss, and that some of these EF skills contribute to speech processing under degraded listening conditions.

Trace gas and particle emissions from open biomass burning in Mexico

Treesearch

R. J. Yokelson; I. R. Burling; Shawn Urbanski; E. L. Atlas; K. Adachi; P. R. Buseck; C. Wiedinmyer; S. K. Akagi; D. W. Toohey; C. E. Wold

2011-01-01

We report airborne measurements of emission factors (EF) for trace gases and PM2.5 made in southern Mexico in March of 2006 on 6 crop residue fires, 3 tropical dry forest fires, 8 savanna fires, 1 garbage fire, and 7 mountain pine-oak forest fires. The savanna fire EF were measured early in the local dry season and when compared to EF measured late in the African dry...

Assessment of executive functioning in children and young adults treated for frontal lobe tumours using ecologically valid tests.

PubMed

Longaud-Valès, A; Chevignard, M; Dufour, C; Grill, J; Puget, S; Sainte-Rose, C; Valteau-Couanet, D; Dellatolas, G

2016-08-01

There is a lack of studies assessing executive functions (EF) using ecologically valid tests in children with frontal lobe lesions. This study aimed to (1) evaluate EF in children, adolescents and young adults treated for childhood frontal lobe tumours, (2) identify factors influencing performance, such as age at diagnosis or type of treatment, and (3) examine correlations between intellectual ability and classical and ecological tests of EF. Twenty-one patients, aged 8-27 years, treated for a childhood benign or malignant frontal lobe tumour, and 42 healthy controls (matched for gender, age and socio-economic status) were assessed using classical tests of EF, and the BADS-C ecological battery. Patients also underwent assessment of intellectual ability and parent and teacher ratings of the BRIEF questionnaire. IQ scores ranged from 45 to 125 (mean FSIQ = 84) and were lower in case of epilepsy, hydrocephalus and lower parental education. Patients displayed deficits in most, but not all measures of EF. Most classical and ecological measures of EF were strongly correlated to IQ. This study confirms the frequency of EF deficits in this population; it also highlights the utility of ecological measures of EF and some limitations of classical tests of EF in children.

Formation of ethyl ferulate from feruloylated oligosaccharide by transesterification of rice koji enzyme under sake mash conditions.

PubMed

Suzuki, Nobukazu; Ito, Toshihiko; Hiroshima, Kai; Tokiwano, Tetsuo; Hashizume, Katsumi

2016-03-01

Formation of ethyl ferulate (EF) and ferulic acid (FA) under sake mash conditions was studied using feruloylated oligosaccharide (FO), prepared from rice grains, as the substrate for rice koji enzyme. EF and FA were produced from FO over six times faster than from alkyl ferulates however, under the same ethanol concentration, only small differences were observed between the EF/FA ratios when either FO or methyl ferulate were used as substrates. Esterification and hydrolysis of FO or methyl ferulate showed similar pH dependencies and similar EF/FA ratios for each substrate in all of the pH ranges tested. Ethanol concentration clearly affected the EF/FA ratio; the ratio increased as ethanol concentration increased. Formation of EF and FA in the sake mash simulated rice digest was accelerated by addition of exogenous FO. These results indicated that supply of FO to sake mash is a crucial step for EF and FA formation, and ethanol is an influencing factor in the EF/FA ratio. The rice koji enzyme reaction suggested that EF and FA are formed through a common feruloylated enzyme intermediate complex by transesterification or hydrolysis, and these reactions occur competitively. Copyright © 2015 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Remitting Seronegative Symmetrical Synovitis with Pitting Edema Syndrome in a Chronic Hemodialysis Patient

PubMed Central

Yamada, Shunsuke; Fuyuno, Seiya; Eriguchi, Masahiro; Tsuruya, Kazuhiko; Kitazono, Takanari

2012-01-01

A 75-year-old male who was undergoing chronic hemodialysis developed abrupt-onset pitting edema and pain in the dorsum of both hands and feet. Biochemical analysis disclosed increased C-reactive protein, and negative rheumatoid factor and antinuclear antibody. Radiological examination showed no bony erosion. Computed tomography and gallium scintigraphy revealed no active infection or neoplasms. The clinical diagnosis was remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome. The pitting edema and inflammatory response quickly subsided after low-dose prednisolone therapy. This case demonstrates that RS3PE syndrome could be a differential diagnosis in elderly patients undergoing dialysis who develop pitting edema and joint pain. PMID:22431931

Individual risk factors for deep infection and compromised fracture healing after intramedullary nailing of tibial shaft fractures: a single centre experience of 480 patients.

PubMed

Metsemakers, W-J; Handojo, K; Reynders, P; Sermon, A; Vanderschot, P; Nijs, S

2015-04-01

Despite modern advances in the treatment of tibial shaft fractures, complications including nonunion, malunion, and infection remain relatively frequent. A better understanding of these injuries and its complications could lead to prevention rather than treatment strategies. A retrospective study was performed to identify risk factors for deep infection and compromised fracture healing after intramedullary nailing (IMN) of tibial shaft fractures. Between January 2000 and January 2012, 480 consecutive patients with 486 tibial shaft fractures were enrolled in the study. Statistical analysis was performed to determine predictors of deep infection and compromised fracture healing. Compromised fracture healing was subdivided in delayed union and nonunion. The following independent variables were selected for analysis: age, sex, smoking, obesity, diabetes, American Society of Anaesthesiologists (ASA) classification, polytrauma, fracture type, open fractures, Gustilo type, primary external fixation (EF), time to nailing (TTN) and reaming. As primary statistical evaluation we performed a univariate analysis, followed by a multiple logistic regression model. Univariate regression analysis revealed similar risk factors for delayed union and nonunion, including fracture type, open fractures and Gustilo type. Factors affecting the occurrence of deep infection in this model were primary EF, a prolonged TTN, open fractures and Gustilo type. Multiple logistic regression analysis revealed polytrauma as the single risk factor for nonunion. With respect to delayed union, no risk factors could be identified. In the same statistical model, deep infection was correlated with primary EF. The purpose of this study was to evaluate risk factors of poor outcome after IMN of tibial shaft fractures. The univariate regression analysis showed that the nature of complications after tibial shaft nailing could be multifactorial. This was not confirmed in a multiple logistic regression model, which only revealed polytrauma and primary EF as risk factors for nonunion and deep infection, respectively. Future strategies should focus on prevention in high-risk populations such as polytrauma patients treated with EF. Copyright © 2014 Elsevier Ltd. All rights reserved.

Is Thrombus With Subcutaneous Edema Detected by Ultrasonography Related to Short Peripheral Catheter Failure? A Prospective Observational Study.

PubMed

Takahashi, Toshiaki; Murayama, Ryoko; Oe, Makoto; Nakagami, Gojiro; Tanabe, Hidenori; Yabunaka, Koichi; Arai, Rika; Komiyama, Chieko; Uchida, Miho; Sanada, Hiromi

Short peripheral catheter (SPC) failure is an important clinical problem. The purpose of this study was to clarify the relationship between SPC failure and etiologies such as thrombus, subcutaneous edema, and catheter dislodgment using ultrasonography and to explore the risk factors associated with the etiologies. Two hundred catheters that were in use for infusion, excluding chemotherapy, were observed. Risk factors were examined by logistic regression analysis. Sixty catheters were removed as the result of SPC failure. Frequency of thrombus with subcutaneous edema in SPC failure cases was significantly greater than in those cases where therapy was completed without complications (P < .01). Multivariate analysis demonstrated that 2 or more insertion attempts were significantly associated with thrombus with subcutaneous edema. Results suggest that subsurface skin assessment for catheterization could prevent SPC failure.

Myostatin inhibits eEF2K-eEF2 by regulating AMPK to suppress protein synthesis.

PubMed

Deng, Zhao; Luo, Pei; Lai, Wen; Song, Tongxing; Peng, Jian; Wei, Hong-Kui

2017-12-09

Growth of skeletal muscle is dependent on the protein synthesis, and the rate of protein synthesis is mainly regulated in the stage of translation initiation and elongation. Myostatin, a member of the transforming growth factor-β (TGF-β) superfamily, is a negative regulator of protein synthesis. C2C12 myotubes was incubated with 0, 0.01, 0.1, 1, 2, 3 μg/mL myostatin recombinant protein, and then we detected the rates of protein synthesis by the method of SUnSET. We found that high concentrations of myostatin (2 and 3 μg/mL) inhibited protein synthesis by blocking mTOR and eEF2K-eEF2 pathway, while low concentration of myostatin (0.01, 0.1 and 1 μg/mL) regulated eEF2K-eEF2 pathway activity to block protein synthesis without affected mTOR pathway, and myostatin inhibited eEF2K-eEF2 pathway through regulating AMPK pathway to suppress protein synthesis. It provided a new mechanism for myostatin regulating protein synthesis and treating muscle atrophy. Copyright © 2017. Published by Elsevier Inc.

Temporal trends and factors associated with diabetes mellitus among patients hospitalized with heart failure: Findings from Get With The Guidelines-Heart Failure registry.

PubMed

Echouffo-Tcheugui, Justin B; Xu, Haolin; DeVore, Adam D; Schulte, Phillip J; Butler, Javed; Yancy, Clyde W; Bhatt, Deepak L; Hernandez, Adrian F; Heidenreich, Paul A; Fonarow, Gregg C

2016-12-01

The contribution of diabetes to the burden of heart failure (HF) remains largely undescribed. Assessing diabetes temporal trends among US patients hospitalized with HF and their relation with quality measures in real-world practice can help to define this burden. Using data from the Get With the Guidelines-Heart Failure registry, we assessed temporal trends in diabetes prevalence among patients with HF and in subgroups with reduced ejection fraction (HFrEF; EF < 40%), borderline EF (HFbEF; 40%≤EF <50%), or preserved EF (HFpEF; EF ≥ 50%), hospitalized between 2005 and 2015. Logistic regression was used to assess whether in-hospital outcomes and HF quality of care were related to trends. Among 364,480 HF hospitalizations, 160,171 had diabetes (44.0% overall, 41.8% in HFrEF, 46.7% in HFbEF, 45.5% in HFpEF). There was a temporal increase in diabetes frequency in HF patients (43.2%-45.8%; P trend <.0001), including among those with HFrEF (42.0%-43.6%; P trend <.0001), HFbEF (46.0%-49.2%; P trend <.0001), or HFpEF (43.6%-46.8%, P trend <.0001). Diabetic patients had a longer hospital stay (adjusted odds ratio 1.14, 95% CI 1.12-1.16), but lower in-hospital mortality (adjusted odds ratio 0.93 [0.89-0.97]) compared with those without diabetes, with limited differences in quality measures. Temporal trends in diabetes were not associated with in-hospital mortality or length of stay. There were no temporal interactions of most HF quality measures with diabetes status. Approximately 44% of hospitalized HF patients have diabetes, and this proportion has been increasing over the past 10years, particularly among those patients with new-onset HFpEF. Copyright © 2016 Elsevier Inc. All rights reserved.

Black carbon, particle number concentration and nitrogen oxide emission factors of random in-use vehicles measured with the on-road chasing method

NASA Astrophysics Data System (ADS)

Ježek, I.; Katrašnik, T.; Westerdahl, D.; Močnik, G.

2015-06-01

The chasing method was used in an on-road measurement campaign, and emission factors (EF) of black carbon (BC), particle number (PN) and nitrogen oxides (NOx) were determined for 139 individual vehicles of different types encountered on the roads. The aggregated results provide EFs for BC, NOx and PN for three vehicle categories: goods vehicles, gasoline and diesel passenger cars. This is the first on-road measurement study where BC EFs of numerous individual diesel cars were determined in real-world driving conditions. We found good agreement between EFs of goods vehicles determined in this campaign and the results of previous studies that used either chasing or remote sensing measurement techniques. The composition of the sampled car fleet determined from the national vehicle registry information is reflective of Eurostat statistical data on the Slovenian and European vehicle fleet. The median BC EF of diesel and gasoline cars that were in use for less than 5 years, decreased by 60 and 47% from those in use for 5-10 years, respectively, the median NOx and PN EFs, of goods vehicles that were in use for less than five years, decreased from those in use for 5-10 years by 52 and 67%, respectively. The influence of engine maximum power of the measured EFs showed an increase in NOx EF from least to more powerful vehicles with diesel engines. Finally a disproportionate contribution of high emitters to the total emissions of the measured fleet was found; the top 25% of emitting diesel cars contributed 63, 47 and 61% of BC, NOx and PN emissions respectively. With the combination of relatively simple on-road measurements with sophisticated post processing individual vehicles EF can be determined and useful information about the fleet emissions can be obtained by exactly representing vehicles which contribute disproportionally to vehicle fleet emissions; and monitor how the numerous emission reduction approaches are reflected in on-road driving conditions.

Effect of fuels and domestic heating appliance types on emission factors of selected organic pollutants.

PubMed

Šyc, Michal; Horák, Jiří; Hopan, František; Krpec, Kamil; Tomšej, Tomáš; Ocelka, Tomáš; Pekárek, Vladimír

2011-11-01

This study reports on the first complex data set of emission factors (EFs) of selected pollutants from combustion of five fuel types (lignite, bituminous coal, spruce, beech, and maize) in six different domestic heating appliances of various combustion designs. The effect of fuel as well as the effect of boiler type was studied. In total, 46 combustion runs were performed, during which numerous EFs were measured, including the EFs of particulate matter (PM), carbon monoxide, polyaromatic hydrocarbons (PAH), hexachlorobenzene (HxCBz), polychlorinated dibenzo-p-dioxins and furans (PCDD/F), etc. The highest EFs of nonchlorinated pollutants were measured for old-type boilers with over-fire and under-fire designs and with manual stoking and natural draft. Emissions of the above-mentioned pollutants from modern-type boilers (automatic, downdraft) were 10 times lower or more. The decisive factor for emission rate of nonchlorinated pollutants was the type of appliance; the type of fuel plays only a minor role. Emissions of chlorinated pollutants were proportional mainly to the chlorine content in fuel, but the type of appliance also influenced the rate of emissions significantly. Surprisingly, higher EFs of PCDD/F from combustion of chlorinated bituminous coal were observed for modern-type boilers (downdraft, automatic) than for old-type ones. On the other hand, when bituminous coal was burned, higher emissions of HxCBz were found for old-type boilers than for modern-type ones.

Simple Predictive Model of Early Failure among Patients Undergoing First-Time Arteriovenous Fistula Creation.

PubMed

Eslami, Mohammad H; Zhu, Clara K; Rybin, Denis; Doros, Gheorghe; Siracuse, Jeffrey J; Farber, Alik

2016-08-01

Native arteriovenous fistulas (AVFs) have a high 1 year failure rate leading to a need for secondary procedures. We set out to create a predictive model of early failure in patients undergoing first-time AVF creation, to identify failure-associated factors and stratify initial failure risk. The Vascular Study Group of New England (VSGNE) (2010-2014) was queried to identify patients undergoing first-time AVF creation. Patients with early (within 3 months postoperation) AVF failure (EF) or no failure (NF) were compared, failure being defined as any AVF that could not be used for dialysis. A multivariate logistic regression predictive model of EF based on perioperative clinical variables was created. Backward elimination with alpha level of 0.2 was used to create a parsimonious model. We identified 376 first-time AVF patients with follow-up data available in VSGNE. EF rate was 17.5%. Patients in the EF group had lower rates of hypertension (80.3% vs. 93.2%, P = 0.003) and diabetes (47.0% vs. 61.3%, P = 0.039). EF patients were also more likely to have radial artery inflow (57.6% vs. 38.4%, P = 0.011) and have forearm cephalic vein outflow (57.6% vs. 36.5%, P = 0.008). Additionally, the EF group was noted to have significantly smaller mean diameters of target artery (3.1 ± 0.9 vs. 3.6 ± 1.1, P = 0.002) and vein (3.1 ± 0.7 vs. 3.6 ± 0.9, P < 0.001). Multivariate analyses revealed that hypertension, diabetes, and vein larger than 3 mm were protective of EF (P < 0.05). The discriminating ability of this model was good (C-statistic = 0.731) and the model fits the data well (Hosmer-Lemeshow P = 0.149). β-estimates of significant factors were used to create a point system and assign probabilities of EF. We developed a simple model that robustly predicts first-time AVF EF and suggests that anatomical and clinical factors directly affect early AVF outcomes. The risk score has the potential to be used in clinical settings to stratify risk and make informed follow-up plans for AVF patients. Copyright © 2016 Elsevier Inc. All rights reserved.

eEF2K/eEF2 Pathway Controls the Excitation/Inhibition Balance and Susceptibility to Epileptic Seizures.

PubMed

Heise, Christopher; Taha, Elham; Murru, Luca; Ponzoni, Luisa; Cattaneo, Angela; Guarnieri, Fabrizia C; Montani, Caterina; Mossa, Adele; Vezzoli, Elena; Ippolito, Giulio; Zapata, Jonathan; Barrera, Iliana; Ryazanov, Alexey G; Cook, James; Poe, Michael; Stephen, Michael Rajesh; Kopanitsa, Maksym; Benfante, Roberta; Rusconi, Francesco; Braida, Daniela; Francolini, Maura; Proud, Christopher G; Valtorta, Flavia; Passafaro, Maria; Sala, Mariaelvina; Bachi, Angela; Verpelli, Chiara; Rosenblum, Kobi; Sala, Carlo

2017-03-01

Alterations in the balance of inhibitory and excitatory synaptic transmission have been implicated in the pathogenesis of neurological disorders such as epilepsy. Eukaryotic elongation factor 2 kinase (eEF2K) is a highly regulated, ubiquitous kinase involved in the control of protein translation. Here, we show that eEF2K activity negatively regulates GABAergic synaptic transmission. Indeed, loss of eEF2K increases GABAergic synaptic transmission by upregulating the presynaptic protein Synapsin 2b and α5-containing GABAA receptors and thus interferes with the excitation/inhibition balance. This cellular phenotype is accompanied by an increased resistance to epilepsy and an impairment of only a specific hippocampal-dependent fear conditioning. From a clinical perspective, our results identify eEF2K as a potential novel target for antiepileptic drugs, since pharmacological and genetic inhibition of eEF2K can revert the epileptic phenotype in a mouse model of human epilepsy. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

The Effect of Executive Function on Science Achievement Among Normally Developing 10-Year Olds

NASA Astrophysics Data System (ADS)

Lederman, Sheri G.

Executive function (EF) is an umbrella term used to identify a set of discrete but interrelated cognitive abilities that enable individuals to engage in goal-directed, future-oriented action in response to a novel context. Developmental studies indicate that EF is predictive of reading and math achievement in middle childhood. The purpose of this study was to identify the association between EF and science achievement among normally developing 10 year olds. A sample of fifth grade students from a Northeastern suburban community participated in tests of EF, science, and intelligence. Consistent with adult models of EF, principal components analysis identified a three-factor model of EF organization in middle childhood, including cognitive flexibility, working memory, and inhibition. Multiple regression analyses revealed that executive function processes of cognitive flexibility, working memory, and inhibition were all predictive of science performance. Post hoc analyses revealed that high-performing science students differed significantly from low-performing students in both cognitive flexibility and working memory. These findings suggest that complex academic demands specific to science achievement rely on the emergence and maturation of EF components.

Activation of Elongation Factor G by Phosphate Analogues

PubMed Central

Salsi, Enea; Farah, Elie

2016-01-01

EF-G is a universally conserved translational GTPase that promotes the translocation of tRNA and mRNA through the ribosome. EF-G binds to the ribosome in a GTP-bound form and subsequently catalyzes GTP hydrolysis. The contribution of the ribosome-stimulated GTP hydrolysis by EF-G to tRNA/mRNA translocation remains debated. Here, we show that while EF-G•GDP does not stably bind to the ribosome and induce translocation, EFG• GDP in complex with phosphate group analogues BeF3− and AlF4− promotes the translocation of tRNA and mRNA. Furthermore, the rates of mRNA translocation induced by EF-G in the presence of GTP and a non-hydrolysable analogue of GTP, GDP•BeF3−are similar. Our results are consistent with the model suggesting that GTP hydrolysis is not directly coupled to mRNA/tRNA translocation. Hence, GTP binding is required to induce the activated, translocation-competent conformation of EF-G while GTP hydrolysis triggers EF-G release from the ribosome. PMID:27063503

Catching Fish and Avoiding Sharks: Investigating Factors That Influence Developmentally Appropriate Measurement of Preschoolers' Inhibitory Control.

PubMed

Howard, Steven J; Okely, Anthony D

2015-09-01

Although researchers agree that the first 5 years of life are critical for children's developing executive functions (EFs), further advances are hindered by a lack of consensus on the design and selection of developmentally appropriate EF tasks for young children. Given this debate, well-established adult measures of EF routinely have been adapted for young children. Given young children's comparatively limited cognitive capacities, however, such adaptations do not guarantee that the task's critical EF demands are retained. To investigate this possibility, the current study examined the characteristics that optimize measurement of young children's EFs-specifically, their inhibitory control-using the go/no-go (GNG) task as an exemplar. Sixty preschoolers completed six GNG tasks differing in stimulus animation, presentation time, and response location. Comparison EF tasks were administered to examine concurrent validity of GNG variants. Results indicated effects of stimulus presentation time and response location, with animation further enhancing task validity and reliability. This suggests that current GNG tasks deflate estimates of young children's ability to inhibit, with implications for future design and selection of developmentally appropriate EF tasks.

Links between theory of mind and executive function in young children with autism: clues to developmental primacy.

PubMed

Pellicano, Elizabeth

2007-07-01

There has been much theoretical discussion of a functional link between theory of mind (ToM) and executive function (EF) in autism. This study sought to establish the relationship between ToM and EF in young children with autism (M = 5 years, 6 months) and to examine issues of developmental primacy. Thirty children with autism and 40 typically developing children, matched on age and ability, were assessed on a battery of tasks measuring ToM (1st- and 2nd-order false belief) and components of EF (planning, set shifting, inhibition). A significant correlation emerged between ToM and EF variables in the autism group, independent of age and ability, while ToM and higher order planning ability remained significantly related in the comparison group. Examination of the pattern of ToM-EF impairments in the autism group revealed dissociations in 1 direction only: impaired ToM with intact EF. These findings support the view that EF may be 1 important factor in the advancement of ToM understanding in autism. The theoretical implications of these findings are discussed. Copyright 2007 APA.

Publication Metrics of Dental Journals - What is the Role of Self Citations in Determining the Impact Factor of Journals?

PubMed

Elangovan, Satheesh; Allareddy, Veerasathpurush

2015-09-01

The objectives of the present study are to examine the publication metrics of dental journals and to delineate the role of self citations in determining the impact factor of journals. The Journal Citation Reports database was used. All dental journals that had an impact factor assigned for year 2013 were selected. The outcomes were Impact Factor (IF), Eigenfactor™ (EF), article influence score (AIS), and proportion of self-citations to total citations. Independent variables were geographic region of journal and ranking of journal (based on IF). Non-parametric tests were used to examine the associations between outcomes and independent variables. During the year 2013, 82 journals in dentistry had an IF. Mean IF was 1.489 and mean IF without including self-citations was 1.231. Mean EF scores and AIS were .00458 and .5141 respectively. Mean percentage of self cites to total citations for all dental journals was 12.24%. Higher ranking journals were associated with significantly higher EF and AIS. Journals published in USA/Canada or Europe were associated with higher IF and EF compared to those published in other regions. There were no differences in percentages of self citations to total citations either across journal rankings or geographic region. Top ranking journals tend to have higher IFs due to higher EF and AIS rather than by self-citations. Self-citations increase the impact factors of dental journals by 21%. There was no geographic influence in the percentage of self-citations to total citations thus indicating a healthy dental scientific publishing environment. Copyright © 2015 Elsevier Inc. All rights reserved.

Black carbon, particle number concentration and nitrogen oxide emission factors of random in-use vehicles measured with the on-road chasing method

NASA Astrophysics Data System (ADS)

Ježek, I.; Katrašnik, T.; Westerdahl, D.; Močnik, G.

2015-10-01

The chasing method was used in an on-road measurement campaign, and emission factors (EF) of black carbon (BC), particle number (PN) and nitrogen oxides (NOx) were determined for 139 individual vehicles of different types encountered on the roads. The aggregated results provide EFs for BC, NOx and PN for three vehicle categories: goods vehicles, gasoline and diesel passenger cars. This is the first on-road measurement study where BC EFs of numerous individual diesel cars were determined in real-world driving conditions. We found good agreement between EFs of goods vehicles determined in this campaign and the results of previous studies that used either chasing or remote-sensing measurement techniques. The composition of the sampled car fleet determined from the national vehicle registry information is reflective of Eurostat statistical data on the Slovenian and European vehicle fleet. The median BC EF of diesel and gasoline cars that were in use for less than 5 years decreased by 60 and 47 % from those in use for 5-10 years, respectively; the median NOx and PN EFs of goods vehicles that were in use for less than 5 years decreased from those in use for 5-10 years by 52 and 67 %, respectively. Surprisingly, we found an increase of BC EFs in the newer goods vehicle fleet compared to the 5-10-year old one. The influence of engine maximum power of the measured EFs showed an increase in NOx EF from least to more powerful vehicles with diesel engines. Finally, a disproportionate contribution of high emitters to the total emissions of the measured fleet was found; the top 25 % of emitting diesel cars contributed 63, 47 and 61 % of BC, NOx and PN emissions respectively. With the combination of relatively simple on-road measurements and sophisticated post processing, individual vehicle EF can be determined and useful information about the fleet emissions can be obtained by exactly representing vehicles which contribute disproportionally to vehicle fleet emissions; and monitor how the numerous emission reduction approaches are reflected in on-road driving conditions.

The Conformational Change in Elongation Factor Tu Involves Separation of Its Domains

DOE PAGES

Lai, Jonathan; Ghaemi, Zhaleh; Luthey-Schulten, Zaida

2017-10-18

Elongation factor Tu (EF-Tu) is a highly conserved GTPase that is responsible for supplying the aminoacylated tRNA to the ribosome. Upon binding to the ribosome, EF-Tu undergoes GTP hydrolysis, which drives a major conformational change, triggering the release of aminoacylated tRNA to the ribosome. Using a combination of molecular simulation techniques, we studied the transition between the pre- and post-hydrolysis structures through two distinct pathways. Here, we show that the transition free energy is minimal along a non-intuitive pathway that involves “separation” of the GTP binding domain (domain 1) from the OB folds (domains 2 and 3), followed by domainmore » 1 rotation, and, eventually, locking the EF-Tu conformation in the post-hydrolysis state. The domain separation also leads to a slight extension of the linker connecting domain 1 to domain 2. Using docking tools and correlation-based analysis, we identified and characterized the EF-Tu conformations that release the tRNA. These calculations suggest that EF-Tu can release the tRNA before the domains separate and after domain 1 rotates by 25°. Lastly, we also examined the EF-Tu conformations in the context of the ribosome. Given the high degrees of sequence similarity with other translational GTPases, we predict a similar separation mechanism is followed.« less

The Conformational Change in Elongation Factor Tu Involves Separation of Its Domains

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lai, Jonathan; Ghaemi, Zhaleh; Luthey-Schulten, Zaida

Elongation factor Tu (EF-Tu) is a highly conserved GTPase that is responsible for supplying the aminoacylated tRNA to the ribosome. Upon binding to the ribosome, EF-Tu undergoes GTP hydrolysis, which drives a major conformational change, triggering the release of aminoacylated tRNA to the ribosome. Using a combination of molecular simulation techniques, we studied the transition between the pre- and post-hydrolysis structures through two distinct pathways. Here, we show that the transition free energy is minimal along a non-intuitive pathway that involves “separation” of the GTP binding domain (domain 1) from the OB folds (domains 2 and 3), followed by domainmore » 1 rotation, and, eventually, locking the EF-Tu conformation in the post-hydrolysis state. The domain separation also leads to a slight extension of the linker connecting domain 1 to domain 2. Using docking tools and correlation-based analysis, we identified and characterized the EF-Tu conformations that release the tRNA. These calculations suggest that EF-Tu can release the tRNA before the domains separate and after domain 1 rotates by 25°. Lastly, we also examined the EF-Tu conformations in the context of the ribosome. Given the high degrees of sequence similarity with other translational GTPases, we predict a similar separation mechanism is followed.« less

Eukaryotic elongation factor 2 kinase regulates the synthesis of microtubule-related proteins in neurons.

PubMed

Kenney, Justin W; Genheden, Maja; Moon, Kyung-Mee; Wang, Xuemin; Foster, Leonard J; Proud, Christopher G

2016-01-01

Modulation of the elongation phase of protein synthesis is important for numerous physiological processes in both neurons and other cell types. Elongation is primarily regulated via eukaryotic elongation factor 2 kinase (eEF2K). However, the consequence of altering eEF2K activity on the synthesis of specific proteins is largely unknown. Using both pharmacological and genetic manipulations of eEF2K combined with two protein-labeling techniques, stable isotope labeling of amino acids in cell culture and bio-orthogonal non-canonical amino acid tagging, we identified a subset of proteins whose synthesis is sensitive to inhibition of eEF2K in murine primary cortical neurons. Gene ontology (GO) analyses indicated that processes related to microtubules are particularly sensitive to eEF2K inhibition. Our findings suggest that eEF2K likely contributes to neuronal function by regulating the synthesis of microtubule-related proteins. Modulation of the elongation phase of protein synthesis is important for numerous physiological processes in neurons. Here, using labeling of new proteins coupled with proteomic techniques in primary cortical neurons, we find that the synthesis of microtubule-related proteins is up-regulated by inhibition of elongation. This suggests that translation elongation is a key regulator of cytoskeletal dynamics in neurons. © 2015 The Authors. Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of International Society for Neurochemistry.

Structure of the Acinetobacter baumannii dithiol oxidase DsbA bound to elongation factor EF-Tu reveals a novel protein interaction site.

PubMed

Premkumar, Lakshmanane; Kurth, Fabian; Duprez, Wilko; Grøftehauge, Morten K; King, Gordon J; Halili, Maria A; Heras, Begoña; Martin, Jennifer L

2014-07-18

The multidrug resistant bacterium Acinetobacter baumannii is a significant cause of nosocomial infection. Biofilm formation, that requires both disulfide bond forming and chaperone-usher pathways, is a major virulence trait in this bacterium. Our biochemical characterizations show that the periplasmic A. baumannii DsbA (AbDsbA) enzyme has an oxidizing redox potential and dithiol oxidase activity. We found an unexpected non-covalent interaction between AbDsbA and the highly conserved prokaryotic elongation factor, EF-Tu. EF-Tu is a cytoplasmic protein but has been localized extracellularly in many bacterial pathogens. The crystal structure of this complex revealed that the EF-Tu switch I region binds to the non-catalytic surface of AbDsbA. Although the physiological and pathological significance of a DsbA/EF-Tu association is unknown, peptides derived from the EF-Tu switch I region bound to AbDsbA with submicromolar affinity. We also identified a seven-residue DsbB-derived peptide that bound to AbDsbA with low micromolar affinity. Further characterization confirmed that the EF-Tu- and DsbB-derived peptides bind at two distinct sites. These data point to the possibility that the non-catalytic surface of DsbA is a potential substrate or regulatory protein interaction site. The two peptides identified in this work together with the newly characterized interaction site provide a novel starting point for inhibitor design targeting AbDsbA. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Predictive potential of macrophage migration inhibitory factor (MIF) in patients with heart failure with preserved ejection fraction (HFpEF).

PubMed

Luedike, Peter; Alatzides, Georgios; Papathanasiou, Maria; Heisler, Martin; Pohl, Julia; Lehmann, Nils; Rassaf, Tienush

2018-05-04

Prognostication in heart failure with preserved ejection fraction (HFpEF) is challenging and novel biomarkers are urgently needed. Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine that plays a crucial role in cardiovascular and various inflammatory diseases. Whether MIF is involved in HFpEF is unknown. Sixty-two patients with HFpEF were enrolled and followed up for 180 days. MIF plasma levels as well as natriuretic peptide (NP) levels were assessed. High MIF levels significantly predicted the combined end-point of all-cause death or hospitalization at 180 days in the univariate analysis (HR 2.41, 95% CI 1.12-5.19, p = 0.025) and after adjustment for relevant covariates in a Cox proportional hazard regression model (HR 2.35, 95% CI 1.05-5.27, p = 0.0374). Furthermore, MIF levels above the median were associated with higher pulmonary artery systolic pressure (PASP) as assessed by echocardiography (PASP 31 mmHg vs 48 mmHg in the low- and high-MIF group, respectively, p = 0.017). NPs significantly correlated with MIF in HFpEF patients (BNP p = 0.011; r = 0.32; NT-proBNP p = 0.027; r = 0.28). MIF was associated with clinical outcomes and might be involved in the pathophysiology of pulmonary hypertension in patients with HFpEF. These first data on MIF in HFpEF should stimulate further research to elucidate the role of this cytokine in heart failure. Trial registration NCT03232671.

Elongation factor P is dispensable in Escherichia coli and Pseudomonas aeruginosa.

PubMed

Balibar, Carl J; Iwanowicz, Dorothy; Dean, Charles R

2013-09-01

Elongation factor P (EF-P) is a highly conserved ribosomal initiation factor responsible for stimulating formation of the first peptide bond. Its essentiality has been debated and may differ depending on the organism. Here, we demonstrate that EF-P is dispensable in Escherichia coli and Pseudomonas aeruginosa under laboratory growth conditions. Although knockouts are viable, growth rates are diminished compared with wild-type strains. Despite this cost in fitness, these mutants are not more susceptible to a wide range of antibiotics; including ribosome targeting antibiotics, such as lincomycin, chloramphenicol, and streptomycin, which have been shown previously to disrupt EF-P function in vitro. In Pseudomonas, knockout of efp leads to an upregulation of mexX, a phenotype previously observed with other genetic lesions affecting ribosome function and that can be induced by the treatment with antibiotics affecting protein synthesis.

Enhancement factor statistics of surface enhanced Raman scattering in multiscale heterostructures of nanoparticles.

PubMed

Zito, Gianluigi; Rusciano, Giulia; Sasso, Antonio

2016-08-07

Suitable metal nanostructures may induce surface-enhanced Raman scattering (SERS) enhancement factors (EFs) large-enough to reach single-molecule sensitivity. However, the gap hot-spot EF probability density function (PDF) has the character of a long-tail distribution, which dramatically mines the reproducibility of SERS experiments. Herein, we carry out electrodynamic calculations based on a 3D finite element method of two plasmonic nanostructures, combined with Monte Carlo simulations of the EF statistics under different external conditions. We compare the PDF produced by a homodimer of nanoparticles with that provided by a self-similar trimer. We show that the PDF is sensitive to the spatial distribution of near-field enhancement specifically supported by the nanostructure geometry. Breaking the symmetry of the plasmonic system is responsible for inducing particular modulations of the PDF tail resembling a multiple Poisson distribution. We also study the influence that molecular diffusion towards the hottest hot-spot, or selective hot-spot targeting, might have on the EF PDF. Our results quantitatively assess the possibility of designing the response of a SERS substrate so as to contain the intrinsic EF PDF variance and significantly improving, in principle, the reproducibility of SERS experiments.

Factors related to outcome in heart failure with a preserved (or normal) left ventricular ejection fraction.

PubMed

Sanderson, John E

2016-07-01

Heart failure with a preserved ejection faction (HFpEF) is a growing and expensive cause of heart failure (HF) affecting particularly the elderly. It differs in substantial ways in addition to the normal left ventricular ejection fraction, from the more easily recognized form of heart failure with a reduced ejection fraction (HFrEF or 'systolic heart failure') and unlike HFrEF there have been little advances in treatment. In part, this relates to the complexity of the pathophysiology and identifying the correct targets. In HFpEF, there appears to be widespread stiffening of the vasculature and the myocardium affecting ventricular function (both systolic and diastolic), impeding ventricular suction, and thus early diastolic filling leading to breathlessness on exertion and later atrial failure and fibrillation. Left ventricular ejection fraction tends to gradually decline and some evolve into HFrEF. Most patients also have a mixture of several co-morbidities including hypertension, diabetes, obesity, poor renal function, lack of fitness, and often poor social conditions. Therefore, many factors may influence outcome in an individual patient. In this review, the epidemiology, possible causation, pathophysiology, the influence of co-morbidities and some of the many potential predictors of outcome will be considered.

Vaccination with Eimeria tenella elongation factor-1α recombinant protein induces protective immunity against E. tenella and E. maxima infections.

PubMed

Lin, Rui-Qing; Lillehoj, Hyun S; Lee, Seung Kyoo; Oh, Sungtaek; Panebra, Alfredo; Lillehoj, Erik P

2017-08-30

Avian coccidiosis is caused by multiple species of the apicomplexan protozoan, Eimeria, and is one of the most economically devastating enteric diseases for the poultry industry worldwide. Host immunity to Eimeria infection, however, is relatively species-specific. The ability to immunize chickens against different species of Eimeria using a single vaccine will have a major beneficial impact on commercial poultry production. In this paper, we describe the molecular cloning, purification, and vaccination efficacy of a novel Eimeria vaccine candidate, elongation factor-1α (EF-1α). One day-old broiler chickens were given two subcutaneous immunizations one week apart with E. coli-expressed E. tenella recombinant (r)EF-1α protein and evaluated for protection against challenge infection with E. tenella or E. maxima. rEF-1α-vaccinated chickens exhibited increased body weight gains, decreased fecal oocyst output, and greater serum anti-EF-1α antibody levels following challenge infection with either E. tenella or E. maxima compared with unimmunized controls. Vaccination with EF-1α may represent a new approach to inducing cross-protective immunity against avian coccidiosis in the field. Published by Elsevier B.V.

Effective scheme to determine accurate defect formation energies and charge transition levels of point defects in semiconductors

NASA Astrophysics Data System (ADS)

Yao, Cang Lang; Li, Jian Chen; Gao, Wang; Tkatchenko, Alexandre; Jiang, Qing

2017-12-01

We propose an effective method to accurately determine the defect formation energy Ef and charge transition level ɛ of the point defects using exclusively cohesive energy Ecoh and the fundamental band gap Eg of pristine host materials. We find that Ef of the point defects can be effectively separated into geometric and electronic contributions with a functional form: Ef=χ Ecoh+λ Eg , where χ and λ are dictated by the geometric and electronic factors of the point defects (χ and λ are defect dependent). Such a linear combination of Ecoh and Eg reproduces Ef with an accuracy better than 5% for electronic structure methods ranging from hybrid density-functional theory (DFT) to many-body random-phase approximation (RPA) and experiments. Accordingly, ɛ is also determined by Ecoh/Eg and the defect geometric/electronic factors. The identified correlation is rather general for monovacancies and interstitials, which holds in a wide variety of semiconductors covering Si, Ge, phosphorenes, ZnO, GaAs, and InP, and enables one to obtain reliable values of Ef and ɛ of the point defects for RPA and experiments based on semilocal DFT calculations.

Apatinib in refractory radiation-induced brain edema: A case report.

PubMed

Hu, Wei Guo; Weng, Yi Ming; Dong, Yi; Li, Xiang Pan; Song, Qi-Bin

2017-11-01

Apatinib is a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor-2, which has observed to be effective and safe in refractory radiation-induced brain edema, like Avastin did. Till now, there is no case report after apatinib came in the market. Two patients who received brain radiotherapy developed clinical manifestations of brain edema, including dizziness, headache, limb activity disorder, and so on. Two patients were both diagnosed as refractory radiation-induced brain edema. Two patients received apatinib (500 mg/day) for 2 and 4 weeks. Two patients got symptomatic improvements from apatinib in different degrees. Magnetic resonance imaging after apatinib treatments showed that compared with pre-treatment imaging, the perilesional edema reduced dramatically. However, the toxicity of apatinib was controllable and tolerable. Apatinib can obviously relieve the symptoms of refractory radiation-induced brain edema and improve the quality of life, which offers a new method for refractory radiation-induced brain edema in clinical practices. But that still warrants further investigation in the prospective study.

"It is our exercise family": experiences of ethnic older adults in a group-based exercise program.

PubMed

Chiang, Kuan-Chun; Seman, Leslie; Belza, Basia; Tsai, Jenny Hsin-Chun

2008-01-01

Enhance Fitness (EF) (formerly the Lifetime Fitness Program) is an evidence-based community exercise program for older adults. From 1998 to 2005, participation of ethnic older adults increased significantly. However, little research is available about what ethnic older adults want or need to continue participation in exercise programs. The purpose of this study was to examine how physical environment, social environment, and individual biology and behavior influence adherence to exercise for ethnic older adults participating in EF. Six focus groups were conducted with 52 older adults participating in EF. Facilitators asked questions about factors that helped participants continue exercising in EF. Interviews were audiotaped and transcribed. Transcripts were systematically reviewed using content analysis. Focus group participants were Chinese (n = 21, 40%), African American (n = 18, 35%), white (n = 10, 19%), and Japanese (n = 3, 6%). Mean (SD) age was 76 years (7.4). Participants had, on average, participated in EF for 44 months (SD = 37.8). Results revealed four themes related to adherence. First, environmental factors that promoted adherence were location of the classes, transportation, weather, and the facility. Second, design of the exercise program that encouraged adherence included exercise content and type of delivery. Third, social support factors that encouraged adherence were the socializing and support between class participants and support from family, health care providers, and the class instructors. Finally, individual factors that encouraged adherence were personality traits and feelings, past physical activity experience, health benefits, and mental stimulation. Findings from this study suggest strategies for developing community-based physical activity programs for older adults from ethnically diverse communities.

Up-regulation of eEF1A2 promotes proliferation and inhibits apoptosis in prostate cancer.

PubMed

Sun, Yue; Du, Chengli; Wang, Bo; Zhang, Yanling; Liu, Xiaoyan; Ren, Guoping

2014-07-18

eEF1A2 is a protein translation factor involved in protein synthesis, which possesses important function roles in cancer development. This study aims at investigating the expression pattern of eEF1A2 in prostate cancer and its potential role in prostate cancer development. We examined the expression level of eEF1A2 in 30 pairs of prostate cancer tissues by using RT-PCR and immunohistochemical staining (IHC). Then we applied siRNA specifically targeting eEF1A2 to down-regulate its expression in DU-145 and PC-3 cells. Flow cytometer was used to explore apoptosis and Western-blot was used to detect the pathway proteins of apoptosis. Our results showed that the expression level of eEF1A2 in prostate cancer tissues was significantly higher compared to their corresponding normal tissues. Reduction of eEF1A2 expression in DU-145 and PC-3 cells led to a dramatic inhibition of proliferation accompanied with enhanced apoptosis rate. Western blot revealed that apoptosis pathway proteins (caspase3, BAD, BAX, PUMA) were significantly up-regulated after suppression of eEF1A2. More importantly, the levels of eEF1A2 and caspase3 were inversely correlated in prostate cancer tissues. Our data suggests that eEF1A2 plays an important role in prostate cancer development, especially in inhibiting apoptosis. So eEF1A2 might serve as a potential therapeutic target in prostate cancer. Copyright © 2014 Elsevier Inc. All rights reserved.

Reducing Periorbital Edema and Ecchymosis after Rhinoplasty: Literature Review and Personal Approach.

PubMed

Tasman, Abel-Jan

2018-02-01

Postoperative periorbital edema and ecchymosis are most bothersome to rhinoplasty patients. The degree of swelling and bruising is influenced by several factors, and numerous prophylactic and therapeutic measures have been described in the literature. This article reviews the current literature and concludes with the author's suggestions on how to best minimize postoperative periorbital edema and ecchymosis. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Analysis of Fulminant Cerebral Edema in Acute Pediatric Encephalitis.

PubMed

Lan, Shih-Yun; Lin, Jainn-Jim; Hsia, Shao-Hsuan; Wang, Huei-Shyong; Chiu, Cheng-Hsun; Lin, Kuang-Lin

2016-10-01

Acute pediatric encephalitis with fulminant cerebral edema can rapidly become fatal or result in devastating neurological sequelae. All cases coded with the discharge diagnosis of acute encephalitis between January 2000 and December 2010 were reviewed. Of the 1038 children with acute pediatric encephalitis, 25 were enrolled in our study with ages ranging from 5 months to 16 years. The major neurological symptoms included an altered level of consciousness (72%), vomiting (60%), and headache (48%). The onset of neurological symptoms to signs of brain herniation ranged from 0 days to 9 days. Nineteen (76%) patients had a seizure 24-48 hours prior to showing signs of fulminant cerebral edema, and 12 (48%) patients developed status epilepticus. Sixteen patients died, and no survivors returned to baseline. Risk factors for seizures and status epilepticus were compared between the fulminant cerebral edema group (n = 25, 19 seizures, including 12 status epilepticus) and control group (nonfulminant cerebral edema) (n = 1013, 444 seizures, including 141 status epilepticus; p = 0.001 for seizures and p < 0.001 for status epilepticus). Our findings indicate that preceding seizures and status epilepticus are significant risk factors for fulminant cerebral edema in children with acute encephalitis. Copyright © 2016. Published by Elsevier B.V.

Fluid intelligence and executive functioning more alike than different?

PubMed

van Aken, Loes; Kessels, Roy P C; Wingbermühle, Ellen; van der Veld, William M; Egger, Jos I M

2016-02-01

Fluid intelligence (Gf) has been related to executive functioning (EF) in previous studies, and it is also known to be correlated with crystallized intelligence (Gc). The present study includes representative measures of Gf, Gc, and EF frequently used in clinical practice to examine this Gf-EF relation. It is hypothesised that the Gf-EF relation is higher than the Gc-EF relation, and that working memory in particular (as a measure of EF) shows a high contribution to this relation. Confirmatory factor analysis was performed on a mixed neuropsychiatric and non-clinical sample consisting of 188 participants, using the Kaufman Adolescent and Adult Intelligence Test, and three executive tasks of the Cambridge Neuropsychological Test Automated Battery, covering working memory, planning skills, and set shifting. The model fitted the data well [χ²(24)=35.25, p=0.07, RMSEA=0.050]. A very high correlation between Gf and EF was found (0.91), with working memory being the most profound indicator. A moderate to high correlation between Gc and EF was present. Current results are consistent with findings of a strong relation between Gf and working memory. Gf and EF are highly correlated. Gf dysfunction in neuropsychiatric patients warrants further EF examination and vice versa. It is discussed that results confirm the need to distinguish between specific versus general fluid/executive functioning, the latter being more involved when task complexity and novelty increase. This distinction can provide a more refined differential diagnosis and improve neuropsychiatric treatment indication.

Hypertension and Heart Failure with Preserved Ejection Fraction: Connecting the Dots.

PubMed

Tsioufis, Costas; Georgiopoulos, Georgios; Oikonomou, Dimitrios; Thomopoulos, Costas; Katsiki, Niki; Kasiakogias, Alexandros; Chrysochoou, Christina; Konstantinidis, Dimitrios; Kalos, Theodoros; Tousoulis, Dimitrios

2017-01-01

Heart failure (HF) with preserved ejection fraction (EF) (HFpEF) accounts for approximately 50% of HF cases and its prevalence relative to HF with reduced EF is rising. Hypertension (HT) is the most common co-morbidity in HFpEF patients and it is implicated in both the pathogenesis and the prognosis of the disease. Therefore, HT is a modifiable risk factor of high yield in HFpEF. We reviewed the literature for epidemiologic data supporting the co-aggregation of the two entities as well as patho-physiologic mechanisms linking HT to HFpEF. Most importantly, we focused on treatment options targeting HT as a preventive strategy for delaying the progression of diastolic dysfunction or decreasing the odds for developing HFpEF. Along this line, we summarized the evidence and efficacy associated with different classes of antihypertensive medications in HFpEF patients. Finally, non-pharmacological approaches, including renal denervation and lifestyle modifications, to achieve optimal blood pressure (BP) control in HFpEF patients are reported. Unfortunately, no specific antihypertensive treatment has established a major survival benefit in this high risk subjects. Until the results of the efficacy of the novel drug LCZ696 (valsartan/ sacubitril) are available, the continuous monitoring and lowering of the BP by pharmacological and non-pharmacological means should be considered the major preventive and treatment strategy in HFpEF patients. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

[Risk factors associated with work-related accidents in the construction industry in the Valley of Mexico].

PubMed

Sarmiento-Salinas, Rodrigo; López-Rojas, Pablo; Marín-Cotoñieto, Irma Araceli; Godínez-Rocha, Arturo; Haro-García, Luis; Salinas-Tovar, Santiago

2004-01-01

Our aim was to describe construction-industry, work-related accident prevalence in, associated factors in, and potential impact on affiliated workers of the Mexican Institute of Social Security (Instituto Mexicano del Seguro Social, IMSS) in the Valley of Mexico. Prevalent cases in a retrospective case-control design. These include 385 construction-industry workers who were found to have construction work-related accidents in 2001. Controls comprised 385 active construction-industry workers without work-related accident background paired by gender, workplace, and worksite. Work-related accident prevalence in construction workers was 5.5%; most important risk factors and etiology fraction (Ef) included the following: age 16-20 years odds ratio, OR = 1.58, 95% confidence interval (95% CI) 1.40-10.7, p = 0.001, Ef 0.36; eventual insurance, OR = 3.7, 95% CI, 2.16-26.45, p = 0.001), Ef, 0.72, and no training for job, OR = 5.3, 95% CI, 4.9-69.2, p = 0.01), Ef: 0.81. Variables not showing significance were included salary, work shift, and workday. Work-related accident prevalence maintains its preponderance in the Valley of Mexico construction industry; identified risk factors are potentially modifiable, among which job training acquires unquestionable relevance.

Emodin inhibits coxsackievirus B3 replication via multiple signalling cascades leading to suppression of translation.

PubMed

Zhang, Huifang M; Wang, Fengping; Qiu, Ye; Ye, Xin; Hanson, Paul; Shen, Hongxing; Yang, Decheng

2016-02-15

CVB3 (coxsackievirus 3) is a primary causal agent of viral myocarditis. Emodin is a natural compound isolated from certain plant roots. In the present study, we found that emodin inhibited CVB3 replication in vitro and in mice, and now we report an unrecognized mechanism by which emodin inhibits CVB3 replication through suppression of viral protein translation via multiple pathways. On one hand, emodin treatment inhibited Akt/mTOR (mammalian target of rapamycin) signalling and activated 4EBP1 (eukaryotic initiation factor 4R-binding protein 1), leading to suppression of translation initiation of ribosomal protein L32 encoded by a 5'-TOP (terminal oligopyrimidine) mRNA. On the other hand, emodin treatment differentially regulated multiple signal cascades, including Akt/mTORC1/p70(S6K) (p70 S6 kinase), ERK1/2 (extracellular-signal-regulated kinase 1/2)/p90(RSK) (p90 ribosomal S6 kinase) and Ca(2+)/calmodulin, leading to activation of eEF2K (eukaryotic elongation factor 2 kinase) and subsequent inactivation of eEF2 (eukaryotic elongation factor 2), resulting in inhibition of CVB3 VP1 (viral protein 1) synthesis. These data imply that eEF2K is a major factor mediating cross-talk of different arms of signalling cascades in this signal network. This notion was verified by either overexpressing eEF2K or treating the cells with siRNAs or eEF2K inhibitor A484954. We showed further that the emodin-induced decrease in p70(S6K) phosphorylation plays a dominant positive role in activation of eEF2K and in turn in conferring the antiviral effect of emodin. This finding was further solidified by expressing constitutively active and dominant-negative Akt. Collectively, our data reveal that emodin inhibits viral replication through impairing translational machinery and suppression of viral translation elongation. © 2016 Authors; published by Portland Press Limited.

Extending the ‘cross-disorder’ relevance of executive functions to dimensional neuropsychiatric traits in youth

PubMed Central

McGrath, Lauren M.; Braaten, Ellen B.; Doty, Nathan D.; Willoughby, Brian L.; Wilson, H. Kent; O’Donnell, Ellen H.; Colvin, Mary K.; Ditmars, Hillary L.; Blais, Jessica E.; Hill, Erin N.; Metzger, Aaron; Perlis, Roy H.; Willcutt, Erik G.; Smoller, Jordan W.; Waldman, Irwin D.; Faraone, Stephen V.; Seidman, Larry J.; Doyle, Alysa E.

2016-01-01

Background Evidence that different neuropsychiatric conditions share genetic liability has increased interest in phenotypes with ‘cross-disorder’ relevance, as they may contribute to revised models of psychopathology. Cognition is a promising construct for study; yet, evidence that the same cognitive functions are impaired across different forms of psychopathology comes primarily from separate studies of individual categorical diagnoses versus controls. Given growing support for dimensional models that cut across traditional diagnostic boundaries, we aimed to determine, within a single cohort, whether performance on measures of executive functions (EFs) predicted dimensions of different psychopathological conditions known to share genetic liability. Methods Data are from 393 participants, ages 8 to 17, consecutively enrolled in the Longitudinal Study of Genetic Influences on Cognition (LOGIC). This project is conducting deep phenotyping and genomic analyses in youth referred for neuropsychiatric evaluation. Using structural equation modeling, we examined whether EFs predicted variation in core dimensions of autism spectrum disorder, bipolar illness and schizophrenia, including social responsiveness, mania/emotion regulation, and positive symptoms of psychosis, respectively. Results We modeled three cognitive factors (working memory, shifting, and executive processing speed) that loaded on a second-order EF factor. The EF factor predicted variation in our three target traits but not in a negative control (somatization). Moreover, this EF factor was primarily associated with the overlapping (rather than unique) variance across the three outcome measures, suggesting it related to a general increase in psychopathology symptoms across those dimensions. Conclusions Findings extend support for the relevance of cognition to neuropsychiatric conditions that share underlying genetic risk. They suggest that higher-order cognition, including EFs, relate to the dimensional spectrum of each of these disorders and not just the clinical diagnoses. Moreover, results have implications for bottom-up models linking genes, cognition, and a general psychopathology liability. PMID:26411927

76 FR 53477 - Medicare Program; Meeting of the Medicare Evidence Development and Coverage Advisory Committee...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-26

... macular edema (DME). This meeting is open to the public in accordance with the Federal Advisory Committee... regarding antivascular endothelial growth factor (anti-VEGF) treatment of diabetic macular edema (DME...

Performance evaluation of structure based and ligand based virtual screening methods on ten selected anti-cancer targets.

PubMed

Ramasamy, Thilagavathi; Selvam, Chelliah

2015-10-15

Virtual screening has become an important tool in drug discovery process. Structure based and ligand based approaches are generally used in virtual screening process. To date, several benchmark sets for evaluating the performance of the virtual screening tool are available. In this study, our aim is to compare the performance of both structure based and ligand based virtual screening methods. Ten anti-cancer targets and their corresponding benchmark sets from 'Demanding Evaluation Kits for Objective In silico Screening' (DEKOIS) library were selected. X-ray crystal structures of protein-ligand complexes were selected based on their resolution. Openeye tools such as FRED, vROCS were used and the results were carefully analyzed. At EF1%, vROCS produced better results but at EF5% and EF10%, both FRED and ROCS produced almost similar results. It was noticed that the enrichment factor values were decreased while going from EF1% to EF5% and EF10% in many cases. Published by Elsevier Ltd.

Fluctuations between multiple EF-G-induced chimeric tRNA states during translocation on the ribosome

NASA Astrophysics Data System (ADS)

Adio, Sarah; Senyushkina, Tamara; Peske, Frank; Fischer, Niels; Wintermeyer, Wolfgang; Rodnina, Marina V.

