Role of CYP2E1 immunoglobulin G4 subclass antibodies and complement in pathogenesis of idiosyncratic drug-induced hepatitis.

PubMed

Njoku, Dolores B; Mellerson, Jenelle L; Talor, Monica V; Kerr, Douglas R; Faraday, Nauder R; Outschoorn, Ingrid; Rose, Noel R

2006-02-01

Idiosyncratic drug-induced hepatitis (IDDIH) is the third most common cause for acute liver failure in the United States. Previous studies have attempted to identify susceptible patients or early stages of disease with various degrees of success. To determine if total serum immunoglobulin subclasses, CYP2E1-specific subclass autoantibodies, complement components, or immune complexes could distinguish persons with IDDIH from others exposed to drugs, we studied persons exposed to halogenated volatile anesthetics, which have been associated with IDDIH and CYP2E1 autoantibodies. We found that patients with anesthetic-induced IDDIH had significantly elevated levels of CYP2E1-specific immunoglobulin G4 (IgG4) autoantibodies, while anesthetic-exposed healthy persons had significantly elevated levels of CYP2E1-specific IgG1 autoantibodies. Anesthetic IDDIH patients had significantly lower levels of C4a, C3a, and C5a compared to anesthetic-exposed healthy persons. C1q- and C3d-containing immune complexes were significantly elevated in anesthetic-exposed persons. In conclusion, our data suggest that anesthetic-exposed persons develop CYP2E1-specific IgG1 autoantibodies which may form detectable circulating immune complexes subsequently cleared by classical pathway activation of the complement system. Persons susceptible to anesthetic-induced IDDIH develop CYP2E1-specific IgG4 autoantibodies which form small, nonprecipitating immune complexes that escape clearance because of their size or by direct inhibition of complement activation.

Role of CYP2E1 Immunoglobulin G4 Subclass Antibodies and Complement in Pathogenesis of Idiosyncratic Drug-Induced Hepatitis

PubMed Central

Njoku, Dolores B.; Mellerson, Jenelle L.; Talor, Monica V.; Kerr, Douglas R.; Faraday, Nauder R.; Outschoorn, Ingrid; Rose, Noel R.

2006-01-01

Idiosyncratic drug-induced hepatitis (IDDIH) is the third most common cause for acute liver failure in the United States. Previous studies have attempted to identify susceptible patients or early stages of disease with various degrees of success. To determine if total serum immunoglobulin subclasses, CYP2E1-specific subclass autoantibodies, complement components, or immune complexes could distinguish persons with IDDIH from others exposed to drugs, we studied persons exposed to halogenated volatile anesthetics, which have been associated with IDDIH and CYP2E1 autoantibodies. We found that patients with anesthetic-induced IDDIH had significantly elevated levels of CYP2E1-specific immunoglobulin G4 (IgG4) autoantibodies, while anesthetic-exposed healthy persons had significantly elevated levels of CYP2E1-specific IgG1 autoantibodies. Anesthetic IDDIH patients had significantly lower levels of C4a, C3a, and C5a compared to anesthetic-exposed healthy persons. C1q- and C3d-containing immune complexes were significantly elevated in anesthetic-exposed persons. In conclusion, our data suggest that anesthetic-exposed persons develop CYP2E1-specific IgG1 autoantibodies which may form detectable circulating immune complexes subsequently cleared by classical pathway activation of the complement system. Persons susceptible to anesthetic-induced IDDIH develop CYP2E1-specific IgG4 autoantibodies which form small, nonprecipitating immune complexes that escape clearance because of their size or by direct inhibition of complement activation. PMID:16467335

Autoantibody heritability in thyroiditis: IgG subclass contributions.

PubMed

Outschoorn, Ingrid M; Talor, Monica V; Hoffman, William H; Rowley, Merrill J; Mackay, Ian R; Rose, Noel R; Burek, C Lynne

2011-05-01

Using a simple screening technique called regression of offspring on mid-parent (ROMP) to examine the role of IgG subclasses in affected and unaffected siblings of children and adolescents with autoimmune thyroid disease and their parents, both total-restricted and subclass-restricted autoantibodies to thyroglobulin (Tg) were assayed quantitatively for each of the IgG subclasses. There was a significant correlation of anti-Tg titer of probands with parental titers in thyrotoxicosis (TT), (R(2) = 0.569, p = 0.001), but not in chronic lymphocytic thyroiditis. The most striking correlation was in TT patients of African-American ancestry, (R(2) = 0.9863, p = 0.0007). Additional insight is provided by examining the contributions of the IgG subclasses individually, particularly those whose concentrations appear not to have direct influence on the total IgG titers. Thus, using small numbers of patients, and assaying the IgG subclass distributions, as well as any other immunoglobulin isotypes that are significantly altered in autoantibody assays, ROMP can be performed rapidly to ascertain which quantifiable parameters may be usefully extended to predict disease onset and progression.

Separation of the principal HDL subclasses by iodixanol ultracentrifugation

PubMed Central

Harman, Nicola L.; Griffin, Bruce A.; Davies, Ian G.

2013-01-01

HDL subclasses detection, in cardiovascular risk, has been limited due to the time-consuming nature of current techniques. We have developed a time-saving and reliable separation of the principal HDL subclasses employing iodixanol density gradient ultracentrifugation (IxDGUC) combined with digital photography. HDL subclasses were separated in 2.5 h from prestained plasma on a three-step iodixanol gradient. HDL subclass profiles were generated by digital photography and gel scan software. Plasma samples (n = 46) were used to optimize the gradient for the resolution of HDL heterogeneity and to compare profiles generated by IxDGUC with gradient gel electrophoresis (GGE); further characterization from participants (n = 548) with a range of lipid profiles was also performed. HDL subclass profiles generated by IxDGUC were comparable to those separated by GGE as indicated by a significant association between areas under the curve for both HDL2 and HDL3 (HDL2, r = 0.896, P < 0.01; HDL3, r = 0.894, P < 0.01). The method was highly reproducible, with intra- and interassay coefficient of variation percentage < 5 for percentage area under the curve HDL2 and HDL3, and < 1% for peak Rf and peak density. The method provides time-saving and cost-effective detection and preparation of the principal HDL subclasses. PMID:23690506

The Biology of IgG Subclasses and Their Clinical Relevance to Transplantation.

PubMed

Valenzuela, Nicole M; Schaub, Stefan

2018-01-01

Immunoglobulin G (IgG) is the dominant immunoglobulin and can be divided into 4 distinct subclasses. The evolution of IgG subclass switches is regulated by interaction with T cells and follows a 1-way direction (IgG3 → IgG1 → IgG2 → IgG4). Based on their structure, the 4 IgG subclasses can initiate different effector function such as complement activation, recruitment of various cells by Fc receptors, and agonistic signaling. Using current assays for HLA antibody detection as a template and replacing the generic reporter antibody with IgG subclass-specific reporter antibodies, it is possible to investigate the IgG subclasses of HLA antibodies. There are 15 different IgG subclass compositions possible. Based on the capability to activate the complement system and the class switch direction, 3 arbitrary patterns can be defined (ie, only complement-binding subclasses [IgG3 and/or IgG1], expansion to noncomplement-binding subclasses [IgG3 and/or IgG1 plus IgG2 and/or IgG4], and switch to noncomplement-binding subclasses [IgG2 and/or IgG4]). The latter group accounts for less than 5%, whereas the former 2 groups have a similar prevalence close to 50%. In the past 5 years, several studies correlated the IgG subclass pattern with occurrence of antibody-mediated rejection and allograft outcomes. Because of differences of the used IgG subclass assay, the time point of analyses, and the definition of outcomes, a clear picture has not emerged yet. Future needs are standardization of the assay, a more detailed knowledge of the initiated effector functions, and more well-designed clinical studies also looking at changes of the IgG subclass pattern over time.

Role of immunoglobulin G subclasses in Q fever.

PubMed

Camacho, M T; Outschoorn, I; Tellez, A

1995-12-01

The progression of Q fever to either acute or chronic disease has been attributed both to biological characteristics of the bacteria and to the host immune response. In order to determine whether a specific immunoglobulin G (IgG) subclass distribution could play a diagnostic or prognostic role in Q fever, IgG subclass levels were measured in patients with acute or chronic disease. It was observed that (i) IgG1 and IgG3 levels were elevated in patients with chronic Q fever compared to patients with acute disease or normal controls; (ii) variations over time reflected inverse complementary relationships of subclass levels, such as between IgG1 and IgG3 compared with IgG2 and IgG4, or an inverse relationship between IgG1 and IgG2; (iii) variations in IgG2 and IgG3 total subclass levels during follow-up of patients with chronic Q fever showed a decrease in IgG2 with a concomitant increase in IgG3 two years from disease onset. These findings indicate that measurements of IgG subclasses may be a simple, additional tool useful in the diagnosis of Q fever. This data raises the question of an unusual immunoregulatory mechanism in Q fever that is implicated in the presentation of the clinical disease.

Change-in-ratio estimators for populations with more than two subclasses

USGS Publications Warehouse

Udevitz, Mark S.; Pollock, Kenneth H.

1991-01-01

Change-in-ratio methods have been developed to estimate the size of populations with two or three population subclasses. Most of these methods require the often unreasonable assumption of equal sampling probabilities for individuals in all subclasses. This paper presents new models based on the weaker assumption that ratios of sampling probabilities are constant over time for populations with three or more subclasses. Estimation under these models requires that a value be assumed for one of these ratios when there are two samples. Explicit expressions are given for the maximum likelihood estimators under models for two samples with three or more subclasses and for three samples with two subclasses. A numerical method using readily available statistical software is described for obtaining the estimators and their standard errors under all of the models. Likelihood ratio tests that can be used in model selection are discussed. Emphasis is on the two-sample, three-subclass models for which Monte-Carlo simulation results and an illustrative example are presented.

Alterations in IgG subclasses in acquired immune deficiency syndrome.

PubMed

Outschoorn, I M; Lluberes, R; Natta, C L

1989-01-01

Decreased IgG subclass levels in pyogenic infections and immunocompromised situations have been described. A study was made to determine IgG subclass levels in four groups of 68 Hispanic patients. The first group consisted of 25 terminal patients with AIDS, the second group of 20 i.v. drug abusers, and the third group of eight hospital patients with neither a diagnosis of AIDS/ARC nor a history of i.v. drug abuse. IgG subclass levels of these 53 cases were compared with those of a fourth group of 15 normal controls. The total IgG, IgA, and IgM levels as well as the four IgG subclass concentrations were measured by radial immunodiffusion using appropriate standards and specific antisera. The first two groups had similar values, with an average IgG level of 10.37 g/liter; IgA, 2.68; and IgM, 1.78; subclass levels were IgG1, 6.68 g/liter; IgG2, 2.77; IgG3, 0.34; and IgG4, 0.68. These were significantly lower than those of controls, except for IgG4. Determination of minor subclasses may offer some possibilities for immunomodulation and therapy and could be useful in terms of prognosis.

Age related IgG subclass concentrations in asthma.

PubMed

Hoeger, P H; Niggemann, B; Haeuser, G

1994-03-01

The prevalence of IgG subclass deficiency in asthma is still controversial. Earlier studies often included patients receiving treatment with systemic steroids which can induce hypogammaglobulinaemia. Concentrations of IgG subclasses were studies in 200 children (aged 2-17 years) with asthma (mean asthma severity score (ASS) 2, range 1-4) who had not received systemic steroids for at least six weeks before investigation, and in 226 healthy age matched controls. The mean concentrations of IgG subclasses in children with asthma were within the 1SD range of those of the control group. In the group with asthma there was a trend towards higher levels of IgG1 and IgG4, whereas the number of children with low concentrations of IgG2 (< 2 SD of control serum samples; absolute concentrations 0.08-1.25 g/l) was slightly greater than in the group who did not have asthma (4.5 v 2.2%). Patients with subnormal concentrations of IgG2 could not be distinguished clinically or on the basis of case history and additional immunological studies did not show further abnormalities. Patients with severe asthma (ASS 3-4) had significantly higher concentrations of IgG4 (mean (SE) 0.53 (0.09) v 0.26 (0.04) g/l) than patients with mild asthma (ASS 1). No significant difference in subclass concentration was found between patients with atopic and those with non-atopic asthma. It is concluded that in an unselected group of children with asthma the mean IgG subclass concentrations do not differ significantly from a group of healthy age matched controls.

40 CFR 141.858 - Repeat monitoring and E. coli requirements.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 24 2013-07-01 2013-07-01 false Repeat monitoring and E. coli....858 Repeat monitoring and E. coli requirements. (a) Repeat monitoring. (1) If a sample taken under... exceeded. (b) Escherichia coli (E. coli) testing. (1) If any routine or repeat sample is total coliform...

Anti-food and anti-microbial IgG subclass antibodies in inflammatory bowel disease.

PubMed

Jansen, Anke; Mandić, Ana D; Bennek, Eveline; Frehn, Lisa; Verdier, Julien; Tebrügge, Irene; Lutz, Holger; Streetz, Konrad; Trautwein, Christian; Sellge, Gernot

2016-12-01

Inflammatory bowel disease (IBD), particularly Crohn's disease (CD), is associated with increased microbial-specific IgG and IgA antibodies, whereas alterations of anti-food antibodies are still disputed. The knowledge about IgG subclass antibodies in IBD is limited. In this study we analysed IgG subclass antibodies specific for nutritional and commensal antigens in IBD patients and controls. Serum IgG1, IgG2, IgG3 and IgG4 specific for wheat and milk extracts, purified ovalbumin, Escherichia coli and Bacteroides fragilis lysates and mannan from Saccharomyces cerevisiae were analysed by ELISA in patients with CD (n = 56), ulcerative colitis (UC; n = 29), acute gastroenteritis/colitis (n = 12) as well as non-inflammatory controls (n = 62). Anti-Saccharomyces cerevisiae antibodies (ASCA) of all IgG subclasses and anti-B. fragilis IgG1 levels were increased in CD patients compared to UC patients and controls. The discriminant validity of ASCA IgG2 and IgG4 was comparable with that of ASCA pan-IgG and IgA, whereas it was inferior for ASCA IgG1/IgG3 and anti-B. fragilis IgG1. Complicated CD defined by the presence of perianal, stricturing or penetrating disease phenotypes was associated with increased ASCA IgG1/IgG3/IgG4, anti-B. fragilis IgG1 and anti-E. coli IgG1 levels. Anti-food IgG subclass levels were not different between IBD patients and controls and did not correlate with food intolerance. In contrast to anti-microbial Abs, food-specific IgG responses were predominately of the IgG4 isotype and all food-specific IgG subclass levels correlated negatively with age. Our study supports the notion that the adaptive immune recognition of food and commensal antigens are differentially regulated.

An intersectional gene regulatory strategy defines subclass diversity of C. elegans motor neurons.

PubMed

Kratsios, Paschalis; Kerk, Sze Yen; Catela, Catarina; Liang, Joseph; Vidal, Berta; Bayer, Emily A; Feng, Weidong; De La Cruz, Estanisla Daniel; Croci, Laura; Consalez, G Giacomo; Mizumoto, Kota; Hobert, Oliver

2017-07-05

A core principle of nervous system organization is the diversification of neuron classes into subclasses that share large sets of features but differ in select traits. We describe here a molecular mechanism necessary for motor neurons to acquire subclass-specific traits in the nematode Caenorhabditis elegans . Cholinergic motor neuron classes of the ventral nerve cord can be subdivided into subclasses along the anterior-posterior (A-P) axis based on synaptic connectivity patterns and molecular features. The conserved COE-type terminal selector UNC-3 not only controls the expression of traits shared by all members of a neuron class, but is also required for subclass-specific traits expressed along the A-P axis. UNC-3, which is not regionally restricted, requires region-specific cofactors in the form of Hox proteins to co-activate subclass-specific effector genes in post-mitotic motor neurons. This intersectional gene regulatory principle for neuronal subclass diversification may be conserved from nematodes to mice.