2015-06-01

The coupled translocation of transfer RNA and messenger RNA through the ribosome entails large-scale structural rearrangements, including step-wise movements of the tRNAs. Recent structural work has visualized intermediates of translocation induced by elongation factor G (EF-G) with tRNAs trapped in chimeric states with respect to 30S and 50S ribosomal subunits. The functional role of the chimeric states is not known. Here we follow the formation of translocation intermediates by single-molecule fluorescence resonance energy transfer. Using EF-G mutants, a non-hydrolysable GTP analogue, and fusidic acid, we interfere with either translocation or EF-G release from the ribosome and identify several rapidly interconverting chimeric tRNA states on the reaction pathway. EF-G engagement prevents backward transitions early in translocation and increases the fraction of ribosomes that rapidly fluctuate between hybrid, chimeric and posttranslocation states. Thus, the engagement of EF-G alters the energetics of translocation towards a flat energy landscape, thereby promoting forward tRNA movement.

Severe periorbital edema secondary to STI571 (Gleevec).

PubMed

Esmaeli, Bita; Prieto, Victor G; Butler, Charles E; Kim, Stella K; Ahmadi, M Amir; Kantarjian, Hagop M; Talpaz, Moshe

2002-08-15

STI571 (imatinib mesylate; Gleevec) is a selective inhibitor of the bcr-abl, c-kit, and platelet-derived growth factor receptor tyrosine kinases. Mild periorbital edema has been noted as a common side effect in Phase I and II trials of this drug for the treatment of patients with chronic myelogenous leukemia and gastrointestinal stromal tumors. The authors report the case of male patient age 63 years who developed severe periorbital edema after treatment with STI571 for chronic myelogenous leukemia. His edema was severe enough to cause visual obstruction due to lower eyelid festoons that ultimately required surgical debulking. Histopathologic analysis of specimens of the excised upper and lower eyelid tissue revealed dermal dendrocytes that expressed the platelet-derived growth factor receptor and c-kit tyrosine kinases, suggesting a possible role for dermal dendrocytes in the development of this toxic effect. Copyright 2002 American Cancer Society.DOI 10.1002/cncr.10729

Sarcoidosis with high serum levels of vascular endothelial growth factor (VEGF), showing RS3PE-like symptoms in extremities.

PubMed

Matsuda, Masayuki; Sakurai, Kumi; Fushimi, Tomohisa; Yamamoto, Kanji; Rokuhara, Shiho; Hosaka, Naritoshi; Ikeda, Shu-ichi

2004-06-01

We report a patient with sarcoidosis who showed edema in the distal portion of all extremities, particularly the legs, as seen in remitting seronegative symmetrical synovitis with pitting edema (RS3PE). Magnetic resonance imaging demonstrated diffuse abnormal intensity in subcutaneous tissues of both legs, and skin biopsy led to a diagnosis of sarcoidosis. Vascular endothelial growth factor (VEGF) showed a high serum level, which decreased soon after starting oral prednisolone, in parallel with an improvement in the limb edema. In this patient VEGF as well as infiltration by sarcoid granuloma in the skin might have played an important role in the pathogenesis of RS3PE-like symptoms in the extremities. When painful pitting edema is seen predominantly in the distal portion of all extremities, sarcoidosis as well as RS3PE should be considered as a possible diagnosis.

Serum VEGF-C levels as a candidate biomarker of hypervolemia in chronic kidney disease

PubMed Central

Sahutoglu, Tuncay; Sakaci, Tamer; Hasbal, Nuri B.; Ahbap, Elbis; Kara, Ekrem; Sumerkan, Mutlu C.; Sevinc, Mustafa; Akgol, Cuneyt; Koc, Yener; Basturk, Taner; Unsal, Abdulkadir

2017-01-01

Abstract Attaining and maintaining optimal “dry weight” is one of the principal goals during maintenance hemodialysis (MHD). Recent studies have shown a close relationship between Na+ load and serum vascular endothelial growth factor-C (VEGF-C) levels; thus, we aimed to investigate the role of VEGF-C as a candidate biomarker of hypervolemia. Physical examination, basic laboratory tests, N-terminal pro b-type natriuretic peptide (NT-ProBNP), echocardiography, and bioimpedance spectroscopy data of 3 groups of study subjects (euvolemic MHD patients, healthy controls, and hypervolemic chronic kidney disease [CKD] patients) were analyzed. Research data for MHD patients were obtained both before the first and after the last hemodialysis (HD) sessions of the week. Data of 10 subjects from each study groups were included in the analysis. Serum VEGF-C levels were significantly higher in hypervolemic CKD versus in MHD patients both before the first and after the last HD sessions (P = .004 and P = .000, respectively). Healthy controls had serum VEGF-C levels similar to and higher than MHD patients before the first and after the last HD sessions of the week (P = .327 and P = .021, respectively). VEGF-C levels were correlated with bioimpedance spectroscopy results (r2 0.659, P = .000) and edema (r2 0.494, P =0.006), but not with ejection fraction (EF) (r2 −0.251, P = .134), blood pressures (systolic r2 0.037, P = 0.824, diastolic r2 −0.067, P = .691), and NT-ProBNP (r2 −0.047, P = .773). These findings suggest that serum VEGF-C levels could be a potential new biomarker of hypervolemia. The lack of correlation between VEGF-C and EF may hold a promise to eliminate this common confounder. Further studies are needed to define the clinical utility of VEGF-C in volume management. PMID:28471955

Family demographic profiles and their relationship with the quality of executive functioning subcomponents in kindergarten.

PubMed

Vandenbroucke, Loren; Verschueren, Karine; Ceulemans, Eva; De Smedt, Bert; De Roover, Kim; Baeyens, Dieter

2016-06-01

Executive functioning (EF), needed for goal-oriented behaviour, thoughts, and emotions, is important for various life domains. This study examined the relationship between family demographics and EF subcomponents. A kindergarten sample was tested on subcomponents of working memory, inhibition, and cognitive flexibility. Parents provided information on demographic variables. For 78 children both EF and demographic data were available. First, demographic profiles were identified within the sample. Two profiles were found: A low-risk profile of mainly two-biological-parent, high-income families with a highly educated mother who did not smoke during pregnancy and a high-risk profile of low-income families with a young, low-educated mother who more often smoked during pregnancy. Second, children with different demographic profiles were compared on EF subcomponents. Results indicate differential relations between family demographics and EF subcomponents: Whereas for most EF subcomponents no association with family demographics was found, high-risk children performed better on response shifting and tended to perform worse on verbal memory than low-risk children. Parenting stress decreased performance only for high-risk children. Although this study found limited impact of family demographics for EF, further longitudinal research can provide nuanced insights about which factors influence specific EF subcomponents during which developmental periods and guide targeted prevention of EF difficulties. © 2015 The British Psychological Society.

Regulation of cellular function via electromagnetic field frequency and extracellular environment: A theoretical- experimental approach

NASA Astrophysics Data System (ADS)

Taghian, Toloo; Sheikh, Abdul; Narmoneva, Daria; Kogan, Andrei

2015-03-01

Application of external electric field (EF) as a non-pharmacological, non-invasive tool to control cell function is of great therapeutic interest. We developed a theoretical-experimental approach to investigate the biophysical mechanisms of EF interaction with cells in electrode-free physiologically-relevant configuration. Our numerical results demonstrated that EF frequency is the major parameter to control cell response to EF. Non-oscillating or low-frequency EF leads to charge accumulation on the cell surface membrane that may mediate membrane initiated cell responses. In contrast, high-frequency EF penetrates the cell membrane and reaches cell cytoplasm, where it may directly activate intracellular responses. The theoretical predictions were confirmed in our experimental studies of the effects of applied EF on vascular cell function. Results show that non-oscillating EF increases vascular endothelial growth factor (VEGF) expression while field polarity controls cell adhesion rate. High-frequency, but not low frequency, EF provides differential regulation of cytoplasmic focal adhesion kinase and VEGF expression depending on the substrate, with increased expression in cells cultured on RGD-rich synthetic hydrogels, and decreased expression for matrigel culture. The authors acknowledge the financial support from the NSF (DMR-1206784 & DMR-0804199 to AK); the NIH (1R21 DK078814-01A1 to DN) and the University of Cincinnati (Interdisciplinary Faculty Research Support Grant to DN and AK).

VEGF inhibitors in the treatment of cerebral edema in patients with brain cancer

PubMed Central

Gerstner, Elizabeth R.; Duda, Dan G.; di Tomaso, Emmanuelle; Ryg, Peter A.; Loeffler, Jay S.; Sorensen, A. Gregory; Ivy, Percy; Jain, Rakesh K.; Batchelor, Tracy T.

2016-01-01

Most brain tumors oversecrete vascular endothelial growth factor (VEGF), which leads to an abnormally permeable tumor vasculature. This hyperpermeability allows fluid to leak from the intravascular space into the brain parenchyma, which causes vasogenic cerebral edema and increased interstitial fluid pressure. Increased interstitial fluid pressure has an important role in treatment resistance by contributing to tumor hypoxia and preventing adequate tumor penetration of chemotherapy agents. In addition, edema and the corticosteroids needed to control cerebral edema cause significant morbidity and mortality. Agents that block the VEGF pathway are able to decrease vascular permeability and, thus, cerebral edema, by restoring the abnormal tumor vasculature to a more normal state. Decreasing cerebral edema minimizes the adverse effects of corticosteroids and could improve clinical outcomes. Anti-VEGF agents might also be useful in other cancer-related conditions that increase vascular permeability, such as malignant pleural effusions or ascites. PMID:19333229

TRPC3- and ETB receptor-mediated PI3K/AKT activation induces vasogenic edema formation following status epilepticus.

PubMed

Kim, Ji-Eun; Kang, Tae-Cheon

2017-10-01

Status epilepticus (SE, a prolonged seizure activity) is a high risk factor of developing vasogenic edema, which leads to secondary complications following SE. In the present study, we investigated whether transient receptor potential canonical channel-3 (TRPC3) may link vascular endothelial growth factor (VEGF) pathway to NFκB/ET B receptor axis in the rat piriform cortex during vasogenic edema formation. Following SE, TRPC3 and ET B receptor independently activated phosphatidylinositol 3 kinase (PI3K)/AKT/eNOS signaling pathway. SN50 (a NFκB inhibitor) attenuated the up-regulations of eNOS, TRPC3 and ET B receptor expressions following SE, accompanied by reductions in PI3K/AKT phosphorylations. Inhibition of SE-induced VEGF over-expression by leptomycin B also abrogated PI3K and AKT phosphorylations, but not TRPC3 expression. Wortmannin (a PI3K inhibitor) and 3CAI (an AKT inhibitor) effectively inhibited up-regulation of eNOS expressions and vasogenic edema lesion following SE. These findings indicate that PI3K/AKT may be common down-stream molecules for TRPC3- and ET B receptor signaling pathways during vasogenic edema formation. In addition, the present data demonstrate for the first time that TRPC3 may integrate VEGF- and NFκB-mediated vasogenic edema formation following SE. Thus, we suggest that PI3K/AKT signaling pathway may be one of considerable therapeutic targets for vasogenic edema. Copyright © 2017 Elsevier B.V. All rights reserved.

Ecological footprint model using the support vector machine technique.

PubMed

Ma, Haibo; Chang, Wenjuan; Cui, Guangbai

2012-01-01

The per capita ecological footprint (EF) is one of the most widely recognized measures of environmental sustainability. It aims to quantify the Earth's biological resources required to support human activity. In this paper, we summarize relevant previous literature, and present five factors that influence per capita EF. These factors are: National gross domestic product (GDP), urbanization (independent of economic development), distribution of income (measured by the Gini coefficient), export dependence (measured by the percentage of exports to total GDP), and service intensity (measured by the percentage of service to total GDP). A new ecological footprint model based on a support vector machine (SVM), which is a machine-learning method based on the structural risk minimization principle from statistical learning theory was conducted to calculate the per capita EF of 24 nations using data from 123 nations. The calculation accuracy was measured by average absolute error and average relative error. They were 0.004883 and 0.351078% respectively. Our results demonstrate that the EF model based on SVM has good calculation performance.

Identifying Component-Processes of Executive Functioning that Serve as Risk Factors for the Alcohol-Aggression Relation

PubMed Central

Giancola, Peter R.; Godlaski, Aaron J.; Roth, Robert M.

2011-01-01

The present investigation determined how different component-processes of executive functioning (EF) served as risk factors for intoxicated aggression. Participants were 512 (246 men and 266 women) healthy social drinkers between 21 and 35 years of age. EF was measured using the Behavior Rating Inventory of Executive Functioning – Adult Version (BRIEF-A; Roth, Isquith, & Gioia, 2005) that assesses nine EF components. Following the consumption of either an alcohol or a placebo beverage, participants were tested on a modified version of the Taylor Aggression Paradigm (Taylor, 1967) in which mild electric shocks were received from, and administered to, a fictitious opponent. Aggressive behavior was operationalized as the shock intensities and durations administered to the opponent. Although a general BRIEF-A EF construct consisting of all nine components predicted intoxicated aggression, the best predictor involved one termed the Behavioral Regulation Index which comprises component processes such as inhibition, emotional control, flexible thinking, and self-monitoring. PMID:21875167

Synthesis of EF24-tripeptide chloromethyl ketone: a novel curcumin-related anticancer drug delivery system.

PubMed

Sun, Aiming; Shoji, Mamoru; Lu, Yang J; Liotta, Dennis C; Snyder, James P

2006-06-01

The blood coagulation cascade includes a step in which the soluble protein, factor VIIa (fVIIa), complexes with its transmembrane receptor, tissue factor (TF). The fVIIa/TF protein-protein complex is subsequently drawn into the cell by endocytosis. The observation that TF is aberrantly and abundantly expressed on many cancer cells offers an opportunity to specifically target those cells with an effective anticancer drug. Thus, we propose a new drug delivery system, drug-linker-Phe-Phe-Arg-mk-fVIIa, which can associate with TF on the surface of cancer cells, but release the cytotoxic agent in the cytoplasm. Synthetic procedures have been developed for the preparation of phenylalanine-phenylalanine-arginine chloromethyl ketone, (FFRck) followed by coupling with the cytotoxin EF24 and subsequently fVIIa to give EF-24-FFRmk-fVIIa. When breast cancer cells (MDA-MB-231) and human melanoma cells (RPMI-7951) are treated with the complex, the cells are arrested to a greater extent than EF24 alone by comparison with controls.

Surface microlayer enrichment of volatile organic compounds and semi-volatile organic compounds in drinking water source.

PubMed

Huang, Zhi; Zhou, Wen; Yu, Ya-juan; Zhang, Ai-qian; Han, Shuo-kui; Wang, Lian-sheng

2004-01-01

Enrichment of volatile organic compounds(VOC) and semi-volatility organic compounds(SVOC) in surface microlayer(SM) of three drinking water sources were studied. The enrichment factor(EFs) were 0.67 to 13.37 and 0.16 to 136, respectively. The results showed some VOC and most SVOC could enrich in SM. Some EFs of SVOC was quite high. Suspension and temperature could affect EFs of SVOC, slim wind and water movement do not destroy enrichment of organic in SM.

Associations between early life adversity and executive function in children adopted internationally from orphanages

PubMed Central

Hostinar, Camelia E.; Stellern, Sarah A.; Schaefer, Catherine; Carlson, Stephanie M.; Gunnar, Megan R.

2012-01-01

Executive function (EF) abilities are increasingly recognized as an important protective factor for children experiencing adversity, promoting better stress and emotion regulation as well as social and academic adjustment. We provide evidence that early life adversity is associated with significant reductions in EF performance on a developmentally sensitive battery of laboratory EF tasks that measured cognitive flexibility, working memory, and inhibitory control. Animal models also suggest that early adversity has a negative impact on the development of prefrontal cortex-based cognitive functions. In this study, we report EF performance 1 y after adoption in 2.5- to 4-y-old children who had experienced institutional care in orphanages overseas compared with a group of age-matched nonadopted children. To our knowledge, this is the youngest age and the soonest after adoption that reduced EF performance has been shown using laboratory measures in this population. EF reductions in performance were significant above and beyond differences in intelligence quotient. Within the adopted sample, current EF was associated with measures of early deprivation after controlling for intelligence quotient, with less time spent in the birth family before placement in an institution and lower quality of physical/social care in institutions predicting poorer performance on the EF battery. PMID:23047689

Associations between early life adversity and executive function in children adopted internationally from orphanages.

PubMed

Hostinar, Camelia E; Stellern, Sarah A; Schaefer, Catherine; Carlson, Stephanie M; Gunnar, Megan R

2012-10-16

Executive function (EF) abilities are increasingly recognized as an important protective factor for children experiencing adversity, promoting better stress and emotion regulation as well as social and academic adjustment. We provide evidence that early life adversity is associated with significant reductions in EF performance on a developmentally sensitive battery of laboratory EF tasks that measured cognitive flexibility, working memory, and inhibitory control. Animal models also suggest that early adversity has a negative impact on the development of prefrontal cortex-based cognitive functions. In this study, we report EF performance 1 y after adoption in 2.5- to 4-y-old children who had experienced institutional care in orphanages overseas compared with a group of age-matched nonadopted children. To our knowledge, this is the youngest age and the soonest after adoption that reduced EF performance has been shown using laboratory measures in this population. EF reductions in performance were significant above and beyond differences in intelligence quotient. Within the adopted sample, current EF was associated with measures of early deprivation after controlling for intelligence quotient, with less time spent in the birth family before placement in an institution and lower quality of physical/social care in institutions predicting poorer performance on the EF battery.

Executive functions in adults with developmental dyslexia.

PubMed

Smith-Spark, James H; Henry, Lucy A; Messer, David J; Edvardsdottir, Elisa; Zięcik, Adam P

2016-01-01

Executive functioning (EF) deficits are well recognized in developmental dyslexia, yet the majority of studies have concerned children rather than adults, ignored the subjective experience of the individual with dyslexia (with regard to their own EFs), and have not followed current theoretical perspectives on EFs. The current study addressed these shortfalls by administering a self-report measure of EF (BRIEF-A; Roth, Isquith, & Gioia, 2005) and experimental tasks to IQ-matched groups of adults with and without dyslexia. The laboratory-based tasks tested the three factors constituting the framework of EF proposed by Miyake et al. (2000). In comparison to the group without dyslexia, the participants with dyslexia self-reported more frequent EF problems in day-to-day life, with these difficulties centering on metacognitive processes (working memory, planning, task monitoring, and organization) rather than on the regulation of emotion and behaviour. The participants with dyslexia showed significant deficits in EF (inhibition, set shifting, and working memory). The findings indicated that dyslexia-related problems have an impact on the daily experience of adults with the condition. Further, EF difficulties are present in adulthood across a range of laboratory-based measures, and, given the nature of the experimental tasks presented, extend beyond difficulties related solely to phonological processing. Copyright © 2016 Elsevier Ltd. All rights reserved.

Comparison of 5-Year Outcomes After Coronary Artery Bypass Grafting in Heart Failure Patients With Versus Without Preserved Left Ventricular Ejection Fraction (from the CREDO-Kyoto CABG Registry Cohort-2).

PubMed

Marui, Akira; Nishiwaki, Noboru; Komiya, Tatsuhiko; Hanyu, Michiya; Tanaka, Shiro; Kimura, Takeshi; Sakata, Ryuzo

2015-08-15

Heart failure (HF) with reduced left ventricular (LV) ejection fraction (HFrEF) is regarded as an independent risk factor for poor outcomes after coronary artery bypass grafting (CABG). However, the impact of HF with preserved EF (HFpEF) still has been unclear. We identified 1,877 patients who received isolated CABG of 15,939 patients who underwent first coronary revascularization enrolled in the CREDO-Kyoto (Coronary REvascularization Demonstrating Outcome Study in Kyoto) Registry Cohort-2. Of them, 1,489 patients had normal LV function (LVEF >50% without a history of HF; Normal group), 236 had HFrEF (LVEF ≤50% with HF), and 152 had HFpEF (LVEF >50% with HF). Preoperative LVEF was the lowest in the HFrEF group (62 ± 12%, 36 ± 9%, and 61 ± 7% for the Normal, HFrEF, and HFpEF groups, respectively; p <0.001). Unadjusted 30-day mortality rate was the highest in the HFrEF group (0.5%, 3.0%, and 0.7%; p = 0.003). However, cumulative incidences of all-cause death at 5-year was the highest in the HFpEF group (14%, 27%, and 32%, respectively; p <0.001). After adjusting confounders, the risk of all-cause death in the HFpEF group was greater than the Normal group (hazard ratio [HR] 1.42; 95% confidence interval [CI] 1.02 to 1.97; p = 0.04). The risk of all-cause death was not different between the HFpEF and the HFrEF groups (HR 0.88; 95% CI 0.61 to 1.29; p = 0.52). In addition, the risks of cardiac death and sudden death in the HFpEF group were greater than the Normal group (HR 2.14, 95% CI 1.32 to 3.49, p = 0.002; and HR 3.60, 95% CI 1.55 to 8.36, p = 0.003, respectively), and the risks of those end points were not different between the HFrEF and the HFpEF groups. Despite low 30-day mortality rate after CABG in patients with HFpEF, HFpEF was associated with high risks of long-term death and cardiovascular events. Patients with HFpEF, as well as HFrEF, should be carefully operated and followed up. Copyright © 2015 Elsevier Inc. All rights reserved.

Can the origin of some metals in the seagrass Posidonia oceanica be determined by the indexes of metals pollutions?

PubMed

Stanković, Slavka; Jović, Mihajlo; Tanaskovski, Bojan; Mihajlović, Marija L; Joksimović, Danijela; Pezo, Lato

2015-06-01

To assess metal pollution, Fe, Mn, Cu, Zn, Pb, Ni, Co, As, Cd, and Hg contents in samples of the seagrass Posidonia oceanica and surface sediment, collected at eight locations along the Montenegrin coast, were determined. The metal pollution index (MPI) and metal enrichment factor (EF) were then calculated. MPI and EF were lower in sediment than in P. oceanica at the same locations. This was very evident for EF values of Hg and Cd. Based on the Pearson's correlations and EF values, it was possible to conclude that the last two metals' content in the seagrass did not originate from the crustal sources or natural weathering processes.

Specificity of executive function and theory of mind performance in relation to attention-deficit/hyperactivity symptoms in autism spectrum disorders.

PubMed

Lukito, Steve; Jones, Catherine R G; Pickles, Andrew; Baird, Gillian; Happé, Francesca; Charman, Tony; Simonoff, Emily

2017-01-01

Individuals with autism spectrum disorder (ASD) frequently demonstrate symptoms of attention-deficit/hyperactivity disorder (ADHD). Previous findings in children with ASD have suggested that these symptoms are associated with an impairment in executive function (EF) abilities. However, studies rarely considered this association within a single framework that controls for other related factors such as Theory of Mind (ToM) abilities and ASD symptoms. We used structural equation modeling to explore the relations among EF, ToM, and symptoms of ASD and ADHD, using data from a population-based sample of 100 adolescents with ASD and full-scale IQ ≥ 50 (the Special Needs and Autism Project (SNAP) cohort). The study used a multi-measure and multi-informant approach, where performance of inhibition, planning, switching, and working memory tasks indexed EF and performance on tasks involving mentalizing indexed ToM. Measures of ASD and ADHD symptoms included parent and teacher reports and direct observation of the children. Shared source of symptom reporting was accounted for with a parental rating latent factor indexed by symptom measures reported by parents. Impairments in EF abilities were specifically associated with ADHD symptoms while impaired ToM was specifically associated with ASD symptoms, when accounting for the associations of each cognitive domain with the other factors. ASD and ADHD symptom latent factors were also correlated, but this association became nonsignificant once the shared source of reporting from parents was accounted for and within a model that also controlled for the correlated pathway between EF and ToM factors. The specific relations between the cognitive domains and behavioral symptoms remained even after controlling for IQ. In this ASD sample, symptoms of ADHD and ASD are underpinned by separate cognitive domains. The association between EF and ToM impairments is a likely partial explanation for the co-occurrence of ADHD symptoms in ASD, but the role of shared reporting effects is also important and supports the inclusion of independent informants and objective measures in future research.

Predictors and Prognostic Value of Worsening Renal Function During Admission in HFpEF Versus HFrEF: Data From the KorAHF (Korean Acute Heart Failure) Registry.

PubMed

Kang, Jeehoon; Park, Jin Joo; Cho, Young-Jin; Oh, Il-Young; Park, Hyun-Ah; Lee, Sang Eun; Kim, Min-Seok; Cho, Hyun-Jai; Lee, Hae-Young; Choi, Jin Oh; Hwang, Kyung-Kuk; Kim, Kye Hun; Yoo, Byung-Su; Kang, Seok-Min; Baek, Sang Hong; Jeon, Eun-Seok; Kim, Jae-Joong; Cho, Myeong-Chan; Chae, Shung Chull; Oh, Byung-Hee; Choi, Dong-Ju

2018-03-13

Worsening renal function (WRF) is associated with adverse outcomes in patients with heart failure. We investigated the predictors and prognostic value of WRF during admission, in patients with preserved ejection fraction (HFpEF) versus those with reduced ejection fraction (HFrEF). A total of 5625 patients were enrolled in the KorAHF (Korean Acute Heart Failure) registry. WRF was defined as an absolute increase in creatinine of ≥0.3 mg/dL. Transient WRF was defined as recovery of creatinine at discharge, whereas persistent WRF was indicated by a nonrecovered creatinine level. HFpEF and HFrEF were defined as a left ventricle ejection fraction ≥50% and ≤40%, respectively. Among the total population, WRF occurred in 3101 patients (55.1%). By heart failure subgroup, WRF occurred more frequently in HFrEF (57.0% versus 51.3%; P <0.001 in HFrEF and HFpEF). Prevalence of WRF increased as creatinine clearance decreased in both heart failure subgroups. Among various predictors of WRF, chronic renal failure was the strongest predictor. WRF was an independent predictor of adverse in-hospital outcomes (HFrEF: odds ratio; 2.75; 95% confidence interval, 1.50-5.02; P =0.001; HFpEF: odds ratio, 9.48; 95% confidence interval, 1.19-75.89; P =0.034) and 1-year mortality (HFrEF: hazard ratio, 1.41; 95% confidence interval, 1.12-1.78; P =0.004 versus HFpEF: hazard ratio, 1.72; 95% confidence interval, 1.23-2.42; P =0.002). Transient WRF was a risk factor for 1-year mortality, whereas persistent WRF had no additive risk compared to transient WRF. In patients with acute heart failure patients, WRF is an independent predictor of adverse in-hospital and follow-up outcomes in both HFrEF and HFpEF, though with a different effect size. URL: https://www.clinicaltrials.gov. Unique identifier: NCT01389843. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Revisiting Executive Function Measurement: Implications for Lifespan Development

ERIC Educational Resources Information Center

Wiebe, Sandra A.; McFall, G. Peggy

2014-01-01

Since Miyake and his colleagues (2000) published their seminal paper on the use of confirmatory factor analysis (CFA) to parse executive function (EF), CFA methods have become ubiquitous in EF research. In their interesting and thoughtful Focus article, "Executive Function: Formative Versus Reflective Measurement," Willoughby and…

How preschool executive functioning predicts several aspects of math achievement in Grades 1 and 3: A longitudinal study.

PubMed

Viterbori, Paola; Usai, M Carmen; Traverso, Laura; De Franchis, Valentina

2015-12-01

This longitudinal study analyzes whether selected components of executive function (EF) measured during the preschool period predict several indices of math achievement in primary school. Six EF measures were assessed in a sample of 5-year-old children (N = 175). The math achievement of the same children was then tested in Grades 1 and 3 using both a composite math score and three single indices of written calculation, arithmetical facts, and problem solving. Using previous results obtained from the same sample of children, a confirmatory factor analysis examining the latent EF structure in kindergarten indicated that a two-factor model provided the best fit for the data. In this model, inhibition and working memory (WM)-flexibility were separate dimensions. A full structural equation model was then used to test the hypothesis that math achievement (the composite math score and single math scores) in Grades 1 and 3 could be explained by the two EF components comprising the kindergarten model. The results indicate that the WM-flexibility component measured during the preschool period substantially predicts mathematical achievement, especially in Grade 3. The math composite scores were predicted by the WM-flexibility factor at both grade levels. In Grade 3, both problem solving and arithmetical facts were predicted by the WM-flexibility component. The results empirically support interventions that target EF as an important component of early childhood mathematics education. Copyright © 2015 Elsevier Inc. All rights reserved.

Emission factors for gaseous and particulate pollutants from offshore diesel engine vessels in China

NASA Astrophysics Data System (ADS)

Zhang, Fan; Chen, Yingjun; Tian, Chongguo; Lou, Diming; Li, Jun; Zhang, Gan; Matthias, Volker

2016-05-01

Shipping emissions have significant influence on atmospheric environment as well as human health, especially in coastal areas and the harbour districts. However, the contribution of shipping emissions on the environment in China still need to be clarified especially based on measurement data, with the large number ownership of vessels and the rapid developments of ports, international trade and shipbuilding industry. Pollutants in the gaseous phase (carbon monoxide, sulfur dioxide, nitrogen oxides, total volatile organic compounds) and particle phase (particulate matter, organic carbon, elemental carbon, sulfates, nitrate, ammonia, metals) in the exhaust from three different diesel-engine-powered offshore vessels in China (350, 600 and 1600 kW) were measured in this study. Concentrations, fuel-based and power-based emission factors for various operating modes as well as the impact of engine speed on emissions were determined. Observed concentrations and emission factors for carbon monoxide, nitrogen oxides, total volatile organic compounds, and particulate matter were higher for the low-engine-power vessel (HH) than for the two higher-engine-power vessels (XYH and DFH); for instance, HH had NOx EF (emission factor) of 25.8 g kWh-1 compared to 7.14 and 6.97 g kWh-1 of DFH, and XYH, and PM EF of 2.09 g kWh-1 compared to 0.14 and 0.04 g kWh-1 of DFH, and XYH. Average emission factors for all pollutants except sulfur dioxide in the low-engine-power engineering vessel (HH) were significantly higher than that of the previous studies (such as 30.2 g kg-1 fuel of CO EF compared to 2.17 to 19.5 g kg-1 fuel in previous studies, 115 g kg-1 fuel of NOx EF compared to 22.3 to 87 g kg-1 fuel in previous studies and 9.40 g kg-1 fuel of PM EF compared to 1.2 to 7.6 g kg-1 fuel in previous studies), while for the two higher-engine-power vessels (DFH and XYH), most of the average emission factors for pollutants were comparable to the results of the previous studies, engine type was one of the most important influence factors for the differences. Emission factors for all three vessels were significantly different during different operating modes. Organic carbon and elemental carbon were the main components of particulate matter, while water-soluble ions and elements were present in trace amounts. The test inland ships and some test offshore vessels in China always had higher EFs for CO, NOx, and PM than previous studies. Besides, due to the significant influence of engine type on shipping emissions and that no accurate local EFs could be used in inventory calculation, much more measurement data for different vessels in China are still in urgent need. Best-fit engine speeds during actual operation should be based on both emission factors and economic costs.

Riser Pattern Is a Novel Predictor of Adverse Events in Heart Failure Patients With Preserved Ejection Fraction.

PubMed

Komori, Takahiro; Eguchi, Kazuo; Saito, Toshinobu; Hoshide, Satoshi; Kario, Kazuomi

2017-01-25

The cardiovascular prognosis of heart failure with preserved ejection fraction (HFpEF) has been shown to be similar to that of heart failure with reduced ejection fraction (HFrEF). It is unknown which factors predict cardiovascular outcome in HFpEF. We tested the hypothesis that the abnormal pattern of circadian blood pressure (BP) rhythm known as the riser BP pattern is associated with adverse outcomes in HFpEF.Methods and Results:We performed a prospective, observational cohort study of hospitalized HF patients who underwent ambulatory BP monitoring (ABPM). Five hundred and sixteen hospitalized HF patients (age, 69±13 years; male, n=321 [62%]; female, n=195 [38%]) were followed up for a median 20.9 months. The composite outcome consisting of all-cause mortality and cardiovascular events was observed in 220 patients. On Kaplan-Meier analysis, the riser BP pattern subgroup had a significantly higher incidence of the composite outcome than the other subgroups of HFpEF patients (HR, 3.01; 95% CI: 1.54-6.08, P<0.01), but not the HFrEF patients. The riser BP pattern was found to be a novel predictor of cardiovascular outcome in HFpEF patients.

Formation of ethyl ferulate by rice koji enzyme in sake and mirin mash conditions.

PubMed

Hashizume, Katsumi; Ito, Toshihiko; Ishizuka, Takahiro; Takeda, Naoki

2013-08-01

Formation mechanism of ethyl ferulate (EF) in sake and mirin mash conditions was investigated to understand EF level control in the manufacturing process. Rice koji formed EF from ferulic acid (FA) and ethanol and decomposed EF to FA. This did not occur in sake yeast and chemical esterification was rare. Esterification of FA and hydrolysis of EF by rice koji might be due to feruloyl esterase(s). The rice koji enzyme showed normal Michaelis-Menten kinetics for FA in ethyl esterification and for EF in hydrolysis, but not for ethanol in the esterification reaction. Substrate specificity of the rice koji enzyme for hydroxycinnamic acids suggested that the main enzyme involved might be similar to type A feruloyl esterase. We studied the rice koji enzyme properties, short-term digestion of steamed rice grains with exogenous ethanol and small scale mirin making with pH adjustment. Our results suggested differences in the esterification and hydrolysis properties of the enzyme, in particular, different pH dependencies and different behaviors under high ethanol conditions; these factors might cause the differing EF levels in sake and mirin mashes. Copyright © 2013 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Paradoxical Roles of Elongation Factor-2 Kinase in Stem Cell Survival *

PubMed Central

Liao, Yi; Chu, Hsueh-Ping; Hu, Zhixian; Merkin, Jason J.; Chen, Jianmin; Liu, Zuguo; Degenhardt, Kurt; White, Eileen; Ryazanov, Alexey G.

2016-01-01

Protein synthesis inhibition is an immediate response during stress to switch the composition of protein pool in order to adapt to the new environment. It was reported that this response could be either protective or deleterious. However, how cells choose to live or die upon protein synthesis inhibition is largely unknown. Previously, we have shown that elongation factor-2 kinase (eEF2K), a protein kinase that suppresses protein synthesis during elongation phase, is a positive regulator of apoptosis both in vivo and in vitro. Consistently, here we report that knock-out of eEF2K protects mice from a lethal dose of whole-body ionizing radiation at 8 Gy by reducing apoptosis levels in both bone marrow and gastrointestinal tracts. Surprisingly, similar to the loss of p53, eEF2K deficiency results in more severe damage to the gastrointestinal tract at 20 Gy with the increased mitotic cell death in small intestinal stem cells. Furthermore, using epithelial cell lines, we showed that eEF2K is required for G2/M arrest induced by radiation to prevent mitotic catastrophe in a p53-independent manner. Specifically, we observed the elevation of Akt/ERK activity as well as the reduction of p21 expression in Eef2k−/− cells. Therefore, eEF2K also provides a protective strategy to maintain genomic integrity by arresting cell cycle in response to stress. Our results suggest that protective versus pro-apoptotic roles of eEF2K depend on the type of cells: eEF2K is protective in highly proliferative cells, such as small intestinal stem cells and cancer cells, which are more susceptible to mitotic catastrophe. PMID:27466362

An Improved Approach to Estimate Methane Emissions from Coal Mining in China.

PubMed

Zhu, Tao; Bian, Wenjing; Zhang, Shuqing; Di, Pingkuan; Nie, Baisheng

2017-11-07

China, the largest coal producer in the world, is responsible for over 50% of the total global methane (CH 4 ) emissions from coal mining. However, the current emission inventory of CH4 from coal mining has large uncertainties because of the lack of localized emission factors (EFs). In this study, province-level CH4 EFs from coal mining in China were developed based on the data analysis of coal production and corresponding discharged CH4 emissions from 787 coal mines distributed in 25 provinces with different geological and operation conditions. Results show that the spatial distribution of CH 4 EFs is highly variable with values as high as 36 m3/t and as low as 0.74 m3/t. Based on newly developed CH 4 EFs and activity data, an inventory of the province-level CH4 emissions was built for 2005-2010. Results reveal that the total CH 4 emissions in China increased from 11.5 Tg in 2005 to 16.0 Tg in 2010. By constructing a gray forecasting model for CH 4 EFs and a regression model for activity, the province-level CH 4 emissions from coal mining in China are forecasted for the years of 2011-2020. The estimates are compared with other published inventories. Our results have a reasonable agreement with USEPA's inventory and are lower by a factor of 1-2 than those estimated using the IPCC default EFs. This study could help guide CH 4 mitigation policies and practices in China.

Correction of murine hemophilia A following nonmyeloablative transplantation of hematopoietic stem cells engineered to encode an enhanced human factor VIII variant using a safety-augmented retroviral vector

PubMed Central

Ramezani, Ali

2009-01-01

Insertional mutagenesis by retroviral vectors is a major impediment to the clinical application of hematopoietic stem cell gene transfer for the treatment of hematologic disorders. We recently developed an insulated self-inactivating gammaretroviral vector, RMSinOFB, which uses a novel enhancer-blocking element that significantly decreases genotoxicity of retroviral integration. In this study, we used the RMSinOFB vector to evaluate the efficacy of a newly bioengineered factor VIII (fVIII) variant (efVIII)—containing a combination of A1 domain point mutations (L303E/F309S) and an extended partial B domain for improved secretion plus A2 domain mutations (R484A/R489A/P492A) for reduced immunogenicity—toward successful treatment of murine hemophilia A. In cell lines, efVIII was secreted at up to 6-fold higher levels than an L303E/F309S A1 domain–only fVIII variant (sfVIIIΔB). Most important, when compared with a conventional gammaretroviral vector expressing sfVIIIΔB, lower doses of RMSin-efVIII-OFB–transduced hematopoietic stem cells were needed to generate comparable curative fVIII levels in hemophilia A BALB/c mice after reduced-intensity total body irradiation or nonmyeloablative chemotherapy conditioning regimens. These data suggest that the safety-augmented RMSin-efVIII-OFB platform represents an encouraging step in the development of a clinically appropriate gene addition therapy for hemophilia A. PMID:19470695

Endogenous ADP-ribosylation of elongation factor 2 in polyoma virus-transformed baby hamster kidney cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fendrick, J.L.; Iglewski, W.J.

1989-01-01

Polyoma virus-transformed baby hamster kidney (pyBHK) cells were cultured in medium containing ({sup 32}P)orthophosphate and 105 (vol/vol) fetal bovine serum. A {sup 32}P-labeled protein with an apparent molecular mass of 97 kDa was immunoprecipitated from cell lysates with antiserum to ADP-ribosylated elongation factor 2 (EF-2). The {sup 32}P labeling of the protein was enhanced by culturing cells in medium containing 2% serum instead of 10% serum. The {sup 32}P label was completely removed from the protein by treatment with snake venom phosphodiesterase and the digestion product was identified as ({sup 32}P)AMP, indicating the protein was mono-ADP-ribosylated. HPLC analysis of trypticmore » peptides of the {sup 32}P-labeled 97-kDa protein and purified EF-2, which was ADP-ribosylated in vitro with diphtheria toxin fragment A and ({sup 32}P)NAD, demonstrated an identical labeled peptide in the two proteins. The data strongly suggest that EF-2 was endogenously ADP-ribosylated in pyBHK cells. Maximum incorporation of radioactivity in EF-2 occurred by 12 hr and remained constant over the subsequent 12 hr. It was estimated that 30-35% of the EF-2 was ADP-ribosylated in cells cultured in medium containing 2% serum. When {sup 32}P-labeled cultures were incubated in medium containing unlabeled phosphate, the {sup 32}P label was lost from the EF-2 within 30 min.« less

Consecutive interactions with HSP90 and eEF1A underlie a functional maturation and storage pathway of AID in the cytoplasm

PubMed Central

Methot, Stephen P.; Litzler, Ludivine C.; Trajtenberg, Felipe; Zahn, Astrid; Robert, Francis; Pelletier, Jerry; Buschiazzo, Alejandro; Magor, Brad G.

2015-01-01

Activation-induced deaminase (AID) initiates mutagenic pathways to diversify the antibody genes during immune responses. The access of AID to the nucleus is limited by CRM1-mediated nuclear export and by an uncharacterized mechanism of cytoplasmic retention. Here, we define a conformational motif in AID that dictates its cytoplasmic retention and demonstrate that the translation elongation factor eukaryotic elongation factor 1 α (eEF1A) is necessary for AID cytoplasmic sequestering. The mechanism is independent of protein synthesis but dependent on a tRNA-free form of eEF1A. Inhibiting eEF1A prevents the interaction with AID, which accumulates in the nucleus and increases class switch recombination as well as chromosomal translocation byproducts. Most AID is associated to unspecified cytoplasmic complexes. We find that the interactions of AID with eEF1A and heat-shock protein 90 kD (HSP90) are inversely correlated. Despite both interactions stabilizing AID, the nature of the AID fractions associated with HSP90 or eEF1A are different, defining two complexes that sequentially produce and store functional AID in the cytoplasm. In addition, nuclear export and cytoplasmic retention cooperate to exclude AID from the nucleus but might not be functionally equivalent. Our results elucidate the molecular basis of AID cytoplasmic retention, define its functional relevance and distinguish it from other mechanisms regulating AID. PMID:25824822

The C-terminal helix of ribosomal P stalk recognizes a hydrophobic groove of elongation factor 2 in a novel fashion.

PubMed

Tanzawa, Takehito; Kato, Koji; Girodat, Dylan; Ose, Toyoyuki; Kumakura, Yuki; Wieden, Hans-Joachim; Uchiumi, Toshio; Tanaka, Isao; Yao, Min

2018-04-06

Archaea and eukaryotes have ribosomal P stalks composed of anchor protein P0 and aP1 homodimers (archaea) or P1•P2 heterodimers (eukaryotes). These P stalks recruit translational GTPases to the GTPase-associated center in ribosomes to provide energy during translation. The C-terminus of the P stalk is known to selectively recognize GTPases. Here we investigated the interaction between the P stalk and elongation factor 2 by determining the structures of Pyrococcus horikoshii EF-2 (PhoEF-2) in the Apo-form, GDP-form, GMPPCP-form (GTP-form), and GMPPCP-form bound with 11 C-terminal residues of P1 (P1C11). Helical structured P1C11 binds to a hydrophobic groove between domain G and subdomain G' of PhoEF-2, where is completely different from that of aEF-1α in terms of both position and sequence, implying that such interaction characteristic may be requested by how GTPases perform their functions on the ribosome. Combining PhoEF-2 P1-binding assays with a structural comparison of current PhoEF-2 structures and molecular dynamics model of a P1C11-bound GDP form, the conformational changes of the P1C11-binding groove in each form suggest that in response to the translation process, the groove has three states: closed, open, and release for recruiting and releasing GTPases.

The Use of Canonical Correlation Analysis to Assess the Relationship Between Executive Functioning and Verbal Memory in Older Adults

PubMed Central

Moreira, Pedro Silva; Santos, Nadine Correia; Sousa, Nuno

2015-01-01

Executive functioning (EF), which is considered to govern complex cognition, and verbal memory (VM) are constructs assumed to be related. However, it is not known the magnitude of the association between EF and VM, and how sociodemographic and psychological factors may affect this relationship, including in normal aging. In this study, we assessed different EF and VM parameters, via a battery of neurocognitive/psychological tests, and performed a Canonical Correlation Analysis (CCA) to explore the connection between these constructs, in a sample of middle-aged and older healthy individuals without cognitive impairment (N = 563, 50+ years of age). The analysis revealed a positive and moderate association between EF and VM independently of gender, age, education, global cognitive performance level, and mood. These results confirm that EF presents a significant association with VM performance. PMID:28138465

Family matters: Intergenerational and interpersonal processes of executive function and attentive behavior

PubMed Central

Deater-Deckard, Kirby

2014-01-01

Individual differences in self-regulation include executive function (EF) components that serve self-regulation of attentive behavior by modulating reactive responses to the environment. These factors “run in families”. The purpose of this review is to summarize a program of research that addresses familial inter-generational transmission and inter-personal processes in development. Self-regulation of attentive behavior involves inter-related aspects of executive function (EF) including attention, inhibitory control, and working memory. Individual differences in EF skills develop in systematic ways over childhood, resulting in moderately stable differences between people by early adolescence. Through complex gene-environment transactions, EF is transmitted across generations within parent-child relationships that provide powerful socialization and experiential contexts in which EF and related attentive behavior are forged and practiced. Families matter as parents regulate home environments and themselves as best they can while also supporting cognitive self-regulation of attentive behavior in their children. PMID:25197171

Eukaryotic elongation factor 2 is a prognostic marker and its kinase a potential therapeutic target in HCC

PubMed Central

Pott, Leona L; Hagemann, Sascha; Reis, Henning; Lorenz, Kristina; Bracht, Thilo; Herold, Thomas; Skryabin, Boris V; Megger, Dominik A; Kälsch, Julia; Weber, Frank; Sitek, Barbara; Baba, Hideo A

2017-01-01

Hepatocellular carcinoma is a cancer with increasing incidence and largely refractory to current anticancer drugs. Since Sorafenib, a multikinase inhibitor has shown modest efficacy in advanced hepatocellular carcinoma additional treatments are highly needed. Protein phosphorylation via kinases is an important post-translational modification to regulate cell homeostasis including proliferation and apoptosis. Therefore kinases are valuable targets in cancer therapy. To this end we performed 2D differential gel electrophoresis and mass spectrometry analysis of phosphoprotein-enriched lysates of tumor and corresponding non-tumorous liver samples to detect differentially abundant phosphoproteins to screen for novel kinases as potential drug targets. We identified 34 differentially abundant proteins in phosphoprotein enriched lysates. Expression and distribution of the candidate protein eEF2 and its phosphorylated isoform was validated immunohistochemically on 78 hepatocellular carcinoma and non-tumorous tissue samples. Validation showed that total eEF2 and phosphorylated eEF2 at threonine 56 are prognostic markers for overall survival of HCC-patients. The activity of the regulating eEF2 kinase, compared between tumor and non-tumorous tissue lysates by in vitro kinase assays, is more than four times higher in tumor tissues. Functional analyzes regarding eEF2 kinase were performed in JHH5 cells with CRISPR/Cas9 mediated eEF2 kinase knock out. Proliferation and growth is decreased in eEF2 kinase knock out cells. Conclusion eEF2 and phosphorylated eEF2 are prognostic markers for survival of hepatocellular carcinoma patients and the regulating eEF2 kinase is a potential drug target for tumor therapy. PMID:28060762

Eukaryotic elongation factor 2 is a prognostic marker and its kinase a potential therapeutic target in HCC.

PubMed

Pott, Leona L; Hagemann, Sascha; Reis, Henning; Lorenz, Kristina; Bracht, Thilo; Herold, Thomas; Skryabin, Boris V; Megger, Dominik A; Kälsch, Julia; Weber, Frank; Sitek, Barbara; Baba, Hideo A

2017-02-14

Hepatocellular carcinoma is a cancer with increasing incidence and largely refractory to current anticancer drugs. Since Sorafenib, a multikinase inhibitor has shown modest efficacy in advanced hepatocellular carcinoma additional treatments are highly needed. Protein phosphorylation via kinases is an important post-translational modification to regulate cell homeostasis including proliferation and apoptosis. Therefore kinases are valuable targets in cancer therapy. To this end we performed 2D differential gel electrophoresis and mass spectrometry analysis of phosphoprotein-enriched lysates of tumor and corresponding non-tumorous liver samples to detect differentially abundant phosphoproteins to screen for novel kinases as potential drug targets. We identified 34 differentially abundant proteins in phosphoprotein enriched lysates. Expression and distribution of the candidate protein eEF2 and its phosphorylated isoform was validated immunohistochemically on 78 hepatocellular carcinoma and non-tumorous tissue samples. Validation showed that total eEF2 and phosphorylated eEF2 at threonine 56 are prognostic markers for overall survival of HCC-patients. The activity of the regulating eEF2 kinase, compared between tumor and non-tumorous tissue lysates by in vitro kinase assays, is more than four times higher in tumor tissues. Functional analyzes regarding eEF2 kinase were performed in JHH5 cells with CRISPR/Cas9 mediated eEF2 kinase knock out. Proliferation and growth is decreased in eEF2 kinase knock out cells. eEF2 and phosphorylated eEF2 are prognostic markers for survival of hepatocellular carcinoma patients and the regulating eEF2 kinase is a potential drug target for tumor therapy.

Subclinical atherosclerosis and hyperandrogenemia are independent risk factors for increased epicardial fat thickness in patients with PCOS and idiopathic hirsutism.

PubMed

Cakir, Evrim; Doğan, Mehmet; Topaloglu, Oya; Ozbek, Mustafa; Cakal, Erman; Vural, Mustafa Gokhan; Yeter, Ekrem; Delibasi, Tuncay

2013-01-01

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders affecting reproductive-age women and is reported to be associated with an increased risk of cardiovascular disease and early atherosclerosis. Epicardial fat thickness (EF) is clinically related to subclinical atherosclerosis and visceral fat changes. Therefore, the objective of this study is to compare the carotid artery intima-media thickness (CIMT), EF and cardiometabolic risk factors in patients with PCOS, patients with idiopathic hirsutism (IH) and healthy controls. This cross-sectional controlled study was conducted in a training and research hospital. The study population consisted of 50 reproductive-age PCOS women, 34 women with IH and 39 control subjects. We evaluated anthropometric, hormonal and metabolic parameters as well as CIMT and EF measurements in PCOS patients, IH patients and controls. The mean fasting insulin, HOMA-IR, hsCRP, GGT, CIMT, and EF levels were significantly higher in patients with PCOS and IH (p < 0.05). A significant positive correlation was found between EF and age, BMI, WHR, Ferriman Gallwey score (FG), fasting insulin, HOMA-IR, triglyceride, total cholesterol, LDL-C, 17 OH progesterone, free testosterone, CIMT, hsCRP, and GGT, whereas a significant negative correlation was observed between EF and HDL-C (p < 0.05). In the multiple linear regression analyses, EF was found to be associated with the FG (β coefficient: 0.389, p < 0.001), CIMT (β coefficient: 0.376, p < 0.001) and free testosterone levels (β coefficient: 0.173, p < 0.038). EF appears to be a marker that will enable the detection of the cardiometabolic response in patients with PCOS and IH, even at an early stage. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Corneal edema after phacoemulsification

PubMed Central

Sharma, Namrata; Singhal, Deepali; Nair, Sreelakshmi P; Sahay, Pranita; Sreeshankar, SS; Maharana, Prafulla Kumar

2017-01-01

Phacoemulsification is the most commonly performed cataract surgery in this era. With all the recent advances in investigations and management of cataract through phacoemulsification, most of the patients are able to achieve excellent visual outcome. Corneal edema after phacoemulsification in the immediate postoperative period often leads to patient dissatisfaction and worsening of outcome. Delayed onset corneal edema often warrants endothelial keratoplasty. This review highlights the etiopathogenesis, risk factors, and management of corneal edema in the acute phase including descemet's membrane detachment (DMD) and toxic anterior segment syndrome. Various investigative modalities such as pachymetry, specular microscopy, anterior segment optical coherence tomography, and confocal microscopy have been discussed briefly. PMID:29208818

Remitting seronegative symmetrical synovitis with pitting edema (RS3PE syndrome).

PubMed

Hung, S C; Kung, Y Y; Lin, H Y

1999-07-01

A 63-year-old man presented with acute symmetrical polysynovitis associated with pitting edema of both the hands and feet. He was seronegative for rheumatoid factor and no radiologically evident erosion was noted in the joints of his hands and feet. Evaluation excluded congestive heart failure, nephrotic syndrome, and hypothyroidism as the cause of edema. Treatment with nonsteroidal anti-inflammatory drugs and low-dose steroids induced complete remission. The clinical manifestations of this patients were consistent with those of a distinctive, although rare, form of arthritis called remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome. This syndrome has a good prognosis in elderly patients.

Emission factors of atmospheric and climatic pollutants from crop residues burning.

PubMed

Santiago-De La Rosa, Naxieli; González-Cardoso, Griselda; Figueroa-Lara, José de Jesús; Gutiérrez-Arzaluz, Mirella; Octaviano-Villasana, Claudia; Ramírez-Hernández, Irma Fabiola; Mugica-Álvarez, Violeta

2018-04-13

Biomass burning is a common agricultural practice, because it allows elimination of postharvesting residues; nevertheless, it involves an inefficient combustion process that generates atmospheric pollutants emission, which has implications on health and climate change. This work focuses on the estimation of emission factors (EFs) of PM 2.5 , PM 10 , organic carbon (OC), elemental carbon (EC), carbon monoxide (CO), carbon dioxide (CO 2 ), and methane (CH 4 ) of residues from burning alfalfa, barley, beans, cotton, maize, rice, sorghum, and wheat in Mexico. Chemical characteristics of the residues were determined to establish their relationship with EFs, as well as with the modified combustion efficiency (MCE). Essays were carried out in an open combustion chamber with isokinetic sampling, following modified EPA 201-A method. EFs did not present statistical differences among different varieties of the same crop, but were statistically different among different crops, showing that generic values of EFs for all the agricultural residues can introduce significant uncertainties when used for climatic and atmospheric pollutant inventories. EFs of PM 2.5 ranged from 1.19 to 11.30 g kg -1 , and of PM 10 from 1.77 to 21.56 g kg -1 . EFs of EC correlated with lignin content, whereas EFs of OC correlated inversely with carbon content. EFs of EC and OC in PM 2.5 ranged from 0.15 to 0.41 g kg -1 and from 0.33 to 5.29 g kg -1 , respectively, and in PM 10 , from 0.17 to 0.43 g kg -1 and from 0.54 to 11.06 g kg -1 . CO 2 represented the largest gaseous emissions volume with 1053.35-1850.82 g kg -1 , whereas the lowest was CH 4 with 1.61-5.59 g kg -1 . CO ranged from 28.85 to 155.71 g kg -1 , correlating inversely with carbon content and MCE. EFs were used to calculate emissions from eight agricultural residues burning in the country during 2016, to know the potential mitigation of climatic and atmospheric pollutants, provided this practice was banned. The emission factors of particles, short-lived climatic pollutants, and atmospheric pollutants from the crop residues burning of eight agricultural wastes crops, determined in this study using a standardized method, provides better knowledge of the emissions of those species in Latin America and other developing countries, and can be used as inputs in air quality models and climatic studies. The EFs will allow the development of more accurate inventories of aerosols and gaseous pollutants, which will lead to the design of effective mitigation strategies and planning processes for sustainable agriculture.

Global time trends in PAH emissions from motor vehicles

NASA Astrophysics Data System (ADS)

Shen, Huizhong; Tao, Shu; Wang, Rong; Wang, Bin; Shen, Guofeng; Li, Wei; Su, Shenshen; Huang, Ye; Wang, Xilong; Liu, Wenxin; Li, Bengang; Sun, Kang

2011-04-01

Emission from motor vehicles is the most important source of polycyclic aromatic hydrocarbons (PAHs) in urban areas. Emission factors of individual PAHs for motor vehicles reported in the literature varied 4 to 5 orders of magnitude, leading to high uncertainty in emission inventory. In this study, key factors affecting emission factors of PAHs (EF PAH) for motor vehicles were evaluated quantitatively based on thousands of EF PAH measured in 16 countries for over 50 years. The result was used to develop a global emission inventory of PAHs from motor vehicles. It was found that country and vehicle model year are the most important factors affecting EF PAH, which can be quantified using a monovariate regression model with per capita gross domestic production (purchasing power parity) as a sole independent variable. On average, 29% of variation in log-transformed EF PAH could be explained by the model, which was equivalent to 90% reduction in overall uncertainty on arithmetic scale. The model was used to predict EF PAH and subsequently PAH emissions from motor vehicles for various countries in the world during a period from 1971 to 2030. It was estimated that the global emission reached its peak value of approximate 101 Gg in 1978 and decreased afterwards due to emission control in developed countries. The annual emission picked up again since 1990 owing to accelerated energy consumption in China and other developing countries. With more and more rigid control measures taken in the developing world, global emission of PAHs is currently passing its second peak. It was predicted that the emission would decrease from 77 Gg in 2010 to 42 Gg in 2030.

The test-retest reliability of the latent construct of executive function depends on whether tasks are represented as formative or reflective indicators.

PubMed

Willoughby, Michael T; Kuhn, Laura J; Blair, Clancy B; Samek, Anya; List, John A

2017-10-01

This study investigates the test-retest reliability of a battery of executive function (EF) tasks with a specific interest in testing whether the method that is used to create a battery-wide score would result in differences in the apparent test-retest reliability of children's performance. A total of 188 4-year-olds completed a battery of computerized EF tasks twice across a period of approximately two weeks. Two different approaches were used to create a score that indexed children's overall performance on the battery-i.e., (1) the mean score of all completed tasks and (2) a factor score estimate which used confirmatory factor analysis (CFA). Pearson and intra-class correlations were used to investigate the test-retest reliability of individual EF tasks, as well as an overall battery score. Consistent with previous studies, the test-retest reliability of individual tasks was modest (rs ≈ .60). The test-retest reliability of the overall battery scores differed depending on the scoring approach (r mean  = .72; r factor_ score  = .99). It is concluded that the children's performance on individual EF tasks exhibit modest levels of test-retest reliability. This underscores the importance of administering multiple tasks and aggregating performance across these tasks in order to improve precision of measurement. However, the specific strategy that is used has a large impact on the apparent test-retest reliability of the overall score. These results replicate our earlier findings and provide additional cautionary evidence against the routine use of factor analytic approaches for representing individual performance across a battery of EF tasks.

Cognition in Huntington's disease in manifest, premanifest and converting gene carriers over ten years.

PubMed

Hart, Ellen P; Dumas, Eve M; Giltay, Erik J; Middelkoop, Huub A M; Roos, Raymund A C

2013-01-01

Cognitive decline in Huntington's disease (HD) remains an area of inconsistencies, especially far from disease onset. To clarify the course of cognition in premanifest HD. Twenty-six premanifest HD, 19 manifest HD, and 87 control subjects were followed for ten years, using an extensive cognitive battery. Differences in baseline levels and change over time, on four factors (motor speed, global cognition, executive functioning (EF), and memory) were examined, using multilevel regression analyses. Converters were additionally analysed as a separate group. Also, the influence of motor speed and predicted years to disease onset on the cognitive factors was studied. Manifest HD subjects showed lower baseline scores compared to controls on the motor speed (p=0.002), memory (p<0.001) and EF (p<0.001). They additionally deteriorated over the ten-year follow-up on memory (p=0.01). Converters deteriorated on EF (p=0.04). Further analyses of premanifest subjects 'far from and close to predicted onset' revealed lower baseline scores for the 'close' group on EF, as compared to controls (p=0.001). They also deteriorated on memory (p=0.01). Motor speed substantially mediated the results of the three cognitive factors; when added as covariate to the model several baseline and slope differences for the cognitive factors ceased to be significant. Memory and EF are highly sensitive for ascertaining deterioration in premanifest HD gene carriers, especially in subjects close to onset. Lack of deterioration for the subjects further away from onset suggests that both domains are largely unaffected in those far from onset. Also, motor influence on cognition is substantial and should be taken into account in cognitive HD research.

[Macular Edema in Uveitis - Steroids or VEGF Inhibitors?

PubMed

Heinz, Carsten; Heiligenhaus, Arnd

2017-06-09

Macular edema in uveitis patients is certainly the most frequent complication leading to a permanent and irreversible reduction in vision during the course of the disease. Thanks to optical coherence tomography (OCT) technology and fluorescein angiography (FAG), significantly more macular edemas are detected. Macular edema can be found in various uveitis varieties and can show different clinical patterns. All macular edema should be treated. Macular edema with active inflammation usually reacts very well to general uveitis treatment. In the case of eyes without visible inflammation, however, the response to such therapy is usually less effective. According to the latest treatment recommendations, dexamethasone implants should be used as the first intravitreal therapy. Vascular endothelial growth factor inhibitors (VEGF inhibitors) are second-line treatment regimens. The choice of therapy is, therefore, primarily based on the degree of inflammation and the individual complications, such as glaucoma, lens situation or previous increase in IOP after steroid administration. These individual complications may allow using VEGF inhibitors as first line treatment. An improvement in the macular edema can be achieved with both groups of active substances. Georg Thieme Verlag KG Stuttgart · New York.

Apatinib in refractory radiation-induced brain edema

PubMed Central

Hu, Wei Guo; Weng, Yi Ming; Dong, Yi; Li, Xiang Pan; Song, Qi-Bin

2017-01-01

Abstract Rationale: Apatinib is a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor-2, which has observed to be effective and safe in refractory radiation-induced brain edema, like Avastin did. Till now, there is no case report after apatinib came in the market. Patient concerns: Two patients who received brain radiotherapy developed clinical manifestations of brain edema, including dizziness, headache, limb activity disorder, and so on. Diagnoses: Two patients were both diagnosed as refractory radiation-induced brain edema. Interventions: Two patients received apatinib (500 mg/day) for 2 and 4 weeks. Outcomes: Two patients got symptomatic improvements from apatinib in different degrees. Magnetic resonance imaging after apatinib treatments showed that compared with pre-treatment imaging, the perilesional edema reduced dramatically. However, the toxicity of apatinib was controllable and tolerable. Lessons: Apatinib can obviously relieve the symptoms of refractory radiation-induced brain edema and improve the quality of life, which offers a new method for refractory radiation-induced brain edema in clinical practices. But that still warrants further investigation in the prospective study. PMID:29145238

Modeling nitrous oxide emission from rivers: a global assessment.

PubMed

Hu, Minpeng; Chen, Dingjiang; Dahlgren, Randy A

2016-11-01

Estimates of global riverine nitrous oxide (N 2 O) emissions contain great uncertainty. We conducted a meta-analysis incorporating 169 observations from published literature to estimate global riverine N 2 O emission rates and emission factors. Riverine N 2 O flux was significantly correlated with NH 4 , NO 3 and DIN (NH 4  + NO 3 ) concentrations, loads and yields. The emission factors EF(a) (i.e., the ratio of N 2 O emission rate and DIN load) and EF(b) (i.e., the ratio of N 2 O and DIN concentrations) values were comparable and showed negative correlations with nitrogen concentration, load and yield and water discharge, but positive correlations with the dissolved organic carbon : DIN ratio. After individually evaluating 82 potential regression models based on EF(a) or EF(b) for global, temperate zone and subtropical zone datasets, a power function of DIN yield multiplied by watershed area was determined to provide the best fit between modeled and observed riverine N 2 O emission rates (EF(a): R 2  = 0.92 for both global and climatic zone models, n = 70; EF(b): R 2  = 0.91 for global model and R 2  = 0.90 for climatic zone models, n = 70). Using recent estimates of DIN loads for 6400 rivers, models estimated global riverine N 2 O emission rates of 29.6-35.3 (mean = 32.2) Gg N 2 O-N yr -1 and emission factors of 0.16-0.19% (mean = 0.17%). Global riverine N 2 O emission rates are forecasted to increase by 35%, 25%, 18% and 3% in 2050 compared to the 2000s under the Millennium Ecosystem Assessment's Global Orchestration, Order from Strength, Technogarden, and Adapting Mosaic scenarios, respectively. Previous studies may overestimate global riverine N 2 O emission rates (300-2100 Gg N 2 O-N yr -1 ) because they ignore declining emission factor values with increasing nitrogen levels and channel size, as well as neglect differences in emission factors corresponding to different nitrogen forms. Riverine N 2 O emission estimates will be further enhanced through refining emission factor estimates, extending measurements longitudinally along entire river networks and improving estimates of global riverine nitrogen loads. © 2016 John Wiley & Sons Ltd.

Heart Failure with Preserved Ejection Fraction - Concept, Pathophysiology, Diagnosis and Challenges for Treatment.

PubMed

Miljkovik, Lidija Veterovska; Spiroska, Vera

2015-09-15

Heart failure (HF) with preserved left ventricular (LV) ejection fraction (HFpEF) occurs in 40 to 60% of the patients with HF, with a prognosis which is similar to HF with reduced ejection fraction (HFrEF). HFpEF pathophysiology is different from that of HFrEF, and has been characterized with diastolic dysfunction. Diastolic dysfunction has been defined with elevated left ventricular stiffness, prolonged iso-volumetric LV relaxation, slow LV filing and elevated LV end-diastolic pressure. Arterial hypertension occurs in majority cases with HFpEF worldwide. Patients are mostly older and obese. Diabetes mellitus and atrial fibrillation appear proportionally in a high frequency of patients with HFpEF. The HFpEF diagnosis is based on existence of symptoms and signs of heart failure, normal or approximately normal ejection and diagnosing of LV diastolic dysfunction by means of heart catheterization or Doppler echocardiography and/or elevated concentration of plasma natriuretic peptide. The present recommendations for HFpEF treatment include blood pressure control, heart chamber frequency control when atrial fibrillation exists, in some situations even coronary revascularization and an attempt for sinus rhythm reestablishment. Up to now, it is considered that no medication or a group of medications improve the survival of HFpEF patients. Due to these causes and the bad prognosis of the disorder, rigorous control is recommended of the previously mentioned precipitating factors for this disorder. This paper presents a universal review of the most important parameters which determine this disorder.

Potentiation of Schaffer-Collateral CA1 Synaptic Transmission by eEF2K and p38 MAPK Mediated Mechanisms.

PubMed

Weng, Weiguang; Chen, Ying; Wang, Man; Zhuang, Yinghan; Behnisch, Thomas

2016-01-01

The elongation factor 2 kinase (eEF2K), likewise known as CaMKIII, has been demonstrated to be involved in antidepressant responses of NMDA receptor antagonists. Even so, it remains open whether direct inhibition of eEF2K without altering up-stream or other signaling pathways affects hippocampal synaptic transmission and neuronal network synchrony. Inhibition of eEF2K by the selective and potent eEF2K inhibitor A-484954 induced a fast pre-synaptically mediated enhancement of synaptic transmission and synchronization of neural network activity. The eEF2K-inhibition mediated potentiation of synaptic transmission of hippocampal CA1 neurons is most notably independent of protein synthesis and does not rely on protein kinase C, protein kinase A or mitogen-activated protein kinase (MAPK)/extracellular signal-regulated protein kinase 1/2. Moreover, the strengthening of synaptic transmission in the response to the inhibition of eEF2K was strongly attenuated by the inhibition of p38 MAPK. In addition, we show the involvement of barium-sensitive and more specific the TWIK-related potassium-1 (TREK-1) channels in the eEF2K-inhibition mediated potentiation of synaptic transmission. These findings reveal a novel pathway of eEF2K mediated regulation of hippocampal synaptic transmission. Further research is required to study whether such compounds could be beneficial for the development of mood disorder treatments with a fast-acting antidepressant response.

eEF1A Controls ascospore differentiation through elevated accuracy, but controls longevity and fruiting body formation through another mechanism in Podospora anserina.

PubMed Central

Silar, P; Lalucque, H; Haedens, V; Zickler, D; Picard, M

2001-01-01

Antisuppressor mutations in the eEF1A gene of Podospora anserina were previously shown to impair ascospore formation, to drastically increase life span, and to permit the development of the Crippled Growth degenerative process. Here, we show that eEF1A controls ascospore formation through accuracy level maintenance. Examination of antisuppressor mutant perithecia reveals two main cytological defects, mislocalization of spindle and nuclei and nuclear death. Antisuppression levels are shown to be highly dependent upon both the mutation site and the suppressor used, precluding any correlation between antisuppression efficiency and severity of the sporulation impairment. Nevertheless, severity of ascospore differentiation defect is correlated with resistance to paromomycin. We also show that eEF1A controls fruiting body formation and longevity through a mechanism(s) different from accuracy control. In vivo, GFP tagging of the protein in a way that partly retains its function confirmed earlier cytological observation; i.e., this factor is mainly diffuse within the cytosol, but may transiently accumulate within nuclei or in defined regions of the cytoplasm. These data emphasize the fact that the translation apparatus exerts a global regulatory control over cell physiology and that eEF1A is one of the key factors involved in this monitoring. PMID:11514440

Expression of the mucus adhesion genes Mub and MapA, adhesion-like factor EF-Tu and bacteriocin gene plaA of Lactobacillus plantarum 423, monitored with real-time PCR.

PubMed

Ramiah, K; van Reenen, C A; Dicks, L M T

2007-05-30

Expression of the mucus adhesion genes Mub and MapA, adhesion-like factor EF-Tu and bacteriocin gene plaA by Lactobacillus plantarum 423, grown in the presence of bile, pancreatin and at low pH, was studied by real-time PCR. Mub, MapA and EF-Tu were up-regulated in the presence of mucus, proportional to increasing concentrations. Expression of MapA was up-regulated in the presence of 3.0 g/l bile and 3.0 g/l pancreatin at pH 6.5. Similar results were recorded in the presence of 10.0 g/l bile and 10.0 g/l pancreatin at pH 6.5. Expression of Mub was down-regulated in the presence of bile and pancreatin, whilst the expression of EF-Tu and plaA remained unchanged. Expression of Mub and MapA remained unchanged at pH 4.0, whilst expression of EF-Tu and plaA were up-regulated. Expression of MapA was down-regulated in the presence of 1.0 g/l l-cysteine HCl, suggesting that the gene is regulated by transcription attenuation that involves cysteine.

Global emission of black carbon from motor vehicles from 1960 to 2006.

PubMed

Wang, Rong; Tao, Shu; Shen, Huizhong; Wang, Xilong; Li, Bengang; Shen, Guofeng; Wang, Bin; Li, Wei; Liu, Xiaopeng; Huang, Ye; Zhang, Yanyan; Lu, Yan; Ouyang, Huiling

2012-01-17

Black carbon (BC) is a key short-lived climate change forcer. Motor vehicles are important sources of BC in the environment. BC emission factors (EF(BC)), defined as BC emitted per mass of fuel consumed, are critical in the development of BC emission inventories for motor vehicles. However, measured EF(BC) for motor vehicles vary in orders of magnitude, which is one of the major sources of uncertainty in the estimation of emissions. In this study, the main factors affecting EF(BC) for motor vehicles were investigated based on 385 measured EF(BC) collected from the literature. It was found that EF(BC) for motor vehicles of a given year in a particular country can be predicted using gross domestic product per capita (GDP(c)), temperature, and the year a country's GDP(c) reached 3000 USD (Y(3000)). GDP(c) represents technical progress in terms of emission control, while Y(3000) suggest the technical transfer from developed to developing countries. For global BC emission calculations, 87 and 64% of the variation can be eliminated for diesel and gasoline vehicles by using this model. In addition to a reduction in uncertainty, the model can be used to develop a global on-road vehicle BC emission inventory with spatial and temporal resolution.

The phylogenetic position of an Armillaria species from Amami-Oshima, a subtropical island of Japan, based on elongation factor and ITS sequences

Treesearch

Yuko Ota; Mee-Sook Kim; Hitoshi Neda; Ned B. Klopfenstein; Eri Hasegawa

2011-01-01

An undetermined Armillaria species was collected on Amami-Oshima, a subtropical island of Japan. The phylogenetic position of the Armillaria sp. was determined using sequences of the elongation factor-1a (EF-1a) gene and the internal transcribed spacer (ITS) region (ITS1-5.8S-ITS2) of ribosomal DNA (rDNA). The phylogenetic analyses based on EF-1a and ITS sequences...

Sleep and executive functions in older adults: A systematic review

PubMed Central

Holanda, Francisco Wilson Nogueira; de Almondes, Katie Moraes

2016-01-01

ABSTRACT Introduction: A recent increase in studies suggests a role of age-related sleep changes in executive functions (EF). However, this relationship remains unclear and mixed results have emerged. Objective: To investigate how age-related sleep changes may play an important role in the extent to which healthy older adults exhibit decline in EF. Methods: A systematic strategy was employed to identify the available literature on age-related sleep changes and EF. Results: Of the 465 studies identified, 26 were included. Results suggest that multiple sleep parameters differ in the way they benefit or impair EF. Parameters such as greater wake after sleep onset and lower sleep efficiency, in addition to circadian fragmentation of sleep, showed more consistent results and are potentially correlated with worsening in EF measures. However, other results seem inconclusive. Conclusion: These findings were discussed based on the prefrontal circuitry vulnerability model, in which sleep has been identified as a beneficial factor for prefrontal cortex functioning and hence for EF, which relies mostly on this brain area and its related networks. PMID:29213454

Effect of aging and long-term erectile function after iodine-125 prostate brachytherapy.

PubMed

Keyes, Mira; Pickles, Tom; Crook, Juanita; McKenzie, Michael; Cheung, Arthur; Spadinger, Ingrid; LaPointe, Vincent; Bachand, W Francois; Morris, James

2015-01-01

To evaluate long-term erectile function (EF) in men treated with iodine-125 prostate brachytherapy (PB) and to determine factors predictive for erectile dysfunction (ED), including natural decline because of aging. Two thousand nine hundred twenty-nine patients (implanted July 1989-June 2012) with baseline EF and greater than 10-month followup (FU) are included. About 78.9% had full and 7.9% had partial EF at baseline. EF was assessed on a physician-reported three-point scale. Poisson regression with generalized estimating equations was used to assess predictors of ED and Kaplan-Meier curves time to ED. The effect of aging was calculated from the declining rate of baseline EF seen in sequential 5-year age cohorts and from the Massachusetts Male Aging Study. The median age was 66 years and median FU 3.5 years (maximum 14 years). About 1142 patients had more than 5 years of FU, and 43% had received 6 months of androgen deprivation therapy (ADT). Significant drop in EF was seen at 6 weeks after PB, with gradual decline thereafter. EF preservation at 5 years for age younger than 55, 56-59, 60-64, 65-69, and 70 year and older was 82%, 73%, 58%, 39%, and 23%, respectively. Comparisons of the 5-year age-related and treatment-related EF decline show that 50% of the long-term EF decline is related to aging. On univariate and multivariate analyses, age at implant, length of FU, hypertension, diabetes, and use of ADT (all p < 0.01) were significant predictors of ED. More than 80% of young men have EF preserved 5 years after PB. Age, ADT, history of hypertension, and the natural decline in EF have negative impact on long-term EF after PB. Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.

Comorbidity and ventricular and vascular structure and function in heart failure with preserved ejection fraction: a community-based study.

PubMed

Mohammed, Selma F; Borlaug, Barry A; Roger, Véronique L; Mirzoyev, Sultan A; Rodeheffer, Richard J; Chirinos, Julio A; Redfield, Margaret M

2012-11-01

Patients with heart failure and preserved ejection fraction (HFpEF) display increased adiposity and multiple comorbidities, factors that in themselves may influence cardiovascular structure and function. This has sparked debate as to whether HFpEF represents a distinct disease or an amalgamation of comorbidities. We hypothesized that fundamental cardiovascular structural and functional alterations are characteristic of HFpEF, even after accounting for body size and comorbidities. Comorbidity-adjusted cardiovascular structural and functional parameters scaled to independently generated and age-appropriate allometric powers were compared in community-based cohorts of HFpEF patients (n=386) and age/sex-matched healthy n=193 and hypertensive, n=386 controls. Within HFpEF patients, body size and concomitant comorbidity-adjusted cardiovascular structural and functional parameters and survival were compared in those with and without individual comorbidities. Among HFpEF patients, comorbidities (obesity, anemia, diabetes mellitus, and renal dysfunction) were each associated with unique clinical, structural, functional, and prognostic profiles. However, after accounting for age, sex, body size, and comorbidities, greater concentric hypertrophy, atrial enlargement and systolic, diastolic, and vascular dysfunction were consistently observed in HFpEF compared with age/sex-matched normotensive and hypertensive. Comorbidities influence ventricular-vascular properties and outcomes in HFpEF, yet fundamental disease-specific changes in cardiovascular structure and function underlie this disorder. These data support the search for mechanistically targeted therapies in this disease.

A secure base from which to regulate: Attachment security in toddlerhood as a predictor of executive functioning at school entry.

PubMed

Bernier, Annie; Beauchamp, Miriam H; Carlson, Stephanie M; Lalonde, Gabrielle

2015-09-01

In light of emerging evidence suggesting that the affective quality of parent-child relationships may relate to individual differences in young children's executive functioning (EF) skills, the aim of this study was to investigate the prospective associations between attachment security in toddlerhood and children's EF skills in kindergarten. Mother-child dyads (N = 105) participated in 2 toddlerhood visits in their homes, when children were 15 months and 2 years of age. Mother-child attachment security was assessed with the Attachment Q-Sort during both these visits. When children were in kindergarten (ages 5-6), they were administered a battery of EF tasks, and their teachers completed the Behavior Rating Inventory of Executive Function to assess children's EF problems. The results indicated that kindergarteners who were more securely attached to their mothers in toddlerhood showed better performance on all EF tasks, and were considered by their teachers to present fewer EF problems in everyday school situations. These results held above family socioeconomic status (SES) and child age, sex, and general cognitive functioning. The fact that early attachment security uniquely predicted both teacher reports and children's objective EF task performance suggests that parent-child attachment may be a promising factor to consider in the continuing search for the social antecedents of young children's EF. (c) 2015 APA, all rights reserved).

Left ventricular ejection fraction to predict early mortality in patients with non-ST-segment elevation acute coronary syndromes.

PubMed

Bosch, Xavier; Théroux, Pierre

2005-08-01

Improvement in risk stratification of patients with non-ST-segment elevation acute coronary syndrome (ACS) is a gateway to a more judicious treatment. This study examines whether the routine determination of left ventricular ejection fraction (EF) adds significant prognostic information to currently recommended stratifiers. Several predictors of inhospital mortality were prospectively characterized in a registry study of 1104 consecutive patients, for whom an EF was determined, who were admitted for an ACS. Multiple regression models were constructed using currently recommended clinical, electrocardiographic, and blood marker stratifiers, and values of EF were incorporated into the models. Age, ST-segment shifts, elevation of cardiac markers, and the Thrombolysis in Myocardial Infarction (TIMI) risk score all predicted mortality (P < .0001). Adding EF into the model improved the prediction of mortality (C statistic 0.73 vs 0.67). The odds of death increased by a factor of 1.042 for each 1% decrement in EF. By receiver operating curves, an EF cutoff of 48% provided the best predictive value. Mortality rates were 3.3 times higher within each TIMI risk score stratum in patients with an EF of 48% or lower as compared with those with higher. The TIMI risk score predicts inhospital mortality in a broad population of patients with ACS. The further consideration of EF adds significant prognostic information.

Two programmed cell death systems in Escherichia coli: an apoptotic-like death is inhibited by the mazEF-mediated death pathway.

PubMed

Erental, Ariel; Sharon, Idith; Engelberg-Kulka, Hanna

2012-01-01

In eukaryotes, the classical form of programmed cell death (PCD) is apoptosis, which has as its specific characteristics DNA fragmentation and membrane depolarization. In Escherichia coli a different PCD system has been reported. It is mediated by the toxin-antitoxin system module mazEF. The E. coli mazEF module is one of the most thoroughly studied toxin-antitoxin systems. mazF encodes a stable toxin, MazF, and mazE encodes a labile antitoxin, MazE, which prevents the lethal effect of MazF. mazEF-mediated cell death is a population phenomenon requiring the quorum-sensing pentapeptide NNWNN designated Extracellular Death Factor (EDF). mazEF is triggered by several stressful conditions, including severe damage to the DNA. Here, using confocal microscopy and FACS analysis, we show that under conditions of severe DNA damage, the triggered mazEF-mediated cell death pathway leads to the inhibition of a second cell death pathway. The latter is an apoptotic-like death (ALD); ALD is mediated by recA and lexA. The mazEF-mediated pathway reduces recA mRNA levels. Based on these results, we offer a molecular model for the maintenance of an altruistic characteristic in cell populations. In our model, the ALD pathway is inhibited by the altruistic EDF-mazEF-mediated death pathway.

A meta-analysis of fertilizer-induced soil NO and combined NO+N2 O emissions.

PubMed

Liu, Shuwei; Lin, Feng; Wu, Shuang; Ji, Cheng; Sun, Yi; Jin, Yaguo; Li, Shuqing; Li, Zhaofu; Zou, Jianwen

2017-06-01

Soils are among the important sources of atmospheric nitric oxide (NO) and nitrous oxide (N 2 O), acting as a critical role in atmospheric chemistry. Updated data derived from 114 peer-reviewed publications with 520 field measurements were synthesized using meta-analysis procedure to examine the N fertilizer-induced soil NO and the combined NO+N 2 O emissions across global soils. Besides factors identified in earlier reviews, additional factors responsible for NO fluxes were fertilizer type, soil C/N ratio, crop residue incorporation, tillage, atmospheric carbon dioxide concentration, drought and biomass burning. When averaged across all measurements, soil NO-N fluxes were estimated to be 4.06 kg ha -1  yr -1 , with the greatest (9.75 kg ha -1  yr -1 ) in vegetable croplands and the lowest (0.11 kg ha -1  yr -1 ) in rice paddies. Soil NO emissions were more enhanced by synthetic N fertilizer (+38%), relative to organic (+20%) or mixed N (+18%) sources. Compared with synthetic N fertilizer alone, synthetic N fertilizer combined with nitrification inhibitors substantially reduced soil NO emissions by 81%. The global mean direct emission factors of N fertilizer for NO (EF NO ) and combined NO+N 2 O (EF c ) were estimated to be 1.16% and 2.58%, with 95% confidence intervals of 0.71-1.61% and 1.81-3.35%, respectively. Forests had the greatest EF NO (2.39%). Within the croplands, the EF NO (1.71%) and EF c (4.13%) were the greatest in vegetable cropping fields. Among different chemical N fertilizer varieties, ammonium nitrate had the greatest EF NO (2.93%) and EF c (5.97%). Some options such as organic instead of synthetic N fertilizer, decreasing N fertilizer input rate, nitrification inhibitor and low irrigation frequency could be adopted to mitigate soil NO emissions. More field measurements over multiyears are highly needed to minimize the estimate uncertainties and mitigate soil NO emissions, particularly in forests and vegetable croplands. © 2016 John Wiley & Sons Ltd.

Increased expression of stathmin and elongation factor 1α in precancerous nodules with telomere dysfunction in hepatitis B viral cirrhotic patients

PubMed Central

2014-01-01

Background Telomere dysfunction is important in carcinogenesis, and recently, stathmin and elongation factor 1α (EF1α) were reported to be up-regulated in telomere dysfunctional mice. Methods In the present study, the expression levels of stathmin and EF1α in relation to telomere length, telomere dysfunction-induced foci (TIF), γ-H2AX, and p21WAF1/CIP1 expression were assessed in specimens of hepatitis B virus (HBV)-related multistep hepatocarcinogenesis, including 13 liver cirrhosis specimens, 14 low-grade dysplastic nodules (DN), 17 high-grade DNs, and 14 hepatocellular carcinomas (HCC). Five normal liver specimens were used as controls. TIF were analyzed by telomere fluorescent in situ hybridization (FISH) combined with immunostaining, while the protein expressions of stathmin, EF1α, γ-H2AX, and p21WAF1/CIP1 were detected by immunohistochemistry. Result The expressions of stathmin and EF1α gradually increased as multistep hepatocarcinogenesis progressed, showing the highest levels in HCC. Stathmin mRNA levels were higher in high-grade DNs than normal liver and liver cirrhosis, whereas EF1α mRNA expression did not show such a difference. The protein expressions of stathmin and EF1α were found in DNs of precancerous lesions, whereas they were absent or present at very low levels in normal liver and liver cirrhosis. Stathmin histoscores were higher in high-grade DNs and low-grade DNs than in normal liver (all, P < 0.05). EF1α histoscores were higher in high-grade DNs than in normal liver and liver cirrhosis (all, P < 0.05). Stathmin mRNA levels and histoscores, as well as EF1α histoscores (but not mRNA levels), were positively correlated with telomere shortening and γ-H2AX labeling index (all, P < 0.05). EF1α histoscores were also positively correlated with TIF (P < 0.001). Significantly greater inactivation of p21WAF1/CIP1 was observed in low-grade DNs, high-grade DNs, and HCC, compared to liver cirrhosis (all, P < 0.05). p21WAF1/CIP1 labeling index was inversely correlated with TIF, stathmin mRNA level, and EF1α histoscore (all, P < 0.05). Conclusion Stathmin and EF1α are suggested to be closely related to telomere dysfunction, DNA damage, and inactivation of p21WAF1/CIP1 in HBV-related multistep hepatocarcinogenesis. Accordingly, assessment of stathmin and EF1α levels as a reflection of telomere dysfunction may be helpful in evaluating the biological characteristics of precancerous hepatic nodules in hepatitis B viral cirrhotic patients. PMID:24885363

Increased expression of stathmin and elongation factor 1α in precancerous nodules with telomere dysfunction in hepatitis B viral cirrhotic patients.

PubMed

Ahn, Ei Yong; Yoo, Jeong Eun; Rhee, Hyungjin; Kim, Myung Soo; Choi, Junjeong; Ko, Jung Eun; Lee, Jee San; Park, Young Nyun

2014-05-31

Telomere dysfunction is important in carcinogenesis, and recently, stathmin and elongation factor 1α (EF1α) were reported to be up-regulated in telomere dysfunctional mice. In the present study, the expression levels of stathmin and EF1α in relation to telomere length, telomere dysfunction-induced foci (TIF), γ-H2AX, and p21WAF1/CIP1 expression were assessed in specimens of hepatitis B virus (HBV)-related multistep hepatocarcinogenesis, including 13 liver cirrhosis specimens, 14 low-grade dysplastic nodules (DN), 17 high-grade DNs, and 14 hepatocellular carcinomas (HCC). Five normal liver specimens were used as controls. TIF were analyzed by telomere fluorescent in situ hybridization (FISH) combined with immunostaining, while the protein expressions of stathmin, EF1α, γ-H2AX, and p21WAF1/CIP1 were detected by immunohistochemistry. The expressions of stathmin and EF1α gradually increased as multistep hepatocarcinogenesis progressed, showing the highest levels in HCC. Stathmin mRNA levels were higher in high-grade DNs than normal liver and liver cirrhosis, whereas EF1α mRNA expression did not show such a difference. The protein expressions of stathmin and EF1α were found in DNs of precancerous lesions, whereas they were absent or present at very low levels in normal liver and liver cirrhosis. Stathmin histoscores were higher in high-grade DNs and low-grade DNs than in normal liver (all, P<0.05). EF1α histoscores were higher in high-grade DNs than in normal liver and liver cirrhosis (all, P<0.05). Stathmin mRNA levels and histoscores, as well as EF1α histoscores (but not mRNA levels), were positively correlated with telomere shortening and γ-H2AX labeling index (all, P<0.05). EF1α histoscores were also positively correlated with TIF (P<0.001). Significantly greater inactivation of p21WAF1/CIP1 was observed in low-grade DNs, high-grade DNs, and HCC, compared to liver cirrhosis (all, P<0.05). p21WAF1/CIP1 labeling index was inversely correlated with TIF, stathmin mRNA level, and EF1α histoscore (all, P<0.05). Stathmin and EF1α are suggested to be closely related to telomere dysfunction, DNA damage, and inactivation of p21WAF1/CIP1 in HBV-related multistep hepatocarcinogenesis. Accordingly, assessment of stathmin and EF1α levels as a reflection of telomere dysfunction may be helpful in evaluating the biological characteristics of precancerous hepatic nodules in hepatitis B viral cirrhotic patients.

Distribution and Phylogeny of EFL and EF-1α in Euglenozoa Suggest Ancestral Co-Occurrence Followed by Differential Loss

PubMed Central

Gile, Gillian H.; Faktorová, Drahomíra; Castlejohn, Christina A.; Burger, Gertraud; Lang, B. Franz; Farmer, Mark A.; Lukeš, Julius; Keeling, Patrick J.

2009-01-01

Background The eukaryotic elongation factor EF-1α (also known as EF1A) catalyzes aminoacyl-tRNA binding by the ribosome during translation. Homologs of this essential protein occur in all domains of life, and it was previously thought to be ubiquitous in eukaryotes. Recently, however, a number of eukaryotes were found to lack EF-1α and instead encode a related protein called EFL (for EF-Like). EFL-encoding organisms are scattered widely across the tree of eukaryotes, and all have close relatives that encode EF-1α. This intriguingly complex distribution has been attributed to multiple lateral transfers because EFL's near mutual exclusivity with EF-1α makes an extended period of co-occurrence seem unlikely. However, differential loss may play a role in EFL evolution, and this possibility has been less widely discussed. Methodology/Principal Findings We have undertaken an EST- and PCR-based survey to determine the distribution of these two proteins in a previously under-sampled group, the Euglenozoa. EF-1α was found to be widespread and monophyletic, suggesting it is ancestral in this group. EFL was found in some species belonging to each of the three euglenozoan lineages, diplonemids, kinetoplastids, and euglenids. Conclusions/Significance Interestingly, the kinetoplastid EFL sequences are specifically related despite the fact that the lineages in which they are found are not sisters to one another, suggesting that EFL and EF-1α co-occurred in an early ancestor of kinetoplastids. This represents the strongest phylogenetic evidence to date that differential loss has contributed to the complex distribution of EFL and EF-1α. PMID:19357788

Dual Endothelin-A/Endothelin-B Receptor Blockade and Cardiac Remodeling in Heart Failure With Preserved Ejection Fraction

PubMed Central

Valero-Munoz, Maria; Li, Shanpeng; Wilson, Richard M.; Boldbaatar, Batbold; Iglarz, Marc; Sam, Flora

2017-01-01

Background Despite the increasing prevalence of heart failure with preserved ejection fraction (HFpEF) in humans, there remains no evidence-based therapies for HFpEF. Endothelin-1 (ET-1) antagonists are a possibility because elevated ET-1 levels are associated with adverse cardiovascular effects, such as arterial and pulmonary vasoconstriction, impaired left ventricular (LV) relaxation, and stimulation of LV hypertrophy. LV hypertrophy is a common phenotype in HFpEF, particularly when associated with hypertension. Methods and Results In the present study, we found that ET-1 levels were significantly elevated in patients with chronic stable HFpEF. We then sought to investigate the effects of chronic macitentan, a dual ET-A/ET-B receptor antagonist, on cardiac structure and function in a murine model of HFpEF induced by chronic aldosterone infusion. Macitentan caused LV hypertrophy regression independent of blood pressure changes in HFpEF. Although macitentan did not modulate diastolic dysfunction in HFpEF, it significantly reduced wall thickness and relative wall thickness after 2 weeks of therapy. In vitro studies showed that macitentan decreased the aldosterone-induced cardiomyocyte hypertrophy. These changes were mediated by a reduction in the expression of cardiac myocyte enhancer factor 2a. Moreover, macitentan improved adverse cardiac remodeling, by reducing the stiffer cardiac collagen I and titin n2b expression in the left ventricle of mice with HFpEF. Conclusions These findings indicate that dual ET-A/ET-B receptor inhibition improves HFpEF by abrogating adverse cardiac remodeling via antihypertrophic mechanisms and by reducing stiffness. Additional studies are needed to explore the role of dual ET-1 receptor antagonists in patients with HFpEF. PMID:27810862

Dual Endothelin-A/Endothelin-B Receptor Blockade and Cardiac Remodeling in Heart Failure With Preserved Ejection Fraction.

PubMed

Valero-Munoz, Maria; Li, Shanpeng; Wilson, Richard M; Boldbaatar, Batbold; Iglarz, Marc; Sam, Flora

2016-11-01

Despite the increasing prevalence of heart failure with preserved ejection fraction (HFpEF) in humans, there remains no evidence-based therapies for HFpEF. Endothelin-1 (ET-1) antagonists are a possibility because elevated ET-1 levels are associated with adverse cardiovascular effects, such as arterial and pulmonary vasoconstriction, impaired left ventricular (LV) relaxation, and stimulation of LV hypertrophy. LV hypertrophy is a common phenotype in HFpEF, particularly when associated with hypertension. In the present study, we found that ET-1 levels were significantly elevated in patients with chronic stable HFpEF. We then sought to investigate the effects of chronic macitentan, a dual ET-A/ET-B receptor antagonist, on cardiac structure and function in a murine model of HFpEF induced by chronic aldosterone infusion. Macitentan caused LV hypertrophy regression independent of blood pressure changes in HFpEF. Although macitentan did not modulate diastolic dysfunction in HFpEF, it significantly reduced wall thickness and relative wall thickness after 2 weeks of therapy. In vitro studies showed that macitentan decreased the aldosterone-induced cardiomyocyte hypertrophy. These changes were mediated by a reduction in the expression of cardiac myocyte enhancer factor 2a. Moreover, macitentan improved adverse cardiac remodeling, by reducing the stiffer cardiac collagen I and titin n2b expression in the left ventricle of mice with HFpEF. These findings indicate that dual ET-A/ET-B receptor inhibition improves HFpEF by abrogating adverse cardiac remodeling via antihypertrophic mechanisms and by reducing stiffness. Additional studies are needed to explore the role of dual ET-1 receptor antagonists in patients with HFpEF. © 2016 American Heart Association, Inc.

[Ecological Footprint Evolution Characteristics and Its Influencing Factors in China from 2000 to 2010].

PubMed

Huang, Bao-rong; Cui, Shu-hong; Li, Ying-ming

2016-02-15

According to global average land productivities in 2000, this study calculated ecological footprint (EF) in China from 2000 to 2010, and analyzed its dynamic characteristics and socio-economic driving forces. The results showed that the total EF in China increased from 1.769 to 3.259 billion global hectares (gha) from 2000 to 2010, and its annual growth rate was 6.30%. Carbon Footprint was the fastest growth type of EF. It increased from 0.742 to 1.805 billion gha, and its annual growth rate was 9.29%. The net increase of cropland Footprint was also large in comparison to other types of Footprint. It increased from 0.678 to 0.891 billion gha. Per capita EF in China increased from 1.40 to 2.43 gha in this period. Although it was still below the world average level, it was far beyond per capita ecological carrying capacity in China, which led to serious ecological deficit and severe ecological crisis in China. The fast growth of per capita EF was the main driving force for the growth of total EF in China during the study period. Further, the growth of per capita EF was positively influenced by the growth of per capita consumption of products and severs, which was driven by economic growth and urbanization. Meanwhile, a large amount of exports of resource-intensive products in international trade was also an important driving force for EF growth. According to the evolution route of per capita EF in developed countries, along with China moving from middle-income to high-income country, per capita EF will maintain rapid growth, and ecological deficit in China will further exacerbate.

Neural correlates of executive functions in patients with obesity.

PubMed

Ho, Ming-Chou; Chen, Vincent Chin-Hung; Chao, Seh-Huang; Fang, Ching-Tzu; Liu, Yi-Chun; Weng, Jun-Cheng

2018-01-01

Obesity is one of the most challenging problems in human health and is recognized as an important risk factor for many chronic diseases. It remains unclear how the neural systems (e.g., the mesolimbic "reward" and the prefrontal "control" neural systems) are correlated with patients' executive function (EF), conceptualized as the integration of "cool" EF and "hot" EF. "Cool" EF refers to relatively abstract, non-affective operations such as inhibitory control and mental flexibility. "Hot" EF refers to motivationally significant affective operations such as affective decision-making. We tried to find the correlation between structural and functional neuroimaging indices and EF in obese patients. The study population comprised seventeen patients with obesity (seven males and 10 females, BMI = 37.99 ± 5.40, age = 31.82 ± 8.75 year-old) preparing to undergo bariatric surgery. We used noninvasive diffusion tensor imaging, generalized q-sampling imaging, and resting-state functional magnetic resonance imaging to examine the neural correlations between structural and functional neuroimaging indices and EF performances in patients with obesity. We reported that many brain areas are correlated to the patients' EF performances. More interestingly, some correlations may implicate the possible associations of EF and the incentive motivational effects of food. The neural correlation between the left precuneus and middle occipital gyrus and inhibitory control may suggest that patients with a better ability to detect appetitive food may have worse inhibitory control. Also, the neural correlation between the superior frontal blade and affective decision-making may suggest that patients' affective decision-making may be associated with the incentive motivational effects of food. Our results provide evidence suggesting neural correlates of EF in patients with obesity.

Enhance®Fitness Dissemination and Implementation,: 2010-2015: A Scoping Review.

PubMed

Petrescu-Prahova, Miruna G; Eagen, Thomas J; Fishleder, Sarah L; Belza, Basia

2017-03-01

Physical activity has many benefits for older adult physical and mental health. Enhance ® Fitness (EF) is an evidence-based group exercise program delivered by community-based organizations. The purpose of this study was to review recent evidence on the dissemination and implementation of EF. A scoping review of qualitative and quantitative studies with EF as main focus was conducted. CINAHL, PubMed, PubMed Central, SCOPUS, Web of Science, PsycINFO, and Google Scholar were searched between October and November 2015 for data-based studies on EF published in 2010-2015. Two team members abstracted each paper independently using a data abstraction tool. Results were summarized using the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework. Seventeen publications met inclusion criteria. EF has reached and is effective across a broad population base, including individuals with low SES and diverse ethnic/racial backgrounds. EF participation may be associated with reduced risk for falls requiring medical care, and is associated with fewer hospital admissions. Analyses of medical cost savings from EF participation and program implementation costs suggest economic benefits of EF implementation for communities. Organization-level maintenance is facilitated by program-specific and organizational factors, such as instructor training and funding. Individual-level maintenance is facilitated by program structure, absence of pain, and increased quality of life. More-rigorous evidence is needed about the association between participation in EF and conditions such as falls. Evaluation of program fidelity, adaptations, and sustainability is limited; more-systematic examination across population groups and types of organizations would help ensure older adults continue to benefit from EF participation. Copyright © 2016 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

Impaired associative taste learning and abnormal brain activation in kinase-defective eEF2K mice.

PubMed

Gildish, Iness; Manor, David; David, Orit; Sharma, Vijendra; Williams, David; Agarwala, Usha; Wang, Xuemin; Kenney, Justin W; Proud, Chris G; Rosenblum, Kobi

2012-02-24

Memory consolidation is defined temporally based on pharmacological interventions such as inhibitors of mRNA translation (molecular consolidation) or post-acquisition deactivation of specific brain regions (systems level consolidation). However, the relationship between molecular and systems consolidation are poorly understood. Molecular consolidation mechanisms involved in translation initiation and elongation have previously been studied in the cortex using taste-learning paradigms. For example, the levels of phosphorylation of eukaryotic elongation factor 2 (eEF2) were found to be correlated with taste learning in the gustatory cortex (GC), minutes following learning. In order to isolate the role of the eEF2 phosphorylation state at Thr-56 in both molecular and system consolidation, we analyzed cortical-dependent taste learning in eEF2K (the only known kinase for eEF2) ki mice, which exhibit reduced levels of eEF2 phosphorylation but normal levels of eEF2 and eEF2K. These mice exhibit clear attenuation of cortical-dependent associative, but not of incidental, taste learning. In order to gain a better understanding of the underlying mechanisms, we compared brain activity as measured by MEMRI (manganese-enhanced magnetic resonance imaging) between eEF2K ki mice and WT mice during conditioned taste aversion (CTA) learning and observed clear differences between the two but saw no differences under basal conditions. Our results demonstrate that adequate levels of phosphorylation of eEF2 are essential for cortical-dependent associative learning and suggest that malfunction of memory processing at the systems level underlies this associative memory impairment. © 2012 Cold Spring Harbor Laboratory Press

Does Maternal Depression Predict Young Children's Executive Function?--A 4-Year Longitudinal Study

ERIC Educational Resources Information Center

Hughes, Claire; Roman, Gabriela; Hart, Martha J.; Ensor, Rosie

2013-01-01

Background: Building on reports that parental maltreatment and neglect adversely affect young children's executive function (EF), this longitudinal study examined whether exposure to a more common risk factor, mothers' depressive symptoms, predicted individual differences in EF at school-age. Methods: We followed up at age 6 a socially diverse…

Development of Hot Exhaust Emission Factors for Iranian-Made Euro-2 Certified Light-Duty Vehicles.

PubMed

Banitalebi, Ehsan; Hosseini, Vahid

2016-01-05

Emission factors (EFs) are fundamental, necessary data for air pollution research and scenario implementation. With the vision of generating national EFs of the Iranian transportation system, a portable emission measurement system (PEMS) was used to develop the basic EFs for a statistically significant sample of Iranian gasoline-fueled privately owned light duty vehicles (LDVs) operated in Tehran. A smaller sample size of the same fleet was examined by chassis dynamometer (CD) bag emission measurement tests to quantify the systematic differences between the PEMS and CD methods. The selected fleet was tested over four different routes of uphill highways, flat highways, uphill urban streets, and flat urban streets. Real driving emissions (RDEs) and fuel consumption (FC) rates were calculated by weighted averaging of the results from each route. The activity of the fleet over each route type was assumed as a weighting factor. The activity data were obtained from a Tehran traffic model. The RDEs of the selected fleet were considerably higher than the certified emission levels of all vehicles. Differences between Tehran real driving cycles and the New European Driving Cycle (NEDC) was attributed to the lower loading of NEDC. A table of EFs based on RDEs was developed for the sample fleet.

SunRiSE - measuring translation elongation at single-cell resolution by means of flow cytometry.

PubMed

Argüello, Rafael J; Reverendo, Marisa; Mendes, Andreia; Camosseto, Voahirana; Torres, Adrian G; Ribas de Pouplana, Lluis; van de Pavert, Serge A; Gatti, Evelina; Pierre, Philippe

2018-05-31

The rate at which ribosomes translate mRNAs regulates protein expression by controlling co-translational protein folding and mRNA stability. Many factors regulate translation elongation, including tRNA levels, codon usage and phosphorylation of eukaryotic elongation factor 2 (eEF2). Current methods to measure translation elongation lack single-cell resolution, require expression of multiple transgenes and have never been successfully applied ex vivo Here, we show, by using a combination of puromycilation detection and flow cytometry (a method we call 'SunRiSE'), that translation elongation can be measured accurately in primary cells in pure or heterogenous populations isolated from blood or tissues. This method allows for the simultaneous monitoring of multiple parameters, such as mTOR or S6K1/2 signaling activity, the cell cycle stage and phosphorylation of translation factors in single cells, without elaborated, costly and lengthy purification procedures. We took advantage of SunRiSE to demonstrate that, in mouse embryonic fibroblasts, eEF2 phosphorylation by eEF2 kinase (eEF2K) mostly affects translation engagement, but has a surprisingly small effect on elongation, except after proteotoxic stress induction.This article has an associated First Person interview with the first author of the paper. © 2018. Published by The Company of Biologists Ltd.

Medulloblastoma in China: Clinicopathologic Analyses of SHH, WNT, and Non-SHH/WNT Molecular Subgroups Reveal Different Therapeutic Responses to Adjuvant Chemotherapy

PubMed Central

Ren, Yong; Yao, Yu; Li, Kay Ka-Wai; Ng, Ho-Keung; Mao, Ying; Zhou, Liang-Fu; Zhong, Ping

2014-01-01

Medulloblastoma (MB) is one of the most common primary central nervous system tumors in children. Data is lacking of a large cohort of medulloblastoma patients in China. Also, our knowledge on the sensitivity of different molecular subgroups of MB to adjuvant radiation therapy (RT) or chemotherapy (CHT) is still limited. The authors performed a retrospective study of 173 medulloblastoma patients treated at two institutions from 2002 to 2011. Formalin-fixed paraffin embedded (FFPE) tissues were available in all the cases and sections were stained to classify histological and molecular subgroups. Univariate and multivariate analyses were used to investigate prognostic factors. Of 173 patients, there were 118 children and 55 adults, 112 males and 61 females. Estimated 5-year overall survival (OS) rates for all patients, children and adults were 52%, 48% and 63%, respectively. After multivariate analysis, postoperative primary radiation therapy (RT) and chemotherapy (CHT) were revealed as favorable prognostic factors influencing OS and EFS. Postoperative primary chemotherapy (CHT) was found significantly improving the survival of children (p<0.001) while it was not a significant prognostic factor for adult patients. Moreover, patients in WNT subtype had better OS (p = 0.028) than others (SHH and Non-SHH/WNT subtypes) given postoperative adjuvant therapies. Postoperative primary RT was found to be a strong prognostic factor influencing the survival in all histological and molecular subgroups (p<0.001). Postoperative primary CHT was found significantly to influence the survival of classic medulloblastoma (CMB) (OS p<0.001, EFS p<0.001), SHH subgroup (OS p = 0.020, EFS p = 0.049) and WNT subgroup (OS p = 0.003, EFS p = 0.016) but not in desmoplastic/nodular medulloblastoma (DMB) (OS p = 0.361, EFS p = 0.834) and Non-SHH/WNT subgroup (OS p = 0.127, EFS p = 0.055). Our study showed postoperative primary CHT significantly influence the survival of CMB, SHH subgroup and WNT subgroup but not in DMB and Non-SHH/WNT subgroup of MB. PMID:24932704

Studies of elongation factor Tu in Streptococcus faecium (ATCC 9790)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bourbeau, P.P.

1986-01-01

It has been known for over twenty years that elongation factor Tu (Ef-Tu) is one of the proteins involved in protein synthesis in bacteria. Several years ago, it was proposed that Ef-Tu may, in addition, have other structural functions in bacterial. The author's research has examined the function of Ef-Tu in Streptococcus faecium. Using an antibiotic kirromycin, which specifically inhibits Ef-Tu function, the effects upon a number of cellular parameters were determined. Inhibition of both protein and RNA synthesis was found to be similar to the effect of chloramphenicol. Using the residual division technique for the determination of cell cyclemore » events with both heterogeneous and sucrose gradient fractionated cell populations, a kirromycin sensitive event was detected between 8 min. (Td = 30 min.) and 19 min. (Td = 175 min.) later in the cell cycle than the chloramphenical sensitive event. This suggests that kirromycin is inhibiting a terminal cell cycle event which is in addition to the inhibition of protein synthesis. Purification of Ef-Tu was performed using two different methods: ion exchange and molecular exclusion chromatography; and GDP affinity chromatography. Various schemes were employed to try and obtain optimum cellular fractionation, allowing for both proper separation of ribosomes from the other cellular fractions and retention of enzymatic activity by Ef-Tu as determined by a /sup 3/H-GDP binding assay. Analysis of the cell cycle of S. faecium using the residual division technique was also performed. In addition, certain cell wall antibiotics were used to determine if other cell cycle events could be determined using the residual division technique.« less

Hydrogeological Controls on Regional-Scale Indirect Nitrous Oxide Emission Factors for Rivers.

PubMed

Cooper, Richard J; Wexler, Sarah K; Adams, Christopher A; Hiscock, Kevin M

2017-09-19

Indirect nitrous oxide (N 2 O) emissions from rivers are currently derived using poorly constrained default IPCC emission factors (EF 5r ) which yield unreliable flux estimates. Here, we demonstrate how hydrogeological conditions can be used to develop more refined regional-scale EF 5r estimates required for compiling accurate national greenhouse gas inventories. Focusing on three UK river catchments with contrasting bedrock and superficial geologies, N 2 O and nitrate (NO 3 - ) concentrations were analyzed in 651 river water samples collected from 2011 to 2013. Unconfined Cretaceous Chalk bedrock regions yielded the highest median N 2 O-N concentration (3.0 μg L -1 ), EF 5r (0.00036), and N 2 O-N flux (10.8 kg ha -1 a -1 ). Conversely, regions of bedrock confined by glacial deposits yielded significantly lower median N 2 O-N concentration (0.8 μg L -1 ), EF 5r (0.00016), and N 2 O-N flux (2.6 kg ha -1 a -1 ), regardless of bedrock type. Bedrock permeability is an important control in regions where groundwater is unconfined, with a high N 2 O yield from high permeability chalk contrasting with significantly lower median N 2 O-N concentration (0.7 μg L -1 ), EF 5r (0.00020), and N 2 O-N flux (2.0 kg ha -1 a -1 ) on lower permeability unconfined Jurassic mudstone. The evidence presented here demonstrates EF 5r can be differentiated by hydrogeological conditions and thus provide a valuable proxy for generating improved regional-scale N 2 O emission estimates.

Integrating affective and cognitive correlates of heart rate variability: A structural equation modeling approach

PubMed Central

Mann, Sarah L.; Selby, Edward A.; Bates, Marsha E.; Contrada, Richard J.

2016-01-01

High frequency heart rate variability (HRV) is a measure of neurocardiac communication thought to reflect predominantly parasympathetic cardiac regulation. Low HRV has been associated empirically with clinical and subclinical levels of anxiety and depression and, more recently, high levels of HRV have been associated with better performance on some measures of executive functioning (EF). These findings have offered support for theories proposing HRV as an index measure of a broad, self-regulatory capacity underlying aspects of emotion regulation and executive control. This study sought to test that proposition by using a structural equation modeling approach to examine the relationships of HRV to negative affect (NA) and EF in a large sample of U.S. adults ages 30s–80s. HRV was modeled as a predictor of an NA factor (self-reported trait anxiety and depression symptoms) and an EF factor (performance on three neuropsychological tests tapping facets of executive abilities). Alternative models also were tested to determine the utility of HRV for predicting NA and EF, with and without statistical control of demographic and health-related covariates. In the initial structural model, HRV showed a significant positive relationship to EF and a nonsignificant relationship to NA. In a covariate-adjusted model, HRV’s associations with both constructs were nonsignificant. Age emerged as the only significant predictor of NA and EF in the final model, showing inverse relationships to both. Findings may reflect population and methodological differences from prior research; they also suggest refinements to the interpretations of earlier findings and theoretical claims regarding HRV. PMID:26168884

Translation elongation factor EF-Tu modulates filament formation of actin-like MreB protein in vitro.

PubMed

Defeu Soufo, Hervé Joël; Reimold, Christian; Breddermann, Hannes; Mannherz, Hans G; Graumann, Peter L

2015-04-24

EF-Tu has been shown to interact with actin-like protein MreB and to affect its localization in Escherichia coli and in Bacillus subtilis cells. We have purified YFP-MreB in an active form, which forms filaments on glass slides in vitro and was active in dynamic light-scattering assays, polymerizing in milliseconds after addition of magnesium. Purified EF-Tu enhanced the amount of MreB filaments, as seen by sedimentation assays, the speed of filament formation and the length of MreB filaments in vitro. EF-Tu had the strongest impact on MreB filaments in a 1:1 ratio, and EF-Tu co-sedimented with MreB filaments, revealing a stoichiometric interaction between both proteins. This was supported by cross-linking assays where 1:1 species were well detectable. When expressed in E. coli cells, B. subtilis MreB formed filaments and induced the formation of co-localizing B. subtilis EF-Tu structures, indicating that MreB can direct the positioning of EF-Tu structures in a heterologous cell system. Fluorescence recovery after photobleaching analysis showed that MreB filaments have a higher turnover in B. subtilis cells than in E. coli cells, indicating different filament kinetics in homologous or heterologous cell systems. The data show that MreB can direct the localization of EF-Tu in vivo, which in turn positively affects the formation and dynamics of MreB filaments. Thus, EF-Tu is a modulator of the activity of a bacterial actin-like protein. Copyright © 2015. Published by Elsevier Ltd.

Diphenyl difluoroketone: a curcumin derivative with potent in vivo anticancer activity.