40 CFR 141.858 - Repeat monitoring and E. coli requirements.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 23 2014-07-01 2014-07-01 false Repeat monitoring and E. coli....858 Repeat monitoring and E. coli requirements. (a) Repeat monitoring. (1) If a sample taken under... volume repeat sample(s) in one or more sample containers of any size, as long as the total volume...

IgG subclass alterations in adult asthma.

PubMed

Outschoorn, I M; Natta, C L

1992-01-01

Immunoglobulin levels were measured in serum samples of 12 black adult non-smoking asthmatic patients, 11 females and 1 male, and compared with 15 age-, sex-matched normal controls. Their total IgG, IgA and IgM levels were within the normal range. However, on quantitation of subclasses, IgG1 levels were significantly above normal, while IgG2 and IgG3 levels were significantly lower than those of controls. No significant differences were found between the two groups when IgG4 levels were compared. These studies as well as those of others suggest that immunoglobulin administration, particularly of individual subclasses, might prove to be a beneficial addition in the management of this condition.

Accumulate Repeat Accumulate Coded Modulation

NASA Technical Reports Server (NTRS)

Abbasfar, Aliazam; Divsalar, Dariush; Yao, Kung

2004-01-01

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

[Antiviral activity of IgG subclasses of immunoglobulin preparations for intravenous use].

PubMed

Litwińska, B; Bucholc, B; Biesiadecka, A; Kańtoch, M

1993-01-01

Preparations of human immunoglobulins for intravenous use (IVIG) should contain proper percentage of IgG subclasses, responding to physiological preparations with preserved activity of antibodies. The study was aimed at establishment of activity against measles, CMV and HSV viruses in individual subclasses of Bioglobulin (Biomed, Warszawa) and a comparison with preparation Polygam (Baxter, USA). Indirect immunofluorescence test was used. The results revealed presence of antiviral activity mostly in subclass IgG1 and also in IgG3, which is in keeping with results obtained by other authors. We have found an anti-HSV activity in a subclass IgG2 and IgG4 in IVIG preparations which was not yet described in the literature; it is confirmed, however, in investigations with application of sera of HSV-positive persons. These discrepancies may be caused by different methods of detection. Viral antigens in ELISA and IF tests may differ among themselves by content of individual epitopes. Basing on obtained results it can be stated that Polish preparation Bioglobulin (in which for the first time antiviral activity was determined in subclasses) is comparable with Polygam.

High-density lipoprotein particle subclass heterogeneity and incident coronary heart disease.

PubMed

Akinkuolie, Akintunde O; Paynter, Nina P; Padmanabhan, Latha; Mora, Samia

2014-01-01

Raising the cholesterol of high-density lipoprotein (HDL) particles is targeted as a cardiovascular disease prevention strategy. However, HDL particles are heterogeneous in composition and structure, which may relate to differences in antiatherogenic potential. We prospectively evaluated the association of HDL subclasses, defined by a recently proposed nomenclature, with incident coronary heart disease (CHD). Baseline HDL particle concentrations were measured by nuclear magnetic resonance spectroscopy and categorized into 5 subclasses (very large, large, medium, small, and very small) among 26 332 initially healthy women. During a median follow-up of 17 years, 969 cases of incident CHD (myocardial infarction, revascularization, and CHD death) were ascertained. In Cox models that adjusted for age, race/ethnicity, blood pressure, smoking, postmenopausal status, and hormone therapy, associations with incident CHD were inverse (P trend<0.0001) for concentrations of very large (hazard ratio for top versus bottom quartile, 0.49; 95% confidence interval, 0.41-0.60), large (0.54; 0.45-0.64), and medium (0.69; 0.58-0.83) HDL subclasses. Conversely, hazard ratios (95% confidence intervals) for small and very small HDL were 1.22 (1.01-1.46; P trend=0.08) and 1.67 (1.39-2.02; P trend<0.0001), respectively. However, after additionally adjusting for metabolic and lipoprotein variables, associations for the spectrum of large, medium, and small HDL subclasses were inverse (P trend<0.05 for large and small and 0.07 for medium), whereas subclasses at either end of the spectrum were not associated with CHD (P trend=0.97 for very large and 0.21 for very small HDL). In this prospective study, associations with incident CHD differed by HDL particle subclass, which may be relevant for developing HDL-modulating therapies. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00000479.

Biophysical and Functional Characterization of Rhesus Macaque IgG Subclasses

PubMed Central

Boesch, Austin W.; Osei-Owusu, Nana Yaw; Crowley, Andrew R.; Chu, Thach H.; Chan, Ying N.; Weiner, Joshua A.; Bharadwaj, Pranay; Hards, Rufus; Adamo, Mark E.; Gerber, Scott A.; Cocklin, Sarah L.; Schmitz, Joern E.; Miles, Adam R.; Eckman, Joshua W.; Belli, Aaron J.; Reimann, Keith A.; Ackerman, Margaret E.

2016-01-01

Antibodies raised in Indian rhesus macaques [Macaca mulatta (MM)] in many preclinical vaccine studies are often evaluated in vitro for titer, antigen-recognition breadth, neutralization potency, and/or effector function, and in vivo for potential associations with protection. However, despite reliance on this key animal model in translation of promising candidate vaccines for evaluation in first in man studies, little is known about the properties of MM immunoglobulin G (IgG) subclasses and how they may compare to human IgG subclasses. Here, we evaluate the binding of MM IgG1, IgG2, IgG3, and IgG4 to human Fc gamma receptors (FcγR) and their ability to elicit the effector functions of human FcγR-bearing cells, and unlike in humans, find a notable absence of subclasses with dramatically silent Fc regions. Biophysical, in vitro, and in vivo characterization revealed MM IgG1 exhibited the greatest effector function activity followed by IgG2 and then IgG3/4. These findings in rhesus are in contrast with the canonical understanding that IgG1 and IgG3 dominate effector function in humans, indicating that subclass-switching profiles observed in rhesus studies may not strictly recapitulate those observed in human vaccine studies. PMID:28018355

Observations of Soft Gamma Repeaters

NASA Technical Reports Server (NTRS)

Kouveliotou, Chryssa

2004-01-01

Magnetars (Soft Gamma Repeaters and Anomalous X-ray Pulsars) are a subclass of neutron stars characterized by their recurrent X-ray bursts. While in an active (bursting) state (lasting anywhere between days and years), they are emit&ng hundreds of predominantly soft (kT=30 kev), short (0.1-100 ms long) events. Their quiescent source x-ray light ewes exhibit puhlions rotational period rate changes (spin-down) indicate that their magnetic fields are extremely high, of the order of 10^14- 10^l5 G. Such high B-field objects, dubbed "magnetars", had been predicted to exist in 1992, but the first concrete observational evidence were obtained in 1998 for two of these sources. I will discuss here the history of Soft Gamma Repeaters, and their spectral, timing and flux characteristics both in the persistent and their burst emission.

Efficacies of roadway safety improvements across functional subclasses of rural two-lane highways.

PubMed

Labi, Samuel

2011-08-01

Highway crash occurrence is a leading cause of unnatural deaths, and highway agencies continually seek to identify engineering measures to reduce crashes and to assess the efficacy of such measures. Most past studies on the effectiveness of roadway improvements in terms of crash reduction considered all rural two-lane sections as a single category of roads. However, it may be hypothesized that the differences in the mobility and accessibility characteristics that are reflected in (and due to) the different design standards between different functional subclasses in the rural two-lane highway system can lead to differences in efficacies of safety improvements at these subclasses. This paper investigates the efficacy of roadway improvements, in terms of crash reduction, at the various subclasses of rural two-lane highways. An empirical analysis of safety performance at each of the three subclasses of rural two-lane highways was carried out using the negative binomial modeling technique. For each subclass, crash prediction models were developed separately for the three levels of crash severity: property-damage only, injury, and fatal/injury. The crash factors that were considered include lane width, shoulder width, pavement surface friction, pavement condition, and horizontal and vertical alignments. After having developed the safety performance functions, the effectiveness (in terms of the extent of crash reduction, for different levels of crash severity) of highway safety enhancements at each highway subclass were determined using the theoretical concepts established in past literature. These enhancements include widening lanes, widening shoulders, enhancing pavement surface friction, and improving the vertical or horizontal alignment. The study found that there is empirical evidence to justify the decomposition of the family of rural two-lane roads into its constituent subclasses for purposes of analyzing the effectiveness of safety enhancement projects and thus to

Dietary fatty acids were not independently associated with lipoprotein subclasses in elderly women.

PubMed

Alaghehband, Fatemeh Ramezan; Lankinen, Maria; Värri, Miika; Sirola, Joonas; Kröger, Heikki; Erkkilä, Arja T

2017-07-01

Dietary fatty acids are known to affect serum lipoproteins; however, little is known about the associations between consumption of dietary fatty acids and lipoprotein subclasses. In this study, we hypothesized that there is an association between dietary fatty acids and lipoprotein subclasses and investigated the cross-sectional association of dietary fat intake with subclasses of lipoproteins in elderly women. Altogether, 547 women (aged ≥65 years) who were part of OSTPRE cohort participated. Dietary intake was assessed by 3-day food records, lifestyle, and health information obtained through self-administrated questionnaires, and lipoprotein subclasses were determined by nuclear magnetic resonance spectroscopy. To analyze the associations between fatty acids and lipoprotein subclasses, we used Pearson and Spearman correlation coefficients and the analysis of covariance (ANCOVA) test with, adjustment for physical activity, body mass index, age, smoking status, and intake of lipid-lowering drugs. There were significant correlations between saturated fatty acids (SFA; % of energy) and concentrations of large, medium, and small low-density lipoproteins (LDL); total cholesterol in large, medium, and small LDL; and phospholipids in large, medium, and small LDL, after correction for multiple testing. After adjustment for covariates, the higher intake of SFA was associated with smaller size of LDL particles (P = .04, ANCOVA) and lower amount of triglycerides in small very low-density lipoproteins (P = .046, ANCOVA). However, these associations did not remain significant after correction for multiple testing. In conclusion, high intake of SFA may be associated with the size of LDL particles, but the results do not support significant, independent associations between dietary fatty acids and lipoprotein subclasses. Copyright © 2017 Elsevier Inc. All rights reserved.

The effect of exercise on plasma lipids and LDL subclass metabolism in miniature swine.

PubMed

Stucchi, A F; Terpstra, A H; Foxall, T L; Nicolosi, R J; Smith, S C

1991-05-01

The effects of exercise on plasma lipids and lipoproteins, high density lipoprotein (HDL) subclass cholesterol levels, and low density lipoprotein (LDL) subclass composition and metabolism were studied in Yucatan miniature swine following 2 yr of training. The exercise protocol produced significant training effects. Post-heparin lipolytic activity was also significantly increased. Although plasma cholesterol and triglycerides did not differ significantly (P = 0.08) between the exercised and control groups, multivariate analysis indicated a strong association between lipoprotein lipase (LPL) and HDL2-C (P less than 0.0001). Although HDL-C levels rose only slightly (P less than 0.09) with exercise, a significant shift was noted in the distribution of cholesterol from the HDL3 to the HDL2 fractions, perhaps mediated by the substantial increase in LPL activity. Exercise had little effect on the chemical composition of the major lipoprotein classes; however, the triglyceride content of the lighter LDL1 subclass was significantly reduced. In the more dense LDL2 subclass, exercise resulted in a significant decrease in triglycerides concomitant with a significant increase in free cholesterol levels. In contrast with the small reductions in fractional catabolic rates (FCR) in either subclass, production rates of the exercised group were reduced, which accounted for the reduction in LDL subclass pool size. These data indicate that exercise produces subtle but significant changes in lipoprotein metabolism that have been previously associated with reduced risk of atherosclerosis.

Absolute Quantitation of Glycoforms of Two Human IgG Subclasses Using Synthetic Fc Peptides and Glycopeptides

NASA Astrophysics Data System (ADS)

Roy, Rini; Ang, Evelyn; Komatsu, Emy; Domalaon, Ronald; Bosseboeuf, Adrien; Harb, Jean; Hermouet, Sylvie; Krokhin, Oleg; Schweizer, Frank; Perreault, Hélène

2018-05-01

Immunoglobulins, such as immunoglobulin G (IgG), are of prime importance in the immune system. Polyclonal human IgG comprises four subclasses, of which IgG1 and IgG2 are the most abundant in healthy individuals. In an effort to develop an absolute MALDI-ToF-MS quantitative method for these subclasses and their Fc N-glycoforms, (glyco)peptides were synthesized using a solid-phase approach and used as internal standards. Tryptic digest glycopeptides from monoclonal IgG1 and IgG2 samples were first quantified using EEQYN(GlcNAc)STYR and EEQFN(GlcNAc)STFR standards, respectively. For IgG1, a similar glycopeptide where tyrosine (Y) was isotopically labelled was used to quantify monoclonal IgG1 that had been treated with the enzyme Endo-F2, i.e., yielding tryptic glycopeptide EEQYN(GlcNAc)STYR. The next step was to quantify single subclasses within polyclonal human IgG samples. Although ion abundances in the MALDI spectra often showed higher signals for IgG2 than IgG1, depending on the spotting solvent used, determination of amounts using the newly developed quantitative method allowed to obtain accurate concentrations where IgG1 species were predominant. It was observed that simultaneous analysis of IgG1 and IgG2 yielded non-quantitative results and that more success was obtained when subclasses were quantified one by one. More experiments served to assess the respective extraction and ionization efficiencies of EEQYNSTYR/EEQFNSTFR and EEQYN(GlcNAc)STYR/EEQFN(GlcNAc)STFR mixtures under different solvent and concentration conditions.

A family study of IgG subclasses in sickle cell anemia.

PubMed

Outschoorn, I M; Natta, C

1983-01-01

Three siblings with sickle cell anemia were studied immunologically and hematologically. Their patterns of Protein A-Sepharose chromatography distribution showed considerable heterogeneity, particularly with respect to the IgG2 and IgG3 subclasses, even though their hematological make up was similar. An attempt was made to correlate their IgG2: IgG1 subclass ratios with their clinical history of recurrent bacterial infections, as well as a possible compensatory IgG3 heterogeneity.

Effect of pistachio consumption on plasma lipoprotein subclasses in pre-diabetic subjects.

PubMed

Hernández-Alonso, P; Salas-Salvadó, J; Baldrich-Mora, M; Mallol, R; Correig, X; Bulló, M

2015-04-01

Nuts have been demonstrated to improve several cardiovascular risk factors and the lipid profile in diabetic and pre-diabetic subjects. However, analysis of conventional serum lipid profiles does not completely explain the atherogenic risk associated with pre-diabetes. We therefore investigated whether chronic consumption of pistachio modifies the lipoprotein subclasses to a healthier profile in pre-diabetic subjects. Randomized cross-over clinical trial in 54 subjects with pre-diabetes. Subjects consumed a pistachio-supplemented diet (PD, 50% carbohydrates, 33% fat, including 57 g/d of pistachios daily) and a control diet (CD, 55% carbohydrates, 30% fat) for 4 months each, separated by a 2-week wash-out. Diets were isocaloric and matched for protein, fiber and saturated fatty acids. Nuclear magnetic resonance (NMR) was performed to determine changes in plasma lipoprotein subclasses. Small low-density lipoprotein particles (sLDL-P) significantly decreased after pistachio consumption compared to the nut-free diet (P = 0.023). The non-high-density lipoprotein particles (non-HDL-P i.e. VLDL-P plus LDL-P) significantly decreased under the PD compared to CD (P = 0.041). The percentage of sHDL-P increased by 2.23% after the PD compared with a reduction of 0.08% after the CD (P = 0.014). Consequently, the overall size of HDL-P significantly decreased in the PD (P = 0.007). Chronic pistachio consumption could modify the lipoprotein particle size and subclass concentrations independently of changes in total plasma lipid profile, which may help to explain the decreased risk of cardiovascular disease and mortality associated with those individuals who frequently consumed nuts. This study is registered at www.clinicaltrials.gov as NCT01441921. Copyright © 2015 Elsevier B.V. All rights reserved.