PubMed

Subramaniam, Dharmalingam; May, Randal; Sureban, Sripathi M; Lee, Katherine B; George, Robert; Kuppusamy, Periannan; Ramanujam, Rama P; Hideg, Kalman; Dieckgraefe, Brian K; Houchen, Courtney W; Anant, Shrikant

2008-03-15

Diphenyl difluoroketone (EF24), a molecule having structural similarity to curcumin, was reported to inhibit proliferation of a variety of cancer cells in vitro. However, the efficacy and in vivo mechanism of action of EF24 in gastrointestinal cancer cells have not been investigated. Here, we assessed the in vivo therapeutic effects of EF24 on colon cancer cells. Using hexosaminidase assay, we determined that EF24 inhibits proliferation of HCT-116 and HT-29 colon and AGS gastric adenocarcinoma cells but not of mouse embryo fibroblasts. Furthermore, the cancer cells showed increased levels of activated caspase-3 and increased Bax to Bcl-2 and Bax to Bcl-xL ratios, suggesting that the cells were undergoing apoptosis. At the same time, cell cycle analysis showed that there was an increased number of cells in the G(2)-M phase. To determine the effects of EF24 in vivo, HCT-116 colon cancer xenografts were established in nude mice and EF24 was given i.p. EF24 significantly suppressed the growth of colon cancer tumor xenografts. Immunostaining for CD31 showed that there was a lower number of microvessels in the EF24-treated animals coupled with decreased cyclooxygenase-2, interleukin-8, and vascular endothelial growth factor mRNA and protein expression. Western blot analyses also showed decreased AKT and extracellular signal-regulated kinase activation in the tumors. Taken together, these data suggest that the novel curcumin-related compound EF24 is a potent antitumor agent that induces caspase-mediated apoptosis during mitosis and has significant therapeutic potential for gastrointestinal cancers.

Real-world automotive particulate matter and PAH emission factors and profile concentrations: Results from an urban tunnel experiment in Naples, Italy

NASA Astrophysics Data System (ADS)

Riccio, A.; Chianese, E.; Monaco, D.; Costagliola, M. A.; Perretta, G.; Prati, M. V.; Agrillo, G.; Esposito, A.; Gasbarra, D.; Shindler, L.; Brusasca, G.; Nanni, A.; Pozzi, C.; Magliulo, V.

2016-09-01

On-road particulate matter (PM) mass was measured during a sampling campaign in March of 2015 in the '4 giornate' tunnel in Naples, Italy. Two sets of samples were collected at both sides of the tunnel, each set representing the daily cycle at a 1 h time resolution. Distance-based - mass per kilometer - and fuel-based - mass per burned fuel - emission factors (EFs) were calculated using mass concentrations, traffic flow rates and wind speed as a function of fleet composition. Also, chemical analyses were performed for polycyclic aromatic hydrocarbons (PAHs). Due to the high traffic volume, particle mass concentration at the tunnel exit was always significantly elevated relative to entrance concentration; depending on the hour of the day, PM10 concentration ranged between 300 μg/m3, during the early afternoon, and 600 μg/m3 during rush hours at the tunnel exit. Correspondingly, PAHs achieved concentrations as high as 1450 ng/m3, and benzo(a)pyrene, a surely carcinogenic compound, achieved concentrations as high as 69 ng/m3, raising serious concerns in relation to population exposure close to this urban tunnel. Distance-based and fuel-based emission factors for CO2, PM10 and PAHs were estimated, but while the EF for CO2 was within the range of expected values, the present study found much higher EFs for particulate matter and PAHs. According to the national official statistics from ISPRA (the Italian Institute for the Protection and Research on Environment), derived from the COPERT database, we expected an EF for particulate matter of about 55 mg/km, but the EF estimated from measurements taken at both sides of the tunnel was about four times higher than that expected; also, benzo(a)pyrene achieved an average EF of 2.7 μg/km, about three times higher than that expected from the ISPRA database.

Pathophysiology, Evaluation, and Management of Edema in Childhood Nephrotic Syndrome.

PubMed

Ellis, Demetrius

2015-01-01

Generalized edema is a major presenting clinical feature of children with nephrotic syndrome (NS) exemplified by such primary conditions as minimal change disease (MCD). In these children with classical NS and marked proteinuria and hypoalbuminemia, the ensuing tendency to hypovolemia triggers compensatory physiological mechanisms, which enhance renal sodium (Na(+)) and water retention; this is known as the "underfill hypothesis." Edema can also occur in secondary forms of NS and several other glomerulonephritides, in which the degree of proteinuria and hypoalbuminemia, are variable. In contrast to MCD, in these latter conditions, the predominant mechanism of edema formation is "primary" or "pathophysiological," Na(+) and water retention; this is known as the "overfill hypothesis." A major clinical challenge in children with these disorders is to distinguish the predominant mechanism of edema formation, identify other potential contributing factors, and prevent the deleterious effects of diuretic regimens in those with unsuspected reduced effective circulatory volume (i.e., underfill). This article reviews the Starling forces that become altered in NS so as to tip the balance of fluid movement in favor of edema formation. An understanding of these pathomechanisms then serves to formulate a more rational approach to prevention, evaluation, and management of such edema.

Natural History of Perihematomal Edema and Impact on Outcome After Intracerebral Hemorrhage.

PubMed

Wu, Teddy Y; Sharma, Gagan; Strbian, Daniel; Putaala, Jukka; Desmond, Patricia M; Tatlisumak, Turgut; Davis, Stephen M; Meretoja, Atte

2017-04-01

Edema may worsen outcome after intracerebral hemorrhage (ICH). We assessed its natural history, factors influencing growth, and association with outcome. We estimated edema volumes in ICH patients from the Helsinki ICH study using semiautomated planimetry. We assessed the correlation between edema extension distance (EED) and time from ICH onset, creating an edema growth trajectory model up to 3 weeks. We interpolated expected EED at 72 hours and identified clinical and imaging characteristics associated with faster edema growth. Association of EED and mortality was assessed using logistic regression adjusting for predictors of ICH outcome. From 1013 consecutive patients, 861 were included. There was a strong inverse correlation between EED growth rate (cm/d) and time from onset (days): EED growth=0.162*days exp(-0.927), R 2 =0.82. Baseline factors associated with larger than expected EED were older age (71 versus 68; P =0.002), higher National Institutes of Health Stroke Scale score (14 versus 8; P <0.001), and lower Glasgow Coma scale score (13 versus 15; P <0.001), larger ICH volume (19.7 versus 12.7 mL; P <0.001), larger initial EED (0.42 versus 0.30; P <0.001), irregularly shaped hematoma (55% versus 42%; P <0.001), and higher glucose (7.6 versus 6.9 mmol/L; P =0.001). Patients with faster edema growth had more midline shift (50% versus 31%; P <0.001), herniation (12% versus 4%; P <0.001), and higher 6-month (46% versus 26%; P <0.001) mortality. In the logistic regression model, higher-than-expected EED was associated with 6-month mortality (odds ratio, 1.60; 95% confidence interval, 1.04-2.46; P =0.032). Edema growth can be readily monitored and is an independent determinant of mortality after ICH, providing an important treatment target for strategies to improve patient outcome. © 2017 American Heart Association, Inc.

Haploinsufficiency for Translation Elongation Factor eEF1A2 in Aged Mouse Muscle and Neurons Is Compatible with Normal Function

PubMed Central

Griffiths, Lowri A.; Doig, Jennifer; Churchhouse, Antonia M. D.; Davies, Faith C. J.; Squires, Charlotte E.; Newbery, Helen J.; Abbott, Catherine M.

2012-01-01

Translation elongation factor isoform eEF1A2 is expressed in muscle and neurons. Deletion of eEF1A2 in mice gives rise to the neurodegenerative phenotype “wasted” (wst). Mice homozygous for the wasted mutation die of muscle wasting and neurodegeneration at four weeks post-natal. Although the mutation is said to be recessive, aged heterozygous mice have never been examined in detail; a number of other mouse models of motor neuron degeneration have recently been shown to have similar, albeit less severe, phenotypic abnormalities in the heterozygous state. We therefore examined the effects of ageing on a cohort of heterozygous +/wst mice and control mice, in order to establish whether a presumed 50% reduction in eEF1A2 expression was compatible with normal function. We evaluated the grip strength assay as a way of distinguishing between wasted and wild-type mice at 3–4 weeks, and then performed the same assay in older +/wst and wild-type mice. We also used rotarod performance and immunohistochemistry of spinal cord sections to evaluate the phenotype of aged heterozygous mice. Heterozygous mutant mice showed no deficit in neuromuscular function or signs of spinal cord pathology, in spite of the low levels of eEF1A2. PMID:22848658

Nanoparticle-nanoparticle vs. nanoparticle-substrate hot spot contributions to the SERS signal: studying Raman labelled monomers, dimers and trimers.

PubMed

Sergiienko, Sergii; Moor, Kamila; Gudun, Kristina; Yelemessova, Zarina; Bukasov, Rostislav

2017-02-08

We used a combination of Raman microscopy, AFM and TEM to quantify the influence of dimerization on the surface enhanced Raman spectroscopy (SERS) signal for gold and silver nanoparticles (NPs) modified with Raman reporters and situated on gold, silver, and aluminum films and a silicon wafer. The overall increases in the mean SERS enhancement factor (EF) upon dimerization (up by 43% on average) and trimerisation (up by 96% on average) of AuNPs and AgNPs on the studied metal films are within a factor of two, which is moderate when compared to most theoretical models. However, the maximum ratio of EFs for some dimers to the mean EF of monomers can be as high as 5.5 for AgNPs on a gold substrate. In contrast, for dimerization and trimerization of gold and silver NPs on silicon, the mean EF increases by 1-2 orders of magnitude relative to the mean EF of single NPs. Therefore, hot spots in the interparticle gap between gold nanoparticles rather than hot spots between Au nanoparticles and the substrate dominate SERS enhancement for dimers and trimers on a silicon substrate. However, Raman labeled noble metal nanoparticles on plasmonic metal films generate on average SERS enhancement of the same order of magnitude for both types of hot spot zones (e.g. NP/NP and NP/metal film).

Real-World Emission Factors of Gaseous and Particulate Pollutants from Marine Fishing Boats and Their Total Emissions in China.

PubMed

Zhang, Fan; Chen, Yingjun; Chen, Qi; Feng, Yanli; Shang, Yu; Yang, Xin; Gao, Huiwang; Tian, Chongguo; Li, Jun; Zhang, Gan; Matthias, Volker; Xie, Zhiyong

2018-04-17

Pollutants from fishing boats have generally been neglected worldwide, and there is an acute shortage of measured emission data, especially in China. Therefore, on-board measurements of pollutants emitted from 12 different fishing boats in China (including gill net, angling, and trawler boats) were carried out in this study to investigate emission factors (EFs), characteristics and total emissions. The average EFs for CO 2 , CO, NO x , PM, and SO 2 were 3074 ± 55.9, 50.6 ± 31.7, 54.2 ± 30.7, 9.54 ± 2.24, and 5.94 ± 6.38 g (kg fuel) -1 , respectively, which were higher than those from previous studies of fishing boats. When compared to medium-speed and slow-speed engine vessels, high-speed engines on fishing boats had higher CO EFs but lower NO x EFs. Notably, when fishing boats were in low-load conditions, they always had higher EFs of CO, PM, and NO 2 compared to other operating modes. The estimated results showed that emissions from motor-powered fishing boats in China in 2012 (232, 379, and 61.8 kt CO, NO x and PM) accounted for 10.7%, 10.9%, and 19.3% of the total CO, NO x and PM emitted from nonroad mobile sources, which means significant contribution of fishing boats to air pollution, especially in southern China areas.

Executive Function in Very Preterm Children at Early School Age

ERIC Educational Resources Information Center

Aarnoudse-Moens, Cornelieke S. H.; Smidts, Diana P.; Oosterlaan, Jaap; Duivenvoorden, Hugo J.; Weisglas-Kuperus, Nynke

2009-01-01

We examined whether very preterm ([less than or equal to] 30 weeks gestation) children at early school age have impairments in executive function (EF) independent of IQ and processing speed, and whether demographic and neonatal risk factors were associated with EF impairments. A consecutive sample of 50 children (27 boys and 23 girls) born very…

Characterization and cytotoxicity of PAHs in PM2.5 emitted from residential solid fuel burning in the Guanzhong Plain, China.

PubMed

Sun, Jian; Shen, Zhenxing; Zeng, Yaling; Niu, Xinyi; Wang, Jinhui; Cao, Junji; Gong, Xuesong; Xu, Hongmei; Wang, Taobo; Liu, Hongxia; Yang, Liu

2018-05-28

The emission factors (EFs) of polycyclic aromatic hydrocarbons (PAHs) in PM 2.5 were measured from commonly used stoves and fuels in the rural Guanzhong Plain, China. The toxicity of the PM 2.5 also was measured using in vitro cellular tests. EFs of PAHs varied from 0.18 mg kg -1 (maize straw charcoal burning in a clean stove) to 83.3 mg kg -1 (maize straw burning in Heated Kang). The two largest influencing factors on PAH EFs were air supply and volatile matter proportion in fuel. Improvements in these two factors could decrease not only EFs of PAHs but also the proportion of 3-ring to 5-ring PAHs. Exposure to PM 2.5 extracts caused a concentration-dependent decline in cell viability but an increase in reactive oxygen species (ROS), tumor necrosis factor a (TNF-α) and interleukin 6 (IL-6). PM 2.5 emitted from maize burning in Heated Kang showed the highest cytotoxicity, and EFs of ROS and inflammatory factors were the highest as well. In comparison, maize straw charcoal burning in a clean stove showed the lowest cytotoxicity, which indicated a clean stove and fuel treatment were both efficient methods for reducing cytotoxicity of primary PM 2.5 . The production of these bioreactive factors were highly correlated with 3-ring and 4-ring PAHs. Specifically, pyrene, anthracene and benzo(a)anthracene had the highest correlations with ROS production (R = 0.85, 0.81 and 0.80, respectively). This study shows that all tested stoves emitted PM 2.5 that was cytotoxic to human cells; thus, there may be no safe levels of exposure to PM 2.5 emissions from cooking and heating stoves using solid fuels. The study may also provide a new approach for evaluating the cytotoxicity of primary emitted PM 2.5 from solid fuel burning as well as other PM 2.5 sources. Copyright © 2018 Elsevier Ltd. All rights reserved.

All for One: Contributions of Age, Socioeconomic Factors, Executive Functioning, and Social Cognition to Moral Reasoning in Childhood

PubMed Central

Vera-Estay, Evelyn; Seni, Anne G.; Champagne, Caroline; Beauchamp, Miriam H.

2016-01-01

Moral reasoning (MR) is a socio-cognitive skill essential to appropriate social functioning in childhood, and evolves in quality and complexity during ontogenetic development. Past research suggests that MR is related to age, socioeconomic factors, as well as some social and cognitive skills, such as executive functioning (EF), theory of mind (ToM), empathy, and affect recognition. However, their contributions have been studied in silos rather than comprehensively, with little integration of the relative and combined contribution of these skills to MR. Furthermore, few studies have addressed the putative links between these factors in childhood, a period during which these skills are in maturation. The aim of this study was to explore what factors predict moral maturity in typically developing children (n = 76, 47.4% males, M = 9.2, SD = 1.67 years), explore the potential moderating and mediating role of executive functions and social cognition in the relationship between age and MR maturity, and identify the specific contributions of age, socioeconomic factors, EF, and social cognition, using an innovative visual MR assessment tool (So-Moral). The results indicate that MR maturity was correlated with age, EF (inhibition, verbal fluency, and attentional control), and social cognition (ToM and affect recognition). Neither EF nor social cognition moderated the effect of age on MR maturity. However, verbal fluency and third-order false beliefs had a moderating role in this link. MR maturity in children was predicted by three variables from each of the three domains: age, verbal fluency, and third-order ToM. These results contribute to a better understanding of the underpinnings of MR during childhood, suggesting that MR is not reducible to general developmental factors such as age, but that higher order skills, such EF and social cognition also contribute to moral maturity. The findings have relevance for both typically developing and clinical populations in which social skills may be reduced, as well as for the identification of potential loci for intervention in children at-risk for socially maladaptive behaviors. PMID:27014110

LDH is an adverse prognostic factor independent of ISS in transplant-eligible myeloma patients receiving bortezomib-based induction regimens.

PubMed

Chim, Chor Sang; Sim, Joycelyn; Tam, Sidney; Tse, Eric; Lie, Albert Kwok Wai; Kwong, Yok Lam

2015-04-01

Serum lactate dehydrogenase (LDH) has been an adverse prognostic factor for myeloma but does not feature in the International Staging System (ISS). We examined whether elevated serum LDH at diagnosis remains an adverse risk factor independent of ISS for survivals transplant-eligible myeloma patients receiving early/frontline bortezomib-based induction, followed by autologous stem cell transplantation (ASCT). Seventy-seven transplant-eligible Chinese patients received three induction regimens [staged approach (N = 25), PAD (N = 19), VTD (N = 33)], followed by ASCT and thalidomide maintenance. Five-year overall (OS) and event-free (EFS) survivals were 66.4% and 36.2%. There was no difference in demographics, complete remission/near complete remission (CR/nCR rates postinduction or ASCT, and survivals among patients induced by the three induction regimens. Elevated LDH was associated with male gender (P = 0.006), ISS III (P = 0.042) and serum β2-microglobulin (P = 0.040). Univariate analysis showed that elevated LDH, ISS III, high β2-microglobulin, and failure to attain CR/nCR post-ACST were risk factors adversely impacting both OS and EFS. Multivariate analysis showed that elevated LDH was the only factor impacting both OS (P = 0.007) and EFS (P = 0.008). In this uniformly treated cohort of transplant-eligible myeloma patients, elevated serum LDH is an adverse risk factor independent of ISS for both OS and EFS. Bortezomib-based induction/ASCT regimen had not abolished the adverse impact of elevated LDH. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Target oriented drugs against leishmania. Annual summary report no. 2, 1 May 1980-30 April 1981

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zehavi, U.; El-On, J.

1981-01-31

Excreted Factor (EF) is a carbohydrate-rich material released by different strains of Leishmania during growth. It has antigenic properties similar to those of the intact parasite and plays a role in the infective process. Isolation and purification of EF is necessary for study of its biological function, its use for diagnostic purposes, its use in immunization experiments, the study of its biosynthesis, and the preparation of inhibitors of particular biosynthetic steps. Purification of EF by affinity chromatography was markedly improved by introducing Ricinus lectin (specific for galactose) column. This enabled us to obtain more reliable amino acid and sugar analysismore » and will be instrumental in more advanced physical, chemical, and immunological studies. We have developed a radioimmunoassay for leishmaniasis utilizing purified EF. The assay can distinguish between Leishmania strains and once further developed, should prove most valuable for the diagnosis of the disease. EF plays a role in the infective process of Leishmania. We have now shown that surface carbohydrate, related to EF, plays a role in the initial attachment of Leishmania promastigots to macrophages - a stage that is a prelude to their engulfment by the macrophages followed by multiplication in their cells.« less

Parents' Executive Functioning and Involvement in Their Child's Education: An Integrated Literature Review.

PubMed

Wilson, Damali M; Gross, Deborah

2018-04-01

Parents' involvement in their children's education is integral to academic success. Several education-based organizations have identified recommendations for how parents can best support their children's learning. However, executive functioning (EF), a high-ordered cognitive skill set, contributes to the extent to which parents can follow through with these recommendations. This integrative review of the literature describes how executive function can affect parents' ability to facilitate and actively participate in their child's education and provides strategies for all school staff to strengthen parent-school partnerships when parents have limitations in EF. EF skills are fluid and influenced by several factors, including parental age, sleep, stress, and mood/affect. Despite possible limitations in parental EF, there are strategies school personnel can employ to strengthen partnership with parents to support their children's academic success. As reforms in education call for increased customization and collaboration with families, parental EF is an important consideration for school personnel. Awareness and understanding of how parents' EF affects children's learning will help schools better support parents in supporting their children's academic success. © 2018 The Authors. Journal of School Health published by Wiley Periodicals, Inc. on behalf of American School Health Association.

Diphenyl difluoroketone: a potent chemotherapy candidate for human hepatocellular carcinoma.

PubMed

Liang, Yingjian; Yin, Dalong; Hou, Limin; Zheng, Tongsen; Wang, Jiabei; Meng, Xianzhi; Lu, Zhaoyang; Song, Xuan; Pan, Shangha; Jiang, Hongchi; Liu, Lianxin

2011-01-01

Diphenyl difluoroketone (EF24), a molecule having structural similarity to curcumin, was recently reported to inhibit proliferation of various cancer cells significantly. Here we try to determine the effect and mechanism of EF24 on hepatocellular carcinoma. 2 µM EF24 was found to inhibit the proliferation of PLC/PRF/5, Hep3B, HepG2, SK-HEP-1 and Huh 7 cell lines. However, even 8 µM EF24 treatment did not affect the proliferation of normal liver LO2 cells. Accordingly, 20 mg/kg/d EF24 inhibited the growth of the tumor xenografts conspicuously while causing no apparent change in liver, spleen or body weight. In addition, significant apoptosis and G(2)/M phase cell cycle arrest were found using flow cytometry. Besides, caspases and PARP activation and features typical of apoptosis including fragmented nuclei with condensed chromatin were also observed. Furthermore, the mechanism was targeted at the reduction of nuclear factor kappa b (NF-κB) pathway and the NF-κB-regulated gene products Bcl-2, COX-2, Cyclin B1. Our study has offered a strategy that EF24 being a therapeutic agent for hepatocellular carcinoma.

Diphenyl Difluoroketone: A Potent Chemotherapy Candidate for Human Hepatocellular Carcinoma

PubMed Central

Hou, Limin; Zheng, Tongsen; Wang, Jiabei; Meng, Xianzhi; Lu, Zhaoyang; Song, Xuan; Pan, Shangha; Jiang, Hongchi; Liu, Lianxin

2011-01-01

Diphenyl difluoroketone (EF24), a molecule having structural similarity to curcumin, was recently reported to inhibit proliferation of various cancer cells significantly. Here we try to determine the effect and mechanism of EF24 on hepatocellular carcinoma. 2 µM EF24 was found to inhibit the proliferation of PLC/PRF/5, Hep3B, HepG2, SK-HEP-1 and Huh 7 cell lines. However, even 8 µM EF24 treatment did not affect the proliferation of normal liver LO2 cells. Accordingly, 20 mg/kg/d EF24 inhibited the growth of the tumor xenografts conspicuously while causing no apparent change in liver, spleen or body weight. In addition, significant apoptosis and G2/M phase cell cycle arrest were found using flow cytometry. Besides, caspases and PARP activation and features typical of apoptosis including fragmented nuclei with condensed chromatin were also observed. Furthermore, the mechanism was targeted at the reduction of nuclear factor kappa b (NF-κB) pathway and the NF-κB–regulated gene products Bcl-2, COX-2, Cyclin B1. Our study has offered a strategy that EF24 being a therapeutic agent for hepatocellular carcinoma. PMID:21901145

Understanding Ion Binding Affinity and Selectivity in β-Parvalbumin Using Molecular Dynamics and Mean Spherical Approximation Theory.

PubMed

Kucharski, Amir N; Scott, Caitlin E; Davis, Jonathan P; Kekenes-Huskey, Peter M

2016-08-25

Parvalbumin (PV) is a globular calcium (Ca(2+))-selective protein expressed in a variety of biological tissues. Our computational studies of the rat β-parvalbumin (β-PV) isoform seek to elucidate the molecular thermodynamics of Ca(2+) versus magnesium (Mg(2+)) binding at the protein's two EF-hand motifs. Specifically, we have utilized molecular dynamics (MD) simulations and a mean-field electrolyte model (mean spherical approximation (MSA) theory) to delineate how the EF-hand scaffold controls the "local" thermodynamics of Ca(2+) binding selectivity over Mg(2+). Our MD simulations provide the probability density of metal-chelating oxygens within the EF-hand scaffolds for both Ca(2+) and Mg(2+), as well the conformational strain induced by Mg(2+) relative to Ca(2+) binding. MSA theory utilizes the binding domain oxygen and charge distributions to predict the chemical potential of ion binding, as well as their corresponding concentrations within the binding domain. We find that the electrostatic and steric contributions toward ion binding were similar for Mg(2+) and Ca(2+), yet the latter was 5.5 kcal/mol lower in enthalpy when internal strain within the EF hand was considered. We therefore speculate that beyond differences in dehydration energies for the Ca(2+) versus Mg(2+), strain induced in the β-PV EF hand by cation binding significantly contributes to the nearly 10,000-fold difference in binding affinity reported in the literature. We further complemented our analyses of local factors governing cation binding selectivity with whole-protein (global) contributions, such as interhelical residue-residue contacts and solvent exposure of hydrophobic surface. These contributions were found to be comparable for both Ca(2+)- and Mg(2+)-bound β-PV, which may implicate local factors, EF-hand strain, and dehydration, in providing the primary means of selectivity. We anticipate these methods could be used to estimate metal binding thermodynamics across a broad range of PV sequence homologues and EF-hand-containing, Ca(2+) binding proteins.

The influence of environmental factors on the generalisability of public health research evidence: physical activity as a worked example

PubMed Central

2011-01-01

Background It is rare that decisions about investing in public health interventions in a city, town or other location can be informed by research generated in that specific place. It is therefore necessary to base decisions on evidence generated elsewhere and to make inferences about the extent to which this evidence is generalisable to the place of interest. In this paper we discuss the issues involved in making such inferences, using physical activity as an example. We discuss the ways in which elements of the structural, physical, social and/or cultural environment (environmental factors [EFs]) can shape physical activity (PA) and also how EFs may influence the effectiveness of interventions that aim to promote PA. We then highlight the ways in which EFs may impact on the generalisability of different types of evidence. Discussion We present a framework for thinking about the influence of EFs when assessing the generalisability of evidence from the location in which the evidence was generated (place A) to the location to which the evidence is to be applied (place B). The framework relates to similarities and differences between place A and place B with respect to: a) the distributions of EFs; b) the causal pathways through which EFs or interventions are thought to exert their effect on PA and c) the ways in which EFs interact with each other. We suggest, using examples, how this scheme can be used by public health professionals who are designing, executing, reporting and synthesising research on PA; or designing/implementing interventions. Summary Our analysis and scheme, although developed for physical activity, may potentially be adapted and applied to other evidence and interventions which are likely to be sensitive to influence by elements of the structural, physical, social and/or cultural environment such as the epidemiology of obesity and healthy weight promotion. PMID:22087556

Development of welding emission factors for Cr and Cr(VI) with a confidence level.

PubMed

Serageldin, Mohamed; Reeves, David W

2009-05-01

Knowledge of the emission rate and release characteristics is necessary for estimating pollutant fate and transport. Because emission measurements at a facility's fence line are generally not readily available, environmental agencies in many countries are using emission factors (EFs) to indicate the quantity of certain pollutants released into the atmosphere from operations such as welding. The amount of fumes and metals generated from a welding process is dependent on many parameters, such as electrode composition, voltage, and current. Because test reports on fume generation provide different levels of detail, a common approach was used to give a test report a quality rating on the basis of several highly subjective criteria; however, weighted average EFs generated in this way are not meant to reflect data precision or to be used for a refined risk analysis. The 95% upper confidence limit (UCL) of the unknown population mean was used in this study to account for the uncertainty in the EF test data. Several parametric UCLs were computed and compared for multiple welding EFs associated with several mild, stainless, and alloy steels. Also, several nonparametric statistical methods, including several bootstrap procedures, were used to compute 95% UCLs. For the nonparametric methods, a distribution for calculating the mean, standard deviation, and other statistical parameters for a dataset does not need to be assumed. There were instances when the sample size was small and instances when EFs for an electrode/process combination were not found. Those two points are addressed in this paper. Finally, this paper is an attempt to deal with the uncertainty in the value of a mean EF for an electrode/process combination that is based on test data from several laboratories. Welding EFs developed with a defined level of confidence may be used as input parameters for risk assessment.

Platelet-activating factor dilates efferent arterioles through glomerulus-derived nitric oxide.

PubMed

Arima, S; Ren, Y; Juncos, L A; Ito, S

1996-01-01

Despite evidence that platelet-activating factor (PAF) is produced by the glomerulus, its direct action on the glomerular microcirculation is poorly understood. It was recently reported that at picomolar concentrations, PAF dilates isolated microperfused afferent arterioles (Af-Art) via nitric oxide (NO). The present study tested the hypothesis that PAF acts on the glomerulus to release NO, which in turn controls the resistance of the efferent arteriole (Ef-Art). Rabbit Ef-Art were perfused from the distal end (retrograde perfusion [RP]) to eliminate the influence of the glomerulus, or through the glomerulus from the end of the Af-Art (orthograde perfusion [OP]) to maintain the influence of the glomerulus. Ef-Art were preconstricted by approximately 40% with norepinephrine and increasing doses of PAF were added to both the arteriolar perfusate and bath. Only with OP did PAF at picomolar concentrations cause significant dilation: at 400 pmol, the diameter increased by 64 +/- 11% from the preconstricted level (N = 6, P < 0.01). This dilation was completely abolished by pretreatment with an NO-synthesis inhibitor. To study its possible constrictor action, PAF was added to nonpreconstricted Ef-Art. At nanomolar concentrations, PAF constricted Ef-Art similarly in both RP and OP: at 40 nM, the diameter decreased by 24 +/- 4% (N = 6, P < 0.01) and 20 +/- 2% (N = 6, P < 0.01), respectively. This constriction was attenuated by pretreatment with indomethacin (Indo) in both RP (14 +/- 2%, N = 7; P < 0.02 versus without Indo) and OP (10 +/- 2%, N = 6; P < 0.02 versus without Indo). (1) at picomolar concentrations, PAF stimulates the glomerulus to release NO, which in turn dilates the Ef-Art; and (2) at nanomolar concentrations, PAF constricts the Ef-Art partly through release of cyclooxygenase metabolites. Thus, PAF may play a role in glomerular hemodynamics under various physiological and pathological conditions.

Anthrax Lethal Factor as an Immune Target in Humans and Transgenic Mice and the Impact of HLA Polymorphism on CD4+ T Cell Immunity

PubMed Central

Ascough, Stephanie; Ingram, Rebecca J.; Chu, Karen K.; Reynolds, Catherine J.; Musson, Julie A.; Doganay, Mehmet; Metan, Gökhan; Ozkul, Yusuf; Baillie, Les; Sriskandan, Shiranee; Moore, Stephen J.; Gallagher, Theresa B.; Dyson, Hugh; Williamson, E. Diane; Robinson, John H.; Maillere, Bernard; Boyton, Rosemary J.; Altmann, Daniel M.

2014-01-01

Bacillus anthracis produces a binary toxin composed of protective antigen (PA) and one of two subunits, lethal factor (LF) or edema factor (EF). Most studies have concentrated on induction of toxin-specific antibodies as the correlate of protective immunity, in contrast to which understanding of cellular immunity to these toxins and its impact on infection is limited. We characterized CD4+ T cell immunity to LF in a panel of humanized HLA-DR and DQ transgenic mice and in naturally exposed patients. As the variation in antigen presentation governed by HLA polymorphism has a major impact on protective immunity to specific epitopes, we examined relative binding affinities of LF peptides to purified HLA class II molecules, identifying those regions likely to be of broad applicability to human immune studies through their ability to bind multiple alleles. Transgenics differing only in their expression of human HLA class II alleles showed a marked hierarchy of immunity to LF. Immunogenicity in HLA transgenics was primarily restricted to epitopes from domains II and IV of LF and promiscuous, dominant epitopes, common to all HLA types, were identified in domain II. The relevance of this model was further demonstrated by the fact that a number of the immunodominant epitopes identified in mice were recognized by T cells from humans previously infected with cutaneous anthrax and from vaccinated individuals. The ability of the identified epitopes to confer protective immunity was demonstrated by lethal anthrax challenge of HLA transgenic mice immunized with a peptide subunit vaccine comprising the immunodominant epitopes that we identified. PMID:24788397

Evidence-based review of diabetic macular edema management: Consensus statement on Indian treatment guidelines

PubMed Central

Das, Taraprasad; Aurora, Ajay; Chhablani, Jay; Giridhar, Anantharaman; Kumar, Atul; Raman, Rajiv; Nagpal, Manish; Narayanan, Raja; Natarajan, Sundaram; Ramasamay, Kim; Tyagi, Mudit; Verma, Lalit

2016-01-01

The purpose of the study was to review the current evidence and design a diabetic macular edema (DME) management guideline specific for India. The published DME guidelines from different organizations and publications were weighed against the practice trends in India. This included the recently approved drugs. DME management consisted of control of diabetes and other associated systemic conditions, such as hypertension and hyperlipidemia, and specific therapy to reduce macular edema. Quantification of macular edema is precisely made with the optical coherence tomography and treatment options include retinal laser, intravitreal anti-vascular endothelial growth factors (VEGF), and implantable dexamethasone. Specific use of these modalities depends on the presenting vision and extent of macular involvement. Invariable eyes with center-involving macular edema benefit from intravitreal anti-VEGF or dexamethasone implant therapy, and eyes with macular edema not involving the macula center benefit from retinal laser. The results are illustrated with adequate case studies and frequently asked questions. This guideline prepared on the current published evidence is meant as a guideline for the treating physicians. PMID:26953019

A pentapeptide monocyte locomotion inhibitory factor protects brain ischemia injury by targeting the eEF1A1/endothelial nitric oxide synthase pathway.

PubMed

Zhang, Yuefan; Chen, Jun; Li, Fan; Li, Dong; Xiong, Qinhui; Lin, Yang; Zhang, Dazhi; Wang, Xiao-Fan; Yang, Pengyuan; Rui, Yao-Cheng

2012-10-01

Ischemic stroke is a major cause of death worldwide but lacks viable treatment or treatment targets. Monocyte locomotion inhibitory factor (MLIF) is a small heat-stable pentapeptide produced by Entamoeba histolytica in axenic culture, which is supposed to protect the brain from ischemic injury; the mechanism, however, remains unknown. In this study, we further investigated the mechanism underlying the protective role of MLIF in brain ischemia. A middle cerebral artery occlusion model in rats was used for detecting the effect of MLIF in the brain ischemia in vivo. To identify targets of MLIF in brain endothelial cells, we performed immunoprecipitation of biotin-conjugated MLIF and mass spectrometry. MLIF can protect the brain from ischemic injury in vivo, yielding decreased ischemic volume, prolonged survival, and improved neurological outcome. In vitro studies showed that MLIF displayed protective effects through inhibition of expression of pathological inflammatory adhesion molecules and enhancing endothelial nitric oxide synthase expression and nitric oxide release in the cerebrovascular endothelium. The target screening experiments demonstrated binding of MLIF to the ribosomal protein translation elongation factor eEF1A1. MLIF enhanced endothelial nitric oxide synthase expression through stabilization of endothelial nitric oxide synthase mRNA, and eEF1A1 was shown to be necessary for this enhanced expression. Knockdown of eEF1A1 or inhibition of endothelial nitric oxide synthase attenuated MLIF-mediated inhibition of adhesion molecule expression. In this study, we identified a new potential pharmacologically targetable mechanism underlying MLIF's protective effects in brain ischemia through the eEF1A1/endothelial nitric oxide synthase pathway.

Loss of diphthamide pre-activates NF-κB and death receptor pathways and renders MCF7 cells hypersensitive to tumor necrosis factor.

PubMed

Stahl, Sebastian; da Silva Mateus Seidl, Ana Rita; Ducret, Axel; Kux van Geijtenbeek, Sabine; Michel, Sven; Racek, Tomas; Birzele, Fabian; Haas, Alexander K; Rueger, Ruediger; Gerg, Michael; Niederfellner, Gerhard; Pastan, Ira; Brinkmann, Ulrich

2015-08-25

The diphthamide on human eukaryotic translation elongation factor 2 (eEF2) is the target of ADP ribosylating diphtheria toxin (DT) and Pseudomonas exotoxin A (PE). This modification is synthesized by seven dipthamide biosynthesis proteins (DPH1-DPH7) and is conserved among eukaryotes and archaea. We generated MCF7 breast cancer cell line-derived DPH gene knockout (ko) cells to assess the impact of complete or partial inactivation on diphthamide synthesis and toxin sensitivity, and to address the biological consequence of diphthamide deficiency. Cells with heterozygous gene inactivation still contained predominantly diphthamide-modified eEF2 and were as sensitive to PE and DT as parent cells. Thus, DPH gene copy number reduction does not affect overall diphthamide synthesis and toxin sensitivity. Complete inactivation of DPH1, DPH2, DPH4, and DPH5 generated viable cells without diphthamide. DPH1ko, DPH2ko, and DPH4ko harbored unmodified eEF2 and DPH5ko ACP- (diphthine-precursor) modified eEF2. Loss of diphthamide prevented ADP ribosylation of eEF2, rendered cells resistant to PE and DT, but does not affect sensitivity toward other protein synthesis inhibitors, such as saporin or cycloheximide. Surprisingly, cells without diphthamide (independent of which the DPH gene compromised) were presensitized toward nuclear factor of kappa light polypeptide gene enhancer in B cells (NF-κB) and death-receptor pathways without crossing lethal thresholds. In consequence, loss of diphthamide rendered cells hypersensitive toward TNF-mediated apoptosis. This finding suggests a role of diphthamide in modulating NF-κB, death receptor, or apoptosis pathways.

Gene expression of human lung cancer cell line CL1-5 in response to a direct current electric field.

PubMed

Huang, Ching-Wen; Chen, Huai-Yi; Yen, Meng-Hua; Chen, Jeremy J W; Young, Tai-Horng; Cheng, Ji-Yen

2011-01-01

Electrotaxis is the movement of adherent living cells in response to a direct current (dc) electric field (EF) of physiological strength. Highly metastatic human lung cancer cells, CL1-5, exhibit directional migration and orientation under dcEFs. To understand the transcriptional response of CL1-5 cells to a dcEF, microarray analysis was performed in this study. A large electric-field chip (LEFC) was designed, fabricated, and used in this study. CL1-5 cells were treated with the EF strength of 0 mV/mm (the control group) and 300 mV/mm (the EF-treated group) for two hours. Signaling pathways involving the genes that expressed differently between the two groups were revealed. It was shown that the EF-regulated genes highly correlated to adherens junction, telomerase RNA component gene regulation, and tight junction. Some up-regulated genes such as ACVR1B and CTTN, and some down-regulated genes such as PTEN, are known to be positively and negatively correlated to cell migration, respectively. The protein-protein interactions of adherens junction-associated EF-regulated genes suggested that platelet-derived growth factor (PDGF) receptors and ephrin receptors may participate in sensing extracellular electrical stimuli. We further observed a high percentage of significantly regulated genes which encode cell membrane proteins, suggesting that dcEF may directly influence the activity of cell membrane proteins in signal transduction. In this study, some of the EF-regulated genes have been reported to be essential whereas others are novel for electrotaxis. Our result confirms that the regulation of gene expression is involved in the mechanism of electrotactic response.

Assessing the dysexecutive syndrome in dementia.

PubMed

Gansler, David A; Huey, Edward D; Pan, Jessica J; Wasserman, Eric; Grafman, Jordan H

2017-03-01

We compared performance on tests of dysexecutive behaviour (DB) and executive function (EF) in patients with behavioural variant frontotemporal dementia (bvFTD), primary progressive aphasia (PPA) and corticobasal syndrome (CBS). Patients diagnosed with bvFTD (n=124), PPA (n=34) and CBS (n=85) were recruited. EF was measured with the Delis-Kaplan Executive Function System (DKEFS: performance based), and DB was measured with the Frontal Systems Behavior Scale (FrSBe: caregiver-report based). Confirmatory factor analysis characterised the relationship between EF and DB, binary logistic regression evaluated the incremental diagnostic utility of the measures and neuroimaging data from 110 patients identified neural correlates. EF was lowest and DB was highest in bvFTD participants. EF and DB were distinct but related (r=-0.48). Measures correctly classified 89% of bvFTD from CBS patients and 93% of bvFTD from PPA patients-30% and 13% above base rates (59%, 80%), respectively. All modalities were useful in identifying CBS and PPA, whereas DB alone was useful for identifying bvFTD. EF was uniquely associated with caudal left dorsolateral prefrontal and lateral temporo-parietal cortices. DB was uniquely associated with the cingulate (R>L), right subcallosal and right anterior frontal cortex. EF and DB were associated with the rostral dorsolateral prefrontal cortex bilaterally. EF and DB measures displayed criterion and construct validity, had incremental utility at low DB levels (CBS and PPA) and were associated with overlapping and distinct neural correlates. EF and DB procedures can conjointly provide useful diagnostic and descriptive information in identifying and ruling out the dysexecutive syndrome. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Electromagnetic enhancement of ordered silver nanorod arrays evaluated by discrete dipole approximation.

PubMed

Wei, Guoke; Wang, Jinliang; Chen, Yu

2015-01-01

The enhancement factor (EF) of surface-enhanced Raman scattering (SERS) from two-dimensional (2D) hexagonal silver nanorod (AgNR) arrays were investigated in terms of electromagnetic (EM) mechanism by using the discrete dipole approximation (DDA) method. The dependence of EF on several parameters, i.e., structure, length, excitation wavelength, incident angle and polarization, and gap size has been investigated. "Hotspots" were found distributed in the gaps between adjacent nanorods. Simulations of AgNR arrays of different lengths revealed that increasing the rod length from 374 to 937 nm (aspect ratio from 2.0 to 5.0) generated more "hotspots" but not necessarily increased EF under both 514 and 532 nm excitation. A narrow lateral gap (in the incident plane) was found to result in strong EF, while the dependence of EF on the diagonal gap (out of the incident plane) showed an oscillating behavior. The EF of the array was highly dependent on the angle and polarization of the incident light. The structure of AgNR and the excitation wavelength were also found to affect the EF. The EF of random arrays was stronger than that of an ordered one with the same average gap of 21 nm, which could be explained by the exponential dependence of EF on the lateral gap size. Our results also suggested that absorption rather than extinction or scattering could be a good indicator of EM enhancement. It is expected that the understanding of the dependence of local field enhancement on the structure of the nanoarrays and incident excitations will shine light on the optimal design of efficient SERS substrates and improved performance.

Enhanced jump performance when providing augmented feedback compared to an external or internal focus of attention.

PubMed

Keller, Martin; Lauber, Benedikt; Gottschalk, Marius; Taube, Wolfgang

2015-01-01

Factors such as an external focus of attention (EF) and augmented feedback (AF) have been shown to improve performance. However, the efficacy of providing AF to enhance motor performance has never been compared with the effects of an EF or an internal focus of attention (IF). Therefore, the aim of the present study was to identify which of the three conditions (AF, EF or IF) leads to the highest performance in a countermovement jump (CMJ). Nineteen volunteers performed 12 series of 8 maximum CMJs. Changes in jump height between conditions and within the series were analysed. Jump heights differed between conditions (P < 0.001), resulting in best performance with AF (32.04 ± 7.11 cm), followed by EF (31.21 ± 6.67 cm) and IF (30.77 ± 6.87 cm). Significantly different (P < 0.001) within-series effects of higher jump heights at the end of the series in AF (+1.60%) and lower jump heights at the end of the series in EF (-1.79%) and IF (-1.68%) were observed. Muscle activity did not differ between conditions. The differences between conditions and within the series provide evidence that AF leads to higher performance and better progression within one series than EF and IF. Consequently, AF seems to outperform EF and IF when maximising jump height.

Sacubitril/Valsartan: A Novel Cardiovascular Combination Agent.

PubMed

Sible, Alexandra M; Nawarskas, James J; Alajajian, David; Anderson, Joe R

2016-01-01

Sacubitril/valsartan [LCZ696 (Entresto), Novartis Pharmaceuticals Corp.] is the first in a new class of drugs that combines neprilysin inhibition with angiotensin II receptor antagonism, the combination of which acts to increase endogenous natriuretic peptides while inhibiting the renin-angiotensin-aldosterone system. Sacubitril/valsartan has been studied in the treatment of hypertension, heart failure with reduced ejection fraction (HFrEF), and heart failure with preserved ejection fraction (HFpEF) and has demonstrated clinical efficacy in blood pressure reduction in hypertensive patients with and without HFpEF and a reduction in hospitalizations and mortality for patients with HFrEF. Research to evaluate clinical outcomes in HFpEF is ongoing. Sacubitril/valsartan is approved to reduce hospitalization and risk of cardiovascular death for patients with HFrEF in New York Heart Association (NYHA) functional class II-IV. The product is as well tolerated as an angiotensin-converting enzyme inhibitor, with the most common side effect being hypotension. Expectedly, it is much more costly than generic angiotensin-converting enzyme inhibitors or angiotensin receptor antagonists, which will be a factor in determining how widespread the use of this agent will be. In summary, although the number of published studies evaluating its use is limited, sacubitril/valsartan represents a promising new treatment option for patients with HFrEF. Ongoing studies will continue to refine the role of this agent in clinical practice.

Investigating a method for estimating direct nitrous oxide emissions from grazed pasture soils in New Zealand using NZ-DNDC.

PubMed

Giltrap, Donna L; Ausseil, Anne-Gaelle E; Thakur, Kailash P; Sutherland, M Anne

2013-11-01

In this study, we developed emission factor (EF) look-up tables for calculating the direct nitrous oxide (N2O) emissions from grazed pasture soils in New Zealand. Look-up tables of long-term average direct emission factors (and their associated uncertainties) were generated using multiple simulations of the NZ-DNDC model over a representative range of major soil, climate and management conditions occurring in New Zealand using 20 years of climate data. These EFs were then combined with national activity data maps to estimate direct N2O emissions from grazed pasture in New Zealand using 2010 activity data. The total direct N2O emissions using look-up tables were 12.7±12.1 Gg N2O-N (equivalent to using a national average EF of 0.70±0.67%). This agreed with the amount calculated using the New Zealand specific EFs (95% confidence interval 7.7-23.1 Gg N2O-N), although the relative uncertainty increased. The high uncertainties in the look-up table EFs were primarily due to the high uncertainty of the soil parameters within the selected soil categories. Uncertainty analyses revealed that the uncertainty in soil parameters contributed much more to the uncertainty in N2O emissions than the inter-annual weather variability. The effect of changes to fertiliser applications was also examined and it was found that for fertiliser application rates of 0-50 kg N/ha for sheep and beef and 60-240 kg N/ha for dairy the modelled EF was within ±10% of the value simulated using annual fertiliser application rates of 15 kg N/ha and 140 kg N/ha respectively. Copyright © 2013 Elsevier B.V. All rights reserved.

Influence of image-defined risk factors on the outcome of patients with localised neuroblastoma. A report from the LNESG1 study of the European International Society of Paediatric Oncology Neuroblastoma Group.

PubMed

Monclair, Tom; Mosseri, Véronique; Cecchetto, Giovanni; De Bernardi, Bruno; Michon, Jean; Holmes, Keith

2015-09-01

The European multicenter study LNESG1 was designed to evaluate the safety and efficacy of surgical treatment alone in patients with localised neuroblastoma. In a retrospective, observational study we examined the impact of image-defined risk factors (IDRF) on operative complications and survival (EFS and OS). 534 patients with localised, non-MYCN amplified neuroblastoma were recruited between 1995 and 1999. Group 1 consisted of 291 patients without IDRF (Stage L1 in the International Neuroblastoma Risk Group (INRG) staging system), all treated with primary surgery. Group 2: 118 patients with IDRF (INRG Stage L2), also treated with primary surgery. Group 3: 125 patients in whom primary surgery was not attempted, 106 receiving neo-adjuvant chemotherapy. In L1 patients (Group 1) 5-year EFS was 92% and OS 98%. In L2 patients (Group 2 and 3) EFS was 79% and OS 89%. The differences in both EFS and OS were significant. EFS and OS in Group 2 (86% and 95%) were significantly better than 73% and 83% in Group 3. In INSS stage 1, 2 and 3, EFS were respectively 94%, 81% and 76%. Except between stage 2 and 3 the differences were significant. OS were respectively 99%, 93% and 83%, all significantly different. The 17% operative complication rate in L2 patients was significantly higher than 5% in L1 patients. In localised neuroblastoma, IDRF at diagnosis are associated with worse survival rates and higher rates of operative complications. The impact of IDRF should become an integrated part of therapy planning. © 2015 Wiley Periodicals, Inc.

Structural characterization of ribosome recruitment and translocation by type IV IRES.

PubMed

Murray, Jason; Savva, Christos G; Shin, Byung-Sik; Dever, Thomas E; Ramakrishnan, V; Fernández, Israel S

2016-05-09

Viral mRNA sequences with a type IV IRES are able to initiate translation without any host initiation factors. Initial recruitment of the small ribosomal subunit as well as two translocation steps before the first peptidyl transfer are essential for the initiation of translation by these mRNAs. Using electron cryomicroscopy (cryo-EM) we have structurally characterized at high resolution how the Cricket Paralysis Virus Internal Ribosomal Entry Site (CrPV-IRES) binds the small ribosomal subunit (40S) and the translocation intermediate stabilized by elongation factor 2 (eEF2). The CrPV-IRES restricts tvhe otherwise flexible 40S head to a conformation compatible with binding the large ribosomal subunit (60S). Once the 60S is recruited, the binary CrPV-IRES/80S complex oscillates between canonical and rotated states (Fernández et al., 2014; Koh et al., 2014), as seen for pre-translocation complexes with tRNAs. Elongation factor eEF2 with a GTP analog stabilizes the ribosome-IRES complex in a rotated state with an extra ~3 degrees of rotation. Key residues in domain IV of eEF2 interact with pseudoknot I (PKI) of the CrPV-IRES stabilizing it in a conformation reminiscent of a hybrid tRNA state. The structure explains how diphthamide, a eukaryotic and archaeal specific post-translational modification of a histidine residue of eEF2, is involved in translocation.

A Latent Variable Approach to Determining the Structure of Executive Function in Preschool Children

ERIC Educational Resources Information Center

Miller, Michael R.; Giesbrecht, Gerald F.; Muller, Ulrich; McInerney, Robert J.; Kerns, Kimberly A.

2012-01-01

The composition of executive function (EF) in preschool children was examined using confirmatory factor analysis (CFA). A sample of 129 children between 3 and 5 years of age completed a battery of EF tasks. Using performance indicators of working memory and inhibition similar to previous CFA studies with preschoolers, we replicated a unitary EF…

RESEARCH INVESTIGATIONS ON THE PROTEOME: 1. MECHANISMS OF REGULATING PROTEIN SYNTHESIS, AND 2. GLOBAL CHARACTERIZATION OF PROTEOMIC RESPONSES TO ARSENIC EXPOSURES

EPA Science Inventory

Eukaryotic Elongation Factor 2 (eEF2) mediates translocation in protein synthesis. eEF2 is modified by two post-translational modifications: the phosphorylation of Thr57 in the G domain and a unique conversion of His699 to diphthamide at the tip of domain IV. Diphthamide is the t...

The Role of the Executive Functions in School Achievement at the End of Grade 1

ERIC Educational Resources Information Center

Monette, Sebastien; Bigras, Marc; Guay, Marie-Claude

2011-01-01

The aim of this study was to determine the role of executive functions (EFs) in early school achievement when a variety of potential confounding factors were controlled. Measures of EF (inhibition, flexibility, and working memory) and school readiness were administered to a sample of 85 kindergartners (39 boys and 46 girls, 5-6 years old). School…

A Comparison of Inventoried and Measured U.S. Urban/Industrial Hg Emission Factors during the NOMADSS Experiment

NASA Astrophysics Data System (ADS)

Ambrose, J. L., II; Gratz, L.; Jaffe, D. A.; Apel, E. C.; Campos, T. L.; Flocke, F. M.; Guenther, A. B.; Hornbrook, R. S.; Karl, T.; Kaser, L.; Knapp, D. J.; Weinheimer, A. J.; Cantrell, C. A.; Mauldin, L.; Yuan, B.

2014-12-01

We performed an airborne survey of some large anthropogenic mercury (Hg) emission sources in the Southeast U.S. during the 2013 Nitrogen, Oxidants, Mercury and Aerosol Distribution, Sources, and Sinks (NOMADSS) experiment. The observations included speciated atmospheric Hg, and tracers of urban/industrial emissions and associated photochemistry (e.g., carbon monoxide, CO; carbon dioxide, CO2; sulfur dioxide, SO2; nitrogen oxides (NOx); volatile organic compounds, VOCs; ozone, O3; hydroxyl radical, HO·; sulfuric acid, H2SO4) and were made from the National Science Foundation's/National Center for Atmospheric Research's C-130 research aircraft. Mercury was measured using the University of Washington's Detector for Oxidized Hg Species. We derived Hg emission factors (EF) for several U.S. urban areas and large industrial point sources, including coal-fired power plants (CFPPs) in Louisiana, Pennsylvania, Texas, and West Virginia. We compared our measured Hg EFs with inventory-based values from two separate Hg emission inventories provided by the U.S. Environmental Protection Agency - the National Emissions Inventory (NEI) and the Toxics Release Inventory (TRI). We also performed an inter-comparison of the inventory-based Hg EFs. For the CFPPs sampled, we find that actual Hg emissions differed from inventoried values by more than a factor of two in some cases. Measured Hg EFs were weakly correlated with values reported in the NEI: m = 0.71; r2 = 0.47 (p = 0.06; n = 8), whereas EFs derived from the TRI were not meaningfully predictive of the measured values: m = -3.3; r2 = 0.61 (p < 0.05; n = 8). Median absolute differences between measured and inventory-based EFs were ≥50%, relative to the inventory values. The median absolute average difference between the Hg EFs reported in the two inventories was approximately 40%. Our results place quantitative constraints on uncertainties associated with the inventoried Hg emissions. Additionally, our results suggest that the current formulation of the Hg emission inventories critically limits our ability to accurately predict the transport and fate of U.S. urban/industrial emissions of Hg to the atmosphere. These findings are broadly relevant to the design and use of emission inventories for industrial hazardous air pollutants.

Road vehicle emission factors development: A review

NASA Astrophysics Data System (ADS)

Franco, Vicente; Kousoulidou, Marina; Muntean, Marilena; Ntziachristos, Leonidas; Hausberger, Stefan; Dilara, Panagiota

2013-05-01

Pollutant emissions need to be accurately estimated to ensure that air quality plans are designed and implemented appropriately. Emission factors (EFs) are empirical functional relations between pollutant emissions and the activity that causes them. In this review article, the techniques used to measure road vehicle emissions are examined in relation to the development of EFs found in emission models used to produce emission inventories. The emission measurement techniques covered include those most widely used for road vehicle emissions data collection, namely chassis and engine dynamometer measurements, remote sensing, road tunnel studies and portable emission measurements systems (PEMS). The main advantages and disadvantages of each method with regards to emissions modelling are presented. A review of the ways in which EFs may be derived from test data is also performed, with a clear distinction between data obtained under controlled conditions (engine and chassis dynamometer measurements using standard driving cycles) and measurements under real-world operation.

Pathophysiology, Evaluation, and Management of Edema in Childhood Nephrotic Syndrome

PubMed Central

Ellis, Demetrius

2016-01-01

Generalized edema is a major presenting clinical feature of children with nephrotic syndrome (NS) exemplified by such primary conditions as minimal change disease (MCD). In these children with classical NS and marked proteinuria and hypoalbuminemia, the ensuing tendency to hypovolemia triggers compensatory physiological mechanisms, which enhance renal sodium (Na+) and water retention; this is known as the “underfill hypothesis.” Edema can also occur in secondary forms of NS and several other glomerulonephritides, in which the degree of proteinuria and hypoalbuminemia, are variable. In contrast to MCD, in these latter conditions, the predominant mechanism of edema formation is “primary” or “pathophysiological,” Na+ and water retention; this is known as the “overfill hypothesis.” A major clinical challenge in children with these disorders is to distinguish the predominant mechanism of edema formation, identify other potential contributing factors, and prevent the deleterious effects of diuretic regimens in those with unsuspected reduced effective circulatory volume (i.e., underfill). This article reviews the Starling forces that become altered in NS so as to tip the balance of fluid movement in favor of edema formation. An understanding of these pathomechanisms then serves to formulate a more rational approach to prevention, evaluation, and management of such edema. PMID:26793696

Longitudinal Links between Executive Function, Anger, and Aggression in Middle Childhood.

PubMed

Rohlf, Helena L; Holl, Anna K; Kirsch, Fabian; Krahé, Barbara; Elsner, Birgit

2018-01-01

Previous research has indicated that executive function (EF) is negatively associated with aggressive behavior in childhood. However, there is a lack of longitudinal studies that have examined the effect of deficits in EF on aggression over time and taken into account different forms and functions of aggression at the same time. Furthermore, only few studies have analyzed the role of underlying variables that may explain the association between EF and aggression. The present study examined the prospective paths between EF and different forms (physical and relational) and functions (reactive and proactive) of aggression. The habitual experience of anger was examined as a potential underlying mechanism of the link between EF and aggression, because the tendency to get angry easily has been found to be both a consequence of deficits in EF and a predictor of aggression. The study included 1,652 children (between 6 and 11 years old at the first time point), who were followed over three time points (T1, T2, and T3) covering 3 years. At T1, a latent factor of EF comprised measures of planning, rated via teacher reports, as well as inhibition, set shifting, and working-memory updating, assessed experimentally. Habitual anger experience was assessed via parent reports at T1 and T2. The forms and functions of aggression were measured via teacher reports at all three time points. Structural equation modeling revealed that EF at T1 predicted physical, relational, and reactive aggression at T3, but was unrelated to proactive aggression at T3. Furthermore, EF at T1 was indirectly linked to physical aggression at T3, mediated through habitual anger experience at T2. The results indicate that deficits in EF influence the later occurrence of aggression in middle childhood, and the tendency to get angry easily mediates this relation.

Executive function and falls in older adults: new findings from a five-year prospective study link fall risk to cognition.

PubMed

Mirelman, Anat; Herman, Talia; Brozgol, Marina; Dorfman, Moran; Sprecher, Elliot; Schweiger, Avraham; Giladi, Nir; Hausdorff, Jeffrey M

2012-01-01

Recent findings suggest that executive function (EF) plays a critical role in the regulation of gait in older adults, especially under complex and challenging conditions, and that EF deficits may, therefore, contribute to fall risk. The objective of this study was to evaluate if reduced EF is a risk factor for future falls over the course of 5 years of follow-up. Secondary objectives were to assess whether single and dual task walking abilities, an alternative window into EF, were associated with fall risk. We longitudinally followed 256 community-living older adults (age: 76.4±4.5 yrs; 61% women) who were dementia free and had good mobility upon entrance into the study. At baseline, a computerized cognitive battery generated an index of EF, attention, a closely related construct, and other cognitive domains. Gait was assessed during single and dual task conditions. Falls data were collected prospectively using monthly calendars. Negative binomial regression quantified risk ratios (RR). After adjusting for age, gender and the number of falls in the year prior to the study, only the EF index (RR: .85; CI: .74-.98, p = .021), the attention index (RR: .84; CI: .75-.94, p = .002) and dual tasking gait variability (RR: 1.11; CI: 1.01-1.23; p = .027) were associated with future fall risk. Other cognitive function measures were not related to falls. Survival analyses indicated that subjects with the lowest EF scores were more likely to fall sooner and more likely to experience multiple falls during the 66 months of follow-up (p<0.02). These findings demonstrate that among community-living older adults, the risk of future falls was predicted by performance on EF and attention tests conducted 5 years earlier. The present results link falls among older adults to cognition, indicating that screening EF will likely enhance fall risk assessment, and that treatment of EF may reduce fall risk.

Longitudinal Links between Executive Function, Anger, and Aggression in Middle Childhood

PubMed Central

Rohlf, Helena L.; Holl, Anna K.; Kirsch, Fabian; Krahé, Barbara; Elsner, Birgit

2018-01-01

Previous research has indicated that executive function (EF) is negatively associated with aggressive behavior in childhood. However, there is a lack of longitudinal studies that have examined the effect of deficits in EF on aggression over time and taken into account different forms and functions of aggression at the same time. Furthermore, only few studies have analyzed the role of underlying variables that may explain the association between EF and aggression. The present study examined the prospective paths between EF and different forms (physical and relational) and functions (reactive and proactive) of aggression. The habitual experience of anger was examined as a potential underlying mechanism of the link between EF and aggression, because the tendency to get angry easily has been found to be both a consequence of deficits in EF and a predictor of aggression. The study included 1,652 children (between 6 and 11 years old at the first time point), who were followed over three time points (T1, T2, and T3) covering 3 years. At T1, a latent factor of EF comprised measures of planning, rated via teacher reports, as well as inhibition, set shifting, and working-memory updating, assessed experimentally. Habitual anger experience was assessed via parent reports at T1 and T2. The forms and functions of aggression were measured via teacher reports at all three time points. Structural equation modeling revealed that EF at T1 predicted physical, relational, and reactive aggression at T3, but was unrelated to proactive aggression at T3. Furthermore, EF at T1 was indirectly linked to physical aggression at T3, mediated through habitual anger experience at T2. The results indicate that deficits in EF influence the later occurrence of aggression in middle childhood, and the tendency to get angry easily mediates this relation. PMID:29535615

Clinical outcome of extended-field irradiation vs. pelvic irradiation using intensity-modulated radiotherapy for cervical cancer.

PubMed

Ouyang, Yi; Wang, Yanhong; Chen, Kai; Cao, Xinping; Zeng, Yiming

2017-12-01

The aim of the present study was to evaluate the distinctions in survival and toxicity between patients with cervical cancer with common iliac node or para-aortic node involvement, who were treated with extended-field intensity-modulated radiotherapy (EF-IMRT) and patients with or without lower involved pelvic nodes, who were treated with pelvic IMRT. A total of 55 patients treated with EF-IMRT and 52 patients treated with pelvic IMRT at the Sun Yat-Sen University Cancer Center (Guangzhou, China) were retrospectively analyzed. Patients treated with EF-IMRT had the highest level of lymph node involvement to the para-aortic or common iliac nodes, while patients treated with pelvic IMRT had no para-aortic or common iliac nodes involved (P<0.001). The median follow-up time was 29.5 months. The 3-year overall survival (OS) rates of EF-IMRT and pelvic IMRT were 79.4 and 82.3% (P=0.45), respectively, and the 3-year disease-free survival (DFS) rates of EF-IMRT and pelvic IMRT were 61.0 and 73.7% (P=0.55), respectively. Cox's regression analysis revealed that EF irradiation was a protective prognostic factor for OS and DFS. A total of 16 patients in the EF-IMRT group and 13 patients in the pelvic IMRT group experienced treatment failure (P=0.67), with the patterns of failure being the same for the two groups (P=0.88). The cumulative incidence of grade 3 and 4 acute toxicities in the EF-IMRT group was 34.5%, in comparison with 19.2% in the pelvic group (P=0.048). The results of the present study suggest that patients with cervical cancer with grossly involved common iliac or para-aortic nodes should be electively subjected to EF irradiation to improve the survival and alter patterns of recurrence. Notably, EF irradiation delivered via IMRT exhibits an increased toxicity incidence, however, this remains within an acceptable range.

Clinical outcome of extended-field irradiation vs. pelvic irradiation using intensity-modulated radiotherapy for cervical cancer

PubMed Central

Ouyang, Yi; Wang, Yanhong; Chen, Kai; Cao, Xinping; Zeng, Yiming

2017-01-01

The aim of the present study was to evaluate the distinctions in survival and toxicity between patients with cervical cancer with common iliac node or para-aortic node involvement, who were treated with extended-field intensity-modulated radiotherapy (EF-IMRT) and patients with or without lower involved pelvic nodes, who were treated with pelvic IMRT. A total of 55 patients treated with EF-IMRT and 52 patients treated with pelvic IMRT at the Sun Yat-Sen University Cancer Center (Guangzhou, China) were retrospectively analyzed. Patients treated with EF-IMRT had the highest level of lymph node involvement to the para-aortic or common iliac nodes, while patients treated with pelvic IMRT had no para-aortic or common iliac nodes involved (P<0.001). The median follow-up time was 29.5 months. The 3-year overall survival (OS) rates of EF-IMRT and pelvic IMRT were 79.4 and 82.3% (P=0.45), respectively, and the 3-year disease-free survival (DFS) rates of EF-IMRT and pelvic IMRT were 61.0 and 73.7% (P=0.55), respectively. Cox's regression analysis revealed that EF irradiation was a protective prognostic factor for OS and DFS. A total of 16 patients in the EF-IMRT group and 13 patients in the pelvic IMRT group experienced treatment failure (P=0.67), with the patterns of failure being the same for the two groups (P=0.88). The cumulative incidence of grade 3 and 4 acute toxicities in the EF-IMRT group was 34.5%, in comparison with 19.2% in the pelvic group (P=0.048). The results of the present study suggest that patients with cervical cancer with grossly involved common iliac or para-aortic nodes should be electively subjected to EF irradiation to improve the survival and alter patterns of recurrence. Notably, EF irradiation delivered via IMRT exhibits an increased toxicity incidence, however, this remains within an acceptable range. PMID:29344136

Hyperdiploidy with 58-66 chromosomes in childhood B-acute lymphoblastic leukemia is highly curable: 58951 CLG-EORTC results.

PubMed

Dastugue, Nicole; Suciu, Stefan; Plat, Geneviève; Speleman, Frank; Cavé, Hélène; Girard, Sandrine; Bakkus, Marleen; Pagès, Marie Pierre; Yakouben, Karima; Nelken, Brigitte; Uyttebroeck, Anne; Gervais, Carine; Lutz, Patrick; Teixeira, Manuel R; Heimann, Pierre; Ferster, Alice; Rohrlich, Pierre; Collonge, Marie Agnès; Munzer, Martine; Luquet, Isabelle; Boutard, Patrick; Sirvent, Nicolas; Karrasch, Matthias; Bertrand, Yves; Benoit, Yves

2013-03-28

The aim of our study was to analyze the factors contributing to heterogeneity of prognosis in patients with hyperdiploidy>50 chromosomes (HD>50), a group of B-cell precursor acute lymphoblastic leukemia with favorable outcome. The 541 HD>50 patients registered prospectively in the 58951 European Organisation for Research and Treatment of Cancer (EORTC) Children's Leukemia Group (CLG) trial, identified by karyotype (446 patients) and by DNA index (DI) (490 patients), had a 6-year event-free survival (EFS) of 89.0% (standard error [SE] = 1.5%) and a 6-year overall survival (OS) of 95.9% (SE = 0.9%). The strongest prognostic factor was the modal number of chromosomes (MNC): the 6-year EFS of 51-53, 54-57, and 58-66 MNC groups were 80%, 89%, and 99%, respectively (P < .0001). Ploidy assessed by DI was also a favorable factor: the higher the DI, the better the outcome. The 6-year EFS of the 3 subgroups of DI < 1.16/≥1.16-<1.24/≥1.24 were 83%, 90%, and 95%, respectively (P = .009). All usual combinations of trisomies (chromosomes 4, 10, 17, 18) were significant favorable factors but had lower EFS when MNC was lower than 58. In multivariate analysis, MNC remained the strongest factor. Consequently, the best indicator for excellent outcome was ploidy assessed by karyotype because patients with 58-66 chromosomes stood every chance of being cured (OS of 100% at 6-year follow-up) with less-intensive therapy. This trial was registered at www.clinicaltrials.gov as #NCT00003728. Registered: http://www.eortc.org/, http://clinicaltrials.gov/show/NCT00003728.

Tumor Volume and Patient Weight as Predictors of Outcome in Children with Intermediate Risk Rhabdomyosarcoma (RMS): A Report from the Children’s Oncology Group

PubMed Central

Rodeberg, David A.; Stoner, Julie A.; Garcia-Henriquez, Norbert; Randall, R. Lor; Spunt, Sheri L.; Arndt, Carola A.; Kao, Simon; Paidas, Charles N.; Million, Lynn; Hawkins, Douglas S.

2010-01-01

Background To compare tumor volume and patient weight vs. traditional factors of tumor diameter and patient age, to determine which parameters best discriminates outcome among intermediate risk RMS patients. Methods Complete patient information for non-metastatic RMS patients enrolled in the Children’s Oncology Group (COG) intermediate risk study D9803 (1999–2005) was available for 370 patients. The Kaplan-Meier method was used to estimate survival distributions. A recursive partitioning model was used to identify prognostic factors associated with event-free survival (EFS). Cox-proportional hazards regression models were used to estimate the association between patient characteristics and the risk of failure or death. Results For all intermediate risk patients with RMS, a recursive partitioning algorithm for EFS suggests that prognostic groups should optimally be defined by tumor volume (transition point 20 cm3), weight (transition point 50 kg), and embryonal histology. Tumor volume and patient weight added significant outcome information to the standard prognostic factors including tumor diameter and age (p=0.02). The ability to resect the tumor completely was not significantly associated with the size of the patient, and patient weight did not significantly modify the association between tumor volume and EFS after adjustment for standard risk factors (p=0.2). Conclusion The factors most strongly associated with EFS were tumor volume, patient weight, and histology. Based on regression modeling, volume and weight are superior predictors of outcome compared to tumor diameter and patient age in children with intermediate risk RMS. Prognostic performance of tumor volume and patient weight should be assessed in an independent prospective study. PMID:24048802

Change the management of patients with heart failure: Rationale and design of the CHAMP-HF registry.

PubMed

DeVore, Adam D; Thomas, Laine; Albert, Nancy M; Butler, Javed; Hernandez, Adrian F; Patterson, J Herbert; Spertus, John A; Williams, Fredonia B; Turner, Stuart J; Chan, Wing W; Duffy, Carol I; McCague, Kevin; Mi, Xiaojuan; Fonarow, Gregg C

2017-07-01

Heart failure (HF) with reduced ejection fraction (HFrEF) is a common and costly condition that diminishes patients' health status and confers a poor prognosis. Despite the availability of multiple guideline-recommended pharmacologic and cardiac device therapies for patients with chronic HFrEF, outcomes remain suboptimal. Currently, there is limited insight into the rationale underlying clinical decisions by health care providers and patient factors that guide the use and intensity of outpatient HF treatments. A better understanding of current practice patterns has the potential to improve patients' outcomes. The CHAnge the Management of Patients with Heart Failure (CHAMP-HF) registry will evaluate the care and outcomes of patients with chronic HFrEF by assessing real-world treatment patterns, as well as the reasons for and barriers to medication treatment changes. CHAMP-HF will enroll approximately 5,000 patients with chronic HFrEF (left ventricular ejection fraction ≤40%) at approximately 150 US sites, and patients will be followed for a maximum duration of 24 months. Participating sites will collect data from both providers (HF history, examination findings, results of diagnostic studies, pharmacotherapy treatment patterns, decision-making factors, and clinical outcomes) and patients (medication adherence and patient-reported outcomes). The CHAMP-HF registry will provide a unique opportunity to study practice patterns and the adoption of new HF therapies across a diverse mix of health care providers and outpatient practices in the United States that care for HFrEF patients. Copyright © 2017 Elsevier Inc. All rights reserved.

Is multifocality a prognostic factor in childhood hepatoblastoma?

PubMed

Saettini, Francesco; Conter, Valentino; Provenzi, Massimo; Rota, Matteo; Giraldi, Eugenia; Foglia, Carlo; Cavalleri, Laura; D'Antiga, Lorenzo

2014-09-01

The aim of this study was to assess the prognostic value of multifocality and the effectiveness of two different therapeutic strategies in patients with newly diagnosed hepatoblastoma. Between 1998 and 2011, 31 patients diagnosed with hepatoblastoma were referred to Ospedale Papa Giovanni XXIII, Bergamo, Italy. Patients were stratified according to SIOPEL protocols into high-risk (HR if AFP <100 ng/mL and/or PRETEXT IV and/or vascular invasion and/or extra-hepatic intra-abdominal disease and/or metastases) and standard-risk (SR, all others). The patient data we evaluated were: multifocality; patient age; gender; platelet count; AFP level at diagnosis, during treatment and follow-up; histotype; gestational age; birth weight; surgery (either resection or transplantation) and chemotherapy regimen adopted before and after surgery. The outcome measures were event free survival (EFS) and overall survival (OS); survival curves were estimated according to Kaplan-Meier. EFS and OS were associated significantly with multifocality (3-year EFS 40% vs. 95%, P = 0.006; 3-year OS 42% vs. 95%, P = 0.004). Multivariate analysis demonstrated that multifocality predicts lower EFS (hazard ratio 10.01, P = 0.007). Other factors at diagnosis did not reach statistical significance. A marked treatment dependent improvement was associated with intensive chemotherapy given both before and after liver transplantation (P = 0.06). Patients diagnosed with multifocal tumors had lower EFS levels. Multifocality should be taken into account for future stratification and further studied to assess genetic profile, immunochemistry and prognostic role. © 2014 Wiley Periodicals, Inc.

Class I and II Small Heat Shock Proteins Together with HSP101 Protect Protein Translation Factors during Heat Stress1[OPEN

PubMed Central

Basha, Eman; Fowler, Mary E.; Kim, Minsoo; Bordowitz, Juliana; Katiyar-Agarwal, Surekha

2016-01-01

The ubiquitous small heat shock proteins (sHSPs) are well documented to act in vitro as molecular chaperones to prevent the irreversible aggregation of heat-sensitive proteins. However, the in vivo activities of sHSPs remain unclear. To investigate the two most abundant classes of plant cytosolic sHSPs (class I [CI] and class II [CII]), RNA interference (RNAi) and overexpression lines were created in Arabidopsis (Arabidopsis thaliana) and shown to have reduced and enhanced tolerance, respectively, to extreme heat stress. Affinity purification of CI and CII sHSPs from heat-stressed seedlings recovered eukaryotic translation elongation factor (eEF) 1B (α-, β-, and γ-subunits) and eukaryotic translation initiation factor 4A (three isoforms), although the association with CI sHSPs was stronger and additional proteins involved in translation were recovered with CI sHSPs. eEF1B subunits became partially insoluble during heat stress and, in the CI and CII RNAi lines, showed reduced recovery to the soluble cell fraction after heat stress, which was also dependent on HSP101. Furthermore, after heat stress, CI sHSPs showed increased retention in the insoluble fraction in the CII RNAi line and vice versa. Immunolocalization revealed that both CI and CII sHSPs were present in cytosolic foci, some of which colocalized with HSP101 and with eEF1Bγ and eEF1Bβ. Thus, CI and CII sHSPs have both unique and overlapping functions and act either directly or indirectly to protect specific translation factors in cytosolic stress granules. PMID:27474115

Fucoxanthin Inhibits the Inflammation Response in Paw Edema Model through Suppressing MAPKs, Akt, and NFκB.

PubMed

Choi, Jun-Hui; Kim, Na-Hyun; Kim, Sung-Jun; Lee, Hyo-Jeong; Kim, Seung

2016-03-01

Undaria pinnatifida is a well-known traditional Korean food with a variety of biological activities. Carrageenan (carr) is commonly used to induce paw edema in animal models. This study was designed to elucidate the processes underlying the anti-inflammatory effect of fucoxanthin isolated from the sporophyll of U. pinnatifida in carr-induced paw edema in ICR mice. Fucoxanthin significantly decreased carr-induced increased nitric oxide levels in the plasma of mice with carr-induced paw edema. Fucoxanthin protected catalase (CAT) and superoxide dismutase (SOD) activity against disruption in mice with carr-induced paw edema. In addition, fucoxanthin repressed carr-induced activation of inducible nitric oxide synthase, cyclooxygenase-2, and nuclear factor kappa B, as well as carr-induced phosphorylation of mitogen-activated protein kinase, extracellular signal-regulated kinase, c-Jun N-terminal kinase, p38, and protein kinase B/Akt. These results suggest that fucoxanthin may have therapeutic potential as a treatment for patients with inflammatory diseases. © 2015 Wiley Periodicals, Inc.

[Effects of mercazolyl and L-thyroxine on the antiedematous activity of immunotropic preparations during development of toxic brain edema and swelling].

PubMed

Platonov, I A; Anashchenkova, T A; Andreeva, T A

2008-01-01

Dysfunction of thyroid gland plays an important role in the pathogenesis of brain edema and swelling. Toxic brain edema and swelling was modeled under condition of hypo- and hyperfunction of thyroid gland. Mercazolyl and L-thyroxine ambiguously influence the development of toxic brain edema and swelling in rats. L-thyroxin (35.7 microg/kg) favors increase in the water content in brain tissue, which can be considered as synergism with the edematous factor and the formation of brain tissue susceptibility to the development of brain edema and swelling. The administration of mercazolyl (5 mg/kg) and L-thyroxin (35.7 microg/kg) with thymogen (10 microg/kg), thymalin (1.2 mg/kg), cycloferon (0.5 mg/kg) results in decreasing brain tissue density as compared to intact animals. Dysfunction of the thyroid gland leads to changes in pharmacodynamics of immune preparations, which results in a decrease of their antiedematous activity.

Temperature dependence of metal-enhanced fluorescence of photosystem I from Thermosynechococcus elongatus.

PubMed

Ashraf, Imran; Konrad, Alexander; Lokstein, Heiko; Skandary, Sepideh; Metzger, Michael; Djouda, Joseph M; Maurer, Thomas; Adam, Pierre M; Meixner, Alfred J; Brecht, Marc

2017-03-23

We report the temperature dependence of metal-enhanced fluorescence (MEF) of individual photosystem I (PSI) complexes from Thermosynechococcus elongatus (T. elongatus) coupled to gold nanoparticles (AuNPs). A strong temperature dependence of shape and intensity of the emission spectra is observed when PSI is coupled to AuNPs. For each temperature, the enhancement factor (EF) is calculated by comparing the intensity of individual AuNP-coupled PSI to the mean intensity of 'uncoupled' PSI. At cryogenic temperature (1.6 K) the average EF was 4.3-fold. Upon increasing the temperature to 250 K the EF increases to 84-fold. Single complexes show even higher EFs up to 441.0-fold. At increasing temperatures the different spectral pools of PSI from T. elongatus become distinguishable. These pools are affected differently by the plasmonic interactions and show different enhancements. The remarkable increase of the EFs is explained by a rate model including the temperature dependence of the fluorescence yield of PSI and the spectral overlap between absorption and emission spectra of AuNPs and PSI, respectively.

Electrostatics effects on Ca(2+) binding and conformational changes in EF-hand domains: Functional implications for EF-hand proteins.

PubMed

Ababou, Abdessamad; Zaleska, Mariola

2015-12-01

Mutations of Gln41 and Lys75 with nonpolar residues in the N-terminal domain of calmodulin (N-Cam) revealed the importance of solvation energetics in conformational change of Ca(2+) sensor EF-hand domains. While in general these domains have polar residues at these corresponding positions yet the extent of their conformational response to Ca(2+) binding and their Ca(2+) binding affinity can be different from N-Cam. Consequently, here we address the charge state of the polar residues at these positions. The results show that the charge state of these polar residues can affect substantially the conformational change and the Ca(2+) binding affinity of our N-Cam variants. Since all the variants kept their conformational activity in the presence of Ca(2+) suggests that the differences observed among them mainly originate from the difference in their molecular dynamics. Hence we propose that the molecular dynamics of Ca(2+) sensor EF-hand domains is a key factor in the multifunctional aspect of EF-hand proteins. Copyright © 2015 Elsevier Inc. All rights reserved.

Association between sleep-disordered breathing and arterial stiffness in heart failure patients with reduced or preserved ejection fraction.

PubMed

Suzuki, Satoshi; Yoshihisa, Akiomi; Sato, Yu; Watanabe, Shunsuke; Yokokawa, Tetsuro; Sato, Takamasa; Oikawa, Masayoshi; Kobayashi, Atsushi; Yamaki, Takayoshi; Kunii, Hiroyuki; Nakazato, Kazuhiko; Suzuki, Hitoshi; Saitoh, Shu-Ichi; Ishida, Takafumi; Takeishi, Yasuchika

2018-06-01

Sleep-disordered breathing (SDB) is associated with arterial stiffness, which may be one of the factors that lead to heart failure (HF). We examined the relationship between pulse wave velocity (PWV) and SDB in patients who have HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF). We measured the apnoea-hypopnoea index (AHI) by polysomnography, echocardiographic parameters, and PWV in 221 HF patients. Age, blood pressure, and PWV were higher in HFpEF (ejection fraction > 50%, n = 70) patients than in HFrEF (ejection fraction < 50%, n = 151) patients. All HF patients were divided into three groups according to AHI: none-to-mild SDB group (AHI < 15 times/h, n = 77), moderate SDB group (15 < AHI < 30 times/h, n = 59), and severe SDB group (AHI > 30 times/h, n = 85). Although blood pressure and echocardiographic parameters did not differ among the three groups, PWV was significantly higher in the severe SDB group than in the none-to-mild and moderate SDB groups (P = 0.002). When the HFrEF and HFpEF patients were analysed separately, PWV was significantly higher in the severe SDB group than in the none-to-mild and moderate SDB groups in patients with HFpEF (P = 0.002), but not in those with HFrEF (P = 0.068). In the multiple regression analysis to determine PWV, the presence of severe SDB was found to be an independent predictor of high PWV in HFpEF (β = 0.234, P = 0.005), but not in HFrEF patients. Severe SDB is associated with elevated arterial stiffness and may be related to the pathophysiology of HF, especially in HFpEF patients. © 2018 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.

[Fluocinolone acetonide (ILUVIEN®) micro-implant for chronic diabetic macular edema].

PubMed

Soubrane, G; Behar-Cohen, F

2015-02-01

Diabetic macular edema (DME) is a frequent complication of diabetic retinopathy and may cause severe visual loss. In this article, we examine the pathophysiology of DME and review various treatment options, such as laser photocoagulation, anti-vascular endothelial growth factor (VEGF) receptor antibodies, and steroids including ILUVIEN(®), which is a new sustained-release, non biodegradable, injectable, intravitreal micro-implant containing fluocinolone acetonide. The results of the FAME (Fluocinolone Acetonide in Diabetic Macular Edema) studies, conducted to evaluate the efficacy and safety of ILUVIEN(®) in DME, are discussed. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Increased survival and cell cycle progression pathways are required for EWS/FLI1-induced malignant transformation.

PubMed

Javaheri, Tahereh; Kazemi, Zahra; Pencik, Jan; Pham, Ha Tt; Kauer, Maximilian; Noorizadeh, Rahil; Sax, Barbara; Nivarthi, Harini; Schlederer, Michaela; Maurer, Barbara; Hofbauer, Maximillian; Aryee, Dave Nt; Wiedner, Marc; Tomazou, Eleni M; Logan, Malcolm; Hartmann, Christine; Tuckermann, Jan P; Kenner, Lukas; Mikula, Mario; Dolznig, Helmut; Üren, Aykut; Richter, Günther H; Grebien, Florian; Kovar, Heinrich; Moriggl, Richard

2016-10-13

Ewing sarcoma (ES) is the second most frequent childhood bone cancer driven by the EWS/FLI1 (EF) fusion protein. Genetically defined ES models are needed to understand how EF expression changes bone precursor cell differentiation, how ES arises and through which mechanisms of inhibition it can be targeted. We used mesenchymal Prx1-directed conditional EF expression in mice to study bone development and to establish a reliable sarcoma model. EF expression arrested early chondrocyte and osteoblast differentiation due to changed signaling pathways such as hedgehog, WNT or growth factor signaling. Mesenchymal stem cells (MSCs) expressing EF showed high self-renewal capacity and maintained an undifferentiated state despite high apoptosis. Blocking apoptosis through enforced BCL2 family member expression in MSCs promoted efficient and rapid sarcoma formation when transplanted to immunocompromised mice. Mechanistically, high BCL2 family member and CDK4, but low P53 and INK4A protein expression synergized in Ewing-like sarcoma development. Functionally, knockdown of Mcl1 or Cdk4 or their combined pharmacologic inhibition resulted in growth arrest and apoptosis in both established human ES cell lines and EF-transformed mouse MSCs. Combinatorial targeting of survival and cell cycle progression pathways could counteract this aggressive childhood cancer.

Increased survival and cell cycle progression pathways are required for EWS/FLI1-induced malignant transformation

PubMed Central

Javaheri, Tahereh; Kazemi, Zahra; Pencik, Jan; Pham, Ha TT; Kauer, Maximilian; Noorizadeh, Rahil; Sax, Barbara; Nivarthi, Harini; Schlederer, Michaela; Maurer, Barbara; Hofbauer, Maximillian; Aryee, Dave NT; Wiedner, Marc; Tomazou, Eleni M; Logan, Malcolm; Hartmann, Christine; Tuckermann, Jan P; Kenner, Lukas; Mikula, Mario; Dolznig, Helmut; Üren, Aykut; Richter, Günther H; Grebien, Florian; Kovar, Heinrich; Moriggl, Richard

2016-01-01

Ewing sarcoma (ES) is the second most frequent childhood bone cancer driven by the EWS/FLI1 (EF) fusion protein. Genetically defined ES models are needed to understand how EF expression changes bone precursor cell differentiation, how ES arises and through which mechanisms of inhibition it can be targeted. We used mesenchymal Prx1-directed conditional EF expression in mice to study bone development and to establish a reliable sarcoma model. EF expression arrested early chondrocyte and osteoblast differentiation due to changed signaling pathways such as hedgehog, WNT or growth factor signaling. Mesenchymal stem cells (MSCs) expressing EF showed high self-renewal capacity and maintained an undifferentiated state despite high apoptosis. Blocking apoptosis through enforced BCL2 family member expression in MSCs promoted efficient and rapid sarcoma formation when transplanted to immunocompromised mice. Mechanistically, high BCL2 family member and CDK4, but low P53 and INK4A protein expression synergized in Ewing-like sarcoma development. Functionally, knockdown of Mcl1 or Cdk4 or their combined pharmacologic inhibition resulted in growth arrest and apoptosis in both established human ES cell lines and EF-transformed mouse MSCs. Combinatorial targeting of survival and cell cycle progression pathways could counteract this aggressive childhood cancer. PMID:27735950

Short-Lived Buildings in China: Impacts on Water, Energy, and Carbon Emissions.

PubMed

Cai, Wenjia; Wan, Liyang; Jiang, Yongkai; Wang, Can; Lin, Lishen

2015-12-15

This paper has changed the vague understanding that "the short-lived buildings have huge environmental footprints (EF)" into a concrete one. By estimating the annual floor space of buildings demolished and calibrating the average building lifetime in China, this paper compared the EF under various assumptive extended buildings' lifetime scenarios based on time-series environmental-extended input-output model. Results show that if the average buildings' lifetime in China can be extended from the current 23.2 years to their designed life expectancy, 50 years, in 2011, China can reduce 5.8 Gt of water withdrawal, 127.1 Mtce of energy consumption, and 426.0 Mt of carbon emissions, each of which is equivalent to the corresponding annual EF of Belgium, Mexico, and Italy. These findings will urge China to extend the lifetime of existing and new buildings, in order to reduce the EF from further urbanization. This paper also verifies that the lifetime of a product or the replacement rate of a sector is a very important factor that influences the cumulative EF. When making policies to reduce the EF, adjusting people's behaviors to extend the lifetime of products or reduce the replacement rate of sectors may be a very simple and cost-effective option.

Modulation of spike coding by subthreshold extracellular electric fields and neuronal morphology

NASA Astrophysics Data System (ADS)

Wei, Xile; Li, Bingjie; Lu, Meili; Yi, Guosheng; Wang, Jiang

2015-07-01

We use a two-compartment model, which includes soma and dendrite, to explore how extracellular subthreshold sinusoidal electric fields (EFs) influence the spike coding of an active neuron. By changing the intensity and the frequency of subthreshold EFs, we find that subthreshold EFs indeed affect neuronal coding remarkably within several stimulus frequency windows where the field effects on spike timing are stronger than that on spiking rate. The field effects are maximized at several harmonics of the intrinsic spiking frequency of an active neuron. Our findings implicate the potential resonance mechanism underlying subthreshold field effects. We also discuss how neuronal morphologic properties constrain subthreshold EF effects on spike timing. The morphologic properties are represented by two parameters, gc and p, where gc is the internal conductance between soma and dendrite and geometric factor p characterizes the proportion of area occupied by soma. We find that the contribution to field effects from the variation of p is stronger than that from gc, which suggests that neuronal geometric features play a crucial role in subthreshold field effects. Theoretically, these insights into how subthreshold sinusoidal EFs modulate ongoing neuron behaviors could contribute to uncovering the relevant mechanism of subthreshold sinusoidal EFs effects on neuronal coding. Furthermore, they are useful in rationally designing noninvasive brain stimulation strategies and developing electromagnetic stimulus techniques.

Seasonal variations in methane and nitrous oxide emissions factors in northern Australian savanna woodlands

NASA Astrophysics Data System (ADS)

Meyer, C. P.(Mick); Cook, Garry; Reisen, Fabienne; Russell-Smith, Jeremy; Maier, Stefan; Schatz, Jon; Yates, Cameron; Watt, Felicity

2010-05-01

Burning of savannas and grasslands consumes more than one third of the total annual biomass burning globally. In Australia, savanna fires emit annually from 2% to 4% of Australia's greenhouse gas emissions. This has led to efforts to reduce savanna burning emissions through early season prescribed burning. These programs aim to change the fire seasonality from predominantly high intensity late season fires which are characterized by low levels of patchiness and high burning efficiencies to early-season fires characterized by low intensity, a high degree of patchiness and low burning efficiency. The result is a net reduction in fire area and associated carbon emissions. Mitigation of greenhouse gas emissions is predicated on there being little change in methane (CH4) or nitrous oxide (N2O) emission factors (EFs) as the fire season progresses, however, recent analysis of the emission characteristics of African savanna fires by Korontzi et al., indicates CH4-EF, in particular, could decline substantially as the fire season progresses. If this also occurs in Australian savanna woodlands, then the current mitigation strategy could be ineffective. To address the issue a series of field campaigns were undertaken in the savanna woodlands of Western Arnhem land, Australia to quantify the variability in CH4 and N2O EFs throughout the fire season. This study compared CH4 and N2O EFs measured in smoke sampled from prescribed burning in late June/early July with those from late season fires in early October. It concentrated on the two major vegetation classes in Western Arnhemland; eucalypt open woodland, in which the fuel is composed predominantly tree leaf-litter supplemented by senescent native Sorghum, and sandstone heaths which are dominated by Spinifex hummocks. There were no significant differences in CH4 EFs between early or late season fires, however there were substantial differences between vegetation classes. The woodland emitted 0.3% of fuel carbon as CH4 compared to 0.15% in the sandstone heathland and pure Spinifex and Sorghum swords. The lower emission factors from the grasses compared to leaf litter can be entirely explained by higher combustion efficiency of grass fires. Emission of N2O were less dependent on combustion conditions; approximately 0.5% of fuel nitrogen was emitted as N2O, however there were no differences between early and late season fires or between vegetation classes. These results compare favorably with previous studies; the CH4-EF is similar to earlier measurements in open woodland, although the N2O-EF is lower than the value of 0.8% reported in previous work. Therefore we conclude that the proposed mitigation strategy is feasible and but the variation in EF with vegetation class calls for further quantification of EFs across all major vegetation types in the savanna regions.

Agmatine Attenuates Brain Edema and Apoptotic Cell Death after Traumatic Brain Injury.

PubMed

Kim, Jae Young; Lee, Yong Woo; Kim, Jae Hwan; Lee, Won Taek; Park, Kyung Ah; Lee, Jong Eun

2015-07-01

Traumatic brain injury (TBI) is associated with poor neurological outcome, including necrosis and brain edema. In this study, we investigated whether agmatine treatment reduces edema and apoptotic cell death after TBI. TBI was produced by cold injury to the cerebral primary motor cortex of rats. Agmatine was administered 30 min after injury and once daily until the end of the experiment. Animals were sacrificed for analysis at 1, 2, or 7 days after the injury. Various neurological analyses were performed to investigate disruption of the blood-brain barrier (BBB) and neurological dysfunction after TBI. To examine the extent of brain edema after TBI, the expression of aquaporins (AQPs), phosphorylation of mitogen-activated protein kinases (MAPKs), and nuclear translocation of nuclear factor-κB (NF-κB) were investigated. Our findings demonstrated that agmatine treatment significantly reduces brain edema after TBI by suppressing the expression of AQP1, 4, and 9. In addition, agmatine treatment significantly reduced apoptotic cell death by suppressing the phosphorylation of MAPKs and by increasing the nuclear translocation of NF-κB after TBI. These results suggest that agmatine treatment may have therapeutic potential for brain edema and neural cell death in various central nervous system diseases.

Management of diabetic macular edema with intravitreal dexamethasone implants: Expert recommendations using a Delphi-based approach.

PubMed

Giovannini, Alfonso; Parravano, Mariacristina; Ricci, Federico; Bandello, Francesco

2018-06-01

Despite being approved and effective, steroids, and especially dexamethasone intravitreal implants, still have a poorly-defined role in management of diabetic macular edema. In order to overcome some of the limitations in current recommendations, a group of experts met to define consensus on some of the most controversial issues on the use of dexamethasone intravitreal implants in daily management of diabetic macular edema. A Delphi-based approach was utilized to develop clinically relevant statements applicable to routine treatment settings. A Steering Committee composed of four experts formulated 30 relevant statements, which were voted upon by a panel of 40 ophthalmologists/retinal specialists from across Italy. Dexamethasone intravitreal implants were considered to be a valid first-line alternative to treatment with an anti-vascular endothelial growth factor agent and should be the first choice in pseudophakic and vitrectomized patients. A Pro Re Nata regimen was felt to be appropriate for retreatment with dexamethasone intravitreal implants while a 6-month waiting period was not considered suitable. Among steroid treatments, dexamethasone intravitreal implants were considered to have the best ocular tolerability. In patients with persistent macular edema after the loading-phase treatment with an anti-vascular endothelial growth factor, consensus was reached that clinicians should consider switching therapy to dexamethasone intravitreal implants. Moreover, dexamethasone intravitreal implants can reduce the treatment burden for individuals who are not able to cope with the more intensive treatment regimen required by anti-vascular endothelial growth factor therapy. While further studies are needed, this survey provides some key recommendations for clinicians treating diabetic macular edema that may be useful when choosing dexamethasone intravitreal implants in daily practice.

CHARACTERIZATION OF PARTICULATE MATTER EMISSION FROM OPEN BURNING OF RICE STRAW

PubMed Central

Oanh, Nguyen Thi Kim; Bich, Thuy Ly; Tipayarom, Danutawat; Manadhar, Bhai R.; Prapat, Pongkiatkul; Simpson, Christopher D.; Liu, L-J Sally

2010-01-01

Emission from field burning of crop residue, a common practice in many parts of the world today, has potential effects on air quality, atmosphere and climate. This study provides a comprehensive size and compositional characterization of particulate matter (PM) emission from rice straw (RS) burning using both in situ experiments (11 spread field burning) and laboratory hood experiments (3 pile and 6 spread burning) that were conducted during 2003–2006 in Thailand. The carbon balance and emission ratio method was used to determine PM emission factors (EF) in the field experiments. The obtained EFs varied from field to hood experiments reflecting multiple factors affecting combustion and emission. In the hood experiments, EFs were found to be depending on the burning types (spread or pile), moisture content and the combustion efficiency. In addition, in the field experiments, burning rate and EF were also influenced by weather conditions, i.e. wind. Hood pile burning produced significantly higher EF (20±8 g kg−1 RS) than hood spread burning (4.7±2.2 g kg−1 RS). The majority of PM emitted from the field burning was PM2.5 with EF of 5.1±0.7 g m−2 or 8.3±2.7 g kg−1 RS burned. The coarse PM fraction (PM10-2.5) was mainly generated by fire attention activities and was relatively small, hence the resulting EF of PM10 (9.4±3.5 g kg−1 RS) was not significantly higher than PM2.5. PM size distribution was measured across 8 size ranges (from <0.4 μm to >9.0 μm). The largest fractions of PM, EC and OC were associated with PM1.1. The most significant components in PM2.5 and PM10 include OC, water soluble ions and levoglucosan. Relative abundance of some methoxyphenols (e.g., acetylsyringone), PAHs (e.g., fluoranthene and pyrene), organochlorine pesticides and PCBs may also serve as additional signatures for the PM emission. Presence of these toxic compounds in PM of burning smoke increases the potential toxic effects of the emission. For illustration, an estimation of the annual RS field burning in Thailand was made using the obtained in situ field burning EFs and preliminary burning activity data. PMID:21243095

Prevalence and Clinical Significance of an E-Reversal Wave in the Left Ventricular Outflow Tract.

PubMed

Pressman, Gregg S; Matejkova, Magdalena; Horrow, Jay C; Pai, Ramdas G

2016-11-15

Diastolic waves are commonly seen in the left ventricular outflow tract on echocardiography. This work focuses on the E-reversal wave (Er) that occurs early in diastole, shortly after the mitral E wave. Factors associated with Er presence and velocity were investigated in a broad patient sample: 100 subjects with normal ejection fraction (EF >55%) and 100 subjects with reduced EF (<45%). Er presence was noted in 58% of the total cohort and correlated inversely with age. It was more common with normal EF (70% vs 45%, p = 0.0005) and was associated with higher mitral E velocity (78.3 ± 23.3 vs 68.4 ± 19.0 cm/s; p = 0.002) and septal e' velocity (6.7 ± 2.5 vs 5.3 ± 2.3 cm/s; p <0.0001). Er velocity was higher in the normal EF group (50 ± 18 vs 34 ± 13 cm/s, p <0.0001) and showed moderate correlation with septal e' velocity (r = 0.43; p <0.0001); 56 subjects experienced major adverse cardiovascular events (MACE) over 1.7 ± 0.3 years of follow-up. Those with an Er had less MACE (particularly heart failure), even after adjustment for multiple clinical and echocardiographic variables (OR 0.28, 95% CI 0.11 to 0.65; p = 0.003). When stratified by EF, the association between Er presence and MACE was significant only in the low EF group. Thus, Er occurs more commonly in younger subjects and those with preserved EF. It is associated with less MACE although this effect appears to be limited to patients with reduced EF. Copyright © 2016 Elsevier Inc. All rights reserved.

The existence of fertile hybrids of closely related model earthworm species, Eisenia andrei and E. fetida.

PubMed

Plytycz, Barbara; Bigaj, Janusz; Osikowski, Artur; Hofman, Sebastian; Falniowski, Andrzej; Panz, Tomasz; Grzmil, Pawel; Vandenbulcke, Franck

2018-01-01

Lumbricid earthworms Eisenia andrei (Ea) and E. fetida (Ef) are simultaneous hermaphrodites with reciprocal insemination capable of self-fertilization while the existence of hybridization of these two species was still debatable. During the present investigation fertile hybrids of Ea and Ef were detected. Virgin specimens of Ea and Ef were laboratory crossed (Ea+Ef) and their progeny was doubly identified. 1 -identified by species-specific maternally derived haploid mitochondrial DNA sequences of the COI gene being either 'a' for worms hatched from Ea ova or 'f' for worms hatched from Ef ova. 2 -identified by the diploid maternal/paternal nuclear DNA sequences of 28s rRNA gene being either 'AA' for Ea, 'FF' for Ef, or AF/FA for their hybrids derived either from the 'aA' or 'fF' ova, respectively. Among offspring of Ea+Ef pairs in F1 generation there were mainly aAA and fFF earthworms resulted from the facilitated self-fertilization and some aAF hybrids from aA ova but none fFA hybrids from fF ova. In F2 generation resulting from aAF hybrids mated with aAA a new generations of aAA and aAF hybrids were noticed, while aAF hybrids mated with fFF gave fFF and both aAF and fFA hybrids. Hybrids intercrossed together produced plenty of cocoons but no hatchlings independently whether aAF+aAF or aAF+fFA were mated. These results indicated that Ea and Ef species, easy to maintain in laboratory and commonly used as convenient models in biomedicine and ecotoxicology, may also serve in studies on molecular basis of interspecific barriers and mechanisms of introgression and speciation. Hypothetically, their asymmetrical hybridization can be modified by some external factors.

Predictors of outcome and methodological issues in children with acute lymphoblastic leukaemia in El Salvador.

PubMed

Bonilla, Miguel; Gupta, Sumit; Vasquez, Roberto; Fuentes, Soad L; deReyes, Gladis; Ribeiro, Raul; Sung, Lillian

2010-12-01

Most children with cancer live in low-income countries (LICs) where risk factors in paediatric acute lymphoblastic leukaemia (ALL) developed in high-income countries may not apply. We describe predictors of survival for children in El Salvador with ALL. We included patients <16 years diagnosed with ALL between January 2001 and July 2007 treated with the El Salvador-Guatemala-Honduras II protocol. Demographic, disease-related, socioeconomic and nutritional variables were examined as potential predictors of event-free survival (EFS) and overall survival (OS). 260/443 patients (58.7%) were classified as standard risk. Standard- and high-risk 5-year EFS were 56.3 ± 4.5% and 48.6 ± 5.5%; 5-year OS were 77.7 ± 3.8% and 61.9 ± 5.8%, respectively. Among standard-risk children, socioeconomic variables such as higher monthly income (hazard ratio [HR] per $100 = 0.84 [95% confidence interval (CI) 0.70-0.99; P=0.04]) and parental secondary education (HR = 0.49, 95% CI 0.29-0.84; P = 0.01) were associated with better EFS. Among high-risk children, higher initial white blood cell (HR per 10×10(9)/L = 1.03, 95% CI 1.02-1.05; P<0.001) predicted worse EFS; socioeconomic variables were not predictive. The difference in EFS and OS appeared related to overestimating OS secondary to poor follow-up after abandonment/relapse. Socioeconomic variables predicted worse EFS in standard-risk children while disease-related variables were predictive in high-risk patients. Further studies should delineate pathways through which socioeconomic status affects EFS in order to design effective interventions. EFS should be the primary outcome in LIC studies. Copyright © 2010 Elsevier Ltd. All rights reserved.

Short Communication: Emission of Oxygenated Polycyclic Aromatic Hydrocarbons from Biomass Pellet Burning in a Modern Burner for Cooking in China.

PubMed

Shen, Guofeng; Wei, Siye; Zhang, Yanyan; Wang, Rong; Wang, Bin; Li, Wei; Shen, Huizhong; Huang, Ye; Chen, Yuanchen; Chen, Han; Wei, Wen; Tao, Shu

2012-12-01

Biomass pellets are undergoing fast deployment widely in the world, including China. To this stage, there were limited studies on the emissions of various organic pollutants from the burning of those pellets. In addition to parent polycyclic aromatic hydrocarbons, oxygenated PAHs (oPAHs) have been received increased concerns. In this study, emission factors of oPAHs (EF oPAHs ) were measured for two types of pellets made from corn straw and pine wood, respectively. Two combustion modes with (mode II) and without (mode I) secondary side air supply in a modern pellet burner were investigated. For the purpose of comparison, EF oPAHs for raw fuels combusted in a traditional cooking stove were also measured. EF oPAHs were 348±305 and 396±387 µg/kg in the combustion mode II for pine wood and corn straw pellets, respectively. In mode I, measured EF oPAHs were 77.7±49.4 and 189±118 µg/kg, respectively. EFs in mode II were higher (2-5 times) than those in mode I mainly due to the decreased combustion temperature under more excess air. Compared to EF oPAHs for raw corn straw and pine wood burned in a traditional cooking stove, total EF oPAHs for the pellets in mode I were significantly lower ( p < 0.05 ), likely due to increased combustion efficiencies and change in fuel properties. However, the difference between raw biomass fuels and the pellets burned in mode II was not statistically significant. Taking both the increased thermal efficiencies and decreased EFs into consideration, substantial reduction in oPAH emission can be expected if the biomass pellets can be extensively used by rural residents.

Association of eating frequency with anthropometric indices and blood pressure in children and adolescents: the CASPIAN-IV Study.

PubMed

Kelishadi, Roya; Qorbani, Mostafa; Motlagh, Mohammad Esmaeil; Heshmat, Ramin; Ardalan, Gelayol; Bahreynian, Maryam

2016-01-01

This study was conducted to explore the association of eating frequency (EF) with anthropometric indices and blood pressure (BP) in children and adolescents. This nationwide cross-sectional study was performed on a multi-stage sample of 14,880 students, aged 6-18 years, living in 30 provinces in Iran. Parents were asked to report dietary intake of children as frequency of food groups and/or items. EF was defined as the sum of the daily consumption frequency of main meals and snacks. Association of EF with weight disorders, abdominal obesity, and elevated BP was assessed using different logistic regression models adjusted for potential confounding factors. Eating more frequently (≥ 6 vs. ≤ 3) was found among students who were at younger age (11.91 vs. 13.29 years) (p<0.001). Students who reported an EF of 4 (OR: 0.67, CI: 0.57-0.79), 5 (OR: 0.74, CI: 0.62-0.87), and 6 (OR: 0.54, CI: 0.44-0.65) had lower odds of being obese compared to those who had EF ≤ 3. Having EF of 4 (OR: 0.82, CI: 0.71-0.94), 5 (OR: 0.86, CI: 0.74-0.99), and ≥ 6 (OR: 0.73, CI: 0.63-0.85) was related to lower prevalence of abdominal adiposity. Higher EF was associated with lower mean values of anthropometric and BP measures, as well as with lower prevalence of generalized and abdominal obesity in children and adolescents. Longitudinal studies are needed to assess the long-term effects of EF on body composition in the pediatric age group. Copyright © 2016 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Transcatheter Interatrial Shunt Device for the Treatment of Heart Failure: Rationale and Design of the Randomized Trial to REDUCE Elevated Left Atrial Pressure in Heart Failure (REDUCE LAP-HF I).

PubMed

Feldman, Ted; Komtebedde, Jan; Burkhoff, Daniel; Massaro, Joseph; Maurer, Mathew S; Leon, Martin B; Kaye, David; Silvestry, Frank E; Cleland, John G F; Kitzman, Dalane; Kubo, Spencer H; Van Veldhuisen, Dirk J; Kleber, Franz; Trochu, Jean-Noël; Auricchio, Angelo; Gustafsson, Finn; Hasenfuβ, Gerd; Ponikowski, Piotr; Filippatos, Gerasimos; Mauri, Laura; Shah, Sanjiv J

2016-07-01

Heart failure with preserved ejection fraction (HFpEF), a major public health problem with high morbidity and mortality rates, remains difficult to manage because of a lack of effective treatment options. Although HFpEF is a heterogeneous clinical syndrome, elevated left atrial pressure-either at rest or with exertion-is a common factor among all forms of HFpEF and one of the primary reasons for dyspnea and exercise intolerance in these patients. On the basis of clinical experience with congenital interatrial shunts in mitral stenosis, it has been hypothesized that the creation of a left-to-right interatrial shunt to decompress the left atrium (without compromising left ventricular filling or forward cardiac output) is a rational, nonpharmacological strategy for alleviating symptoms in patients with HFpEF. A novel transcatheter interatrial shunt device has been developed and evaluated in patients with HFpEF in single-arm, nonblinded clinical trials. These studies have demonstrated the safety and potential efficacy of the device. However, a randomized, placebo-controlled evaluation of the device is required to further evaluate its safety and efficacy in patients with HFpEF. In this article, we give the rationale for a therapeutic transcatheter interatrial shunt device in HFpEF, and we describe the design of REDUCE Elevated Left Atrial Pressure in Heart Failure (REDUCE LAP-HF I), the first randomized controlled trial of a device-based therapy to reduce left atrial pressure in HFpEF. URL: http://www.clinicaltrials.gov. Unique identifier: NCT02600234. © 2016 American Heart Association, Inc.

The effect of monascin on hematoma clearance and edema after intracerebral hemorrhage in rats.

PubMed

Wang, Juan; Wang, Gaiqing; Yi, Jinying; Xu, Yi; Duan, Shuna; Li, Tong; Sun, Xin-Gang; Dong, Liang

2017-09-01

Intracerebral hemorrhage (ICH) is a particularly devastating form of stroke with high mortality and morbidity. Hematomas are the primary cause of neurologic deficits associated with ICH. The products of hematoma are recognized as neurotoxins and the main contributors to edema formation and tissue damage after ICH. Finding a means to efficiently promote absorption of hematoma is a novel clinical challenge for ICH. Peroxisome proliferator-activated receptor gamma (PPARγ) and nuclear factor erythroid 2-related factor 2 (Nrf2), had been shown that, can take potential roles in the endogenous hematoma clearance. However, monascin, a novel natural Nrf2 activator with PPARγ agonist, has not been reported to play a role in ICH. This study was designed to evaluate the effect of monascin on neurological deficits, hematoma clearance and edema extinction in a model of ICH in rats. 164 adult male Sprague-Dawley (SD) rats were randomly divided into sham; vehicle; monascin groups with low dosages (1mg/kg/day), middle dosages (5mg/kg/day) and high dosages (10mg/kg/day) respectively. Animals were euthanized at 1, 3 and 7days following neurological evaluation after surgery. We examined the effect of monascin on the brain water contents, blood brain barrier (BBB) permeability and hemoglobin levels, meanwhile reassessed the volume of hematoma and edema around the hematoma by Magnetic Resonance Imaging (MRI) in each group. The high dosage of monascin significantly improved neurological deficits, reduced the volume of hematoma in 1-7days after ICH, decreased BBB permeability and edema formation in 1-3days following ICH. Our study demonstrated that the high dosage of monascin played a neuroprotective role in ICH through reducing BBB permeability, edema and hematoma volume. Copyright © 2017 Elsevier Inc. All rights reserved.

Risk Factors Related to Lower Limb Edema, Compression, and Physical Activity During Pregnancy: A Retrospective Study.

PubMed

Ochalek, Katarzyna; Pacyga, Katarzyna; Curyło, Marta; Frydrych-Szymonik, Aleksandra; Szygula, Zbigniew

2017-06-01

The aim of the article was to assess risk factors and to analyze methods applied in the prevention and treatment of lower limb edema in pregnant women with a particular focus on compression therapy and exercise. Fifty-four women during the early 24-hour period following delivery were assigned to two groups-either to a group with swellings of lower limbs during pregnancy, located mostly in the region of feet and lower legs (Group A, n = 42), or to a group without edema (Group B, n = 12). Two subgroups, namely A1 and A2, were additionally distinguished in Group A. Compression therapy that consisted in wearing circular-knit compression garments, usually at compression level 1 (ccl1), with three cases of compression level 2 (ccl2) was applied only in Group A1 (n = 18 women). The analysis has led to a conclusion that there is a link between the occurrence of edema during pregnancy on the one hand and the pregravidity episodes of venous conditions (vascular insufficiency and thrombosis, p < 0.05) and the lack of physical exercise during pregnancy (p = 0.01) on the other hand. However, interdependence between the occurrence of edema and the number of times a female had been pregnant, physical activity before gravidity, or body mass index before gravidity has not been identified. Only 33% of the analyzed women applied compression therapy during pregnancy; a half of them continued to apply compression during the postpartum period. Compression therapy in combination with proper physical exercises appears to be an effective means to prevent and treat venous thrombosis and lower limb edema in pregnant women, yet further research in line with the principles of evidence-based medicine is required.

The Drosophila melanogaster Eip74EF-PA transcription factor directly binds the sciarid BhC4-1 promoter.