Bovine IgG subclasses and fertility of Echinococcus granulosus hydatid cysts.

PubMed

Riesle, Silke; García, María Pía; Hidalgo, Christian; Galanti, Norbel; Saenz, Leonardo; Paredes, Rodolfo

2014-09-15

Hydatidosis is an important zoonotic disease of worldwide distribution, causing important health problems to humans and major economical losses in infected livestock. Echinococcus granulosus, the etiological agent of hydatid disease, induces a humoral immune response in the intermediate host (human and herbivorous) against hydatid cyst antigens. Specifically, IgGs are found in the laminar and germinal layers and inside the lumen of fertile and infertile hydatid cysts. In the germinal layer of infertile cysts IgGs are found in an order of magnitude greater than in the germinal layer of fertile cysts; a fraction of those IgGs are associated with high affinity to germinal layer proteins, suggesting their binding to specific parasite antigens. We have previously shown that those immunoglobulins, bound with high affinity to the germinal layer of hydatid cysts, induce apoptosis leading to cyst infertility. In the present work the presence of IgG1 and IgG2 subclasses in the germinal layer of both fertile and infertile hydatid cysts is reported. IgG1 is the most relevant immunoglobulin subclass present in the germinal layer of infertile cysts and bound with high affinity to that parasite structure. Contrarily, though the IgG2 subclass was also found in the germinal and adventitial layers, those immunoglobulins show low affinity to parasite antigens. We propose that the binding of an IgG1 subclass to parasite antigens present in the germinal layer is involved in the mechanism of cyst infertility. Copyright © 2014 Elsevier B.V. All rights reserved.

Serum IgG subclass levels and risk of exacerbations and hospitalizations in patients with COPD.

PubMed

Leitao Filho, Fernando Sergio; Ra, Seung Won; Mattman, Andre; Schellenberg, Robert S; Criner, Gerard J; Woodruff, Prescott G; Lazarus, Stephen C; Albert, Richard; Connett, John E; Han, Meilan K; Martinez, Fernando J; Leung, Janice M; Paul Man, S F; Aaron, Shawn D; Reed, Robert M; Sin, Don D

2018-02-14

The literature is scarce regarding the prevalence and clinical impact of IgG subclass deficiency in COPD. We investigated the prevalence of IgG subclass deficiencies and their association with exacerbations and hospitalizations using subjects from two COPD cohorts. We measured IgG subclass levels using immunonephelometry in serum samples from participants enrolled in two previous COPD trials: Macrolide Azithromycin for Prevention of Exacerbations of COPD (MACRO; n = 976) and Simvastatin for the Prevention of Exacerbations in Moderate-to-Severe COPD (STATCOPE; n = 653). All samples were collected from clinically stable participants upon entry into both studies. IgG subclass deficiency was diagnosed when IgG subclass levels were below their respective lower limit of normal: IgG1 < 2.8 g/L; IgG2 < 1.15 g/L; IgG3 < 0.24 g/L; and IgG4 < 0.052 g/L. To investigate the impact of IgG subclass levels on time to first exacerbation or hospitalization, we log-transformed IgG levels and performed Cox regression models, with adjustments for confounders. One or more IgG subclass deficiencies were found in 173 (17.7%) and 133 (20.4%) participants in MACRO and STATCOPE, respectively. Lower IgG1 or IgG2 levels resulted in increased risk of exacerbations with adjusted hazard ratios (HR) of 1.30 (95% CI, 1.10-1.54, p < 0.01) and 1.19 (95% CI, 1.05-1.35, p < 0.01), respectively in the MACRO study, with STATCOPE yielding similar results. Reduced IgG1 or IgG2 levels were also associated with increased risk of hospitalizations: the adjusted HR for IgG1 and IgG2 was 1.52 (95% CI: 1.15-2.02, p < 0.01) and 1.33 (95% CI, 1.08-1.64, p < 0.01), respectively for the MACRO study; in STATCOPE, only IgG2 was an independent predictor of hospitalization. In our multivariate Cox models, IgG3 and IgG4 levels did not result in significant associations for both outcomes in either MACRO or STATCOPE cohorts. Approximately 1 in 5 COPD patients had one or more Ig

Serum IgG subclass antibodies to a variety of food antigens in patients with coeliac disease.

PubMed Central

Hvatum, M; Scott, H; Brandtzaeg, P

1992-01-01

Levels of serum IgA, IgG, and IgG subclass antibodies to a variety of dietary antigens were determined by enzyme linked immunosorbent assays in 14 adults with untreated coeliac disease and in 10 disease controls selected because of raised total IgG activities. The untreated coeliacs showed somewhat higher total IgG activity (p approximately 0.05) and significantly raised IgA and IgG1 + IgG3 activities to gliadin but reduced IgG4 activity (p less than 0.02) compared with the controls. High IgA and IgG1 + IgG3 activities were positively correlated (r = 0.67, p less than 0.01), and so were IgG and IgG4 activities (r = 0.64, p less than 0.02). Conversely, a high IgG2 response to gliadin appeared related to a low IgA response (r = 0.55, p less than 0.05). The IgG2 response was most prominent to oat flour antigens, followed by IgG1; and the main response to soy antigens resided in IgG1, followed by IgG2 in both disease groups. There was no difference in antibody activities to oat and soy between the two groups, and raised activity to bovine serum albumin was seldom encountered. The IgA activity to alpha-lactalbumin and ovalbumin tended to be increased in the coeliacs compared with the controls. The IgG4 subclass dominated the IgG response to beta-lactoglobulin and ovalbumin and was often raised to alpha-lactalbumin, especially in the disease controls. The IgG subclass pattern to casein parallelled that to gliadin with dominance of the IgG1- and IgG3-subclass activities, especially in the coeliacs. The phlogistic potential of a response in these two subclasses might be relevant to the pathogenesis of coeliac disease and could contribute to a raised IgA gliadin response by increasing mucosal permeability. IgA activity seemed to be highest against antigens usually involved in IgE mediated food allergy. PMID:1612478

Association between habitual dietary intake and lipoprotein subclass profile in healthy young adults.

PubMed

Bogl, L H; Pietiläinen, K H; Rissanen, A; Kangas, A J; Soininen, P; Rose, R J; Ala-Korpela, M; Kaprio, J

2013-11-01

Nutritional epidemiology is increasingly shifting its focus from studying single nutrients to the exploration of the whole diet utilizing dietary pattern analysis. We analyzed associations between habitual diet (including macronutrients, dietary patterns, biomarker of fish intake) and lipoprotein particle subclass profile in young adults. Complete dietary data (food-frequency questionnaire) and lipoprotein subclass profile (via nuclear magnetic resonance spectroscopy) were available for 663 subjects from the population-based FinnTwin12 study (57% women, age: 21-25 y). The serum docosahexaenoic to total fatty acid ratio was used as a biomarker of habitual fish consumption. Factor analysis identified 5 dietary patterns: "Fruit and vegetables", "Meat", "Sweets and desserts", "Junk food" and "Fish". After adjustment for sex, age, body mass index, waist circumference, physical activity, smoking status and alcohol intake, the "Junk food" pattern was positively related to serum triglycerides (r = 0.12, P = 0.002), a shift in the subclass distribution of VLDL toward larger particles (r = 0.12 for VLDL size, P < 0.001) and LDL toward smaller particles (r = -0.15 for LDL size, P < 0.001). In addition, higher scores on this pattern were positively correlated with concentrations of small, dense HDL (r = 0.16, P < 0.001). Habitual fish intake associated negatively with VLDL particle diameter ("Fish" pattern and biomarker) and positively with HDL particle diameter (biomarker). Our results suggest that in young adults, higher habitual fish consumption is related to favorable subclass distributions of VLDL and HDL, while junk food intake is associated with unfavorable alterations in the distribution of all lipoprotein subclasses independent of adiposity and other lifestyle factors. Copyright © 2012 Elsevier B.V. All rights reserved.

IgG Donor-Specific Anti-Human HLA Antibody Subclasses and Kidney Allograft Antibody-Mediated Injury.

PubMed

Lefaucheur, Carmen; Viglietti, Denis; Bentlejewski, Carol; Duong van Huyen, Jean-Paul; Vernerey, Dewi; Aubert, Olivier; Verine, Jérôme; Jouven, Xavier; Legendre, Christophe; Glotz, Denis; Loupy, Alexandre; Zeevi, Adriana

2016-01-01

Antibodies may have different pathogenicities according to IgG subclass. We investigated the association between IgG subclasses of circulating anti-human HLA antibodies and antibody-mediated kidney allograft injury. Among 635 consecutive kidney transplantations performed between 2008 and 2010, we enrolled 125 patients with donor-specific anti-human HLA antibodies (DSA) detected in the first year post-transplant. We assessed DSA characteristics, including specificity, HLA class specificity, mean fluorescence intensity (MFI), C1q-binding, and IgG subclass, and graft injury phenotype at the time of sera evaluation. Overall, 51 (40.8%) patients had acute antibody-mediated rejection (aABMR), 36 (28.8%) patients had subclinical ABMR (sABMR), and 38 (30.4%) patients were ABMR-free. The MFI of the immunodominant DSA (iDSA, the DSA with the highest MFI level) was 6724±464, and 41.6% of patients had iDSA showing C1q positivity. The distribution of iDSA IgG1-4 subclasses among the population was 75.2%, 44.0%, 28.0%, and 26.4%, respectively. An unsupervised principal component analysis integrating iDSA IgG subclasses revealed aABMR was mainly driven by IgG3 iDSA, whereas sABMR was driven by IgG4 iDSA. IgG3 iDSA was associated with a shorter time to rejection (P<0.001), increased microcirculation injury (P=0.002), and C4d capillary deposition (P<0.001). IgG4 iDSA was associated with later allograft injury with increased allograft glomerulopathy and interstitial fibrosis/tubular atrophy lesions (P<0.001 for all comparisons). Integrating iDSA HLA class specificity, MFI level, C1q-binding status, and IgG subclasses in a Cox survival model revealed IgG3 iDSA and C1q-binding iDSA were strongly and independently associated with allograft failure. These results suggest IgG iDSA subclasses identify distinct phenotypes of kidney allograft antibody-mediated injury. Copyright © 2016 by the American Society of Nephrology.

[EFFICACY OF IVIG TREATMENT IN BRONCHIECTASIS ASSOCIATED WITH IGG SUBCLASS DEFICIENCY].

PubMed

Shostak, Yael; Kramer, Mordechai R

2017-11-01

Bronchiectasis is characterized by an abnormal dilatation of the bronchi leading to a chronic inflammatory process, airway blockage and impaired clearance of secretions. The damage to the airways is usually progressive and is the result of several pathogenic processes. In the past, healing of infections (especially pulmonary tuberculosis) was the main cause of airway dilatation and progression of chronic inflammation. Today, congenital illnesses, anatomical defects and immune deficiency play an important role in the pathogenesis of bronchiectasis formation. The immunoglobulin repertoire is vital for effective host protection against a wide variety of pathogens. Primary antibody deficiency diseases are defects of the humoral arm of the immune system and involve an absence/reduced levels of one or more immunoglobulin classes/subclasses or defects of specific antibody formation. Immunoglobulin G (IGG) subclass deficiency can occur in a healthy person and could be without clinical significance. However, in recent years there is emerging evidence that in patients with recurrent infections, early diagnosis of antibody deficiency affects the prognosis and prevention of ongoing lung damage. The use of IVIG has contributed significantly to the survival rate in primary antibody deficiencies. There is limited literature on the treatment of IVIG for patients with IGG subclass deficiency. However, all studies presented so far demonstrated that immunoglobulin therapy reduced the rate of bacterial infections, days of antibiotic usage, hospital admissions and significantly increased patients' quality of life. Therefore, in the appropriate clinical setting, ie: a patient with bronchiectasis and recurrent infections, it is justified to test whether there are humoral immune defects such as IGG subclass deficiency. In a patient with proven deficiency, we should recommend to start IVIG treatment until clinical benefit is achieved.

Exploring antecedents of consumer satisfaction and repeated search behavior on e-health information.

PubMed

Lee, Yun Jung; Park, Jungkun; Widdows, Richard

2009-03-01

E-health information has become an important resource for people seeking health information. Even though many studies have been conducted to examine the quality of e-health information, only a few studies have explored the effects of the information seekers' motivations on the perceived quality of e-health information. There is even less information about repeated searches for e-health information after the users' initial experience of e-health information use. Using an online survey of information seekers, 252 e-health information users' responses were collected. The research examines the relationship among motivation, perceived quality, satisfaction, and intention to repeat-search e-health information. The results identify motivations to search e-health information and confirm the relationship among motivation, perceived quality dimensions, and satisfaction and intention to repeat searches for e-health information.

Large scale aggregate microarray analysis reveals three distinct molecular subclasses of human preeclampsia.

PubMed

Leavey, Katherine; Bainbridge, Shannon A; Cox, Brian J

2015-01-01

Preeclampsia (PE) is a life-threatening hypertensive pathology of pregnancy affecting 3-5% of all pregnancies. To date, PE has no cure, early detection markers, or effective treatments short of the removal of what is thought to be the causative organ, the placenta, which may necessitate a preterm delivery. Additionally, numerous small placental microarray studies attempting to identify "PE-specific" genes have yielded inconsistent results. We therefore hypothesize that preeclampsia is a multifactorial disease encompassing several pathology subclasses, and that large cohort placental gene expression analysis will reveal these groups. To address our hypothesis, we utilized known bioinformatic methods to aggregate 7 microarray data sets across multiple platforms in order to generate a large data set of 173 patient samples, including 77 with preeclampsia. Unsupervised clustering of these patient samples revealed three distinct molecular subclasses of PE. This included a "canonical" PE subclass demonstrating elevated expression of known PE markers and genes associated with poor oxygenation and increased secretion, as well as two other subclasses potentially representing a poor maternal response to pregnancy and an immunological presentation of preeclampsia. Our analysis sheds new light on the heterogeneity of PE patients, and offers up additional avenues for future investigation. Hopefully, our subclassification of preeclampsia based on molecular diversity will finally lead to the development of robust diagnostics and patient-based treatments for this disorder.

A quantitative ELISA for antigen-specific IgG subclasses using equivalence dilutions of anti-kappa and anti-subclass specific secondary reagents. Application to the study of the murine immune response against the capsular polysaccharide of Neisseria meningitidis serogroup B.

PubMed

Colino, J; Diez, M; Outschoorn, I

1996-04-19

We have developed an enzyme-linked immunosorbent assay (ELISA) to measure murine antigen-specific IgG antibodies of defined subclass using precalibrated equivalence dilutions of anti-kappa (in the standard) and each anti-IgG subclass-specific polyclonal secondary antibody (in the test sample). The calibration of secondary reagents could be carried out easily with a set of monoclonal antibodies (MoAbs) specific for all IgG subclasses. These MoAbs do not require purification or standardization. In addition the MoAbs can be of different antigenic specificity. Once the equivalence dilutions have been determined, they can be applied in a quantitative ELISA using the same antigen in the standard and sample, and using only one IgG subclass standard for the determination of all the IgG subclasses. The method is easy to standardize for many antigenic systems. It is particularly useful when the only standard available is one standardized MoAb of the appropriate specificity, and it could be adapted to use with standard polyclonal antibodies having a known content of total antigen-specific IgG bearing kappa chains but unknown IgG subclass composition. The use of this method to quantitate IgG specific for the capsular polysaccharide of Neisseria meningitidis serogroup B (CpsB) gave highly reproducible measures with an interbatch CV of 5-6% similar for all IgG subclasses and low detection limits ranging from 0.3 ng/well for IgG3 to 0.8 ng/well for IgG2a. The IgG subclass response observed after immunization with live meningococci was mainly IgG2a (74%) and IgG2b (18%). Hyperimmunization modified this IgG distribution to one of mainly IgG3 (62%) and IgG1 (28%) which was maintained in the response to a single immunization 4 weeks later, possibly indicating the generation of resting B cells during continuous stimulation.