PubMed

Frank, Henrique Oliveira; Sanchez, Danilo Garcia; de Freitas Oliveira, Lucas; Kobarg, Jörg; Monesi, Nadia

2017-11-01

The DNA puff BhC4-1 gene of Bradysia hygida (Diptera, Sciaridae) is amplified and expressed in the salivary glands at the end of the last larval instar. Even though there are no BhC4-1 orthologs in Drosophila melanogaster, the mechanisms that regulate BhC4-1 gene expression in B. hygida are for the most part conserved in D. melanogaster. The BhC4-1 promoter contains a 129bp (-186/-58) cis-regulatory module (CRM) that drives developmentally regulated expression in transgenic salivary glands at the onset of metamorphosis. Both in the sciarid and in transgenic D. melanogaster, BhC4-1 gene expression is induced by the increase in ecdysone titers that triggers metamorphosis. Genetic interaction experiments revealed that in the absence of the Eip74EF-PA early gene isoform BhC4-1-lacZ levels of expression in the salivary gland are severely reduced. Here we show that the overexpression of the Eip74EF-PA transcription factor is sufficient to anticipate BhC4-1-lacZ expression in transgenic D. melanogaster. Through yeast one-hybrid assays we confirm that the Eip74EF-PA transcription factor directly binds to the 129 bp sciarid CRM. Together, these results contribute to the characterization of an insect CRM and indicate that the ecdysone gene regulatory network that promotes metamorphosis is conserved between D. melanogaster and the sciarid B. hygida. © 2017 Wiley Periodicals, Inc.

Structural characterization of ribosome recruitment and translocation by type IV IRES

PubMed Central

Murray, Jason; Savva, Christos G; Shin, Byung-Sik; Dever, Thomas E; Ramakrishnan, V; Fernández, Israel S

2016-01-01

Viral mRNA sequences with a type IV IRES are able to initiate translation without any host initiation factors. Initial recruitment of the small ribosomal subunit as well as two translocation steps before the first peptidyl transfer are essential for the initiation of translation by these mRNAs. Using electron cryomicroscopy (cryo-EM) we have structurally characterized at high resolution how the Cricket Paralysis Virus Internal Ribosomal Entry Site (CrPV-IRES) binds the small ribosomal subunit (40S) and the translocation intermediate stabilized by elongation factor 2 (eEF2). The CrPV-IRES restricts the otherwise flexible 40S head to a conformation compatible with binding the large ribosomal subunit (60S). Once the 60S is recruited, the binary CrPV-IRES/80S complex oscillates between canonical and rotated states (Fernández et al., 2014; Koh et al., 2014), as seen for pre-translocation complexes with tRNAs. Elongation factor eEF2 with a GTP analog stabilizes the ribosome-IRES complex in a rotated state with an extra ~3 degrees of rotation. Key residues in domain IV of eEF2 interact with pseudoknot I (PKI) of the CrPV-IRES stabilizing it in a conformation reminiscent of a hybrid tRNA state. The structure explains how diphthamide, a eukaryotic and archaeal specific post-translational modification of a histidine residue of eEF2, is involved in translocation. DOI: http://dx.doi.org/10.7554/eLife.13567.001 PMID:27159451

Diagnosis, Prevention and Management of Postoperative Pulmonary Edema

PubMed Central

Bajwa, SJ Singh; Kulshrestha, A

2012-01-01

Postoperative pulmonary edema is a well-known postoperative complication caused as a result of numerous etiological factors which can be easily detected by a careful surveillance during postoperative period. However, there are no preoperative and intraoperative criteria which can successfully establish the possibilities for development of postoperative pulmonary edema. The aims were to review the possible etiologic and diagnostic challenges in timely detection of postoperative pulmonary edema and to discuss the various management strategies for prevention of this postoperative complication so as to decrease morbidity and mortality. The various search engines for preparation of this manuscript were used which included Entrez (including Pubmed and Pubmed Central), NIH.gov, Medknow.com, Medscape.com, WebMD.com, Scopus, Science Direct, MedHelp.org, yahoo.com and google.com. Manual search was carried out and various text books and journals of anesthesia and critical care medicine were also searched. From the information gathered, it was observed that postoperative cardiogenic pulmonary edema in patients with serious cardiovascular diseases is most common followed by noncardiogenic pulmonary edema which can be due to fluid overload in the postoperative period or it can be negative pressure pulmonary edema (NPPE). NPPE is an important clinical entity in immediate post-extubation period and occurs due to acute upper airway obstruction and creation of acute negative intrathoracic pressure. NPPE carries a good prognosis if promptly diagnosed and appropriately treated with or without mechanical ventilation. PMID:23439791

Electric field-induced suppression of PTEN drives epithelial-to-mesenchymal transition via mTORC1 activation.

PubMed

Yan, Tiantian; Jiang, Xupin; Guo, Xiaowei; Chen, Wen; Tang, Di; Zhang, Junhui; Zhang, Xingyue; Zhang, Dongxia; Zhang, Qiong; Jia, Jiezhi; Huang, Yuesheng

2017-02-01

Naturally occurring electric fields (EFs) are an intrinsic property of wounds. Endogenous EFs in skin wounds play critical roles in the dynamic and well-ordered biological process of wound healing. The epithelial-to-mesenchymal transition (EMT) allows keratinocytes to transition from sedentary cells to motile cells, facilitating wound healing. However, EMT-related studies have been performed without considering endogenous EFs. Thus, the relationship between electrical signals and the EMT remain elusive. Phosphatase and tension homolog (PTEN) and mammalian target of rapamycin complex 1 (mTORC1) are key molecules in sensing electrical cues, and they play significant roles in cellular responses to EFs. In addition, these molecules are closely related to the occurrence of the EMT in other cells. We used primary human keratinocytes to investigate the influence of EFs on the EMT as well as the roles of PTEN and mTORC1 in this process. The effects of EFs on the EMT were investigated by analyzing the levels of specific proteins and transcription factors. The roles of mTORC1 and PTEN and their relationship with each other were studied via pharmacological inhibition or genetic knockdown. A Zeiss imaging system and scratch assays were used to study single-cell motility and monolayer cell migration. EFs induced a range of both biochemical changes (e.g., increased Snail, Slug, vimentin, and N-cadherin expression, decreased E-cadherin expression) and functional changes (e.g., enhanced migratory capacity) that are characteristic of the EMT. EF-stimulated cells exhibited suppressed PTEN expression, and further PTEN downregulation led to the acquisition of more mesenchymal features and the loss of epithelial characteristics, which was accompanied by increased migratory capacity. PTEN overexpression reversed the EF-induced EMT and inhibited the migratory capacity of keratinocytes. EF-induced mTORC1 activation was a required component of the causal relationship between PTEN suppression and the EMT, as mTORC1 inhibition reversed the EMT induced by PTEN downregulation. Our data demonstrate that the EF-induced suppression of PTEN drives the EMT via mTORC1 activation, thereby revealing a new and promising role of EFs in facilitating wound reepithelialization. These results provide a novel perspective regarding the significance of EFs in wound healing; therefore, electrical stimulation offers a new avenue of wound management for improved and accelerated wound healing. Copyright © 2016 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.

Structural rationale for the cross-resistance of tumor cells bearing the A399V variant of elongation factor eEF1A1 to the structurally unrelated didemnin B, ternatin, nannocystin A and ansatrienin B

NASA Astrophysics Data System (ADS)

Sánchez-Murcia, Pedro A.; Cortés-Cabrera, Álvaro; Gago, Federico

2017-10-01

At least four classes of structurally distinct natural products with potent antiproliferative activities target the translation elongation factor eEF1A1, which is best known as the G-protein that delivers amino acyl transfer RNAs (aa-tRNAs) to ribosomes during mRNA translation. We present molecular models in atomic detail that provide a common structural basis for the high-affinity binding of didemnin B, ternatin, ansatrienin B and nannocystin A to eEF1A1, as well as a rationale based on molecular dynamics results that accounts for the deleterious effect of replacing alanine 399 with valine. The proposed binding site, at the interface between domains I and III, is eminently hydrophobic and exists only in the GTP-bound conformation. Drug binding at this site is expected to disrupt neither loading of aa-tRNAs nor GTP hydrolysis but would give rise to stabilization of this particular conformational state, in consonance with reported experimental findings. The experimental solution of the three-dimensional structure of mammalian eEF1A1 has proved elusive so far and the highly homologous eEF1A2 from rabbit muscle has been crystallized and solved only as a homodimer in a GDP-bound conformation. Interestingly, in this dimeric structure the large interdomain cavity where the drugs studied are proposed to bind is occupied by a mostly hydrophobic α-helix from domain I of the same monomer. Since binding of this α-helix and any of these drugs to domain III of eEF1A(1/2) is, therefore, mutually exclusive and involves two distinct protein conformations, one intriguing possibility that emerges from our study is that the potent antiproliferative effect of these natural products may arise not only from inhibition of protein synthesis, which is the current dogma, but also from interference with some other non-canonical functions. From this standpoint, this type of drugs could be considered antagonists of eEF1A1/2 oligomerization, a hypothesis that opens up novel areas of research.

Impressive Suppression of Colon Cancer Growth by Triple Combination SN38/EF24/Melatonin: "Oncogenic" Versus "Onco-Suppressive" Reactive Oxygen Species.

PubMed

Bakalova, Rumiana; Zhelev, Zhivko; Shibata, Sayaka; Nikolova, Biliana; Aoki, Ichio; Higashi, Tatsuya

2017-10-01

The study aimed to investigate the effect of multi-targeted combinations (SN38/EF24; SN38/EF24/melatonin) on the growth of colon cancer in experimental animals and their impact on the ratio "oncogenic"/"onco-suppressive" reactive oxygen species (ROS) - a crucial factor for triggering carcinogenesis, as well as for development of effective therapeutic strategies. The experiments were conducted on colon cancer-grafted mice - non-treated, SN38/EF24-treated and SN38/EF24/melatonin-treated within 22 days. The balance between different types of ROS was measured in vivo by nitroxide-enhanced magnetic resonance imaging (MRI), as well as on isolated tissue specimens by conventional analytical tests. Both combinations significantly suppressed the tumor growth. Impressive anticancer effect was observed in SN38/EF24/melatonin-treated mice - almost complete destruction of the tumor. Both types of ROS (superoxide and hydroperoxides) were elevated in cancer, but the MRI data suggest that the ratio between them tends towards superoxide. SN38/EF24 decreased the level of superoxide, but did not affect the level of hydroperoxides in the cancerous tissue, while SN38/EF24/melatonin decreased the level of superoxide below the control and increased significantly the level of hydroperoxides. The most important observations are that: (i) colon cancer was characterized by a vicious cycle, that ensures a permanent domination of "oncogenic" ROS (as superoxide) over "onco-suppressive" ROS (as hydrogen peroxide); (ii) the anticancer effect of the triple combination EF24/SN38/melatonin was accompanied by decreasing "oncogenic" and increasing "onco-suppressive" ROS; (iii) the ratio between both types of ROS could be a new onco-target for combined therapy; and (iv) nitroxide-enhanced MRI is a valuable tool for analyzing of this ratio. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nakayama, Hironao; Department of Surgery, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115; Division of Cell Growth and Tumor Regulation, Proteo-Science Center, Ehime University, Toon, Ehime 791-0295

Class 3 semaphorins were discovered as a family of axon guidance molecules, but are now known to be involved in diverse biologic processes. In this study, we investigated the anti-angiogenic potential of SEMA3E and SEMA3F (SEMA3E&F) in infantile hemangioma (IH). IH is a common vascular tumor that involves both vasculogenesis and angiogenesis. Our lab has identified and isolated hemangioma stem cells (HemSC), glucose transporter 1 positive (GLUT1{sup +}) endothelial cells (designated as GLUT1{sup sel} cells) based on anti-GLUT1 magnetic beads selection and GLUT1-negative endothelial cells (named HemEC). We have shown that these types of cells play important roles in hemangiogenesis.more » We report here that SEMA3E inhibited HemEC migration and proliferation while SEMA3F was able to suppress the migration and proliferation in all three types of cells. Confocal microscopy showed that stress fibers in HemEC were reduced by SEMA3E&F and that stress fibers in HemSC were decreased by SEMA3F, which led to cytoskeletal collapse and loss of cell motility in both cell types. Additionally, SEMA3E&F were able to inhibit vascular endothelial growth factor (VEGF)-induced sprouts in all three types of cells. Further, SEMA3E&F reduced the level of p-VEGFR2 and its downstream p-ERK in HemEC. These results demonstrate that SEMA3E&F inhibit IH cell proliferation and suppress the angiogenic activities of migration and sprout formation. SEMA3E&F may have therapeutic potential to treat or prevent growth of highly proliferative IH. - Highlights: • SEMA3E&F reduce actin stress fibers and induce cytoskeletal collapse in HemEC. • SEMA3E&F inhibit angiogenic activities of HemEC. • SEMA3E&F can interrupt the VEGF-A-VEGFR2-ERK signaling pathway in HemEC. • Plexin D1 and NRP2 are induced during HemSC/GLUT1{sup sel}-to-EC differentiation.« less

Evidence from paranoid schizophrenia for more than one component of theory of mind

PubMed Central

Scherzer, Peter; Achim, André; Léveillé, Edith; Boisseau, Emilie; Stip, Emmanuel

2015-01-01

We previously reported finding that performance was impaired on four out of five theory of mind (ToM) tests in a group of 21 individuals diagnosed with paranoid schizophrenia (pScz), relative to a non-clinical group of 29 individuals (Scherzer et al., 2012). Only the Reading the Mind in the Eyes Test did not distinguish between groups. A principal components analysis revealed that the results on the ToM battery could be explained by one general ToM factor with the possibility of a latent second factor. As well, the tests were not equally sensitive to the pathology. There was also overmentalization in some ToM tests and under-mentalisation in others. These results led us to postulate that there is more than one component to ToM. We hypothesized that correlations between the different EF measures and ToM tests would differ sufficiently within and between groups to support this hypothesis. We considered the relationship between the performance on eight EF tests and five ToM tests in the same diagnosed and non-clinical individuals as in the first study. The ToM tests shared few EF correlates and each had its own best EF predictor. These findings support the hypothesis of multiple ToM components. PMID:26579026

Magnetic evidence for heavy metal pollution of topsoil in Shanghai, China

NASA Astrophysics Data System (ADS)

Wang, Guan; Liu, Yuan; Chen, Jiao; Ren, Feifan; Chen, Yuying; Ye, Fangzhou; Zhang, Weiguo

2018-03-01

This study presents the results obtained from magnetic susceptibility and heavy metal (Cu, Zn, Pb, and Cr) concentration measurements of soil profiles collected from arable land and urban parks in Baoshan District, an industrial district of Shanghai, China. The study focuses on the investigation of vertical variations in magnetic susceptibilities and heavy metal concentrations and on correlations between magnetic susceptibilities and heavy metal concentrations in soil profiles. The results demonstrate that magnetic enhancement in the surface layer of the soil profile is associated with increased heavy metal pollution. The enrichment factors (EF) and the Tomlinson Pollution Load Index (PLI-EF) are calculated for estimating the level of heavy metal pollution of soil profiles in the study. The significant positive correlations between heavy metal contents, enrichment factors (EF), Tomlinson pollution load index (PLI-CF), modified Tomlinson pollution load index (PLI-EF), and magnetic susceptibility (c) indicate that much of the heavy metal contamination in the study area is linked to combustion derived particulate emissions. The results confirm that the combined magnetic measurement and heavy metal concentration analysis could provide useful information for soil monitoring in urban environments. However, the use of magnetic technique to locate the heavy metal pollution boundary in the soil profile of this studied area should be confirmed by further geochemical analysis.

Eukaryotic translation initiator protein 1A isoform, CCS-3, enhances the transcriptional repression of p21CIP1 by proto-oncogene FBI-1 (Pokemon/ZBTB7A).

PubMed

Choi, Won-Il; Kim, Youngsoo; Kim, Yuri; Yu, Mi-young; Park, Jungeun; Lee, Choong-Eun; Jeon, Bu-Nam; Koh, Dong-In; Hur, Man-Wook

2009-01-01

FBI-1, a member of the POK (POZ and Kruppel) family of transcription factors, plays a role in differentiation, oncogenesis, and adipogenesis. eEF1A is a eukaryotic translation elongation factor involved in several cellular processes including embryogenesis, oncogenic transformation, cell proliferation, and cytoskeletal organization. CCS-3, a potential cervical cancer suppressor, is an isoform of eEF1A. We found that eEF1A forms a complex with FBI-1 by co-immunoprecipitation, SDS-PAGE, and MALDI-TOF Mass analysis of the immunoprecipitate. GST fusion protein pull-downs showed that FBI-1 directly interacts with eEF1A and CCS-3 via the zinc finger and POZ-domain of FBI-1. FBI-1 co-localizes with either eEF1A or CCS-3 at the nuclear periplasm. CCS-3 enhances transcriptional repression of the p21CIP1 gene (hereafter referred to as p21) by FBI-1. The POZ-domain of FBI-1 interacts with the co-repressors, SMRT and BCoR. We found that CCS-3 also interacts with the co-repressors independently. The molecular interaction between the co-repressors and CCS-3 at the POZ-domain of FBI-1 appears to enhance FBI-1 mediated transcriptional repression. Our data suggest that CCS-3 may be important in cell differentiation, tumorigenesis, and oncogenesis by interacting with the proto-oncogene FBI-1 and transcriptional co-repressors. Copyright 2009 S. Karger AG, Basel.

Mechanism of Elongation Factor-G-mediated Fusidic Acid Resistance and Fitness Compensation in Staphylococcus aureus *

PubMed Central

Koripella, Ravi Kiran; Chen, Yang; Peisker, Kristin; Koh, Cha San; Selmer, Maria; Sanyal, Suparna

2012-01-01

Antibiotic resistance in bacteria is often associated with fitness loss, which is compensated by secondary mutations. Fusidic acid (FA), an antibiotic used against pathogenic bacteria Staphylococcus aureus, locks elongation factor-G (EF-G) to the ribosome after GTP hydrolysis. To clarify the mechanism of fitness loss and compensation in relation to FA resistance, we have characterized three S. aureus EF-G mutants with fast kinetics and crystal structures. Our results show that a significantly slower tRNA translocation and ribosome recycling, plus increased peptidyl-tRNA drop-off, are the causes for fitness defects of the primary FA-resistant mutant F88L. The double mutant F88L/M16I is three to four times faster than F88L in both reactions and showed no tRNA drop-off, explaining its fitness compensatory phenotype. The M16I mutation alone showed hypersensitivity to FA, higher activity, and somewhat increased affinity to GTP. The crystal structures demonstrate that Phe-88 in switch II is a key residue for FA locking and also for triggering interdomain movements in EF-G essential for its function, explaining functional deficiencies in F88L. The mutation M16I loosens the hydrophobic core in the G domain and affects domain I to domain II contact, resulting in improved activity both in the wild-type and F88L background. Thus, FA-resistant EF-G mutations causing fitness loss and compensation operate by affecting the conformational dynamics of EF-G on the ribosome. PMID:22767604

Heterologous expression of a plastid EF-Tu reduces protein thermal aggregation and enhances CO2 fixation in wheat (Triticum aestivum) following heat stress.

PubMed

Fu, Jianming; Momcilović, Ivana; Clemente, Thomas E; Nersesian, Natalya; Trick, Harold N; Ristic, Zoran

2008-10-01

Heat stress is a major constraint to wheat production and negatively impacts grain quality, causing tremendous economic losses, and may become a more troublesome factor due to global warming. At the cellular level, heat stress causes denaturation and aggregation of proteins and injury to membranes leading to alterations in metabolic fluxes. Protein aggregation is irreversible, and protection of proteins from thermal aggregation is a strategy a cell uses to tolerate heat stress. Here we report on the development of transgenic wheat (Triticum aestivum) events, expressing a maize gene coding for plastidal protein synthesis elongation factor (EF-Tu), which, compared to non-transgenic plants, display reduced thermal aggregation of leaf proteins, reduced heat injury to photosynthetic membranes (thylakoids), and enhanced rate of CO(2) fixation after exposure to heat stress. The results support the concept that EF-Tu ameliorates negative effects of heat stress by acting as a molecular chaperone. This is the first demonstration of the introduction of a plastidal EF-Tu in plants that leads to protection against heat injury and enhanced photosynthesis after heat stress. This is also the first demonstration that a gene other than HSP gene can be used for improvement of heat tolerance and that the improvement is possible in a species that has a complex genome, hexaploid wheat. The results strongly suggest that heat tolerance of wheat, and possibly other crop plants, can be improved by modulating expression of plastidal EF-Tu and/or by selection of genotypes with increased endogenous levels of this protein.

Imaging Findings Associated with Space-Occupying Edema in Patients with Large Middle Cerebral Artery Infarcts.

PubMed

Horsch, A D; Dankbaar, J W; Stemerdink, T A; Bennink, E; van Seeters, T; Kappelle, L J; Hofmeijer, J; de Jong, H W; van der Graaf, Y; Velthuis, B K

2016-05-01

Prominent space-occupying cerebral edema is a devastating complication occurring in some but not all patients with large MCA infarcts. It is unclear why differences in the extent of edema exist. Better knowledge of factors related to prominent edema formation could aid treatment strategies. This study aimed to identify variables associated with the development of prominent edema in patients with large MCA infarcts. From the Dutch Acute Stroke Study (DUST), 137 patients were selected with large MCA infarcts on follow-up NCCT (3 ± 2 days after stroke onset), defined as ASPECTS ≤4. Prominent edema was defined as a midline shift of ≥5 mm on follow-up. Admission patient and treatment characteristics were collected. Admission CT parameters used were ASPECTS on NCCT and CBV and MTT maps, and occlusion site, clot burden, and collaterals on CTA. Permeability on admission CTP, and day 3 recanalization and reperfusion statuses were obtained if available. Unadjusted and adjusted (age and NIHSS) odds ratios were calculated for all variables in relation to prominent edema. Prominent edema developed in 51 patients (37%). Adjusted odds ratios for prominent edema were higher with lower ASPECTS on NCCT (adjusted odds ratio, 1.32; 95% CI, 1.13-1.55) and CBV (adjusted odds ratio, 1.26; 95% CI, 1.07-1.49), higher permeability (adjusted odds ratio, 2.35; 95% CI, 1.30-4.24), more proximal thrombus location (adjusted odds ratio, 3.40; 95% CI, 1.57-7.37), higher clot burden (adjusted odds ratio, 2.88; 95% CI, 1.11-7.45), and poor collaterals (adjusted odds ratio, 3.93; 95% CI, 1.78-8.69). Extensive proximal occlusion, poor collaterals, and larger ischemic deficits with higher permeability play a role in the development of prominent edema in large MCA infarcts. © 2016 by American Journal of Neuroradiology.

Correlation of Tumor and Peritumoral Edema Volumes with Survival in Patients with Cerebral Metastases.

PubMed

Kerschbaumer, Johannes; Bauer, Marlies; Popovscaia, Marina; Grams, Astrid E; Thomé, Claudius; Freyschlag, Christian F

2017-02-01

Surgical resection in combination with radiotherapy in selected cases remains the best option for patients with cerebral metastases. Postoperative relapse of brain metastases occurs frequently and can be reduced by postoperative whole-brain radiotherapy (WBRT). Continuous spread of tumor cells from the primary lesions is debated as a cause of recurrence. It is well known that in gliomas, infiltration takes place within the surrounding edema. Obviously, most brain metastases are usually associated with peritumoral edema, which may act as an indicator of infiltration and more aggressive tumor biology. Therefore, we aimed to investigate the correlation of tumor and edema volumes with overall survival in patients with cerebral metastases. A total of 143 patients diagnosed with brain metastasis (male:female=1.1:1) who underwent surgical resection were included retrospectively in this analysis. Clinical data were retrieved from electronic patient files. The volumes of tumor and edema calculated by manual delineation. The ratio of edema to tumor volume was calculated, leading to dichotomization of the patients. The median tumor volume was 20.1 cc (range=0.8-90.8 cc) and the median volume of edema 49.5 cc (range=0-179.9 cc). The volume of metastases did not significantly correlate with overall survival. The ratio of edema to tumor volume was also not a prognostic factor in terms of overall survival. Only surgical resection, preoperative recursive partitioning analysis class, and postoperative addition of WBRT, as well as female sex, demonstrated beneficial effects. The extent of edema surrounding cerebral metastases does not appear to influence overall survival in patients suffering from brain metastases, although it seems to be responsible for most of the patients' symptoms. The hypothesis that the extent of edema was disadvantageous concerning survival was supported by our data. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Platelet-activating factor acether (PAF-acether) involvement in acute inflammatory and pain processes.

PubMed

Bonnet, J; Loiseau, A M; Orvoen, M; Bessin, P

1981-12-01

PAF-acether is a potent aggregating agent released by various cells involved in acute inflammatory process. In this paper, exogenous PAF-acether has been investigated for its ability to generate signs of inflammation (edema measured by plethysmometry) and hyperalgesia (Randall-Sellito test) by standard subplantar injection in the rat paw. From 0.005 microgram. PAF-acether induced significant edema of the paw, maximal 1 hour after injection; it was dose-dependent from 0.1 to 5 microgram. Significant dose-dependent hyperalgesia occurred from 1.25 microgram; it reached a plateau from 2 to 4 hours after injection. Both phenomena were long-lasting (greater than 6 h). PAF-acether was 1.5 to 10 times stronger than PGI2 and PGE2 in inducing edema, pain, and in increasing vascular permeability. We investigated the interaction of miscellaneous drugs with the edema and the hyperalgesia caused by 2.5 microgram of PAF-acether. Non-steroidal anti-inflammatory (NSAI) drugs exerted only moderate effects on the edema without affecting hyperalgesia. Edema was highly reduced by various agents: prednisolone, L-cysteine, anti-calcic drugs, theophylline, PGI2, salbutamol, clonidine. All of them, except clonidine, and in contrast to NSAI drugs, were more potent on PAF-acether edema than on kaolin edema; a possible link between these agents is their ability to increase cyclic AMP levels in the cells and consequently to reduce lysosomal enzyme release. PAF-acether itself, injected intra-peritoneally, inhibited PAF-acether edema without preventing pain, at doses inactive on arterial pressure and hematocrit, but inducing marked gastric mucosal damage. Among the drugs tested, including analgesics, only PGI2 and imidazole improved PAF-induced hyperalgesia, showing a dissociation between edema and hyperalgesia not only in their induction (doses of PAF required, time course of the phenomena), but in the drugs able to antagonize their development too.

Exploratory Decision-Tree Modeling of Data from the Randomized REACTT Trial of Tadalafil Versus Placebo to Predict Recovery of Erectile Function After Bilateral Nerve-Sparing Radical Prostatectomy.

PubMed

Montorsi, Francesco; Oelke, Matthias; Henneges, Carsten; Brock, Gerald; Salonia, Andrea; d'Anzeo, Gianluca; Rossi, Andrea; Mulhall, John P; Büttner, Hartwig

2016-09-01

Understanding predictors for the recovery of erectile function (EF) after nerve-sparing radical prostatectomy (nsRP) might help clinicians and patients in preoperative counseling and expectation management of EF rehabilitation strategies. To describe the effect of potential predictors on EF recovery after nsRP by post hoc decision-tree modeling of data from A Study of Tadalafil After Radical Prostatectomy (REACTT). Randomized double-blind double-dummy placebo-controlled trial in 423 men aged <68 yr with adenocarcinoma of the prostate (Gleason ≤7, normal preoperative EF) who underwent nsRP at 50 centers from nine European countries and Canada. Postsurgery 1:1:1 randomization to 9-mo double-blind treatment with tadalafil 5mg once a day (OaD), tadalafil 20mg on demand, or placebo, followed by a 6-wk drug-free-washout, and a 3-mo open-label tadalafil OaD treatment. Three decision-tree models, using the International Index of Erectile Function-Erectile Function (IIEF-EF) domain score at the end of double-blind treatment, washout, and open-label treatment as response variable. Each model evaluated the association between potential predictors: presurgery IIEF domain and IIEF single-item scores, surgical approach, nerve-sparing score (NSS), and postsurgery randomized treatment group. The first decision-tree model (n=422, intention-to-treat population) identified high presurgery sexual desire (IIEF item 12: ≥3.5 and <3.5) as the key predictor for IIEF-EF at the end of double-blind treatment (mean IIEF-EF: 14.9 and 11.1), followed by high confidence to get and maintain an erection (IIEF item 15: ≥3.5 and <3.5; IIEF-EF: 15.4 and 7.1). For patients meeting these criteria, additional non-IIEF-related predictors included robot-assisted laparoscopic surgery (yes or no; IIEF-EF: 19.3 and 12.6), quality of nerve sparing (NSS: <2.5 and ≥2.5; IIEF-EF: 14.3 and 10.5), and treatment with tadalafil OaD (yes and no; IIEF-EF: 17.6 and 14.3). Additional analyses after washout and open-label treatment identified high presurgery intercourse satisfaction as the key predictor. Exploratory decision-tree analyses identified high presurgery sexual desire, confidence, and intercourse satisfaction as key predictors for EF recovery. Patients meeting these criteria might benefit the most from conserving surgery and early postsurgery EF rehabilitation. Strategies for improving EF after surgery should be discussed preoperatively with all patients; this information may support expectation management for functional recovery on an individual patient level. Understanding how patient characteristics and different treatment options affect the recovery of erectile function (EF) after radical surgery for prostate cancer might help physicians select the optimal treatment for their patients. This analysis of data from a clinical trial suggested that high presurgery sexual desire, sexual confidence, and intercourse satisfaction are key factors predicting EF recovery. Patients meeting these criteria might benefit the most from conserving surgery (robot-assisted surgery, perfect nerve sparing) and postsurgery medical rehabilitation of EF. ClinicalTrials.gov, NCT01026818. Copyright © 2016. Published by Elsevier B.V.

Dipeptidyl peptidase IV deficiency increases susceptibility to angiotensin-converting enzyme inhibitor-induced peritracheal edema.

PubMed

Byrd, James Brian; Shreevatsa, Ajai; Putlur, Pradeep; Foretia, Denis; McAlexander, Laurie; Sinha, Tuhin; Does, Mark D; Brown, Nancy J

2007-08-01

Serum dipeptidyl peptidase IV (DPPIV) activity is decreased in some individuals with ACE inhibitor-associated angioedema. ACE and DPPIV degrade substance P, an edema-forming peptide. The contribution of impaired degradation of substance P by DPPIV to the pathogenesis of ACE inhibitor-associated angioedema is unknown. We sought to determine whether DPPIV deficiency results in increased edema formation during ACE inhibition. We also sought to develop an animal model using magnetic resonance imaging to quantify ACE inhibitor-induced edema. The effect of genetic DPPIV deficiency on peritracheal edema was assessed in F344 rats after treatment with saline, captopril (2.5 mg/kg), or captopril plus the neurokinin receptor antagonist spantide (100 mug/kg) by using serial T2-weighted magnetic resonance imaging. Serum dipeptidyl peptidase activity was dramatically decreased in DPPIV-deficient rats (P < .001). The volume of peritracheal edema was significantly greater in captopril-treated DPPIV-deficient rats than in saline-treated DPPIV-deficient rats (P = .001), saline-treated rats of the normal substrain (P < .001), or captopril-treated rats of the normal substrain (P = .001). Cotreatment with spantide attenuated peritracheal edema in captopril-treated DPPIV-deficient rats (P = .005 vs captopril-treated DPPIV-deficient rats and P = .57 vs saline-treated DPPIV-deficient rats). DPPIV deficiency predisposes to peritracheal edema formation when ACE is inhibited through a neurokinin receptor-dependent mechanism. Magnetic resonance imaging is useful for modeling ACE inhibitor-associated angioedema in rats. Genetic or environmental factors that decrease DPPIV activity might increase the risk of ACE inhibitor-associated angioedema.

Diabetic Macular Edema: Current Understanding, Pharmacologic Treatment Options, and Developing Therapies.

PubMed

Miller, Kevin; Fortun, Jorge A

2018-01-01

Diabetic retinopathy and diabetic macular edema comprise a major source of visual disability throughout the developed world. The etiology and pathogenesis of macular edema is intricate and multifactorial, in which the hyperglycemic state in diabetes induces a microangiopathy. Through several inflammatory and vasogenic mediators, including vascular endothelial growth factor (VEGF) upregulation and inflammatory cytokines and chemokines, pathologic changes are induced in the vascular endothelium triggering breakdown of the blood retinal barrier, causing extravasation of fluid into the extracellular space and manifesting clinically as macular edema, resulting in visual loss. The advent of medications targeting the VEGF pathway has led to great clinical improvements compared with the previous standard of care of laser therapy alone, as shown in studies such as RISE, RIDE, VIVID, VISTA, and DRCR. However, analyses have shown that many patients have inadequate response or are nonresponders to anti-VEGF therapy, demonstrating the need for additional therapies to more comprehensively treat this disease. Although corticosteroid treatments and implants have demonstrated some efficacy in adjunctive and supplemental treatment, the need to more adequately treat macular edema remains. Our knowledge of diabetic macular edema continues to grow, leading to new currently available and emerging pharmacotherapies to further enhance our treatment and restore vision in those affected by diabetic macular edema. This review will discuss the pathogenesis of diabetic macular edema and the pharmacologic therapies available for its treatment, including anti-VEGF, steroids, and newer therapies still in development, such as angiopoietin antagonists, Tie2 agonists, kallikrein inhibitors, interleukin inhibitors, and others. Copyright 2018 Asia-Pacific Academy of Ophthalmology.

Class I and II Small Heat Shock Proteins Together with HSP101 Protect Protein Translation Factors during Heat Stress.

PubMed

McLoughlin, Fionn; Basha, Eman; Fowler, Mary E; Kim, Minsoo; Bordowitz, Juliana; Katiyar-Agarwal, Surekha; Vierling, Elizabeth

2016-10-01

The ubiquitous small heat shock proteins (sHSPs) are well documented to act in vitro as molecular chaperones to prevent the irreversible aggregation of heat-sensitive proteins. However, the in vivo activities of sHSPs remain unclear. To investigate the two most abundant classes of plant cytosolic sHSPs (class I [CI] and class II [CII]), RNA interference (RNAi) and overexpression lines were created in Arabidopsis (Arabidopsis thaliana) and shown to have reduced and enhanced tolerance, respectively, to extreme heat stress. Affinity purification of CI and CII sHSPs from heat-stressed seedlings recovered eukaryotic translation elongation factor (eEF) 1B (α-, β-, and γ-subunits) and eukaryotic translation initiation factor 4A (three isoforms), although the association with CI sHSPs was stronger and additional proteins involved in translation were recovered with CI sHSPs. eEF1B subunits became partially insoluble during heat stress and, in the CI and CII RNAi lines, showed reduced recovery to the soluble cell fraction after heat stress, which was also dependent on HSP101. Furthermore, after heat stress, CI sHSPs showed increased retention in the insoluble fraction in the CII RNAi line and vice versa. Immunolocalization revealed that both CI and CII sHSPs were present in cytosolic foci, some of which colocalized with HSP101 and with eEF1Bγ and eEF1Bβ. Thus, CI and CII sHSPs have both unique and overlapping functions and act either directly or indirectly to protect specific translation factors in cytosolic stress granules. © 2016 American Society of Plant Biologists. All Rights Reserved.

Executive Function and Falls in Older Adults: New Findings from a Five-Year Prospective Study Link Fall Risk to Cognition

PubMed Central

Mirelman, Anat; Herman, Talia; Brozgol, Marina; Dorfman, Moran; Sprecher, Elliot; Schweiger, Avraham; Giladi, Nir; Hausdorff, Jeffrey M.

2012-01-01

Background Recent findings suggest that executive function (EF) plays a critical role in the regulation of gait in older adults, especially under complex and challenging conditions, and that EF deficits may, therefore, contribute to fall risk. The objective of this study was to evaluate if reduced EF is a risk factor for future falls over the course of 5 years of follow-up. Secondary objectives were to assess whether single and dual task walking abilities, an alternative window into EF, were associated with fall risk. Methodology/Main Results We longitudinally followed 256 community-living older adults (age: 76.4±4.5 yrs; 61% women) who were dementia free and had good mobility upon entrance into the study. At baseline, a computerized cognitive battery generated an index of EF, attention, a closely related construct, and other cognitive domains. Gait was assessed during single and dual task conditions. Falls data were collected prospectively using monthly calendars. Negative binomial regression quantified risk ratios (RR). After adjusting for age, gender and the number of falls in the year prior to the study, only the EF index (RR: .85; CI: .74–.98, p = .021), the attention index (RR: .84; CI: .75–.94, p = .002) and dual tasking gait variability (RR: 1.11; CI: 1.01–1.23; p = .027) were associated with future fall risk. Other cognitive function measures were not related to falls. Survival analyses indicated that subjects with the lowest EF scores were more likely to fall sooner and more likely to experience multiple falls during the 66 months of follow-up (p<0.02). Conclusions/Significance These findings demonstrate that among community-living older adults, the risk of future falls was predicted by performance on EF and attention tests conducted 5 years earlier. The present results link falls among older adults to cognition, indicating that screening EF will likely enhance fall risk assessment, and that treatment of EF may reduce fall risk. PMID:22768271

Impact of prostate edema on cell survival and tumor control after permanent interstitial brachytherapy for early stage prostate cancers

PubMed Central

Chen, Zhe (Jay); Roberts, Kenneth; Decker, Roy; Pathare, Pradip; Rockwell, Sara; Nath, Ravinder

2011-01-01

Previous studies have shown that the procedure-induced prostate edema during permanent interstitial brachytherapy (PIB) can cause significant variations in the dose delivered to the prostate gland. Because the clinical impact of edema-induced dose variations depends strongly on the magnitude of the edema, the temporal pattern of its resolution and its interplay with the decay of radioactivity and the underlying biological processes of tumor cells (such as tumor potential doubling time), we investigated the impact of edema-induced dose variations on the tumor cell survival and tumor control probability after PIB with the 131Cs, 125I and 103Pd sources used in current clinical practice. The exponential edema resolution model reported by Waterman et al. (Int. J. Radiat. Oncol. Biol. Phys. 41, 1069–1077–1998) was used to characterize the edema evolutions observed previously during clinical PIB for prostate cancer. The concept of biologically effective dose (BED), taking into account tumor cell proliferation and sublethal damage repair during dose delivery, was used to characterize the effects of prostate edema on cell survival and tumor control probability. Our calculation indicated that prostate edema, if not taken into account appropriately, can increase the cell survival and decrease the probability of local control of PIB. The edema-induced increase in cell survival increased with increasing edema severity, decreasing half-life for radioactive decay and decreasing energy of the photons energy emitted by the source. At the doses currently prescribed for PIB and for prostate cancer cells characterized by nominal radiobiology parameters recommended by AAPM TG-137, PIB using 125I sources was less affected by edema than PIB using 131Cs or 103Pd sources due to the long radioactive decay half-life of 125I. The effect of edema on PIB using 131Cs or 103Pd was similar. The effect of edema on 103Pd PIB was slightly greater, even though the decay half-life of 103Pd (17 days) is longer than that of 131Cs (9.7 days), because the advantage of the longer 103Pd decay half-life was negated by the lower effective energy of the photons it emits (~21 keV compared to ~30.4 keV for 131Cs). In addition, the impact of edema could be reduced or enhanced by differences in the tumor characteristics (e.g. potential tumor doubling time or the α/β ratio), and the effect of these factors varied for the different radioactive sources. There is a clear need to consider the effects of prostate edema during the planning and evaluation of permanent interstitial brachytherapy treatments for prostate cancer. PMID:21772076

The impact of prostate edema on cell survival and tumor control after permanent interstitial brachytherapy for early stage prostate cancers

NASA Astrophysics Data System (ADS)

(Jay Chen, Zhe; Roberts, Kenneth; Decker, Roy; Pathare, Pradip; Rockwell, Sara; Nath, Ravinder

2011-08-01

Previous studies have shown that procedure-induced prostate edema during permanent interstitial brachytherapy (PIB) can cause significant variations in the dose delivered to the prostate gland. Because the clinical impact of edema-induced dose variations strongly depends on the magnitude of the edema, the temporal pattern of its resolution and its interplay with the decay of radioactivity and the underlying biological processes of tumor cells (such as tumor potential doubling time), we investigated the impact of edema-induced dose variations on the tumor cell survival and tumor control probability after PIB with the 131Cs, 125I and 103Pd sources used in current clinical practice. The exponential edema resolution model reported by Waterman et al (1998 Int. J. Radiat. Oncol. Biol. Phys. 41 1069-77) was used to characterize the edema evolutions previously observed during clinical PIB for prostate cancer. The concept of biologically effective dose, taking into account tumor cell proliferation and sublethal damage repair during dose delivery, was used to characterize the effects of prostate edema on cell survival and tumor control probability. Our calculation indicated that prostate edema, if not appropriately taken into account, can increase the cell survival and decrease the probability of local control of PIB. The magnitude of an edema-induced increase in cell survival increased with increasing edema severity, decreasing half-life of radioactive decay and decreasing photon energy emitted by the source. At the doses currently prescribed for PIB and for prostate cancer cells characterized by nominal radiobiology parameters recommended by AAPM TG-137, PIB using 125I sources was less affected by edema than PIB using 131Cs or 103Pd sources due to the long radioactive decay half-life of 125I. The effect of edema on PIB using 131Cs or 103Pd was similar. The effect of edema on 103Pd PIB was slightly greater, even though the decay half-life of 103Pd (17 days) is longer than that of 131Cs (9.7 days), because the advantage of the longer 103Pd decay half-life was negated by the lower effective energy of the photons it emits (~21 keV compared to ~30.4 keV for 131Cs). In addition, the impact of edema could be reduced or enhanced by differences in the tumor characteristics (e.g. potential tumor doubling time or the α/β ratio), and the effect of these factors varied for the different radioactive sources. There is a clear need to consider the effects of prostate edema during the planning and evaluation of permanent interstitial brachytherapy treatments for prostate cancer.

An aminoacylation-dependent nuclear tRNA export pathway in yeast.

PubMed

Grosshans, H; Hurt, E; Simos, G

2000-04-01

Yeast Los1p, the homolog of human exportin-t, mediates nuclear export of tRNA. Using fluorescence in situ hybridization, we could show that the export of some intronless tRNA species is not detectably affected by the disruption of LOS1. To find other factors that facilitate tRNA export, we performed a suppressor screen of a synthetically lethal los1 mutant and identified the essential translation elongation factor eEF-1A. Mutations in eEF-1A impaired nuclear export of all tRNAs tested, which included both spliced and intronless species. An even stronger defect in nuclear exit of tRNA was observed under conditions that inhibited tRNA aminoacylation. In all cases, inhibition of tRNA export led to nucleolar accumulation of mature tRNAs. Our data show that tRNA aminoacylation and eEF-1A are required for efficient nuclear tRNA export in yeast and suggest coordination between the protein translation and the nuclear tRNA processing and transport machineries.

An aminoacylation-dependent nuclear tRNA export pathway in yeast

PubMed Central

Grosshans, Helge; Hurt, Ed; Simos, George

2000-01-01

Yeast Los1p, the homolog of human exportin-t, mediates nuclear export of tRNA. Using fluorescence in situ hybridization, we could show that the export of some intronless tRNA species is not detectably affected by the disruption of LOS1. To find other factors that facilitate tRNA export, we performed a suppressor screen of a synthetically lethal los1 mutant and identified the essential translation elongation factor eEF-1A. Mutations in eEF-1A impaired nuclear export of all tRNAs tested, which included both spliced and intronless species. An even stronger defect in nuclear exit of tRNA was observed under conditions that inhibited tRNA aminoacylation. In all cases, inhibition of tRNA export led to nucleolar accumulation of mature tRNAs. Our data show that tRNA aminoacylation and eEF-1A are required for efficient nuclear tRNA export in yeast and suggest coordination between the protein translation and the nuclear tRNA processing and transport machineries. PMID:10766739

Critical assessment of enhancement factor measurements in surface-enhanced Raman scattering on different substrates.

PubMed

Rodrigues, Daniel C; de Souza, Michele L; Souza, Klester S; dos Santos, Diego P; Andrade, Gustavo F S; Temperini, Marcia L A

2015-09-07

The SERS enhancement factor (SERS-EF) is one of the most important parameters that characterizes the ability of a given substrate to enhance the Raman signal for SERS applications. The comparison of SERS intensities and SERS-EF values across different substrates is a common practice to unravel the performance of a given substrate. In this study, it is shown that such a comparison may lack significance if we compare substrates of very distinct nature and optical properties. It is specifically shown that the SERS-EF values for static substrates (e.g. immobilized metallic nanostructures) cannot be compared to those of dynamic ones (e.g. colloidal metal nanoparticle solutions), and that the optical properties for the latter show strong dependence on the metal-molecule interaction dynamics. The most representative experimental results concerning the dynamic substrates have been supported by generalized Mie theory simulations, which are tools used to describe the substrate complexity and the microscopic information not usually taken into account.

Glomerular prostaglandins modulate vascular reactivity of the downstream efferent arterioles.

PubMed

Arima, S; Ren, Y; Juncos, L A; Carretero, O A; Ito, S

1994-03-01

The balance of vascular resistance in afferent (Af-) and efferent arterioles (Ef-Arts) is a crucial factor that determines glomerular hemodynamics. We have recently reported that when Ef-Arts were perfused from the distal end of the Af-Art through the glomerulus (orthograde perfusion; OP), both angiotensin II (Ang II) and norepinephrine (NE) induced much weaker constriction than they did when Ef-Arts were perfused from the distal end (retrograde perfusion; RP). This difference was not affected by inhibiting synthesis of nitric oxide. In the present study, we tested the hypothesis that glomerular prostaglandins (PGs) may modulate vascular reactivity of the downstream Ef-Art. In addition, we examined the possible modulatory role of PGs in the Af-Art responses to Ang II or NE. Both Ang II and NE caused dose-dependent constriction of Ef-Arts with either OP or RP; however, the constriction was stronger in RP. At 10(-8) M, Ang II decreased Ef-Art diameter by 35 +/- 3.5% in OP (N = 9) compared to 73 +/- 3.9% in RP (N = 5), while 10(-6) M NE decreased the diameter by 25 +/- 3.6% in OP (N = 9) compared to 62 +/- 7.2% in RP (N = 5). Pretreatment with 5 x 10(-5) M indomethacin (Indo) did not alter basal diameter with either method of perfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Executive Function Buffers the Association between Early Math and Later Academic Skills.

PubMed

Ribner, Andrew D; Willoughby, Michael T; Blair, Clancy B

2017-01-01

Extensive evidence has suggested that early academic skills are a robust indicator of later academic achievement; however, there is mixed evidence of the effectiveness of intervention on academic skills in early years to improve later outcomes. As such, it is clear there are other contributing factors to the development of academic skills. The present study tests the role of executive function (EF) (a construct made up of skills complicit in the achievement of goal-directed tasks) in predicting 5th grade math and reading ability above and beyond math and reading ability prior to school entry, and net of other cognitive covariates including processing speed, vocabulary, and IQ. Using a longitudinal dataset of N = 1292 participants representative of rural areas in two distinctive geographical parts of the United States, the present investigation finds EF at age 5 strongly predicts 5th grade academic skills, as do cognitive covariates. Additionally, investigation of an interaction between early math ability and EF reveals the magnitude of the association between early math and later math varies as a function of early EF, such that participants who have high levels of EF can "catch up" to peers who perform better on assessments of early math ability. These results suggest EF is pivotal to the development of academic skills throughout elementary school. Implications for further research and practice are discussed.

Maternal depressive symptoms, mother-child interactions, and children's executive function.

PubMed

Gueron-Sela, Noa; Camerota, Marie; Willoughby, Michael T; Vernon-Feagans, Lynne; Cox, Martha J

2018-01-01

This study examined the independent and mediated associations between maternal depression symptoms (MDS), mother-child interaction, and child executive function (EF) in a prospective longitudinal sample of 1,037 children (50% boys) from predominantly low-income and rural communities. When children were 6, 15 and 24 months of age, mothers reported their level of depressive symptomatology. At 24 and 36 months of age, mother-child interactions during play were rated for warmth-sensitivity and harsh-intrusiveness, and dyadic joint attention and maternal language complexity were assessed from a book sharing activity. Children's EF (i.e., inhibitory control, working memory, and set shifting) were assessed at ages 36 and 48 months using a battery of six tasks. Results indicated that MDS at ages 15 and 24 months were negatively associated with children's EF at age 48 months. Additionally, harsh-intrusive mother-child interactions partially mediated this link. Although warmth-sensitivity, dyadic joint attention and maternal language complexity were all longitudinally related to EF, they did not serve as mediating mechanisms between MDS and EF. These results were obtained while controlling for multiple demographic factors, children's earlier cognitive abilities, maternal general distress and childcare experiences. Findings from this study identify 1 mechanism through which early exposure to MDS could be related to children's EF. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Influence of anisotropic conductivity in the skull and white matter on transcranial direct current stimulation via an anatomically realistic finite element head model

NASA Astrophysics Data System (ADS)

Suh, Hyun Sang; Lee, Won Hee; Kim, Tae-Seong

2012-11-01

To establish safe and efficient transcranial direct current stimulation (tDCS), it is of particular importance to understand the electrical effects of tDCS in the brain. Since the current density (CD) and electric field (EF) in the brain generated by tDCS depend on various factors including complex head geometries and electrical tissue properties, in this work, we investigated the influence of anisotropic conductivity in the skull and white matter (WM) on tDCS via a 3D anatomically realistic finite element head model. We systematically incorporated various anisotropic conductivity ratios into the skull and WM. The effects of anisotropic tissue conductivity on the CD and EF were subsequently assessed through comparisons to the conventional isotropic solutions. Our results show that the anisotropic skull conductivity significantly affects the CD and EF distribution: there is a significant reduction in the ratio of the target versus non-target total CD and EF on the order of 12-14%. In contrast, the WM anisotropy does not significantly influence the CD and EF on the targeted cortical surface, only on the order of 1-3%. However, the WM anisotropy highly alters the spatial distribution of both the CD and EF inside the brain. This study shows that it is critical to incorporate anisotropic conductivities in planning of tDCS for improved efficacy and safety.

Soil nitrous oxide emissions after deposition of dairy cow excreta in eastern Canada.

PubMed

Rochette, Philippe; Chantigny, Martin H; Ziadi, Noura; Angers, Denis A; Bélanger, Gilles; Charbonneau, Édith; Pellerin, Doris; Liang, Chang; Bertrand, Normand

2014-05-01

Urine and dung deposited by grazing dairy cows are a major source of nitrous oxide (NO), a potent greenhouse gas that contributes to stratospheric ozone depletion. In this study, we quantified the emissions of NO after deposition of dairy cow excreta onto two grassland sites with contrasting soil types in eastern Canada. Our objectives were to determine the impact of excreta type, urine-N rate, time of the year, and soil type on annual NO emissions. Emissions were monitored on sandy loam and clay soils after spring, summer, and fall urine (5 and 10 g N patch) and dung (1.75 kg fresh weight dung) applications to perennial grasses in two successive years. The mean NO emission factor (EF) for urine was 1.09% of applied N in the clay soil and 0.31% in the sandy loam soil, estimates much smaller than the default Intergovernmental Panel on Climate Change (IPCC) default value for total excreta N (2%). Despite variations in urine composition and in climatic conditions, these soil-specific EFs were similar for the two urine-N application rates. The time of the year when urine was applied had no impact on emissions from the sandy loam soil, but greater EFs were observed after summer (1.59%) than spring (1.14%) and fall (0.55%) applications in the clay soil. Dung deposition impact on NO emission was smaller than that of urine, with a mean EF of 0.15% in the sandy loam soil and 0.08% in the clay soil. Our results suggest (i) that the IPCC default EF overestimates NO emissions from grazing cattle excreta in eastern Canada by a factor of 4.3 and (ii) that a region-specific inventory methodology should account for soil type and should use specific EFs for urine and dung. Copyright © by the American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America, Inc.

Assessing reproductive choices of women and the likelihood of oocyte cryopreservation in the era of elective oocyte freezing.

PubMed

Milman, Lauren W; Senapati, Suneeta; Sammel, Mary D; Cameron, Katherine D; Gracia, Clarisa

2017-05-01

To assess reproductive choices of reproductive-age women in the United States and factors that influence consideration of elective egg freezing (EF). Cross-sectional internet-based survey. Not applicable. One thousand women aged 21-45 years. An anonymous 63-item self-administered questionnaire was distributed to a representative cross-section of women aged 21-45 years, stratified by age <35 years. One-half of the sample had at least one child, and the other one-half did not. All of the participants were interested in having children. Ordinal logistic regression was performed to characterize the association of population characteristics and reproductive knowledge with likelihood to consider EF. Willingness to pay was assessed with the use of a linear prediction model that calculated dollar amounts at varying success rates. Overall, 87.2% of the sample reported awareness of EF for fertility preservation and 25% would consider this option, yet only 29.8% knew what the EF process entails. Once informed of the process, 30% of women changed their level of consideration. In a multivariable model, Asian race, single status, and infertility increased the likelihood of considering EF. Women likely to consider egg freezing would be willing to pay $3,811.55 (95% confidence interval $2,862.66-$4,760.44). If the total cost were $10,000, 91% of the cohort would accept at minimum a 50% chance of successful delivery. This study is one of the largest cohorts of reproductive-age women in the United States addressing reproductive choices and factors associated with the importance of having a biologically related child and the likelihood of considering EF to preserve fertility. This study provides important insight into the willingness to pay for this elective endeavor. Copyright © 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Assessing Reproductive Choices of Women and the Liklihood of Oocyte Cryopreservation in the Era of Elective Oocyte Freezing

PubMed Central

Milman, Lauren W.; Senapati, Suneeta; Sammel, Mary D.; Cameron, Katherine D.; Gracia, Clarisa

2017-01-01

OBJECTIVE To assess reproductive choices of US reproductive age women and factors that influence consideration of elective egg freezing (EF). DESIGN Cross-sectional Internet based survey of 1000 women METHODS An anonymous 63-item self-administered questionnaire was distributed to a representative cross section of reproductive age women age 21–45, stratified by age

Long-Term Results of CCG 5942: A Randomized Comparison of Chemotherapy With and Without Radiotherapy for Children With Hodgkin's Lymphoma—A Report From the Children's Oncology Group

PubMed Central

Wolden, Suzanne L.; Chen, Lu; Kelly, Kara M.; Herzog, Philip; Gilchrist, Gerald S.; Thomson, John; Sposto, Richard; Kadin, Marshall E.; Hutchinson, Raymond J.; Nachman, James

2012-01-01

Purpose In 1995, the Children's Cancer Group (CCG) opened a trial for patients with Hodgkin's lymphoma evaluating whether low-dose involved-field radiation therapy (IFRT) improved event-free survival (EFS) for patients achieving a complete response after chemotherapy. We present the long-term study outcome using final data through March 2007. Patients and Methods Between January 1995 and December 1998, 826 eligible patients were enrolled onto CCG 5942. Four hundred ninety-eight patients achieving an initial complete response to chemotherapy were randomly assigned to receive IFRT or no further therapy. EFS and overall survival (OS) were assessed from the date of study entry or random assignment, as appropriate. Results Ten-year EFS and OS rates for the entire cohort were 83.5% and 92.5%, respectively. In an as-treated analysis for randomly assigned patients, the 10-year EFS and OS rates were 91.2% and 97.1%, respectively, for IFRT and 82.9% and 95.9%, respectively, for no further therapy. For EFS and OS comparisons, P = .004 and P = .50, respectively. Bulk disease, “B” symptoms, and nodular sclerosis histology were risk factors for inferior EFS. Conclusion With a median follow-up of 7.7 years, IFRT produced a statistically significant improvement in EFS but no improvement in OS. For individual patients, the relative risks of relapse versus late effects of IFRT must be considered. Patient and disease characteristics and early response assessment will aid in deciding which patients are most likely to benefit from IFRT. PMID:22649136

Quantifying the physical, social and attitudinal environment of children with cerebral palsy.