A biochemical framework for eIF4E-dependent mRNA export and nuclear recycling of the export machinery.

PubMed

Volpon, Laurent; Culjkovic-Kraljacic, Biljana; Sohn, Hye Seon; Blanchet-Cohen, Alexis; Osborne, Michael J; Borden, Katherine L B

2017-06-01

The eukaryotic translation initiation factor eIF4E acts in the nuclear export and translation of a subset of mRNAs. Both of these functions contribute to its oncogenic potential. While the biochemical mechanisms that underlie translation are relatively well understood, the molecular basis for eIF4E's role in mRNA export remains largely unexplored. To date, over 3000 transcripts, many encoding oncoproteins, were identified as potential nuclear eIF4E export targets. These target RNAs typically contain a ∼50-nucleotide eIF4E sensitivity element (4ESE) in the 3' UTR and a 7-methylguanosine cap on the 5' end. While eIF4E associates with the cap, an unknown factor recognizes the 4ESE element. We previously identified cofactors that functionally interacted with eIF4E in mammalian cell nuclei including the leucine-rich pentatricopeptide repeat protein LRPPRC and the export receptor CRM1/XPO1. LRPPRC simultaneously interacts with both eIF4E bound to the 5' mRNA cap and the 4ESE element in the 3' UTR. In this way, LRPPRC serves as a specificity factor to recruit 4ESE-containing RNAs within the nucleus. Further, we show that CRM1 directly binds LRPPRC likely acting as the export receptor for the LRPPRC-eIF4E-4ESE RNA complex. We also found that Importin 8, the nuclear importer for cap-free eIF4E, imports RNA-free LRPPRC, potentially providing both coordinated nuclear recycling of the export machinery and an important surveillance mechanism to prevent futile export cycles. Our studies provide the first biochemical framework for the eIF4E-dependent mRNA export pathway. © 2017 Volpon et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

Accumulate repeat accumulate codes

NASA Technical Reports Server (NTRS)

Abbasfar, Aliazam; Divsalar, Dariush; Yao, Kung

2004-01-01

In this paper we propose an innovative channel coding scheme called 'Accumulate Repeat Accumulate codes' (ARA). This class of codes can be viewed as serial turbo-like codes, or as a subclass of Low Density Parity Check (LDPC) codes, thus belief propagation can be used for iterative decoding of ARA codes on a graph. The structure of encoder for this class can be viewed as precoded Repeat Accumulate (RA) code or as precoded Irregular Repeat Accumulate (IRA) code, where simply an accumulator is chosen as a precoder. Thus ARA codes have simple, and very fast encoder structure when they representing LDPC codes. Based on density evolution for LDPC codes through some examples for ARA codes, we show that for maximum variable node degree 5 a minimum bit SNR as low as 0.08 dB from channel capacity for rate 1/2 can be achieved as the block size goes to infinity. Thus based on fixed low maximum variable node degree, its threshold outperforms not only the RA and IRA codes but also the best known LDPC codes with the dame maximum node degree. Furthermore by puncturing the accumulators any desired high rate codes close to code rate 1 can be obtained with thresholds that stay close to the channel capacity thresholds uniformly. Iterative decoding simulation results are provided. The ARA codes also have projected graph or protograph representation that allows for high speed decoder implementation.

Habitual intake of flavonoid subclasses and risk of colorectal cancer in 2 large prospective cohorts.

PubMed

Nimptsch, Katharina; Zhang, Xuehong; Cassidy, Aedín; Song, Mingyang; O'Reilly, Éilis J; Lin, Jennifer H; Pischon, Tobias; Rimm, Eric B; Willett, Walter C; Fuchs, Charles S; Ogino, Shuji; Chan, Andrew T; Giovannucci, Edward L; Wu, Kana

2016-01-01

Flavonoids inhibit the growth of colon cancer cells in vitro. In a secondary analysis of a randomized controlled trial, the Polyp Prevention Trial, a higher intake of one subclass, flavonols, was statistically significantly associated with a reduced risk of recurrent advanced adenoma. Most previous prospective studies on colorectal cancer evaluated only a limited number of flavonoid subclasses and intake ranges, yielding inconsistent results. In this study, we examined whether higher habitual dietary intakes of flavonoid subclasses (flavonols, flavones, flavanones, flavan-3-ols, and anthocyanins) were associated with a lower risk of colorectal cancer. Using data from validated food-frequency questionnaires administered every 4 y and an updated flavonoid food composition database, we calculated flavonoid intakes for 42,478 male participants from the Health Professionals Follow-Up Study and for 76,364 female participants from the Nurses' Health Study. During up to 26 y of follow-up, 2519 colorectal cancer cases (1061 in men, 1458 in women) were documented. Intakes of flavonoid subclasses were not associated with risk of colorectal cancer in either cohort. Pooled multivariable adjusted RRs (95% CIs) comparing the highest with the lowest quintiles were 1.04 (0.91, 1.18) for flavonols, 1.01 (0.89, 1.15) for flavones, 0.96 (0.84, 1.10) for flavanones, 1.07 (0.95, 1.21) for flavan-3-ols, and 0.98 (0.81, 1.19) for anthocyanins (all P values for heterogeneity by sex >0.19). In subsite analyses, flavonoid intake was also not associated with colon or rectal cancer risk. Our findings do not support the hypothesis that a higher habitual intake of any flavonoid subclass decreases the risk of colorectal cancer.

Influence of IgG Subclass on Human Antimannan Antibody-Mediated Resistance to Hematogenously Disseminated Candidiasis in Mice

PubMed Central

Nishiya, Casey T.; Boxx, Gayle M.; Robison, Kerry; Itatani, Carol; Kozel, Thomas R.

2015-01-01

Candida albicans is a yeast-like pathogen and can cause life-threatening systemic candidiasis. Its cell surface is enriched with mannan that is resistant to complement activation. Previously, we developed the recombinant human IgG1 antimannan antibody M1g1. M1g1 was found to promote complement activation and phagocytosis and protect mice from systemic candidiasis. Here, we evaluate the influence of IgG subclass on antimannan antibody-mediated protection. Three IgG subclass variants of M1g1 were constructed: M1g2, M1g3, and M1g4. The IgG subclass identity for each variant was confirmed with DNA sequence and subclass-specific antibodies. These variants contain identical M1 Fabs and exhibited similar binding affinities for C. albicans yeast and purified mannan. Yeast cells and hyphae recovered from the kidney of antibody-treated mice with systemic candidiasis showed uniform binding of each variant, indicating constitutive expression of the M1 epitope and antibody opsonization in the kidney. All variants promoted deposition of both murine and human C3 onto the yeast cell surface, with M1g4 showing delayed activation, as determined by flow cytometry and immunofluorescence microscopy. M1g4-mediated complement activation was found to be associated with its M1 Fab that activates the alternative pathway in an Fc-independent manner. Treatment with each subclass variant extended the survival of mice with systemic candidiasis (P < 0.001). However, treatment with M1g1, M1g3, or M1g4, but not with M1g2, also reduced the kidney fungal burden (P < 0.001). Thus, the role of human antimannan antibody in host resistance to systemic candidiasis is influenced by its IgG subclass. PMID:26573736

Indices of anti-dengue immunoglobulin G subclasses in adult Mexican patients with febrile and hemorrhagic dengue in the acute phase.

PubMed

Posadas-Mondragón, Araceli; Aguilar-Faisal, José Leopoldo; Chávez-Negrete, Adolfo; Guillén-Salomón, Edith; Alcántara-Farfán, Verónica; Luna-Rojas, Lucero; Ávila-Trejo, Amanda Marineth; Del Carmen Pacheco-Yépez, Judith

2017-10-01

Heterologous secondary infections are at increased risk of developing dengue hemorrhagic fever (DHF) because of antibody-dependent enhancement (ADE). IgG subclasses can fix and activate complement and bind to Fcɣ receptors. These factors may also play an important role in the development of ADE and thus in the pathogenesis of DHF. The aim of this study was to analyze the indices of anti-dengue IgG subclasses in adult patients with febrile and hemorrhagic dengue in the acute phase. In 2013, 129 patients with dengue fever (DF) and 57 with DHF in Veracruz, Mexico were recruited for this study and anti-dengue IgM and IgG determined by capture ELISA. Anti-dengue IgG subclasses were detected by indirect ELISA. Anti-dengue IgG2 and IgG3 subclasses were detected in patients with dengue. IgG1 increased significantly in the sera of patients with both primary and secondary infections and DHF, but was higher in patients with secondary infections. The IgG4 subclass index was significantly higher in the sera of patients with DHF than in that of those with DF, who were in the early and late acute phase of both primary and secondary infection. In conclusion, indices of subclasses IgG1 and IgG4 were higher in patients with DHF. © 2017 The Societies and John Wiley & Sons Australia, Ltd.

Accumulate-Repeat-Accumulate-Accumulate-Codes

NASA Technical Reports Server (NTRS)

Divsalar, Dariush; Dolinar, Sam; Thorpe, Jeremy

2004-01-01

Inspired by recently proposed Accumulate-Repeat-Accumulate (ARA) codes [15], in this paper we propose a channel coding scheme called Accumulate-Repeat-Accumulate-Accumulate (ARAA) codes. These codes can be seen as serial turbo-like codes or as a subclass of Low Density Parity Check (LDPC) codes, and they have a projected graph or protograph representation; this allows for a high-speed iterative decoder implementation using belief propagation. An ARAA code can be viewed as a precoded Repeat-and-Accumulate (RA) code with puncturing in concatenation with another accumulator, where simply an accumulator is chosen as the precoder; thus ARAA codes have a very fast encoder structure. Using density evolution on their associated protographs, we find examples of rate-lJ2 ARAA codes with maximum variable node degree 4 for which a minimum bit-SNR as low as 0.21 dB from the channel capacity limit can be achieved as the block size goes to infinity. Such a low threshold cannot be achieved by RA or Irregular RA (IRA) or unstructured irregular LDPC codes with the same constraint on the maximum variable node degree. Furthermore by puncturing the accumulators we can construct families of higher rate ARAA codes with thresholds that stay close to their respective channel capacity thresholds uniformly. Iterative decoding simulation results show comparable performance with the best-known LDPC codes but with very low error floor even at moderate block sizes.

Subclass specificities of rabbit antibodies to human antidextran.

PubMed

Outschoorn, I M

1983-03-01

Rabbits were immunized with purified antidextran containing IgG2. Half of the animals were treated with commercial human IgG intravenously to induce tolerance. The antisera were absorbed and/or eluted from IgG-Sepharose columns and the antibodies tested with a panel of at least eight human myeloma proteins of the four IgG subclasses, both kappa and lambda types. All animals produced mainly anti-IgG2 or IgG4, sometimes intechanged between these maxima or between kappa and lambda types over a series of bleedings. Absorption with IgG2 and/or IgG4 myeloma proteins resulted in sera or antibody preparations specific for the IgG1 or IgG3 subclasses, and the amount of those antibodies also varied between bleedings from the same animal. It may be concluded that anti-IgG2 and anti-IgG4 syntheses are related in a complementary manner or are equally likely to be produced in a response to IgG2; while IgG1 and IgG3 are also interrelated, but with an inverse relationship to IgG2 and IgG4. Alternatively anti-IgG2 and anti-IgG4 antibodies could be highly cross-reactive, and so could anti-IgG1 and anti-IgG3 antibodies.

Subclass specificities of rabbit antibodies to human antidextran.

PubMed Central

Outschoorn, I M

1983-01-01

Rabbits were immunized with purified antidextran containing IgG2. Half of the animals were treated with commercial human IgG intravenously to induce tolerance. The antisera were absorbed and/or eluted from IgG-Sepharose columns and the antibodies tested with a panel of at least eight human myeloma proteins of the four IgG subclasses, both kappa and lambda types. All animals produced mainly anti-IgG2 or IgG4, sometimes intechanged between these maxima or between kappa and lambda types over a series of bleedings. Absorption with IgG2 and/or IgG4 myeloma proteins resulted in sera or antibody preparations specific for the IgG1 or IgG3 subclasses, and the amount of those antibodies also varied between bleedings from the same animal. It may be concluded that anti-IgG2 and anti-IgG4 syntheses are related in a complementary manner or are equally likely to be produced in a response to IgG2; while IgG1 and IgG3 are also interrelated, but with an inverse relationship to IgG2 and IgG4. Alternatively anti-IgG2 and anti-IgG4 antibodies could be highly cross-reactive, and so could anti-IgG1 and anti-IgG3 antibodies. PMID:6186599

Complete chloroplast genome sequence of MD-2 pineapple and its comparative analysis among nine other plants from the subclass Commelinidae.

PubMed

Redwan, R M; Saidin, A; Kumar, S V

2015-08-12

Pineapple (Ananas comosus var. comosus) is known as the king of fruits for its crown and is the third most important tropical fruit after banana and citrus. The plant, which is indigenous to South America, is the most important species in the Bromeliaceae family and is largely traded for fresh fruit consumption. Here, we report the complete chloroplast sequence of the MD-2 pineapple that was sequenced using the PacBio sequencing technology. In this study, the high error rate of PacBio long sequence reads of A. comosus's total genomic DNA were improved by leveraging on the high accuracy but short Illumina reads for error-correction via the latest error correction module from Novocraft. Error corrected long PacBio reads were assembled by using a single tool to produce a contig representing the pineapple chloroplast genome. The genome of 159,636 bp in length is featured with the conserved quadripartite structure of chloroplast containing a large single copy region (LSC) with a size of 87,482 bp, a small single copy region (SSC) with a size of 18,622 bp and two inverted repeat regions (IRA and IRB) each with the size of 26,766 bp. Overall, the genome contained 117 unique coding regions and 30 were repeated in the IR region with its genes contents, structure and arrangement similar to its sister taxon, Typha latifolia. A total of 35 repeats structure were detected in both the coding and non-coding regions with a majority being tandem repeats. In addition, 205 SSRs were detected in the genome with six protein-coding genes contained more than two SSRs. Comparative chloroplast genomes from the subclass Commelinidae revealed a conservative protein coding gene albeit located in a highly divergence region. Analysis of selection pressure on protein-coding genes using Ka/Ks ratio showed significant positive selection exerted on the rps7 gene of the pineapple chloroplast with P less than 0.05. Phylogenetic analysis confirmed the recent taxonomical relation among the member of

The effects of exercise on the lipoprotein subclass profile: a meta-analysis of 10 interventions

PubMed Central

Sarzynski, Mark A.; Burton, Jeffrey; Rankinen, Tuomo; Blair, Steven N.; Church, Timothy S.; Després, Jean-Pierre; Hagberg, James M.; Landers-Ramos, Rian; Leon, Arthur S.; Mikus, Catherine R.; Rao, D.C.; Seip, Richard L.; Skinner, James S.; Slentz, Cris A.; Thompson, Paul D.; Wilund, Kenneth R.; Kraus, William E.; Bouchard, Claude

2015-01-01

Objective The goal was to examine lipoprotein subclass responses to regular exercise as measured in 10 exercise interventions derived from six cohorts. Methods Nuclear magnetic resonance spectroscopy was used to quantify average particle size, total and subclass concentrations of very low-density lipoprotein, low-density lipoprotein, and high-density lipoprotein particles (VLDL-P, LDL-P, and HDL-P, respectively) before and after an exercise intervention in 1,555 adults from six studies, encompassing 10 distinct exercise programs: APOE (N=106), DREW (N=385), GERS (N=79), HERITAGE (N=715), STRRIDE I (N=168) and II (N=102). Random-effects meta-analyses were performed to evaluate the overall estimate of mean change across the unadjusted and adjusted mean change values from each exercise group. Results Meta-analysis of unadjusted data showed that regular exercise induced significant decreases in the concentration of large VLDL-P, small LDL-P, and medium HDL-P and mean VLDL-P size, with significant increases in the concentration of large LDL-P and large HDL-P and mean LDL-P size. These changes remained significant in meta-analysis with adjustment for age, sex, race, baseline body mass index, and baseline trait value. Conclusions Despite differences in exercise programs and study populations, regular exercise produced putatively beneficial changes in the lipoprotein subclass profile across 10 exercise interventions. Further research is needed to examine how exercise-induced changes in lipoprotein subclasses may be associated with (concomitant changes in) cardiovascular disease risk. PMID:26520888

Salivary IgG subclasses in individuals with and without homozygous IGHG gene deletions.

PubMed Central

Engström, P E; Norhagen, G; Osipova, L; Helal, A; Wiebe, V; Brusco, A; Carbonara, A O; Lefranc, G; Lefranc, M P

1996-01-01

In this study, the levels of salivary IgG1, IgG2, IgG3 and IgG4 from individuals with and without homozygous immunoglobulin heavy chain constant gene deletions were quantified by enzyme-linked immunosorbent assay (ELISA). To analyse the restriction of salivary IgG subclasses, we used unstimulated whole saliva and sera collected at the same time from individuals with homozygous gene deletions, two with G1 deletion, one with G4 deletion, six with both G2 and G4 deletions and from eight individuals without IGHG gene deletions and expressing all four IgG subclasses. The median values of salivary IgG from individuals with homozygous G1, or G4, or both G2 and G4 deletions, and from individuals expressing all four subclasses were 24.2 mg/l and 23.4 mg/l, respectively. The median values of serum IgG were 13.7 g/l and 15.9 g/l, respectively. Our results show that the salivary and serum IgG levels were both within the normal range in individuals with homozygous gene deletions of either G1, or G4, or both G2 and G4. PMID:8943711

Maximum likelihood decoding analysis of Accumulate-Repeat-Accumulate Codes

NASA Technical Reports Server (NTRS)

Abbasfar, Aliazam; Divsalar, Dariush; Yao, Kung

2004-01-01

Repeat-Accumulate (RA) codes are the simplest turbo-like codes that achieve good performance. However, they cannot compete with Turbo codes or low-density parity check codes (LDPC) as far as performance is concerned. The Accumulate Repeat Accumulate (ARA) codes, as a subclass of LDPC codes, are obtained by adding a pre-coder in front of RA codes with puncturing where an accumulator is chosen as a precoder. These codes not only are very simple, but also achieve excellent performance with iterative decoding. In this paper, the performance of these codes with (ML) decoding are analyzed and compared to random codes by very tight bounds. The weight distribution of some simple ARA codes is obtained, and through existing tightest bounds we have shown the ML SNR threshold of ARA codes approaches very closely to the performance of random codes. We have shown that the use of precoder improves the SNR threshold but interleaving gain remains unchanged with respect to RA code with puncturing.

Some subclasses of multivalent functions involving a certain linear operator

NASA Astrophysics Data System (ADS)

Srivastava, H. M.; Patel, J.

2005-10-01

The authors investigate various inclusion and other properties of several subclasses of the class of normalized p-valent analytic functions in the open unit disk, which are defined here by means of a certain linear operator. Problems involving generalized neighborhoods of analytic functions in the class are investigated. Finally, some applications of fractional calculus operators are considered.

Use of OM-85 BV in children suffering from recurrent respiratory tract infections and subnormal IgG subclass levels.

PubMed

Del-Río-Navarro, B E; Luis Sienra-Monge, J J; Berber, A; Torres-Alcántara, S; Avila-Castañón, L; Gómez-Barreto, D

2003-01-01

Recurrent acute respiratory tract infections (RARTIs) in children are related to IgG subclass deficiencies. The aim of the trial was to evaluate the effect of OM-85 BV in the number of RARTIs as well as in the IgG subclass levels. This was a randomized, double-blind, placebo-controlled clinical trial. Patients of ages three to six years, having three or more documented ARTIs during the last six months with subnormal IgG subclass levels were included. Patients took either one capsule of OM-85 BV (3.5 mg) or placebo orally every day for ten consecutive days per month during three consecutive months. Patients were followed three further months without drug intake. IgG subclass levels were determined before and after treatment. IgG4 levels diminished after the OM-85 BV treatment (-3 [-8.0, -1.0] median difference [95 % CI] p < 0.05 by Wilcoxon test). No other significant changes in IgG subclasses were observed. After six months the patients in the OM-85 BV group (n = 20) experienced 2.8 1.4 (mean SD) ARTIs, while the patients in the placebo group (n = 20) suffered 5.2 1.5 ARTIs (-2.4 [3.3, -1.5] mean difference [95 % CI] p < 0.001 by Student's t test). Three patients with OM-85 BV had gastrointestinal events related to drug administration, as well as three placebo patients. This study demonstrated the clinical benefit of OM-85 BV in patients suffering from RARTIs and subnormal levels of IgG subclasses. This trial opens new perspectives in the research of the mechanism of action of OM-85 BV.

Particle numbers of lipoprotein subclasses and arterial stiffness among middle-aged men from the ERA JUMP study.

PubMed

Vishnu, A; Choo, J; Masaki, K H; Mackey, R H; Barinas-Mitchell, E; Shin, C; Willcox, B J; El-Saed, A; Seto, T B; Fujiyoshi, A; Miura, K; Lee, S; Sutton-Tyrrell, K; Kuller, L H; Ueshima, H; Sekikawa, A

2014-02-01

We examined the association between serum lipoprotein subclasses and the three measures of arterial stiffness, that is, (i) carotid-femoral pulse wave velocity (cfPWV), which is a gold standard measure of central arterial stiffness, (ii) brachial-ankle PWV (baPWV), which is emerging as a combined measure of central and peripheral arterial stiffness and (iii) femoral-ankle PWV (faPWV), which is a measure of peripheral arterial stiffness. Among a population-based sample of 701 apparently healthy Caucasian, Japanese American and Korean men aged 40-49 years, concentrations of lipoprotein particles were assessed by nuclear magnetic resonance (NMR) spectroscopy, and the PWV was assessed with an automated waveform analyzer (VP2000, Omron, Japan). Multiple linear regressions were performed to analyse the association between each NMR lipoprotein subclasses and PWV measures, after adjusting for cardiovascular risk factors and other confounders. A cutoff of P<0.01 was used for determining significance. All PWV measures had significant correlations with total and small low-density lipoprotein particle number (LDL-P) (all P<0.0001) but not LDL cholesterol (LDL-C) (all P>0.1), independent of race and age. In multivariate regression analysis, no NMR lipoprotein subclass was significantly associated with cfPWV (all P>0.01). However, most NMR lipoprotein subclasses had significant associations with both baPWV and faPWV (P<0.01). In this study of healthy middle-aged men, as compared with cfPWV, both baPWV and faPWV had stronger associations with particle numbers of lipoprotein subclasses. Our results may suggest that both baPWV and faPWV are related to arterial stiffness and atherosclerosis, whereas cfPWV may represent arterial stiffness alone.

Specific DNA binding activity of T antigen subclasses varies among different SV40-transformed cell lines.

PubMed

Burger, C; Fanning, E

1983-04-15

Large tumor antigen (T antigen) occurs in at least three different oligomeric subclasses in cells infected or transformed by simian virus 40 (SV40): 5-7 S, 14-16 S, and 23-25 S. The 23-25 S form is complexed with a host phosphoprotein (p53). The DNA binding properties of these three subclasses of T antigen from nine different cell lines and free p53 protein were compared using an immunoprecipitation assay. All three subclasses of T antigen bound specifically to SV40 DNA sequences near the origin of replication. However, the DNA binding activity varied between different cell lines over a 40- to 50-fold range. The 23-25 S and 14-16 S forms from most of the cell lines tested bound much less SV40 origin DNA than 5-7 S T antigen. The free p53 phosphoprotein did not bind specifically to any SV40 DNA sequences.

Association between ethnicity and obesity with high-density lipoprotein (HDL) function and subclass distribution.

PubMed

Woudberg, Nicholas J; Goedecke, Julia H; Blackhurst, Dee; Frias, Miguel; James, Richard; Opie, Lionel H; Lecour, Sandrine

2016-05-11

Obesity and low high-density lipoprotein-cholesterol (HDL-C) levels are associated with cardiovascular risk. Surprisingly, despite a greater prevalence of obesity and lower HDL concentrations than white women, black South African women are relatively protected against ischaemic heart disease. We investigated whether this apparent discrepancy may be related to different HDL function and subclass distribution in black and white, normal-weight and obese South African women (n = 40). HDL functionality was assessed by measuring paraoxonase (PON) activity, platelet activating factor acetylhydrolase (PAF-AH) activity, Oxygen Radical Absorbance Capacity (ORAC) and quantification of the expression of vascular cell adhesion molecule in endothelial cells. PON-1 and PAF-AH expression was determined in isolated HDL and serum using Western blotting. Levels of large, intermediate and small HDL subclasses were measured using the Lipoprint® system. PON activity was lower in white compared to black women (0.49 ± 0.09 U/L vs 0.78 ± 0.10 U/L, p < 0.05), regardless of PON-1 protein levels. Obese black women had lower PAF-AH activity (9.34 ± 1.15 U/L vs 13.89 ± 1.21 U/L, p <0.05) and HDL-associated PAF-AH expression compared to obese white women. Compared to normal-weight women, obese women had lower large HDL, greater intermediate and small HDL; an effect that was more pronounced in white women than black women. There were no differences in antioxidant capacity or anti-inflammatory function across groups. Our data show that both obesity and ethnicity are associated with differences in HDL functionality, while obesity was associated with decreases in large HDL subclass distribution. Measuring HDL functionality and subclass may, therefore, be important factors to consider when assessing cardiovascular risk.

GE-29EXPRESSION SUBCLASS PROFILE IN PSEUDOPROGRESSION AND TRUE PROGRESSION IN NEWLY DIAGNOSED GBM

PubMed Central

Robin, Adam; Raghunathan, Aditya; Leung, Denise; Burmeister, Charlotte; Poisson, Laila; Scarpace, Lisa; Walbert, Tobias; Mikkelsen, Tom; Lee, Ian

2014-01-01

INTRODUCTION: The hallmark of glioblastoma multiforme (GBM) is its penchant for relentless progression. Pseudoprogression describes a post-treatment reaction demonstrating increased edema and contrast enhancement similar to typical tumor progression except that on subsequent imaging without escalation of antitumor therapy these changes stabilize or revert [1]. Accurate identification of pseudoprogression has important implications for therapy and research and potentially prognosis as well. Increased cellular proliferation (Ki-67 indices) and the presence of a methylated O-6-methylguanine-DNA methyltransferase (MGMT) promoter have been associated with higher rates of pseudoprogression [2,3]. However, more sensitive and specific biomarkers of pseudoprogression are needed. This study seeks to identify novel indicators of pseudoprogression. METHODS: Patients were identified using the Hermelin Brain Tumor Center database at Henry Ford Hospital. Tissues from 52 patients with newly diagnosed GBM between 1992 and 2011 were gathered and whole genome sequencing and subtyping was performed by The Cancer Genome Atlas researchers. Retrospective chart review was carried out. Patients were assigned to either pseudoprogression (PP) or true progression (TP) groups based on whether changes suggestive of disease progression on MRI within 2 months of post-operative therapy initiation regressed without additional antitumor therapy during the ensuing 4 months. The incidence of pseudoprogression and GBM subclass were correlated using Fisher's Exact Test. RESULTS: Forty-one of 52 (79%) cases were identified as TP while 11/52 (21%) were found to have PP. In our study population, PP was associated with significantly increased median survival compared with TP (735 versus 313 days, respectively, p < 0.0012). The molecular subclass profile for both groups included a predominance of Mesenchymal and Neural subtypes, revealing no correlation between GBM subclass and the risk of pseudoprogression

Flavonoids, flavonoid subclasses and breast cancer risk: a meta-analysis of epidemiologic studies.

PubMed

Hui, Chang; Qi, Xie; Qianyong, Zhang; Xiaoli, Peng; Jundong, Zhu; Mantian, Mi

2013-01-01

Studies have suggested the chemopreventive effects of flavonoids on carcinogenesis. Yet numbers of epidemiologic studies assessing dietary flavonoids and breast cancer risk have yielded inconsistent results. The association between flavonoids, flavonoid subclasses (flavonols, flavan-3-ols, etc.) and the risk of breast cancer lacks systematic analysis. We aimed to examine the association between flavonoids, each flavonoid subclass (except isoflavones) and the risk of breast cancer by conducting a meta-analysis. We searched for all relevant studies with a prospective cohort or case-control study design published before July 1(st), 2012, using Cochrane library, MEDLINE, EMBASE and PUBMED. Summary relative risks (RR) were calculated using fixed- or random-effects models. All analyses were performed using STATA version 10.0. Twelve studies were included, involving 9 513 cases and 181 906 controls, six of which were prospective cohort studies, and six were case-control studies. We calculated the summary RRs of breast cancer risk for the highest vs lowest categories of each flavonoid subclass respectively. The risk of breast cancer significantly decreased in women with high intake of flavonols (RR=0.88, 95% CI 0.80-0.98) and flavones (RR=0.83, 95% CI: 0.76-0.91) compared with that in those with low intake of flavonols and flavones. However, no significant association of flavan-3-ols (RR=0.93, 95% CI: 0.84-1.02), flavanones (summary RR=0.95, 95% CI: 0.88-1.03), anthocyanins (summary RR=0.97, 95% CI: 0.87-1.08) or total flavonoids (summary RR=0.98, 95% CI: 0.86-1.12) intake with breast cancer risk was observed. Furthermore, summary RRs of 3 case-control studies stratified by menopausal status suggested flavonols, flavones or flavan-3-ols intake is associated with a significant reduced risk of breast cancer in post-menopausal while not in pre-menopausal women. The present study suggests the intake of flavonols and flavones, but not other flavonoid subclasses or total

Distribution of immunoglobulin G (IgG) and A (IgA) subclasses following Q fever vaccination with soluble phase I Coxiella burnetii extract.

PubMed

Camacho, M T; Outschoorn, I; Kovácová, E; Téllez, A

2000-03-06

High levels of IgG1, IgG3 and IgA2 antibodies have been observed in patients with Q fever following Coxiella burnetii infection. This IgG subclass distribution is more typical of viral and autoimmune diseases than of bacterial infections. It seemed, therefore, of interest to carry out a prospective study of the distribution of immunoglobulin subclasses after vaccination with phase I C. burnetii tricloroacetic soluble extracts to detect possible differences with respect to natural infection. The antibody response found in vaccinees was mainly restricted to the IgG1, IgG2 and IgA1 subclasses. These findings confirm differences in isotype distribution when compared to those of patients with acute or chronic Coxiella infections and opens an area of interest with respect to the role of IgA subclasses.

Evidence of IgY subclass diversification in snakes: evolutionary implications.

PubMed

Wang, Tao; Sun, Yi; Shao, Wenwei; Cheng, Gang; Li, Lingxiao; Cao, Zubing; Yang, Zhi; Zou, Huiying; Zhang, Wei; Han, Binyue; Hu, Yang; Ren, Liming; Hu, Xiaoxiang; Guo, Ying; Fei, Jing; Hammarström, Lennart; Li, Ning; Zhao, Yaofeng

2012-10-01

Mammalian IgG and IgE are thought to have evolved from IgY of nonmammalian tetrapods; however, no diversification of IgY subclasses has been reported in reptiles or birds, which are phylogenetically close to mammals. To our knowledge, we report the first evidence of the presence of multiple IgY-encoding (υ) genes in snakes. Two υ genes were identified in the snake Elaphe taeniura, and three υ genes were identified in the Burmese python (Python molurus bivittatus). Although four of the υ genes displayed a conventional four-H chain C region exon structure, one of the υ genes in the Burmese python lacked the H chain C region 2 exon, thus exhibiting a structure similar to that of the mammalian γ genes. We developed mouse mAbs specific for the IgY1 and IgY2 of E. taeniura and showed that both were expressed in serum; each had two isoforms: one full-length and one truncated at the C terminus. The truncation was not caused by alternative splicing or transcriptional termination. We also identified the μ and δ genes, but no α gene, in both snakes. This study provides valuable clues for our understanding of Ig gene evolution in tetrapods.