PubMed

Dickinson, Heather O; Colver, Allan

2011-01-01

To develop an instrument to represent the availability of needed environmental features (EFs) in the physical, social and attitudinal environment of home, school and community for children with cerebral palsy. Following a literature review and qualitative studies, the European Child Environment Questionnaire (ECEQ) was developed to capture whether EFs needed by children with cerebral palsy were available to them: 24, 24 and 12 items related to the physical, social and attitudinal environments, respectively. The ECEQ was administered to parents of 818 children with cerebral palsy aged 8-12 years, in seven European countries. A domain structure was developed using factor analysis. Parents responded to 98% of items. Seven items were omitted from statistical models as the EFs they referred to were available to most children who needed them; two items were omitted as they did not fit well into plausible domains. The final domains, based on 51 items, were: Transport, Physical - home, Physical - community, Physical - school, Social support - home, Social support - community, Attitudes - family and friends, Attitudes - teachers and therapists, Attitudes - classmates. ECEQ was acceptable to parents and can be used to assess both the access children with cerebral palsy have to the EFs that they need and how available individual EFs are.

HLA-G+3027 polymorphism is associated with tumor relapse in pediatric Hodgkin's lymphoma.

PubMed

De Re, Valli; Caggiari, Laura; Mussolin, Lara; d'Amore, Emanuele Stefano; Famengo, Barbara; De Zorzi, Mariangela; Martina, Lia; Elia, Caterina; Pillon, Marta; Santoro, Nicola; Muggeo, Paola; Buffardi, Salvatore; Bianchi, Maurizio; Sala, Alessandra; Farruggia, Piero; Vinti, Luciana; Carosella, Edgardo D; Burnelli, Roberta; Mascarin, Maurizio

2017-12-01

In this study, we tested whether polymorphisms in human leukocyte antigen G (HLA-G) were associated with event-free survival (EFS) in pediatric Hodgkin's lymphoma (HL). We evaluated the association of HLA-G 3'-UTR polymorphisms with EFS in 113 pediatric HL patients treated using the AIEOP LH-2004 protocol. Patients with the +3027-C/A genotype (rs17179101, UTR-7 haplotype) showed lower EFS than those with the +3027-C/C genotype (HR= 3.23, 95%CI: 0.99-10.54, P=0.012). Female patients and systemic B symptomatic patients with the HLA-G +3027 polymorphism showed lower EFS. Multivariate analysis showed that the +3027-A polymorphism (HR 3.17, 95%CI 1.16-8.66, P=0.025) was an independent prognostic factor. Immunohistochemical analysis showed that HL cells from patients with the +3027-C/A genotype did not express HLA-G. Moreover, HLA-G +3027 polymorphism improved EFS prediction when added to the algorithm for therapeutic group classification of pediatric HL patients. Our findings suggest HLA-G +3027 polymorphism is a prognostic marker in pediatric HL patients undergoing treatment according to LH-2004 protocol.

The union of narrative and executive function: different but complementary

PubMed Central

Friend, Margaret; Bates, Raven Phoenix

2014-01-01

Oral narrative production develops dramatically from 3 to 5 years of age, and is a key factor in a child's ability to communicate about the world. Concomitant with this are developments in executive function (EF). For example, executive attention and behavioral inhibition show marked development beginning around 4 years of age. Both EF and oral narrative abilities have important implications for academic success, but the relationship between them is not well understood. The present paper utilizes a cross-lagged design to assess convergent and predictive relations between EF and narrative ability. As a collateral measure, we collected a Language Sample during 10 min of free play. Language Sample did not share significant variance with Narrative Production, thus general language growth from Wave 1 to Wave 2 cannot account for the predictive relations between EF and Narrative. Our findings suggest that although EF and Narrative ability appear independent at each Wave, they nevertheless support each other over developmental time. Specifically, the ability to maintain focus at 4 years supports subsequent narrative ability and narrative ability at 4 years supports subsequent facility and speed in learning and implementing new rules. PMID:24872811

Inhibition by ricin of protein synthesis in vitro. Ribosomes as the target of the toxin

PubMed Central

Montanaro, Lucio; Sperti, Simonetta; Stirpe, Fiorenzo

1973-01-01

1. Ricin (a toxic protein from the seeds of Ricinus communis) is a powerful inhibitor of the poly(U)-directed incorporation of phenylalanine into polypeptides catalysed by isolated rat liver ribosomes and elongation factors 1 and 2 (EF 1 and EF 2). The inhibition can be largely overcome by increasing the concentration of ribosomes. 2. The toxin does not affect the binding of phenylalanyl-tRNA to ribosomes catalysed by EF 1, nor does it inhibit the puromycin reaction used as a test for peptide-bond formation catalysed by ribosomes. 3. Ricin inhibits the ribosome-linked GTP hydrolysis catalysed by EF 2. 4. Ribosomes treated with ricin and washed through sucrose gradients containing 0.6m-NH4Cl are functionally inactive in those assay systems that are sensitive to the presence of added toxin. 5. It is suggested that ricin brings about an irreversible modification of ribosomes which impairs their ability to interact with EF 2. Since ricin inhibits at a molar concentration much lower than that of ribosomes it probably acts catalytically. No added cofactor is necessary for the inhibitory action of the toxin. PMID:4780693

Recipient Risk Factors for Graft Failure in the Cornea Donor Study

PubMed Central

Sugar, Alan; Tanner, Jean Paul; Dontchev, Mariya; Tennant, Brad; Schultze, Robert L.; Dunn, Steven P.; Lindquist, Thomas D.; Gal, Robin L.; Beck, Roy W.; Kollman, Craig; Mannis, Mark J.; Holland, Edward J.

2009-01-01

Purpose Identify recipient factors which may be related to risk of corneal graft failure Design Multi-center prospective, double-masked, controlled clinical trial Participants 1090 subjects undergoing corneal transplantation for a moderate risk condition (principally Fuchs’ dystrophy or pseudophakic corneal edema) Methods Donor corneas were assigned using a random approach without respect to recipient factors, and surgeons were masked to information about the donor cornea including donor age. Surgery and post-operative care were performed according to the surgeons’ usual routines and subjects were followed for five years. Baseline factors were evaluated for their association with graft failure. Main Outcome Measures Graft failure, defined as a regraft or a cloudy cornea that was sufficiently opaque to compromise vision for a minimum of three consecutive months. Results Preoperative diagnosis of pseudophakic/aphakic corneal edema increased graft failure risk approximately 4-fold compared with Fuchs’ dystrophy (27% vs. 7%). Prior glaucoma surgery with preoperative glaucoma medication use substantially increased the graft failure rate. Factors not strongly associated with graft failure included age, gender, diabetes, smoking, and graft size. Conclusion The risk of graft failure is significantly increased in eyes with pseudophakic or aphakic corneal edema compared with Fuchs’ dystrophy, independent of lens status, and in eyes with a history of glaucoma. PMID:19395036

Protective effects of radon inhalation on carrageenan-induced inflammatory paw edema in mice.

PubMed

Kataoka, Takahiro; Teraoka, Junichi; Sakoda, Akihiro; Nishiyama, Yuichi; Yamato, Keiko; Monden, Mayuko; Ishimori, Yuu; Nomura, Takaharu; Taguchi, Takehito; Yamaoka, Kiyonori

2012-04-01

We assessed whether radon inhalation inhibited carrageenan-induced inflammation in mice. Carrageenan (1% v/v) was injected subcutaneously into paws of mice that had or had not inhaled approximately 2,000 Bq/m(3) of radon for 24 h. Radon inhalation significantly increased superoxide dismutase (SOD) and catalase activities and significantly decreased lipid peroxide levels in mouse paws, indicating that radon inhalation activates antioxidative functions. Carrageenan administration induced paw edema and significantly increased tumor necrosis factor-alpha (TNF-α) and nitric oxide in serum. However, radon inhalation significantly reduced carrageenan-induced paw edema. Serum TNF-α levels were lower in the radon-treated mice than in sham-treated mice. In addition, SOD and catalase activities in paws were significantly higher in the radon-treated mice than in the sham-treated mice. These findings indicated that radon inhalation had anti-inflammatory effects and inhibited carrageenan-induced inflammatory paw edema.

A Report of Two Cases of Solid Facial Edema in Acne.

PubMed

Kuhn-Régnier, Sarah; Mangana, Joanna; Kerl, Katrin; Kamarachev, Jivko; French, Lars E; Cozzio, Antonio; Navarini, Alexander A

2017-03-01

Solid facial edema (SFE) is a rare complication of acne vulgaris. To examine the clinical features of acne patients with solid facial edema, and to give an overview on the outcome of previous topical and systemic treatments in the cases so far published. We report two cases from Switzerland, both young men with initially papulopustular acne resistant to topical retinoids. Both cases responded to oral isotretinoin, in one case combined with oral steroids. Our cases show a strikingly similar clinical appearance to the cases described by Connelly and Winkelmann in 1985 (Connelly MG, Winkelmann RK. Solid facial edema as a complication of acne vulgaris. Arch Dermatol. 1985;121(1):87), as well as to cases of Morbihan's disease that occurs as a rare complication of rosacea. Even 30 years after, the cause of the edema remains unknown. In two of the original four cases, a potential triggering factor was identified such as facial trauma or insect bites; however, our two patients did not report such occurrencies. The rare cases of solid facial edema in both acne and rosacea might hold the key to understanding the specific inflammatory pattern that creates both persisting inflammation and disturbed fluid homeostasis which can occur as a slightly different presentation in dermatomyositis, angioedema, Heerfordt's syndrome and other conditions.

Shot noise and Fano factor in tunneling in three-band pseudospin-1 Dirac-Weyl systems

NASA Astrophysics Data System (ADS)

Zhu, Rui; Hui, Pak Ming

2017-06-01

Tunneling through a potential barrier of height V0 in a two-dimensional system with a band structure consisting of three bands with a flat band intersecting the touching apices of two Dirac cones is studied. Results of the transmission coefficient at various incident angles, conductivity, shot noise, and Fano factor in this pseudospin-1 Dirac-Weyl system are presented and contrasted with those in graphene which is typical of a pseudospin-1/2 system. The pseudospin-1 system is found to show a higher transmission and suppressed shot noise in general. Significant differences in the shot noise and Fano factor due to the super Klein tunneling effect that allows perfect transmission at all incident angles under certain conditions are illustrated. For Fermi energy EF =V0 / 2, super Klein tunneling leads to a noiseless conductivity that takes on the maximum value 2e2 DkF / (πh) for 0 ≤EF ≤V0. This gives rise to a minimum Fano factor, in sharp contrast with that of a local maximum in graphene. For EF =V0, the band structure of pseudospin-1 system no longer leads to a quantized value of the conductivity as in graphene. Both the conductivity and the shot noise show a minimum with the Fano factor approaching 1/4, which is different from the value of 1/3 in graphene.

Effect of streptokinase on reperfusion after acute myocardial infarction and its complications: an ex-post facto study.

PubMed

Taheri, Leila; Boroujeni, Ali Zargham; Kargar Jahromi, Marzieh; Charkhandaz, Maryam; Hojat, Mohsen

2015-01-01

Emergency treatment of patients with acute myocardial infarction is very important. Streptokinase in Iran is often as the only clot-busting medication is used. The purpose of using streptokinase medication is to revive the ischemic heart tissue, although has dangerous complications too. Therefore, the present study aimed to determine the effect of streptokinase on reperfusion after acute myocardial infarction and its complications, has been designed and conducted. This is an Ex-post facto study. The study population included patients who suffer from acute myocardial infarction. The sample size was 300 patients, and 2 groups were matched, in variables of age, sex, underlying disease, frequencies and area of MI. Data collection did by researcher making questionnaire, that accept face and content validity by 10 expert researcher, the reliability was conducted with Spearman's test (r=0.85) by Test-retest method. Data analysis did by SPSS software: V 12. Mean of EF in SK group was (46.15±8.11) and in control group was (43.11±12.57). Significant relationship was seen between SK, arrhythmia occurring and improve EF reperfusion by chi-square test (p=0.028), (p=0.020).The most arrhythmia in SK group was Ventricular Tachycardia (20.7%). Significant statistical relation between SK and mortality were found by Chi-square test (p=0.001). But a meaningful statistical relation was not found between SK and pulmonary edema incidence (p=0.071). Nurses of CCU should be aware about SK complications such as hypotension, bleeding and arrhythmias. Proposed compare SK and tissue plasminogen drug in reperfusion and complications effect.

Risk of Heart Failure With Preserved Ejection Fraction in Older Women After Contemporary Radiotherapy for Breast Cancer.

PubMed

Saiki, Hirofumi; Petersen, Ivy A; Scott, Christopher G; Bailey, Kent R; Dunlay, Shannon M; Finley, Randi R; Ruddy, Kathryn J; Yan, Elizabeth; Redfield, Margaret M

2017-04-11

Cardiomyocytes are resistant to radiation. However, cardiac radiation exposure causes coronary microvascular endothelial inflammation, a perturbation implicated in the pathogenesis of heart failure (HF) and particularly HF with preserved ejection fraction (HFpEF). Radiotherapy for breast cancer results in variable cardiac radiation exposure and may increase the risk of HF. We conducted a population-based case-control study of incident HF in 170 female residents of Olmsted County, Minnesota (59 cases and 111 controls), who underwent contemporary (1998-2013) radiotherapy for breast cancer with computed tomography-assisted radiotherapy planning. Controls were matched to cases for age, tumor side, chemotherapy use, diabetes mellitus, and hypertension. Mean cardiac radiation dose (MCRD) in each patient was calculated from the patient's computed tomography images and radiotherapy plan. Mean age at radiotherapy was 69±9 years. Of HF cases, 38 (64%) had EF≥50% (HFpEF), 18 (31%) had EF<50% (HF with reduced EF), and 3 (5%) did not have EF measured. The EF was ≥40% in 50 of the 56 HF cases (89%) with an EF measurement. The mean interval from radiotherapy to HF was 5.8±3.4 years. The odds of HF was higher in patients with a history of ischemic heart disease or atrial fibrillation. The MCRD was 2.5 Gy (range, 0.2-13.1 Gy) and higher in cases (3.3±2.7 Gy) than controls (2.1±2.0 Gy; P =0.004). The odds ratio (95% confidence interval) for HF per log MCRD was 9.1 (3.4-24.4) for any HF, 16.9 (3.9-73.7) for HFpEF, and 3.17 (0.8-13.0) for HF with reduced EF. The increased odds of any HF or HFpEF with increasing MCRD remained significant after adjustment for HF risk factors and in sensitivity analyses matching by cancer stage rather than tumor side. Only 18.6% of patients experienced new or recurrent ischemic events between radiotherapy and the onset of HF. The relative risk of HFpEF increases with increasing cardiac radiation exposure during contemporary conformal breast cancer radiotherapy. These data emphasize the importance of radiotherapy techniques that limit MCRD during breast cancer treatment. Moreover, these data provide further support for the importance of coronary microvascular compromise in the pathophysiology of HFpEF. © 2017 American Heart Association, Inc.

Recent structural studies on Dom34/aPelota and Hbs1/aEF1α: important factors for solving general problems of ribosomal stall in translation

PubMed Central

Kobayashi, Kan; Ishitani, Ryuichiro; Nureki, Osamu

2013-01-01

In the translation process, translating ribosomes usually move on an mRNA until they reach the stop codon. However, when ribosomes translate an aberrant mRNA, they stall. Then, ribosomes are rescued from the aberrant mRNA, and the aberrant mRNA is subsequently degraded. In eukaryotes, Pelota (Dom34 in yeast) and Hbs1 are responsible for solving general problems of ribosomal stall in translation. In archaea, aPelota and aEF1α, homologous to Pelota and Hbs1, respectively, are considered to be involved in that process. In recent years, great progress has been made in determining structures of Dom34/aPelota and Hbs1/aEF1α. In this review, we focus on the functional roles of Dom34/aPelota and Hbs1/aEF1α in ribosome rescue, based on recent structural studies of them. We will also present questions to be answered by future work. PMID:27493551

Near-field engineering of Fano resonances in a plasmonic assembly for maximizing CARS enhancements.

PubMed

He, Jinna; Fan, Chunzhen; Ding, Pei; Zhu, Shuangmei; Liang, Erjun

2016-02-10

Surface enhanced coherent anti-Stokes Raman scattering (SECARS) is a sensitive tool and promising for single molecular detection and chemical selective imaging. However, the enhancement factors (EF) were only 10~100 for colloidal silver and gold nanoparticles usually used as SECARS substrates. In this paper, we present a design of SECARS substrate consisting of three asymmetric gold disks and strategies for maximizing the EF by engineering near-field properties of the plasmonic Fano nanoassembly. It is found that the E-field "hot spots" corresponding to three different frequencies involved in SECARS process can be brought to the same spatial locations by tuning incident orientations, giving rise to highly confined SECARS "hot spots" with the EF reaching single-molecule sensitivity. Besides, an even higher EF of SECARS is achieved by introducing double Fano resonances in this plasmonic nanoassembly via further enlarging the sizes of the constituent disks. These findings put an important step forward to the plasmonic substrate design for SECARS as well as for other nonlinear optical processes.

Design, synthesis, and evaluation of asymmetric EF24 analogues as potential anti-cancer agents for lung cancer.

PubMed

Wu, Jianzhang; Wu, Shoubiao; Shi, Lingyi; Zhang, Shanshan; Ren, Jiye; Yao, Song; Yun, Di; Huang, Lili; Wang, Jiabing; Li, Wulan; Wu, Xiaoping; Qiu, Peihong; Liang, Guang

2017-01-05

The nuclear factor-kappa B (NF-κB) signaling pathway has been targeted for the therapy of various cancers, including lung cancer. EF24 was considered as a potent inhibitor of NF-κB signaling pathway. In this study, a series of asymmetric EF24 analogues were synthesized and evaluated for their anti-cancer activity against three lung cancer cell lines (A549, LLC, H1650). Most of the compounds exhibited good anti-tumor activity. Among them, compound 81 showed greater cytotoxicity than EF24. Compound 81 also possessed a potent anti-migration and anti-proliferative ability against A549 cells in a concentration-dependent manner. Moreover, compound 81 induced lung cancer cells death by inhibiting NF-κB signaling pathway, and activated the JNK-mitochondrial apoptotic pathway by increasing reactive oxygen species (ROS) generation resulting in apoptosis. In summary, compound 81 is a valuable candidate for anti-lung cancer therapy. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Meta-Analysis of the Effects of Computerized Cognitive Training on Executive Functions: a Cross-Disciplinary Taxonomy for Classifying Outcome Cognitive Factors.

PubMed

Webb, Shannon L; Loh, Vanessa; Lampit, Amit; Bateman, Joel E; Birney, Damian P

2018-06-01

The growing prevalence of neurodegenerative disorders associated with aging and cognitive decline has generated increasing cross-disciplinary interest in non-pharmacological interventions, such as computerized cognitive training (CCT), which may prevent or slow cognitive decline. However, inconsistent findings across meta-analytic reviews in the field suggest a lack of cross-disciplinary consensus and on-going debate regarding the benefits of CCT. We posit that a contributing factor is the lack of a theoretically-based taxonomy of constructs and representative tasks typically used. An integration of the Cattell-Horn-Carroll (CHC) taxonomy of broad and narrow cognitive factors and the Miyake unity-diversity theory of executive functions (EF) is proposed (CHC-M) as an attempt to clarify this issue through representing and integrating the disciplines contributing to CCT research. The present study assessed the utility of this taxonomy by reanalyzing the Lampit et al. (2014) meta-analysis of CCT in healthy older adults using the CHC-M framework. Results suggest that: 1) substantively different statistical effects are observed when CHC-M is applied to the Lampit et al. meta-analytic review, leading to importantly different interpretations of the data; 2) typically-used classification practices conflate Executive Function (EF) tasks with fluid reasoning (Gf) and retrieval fluency (Gr), and Attention with sensory perception; and 3) there is theoretical and practical advantage in differentiating attention and working-memory tasks into the narrow shifting, inhibition, and updating EF domains. Implications for clinical practice, particularly for our understanding of EF are discussed.

[Shereshevsky-Turner syndrome: Estrogen replacement therapy and cardiovascular risk factors].

PubMed

Yevstigneeva, O A; Andreeva, E N; Grigoryan, O R; Volevodz, N N; Melnichenko, G A; Dedov, I I

To investigate the impact of menopausal hormone therapy (MHT) on the expression of risk factors for cardiovascular events (CVEs) in patients with Shereshevsky-Turner syndrome (STS); to elaborate an algorithm for patient management using MHT. From 2010 to 2012, a total of 41 patients aged 14 to 35 years with STS were examined in the framework of a prospective observational study. 100 STS case histories in 2000 to 2009 were retrospectively analyzed. The indicators of the so-called cardiometabolic risk, such as body mass index (BMI), lipidogram readings, venous plasma glucose levels, and blood pressure, were estimated in relation to the type of MHT. In the prospective part of the investigation, an angioscan was used to estimate vessel characteristics (stiffness, wall tone, endothelial function (EF)), by using the examination data. 90% of the patients with STS were found to have risk factors for CVEs: atherogenic dyslipidemia (85%; 51% in the general female population of the same age), diastolic hypertension (36%; no more than 5% that is not typical for age-matched healthy general female population). In addition to increased arterial wall stiffness (AWS), obvious EF disorder is typical for STS patients. MHT was accompanied by a dose-dependent (estradiol, at least 2 mg) reduction in diastolic blood pressure by an average of 13% over 24 months, an increase in high density lipoprotein levels by more than 10% over 24 months and also contributedto a decrease in AWS and an improvement in EF. By favorably affecting the EF of vessels and reducing the severity of atherogenic dyslipidemia, MHT potentially enables a reduction in CV risk in patients with STS.

Exploratory Decision-Tree Modeling of Data from the Randomized REACTT Trial of Tadalafil Versus Placebo to Predict Recovery of Erectile Function After Bilateral Nerve-Sparing Radical Prostatectomy

PubMed Central

Montorsi, Francesco; Oelke, Matthias; Henneges, Carsten; Brock, Gerald; Salonia, Andrea; d’Anzeo, Gianluca; Rossi, Andrea; Mulhall, John P.; Büttner, Hartwig

2017-01-01

Background Understanding predictors for the recovery of erectile function (EF) after nerve-sparing radical prostatectomy (nsRP) might help clinicians and patients in preoperative counseling and expectation management of EF rehabilitation strategies. Objective To describe the effect of potential predictors on EF recovery after nsRP by post hoc decision-tree modeling of data from A Study of Tadalafil After Radical Prostatectomy (REACTT). Design, setting, and participants Randomized double-blind double-dummy placebo-controlled trial in 423 men aged <68 yr with adenocarcinoma of the prostate (Gleason ≤7, normal preoperative EF) who underwent nsRP at 50 centers from nine European countries and Canada. Intervention Postsurgery 1:1:1 randomization to 9-mo double-blind treatment with tadalafil 5 mg once a day (OaD), tadalafil 20 mg on demand, or placebo, followed by a 6-wk drug-free-washout, and a 3-mo open-label tadalafil OaD treatment. Outcome measurements and statistical analysis Three decision-tree models, using the International Index of Erectile Function-Erectile Function (IIEF-EF) domain score at the end of double-blind treatment, washout, and open-label treatment as response variable. Each model evaluated the association between potential predictors: presurgery IIEF domain and IIEF single-item scores, surgical approach, nerve-sparing score (NSS), and postsurgery randomized treatment group. Results and limitations The first decision-tree model (n = 422, intention-to-treat population) identified high presurgery sexual desire (IIEF item 12: ≥3.5 and <3.5) as the key predictor for IIEF-EF at the end of double-blind treatment (mean IIEF-EF: 14.9 and 11.1), followed by high confidence to get and maintain an erection (IIEF item 15: ≥3.5 and <3.5; IIEF-EF: 15.4 and 7.1). For patients meeting these criteria, additional non-IIEF–related predictors included robot-assisted laparoscopic surgery (yes or no; IIEF-EF: 19.3 and 12.6), quality of nerve sparing (NSS: <2.5 and ≥2.5; IIEF-EF: 14.3 and 10.5), and treatment with tadalafil OaD (yes and no; IIEF-EF: 17.6 and 14.3). Additional analyses after washout and open-label treatment identified high presurgery intercourse satisfaction as the key predictor. Conclusions Exploratory decision-tree analyses identified high presurgery sexual desire, confidence, and intercourse satisfaction as key predictors for EF recovery. Patients meeting these criteria might benefit the most from conserving surgery and early postsurgery EF rehabilitation. Strategies for improving EF after surgery should be discussed preoperatively with all patients; this information may support expectation management for functional recovery on an individual patient level. Patient summary Understanding how patient characteristics and different treatment options affect the recovery of erectile function (EF) after radical surgery for prostate cancer might help physicians select the optimal treatment for their patients. This analysis of data from a clinical trial suggested that high presurgery sexual desire, sexual confidence, and intercourse satisfaction are key factors predicting EF recovery. Patients meeting these criteria might benefit the most from conserving surgery (robot-assisted surgery, perfect nerve sparing) and postsurgery medical rehabilitation of EF. Trial registration ClinicalTrials.gov, NCT01026818 PMID:26947602

Monitoring the kinetics of the pH driven transition of the anthrax toxin prepore to the pore by biolayer interferometry and surface plasmon resonance

PubMed Central

Naik, Subhashchandra; Brock, Susan; Akkaladevi, Narahari; Tally, Jon; Mcginn-Straub, Wesley; Zhang, Na; Gao, Phillip; Gogol, E. P.; Pentelute, B. L.; Collier, R. John; Fisher, Mark T.

2013-01-01

Domain 2 of the anthrax protective antigen (PA) prepore heptamer unfolds and refolds during endosome acidification to generate an extended 100 Å beta barrel pore that inserts into the endosomal membrane. The PA pore facilitates the pH dependent unfolding and translocation of bound toxin enzymic components, lethal factor (LF) and/or edema factor (EF), from the endosome into the cytoplasm. We constructed immobilized complexes of the prepore with the PA-binding domain of LF (LFN) to monitor the real-time prepore to pore kinetic transition using surface plasmon resonance (SPR) and bio-layer interferometry (BLI). The kinetics of this transition increased as the solution pH was decreased from pH 7.5 to pH 5.0, mirroring acidification of the endosome. Once transitioned, the LFN-PA pore complex was removed from the BLI biosensor tip and deposited onto EM grids, where the PA pore formation was confirmed by negative stain electron microscopy. When the soluble receptor domain (ANTRX2/CMG2) binds the immobilized PA prepore, the transition to the pore state was observed only after the pH was lowered to early or late endosomal pH conditions (5.5 to 5.0 respectively). Once the pore formed, the soluble receptor readily dissociated from the PA pore. Separate binding experiments with immobilized PA pores and soluble receptor indicate that the receptor has a weakened propensity to bind to the transitioned pore. This immobilized anthrax toxin platform can be used to identify or validate potential antimicrobial lead compounds capable of regulating and/or inhibiting anthrax toxin complex formation or pore transitions. PMID:23964683

Interventions for the treatment of uveitic macular edema: a systematic review and meta-analysis

PubMed Central

Karim, Rushmia; Sykakis, Evripidis; Lightman, Susan; Fraser-Bell, Samantha

2013-01-01

Background Uveitic macular edema is the major cause of reduced vision in eyes with uveitis. Objectives To assess the effectiveness of interventions in the treatment of uveitic macular edema. Search strategy Cochrane Central Register of Controlled Trials, Medline, and Embase. There were no language or data restrictions in the search for trials. The databases were last searched on December 1, 2011. Reference lists of included trials were searched. Archives of Ophthalmology, Ophthalmology, Retina, the British Journal of Ophthalmology, and the New England Journal of Medicine were searched for clinical trials and reviews. Selection criteria Participants of any age and sex with any type of uveitic macular edema were included. Early, chronic, refractory, or secondary uveitic macular edema were included. We included trials that compared any interventions of any dose and duration, including comparison with another treatment, sham treatment, or no treatment. Data collection and analysis Best-corrected visual acuity and central macular thickness were the primary outcome measures. Secondary outcome data including adverse effects were collected. Conclusion More results from randomized controlled trials with long follow-up periods are needed for interventions for uveitic macular edema to assist in determining the overall long-term benefit of different treatments. The only intervention with sufficiently robust randomized controlled trials for a meta-analysis was acetazolamide, which was shown to be ineffective in improving vision in eyes with uveitic macular edema, and is clinically now rarely used. Interventions showing promise in this disease include dexamethasone implants, immunomodulatory drugs and anti-vascular endothelial growth-factor agents. When macular edema has become refractory after multiple interventions, pars plana vitrectomy could be considered. The disease pathophysiology is uncertain and the course of disease unpredictable. As there are no clear guidelines from the literature, interventions should be tailored to the individual patient. PMID:23807831

IL-1 or TNF receptor gene deletion delays onset of encephalopathy and attenuates brain edema in experimental acute liver failure.

PubMed

Bémeur, Chantal; Qu, Hong; Desjardins, Paul; Butterworth, Roger F

2010-01-01

Previous reports suggested that brain-derived proinflammatory cytokines are involved in the pathogenesis of hepatic encephalopathy (HE) and brain edema in acute liver failure (ALF). To further address this issue, expression of interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) mRNAs were measured in the brains of mice with acute liver failure resulting from exposure to azoxymethane. In addition, time to severe encephalopathy (coma) was assessed in mice lacking genes coding for interferon-gamma, the tumor necrosis factor receptor-1 or the interleukin-1 type 1 receptor. Interleukin-1beta, tumor necrosis factor-alpha and interferon-gamma expression were quantified using RT-PCR. Significant increases in interleukin-1beta and tumor necrosis factor-alpha mRNA were observed in the frontal cortex of azoxymethane-treated wild-type mice at coma stages of encephalopathy. Interferon-gamma, however, could not be detected in the brains of these animals. Onset of severe encephalopathy (coma) and brain edema in ALF mice were significantly delayed in interleukin-1 type 1 receptor or tumor necrosis factor receptor-1 knockout mice. Deletion of the interferon-gamma gene, on the other hand, had no significative effect on the neurological status or brain water content of acute liver failure mice. These results demonstrate that toxic liver injury resulting from exposure to azoxymethane is associated with selective induction of proinflammatory cytokines in the brain and that deletion of tumor necrosis factor receptor-1 or interlukin-1 type 1 receptor delays the onset of coma and brain edema in this model of acute liver failure. These findings further support a role for selective brain-derived cytokines in the pathogenesis of the cerebral complications in acute liver failure and suggest that anti-inflammatory strategies could be beneficial in their prevention. Copyright 2009 Elsevier Ltd. All rights reserved.

TSOC-HFrEF Registry: A Registry of Hospitalized Patients with Decompensated Systolic Heart Failure: Description of Population and Management

PubMed Central

Wang, Chun-Chieh; Chang, Hung-Yu; Yin, Wei-Hsian; Wu, Yen-Wen; Chu, Pao-Hsien; Wu, Chih-Cheng; Hsu, Chih-Hsin; Wen, Ming-Shien; Voon, Wen-Chol; Lin, Wei-Shiang; Huang, Jin-Long; Chen, Shyh-Ming; Yang, Ning-I; Chang, Heng-Chia; Chang, Kuan-Cheng; Sung, Shih-Hsien; Shyu, Kou-Gi; Lin, Jiunn-Lee; Mar, Guang-Yuan; Chan, Kuei-Chuan; Kuo, Jen-Yuan; Wang, Ji-Hung; Chen, Zhih-Cherng; Tseng, Wei-Kung; Cherng, Wen-Jin

2016-01-01

Introduction Heart failure (HF) is a medical condition with a rapidly increasing incidence both in Taiwan and worldwide. The objective of the TSOC-HFrEF registry was to assess epidemiology, etiology, clinical management, and outcomes in a large sample of hospitalized patients presenting with acute decompensated systolic HF. Methods The TSOC-HFrEF registry was a prospective, multicenter, observational survey of patients presenting to 21 medical centers or teaching hospitals in Taiwan. Hospitalized patients with either acute new-onset HF or acute decompensation of chronic HFrEF were enrolled. Data including demographic characteristics, medical history, primary etiology of HF, precipitating factors for HF hospitalization, presenting symptoms and signs, diagnostic and treatment procedures, in-hospital mortality, length of stay, and discharge medications, were collected and analyzed. Results A total of 1509 patients were enrolled into the registry by the end of October 2014, with a mean age of 64 years (72% were male). Ischemic cardiomyopathy and dilated cardiomyopathy were diagnosed in 44% and 33% of patients, respectively. Coronary artery disease, hypertension, diabetes, and chronic renal insufficiency were the common comorbid conditions. Acute coronary syndrome, non-compliant to treatment, and concurrent infection were the major precipitating factors for acute decompensation. The median length of hospital stay was 8 days, and the in-hospital mortality rate was 2.4%. At discharge, 62% of patients were prescribed either angiotensin-converting enzyme-inhibitors or angiotensin receptor blockers, 60% were prescribed beta-blockers, and 49% were prescribed mineralocorticoid receptor antagonists. Conclusions The TSOC-HFrEF registry provided important insights into the current clinical characteristics and management of hospitalized decompensated systolic HF patients in Taiwan. One important observation was that adherence to guideline-directed medical therapy was suboptimal. PMID:27471353

Role of a ribosomal RNA phosphate oxygen during the EF-G–triggered GTP hydrolysis

PubMed Central

Koch, Miriam; Flür, Sara; Kreutz, Christoph; Ennifar, Eric; Micura, Ronald; Polacek, Norbert

2015-01-01

Elongation factor-catalyzed GTP hydrolysis is a key reaction during the ribosomal elongation cycle. Recent crystal structures of G proteins, such as elongation factor G (EF-G) bound to the ribosome, as well as many biochemical studies, provide evidence that the direct interaction of translational GTPases (trGTPases) with the sarcin-ricin loop (SRL) of ribosomal RNA (rRNA) is pivotal for hydrolysis. However, the precise mechanism remains elusive and is intensively debated. Based on the close proximity of the phosphate oxygen of A2662 of the SRL to the supposedly catalytic histidine of EF-G (His87), we probed this interaction by an atomic mutagenesis approach. We individually replaced either of the two nonbridging phosphate oxygens at A2662 with a methyl group by the introduction of a methylphosphonate instead of the natural phosphate in fully functional, reconstituted bacterial ribosomes. Our major finding was that only one of the two resulting diastereomers, the SP methylphosphonate, was compatible with efficient GTPase activation on EF-G. The same trend was observed for a second trGTPase, namely EF4 (LepA). In addition, we provide evidence that the negative charge of the A2662 phosphate group must be retained for uncompromised activity in GTP hydrolysis. In summary, our data strongly corroborate that the nonbridging proSP phosphate oxygen at the A2662 of the SRL is critically involved in the activation of GTP hydrolysis. A mechanistic scenario is supported in which positioning of the catalytically active, protonated His87 through electrostatic interactions with the A2662 phosphate group and H-bond networks are key features of ribosome-triggered activation of trGTPases. PMID:25941362

Nerve growth factor-enhanced airway responsiveness involves substance P in ferret intrinsic airway neurons.

PubMed

Wu, Z-X; Dey, R D

2006-07-01

Nerve growth factor (NGF), a member of the neurotrophin family, enhances synthesis of neuropeptides in sensory and sympathetic neurons. The aim of this study was to examine the effect of NGF on airway responsiveness and determine whether these effects are mediated through synthesis and release of substance P (SP) from the intrinsic airway neurons. Ferrets were instilled intratracheally with NGF or saline. Tracheal smooth muscle contractility to methacholine and electrical field stimulation (EFS) was assessed in vitro. Contractions of isolated tracheal smooth muscle to EFS at 10 and 30 Hz were significantly increased in the NGF treatment group (10 Hz: 33.57 +/- 2.44%; 30 Hz: 40.12 +/- 2.78%) compared with the control group (10 Hz: 27.24 +/- 2.14%; 30 Hz: 33.33 +/- 2.31%). However, constrictive response to cholinergic agonist was not significantly altered between the NGF treatment group and the control group. The NGF-induced modulation of airway smooth muscle to EFS was maintained in tracheal segments cultured for 24 h, a procedure that causes a significant anatomic and functional loss of SP-containing sensory fibers while maintaining viability of intrinsic airway neurons. The number of SP-containing neurons in longitudinal trunk and superficial muscular plexus and SP nerve fiber density in tracheal smooth muscle all increased significantly in cultured trachea treated with NGF. Pretreatment with CP-99994, an antagonist of neurokinin 1 receptor, attenuated the NGF-induced increased contraction to EFS in cultured segments but had no effect in saline controls. These results show that the NGF-enhanced airway smooth muscle contractile responses to EFS are mediated by the actions of SP released from intrinsic airway neurons.

Measuring impairments of functioning and health in patients with axial spondyloarthritis by using the ASAS Health Index and the Environmental Item Set: translation and cross-cultural adaptation into 15 languages.

PubMed

Kiltz, U; van der Heijde, D; Boonen, A; Bautista-Molano, W; Burgos-Vargas, R; Chiowchanwisawakit, P; Duruoz, T; El-Zorkany, B; Essers, I; Gaydukova, I; Géher, P; Gossec, L; Grazio, S; Gu, J; Khan, M A; Kim, T J; Maksymowych, W P; Marzo-Ortega, H; Navarro-Compán, V; Olivieri, I; Patrikos, D; Pimentel-Santos, F M; Schirmer, M; van den Bosch, F; Weber, U; Zochling, J; Braun, J

2016-01-01

The Assessments of SpondyloArthritis international society Health Index (ASAS HI) measures functioning and health in patients with spondyloarthritis (SpA) across 17 aspects of health and 9 environmental factors (EF). The objective was to translate and adapt the original English version of the ASAS HI, including the EF Item Set, cross-culturally into 15 languages. Translation and cross-cultural adaptation has been carried out following the forward-backward procedure. In the cognitive debriefing, 10 patients/country across a broad spectrum of sociodemographic background, were included. The ASAS HI and the EF Item Set were translated into Arabic, Chinese, Croatian, Dutch, French, German, Greek, Hungarian, Italian, Korean, Portuguese, Russian, Spanish, Thai and Turkish. Some difficulties were experienced with translation of the contextual factors indicating that these concepts may be more culturally-dependent. A total of 215 patients with axial SpA across 23 countries (62.3% men, mean (SD) age 42.4 (13.9) years) participated in the field test. Cognitive debriefing showed that items of the ASAS HI and EF Item Set are clear, relevant and comprehensive. All versions were accepted with minor modifications with respect to item wording and response option. The wording of three items had to be adapted to improve clarity. As a result of cognitive debriefing, a new response option 'not applicable' was added to two items of the ASAS HI to improve appropriateness. This study showed that the items of the ASAS HI including the EFs were readily adaptable throughout all countries, indicating that the concepts covered were comprehensive, clear and meaningful in different cultures.

Measuring impairments of functioning and health in patients with axial spondyloarthritis by using the ASAS Health Index and the Environmental Item Set: translation and cross-cultural adaptation into 15 languages

PubMed Central

Kiltz, U; van der Heijde, D; Boonen, A; Bautista-Molano, W; Burgos-Vargas, R; Chiowchanwisawakit, P; Duruoz, T; El-Zorkany, B; Essers, I; Gaydukova, I; Géher, P; Gossec, L; Grazio, S; Gu, J; Khan, M A; Kim, T J; Maksymowych, W P; Marzo-Ortega, H; Navarro-Compán, V; Olivieri, I; Patrikos, D; Pimentel-Santos, F M; Schirmer, M; van den Bosch, F; Weber, U; Zochling, J; Braun, J

2016-01-01

Introduction The Assessments of SpondyloArthritis international society Health Index (ASAS HI) measures functioning and health in patients with spondyloarthritis (SpA) across 17 aspects of health and 9 environmental factors (EF). The objective was to translate and adapt the original English version of the ASAS HI, including the EF Item Set, cross-culturally into 15 languages. Methods Translation and cross-cultural adaptation has been carried out following the forward–backward procedure. In the cognitive debriefing, 10 patients/country across a broad spectrum of sociodemographic background, were included. Results The ASAS HI and the EF Item Set were translated into Arabic, Chinese, Croatian, Dutch, French, German, Greek, Hungarian, Italian, Korean, Portuguese, Russian, Spanish, Thai and Turkish. Some difficulties were experienced with translation of the contextual factors indicating that these concepts may be more culturally-dependent. A total of 215 patients with axial SpA across 23 countries (62.3% men, mean (SD) age 42.4 (13.9) years) participated in the field test. Cognitive debriefing showed that items of the ASAS HI and EF Item Set are clear, relevant and comprehensive. All versions were accepted with minor modifications with respect to item wording and response option. The wording of three items had to be adapted to improve clarity. As a result of cognitive debriefing, a new response option ‘not applicable’ was added to two items of the ASAS HI to improve appropriateness. Discussion This study showed that the items of the ASAS HI including the EFs were readily adaptable throughout all countries, indicating that the concepts covered were comprehensive, clear and meaningful in different cultures. PMID:27752358

Which AML subsets benefit from leukemic cell priming during chemotherapy? Long-term analysis of the ALFA-9802 GM-CSF study.

PubMed

Thomas, Xavier; Raffoux, Emmanuel; Renneville, Aline; Pautas, Cecile; de Botton, Stephane; Terre, Christine; Gardin, Claude; Hayette, Sandrine; Preudhomme, Claude; Dombret, Herve

2010-04-01

: Priming with granulocytic hematopoietic growth factors may modulate cell cycle kinetics of leukemic cells and render them more susceptible to phase-specific chemotherapeutic agents. In a first report, we have shown that priming with granulocyte-macrophage colony-stimulating factor (GM-CSF) may enhance complete remission (CR) rate and event-free survival (EFS) in younger adults with acute myeloid leukemia (AML). : In this randomized trial, 259 patients with AML were randomized at baseline to receive or not receive GM-CSF concurrently with all cycles of chemotherapy. The effects of GM-CSF on survival were reported herein with a long-term follow-up and studied according to distinct biological subgroups defined on cytogenetics and molecular markers. : The EFS rate was better in the GM-CSF group (43% vs 34%; P = .04). GM-CSF did not improve the outcome in patients from good risk subgroups, while patients from poor risk subgroups benefited from GM-CSF therapy. In this population, the difference in terms of EFS probability was mainly observed in patients with high initial white blood cell count and in those with FLT3-ITD or MLL rearrangement. When combining these 2 molecular abnormalities for comparison of the effect of GM-CSF priming, the difference in terms of EFS was highly significant (5-year EFS, 39% with GM-CSF vs 8% without GM-CSF; P = .007). : Sensitization of leukemic cells and their progenitors by GM-CSF appears as a plausible strategy for improving the outcome of patients with newly diagnosed AML. Patients with poor-prognosis FLT3-ITD or MLL rearrangement might be a good target population to further investigate priming strategies. Cancer 2010. (c) 2010 American Cancer Society.

Use of Hydralazine‐Isosorbide Dinitrate Combination in African American and Other Race/Ethnic Group Patients With Heart Failure and Reduced Left Ventricular Ejection Fraction

PubMed Central

Golwala, Harsh B.; Thadani, Udho; Liang, Li; Stavrakis, Stavros; Butler, Javed; Yancy, Clyde W.; Bhatt, Deepak L.; Hernandez, Adrian F.; Fonarow, Gregg C.

2013-01-01

Background Hydralazine‐isosorbide dinitrate (H‐ISDN) therapy is recommended for African American patients with moderate to severe heart failure with reduced ejection fraction (<40%) (HFrEF), but use, temporal trends, and clinical characteristics associated with H‐ISDN therapy in clinical practice are unknown. Methods and Results An observational analysis of 54 622 patients admitted with HFrEF and discharged home from 207 hospitals participating in the Get With The Guidelines–Heart Failure registry from April 2008 to March 2012 was conducted to assess prescription, trends, and predictors of use of H‐ISDN among eligible patients. Among 11 185 African American patients eligible for H‐ISDN therapy, only 2500 (22.4%) received H‐ISDN therapy at discharge. In the overall eligible population, 5115 of 43 498 (12.6%) received H‐ISDN at discharge. Treatment rates increased over the study period from 16% to 24% among African Americans and from 10% to 13% among the entire HFrEF population. In a multivariable model, factors associated with H‐ISDN use among the entire cohort included younger age; male sex; African American/Hispanic ethnicity; and history of diabetes, hypertension, anemia, renal insufficiency, higher systolic blood pressure, and lower heart rate. In African American patients, these factors were similar; in addition, being uninsured was associated with lower use. Conclusions Overall, few potentially eligible patients with HFrEF are treated with H‐ISDN, and among African‐Americans fewer than one‐fourth of eligible patients received guideline‐recommended H‐ISDN therapy. Improved ways to facilitate use of H‐ISDN therapy in African American patients with HFrEF are needed. PMID:23966379

A Case of Paraneoplastic Remitting Seronegative Symmetrical Synovitis with Pitting Edema Syndrome Improved by Chemotherapy

PubMed Central

Sakamoto, Takahiko; Ota, Shuji; Haruyama, Terunobu; Ishihara, Masashi; Natsume, Maika; Fukasawa, Yoko; Tanzawa, Shigeru; Usui, Ryo; Honda, Takeshi; Ichikawa, Yasuko; Watanabe, Kiyotaka; Seki, Nobuhiko

2017-01-01

The patient was a 69-year-old male who had started experiencing acute-onset pain in both shoulder joints and edema of both hands and feet. His symptoms progressively worsened within 1 month. Laboratory data indicated elevated CRP and erythrocyte sedimentation rate despite the normal range of antinuclear antibodies and rheumatoid factor and normal organ function. Furthermore, imaging data of the hand indicated synovitis without bone erosions. Meanwhile, chest CT revealed a lung tumor, leading to a diagnosis of primary lung adenocarcinoma with EGFR mutation (cT2aN3M0, stage IIIB). Based on these findings, he was diagnosed as suffering from paraneoplastic remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome. Thereafter, his symptoms disappeared as the tumor size was rapidly decreased by gefitinib therapy for lung adenocarcinoma. Currently, RS3PE syndrome can be classified as a vascular endothelial growth factor (VEGF)-associated disorder. Given that his symptoms improved by chemotherapy, the present case further supported the possible hypothesis that paraneoplastic RS3PE syndrome might be caused by tumor-induced VEGF. Therefore, the present case suggested that the symptoms of acute-onset joint pain accompanied by pitting edema in elderly patients should be considered suspicious for a malignant tumor, thereby warranting a detailed full-body examination. PMID:29430239

Sjogren's syndrome presenting as remitting seronegative symmetric synovitis with pitting edema (RS3PE).

PubMed Central

Choi, Young Mi; Sheen, Dong Hyuk; Lee, Yun Jong; Lee, Eun Bong; Song, Yeong Wook

2003-01-01

Remitting seronegative symmetric synovitis with pitting edema (RS3PE) syndrome is characterized by symmetrical and acute synovitis, pitting edema, the absence of rheumatoid factor, increased acute phase reactants, lack of bony erosions on radiography, and benign and short clinical course. Half of all patients with Sjogren's syndrome experience arthritis during the disease course. We here describe the first case of Sjogren's syndrome presenting as RS3PE. She had swelling in knees, ankles, and wrists. After then the swelling spread to her lower legs, feet, face, and both hands. She was admitted to another hospital and was suspected of lupus or rheumatoid arthritis. Three months later, she had dry mouth and had lower lip biopsy. She was admitted to this hospital due to development of swelling in face and lower legs for 3 days. On physical examination, she had pitting edema in both hands and feet dorsum. Laboratory test showed elevated erythrocyte sedimentation rate, positivity of rheumatoid factor, anti-nuclear antibody, and anti-Ro antibody. There was no erosion in the hands radiography. Schirmer's test and lip biopsy was compatible with Sjogren's syndrome. She was diagnosed RS3PE and Sjogren's syndrome. She was begun with prednisolone and her symptoms improved gradually. PMID:12923344

Sjogren's syndrome presenting as remitting seronegative symmetric synovitis with pitting edema (RS3PE).

PubMed

Choi, Young Mi; Sheen, Dong Hyuk; Lee, Yun Jong; Lee, Eun Bong; Song, Yeong Wook

2003-08-01

Remitting seronegative symmetric synovitis with pitting edema (RS3PE) syndrome is characterized by symmetrical and acute synovitis, pitting edema, the absence of rheumatoid factor, increased acute phase reactants, lack of bony erosions on radiography, and benign and short clinical course. Half of all patients with Sjogren's syndrome experience arthritis during the disease course. We here describe the first case of Sjogren's syndrome presenting as RS3PE. She had swelling in knees, ankles, and wrists. After then the swelling spread to her lower legs, feet, face, and both hands. She was admitted to another hospital and was suspected of lupus or rheumatoid arthritis. Three months later, she had dry mouth and had lower lip biopsy. She was admitted to this hospital due to development of swelling in face and lower legs for 3 days. On physical examination, she had pitting edema in both hands and feet dorsum. Laboratory test showed elevated erythrocyte sedimentation rate, positivity of rheumatoid factor, anti-nuclear antibody, and anti-Ro antibody. There was no erosion in the hands radiography. Schirmer's test and lip biopsy was compatible with Sjogren's syndrome. She was diagnosed RS3PE and Sjogren's syndrome. She was begun with prednisolone and her symptoms improved gradually.

Enhanced expressions of FHL2 and iASPP predict poor prognosis in acute myeloid leukemia.

PubMed

Cheng, Zhiheng; Dai, Yifeng; Pang, Yifan; Jiao, Yang; Zhao, Hongmian; Zhang, Zhihui; Qin, Tong; Hu, Ning; Zhang, Yijie; Ke, Xiaoyan; Chen, Yang; Wu, Depei; Shi, Jinlong; Fu, Lin

2018-06-18

iASPP is a negative regulator of the apoptotic function of p53, and it can enhance the ability of hematopoietic stem cells to self-renew and resist chemo- and radiation therapy. Recent study showed that iASPP could impact the proliferation and apoptosis of leukemia cells by interacting with FHL2. However, whether they have prognostic significance in acute myeloid leukemia (AML) is unknown. Eighty-four AML patients with FHL2 and iASPP expression data from The Cancer Genome Atlas database were enrolled in the study. Patients with high expressions of FHL2 and iASPP had significantly shorter event-free survival (EFS) and overall survival (OS) than patients with low expressions (P = 0.005, P = 0.003, respectively). Univariate analysis indicated that high expressions of FHL2 or iASPP were unfavorable for EFS and OS (all P < 0.05), while multivariate analysis confirmed that high FHL2 expression was an independent risk factor for EFS and OS (all P < 0.05). In patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT), however, EFS and OS were not significantly different between FHL2 or iASPP high- and low-expression groups. Our results suggested that high expressions of FHL2 and iASPP were poor prognostic factors for AML, but the prognostic effect might be overcome by allo-HSCT.

Development of emission factors for motorcycles and shared auto-rickshaws using real-world driving cycle for a typical Indian city.

PubMed

Adak, Prasenjit; Sahu, Ravi; Elumalai, Suresh Pandian

2016-02-15

Vehicular emission is one of the most important contributors of urban air pollution. To quantify the impact of traffic on urban air quality, it is necessary to quantify vehicular emission. In many cities of India, such as Dhanbad, shared auto-rickshaw is the pre-dominant mode of transportation. Indian Driving Cycle (IDC) and Modified Indian Driving Cycle (MIDC) are used for emission testing of motorcycles, shared auto-rickshaws and passenger cars in India for regulatory purposes. IDC used for motorcycles and shared auto-rickshaws does not recognize the difference in two vehicle classes in terms of driving pattern. In real world, shared auto-rickshaws, behave differently than motorcycles. To quantify the impact of shared auto-rickshaws on urban air quality accurately, emission factors (EFs) are required to derive from real-world driving cycles (DCs). In heterogeneous traffic, vehicles of one class affect the behavior of vehicles of other classes. To estimate the emissions from different vehicle classes accurately, EFs for motorcycles and passenger cars are also required to be revised. In this study, real-world DCs were developed for motorcycles, shared auto-rickshaws and passenger cars in Dhanbad. Developed DCs were used to calculate EFs for respective classes. Shared auto-rickshaws were found to have the highest deviation from EFs derived using IDC. Copyright © 2015 Elsevier B.V. All rights reserved.

Visualization of two transfer RNAs trapped in transit during elongation factor G-mediated translocation

PubMed Central

Ramrath, David J. F.; Lancaster, Laura; Sprink, Thiemo; Mielke, Thorsten; Loerke, Justus; Noller, Harry F.; Spahn, Christian M. T.

2013-01-01

During protein synthesis, coupled translocation of messenger RNAs (mRNA) and transfer RNAs (tRNA) through the ribosome takes place following formation of each peptide bond. The reaction is facilitated by large-scale conformational changes within the ribosomal complex and catalyzed by elongtion factor G (EF-G). Previous structural analysis of the interaction of EF-G with the ribosome used either model complexes containing no tRNA or only a single tRNA, or complexes where EF-G was directly bound to ribosomes in the posttranslocational state. Here, we present a multiparticle cryo-EM reconstruction of a translocation intermediate containing two tRNAs trapped in transit, bound in chimeric intrasubunit ap/P and pe/E hybrid states. The downstream ap/P-tRNA is contacted by domain IV of EF-G and P-site elements within the 30S subunit body, whereas the upstream pe/E-tRNA maintains tight interactions with P-site elements of the swiveled 30S head. Remarkably, a tight compaction of the tRNA pair can be seen in this state. The translocational intermediate presented here represents a previously missing link in understanding the mechanism of translocation, revealing that the ribosome uses two distinct molecular ratchets, involving both intra- and intersubunit rotational movements, to drive the synchronous movement of tRNAs and mRNA. PMID:24324168

Tenascin in meningioma: expression is correlated with anaplasia, vascular endothelial growth factor expression, and peritumoral edema but not with tumor border shape.

PubMed

Kiliç, Türker; Bayri, Yaşar; Ozduman, Koray; Acar, Melih; Diren, Semin; Kurtkaya, Ozlem; Ekinci, Gazanfer; Buğra, Kuyaş; Sav, Aydin; Ozek, M Memet; Pamir, M Necmettin

2002-07-01

Tenascin is an extracellular matrix glycoprotein that is expressed during embryogenesis, inflammation, angiogenesis, and carcinogenesis. The aim of this study was to investigate how tenascin expression relates to histological grade, angiogenesis, and radiological findings in meningiomas. Twenty typical, 20 atypical, and 5 malignant meningiomas were studied retrospectively. Tenascin expression and vascular endothelial growth factor (VEGF) expression in the tumor tissue were investigated by immunohistochemistry. Tenascin messenger ribonucleic acid expression was also studied by comparative reverse transcriptase-polymerase chain reaction. Magnetic resonance images from each case were assessed for peritumoral edema and tumor border shape. The atypical and malignant meningiomas showed higher levels of tenascin expression than the typical meningiomas. The more sensitive messenger ribonucleic acid-based methods confirmed this finding. Tenascin expression was correlated with peritumoral edema and VEGF expression but not with tumor border shape. In the 13 tumors with marked tenascin expression, peritumoral edema was Grade 0 in one, Grade 1 in three, and Grade 2 in nine specimens. In the same 13 tumors, VEGF expression was Grade 1 in five and Grade 2 in eight specimens, and the findings for tumor border shape were Grade 0 in seven, Grade 1 in four, and Grade 2 in two specimens. In meningiomas, tenascin expression is correlated with anaplasia, tumor-associated edema, and VEGF expression but not with tumor border shape. This protein may play a role in the neoplastic and/or angiogenic processes in atypical and malignant meningiomas and may thus be a potential target for meningioma therapy.

Regression analysis on the variation in efficiency frontiers for prevention stage of HIV/AIDS.