HDL subclasses are heterogeneous in their associations with body fat, as measured by dual-energy X-ray absorptiometry: the Kitakata Kids Health Study.

PubMed

Kouda, Katsuyasu; Nakamura, Harunobu; Fujita, Yuki; Hamada, Masami; Kajita, Etsuko; Nakatani, Yoshimi; Sato, Yuho; Uenishi, Kazuhiro; Iki, Masayuki

2015-04-15

Obesity, defined as the excessive accumulation of body fat, is frequently associated with low concentrations of high-density lipoprotein (HDL) cholesterol. However, HDL particles are heterogeneous in size and composition. HDL subclasses may be differentially associated with body fat. This study investigated associations between the cholesterol concentrations of HDL subclasses, as determined by high-performance liquid chromatography, and body fat variables, as measured by dual-energy X-ray absorptiometry. The source population was all ninth grade students who attended Shiokawa Junior High School in Japan. Cross-sectional data on body fat and serum HDL subclasses were obtained for 87 students (72.5% of the source population). The cholesterol concentration of the large HDL subclass showed a significant (P<0.05) inverse relationship with whole body fat and trunk fat (r=-0.24 and -0.30), whereas the concentration of the small HDL subclass showed a significant positive relationship with these body fat variables (r=0.25 and 0.31). After adjusting for potential confounding factors, the mean concentration of small HDL significantly increased from the lowest to highest tertiles of trunk fat mass index. These results indicate that HDL subclasses are heterogeneous in their associations with body fat variables that were accurately measured by dual-energy X-ray absorptiometry among Japanese students. Copyright © 2015 Elsevier B.V. All rights reserved.

Abnormal serum IgG subclass pattern in children with Down's syndrome.

PubMed

Annerén, G; Magnusson, C G; Lilja, G; Nordvall, S L

1992-05-01

Susceptibility to infections is a well known feature of Down's syndrome. The possible relation between this predisposition and the serum concentrations of the IgG subclasses was studied in 38 children with Down's syndrome aged 1-12 years. An age matched group of 50 healthy children served as controls. The serum concentrations of IgG1 and IgG3 were significantly raised among children with Down's syndrome in all three age groups studied (that is 1-2.5, 4-8, and 9-12 years). The serum concentrations of IgG2 were normal in the first two groups but significantly reduced in the third age group. In contrast, the concentrations of IgG4 among children with Down's syndrome were significantly reduced in all three age groups. Moreover, among the children with Down's syndrome aged 4-12 years 68% (15/22) had IgG4 concentrations below 2 SDs of the geometrical mean of the controls. The results may partially explain the proneness of children with Down's syndrome to infections with encapsulated bacteria. Although the underlying cause of these abnormalities is unknown, IgG subclass determination seems relevant in the clinical evaluation of children with Down's syndrome.

Does Kiitricha (Protista, Ciliophora, Spirotrichea) belong to Euplotida or represent a primordial spirotrichous taxon? With suggestion to establish a new subclass Protohypotrichia.

PubMed

Li, Lifang; Shao, Chen; Song, Weibo; Lynn, Denis H; Chen, Zigui; Shin, Mann Kyoon

2009-02-01

The genus Kiitricha was long assumed to be the most primordial taxon in the Stichotrichia [hypotrichs sensu lato (s. l.)] based on its morphological features and was considered to be an intermediate between heterotrichs and the traditional hypotrichous assemblage. In order to evaluate the phylogenetic position of Kiitricha within the Hypotrichia, we sequenced the small-subunit rRNA gene and the alpha-tubulin gene for a Qingdao population of Kiitricha marina. Phylogenetic trees were constructed and compared to morphological and morphogenetic data. The results show that (i) Kiitricha is positioned near Phacodinium, both of which always form a sister clade to the assemblage including Stichotrichia, Hypotrichia, Oligotrichia and Choreotrichia, (ii) Kiitricha, which may represent an intermediate between heterotrichs (s. l.) and the Stichotrichia-Hypotrichia complex, is probably an ancestor-like form of the latter group and (iii) in contrast to morphological characters, both molecular and ontogenetic data support the separation of Kiitricha from the hypotrichs (s. l.). Thus, Kiitricha might be placed in the class Spirotrichea at about subclass level, next to Phaconidiidia, Hypotrichia and Stichotrichia, which supports the establishment of a new subclass Protohypotrichia n. subclass within the class Spirotrichea, with characterizations including slightly differentiated somatic ciliature (i.e. cirri on the ventral side generally uniform and non-grouped, no clearly defined marginal cirral rows, ciliature on the dorsal side mixed with cirri and dikinetids, no clearly differentiated dorsal kineties) and a unique but intermediate morphogenetic pattern of cortical structures between Hypotrichia and Stichotrichia.

Comprehensive analysis of mycolic acid subclass and molecular species composition of Mycobacterium bovis BCG Tokyo 172 cell wall skeleton (SMP-105).

PubMed

Uenishi, Yuko; Fujita, Yukiko; Kusunose, Naoto; Yano, Ikuya; Sunagawa, Makoto

2008-02-01

The mycobacterial cell envelope consists of a characteristic cell wall skeleton (CWS), a mycoloyl arabinogalactan peptidoglycan complex, and related hydrophobic components that contribute to the cell surface properties. Since mycolic acids have recently been reported to play crucial roles in host immune response, detailed molecular characterization of mycolic acid subclasses and sub-subclasses of CWS from Mycobacterium bovis BCG Tokyo 172 (SMP-105) was performed. Mycolic acids were liberated by alkali hydrolysis from SMP-105, and their methyl esters were separated by silica gel TLC into three subclasses: alpha-, methoxy-, and keto-mycolates. Each mycolate subclass was further separated by silver nitrate (AgNO(3))-coated silica gel TLC into sub-subclasses. Molecular weights of individual mycolic acid were determined by MALDI-TOF mass spectrometry. alpha-Mycolates were sub-grouped into cis, cis-dicyclopropanoic (alpha1), and cis-monocyclopropanoic-cis-monoenoic (alpha2) series; methoxy-mycolates were sub-grouped into cis-monocyclopropanoic (m1), trans-monocyclopropanoic (m2), trans-monoenoic (m3), cis-monocyclopropanoic-trans-monoenoic (m4), cis-monoenoic (m5), and cis-monocyclopropanoic-cis-monoenoic (m6) series; and keto-mycolates were sub-grouped into cis-monocyclopropanoic (k1), trans-monocyclopropanoic (k2), trans-monoenoic (k3), cis-monoenoic (k4), and cis-monocyclopropanoic-cis-monoenoic (k5) series. The position of each functional group, including cyclopropane rings and methoxy and keto groups, was determined by analysis of the meromycolates with fast atom bombardment (FAB) mass spectrometry and FAB mass-mass spectrometry, and the cis/trans ratio of cyclopropane rings and double bonds were determined by NMR analysis of methyl mycolates. Mycolic acid subclass and molecular species composition of SMP-105 showed characteristic features including newly-identified cis-monocyclopropanoic-trans-monoenoic mycolic acid (m4).

Increased sensitivity and high specificity of indirect immunofluorescence in detecting IgG subclasses for diagnosis of bullous pemphigoid.

PubMed

Jankásková, J; Horváth, O N; Varga, R; Arenberger, P; Schmidt, E; Ruzicka, T; Sárdy, M

2018-04-01

Indirect immunofluorescence (IIF) microscopy on monkey oesophagus is an important assay for the diagnosis of bullous pemphigoid (BP). Its relatively low sensitivity (60-80%) may be partly due to insufficient detection of minor IgG subclasses. To determine the operating characteristics of an IgG subclass in IIF. We designed a retrospective, dual-centre, controlled cohort study on sera from 64 BP sera that had been rated as false negatives by traditional IIF microscopy, and assessed circulating IgG 1 , IgG 3 and IgG 4 autoantibodies. The sensitivities of IIF in detecting IgG 1 , IgG 3 , IgG 4 and all three in combination were 45.3%, 18.8%, 32.8% and 48.4%, respectively. Specificities were > 97%. Detection of IgG subclass (especially IgG 1 and IgG 4 ) autoantibodies by IIF on monkey oesophagus can significantly improve diagnostic performance of IIF microscopy for diagnosis of BP. © 2018 British Association of Dermatologists.

FAMILY ANALYSIS OF IMMUNOGLOBULIN CLASSES AND SUBCLASSES IN CHILDREN WITH AUTISTIC DISORDER

PubMed Central

Spiroski, Mirko; Trajkovski, Vladimir; Trajkov, Dejan; Petlichkovski, Aleksandar; Efinska-Mladenovska, Olivija; Hristomanova, Slavica; Djulejic, Eli; Paneva, Meri; Bozhikov, Jadranka

2009-01-01

Autistic disorder is a severe neurodevelopment disorder characterized by a triad of impairments in reciprocal social interaction, verbal and nonverbal communication, and a pattern of repetitive stereotyped activities, behaviours and interests. There are strong lines of evidence to suggest that the immune system plays an important role in the pathogenesis of autistic disorder. The aim of this study was to analyze quantitative plasma concentration of immunoglobulin classes, and subclasses in autistic patients and their families. The investigation was performed retrospectively in 50 persons with autistic disorder in the Republic of Macedonia. Infantile autistic disorder was diagnosed by DSM-IV and ICD-10 criteria. Plasma immunoglobulin classes (IgM, IgA, and IgG) and subclasses (IgG1, IgG2, IgG3, and IgG4) were determined using Nephelometer Analyzer BN-100. Multiple comparisons for the IgA variable have shown statistically significant differences between three pairs: male autistic from the fathers (p = 0,001), female autistic from the mothers (p = 0,008), as well as healthy sisters from the fathers (p = 0,011). Statistically significant differences found between three groups regarding autistic disorder (person with autistic disorder, father/mother of a person with autistic disorder, and brother/sister) independent of sex belongs to IgA, IgG2, and IgG3 variables. Multiple comparisons for the IgA variable have shown statistically significant differences between children with autistic disorder from the fathers and mothers (p < 0,001), and healthy brothers and sisters from the fathers and mothers (p < 0,001). Comparison between healthy children and children with autistic disorder from the same family should be tested for immunoglobulin classes and subclasses in order to avoid differences between generations. PMID:20001993

Family analysis of immunoglobulin classes and subclasses in children with autistic disorder.

PubMed

Spiroski, Mirko; Trajkovski, Vladimir; Trajkov, Dejan; Petlichkovski, Aleksandar; Efinska-Mladenovska, Olivija; Hristomanova, Slavica; Djulejic, Eli; Paneva, Meri; Bozhikov, Jadranka

2009-11-01

Autistic disorder is a severe neurodevelopment disorder characterized by a triad of impairments in reciprocal social interaction, verbal and nonverbal communication, and a pattern of repetitive stereotyped activities, behaviours and interests. There are strong lines of evidence to suggest that the immune system plays an important role in the pathogenesis of autistic disorder. The aim of this study was to analyze quantitative plasma concentration of immunoglobulin classes, and subclasses in autistic patients and their families. The investigation was performed retrospectively in 50 persons with autistic disorder in the Republic of Macedonia. Infantile autistic disorder was diagnosed by DSM-IV and ICD-10 criteria. Plasma immunoglobulin classes (IgM, IgA, and IgG) and subclasses (IgG1, IgG2, IgG3, and IgG4) were determined using Nephelometer Analyzer BN-100. Multiple comparisons for the IgA variable have shown statistically significant differences between three pairs: male autistic from the fathers (p = 0,001), female autistic from the mothers (p = 0,008), as well as healthy sisters from the fathers (p = 0,011). Statistically significant differences found between three groups regarding autistic disorder (person with autistic disorder, father/mother of a person with autistic disorder, and brother/sister) independent of sex belongs to IgA, IgG2, and IgG3 variables. Multiple comparisons for the IgA variable have shown statistically significant differences between children with autistic disorder from the fathers and mothers (p < 0,001), and healthy brothers and sisters from the fathers and mothers (p < 0,001). Comparison between healthy children and children with autistic disorder from the same family should be tested for immunoglobulin classes and subclasses in order to avoid differences between generations.

Nuclear Function of Subclass I Actin-Depolymerizing Factor Contributes to Susceptibility in Arabidopsis to an Adapted Powdery Mildew Fungus1[OPEN

PubMed Central

Inada, Noriko; Higaki, Takumi; Hasezawa, Seiichiro

2016-01-01

Actin-depolymerizing factors (ADFs) are conserved proteins that function in regulating the structure and dynamics of actin microfilaments in eukaryotes. In this study, we present evidence that Arabidopsis (Arabidopsis thaliana) subclass I ADFs, particularly ADF4, functions as a susceptibility factor for an adapted powdery mildew fungus. The null mutant of ADF4 significantly increased resistance against the adapted powdery mildew fungus Golovinomyces orontii. The degree of resistance was further enhanced in transgenic plants in which the expression of all subclass I ADFs (i.e. ADF1–ADF4) was suppressed. Microscopic observations revealed that the enhanced resistance of adf4 and ADF1-4 knockdown plants (ADF1-4Ri) was associated with the accumulation of hydrogen peroxide and cell death specific to G. orontii-infected cells. The increased resistance and accumulation of hydrogen peroxide in ADF1-4Ri were suppressed by the introduction of mutations in the salicylic acid- and jasmonic acid-signaling pathways but not by a mutation in the ethylene-signaling pathway. Quantification by microscopic images detected an increase in the level of actin microfilament bundling in ADF1-4Ri but not in adf4 at early G. orontii infection time points. Interestingly, complementation analysis revealed that nuclear localization of ADF4 was crucial for susceptibility to G. orontii. Based on its G. orontii-infected-cell-specific phenotype, we suggest that subclass I ADFs are susceptibility factors that function in a direct interaction between the host plant and the powdery mildew fungus. PMID:26747284

Biochemical Characterization of CPS-1, a Subclass B3 Metallo-β-Lactamase from a Chryseobacterium piscium Soil Isolate.

PubMed

Gudeta, Dereje Dadi; Pollini, Simona; Docquier, Jean-Denis; Bortolaia, Valeria; Rossolini, Gian Maria; Guardabassi, Luca

2015-12-14

CPS-1 is a subclass B3 metallo-β-lactamase from a Chryseobacterium piscium isolate collected from soil, showing 68% amino acid identity to the GOB-1 enzyme. CPS-1 was overproduced in Escherichia coli Rosetta (DE3), purified by chromatography, and biochemically characterized. This enzyme exhibits a broad-spectrum substrate profile, including penicillins, cephalosporins, and carbapenems, which overall resembles those of L1, GOB-1, and acquired subclass B3 enzymes AIM-1 and SMB-1. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Thyroglobulin autoantibodies switch to immunoglobulin (Ig)G1 and IgG3 subclasses and preserve their restricted epitope pattern after 131I treatment for Graves' hyperthyroidism: the activity of autoimmune disease influences subclass distribution but not epitope pattern of autoantibodies

PubMed Central

Latrofa, F; Ricci, D; Montanelli, L; Piaggi, P; Mazzi, B; Bianchi, F; Brozzi, F; Santini, P; Fiore, E; Marinò, M; Tonacchera, M; Vitti, P

2014-01-01

The subclass distribution of thyroglobulin autoantibodies (TgAb) is debated, whereas their epitope pattern is restricted. Radioidine (131I) treatment for Graves' disease (GD) induces a rise in TgAb levels, but it is unknown whether it modifies subclass distribution and epitope pattern of TgAb as well. We collected sera from GD patients before 131I treatment and 3 and 6 months thereafter. We measured total TgAb, TgAb light chains and TgAb subclasses by enzyme-linked immunosorbent assay (ELISA) in 25 patients. We characterized the TgAb epitope pattern in 30 patients by inhibiting their binding to 125-ITg by a pool of four TgAb-Fab (recognizing Tg epitope regions A, B, C and D) and to Tg in ELISA by each TgAb-Fab. Total TgAb immunoglobulin (Ig)G rose significantly (P = 0·024). TgAb κ chains did not change (P = 0·052), whereas TgAb λ chains increased significantly (P = 0·001) and persistently. We observed a significant rise in IgG1 and IgG3 levels after 131I (P = 0·008 and P = 0·006, respectively), while IgG2 and IgG4 levels did not change. The rise of IgG1 was persistent, that of IgG3 transient. The levels of inhibition of TgAb binding to Tg by the TgAb-Fab pool were comparable. A slight, non-significant reduction of the inhibition by the immune-dominant TgAb-Fab A was observed 3 and 6 months after 131I. We conclude that 131I treatment for GD increases the levels of the complement-activating IgG1 and IgG3 subclasses and does not influence significantly the epitope pattern of TgAb. In autoimmune thyroid disease subclass distribution of autoantibodies is dynamic in spite of a stable epitope pattern. PMID:25134846

What do anti-Toxoplasma gondii IgA and IgG subclasses in human saliva indicate?

PubMed

Cañedo-Solares, I; Gómez-Chávez, F; Luna-Pastén, H; Ortiz-Alegría, L B; Flores-García, Y; Figueroa-Damián, R; Macedo-Romero, C A; Correa, D

2018-05-01

Diagnostic tests for toxoplasmosis are based on serological techniques due to their high sensitivity. Some IgG subclasses are related to clinical outcome in the congenital form. In this work, we determined the levels of IgG, IgA, IgG1, IgG2, IgG3 and IgG4 anti-Toxoplasma gondii antibodies in paired saliva and serum samples from 91 women by indirect ELISA using a crude extract of the RH strain. The levels of IgA, IgG2, IgG3 and IgG4 antibodies and, to a lesser extent, IgG1 did not correlate between saliva and serum, that is, most cases that were positive for one Ig class in a sample were negative or very low in the other, and vice versa. We also observed that most samples of saliva that were positive for one IgG subclass were also positive for at least 2 of the other 3; this contrasted with findings in serum, wherein each person was positive almost exclusively for one subclass, as demonstrated before by us and other researchers. Although these findings are disappointing for the use in diagnosis, the richer response in saliva might indicate local exposure to T. gondii antigens without systemic infection; thus, saliva might be reflecting a local (protective?) response against this protozoan. © 2018 John Wiley & Sons Ltd.

Induction of a Th-1-biased IgG subclass response against equine herpesvirus type 1 in horses previously infected with type 4 virus.

PubMed

Bannai, Hiroshi; Tsujimura, Koji; Kondo, Takashi; Nemoto, Manabu; Yamanaka, Takashi; Sugiura, Takeo; Maeda, Ken; Matsumura, Tomio

2011-04-01

An immunoglobulin G (IgG) subclass response against equine herpesvirus type 1 (EHV-1) infection was investigated in horses that were naïve to EHV-1/4 and those that had previously been exposed to EHV-4. The IgG subclass response was determined by an ELISA using EHV-1-specific recombinant gG protein as an antigen. In most horses naïve to EHV-1/4, IgGa, IgGb, and IgG(T) were induced after experimental infection with EHV-1. In contrast, a subclass response dominated by IgGa and IgGb, with no apparent increase in IgG(T), was observed after EHV-1 infection in horses previously infected with EHV-4. Horses naturally infected with EHV-1 in the field showed similar responses. These results indicated that pre-infection with EHV-4 induced a Th-1-biased IgG subclass response against subsequent EHV-1 infection.

Repeated E-Book Reading and Its Contribution to Learning New Words among Kindergartners

ERIC Educational Resources Information Center

Korat, Ofra; Kozlov-Peretz, Olla; Segal-Drori, Ora

2017-01-01

The contribution of repeated e-book reading with and without word explanation support and its effect on receptive and expressive word learning among preschoolers was examined. Seventy-eight kindergartners were randomly divided into an experimental and a control group. The experimental group received two individual reading sessions of an e-book…

Abnormal serum IgG subclass pattern in children with Down's syndrome.

PubMed Central

Annerén, G; Magnusson, C G; Lilja, G; Nordvall, S L

1992-01-01

Susceptibility to infections is a well known feature of Down's syndrome. The possible relation between this predisposition and the serum concentrations of the IgG subclasses was studied in 38 children with Down's syndrome aged 1-12 years. An age matched group of 50 healthy children served as controls. The serum concentrations of IgG1 and IgG3 were significantly raised among children with Down's syndrome in all three age groups studied (that is 1-2.5, 4-8, and 9-12 years). The serum concentrations of IgG2 were normal in the first two groups but significantly reduced in the third age group. In contrast, the concentrations of IgG4 among children with Down's syndrome were significantly reduced in all three age groups. Moreover, among the children with Down's syndrome aged 4-12 years 68% (15/22) had IgG4 concentrations below 2 SDs of the geometrical mean of the controls. The results may partially explain the proneness of children with Down's syndrome to infections with encapsulated bacteria. Although the underlying cause of these abnormalities is unknown, IgG subclass determination seems relevant in the clinical evaluation of children with Down's syndrome. PMID:1534650

Association among Dietary Flavonoids, Flavonoid Subclasses and Ovarian Cancer Risk: A Meta-Analysis.

PubMed

Hua, Xiaoli; Yu, Lili; You, Ruxu; Yang, Yu; Liao, Jing; Chen, Dongsheng; Yu, Lixiu

2016-01-01

Previous studies have indicated that intake of dietary flavonoids or flavonoid subclasses is associated with the ovarian cancer risk, but presented controversial results. Therefore, we conducted a meta-analysis to derive a more precise estimation of these associations. We performed a search in PubMed, Google Scholar and ISI Web of Science from their inception to April 25, 2015 to select studies on the association among dietary flavonoids, flavonoid subclasses and ovarian cancer risk. The information was extracted by two independent authors. We assessed the heterogeneity, sensitivity, publication bias and quality of the articles. A random-effects model was used to calculate the pooled risk estimates. Five cohort studies and seven case-control studies were included in the final meta-analysis. We observed that intake of dietary flavonoids can decrease ovarian cancer risk, which was demonstrated by pooled RR (RR = 0.82, 95% CI = 0.68-0.98). In a subgroup analysis by flavonoid subtypes, the ovarian cancer risk was also decreased for isoflavones (RR = 0.67, 95% CI = 0.50-0.92) and flavonols (RR = 0.68, 95% CI = 0.58-0.80). While there was no compelling evidence that consumption of flavones (RR = 0.86, 95% CI = 0.71-1.03) could decrease ovarian cancer risk, which revealed part sources of heterogeneity. The sensitivity analysis indicated stable results, and no publication bias was observed based on the results of Funnel plot analysis and Egger's test (p = 0.26). This meta-analysis suggested that consumption of dietary flavonoids and subtypes (isoflavones, flavonols) has a protective effect against ovarian cancer with a reduced risk of ovarian cancer except for flavones consumption. Nevertheless, further investigations on a larger population covering more flavonoid subclasses are warranted.

Association among Dietary Flavonoids, Flavonoid Subclasses and Ovarian Cancer Risk: A Meta-Analysis

PubMed Central

You, Ruxu; Yang, Yu; Liao, Jing; Chen, Dongsheng; Yu, Lixiu

2016-01-01

Background Previous studies have indicated that intake of dietary flavonoids or flavonoid subclasses is associated with the ovarian cancer risk, but presented controversial results. Therefore, we conducted a meta-analysis to derive a more precise estimation of these associations. Methods We performed a search in PubMed, Google Scholar and ISI Web of Science from their inception to April 25, 2015 to select studies on the association among dietary flavonoids, flavonoid subclasses and ovarian cancer risk. The information was extracted by two independent authors. We assessed the heterogeneity, sensitivity, publication bias and quality of the articles. A random-effects model was used to calculate the pooled risk estimates. Results Five cohort studies and seven case-control studies were included in the final meta-analysis. We observed that intake of dietary flavonoids can decrease ovarian cancer risk, which was demonstrated by pooled RR (RR = 0.82, 95% CI = 0.68–0.98). In a subgroup analysis by flavonoid subtypes, the ovarian cancer risk was also decreased for isoflavones (RR = 0.67, 95% CI = 0.50–0.92) and flavonols (RR = 0.68, 95% CI = 0.58–0.80). While there was no compelling evidence that consumption of flavones (RR = 0.86, 95% CI = 0.71–1.03) could decrease ovarian cancer risk, which revealed part sources of heterogeneity. The sensitivity analysis indicated stable results, and no publication bias was observed based on the results of Funnel plot analysis and Egger’s test (p = 0.26). Conclusions This meta-analysis suggested that consumption of dietary flavonoids and subtypes (isoflavones, flavonols) has a protective effect against ovarian cancer with a reduced risk of ovarian cancer except for flavones consumption. Nevertheless, further investigations on a larger population covering more flavonoid subclasses are warranted. PMID:26960146

The different effector function capabilities of the seven equine IgG subclasses have implications for vaccine strategies

PubMed Central

Lewis, Melanie J.; Wagner, Bettina; Woof, Jenny M.

2008-01-01

Recombinant versions of the seven equine IgG subclasses were expressed in CHO cells. All assembled into intact immunoglobulins stabilised by disulphide bridges, although, reminiscent of human IgG4, a small proportion of equine IgG4 and IgG7 were held together by non-covalent bonds alone. All seven IgGs were N-glycosylated. In addition IgG3 appeared to be O-glycosylated and could bind the lectin jacalin. Staphylococcal protein A displayed weak binding for the equine IgGs in the order: IgG1 > IgG3 > IgG4 > IgG7 > IgG2 = IgG5 > IgG6. Streptococcal protein G bound strongly to IgG1, IgG4 and IgG7, moderately to IgG3, weakly to IgG2 and IgG6, and not at all to IgG5. Analysis of antibody effector functions revealed that IgG1, IgG3, IgG4, IgG5 and IgG7, but not IgG2 and IgG6, were able to elicit a strong respiratory burst from equine peripheral blood leukocytes, predicting that the former five IgG subclasses are able to interact with Fc receptors on effector cells. IgG1, IgG3, IgG4 and IgG7, but not IgG2, IgG5 and IgG6, were able to bind complement C1q and activate complement via the classical pathway. The differential effector function capabilities of the subclasses suggest that, for maximum efficacy, equine vaccine strategies should seek to elicit antibody responses of the IgG1, IgG3, IgG4, and IgG7 subclasses. PMID:17669496

[The impact of a 14- day regular physical exercise regime on the concentration of the classes and subclasses of lipoprotein particles in young subjects with a sedentary lifestyle].

PubMed

Sabaka, P; Dukát, A; Oravec, S; Mistríková, L; Baláž, D; Bendžala, M; Gašpar, L

2013-10-01

Recommendations from the cardiological professional companies working in the area of primary prevention of cardiovascular diseases put an emphasis on regular aerobic physical activity. Its positive effect on both cardiovascular and overall mortality has repea-tedly been proven by the observations of prospective and cross sectional epidemiological studies. One of the possible explanations of this positive effect is a change in the concentration of lipoprotein classes and their subclasses, which is expressed as a change in their average size. In a group of young healthy men and women with a sedentary lifestyle we observed the effect of medium intensive physical exercise in the form of a 30- minute slow run per day lasting for 14 days. The concentration of lipoprotein classes and subclasses were determined through the method of a linear electrophoresis in polyacrylamide gel. In the observed group we found a statistically significant decrease of VLDL, large IDL particles, medium sized LDL, small dense LDL, and medium sized HDL particles. In the light of current knowledge all these lipoprotein particles are deemed as atherogenic. Thus, as little as 14 days of regular exercising has a positive effect on the concentration of plasmatic lipoproteins, and emphasises the role of regular physical activity in the primary prevention of cardiovascular diseases.

On certain subclasses of multivalent functions associated with an extended fractional differintegral operator

NASA Astrophysics Data System (ADS)

Patel, J.; Mishra, A. K.

2007-08-01

In the present paper an extended fractional differintegral operator , suitable for the study of multivalent functions is introduced. Various mapping properties and inclusion relationships between certain subclasses of multivalent functions are investigated by applying the techniques of differential subordination. Relevant connections of the definitions and results presented in this paper with those obtained in several earlier works on the subject are also pointed out.

Plastid signalling under multiple conditions is accompanied by a common defect in RNA editing in plastids.

PubMed

Kakizaki, Tomohiro; Yazu, Fumiko; Nakayama, Katsuhiro; Ito-Inaba, Yasuko; Inaba, Takehito

2012-01-01

Retrograde signalling from the plastid to the nucleus, also known as plastid signalling, plays a key role in coordinating nuclear gene expression with the functional state of plastids. Inhibitors that cause plastid dysfunction have been suggested to generate specific plastid signals related to their modes of action. However, the molecules involved in plastid signalling remain to be identified. Genetic studies indicate that the plastid-localized pentatricopeptide repeat protein GUN1 mediates signalling under several plastid signalling-related conditions. To elucidate further the nature of plastid signals, investigations were carried out to determine whether different plastid signal-inducing treatments had similar effects on plastids and on nuclear gene expression. It is demonstrated that norflurazon and lincomycin treatments and the plastid protein import2-2 (ppi2-2) mutation, which causes a defect in plastid protein import, all resulted in similar changes at the gene expression level. Furthermore, it was observed that these three treatments resulted in defective RNA editing in plastids. This defect in RNA editing was not a secondary effect of down-regulation of pentatricopeptide repeat protein gene expression in the nucleus. The results indicate that these three treatments, which are known to induce plastid signals, affect RNA editing in plastids, suggesting an unprecedented link between plastid signalling and RNA editing.

Labor union members play an OLG repeated game

PubMed Central

Kandori, Michihiro; Obayashi, Shinya

2014-01-01

Humans are capable of cooperating with one another even when it is costly and a deviation provides an immediate gain. An important reason is that cooperation is reciprocated or rewarded and deviations are penalized in later stages. For cooperation to be sustainable, not only must rewards and penalties be strong enough but individuals should also have the right incentives to provide rewards and punishments. Codes of conduct with such properties have been studied extensively in game theory (as repeated game equilibria), and the literature on the evolution of cooperation shows how equilibrium behavior might emerge and proliferate in society. We found that community unions, a subclass of labor unions that admits individual affiliations, are ideal to corroborate these theories with reality, because (i) their activities are simple and (ii) they have a structure that closely resembles a theoretical model, the overlapping generations repeated game. A detailed case study of a community union revealed a possible equilibrium that can function under the very limited observability in the union. The equilibrium code of conduct appears to be a natural focal point based on simple heuristic reasoning. The union we studied was created out of necessity for cooperation, without knowing or anticipating how cooperation might be sustained. The union has successfully resolved about 3,000 labor disputes and created a number of offspring. PMID:25024211

A large complement of the predicted Arabidopsis ARM repeat proteins are members of the U-box E3 ubiquitin ligase family.

PubMed

Mudgil, Yashwanti; Shiu, Shin-Han; Stone, Sophia L; Salt, Jennifer N; Goring, Daphne R

2004-01-01

The Arabidopsis genome was searched to identify predicted proteins containing armadillo (ARM) repeats, a motif known to mediate protein-protein interactions in a number of different animal proteins. Using domain database predictions and models generated in this study, 108 Arabidopsis proteins were identified that contained a minimum of two ARM repeats with the majority of proteins containing four to eight ARM repeats. Clustering analysis showed that the 108 predicted Arabidopsis ARM repeat proteins could be divided into multiple groups with wide differences in their domain compositions and organizations. Interestingly, 41 of the 108 Arabidopsis ARM repeat proteins contained a U-box, a motif present in a family of E3 ligases, and these proteins represented the largest class of Arabidopsis ARM repeat proteins. In 14 of these U-box/ARM repeat proteins, there was also a novel conserved domain identified in the N-terminal region. Based on the phylogenetic tree, representative U-box/ARM repeat proteins were selected for further study. RNA-blot analyses revealed that these U-box/ARM proteins are expressed in a variety of tissues in Arabidopsis. In addition, the selected U-box/ARM proteins were found to be functional E3 ubiquitin ligases. Thus, these U-box/ARM proteins represent a new family of E3 ligases in Arabidopsis.