PubMed

Kamae, Maki S; Kamae, Isao; Cohen, Joshua T; Neumann, Peter J

2011-01-01

To investigate how the cost effectiveness of preventing HIV/AIDS varies across possible efficiency frontiers (EFs) by taking into account potentially relevant external factors, such as prevention stage, and how the EFs can be characterized using regression analysis given uncertainty of the QALY-cost estimates. We reviewed cost-effectiveness estimates for the prevention and treatment of HIV/AIDS published from 2002-2007 and catalogued in the Tufts Medical Center Cost-Effectiveness Analysis (CEA) Registry. We constructed efficiency frontier (EF) curves by plotting QALYs against costs, using methods used by the Institute for Quality and Efficiency in Health Care (IQWiG) in Germany. We stratified the QALY-cost ratios by prevention stage, country of study, and payer perspective, and estimated EF equations using log and square-root models. A total of 53 QALY-cost ratios were identified for HIV/AIDS in the Tufts CEA Registry. Plotted ratios stratified by prevention stage were visually grouped into a cluster consisting of primary/secondary prevention measures and a cluster consisting of tertiary measures. Correlation coefficients for each cluster were statistically significant. For each cluster, we derived two EF equations - one based on the log model, and one based on the square-root model. Our findings indicate that stratification of HIV/AIDS interventions by prevention stage can yield distinct EFs, and that the correlation and regression analyses are useful for parametrically characterizing EF equations. Our study has certain limitations, such as the small number of included articles and the potential for study populations to be non-representative of countries of interest. Nonetheless, our approach could help develop a deeper appreciation of cost effectiveness beyond the deterministic approach developed by IQWiG.

Impact of primary and secondary air supply intensity in stove on emissions of size-segregated particulate matter and carbonaceous aerosols from apple tree wood burning

NASA Astrophysics Data System (ADS)

Sun, Jian; Shen, Zhenxing; Zhang, Leiming; Zhang, Qian; Lei, Yali; Cao, Junji; Huang, Yu; Liu, Suixin; Zheng, Chunli; Xu, Hongmei; Liu, Hongxia; Pan, Hua; Liu, Pingping; Zhang, Renjian

2018-04-01

In order to assess emission factors (EF) more accurately from household biomass burning, a series of laboratory-controlled apple tree wood burning tests were conducted to measure the EFs of size-segregated particulate matter (PM) and carbonaceous aerosols. The controlled burning experiments were conducted with designed primary air (PA) and secondary air (SA) supply intensity. An optimum value of 7 m3·h- 1 was found for SA, resulting the highest modified combustion efficiency (92.4 ± 2.5%) as well as the lowest EFs of PM2.5 (0.13 ± 0.01 g·MJ- 1), OC (0.04 ± 0.03 g·MJ- 1) and EC (0.03 ± 0.01 g·MJ- 1). SA values of 7 and 10 m3·h- 1 resulted the lowest EFs for all the different PM sizes. In a test with PA of 6 m3·h- 1 and SA of 7 m3·h- 1, very low EFs were observed for OC1 (8.2%), OC2 (11.2%) and especially OP (Pyrolyzed OC) (0%, not detected), indicating nearly complete combustion under this air supply condition. Besides SA, higher PA was proved to have positive effects on PM and carbonaceous fraction emission reduction. For example, with a fixed SA of 1.5 m3·h- 1, EFs of PM2.5 decreased from 0.64 to 0.27 g·MJ- 1 when PA increased from 6 to 15 m3·h- 1 (P < 0.05). Similar reductions were also observed in EFs of OC, EC and size segregated PM.

Soil and Atmospheric Controls on the Land Surface Energy Balance: A Generalized Framework for Distinguishing Moisture-Limited and Energy-Limited Evaporation Regimes

NASA Astrophysics Data System (ADS)

Haghighi, Erfan; Short Gianotti, Daniel J.; Akbar, Ruzbeh; Salvucci, Guido D.; Entekhabi, Dara

2018-03-01

The relationship between evaporative fraction (EF) and soil moisture (SM) has traditionally been used in atmospheric and land-surface modeling communities to determine the coupling strength between land surfaces and the atmosphere in the context of the dominant evaporation regime (energy or moisture limited). However, observation-based analyses suggest that EF-SM relationship in a given region can shift subject to other environmental factors, potentially influencing the determination of the dominant evaporation regime. This implies more complex dependencies embedded in the conventional EF-SM relationship and that in fact it is a multidimensional function. In this study, we develop a generalized EF framework that explicitly accounts for dependencies on other environmental conditions. We show that large scatter in observed EF-SM relationships is primarily due to the projection of variations in other dimensions and propose a normalization of the EF-SM relationship accounting for the dimensions and dependencies not included in the conventional relationship. In this first study, we focus on bare soil conditions in order to establish the basic theoretical framework. The new generalized EF framework provides new insights into the origin of transition between energy-limited and moisture-limited evaporation regimes (marked by a critical SM), linked to soil type and meteorological input data (primarily wind speed and air temperature, but not solar radiation) dominating the evolution of land surface temperature and thus the relative efficiency of surface energy balance components during surface drying. Our results offer new opportunities to advance predictive capabilities quantifying land-atmosphere coupling for a wide range of present and projected meteorological input data.

Influence of atrial fibrillation on the mortality of patients with heart failure with preserved ejection fraction.

PubMed

Franco, Jonathan; Formiga, Francesc; Cepeda, Jose; Llacer, Pau; Arévalo-Lorido, Juan; Cerqueiro, Jose; González-Franco, Alvaro; Epelde, Francesc; Manzano, Luis; Montero Pérez-Barquero, Manuel

2018-05-23

The impact of atrial fibrillation (AF) on the prognosis of heart failure with preserved ejection fraction (HFpEF) is still the subject of debate. We analysed the influence of AF on the prognosis on mortality and readmission in patients with HFpEF. Prospective observational study in 1,971 patients with HFpEF, who were admitted for acute heart failure. Patients were divided into 2 groups according to the presence or absence of AF. We analysed mortality, readmissions and combined mortality/readmissions at one year follow-up. A total of 1,177 (59%) patients had AF, mean age 80.3 (7.8) years and 1,233 (63%) were women. Patients with HFpEF and AF were older, female, greater valvular aetiology and lower comorbidity measured by the Charlson index. At the one year follow-up, 430 (22%) patients had died and 840 (43%) had been readmitted. In the 2 groups analysed, there was no difference in all-cause mortality (22 vs. 21%; P=.739, AF vs. no-AF, respectively) or cardiovascular causes (9.6 vs. 8.2%; P=.739, AF vs. no-AF, respectively). In the multivariable analysis, factors associated with higher mortality were: age, male, valvular aetiology, uric acid, and comorbidity. In the analysis of the subgroup with HFpEF with AF, the presence of chronic AF compared to de novo AF was associated with higher mortality (HR 1,716; 95% CI 1,099-2,681; P=.018). In patients with HFpEF, the presence of AF is frequent. During the one-year follow-up, the presence of AF does not influence mortality or readmissions in patients with HFpEF. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

Heart Failure With Preserved Ejection Fraction in Diabetes: Mechanisms and Management.

PubMed

Meagher, Patrick; Adam, Mohamed; Civitarese, Robert; Bugyei-Twum, Antoinette; Connelly, Kim A

2018-05-01

Diabetes mellitus (DM) is a major cause of heart failure in the Western world, either secondary to coronary artery disease or from a distinct entity known as "diabetic cardiomyopathy." Furthermore, heart failure with preserved ejection fraction (HFpEF) is emerging as a significant clinical problem for patients with DM. Current clinical data suggest that between 30% and 40% of patients with HFpEF suffer from DM. The typical structural phenotype of the HFpEF heart consists of endothelial dysfunction, increased interstitial and perivascular fibrosis, cardiomyocyte stiffness, and hypertrophy along with advanced glycation end products deposition. There is a myriad of mechanisms that result in the phenotypical HFpEF heart including impaired cardiac metabolism and substrate utilization, altered insulin signalling leading to protein kinase C activation, advanced glycated end products deposition, prosclerotic cytokine activation (eg, transforming growth factor-β activation), along with impaired nitric oxide production from the endothelium. Moreover, recent investigations have focused on the role of endothelial-myocyte interactions. Despite intense research, current therapeutic strategies have had little effect on improving morbidity and mortality in patients with DM and HFpEF. Possible explanations for this include a limited understanding of the role that direct cell-cell communication or indirect cell-cell paracrine signalling plays in the pathogenesis of DM and HFpEF. Additionally, integrins remain another important mediator of signals from the extracellular matrix to cells within the failing heart and might play a significant role in cell-cell cross-talk. In this review we discuss the characteristics and mechanisms of DM and HFpEF to stimulate potential future research for patients with this common, and morbid condition. Copyright © 2018 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

Evolution of molecular weight and fluorescence of effluent organic matter (EfOM) during oxidation processes revealed by advanced spectrographic and chromatographic tools.

PubMed

Chen, Zhiqiang; Li, Mo; Wen, Qinxue; Ren, Nanqi

2017-11-01

Effluent organic matter (EfOM) is an emerging concern to receiving aquatic environment due to its refractory property. The degradation of EfOM in ozonation and other two advanced oxidation processes (AOPs), UV/H 2 O 2 and UV/persulfate (PS), was investigated in this study. Fluorescence spectra coupled with parallel factor analysis (PARAFAC) and two-dimensional correlation gel permeation chromatography (2D-GPC) were used to track the evolution of EfOM during each oxidation process. Results showed that the degradation of EfOM indicated by dissolved organic carbon (DOC), UV 254 and fluorescence components, fitted well with pseudo-first-order kinetic model during the oxidation processes. Ozonation showed higher degradation efficiency than AOPs, while UV/PS was more effective than UV/H 2 O 2 with equimolar oxidants dosage. Ozone and SO· 4 - were more reactive with terrestrial humic-like substances, while hydroxyl radical preferentially reacted with protein-like substances. Organic molecules with higher molecular weight (MW) were susceptible to ozone or radicals. Ozonation could transform higher MW (MW of 3510 and 575) organic matters into lower MW organic matters (MW of 294), while reductions of all the organics were observed in both AOPs. Due to the higher reaction rates between ozone and EfOM, ozonation maybe serve as a pre-treatment for AOPs to reduce the radical and energy consumption and improve mineralization of EfOM by AOPs. The decline in DOC, UV 254 , fluorescence and reduction in oxidants increased with the increase of oxidants dosage, and linear correlations among them were found during the ozonation and AOPs. Copyright © 2017. Published by Elsevier Ltd.

Association of COMT and PRODH gene variants with intelligence quotient (IQ) and executive functions in 22q11.2DS subjects.

PubMed

Carmel, Miri; Zarchi, Omer; Michaelovsky, Elena; Frisch, Amos; Patya, Miriam; Green, Tamar; Gothelf, Doron; Weizman, Abraham

2014-09-01

The 22q11.2 deletion syndrome (22q11.2DS) carries the highest genetic risk factor for the development of schizophrenia. We investigated the association of genetic variants in two schizophrenia candidate genes with executive function (EF) and IQ in 22q11.2DS individuals. Ninety two individuals with 22q11.2 deletion were studied for the genetic association between COMT and PRODH variants and EF and IQ. Subjects were divided into children (under 12 years old), adolescents (between 12 and 18 years old) and adults (older than 18 years), and genotyped for the COMT Val158Met (rs4680) and PRODH Arg185Trp (rs4819756) polymorphisms. The participants underwent psychiatric evaluation and EF assessment. Our main finding is a significant influence of the COMT Val158Met polymorphism on both IQ and EF performance. Specifically, 22q11.2DS subjects with Met allele displayed higher IQ scores in all age groups compared to Val carriers, reaching significance in both adolescents and adults. The Met allele carriers performed better than Val carriers in EF tasks, being statistically significant in the adult group. PRODH Arg185Trp variant did not affect IQ or EF in our 22q11.2DS cohort. In conclusion, functional COMT variant, but not PRODH, affects IQ and EF in 22q11.2DS subjects during neurodevelopment with a maximal effect at adulthood. Future studies should monitor the cognitive performance of the same individuals from childhood to old age. Copyright © 2014 Elsevier Ltd. All rights reserved.

Redox Conditions and Related Color Change in Eastern Equatorial Pacific Sediments: IODP Site U1334

NASA Astrophysics Data System (ADS)

Kordesch, W. E.; Gussone, N. C.; Hathorne, E. C.; Kimoto, K.; Delaney, M. L.

2011-12-01

This study was prompted by a 65 m thick brown-green color change in deep-sea sediments of IODP Site U1334 (0-38 Ma, 4799 m water depth) that corresponds to its equatorial crossing (caused by the Northward movement of the pacific plate). Green sediment is a visual indicator of reducing conditions in sediment due to enhanced organic matter deposition and burial. Here we use geochemical redox indicators to characterize the effect of equatorial upwelling on bottom water. The modern redox signal is captured in porewater profiles (nitrate, manganese, iron, sulfate) while trace metal Enrichment Factors (EF) in bulk sediment (manganese, uranium, molybdenum, rhenium) normalized to the detrital component (titanium) record redox state at burial. To measure export productivity we also measure biogenic barium. Porewater profiles reveal suboxic diagenesis; profiles follow the expected sequence of nitrate, manganese oxide, and iron oxide reduction with increasing depth. Constant sulfate (~28 μM) implies anoxia has not occurred. Bulk sediment Mn EF are enriched (EF > 1) throughout the record (Mn EF = 15-200) while U and Mo enrichment corresponds to green color and equatorial proximity (U EF = 4-19; Mo EF = 0-7). Constant Mn enrichment implies continuous oxygenation. Uranium and Mo enrichment near the equator represents suboxic conditions also seen in the porewater. Low Re concentrations (below detection) provide additional evidence against anoxia. A comparison of Mn EF from total digestions to samples treated with an additional reductive cleaning step distinguishes between Mn-oxides and Mn-carbonates, indicating oxygenated and reducing conditions respectively. Mn-carbonate occurrence agrees with U and Mo EF; conditions were more reducing near the equator. Bio-Ba shows significant variability over this interval (22-99 mmol g-1). Our geochemical results indicate that bottom waters became suboxic at the equator as a result of equatorial upwelling-influenced increases in organic matter sedimentation. Comparison of results to Site U1335 (0-26 Ma, 4327 m water depth) will test the relative importance of equatorial proximity.

The existence of fertile hybrids of closely related model earthworm species, Eisenia andrei and E. fetida

PubMed Central

Bigaj, Janusz; Osikowski, Artur; Hofman, Sebastian; Falniowski, Andrzej; Panz, Tomasz; Grzmil, Pawel; Vandenbulcke, Franck

2018-01-01

Lumbricid earthworms Eisenia andrei (Ea) and E. fetida (Ef) are simultaneous hermaphrodites with reciprocal insemination capable of self-fertilization while the existence of hybridization of these two species was still debatable. During the present investigation fertile hybrids of Ea and Ef were detected. Virgin specimens of Ea and Ef were laboratory crossed (Ea+Ef) and their progeny was doubly identified. 1 –identified by species-specific maternally derived haploid mitochondrial DNA sequences of the COI gene being either ‘a’ for worms hatched from Ea ova or ‘f’ for worms hatched from Ef ova. 2 –identified by the diploid maternal/paternal nuclear DNA sequences of 28s rRNA gene being either ‘AA’ for Ea, ‘FF’ for Ef, or AF/FA for their hybrids derived either from the ‘aA’ or ‘fF’ ova, respectively. Among offspring of Ea+Ef pairs in F1 generation there were mainly aAA and fFF earthworms resulted from the facilitated self-fertilization and some aAF hybrids from aA ova but none fFA hybrids from fF ova. In F2 generation resulting from aAF hybrids mated with aAA a new generations of aAA and aAF hybrids were noticed, while aAF hybrids mated with fFF gave fFF and both aAF and fFA hybrids. Hybrids intercrossed together produced plenty of cocoons but no hatchlings independently whether aAF+aAF or aAF+fFA were mated. These results indicated that Ea and Ef species, easy to maintain in laboratory and commonly used as convenient models in biomedicine and ecotoxicology, may also serve in studies on molecular basis of interspecific barriers and mechanisms of introgression and speciation. Hypothetically, their asymmetrical hybridization can be modified by some external factors. PMID:29370238

Biological effects of exposure to static electric fields in humans and vertebrates: a systematic review.

PubMed

Petri, Anne-Kathrin; Schmiedchen, Kristina; Stunder, Dominik; Dechent, Dagmar; Kraus, Thomas; Bailey, William H; Driessen, Sarah

2017-04-17

High-voltage direct current (HVDC) lines are the technology of choice for the transport of large amounts of energy over long distances. The operation of these lines produces static electric fields (EF), but the data reviewed in previous assessments were not sufficient to assess the need for any environmental limit. The aim of this systematic review was to update the current state of research and to evaluate biological effects of static EF. Using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) recommendations, we collected and evaluated experimental and epidemiological studies examining biological effects of exposure to static EF in humans (n = 8) and vertebrates (n = 40). There is good evidence that humans and animals are able to perceive the presence of static EF at sufficiently high levels. Hair movements caused by electrostatic forces may play a major role in this perception. A large number of studies reported responses of animals (e.g., altered metabolic, immunologic or developmental parameters) to a broad range of static EF strengths as well, but these responses are likely secondary physiological responses to sensory stimulation. Furthermore, the quality of many of the studies reporting physiological responses is poor, which raises concerns about confounding. The weight of the evidence from the literature reviewed did not indicate that static EF have adverse biological effects in humans or animals. The evidence strongly supported the role of superficial sensory stimulation of hair and skin as the basis for perception of the field, as well as reported indirect behavioral and physiological responses. Physical considerations also preclude any direct effect of static EF on internal physiology, and reports that some physiological processes are affected in minor ways may be explained by other factors. While this literature does not support a level of concern about biological effects of exposure to static EF, the conditions that affect thresholds for human detection and possible annoyance at suprathreshold levels should be investigated.

Double Dissociation in the Anatomy of Socioemotional Disinhibition and Executive Functioning in Dementia

PubMed Central

Krueger, Casey E.; Laluz, Victor; Rosen, Howard J.; Neuhaus, John M.; Miller, Bruce L.; Kramer, Joel H.

2010-01-01

Objective To determine if socioemotional disinhibition and executive dysfunction are related to dissociable patterns of brain atrophy in neurodegenerative disease. Previous studies have indicated that behavioral and cognitive dysfunction in neurodegenerative disease are linked to atrophy in different parts of the frontal lobe, but these prior studies did not establish that these relationships were specific, which would best be demonstrated by a double dissociation. Method Subjects included 157 patients with neurodegenerative disease. A semi-automated parcellation program (Freesurfer) was used to generate regional cortical volumes from structural MRI scans. Regions of interest (ROIs) included anterior cingulate cortex (ACC), orbitofrontal cortex (OFC), middle frontal gyrus (MFG) and inferior frontal gyrus (IFG). Socioemotional disinhibition was measured using the Neuropsychiatric Inventory. Principal component analysis including three tasks of executive function (EF; verbal fluency, Stroop Interference, modified Trails) was used to generate a single factor score to represent EF. Results Partial correlations between ROIs, disinhibition, and EF were computed after controlling for total intracranial volume, MMSE, diagnosis, age, and education. Brain regions significantly correlated with disinhibition (ACC, OFC, IFG, and temporal lobes) and EF (MFG) were entered into separate hierarchical regressions to determine which brain regions predicted disinhibition and EF. OFC was the only brain region to significantly predict disinhibition and MFG significantly predicted executive functioning performance. A multivariate general linear model demonstrated a significant interaction between ROIs and cognitive-behavioral functions. Conclusions These results support a specific association between orbitofrontal areas and behavioral management as compared to dorsolateral areas and EF. PMID:21381829

Executive functions in adolescents with binge-eating disorder and obesity.

PubMed

Kittel, Rebekka; Schmidt, Ricarda; Hilbert, Anja

2017-08-01

Binge-eating disorder (BED) in adults is associated with alterations in executive functions (EF) and obesity. Much less is known about these relationships in adolescents, including whether poor EF are associated with eating disorder psychopathology and/or elevated body mass index. This study examined EF in response to neutral stimuli in youth with BED. Adolescents with BED and obesity (n = 22), individually matched adolescents with obesity (n = 22), and normal weight (n = 22) completed neuropsychological tests targeting inhibition (Color-Word Interference Test), sustained attention (D2 Concentration Endurance Test), cognitive flexibility (Comprehensive Trail Making Test), and decision-making (Iowa Gambling Task). Adolescents with BED and obesity displayed significantly poorer inhibitory control compared to normal-weight adolescents. This effect persisted after controlling for the level of secondary education. However, initial differences between adolescents with obesity and normal-weight controls regarding inhibitory control and sustained attention vanished after controlling for education. The three groups did not differ regarding cognitive flexibility and decision-making. Moreover, adolescents with BED and obesity did not perform worse than adolescents with obesity on any of the neuropsychological tests. Overall, our results indicate that adolescent BED is associated with only a few alterations in general EF, specifically inhibitory control, and underline BED and educational level as confounding factors in neuropsychological research on obesity. To further delineate EF profiles of adolescents with BED, future research should focus on EF in response to disorder-related stimuli and experimental settings with high ecological validity. © 2017 Wiley Periodicals, Inc.

NF-κB in The Mechanism of Brain Edema in Acute Liver Failure: Studies in Transgenic Mice

PubMed Central

Jayakumar, A.R.; Bethea, J.R.; Tong, X.Y.; Gomez, J.; Norenberg, M.D.

2014-01-01

Astrocyte swelling and brain edema are major complications of the acute form of hepatic encephalopathy (acute liver failure, ALF). While elevated brain ammonia level is a well-known etiological factor in ALF, the mechanism by which ammonia brings about astrocyte swelling is not well understood. We recently found that astrocyte cultures exposed to ammonia activated nuclear factor-kappaB (NF-κB), and that pharmacological inhibition of such activation led to a reduction in astrocyte swelling. Although these findings suggest the involvement of NF-κB in astrocyte swelling in vitro, it is not known whether NF-κB contributes to the development of brain edema in ALF in vivo. Furthermore, pharmacological agents used to inhibit NF-κB may have non-specific effects. Accordingly, we used transgenic (Tg) mice that have a functional inactivation of astrocytic NF-κB and examined whether these mice are resistant to ALF-associated brain edema. ALF was induced in mice by treatment with the hepatotoxin thioacetamide (TAA). Wild type (WT) mice treated with TAA showed a significant increase in brain water content (1.65%) along with prominent astrocyte swelling and spongiosis of the neuropil, consistent with the presence of cytotoxic edema. These changes were not observed in Tg mice treated with TAA. Additionally, WT mice with ALF showed an increase in inducible nitric oxide synthase (iNOS) immunoreactivity in astrocytes from WT mice treated with TAA (iNOS is known to be activated by NF-κB and to contribute to cell swelling). By contrast, Tg mice treated with TAA did not exhibit brain edema, histological changes nor an increase in iNOS immunoreactivity. We also examined astrocytes cultures derived from Tg mice to determine whether these cells exhibit a lesser degree of swelling and cytopathological changes following exposure to ammonia. Astrocyte cultures derived from Tg mice showed no cell swelling nor morphological abnormalities when exposed to ammonia for 24 h. By contrast, ammonia significantly increased cell swelling (31.7%) in cultured astrocytes from WT mice and displayed cytological abnormalities. Moreover, we observed a lesser increment in inducible nitric oxide synthase and NADPH oxidase activity (both are also known to be activated by NF-κB and to contribute to astrocyte swelling) in astrocyte cultures from Tg mice treated with ammonia, as compared to ammonia-treated WT mice astrocytes. These findings strongly suggest that activation of NF-κB is a critical factor in the development of astrocyte swelling/brain edema in ALF. PMID:21087666

The uncertainty of nitrous oxide emissions from grazed grasslands: A New Zealand case study

NASA Astrophysics Data System (ADS)

Kelliher, Francis M.; Henderson, Harold V.; Cox, Neil R.

2017-01-01

Agricultural soils emit nitrous oxide (N2O), a greenhouse gas and the primary source of nitrogen oxides which deplete stratospheric ozone. Agriculture has been estimated to be the largest anthropogenic N2O source. In New Zealand (NZ), pastoral agriculture uses half the land area. To estimate the annual N2O emissions from NZ's agricultural soils, the nitrogen (N) inputs have been determined and multiplied by an emission factor (EF), the mass fraction of N inputs emitted as N2Osbnd N. To estimate the associated uncertainty, we developed an analytical method. For comparison, another estimate was determined by Monte Carlo numerical simulation. For both methods, expert judgement was used to estimate the N input uncertainty. The EF uncertainty was estimated by meta-analysis of the results from 185 NZ field trials. For the analytical method, assuming a normal distribution and independence of the terms used to calculate the emissions (correlation = 0), the estimated 95% confidence limit was ±57%. When there was a normal distribution and an estimated correlation of 0.4 between N input and EF, the latter inferred from experimental data involving six NZ soils, the analytical method estimated a 95% confidence limit of ±61%. The EF data from 185 NZ field trials had a logarithmic normal distribution. For the Monte Carlo method, assuming a logarithmic normal distribution for EF, a normal distribution for the other terms and independence of all terms, the estimated 95% confidence limits were -32% and +88% or ±60% on average. When there were the same distribution assumptions and a correlation of 0.4 between N input and EF, the Monte Carlo method estimated 95% confidence limits were -34% and +94% or ±64% on average. For the analytical and Monte Carlo methods, EF uncertainty accounted for 95% and 83% of the emissions uncertainty when the correlation between N input and EF was 0 and 0.4, respectively. As the first uncertainty analysis of an agricultural soils N2O emissions inventory using "country-specific" field trials to estimate EF uncertainty, this can be a potentially informative case study for the international scientific community.

Remitting seronegative symmetrical synovitis with pitting edema (RS3PE); a rare association with phyllodes tumour of breast.

PubMed

Sarkar, R N; Phaujdar, Sibaji; Banerjee, Siwalik; Siddhanta, Sattik; De, Dibyendu; Bhattachary, Kuntal; Pal, Hare Krishna

2012-04-01

Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) is a rare entity mainly found in elderly males. It is characterized by pitting edema mainly of dorsum of both hands giving a "boxing glove hand" appearance; rarely involving feet also, acute in onset, negative rheumatoid factor and a good response to low dose corticosteroid therapy. Clinically it almost resembles a case of polymyalgia rheumatica, late onset rheumatoid arthritis or other seronegative spondyloarthropathy.Though there are multiple underlying factors causing this rare entity but it has very close associations with many malignancies.So far its association with solid tumours and hematological malignancies has been reported. Phyllodes tumour of breast shows wide spectrum of activity from a benign condition to a locally aggressive and sometimes metastatic tumour.One fourth of the cases recur after definitive treatment.Our case represent an unusual association with recurrent phyllodes tumour of breast with RS3PE.

Prognostic factors in children and adolescents with acute myeloid leukemia (excluding children with Down syndrome and acute promyelocytic leukemia): univariate and recursive partitioning analysis of patients treated on Pediatric Oncology Group (POG) Study 8821.

PubMed

Chang, M; Raimondi, S C; Ravindranath, Y; Carroll, A J; Camitta, B; Gresik, M V; Steuber, C P; Weinstein, H

2000-07-01

The purpose of the paper was to define clinical or biological features associated with the risk for treatment failure for children with acute myeloid leukemia. Data from 560 children and adolescents with newly diagnosed acute myeloid leukemia who entered the Pediatric Oncology Group Study 8821 from June 1988 to March 1993 were analyzed by univariate and recursive partitioning methods. Children with Down syndrome or acute promyelocytic leukemia were excluded from the study. Factors examined included age, number of leukocytes, sex, FAB morphologic subtype, cytogenetic findings, and extramedullary disease at the time of diagnosis. The overall event-free survival (EFS) rate at 4 years was 32.7% (s.e. = 2.2%). Age > or =2 years, fewer than 50 x 10(9)/I leukocytes, and t(8;21) or inv(16), and normal chromosomes were associated with higher rates of EFS (P value = 0.003, 0.049, 0.0003, 0.031, respectively), whereas the M5 subtype of AML (P value = 0.0003) and chromosome abnormalities other than t(8;21) and inv(16) were associated with lower rates of EFS (P value = 0.0001). Recursive partitioning analysis defined three groups of patients with widely varied prognoses: female patients with t(8;21), inv(16), or a normal karyotype (n = 89) had the best prognosis (4-year EFS = 55.1%, s.e. = 5.7%); male patients with t(8;21), inv(16) or normal chromosomes (n = 106) had an intermediate prognosis (4-year EFS = 38.1%, s.e. = 5.3%); patients with chromosome abnormalities other than t(8;21) and inv(16) (n = 233) had the worst prognosis (4-year EFS = 27.0%, s.e. = 3.2%). One hundred and thirty-two patients (24%) could not be grouped because of missing cytogenetic data, mainly due to inadequate marrow samples. The results suggest that pediatric patients with acute myeloid leukemia can be categorized into three potential risk groups for prognosis and that differences in sex and chromosomal abnormalities are associated with differences in estimates of EFS. These results are tentative and must be confirmed by a large prospective clinical trial.

Validation of reference genes for quantitative RT-PCR studies of gene expression in perennial ryegrass (Lolium perenne L.)

PubMed Central

2010-01-01

Background Perennial ryegrass (Lolium perenne L.) is an important pasture and turf crop. Biotechniques such as gene expression studies are being employed to improve traits in this temperate grass. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) is among the best methods available for determining changes in gene expression. Before analysis of target gene expression, it is essential to select an appropriate normalisation strategy to control for non-specific variation between samples. Reference genes that have stable expression at different biological and physiological states can be effectively used for normalisation; however, their expression stability must be validated before use. Results Existing Serial Analysis of Gene Expression data were queried to identify six moderately expressed genes that had relatively stable gene expression throughout the year. These six candidate reference genes (eukaryotic elongation factor 1 alpha, eEF1A; TAT-binding protein homolog 1, TBP-1; eukaryotic translation initiation factor 4 alpha, eIF4A; YT521-B-like protein family protein, YT521-B; histone 3, H3; ubiquitin-conjugating enzyme, E2) were validated for qRT-PCR normalisation in 442 diverse perennial ryegrass (Lolium perenne L.) samples sourced from field- and laboratory-grown plants under a wide range of experimental conditions. Eukaryotic EF1A is encoded by members of a multigene family exhibiting differential expression and necessitated the expression analysis of different eEF1A encoding genes; a highly expressed eEF1A (h), a moderately, but stably expressed eEF1A (s), and combined expression of multigene eEF1A (m). NormFinder identified eEF1A (s) and YT521-B as the best combination of two genes for normalisation of gene expression data in perennial ryegrass following different defoliation management in the field. Conclusions This study is unique in the magnitude of samples tested with the inclusion of numerous field-grown samples, helping pave the way to conduct gene expression studies in perennial biomass crops under field-conditions. From our study several stably expressed reference genes have been validated. This provides useful candidates for reference gene selection in perennial ryegrass under conditions other than those tested here. PMID:20089196

Selection of reference genes for expression analysis of Kumamoto and Portuguese oysters and their hybrid

NASA Astrophysics Data System (ADS)

Yan, Lulu; Su, Jiaqi; Wang, Zhaoping; Yan, Xiwu; Yu, Ruihai

2017-12-01

Quantitative real-time polymerase chain reaction (qRT-PCR) is a rapid and reliable technique which has been widely used to quantifying gene transcripts (expression analysis). It is also employed for studying heterosis, hybridization breeding and hybrid tolerability of oysters, an ecologically and economically important taxonomic group. For these studies, selection of a suitable set of housekeeping genes as references is crucial for correct interpretation of qRT-PCR data. To identify suitable reference genes for oysters during low temperature and low salinity stresses, we analyzed twelve genes from the gill tissue of Crassostrea sikamea (SS), Crassostrea angulata (AA) and their hybrid (SA), which included three ribosomal genes, 28S ribosomal protein S5 ( RPS5), ribosomal protein L35 ( RPL35), and 60S ribosomal protein L29 ( RPL29); three structural genes, tubulin gamma ( TUBγ), annexin A6 and A7 ( AA6 and AA7); three metabolic pathway genes, ornithine decarboxylase ( OD), glyceraldehyde-3-phosphate dehydrogenase ( GAPDH) and glutathione S-transferase P1 ( GSP); two transcription factors, elongation factor 1 alpha and beta ( EF1α and EF1β); and one protein synthesis gene (ubiquitin ( UBQ). Primers specific for these genes were successfully developed for the three groups of oysters. Three different algorithms, geNorm, NormFinder and BestKeeper, were used to evaluate the expression stability of these candidate genes. BestKeeper program was found to be the most reliable. Based on our analysis, we found that the expression of RPL35 and EF1α was stable under low salinity stress, and the expression of OD, GAPDH and EF1α was stable under low temperature stress in hybrid (SA) oyster; the expression of RPS5 and GAPDH was stable under low salinity stress, and the expression of RPS5, UBQ, GAPDH was stable under low temperature stress in SS oyster; the expression of RPS5, GAPDH, EF1β and AA7 was stable under low salinity stress, and the expression of RPL35, EF1α, GAPDH and EF1β was stable under low temperature stress in AA oyster. Furthermore, to evaluate their suitability, the reference genes were used to quantify six target genes. In conclusion, we have successfully developed primers appropriate for the expression analysis in SS, SA and AA.

Importance of individual amino acids in the Switch I region in eEF2 studied by functional complementation in S. cerevisiae.

PubMed

Bartish, Galyna; Nygård, Odd

2008-05-01

Elongation factor 2 (eEF2) is a member of the G-protein super family. G-proteins undergo conformational changes associated with binding of the guanosine nucleotide and hydrolysis of the bound GTP. These structural rearrangements affects the Switch I region (also known as the Effector loop). We have studied the role of individual amino acids in the Switch I region (amino acids 25-73) of S. cerevisiae eEF2 using functional complementation in yeast. 21 point mutations in the Switch I region were created by site-directed mutagenesis. Mutants K49R, E52Q, A53G, F55Y, K60R, Q63A, T68S, I69M and A73G were functional while mutants R54H, F55N, D57A, D57E, D57S, R59K, R59M, Q63E, R65A, R65N, T68A and T68M were inactive. Expression of mutants K49R, A53G, Q63A, I69M and A73G was associated with markedly decreased growth rates and yeast cells expressing mutants A53G and I69M became temperature sensitive. The functional capacity of eEF2 in which the major part Switch I (amino acids T56 to I69) was converted into the homologous sequence found in EF-G from E. coli was also studied. This protein chimera could functionally replace yeast eEF2 in vivo. Yeast cells expressing this mutant grew extremely slowly, showed increased cell death and became temperature sensitive. The ability of the mutant to replace authentic eEF2 in vivo indicates that the structural rearrangement of Switch I necessary for eEF2 function is similar in eukaryotes and bacteria. The effect of two point mutations in the P-loop was also studied. Mutant A25G but not A25V could functionally replace yeast eEF2 even if cells expressing the mutant grew slowly. The A25G mutation converted the consensus sequences AXXXXGK[T/S] in eEF2 to the corresponding motif GXXXXGK[T/S] found in all other G-proteins, suggesting that the alanine found in the P-loop of peptidyltranslocases are not essential for function.

Effects of trauma, hemorrhagic shock, and chronic stress on lung vascular endothelial growth factor.

PubMed

Loftus, Tyler J; Thomson, Andrew J; Kannan, Kolenkode B; Alamo, Ines G; Ramos, Harry N; Whitley, Elizabeth E; Efron, Philip A; Mohr, Alicia M

2017-04-01

Vascular endothelial growth factor (VEGF) and its receptors (VEGFR-1 and VEGFR-2) regulate vascular permeability and endothelial cell survival. We hypothesized that hemorrhagic shock (HS) and chronic stress (CS) would increase expression of lung VEGF and its receptors, potentiating pulmonary edema in lung tissue. Male Sprague-Dawley rats aged 8-9 wk were randomized: naïve control, lung contusion (LC), LC followed by HS (LCHS), and LCHS with CS in a restraint cylinder for 2 h/d (LCHS/CS). Animals were sacrificed on days 1 and 7. Expressions of lung VEGF, VEGFR-1, and VEGFR-2 were determined by polymerase chain reaction. Lung Injury Score (LIS) was graded on light microscopy by inflammatory cell counts, interstitial edema, pulmonary edema, and alveolar integrity (range: 0 = normal; 8 = severe injury). Seven days after LC, lung VEGF and VEGFR-1 were increased, and lung tissue healed (LIS: 0.8 ± 0.8). However, 7 d after LCHS and LCHS/CS, lung VEGF and VEGFR-1 expressions were decreased. VEGFR-2 was also decreased after LCHS/CS. LIS was elevated 7 d after LCHS and LCHS/CS (6.5 ± 1.0 and 8.2 ± 0.8). Increased LIS after LCHS and LCHS/CS was because of higher inflammatory cell counts, increased interstitial edema, and loss of alveolar integrity, whereas pulmonary edema was unchanged. Elevation of lung VEGF and VEGFR-1 expressions after LC alone was associated with healing of injured lung tissue. Expressions of VEGF, VEGFR-1, and VEGFR-2 were reduced after LCHS and LCHS/CS, and injured lung tissue did not heal. Persistent lung injury after severe trauma was because of inflammation rather than pulmonary edema. Copyright © 2016 Elsevier Inc. All rights reserved.

Quinidine, but Not Eicosanoid Antagonists or Dexamethasone, Protect the Gut from Platelet Activating Factor-Induced Vasoconstriction, Edema and Paralysis

PubMed Central

Lautenschläger, Ingmar; Frerichs, Inéz; Dombrowsky, Heike; Sarau, Jürgen; Goldmann, Torsten; Zitta, Karina; Albrecht, Martin; Weiler, Norbert; Uhlig, Stefan

2015-01-01

Intestinal circulatory disturbances, atony, edema and swelling are of great clinical relevance, but the related mechanisms and possible therapeutic options are poorly characterized, in part because of the difficulties to comprehensively analyze these conditions. To overcome these limitations we have developed a model of the isolated perfused rat small intestine where all of these symptoms can be studied simultaneously. Here we used this model to study the role of eicosanoids, steroids and quinidine in platelet-activating factor (PAF)-induced intestinal disorders. A vascular bolus of PAF (0.5 nmol) triggered release of thromboxane and peptidoleukotrienes into the vascular bed (peak concentration 35 nM and 0.8 nM) and reproduced all symptoms of intestinal failure: mesenteric vasoconstriction, translocation of fluid and macromolecules from the vasculature to the lumen and lymphatics, intestinal edema formation, loss of intestinal peristalsis and decreased galactose uptake. All effects of PAF were abolished by the PAF-receptor antagonist ABT491 (2.5 μM). The COX and LOX inhibitors ASA and AA861 (500 μM, 10 μM) did not exhibit barrier-protective effects and the eicosanoid antagonists SQ29548 and MK571 (10 μM, each) only moderately attenuated the loss of vascular fluid, the redistribution to the lumen and the transfer of FITC dextran to the lumen. The steroid dexamethasone (10 μM) showed no barrier-protective properties and failed to prevent edema formation. Quinidine (100 μM) inhibited the increase in arterial pressure, stabilized all the intestinal barriers, and reduced lymph production and the transfer of FITC dextran to the lymph. While quinidine by itself reduced peristalsis, it also obviated paralysis, preserved intestinal functions and prevented edema formation. We conclude that quinidine exerts multiple protective effects against vasoconstriction, edema formation and paralysis in the intestine. The therapeutic use of quinidine for intestinal ailments deserves further study. PMID:25793535

Hamstring Injuries in Professional Soccer Players: Extent of MRI-Detected Edema and the Time to Return to Play.

PubMed

Crema, Michel D; Godoy, Ivan R B; Abdalla, Rene J; de Aquino, Jose Sanchez; Ingham, Sheila J McNeill; Skaf, Abdalla Y

Discrepancies exist in the literature regarding the association of the extent of injuries assessed on magnetic resonance imaging (MRI) with recovery times. MRI-detected edema in grade 1 hamstring injuries does not affect the return to play (RTP). Retrospective cohort study. Level 4. Grade 1 hamstring injuries from 22 professional soccer players were retrospectively reviewed. The extent of edema-like changes on fluid-sensitive sequences from 1.5-T MRI were evaluated using craniocaudal length, percentage of cross-sectional area, and volume. The time needed to RTP was the outcome. Negative binomial regression analysis tested the measurements of MRI-detected edema-like changes as prognostic factors. The mean craniocaudal length was 7.6 cm (SD, 4.9 cm; range, 0.9-19.1 cm), the mean percentage of cross-sectional area was 23.6% (SD, 20%; range, 4.4%-89.6%), and the mean volume was 33.1 cm 3 (SD, 42.6 cm 3 ; range, 1.1-161.3 cm 3 ). The mean time needed to RTP was 13.6 days (SD, 8.9 days; range, 3-32 days). None of the parameters of extent was associated with RTP. The extent of MRI edema in hamstring injuries does not have prognostic value. Measuring the extent of edema in hamstring injuries using MRI does not add prognostic value in clinical practice.

Comparison of sevelamer and calcium carbonate on endothelial function and inflammation in patients on peritoneal dialysis.

PubMed

Chennasamudram, Sudha P; Noor, Tanjila; Vasylyeva, Tetyana L

2013-06-01

Hyperphosphataemia is a known independent risk factor for cardiovascular mortality. The objective of the study was to compare the effects of two phosphate binders, sevelamer carbonate and calcium carbonate on endothelial function (EF) and inflammation in patients on peritoneal dialysis (PD) with Type 2 diabetes mellitus (T2DM). Fifteen subjects with hyperphosphataemia discontinued all phosphate binders to undergo a two-week washout and were assigned to sevelamer carbonate or calcium carbonate treatments for eight weeks. After a second two-week washout period, subjects crossed over to either of the alternate treatments for another eight weeks. At the beginning and end of each treatment, biomarkers of EF, pro-inflammatory cytokines, serum albumin, calcium, phosphate and lipids were measured. Sevelamer carbonate significantly improved lipid profile compared with calcium carbonate. Amongst the EF and pro-inflammatory biomarkers, sevelamer carbonate decreased serum endothelin-1, plasminogen activator inhibitor-1, C-reactive protein and interleukin-6. Both phosphate binders were effective in decreasing serum phosphate but sevelamer had a positive effect on EF. Treatment with sevelamer carbonate has beneficial effects compared with calcium carbonate in decreasing inflammation and improving EF in patients with T2DM on PD. © 2013 European Dialysis and Transplant Nurses Association/European Renal Care Association.

The Predictive Impact of Biological and Sociocultural Factors on Executive Processing: The Role of Age, Education, and Frequency of Reading and Writing Habits.

PubMed

Cotrena, Charles; Branco, Laura D; Cardoso, Caroline O; Wong, Cristina Elizabeth I; Fonseca, Rochele P

2016-01-01

Although the impact of education and age on executive functions (EF) has been widely studied, the influence of daily cognitive stimulation on EF has not been sufficiently investigated. Therefore, the aim of the present study was to evaluate whether the age, education, and frequency of reading and writing habits (FRWH) of healthy adults could predict their performance on measures of inhibition and cognitive flexibility. Inhibition speed, inhibitory control, and set shifting were assessed using speed, accuracy, and discrepancy scores on the Trail-Making Test (TMT) and Hayling Test. Demographic characteristics and the FRWH were assessed using specialized questionnaires. Regression analyses showed that age and the FRWH predicted speed and accuracy on the TMT. The FRWH predicted both speed and accuracy on the Hayling Test, for which speed and accuracy scores were also partly explained by age and education, respectively. Surprisingly, only the FRWH was associated with Hayling Test discrepancy scores, considered one of the purest EF measures. This highlights the importance of regular cognitive stimulation over the number of years of formal education on EF tasks. Further studies are required to investigate the role of the FRWH so as to better comprehend its relationship with EF and general cognition.

Emissions of Selected Semivolatile Organic Chemicals from Forest and Savannah Fires.

PubMed

Wang, Xianyu; Thai, Phong K; Mallet, Marc; Desservettaz, Maximilien; Hawker, Darryl W; Keywood, Melita; Miljevic, Branka; Paton-Walsh, Clare; Gallen, Michael; Mueller, Jochen F

2017-02-07

The emission factors (EFs) for a broad range of semivolatile organic chemicals (SVOCs) from subtropical eucalypt forest and tropical savannah fires were determined for the first time from in situ investigations. Significantly higher (t test, P < 0.01) EFs (μg kg -1 dry fuel, gas + particle-associated) for polycyclic aromatic hydrocarbons (∑ 13 PAHs) were determined from the subtropical forest fire (7,000 ± 170) compared to the tropical savannah fires (1,600 ± 110), due to the approximately 60-fold higher EFs for 3-ring PAHs from the former. EF data for many PAHs from the eucalypt forest fire were comparable with those previously reported from pine and fir forest combustion events. EFs for other SVOCs including polychlorinated biphenyl (PCB), polychlorinated naphthalene (PCN), and polybrominated diphenyl ether (PBDE) congeners as well as some pesticides (e.g., permethrin) were determined from the subtropical eucalypt forest fire. The highest concentrations of total suspended particles, PAHs, PCBs, PCNs, and PBDEs, were typically observed in the flaming phase of combustion. However, concentrations of levoglucosan and some pesticides such as permethrin peaked during the smoldering phase. Along a transect (10-150-350 m) from the forest fire, concentration decrease for PCBs during flaming was faster compared to PAHs, while levoglucosan concentrations increased.

Pattern of endothelial progenitor cells and apoptotic endothelial cell-derived microparticles in chronic heart failure patients with preserved and reduced left ventricular ejection fraction.

PubMed

Berezin, Alexander E; Kremzer, Alexander A; Martovitskaya, Yulia V; Berezina, Tatyana A; Gromenko, Elena A

2016-02-01

Chronic heart failure (HF) remains a leading cause of cardiovascular (CV) mortality and morbidity worldwide. The aim of the study was to investigate whether the pattern of angiogenic endothelial progenitor cells (EPCs) and apoptotic endothelial cell-derived microparticles (EMPs) would be able to differentiate HF with reduced (HFrEF) and preserved (HFpEF) ejection fraction. One hundred sixty four chronic HF subjects met inclusion criteria. Patients with global left ventricular ejection fraction ≥ 50% were categorized as the HFpEF group (n = 79) and those with ≤ 45% as the HFrEF group (n = 85). Therefore, to compare the circulating levels of biological markers 35 control subjects without HF were included in the study. All control individuals were age- and sex-matched chronic HF patients. The serum level of biomarkers was measured at baseline. The flow cytometric technique was used for predictably distinguishing circulating cell subsets depending on expression of CD45, CD34, CD14, Tie-2, and CD309 antigens and determining endothelial cell-derived microparticles. CD31(+)/annexin V(+) was defined as apoptotic endothelial cell-derived MPs, MPs labeled for CD105(+) or CD62E(+) were determined as MPs produced due to activation of endothelial cells. In multivariate logistic regression model T2DM (R(2) = 0.26; P = 0.001), obesity (R(2) = 0.22; P = 0.001), previous MI (R(2) = 0.17; P = 0.012), galectin-3 (R(2) = 0.67; P = 0.012), CD31(+)/annexin V(+) EMPs (R(2) = 0.11; P = 0.001), NT-proBNP (R(2) = 0.11; P = 0.046), CD14(+) CD309(+) cells (R(2) = 0.058; P = 0.001), and CD14(+) СD309(+) Tie-2(+) cells (R(2) = 0.044; P = 0.028) were found as independent predictors of HFpEF. Using multivariate Cox-regression analysis adjusted etiology (previous myocardial infarction), cardiovascular risk factors (obesity, type 2 diabetes mellitus) we found that NT-proBNP (OR 1.08; 95% CI = 1.03-1.12; P = 0.001) and CD31(+)/annexin V(+) EMPs to CD14(+) CD309(+) cell ratio (OR 1.06; 95% CI = 1.02-1.11; P = 0.02) were independent predictors for HFpEF. We found that CD31(+)/annexin V(+) EMPs to CD14(+) CD309(+) cell ratio added to NT-proBNP, clinical data, and cardiovascular risk factors has exhibited the best discriminate value and higher reliability to predict HFpEF compared with NT-proBNP and clinical data/cardiovascular risk factors alone.

[Edema and the tropics].

PubMed

Holzer, B R

2004-11-01

People visiting or living in tropical or subtropical regions are exposed to various factors, which can lead to edema. Tourists staying for only a short time in the tropics are exposed to different risks, with other disease patterns, than people living in the tropics or immigrants from tropical regions. The differential diagnosis of edema and swelling is extensive and it can sometimes be difficult to distinguish classical edema with fluid retention in the extravascular interstitial space, from lymphedema or swelling due to other aetiologies. The patients often connect the edema to their stay in the tropics although it may have been pre-existing with no obvious relation to their travels. Already the long trip in the plane can lead to an "economy class syndrome" due to deep venous thrombosis. Contacts with animal or plant toxins, parasites or parasitic larvae can produce peripheral edema. The diagnosis can often only be made by taking a meticulous history, checking for eosinophilia and with the help of serological investigations. Chronic lymphedema or elephantiasis of the limbs is often due to blocked lymph vessels by filarial worms. It has to be distinguished from other forms as e.g. podoconiosis due to blockage by mineral particles in barefoot walking people. The trend to book adventure and trekking holidays at high altitude leads to high altitude peripheral edema or non-freezing cold injuries such as frostbites and trench foot. Edema can be an unwanted side effect of a range of drugs e.g. nifedipine, which is used to prevent and treat high altitude pulmonary edema. Protein malnutrition, (Kwashiorkor), and vitamin B6 deficiency, (Beri-Beri) are very rarely observed in immigrants and almost never in tourists. A very painful swelling of fingers and hands in children and young adults of African origin can be observed during a sickle cell crisis. Many protein loosing nephropathies connected with plant and animal toxins but also bacterial, viral or parasitic agents, can lead to edema. But very often edema in tourists or immigrants from the tropics is not related to their stay abroad. To take an accurate history of the itinerary, eating habits and exposure to water etc. is very important. Knowledge of the precise epidemiology and geographic distribution of diseases are essential.

Cloning, sequencing, and transgenic expression of Podospora curvicolla and Sordaria macrospora eEF1A genes: relationship between cytosolic translation and longevity in filamentous fungi.

PubMed

Gagny, B; Rossignol, M; Silar, P

1997-12-01

We have cloned and sequenced the gene encoding the translation elongation factor eEF1A from two filamentous fungi, Podospora curvicolla and Sordaria macrospora. These fungi are close relatives of Podospora anserina and also show senescence syndromes. Comparison of the sequences of the deduced proteins with that of P. anserina reveals that the three proteins differ in several positions. Replacement of the P. anserina gene by either of the two exogenous genes does not entail any modification in P. anserina physiology; the longevity of the fungus is not affected. No alteration of in vivo translational accuracy was detected; however, the exogenous proteins nonetheless promoted a modification of the resistance to the aminoglycoside antibiotic paromomycin. These data suggest that optimization of life span between these closely related fungi has likely not been performed during evolution through modifications of eEF1A activity, despite the fact that mutations in this factor can drastically affect longevity. Copyright 1997 Academic Press.

Anti-citrullinated protein antibody-positive rheumatoid arthritis associated with RS3PE syndrome-like symptoms and an elevated serum vascular endothelial growth factor level in a patient with myasthenia gravis.

PubMed

Horai, Yoshiro; Honda, Mai; Nishino, Ayako; Nakashima, Yoshikazu; Suzuki, Takahisa; Kawashiri, Shin-Ya; Ichinose, Kunihiro; Tamai, Mami; Nakamura, Hideki; Motomura, Masakatsu; Origuchi, Tomoki; Kawakami, Atsushi

2014-01-01

A 73-year-old man with a history of myasthenia gravis (MG) was diagnosed with rheumatoid arthritis (RA) based on a history of polyarthritis and positivity for anti-citrullinated protein antibodies (ACPA). He presented with a high level of serum vascular endothelial growth factor (VEGF) and RS3PE syndrome-like pitting edema in the extremities, which improved following treatment with low-dose prednisolone. This is an interesting case of ACPA-positive RA associated with RS3PE syndrome-like pitting edema and a high VEGF level.

Processing speed, executive function, and academic achievement in children with dextro-transposition of the great arteries: Testing a longitudinal developmental cascade model

PubMed Central

Cassidy, Adam R.; White, Matthew T.; DeMaso, David R.; Newburger, Jane W.; Bellinger, David C.

2016-01-01

Objective To establish executive function (EF) structure/organization and test a longitudinal developmental cascade model linking processing speed (PS) and EF skills at 8-years of age to academic achievement outcomes, both at 8- and 16-years, in a large sample of children/adolescents with surgically-repaired dextro-transposition of the great arteries (d-TGA). Method Data for this study come from the 8-(n = 155) and 16-year (n = 139) time points of the Boston Circulatory Arrest Study and included WISC-III, Trail Making Test, Test of Variables of Attention, and WIAT/WIAT-II tasks. Results A 2-factor model (Working Memory/Inhibition and Shifting) provided the best fit for the EF data, χ2(3) = 1.581, p = .66, RMSEA = 0, CFI = 1, NNFI = 1.044). Working Memory/Inhibition and Shifting factors were not correlated. In the structural equation model, PS was directly related to both EF factors and Reading at 8 years, and was indirectly related to Math and Reading achievement, both concurrently and longitudinally, via its effects on Working Memory/Inhibition. Shifting at 8 years was significantly associated with Math (but not Reading) at 16 years. Conclusions The academic difficulties experienced by children and adolescents with d-TGA may be driven, at least in part, by underlying deficits in processing speed and aspects of executive function. Intervention efforts aimed at bolstering these abilities, particularly if implemented early in development, may prove beneficial in improving academic outcomes and, perhaps by extension, in reducing the stress and diminished self-confidence often associated with academic underachievement. PMID:27077787

Emission factors from small scale appliances burning wood and pellets

NASA Astrophysics Data System (ADS)

Ozgen, Senem; Caserini, Stefano; Galante, Silvia; Giugliano, Michele; Angelino, Elisabetta; Marongiu, Alessandro; Hugony, Francesca; Migliavacca, Gabriele; Morreale, Carmen

2014-09-01

Four manually fed (6-11 kW) firewood burning and two automatic wood pellets (8.8-25 kW) residential heating appliances were tested under real-world operating conditions in order to determine emission factors (EFs) of macropollutants, i.e., carbon monoxide (CO), nitrogen oxides (NOx), non-methane hydrocarbons (NMHC), particulate matter (PM) and trace pollutants such as polycyclic aromatic hydrocarbons (PAH) and dioxins. The results were examined for the influence of different factors (i.e., type of wood, appliance and combustion cycle). The experimental EFs were also compared with the values proposed by the European emission inventory guidebook used in the local inventory in order to evaluate their representativeness of real world emissions. The composite macropollutant EFs for manually fed appliances were: for CO 5858 g GJ-1, for NOx 122 g GJ-1, NMHC 542 g GJ-1, PM 254 g GJ-1, whereas emissions were much lower for automatic pellets appliances: CO 219 g GJ-1, for NOx 66 g GJ-1, NMHC 5 g GJ-1, PM 85 g GJ-1. The highest emissions were generally observed for the open fireplace, however traditional and advanced stoves have the highest overall CO EFs. Especially for the advanced stove real-world emissions are far worse than those measured under cycles used for type testing of residential solid fuel appliances. No great difference is observed for different firewood types in batch working appliances, diversely the quality of the pellets is observed to influence directly the emission performance of the automatic appliances. Benzo(b)fluoranthene is the PAH with the highest contribution (110 mg GJ-1 for manual appliances and 2 mg GJ-1 for automatic devices) followed by benzo(a)pyrene (77 mg GJ-1 for manual appliances and 0.8 mg GJ-1 for automatic devices).