Two peculiar subclasses of cool DB stars - The DBA's and the DBZ's

NASA Technical Reports Server (NTRS)

Shipman, Harry L.

1987-01-01

This paper reviews several recent observational investigations which have demonstrated that a significant number of white dwarfs with He-dominated photospheres contain trace hydrogen. In addition, follow-up work on the Case Blue Star survey has uncovered an analog of GD 40 - another DBZ star. Various scenarios for their origin are discussed. The paper concludes with a brief synopsis of a discussion of how many more subclasses of white dwarf stars might exist and what it would take to discover them.

Flavonoids, Flavonoid Subclasses, and Esophageal Cancer Risk: A Meta-Analysis of Epidemiologic Studies.

PubMed

Cui, Lingling; Liu, Xinxin; Tian, Yalan; Xie, Chen; Li, Qianwen; Cui, Han; Sun, Changqing

2016-06-08

Flavonoids have been suggested to play a chemopreventive role in carcinogenesis. However, the epidemiologic studies assessing dietary intake of flavonoids and esophageal cancer risk have yielded inconsistent results. This study was designed to examine the association between flavonoids, each flavonoid subclass, and the risk of esophageal cancer with a meta-analysis approach. We searched for all relevant studies with a prospective cohort or case-control study design published from January 1990 to April 2016, using PUBMED, EMBASE, and Web of Science. Pooled odds ratios (ORs) were calculated using fixed or random-effect models. In total, seven articles including 2629 cases and 481,193 non-cases were selected for the meta-analysis. Comparing the highest-intake patients with the lowest-intake patients for total flavonoids and for each flavonoid subclass, we found that anthocyanidins (OR = 0.60, 95% CI: 0.49-0.74), flavanones (OR = 0.65, 95% CI: 0.49-0.86), and flavones (OR = 0.78, 95% CI 0.64-0.95) were inversely associated with the risk of esophageal cancer. However, total flavonoids showed marginal association with esophageal cancer risk (OR = 0.78, 95% CI: 0.59-1.04). In conclusion, our study suggested that dietary intake of total flavonoids, anthocyanidins, flavanones, and flavones might reduce the risk of esophageal cancer.

Human IgG subclass cross-species reactivity to mouse and cynomolgus monkey Fcγ receptors.

PubMed

Derebe, Mehabaw G; Nanjunda, Rupesh K; Gilliland, Gary L; Lacy, Eilyn R; Chiu, Mark L

2018-05-01

In therapeutic antibody discovery and early development, mice and cynomolgus monkey are used as animal models to assess toxicity, efficacy and other properties of candidate molecules. As more candidate antibodies are based on human immunoglobulin (IgG) subclasses, many strategies are pursued to simulate the human system in the test animal. However, translation rate from a successful preclinical trial to an approved drug is extremely low. This may partly be due to differences in interaction of human IgG based candidate molecules to endogenous Fcγ receptors of model animals in comparison to those of human Fcγ receptors. In this study, we compare binding characteristics of human IgG subclasses commonly used in drug development (IgG1, IgG2, IgG4) and their respective Fc silent versions (IgG1σ, IgG2σ, IgG4 PAA) to human, mouse, and cynomolgus monkey Fcγ receptors. To control interactions between Fab and Fc domains, the test IgGs all have the same variable region sequences. We found distinct variations of interaction of human IgG subclasses to model animal Fcγ receptors in comparison to their human counterparts. Particularly, cynomolgus monkey Fcγ receptors showed consistently tighter binding to human IgGs than human Fcγ receptors. Moreover, the presumably Fc silent human IgG4 PAA framework bound to cynomolgus monkey FcγRI with nanomolar affinity while only very weak binding was observed for the human FcγRI. Our results highlighted the need for a thorough in vitro affinity characterization of candidate IgGs against model animal Fcγ receptors and careful design of preclinical studies. Copyright © 2018. Published by Elsevier B.V.

Global Mapping of Traditional Chinese Medicine into Bioactivity Space and Pathways Annotation Improves Mechanistic Understanding and Discovers Relationships between Therapeutic Action (Sub)classes

PubMed Central

Mohamad Zobir, Siti Zuraidah; Mohd Fauzi, Fazlin; Liggi, Sonia; Drakakis, Georgios; Fu, Xianjun; Fan, Tai-Ping; Bender, Andreas

2016-01-01

Traditional Chinese medicine (TCM) still needs more scientific rationale to be proven for it to be accepted further in the West. We are now in the position to propose computational hypotheses for the mode-of-actions (MOAs) of 45 TCM therapeutic action (sub)classes from in silico target prediction algorithms, whose target was later annotated with Kyoto Encyclopedia of Genes and Genomes pathway, and to discover the relationship between them by generating a hierarchical clustering. The results of 10,749 TCM compounds showed 183 enriched targets and 99 enriched pathways from Estimation Score ≤ 0 and ≥ 5% of compounds/targets in a (sub)class. The MOA of a (sub)class was established from supporting literature. Overall, the most frequent top three enriched targets/pathways were immune-related targets such as tyrosine-protein phosphatase nonreceptor type 2 (PTPN2) and digestive system such as mineral absorption. We found two major protein families, G-protein coupled receptor (GPCR), and protein kinase family contributed to the diversity of the bioactivity space, while digestive system was consistently annotated pathway motif, which agreed with the important treatment principle of TCM, “the foundation of acquired constitution” that includes spleen and stomach. In short, the TCM (sub)classes, in many cases share similar targets/pathways despite having different indications. PMID:26989424

Molecular characterization and expression analysis of three subclasses of IgT in rainbow trout (Oncorhynchus mykiss)

PubMed Central

Zhang, Nu; Zhang, Xu-Jie; Chen, Dan-Dan; Sunyer, J. Oriol; Zhang, Yong-An

2017-01-01

As the teleost specific immunoglobulin, IgT plays important roles in systemic and mucosal immunity. In the current study, in rainbow trout, we have cloned the heavy chain (Igτ) genes of a secretory form of IgT2 as well as the membrane and secretory forms of a third IgT subclass, termed IgT3. Conserved cysteine and tryptophan residues that are crucial for the folding of the immunoglobulin domain as well as hydrophobic and hydrophilic residues within CART motif were identified in all IgT subclasses. Through analysis of the rainbow trout genome assembly, Igτ3 gene was found localized upstream of Igτ1 gene, while Igτ2 gene situated on another scaffold. At the transcriptional level, Igτ1 was mainly expressed in both systemic and mucosal lymphoid tissues, while Igτ2 was largely expressed in systemic lymphoid organs. After LPS and poly (I:C) treatment, Igτ1 and Igτ2 genes exhibited different expression profiles. Interestingly the transcriptional level of Igτ3 was negligible, although its protein product could be identified in trout serum. Importantly, a previously reported monoclonal antibody directed against trout IgT1 was able to recognize IgT2 and IgT3. These data demonstrate that there exist three subclasses of IgT in rainbow trout, and that their heavy chain genes display different expression patterns during stimulation. Overall, our data reflect the diversity and complexity of immunoglobulin in trout, thus provide a better understanding of the IgT system in the immune response of teleost fish. PMID:28062226

Flavonoids, Flavonoid Subclasses, and Esophageal Cancer Risk: A Meta-Analysis of Epidemiologic Studies

PubMed Central

Cui, Lingling; Liu, Xinxin; Tian, Yalan; Xie, Chen; Li, Qianwen; Cui, Han; Sun, Changqing

2016-01-01

Flavonoids have been suggested to play a chemopreventive role in carcinogenesis. However, the epidemiologic studies assessing dietary intake of flavonoids and esophageal cancer risk have yielded inconsistent results. This study was designed to examine the association between flavonoids, each flavonoid subclass, and the risk of esophageal cancer with a meta-analysis approach. We searched for all relevant studies with a prospective cohort or case-control study design published from January 1990 to April 2016, using PUBMED, EMBASE, and Web of Science. Pooled odds ratios (ORs) were calculated using fixed or random-effect models. In total, seven articles including 2629 cases and 481,193 non-cases were selected for the meta-analysis. Comparing the highest-intake patients with the lowest-intake patients for total flavonoids and for each flavonoid subclass, we found that anthocyanidins (OR = 0.60, 95% CI: 0.49–0.74), flavanones (OR = 0.65, 95% CI: 0.49–0.86), and flavones (OR = 0.78, 95% CI 0.64–0.95) were inversely associated with the risk of esophageal cancer. However, total flavonoids showed marginal association with esophageal cancer risk (OR = 0.78, 95% CI: 0.59–1.04). In conclusion, our study suggested that dietary intake of total flavonoids, anthocyanidins, flavanones, and flavones might reduce the risk of esophageal cancer. PMID:27338463

Sudan ebolavirus long recovered survivors produce GP-specific Abs that are of the IgG1 subclass and preferentially bind FcγRI.

PubMed

Radinsky, Olga; Edri, Avishay; Brusilovsky, Michael; Fedida-Metula, Shlomit; Sobarzo, Ariel; Gershoni-Yahalom, Orly; Lutwama, Julius; Dye, John; Lobel, Leslie; Porgador, Angel

2017-07-20

Ebolavirus is a highly lethal pathogen, causing a severe hemorrhagic disease with a high fatality rate. To better understand immune correlates of protection by virus specific IgG, we investigated the evolution of the Fcγ receptors (FcγRs)-activating capabilities of antiviral IgG in serum samples of long recovered survivors. To this end, longitudinal serum samples from survivors of Sudan ebolavirus (SUDV) infection, studied over years, were examined for the presence of Ebola-GP specific IgG subclasses, and for their binding to FcγRs. We developed a cell-based reporter system to quantitate pathogen-specific antibody binding to FcγRIIIA, FcγRIIA, FcγRIIB and FcγRI. With this system, we demonstrate that anti-GP-specific stimulation of the FcγRI reporter by survivors' sera was substantially high one year after acute infection, with a slight reduction in activity over a decade post infection. We further demonstrate that GP-specific IgG1 is by far the seroprevalent subclass that retained and even enhanced its presence in the sera, over ten years post infection; the prevalence of other GP-specific IgG subclasses was considerably reduced over time. In accordance, GP-specific FcγRI reporter response and GP-specific total IgG1 subclass correlated in the studied group of Ebola survivors. These observations are important for further informing Ebola vaccine and therapeutic development.

Distribution of IgA subclass response to Coxiella burnetii in patients with acute and chronic Q fever.

PubMed

Camacho, M T; Outschoorn, I; Echevarría, C; Kovácová, E; Yebra, M; Maté, I; Auffray, P; Téllez, A

1998-07-01

The progression of Coxiella burnetii infection to acute or chronic Q fever has been attributed to biological characteristics of the bacterium and to the host immune response. We measured whether serum levels of total and specific subclasses IgA1 and IgA2 could be correlated with the course of disease in acute and chronic Q fever infections, and with the occurrence of endocarditis. In patients with chronic infection, total IgA2 levels were significantly increased. Q-fever-specific IgA1 antibodies were detectable in both acute and chronic infections, but only patients with endocarditis had IgA2 antibodies to C. burnetii phase II antigens. These findings indicate that the measurement of IgA subclasses may be a useful aid in the serological diagnosis of Q fever. Our results reinforce the idea that immunologically mediated host factors are important in the pathogenesis of Q fever and in the disease outcome of this infection. Copyright 1998 Academic Press.

Area-specific development of distinct projection neuron subclasses is regulated by postnatal epigenetic modifications

PubMed Central

Harb, Kawssar; Magrinelli, Elia; Nicolas, Céline S; Lukianets, Nikita; Frangeul, Laura; Pietri, Mariel; Sun, Tao; Sandoz, Guillaume; Grammont, Franck; Jabaudon, Denis; Studer, Michèle; Alfano, Christian

2016-01-01

During cortical development, the identity of major classes of long-distance projection neurons is established by the expression of molecular determinants, which become gradually restricted and mutually exclusive. However, the mechanisms by which projection neurons acquire their final properties during postnatal stages are still poorly understood. In this study, we show that the number of neurons co-expressing Ctip2 and Satb2, respectively involved in the early specification of subcerebral and callosal projection neurons, progressively increases after birth in the somatosensory cortex. Ctip2/Satb2 postnatal co-localization defines two distinct neuronal subclasses projecting either to the contralateral cortex or to the brainstem suggesting that Ctip2/Satb2 co-expression may refine their properties rather than determine their identity. Gain- and loss-of-function approaches reveal that the transcriptional adaptor Lmo4 drives this maturation program through modulation of epigenetic mechanisms in a time- and area-specific manner, thereby indicating that a previously unknown genetic program postnatally promotes the acquisition of final subtype-specific features. DOI: http://dx.doi.org/10.7554/eLife.09531.001 PMID:26814051

Repeatability of paired counts.

PubMed

Alexander, Neal; Bethony, Jeff; Corrêa-Oliveira, Rodrigo; Rodrigues, Laura C; Hotez, Peter; Brooker, Simon

2007-08-30

The Bland and Altman technique is widely used to assess the variation between replicates of a method of clinical measurement. It yields the repeatability, i.e. the value within which 95 per cent of repeat measurements lie. The valid use of the technique requires that the variance is constant over the data range. This is not usually the case for counts of items such as CD4 cells or parasites, nor is the log transformation applicable to zero counts. We investigate the properties of generalized differences based on Box-Cox transformations. For an example, in a data set of hookworm eggs counted by the Kato-Katz method, the square root transformation is found to stabilize the variance. We show how to back-transform the repeatability on the square root scale to the repeatability of the counts themselves, as an increasing function of the square mean root egg count, i.e. the square of the average of square roots. As well as being more easily interpretable, the back-transformed results highlight the dependence of the repeatability on the sample volume used.

A Large Complement of the Predicted Arabidopsis ARM Repeat Proteins Are Members of the U-Box E3 Ubiquitin Ligase Family1[w

PubMed Central

Mudgil, Yashwanti; Shiu, Shin-Han; Stone, Sophia L.; Salt, Jennifer N.; Goring, Daphne R.

2004-01-01

The Arabidopsis genome was searched to identify predicted proteins containing armadillo (ARM) repeats, a motif known to mediate protein-protein interactions in a number of different animal proteins. Using domain database predictions and models generated in this study, 108 Arabidopsis proteins were identified that contained a minimum of two ARM repeats with the majority of proteins containing four to eight ARM repeats. Clustering analysis showed that the 108 predicted Arabidopsis ARM repeat proteins could be divided into multiple groups with wide differences in their domain compositions and organizations. Interestingly, 41 of the 108 Arabidopsis ARM repeat proteins contained a U-box, a motif present in a family of E3 ligases, and these proteins represented the largest class of Arabidopsis ARM repeat proteins. In 14 of these U-box/ARM repeat proteins, there was also a novel conserved domain identified in the N-terminal region. Based on the phylogenetic tree, representative U-box/ARM repeat proteins were selected for further study. RNA-blot analyses revealed that these U-box/ARM proteins are expressed in a variety of tissues in Arabidopsis. In addition, the selected U-box/ARM proteins were found to be functional E3 ubiquitin ligases. Thus, these U-box/ARM proteins represent a new family of E3 ligases in Arabidopsis. PMID:14657406

Integrated genetic and epigenetic analysis identifies three different subclasses of colon cancer

PubMed Central

Shen, Lanlan; Toyota, Minoru; Kondo, Yutaka; Lin, E; Zhang, Li; Guo, Yi; Hernandez, Natalie Supunpong; Chen, Xinli; Ahmed, Saira; Konishi, Kazuo; Hamilton, Stanley R.; Issa, Jean-Pierre J.

2007-01-01

Colon cancer has been viewed as the result of progressive accumulation of genetic and epigenetic abnormalities. However, this view does not fully reflect the molecular heterogeneity of the disease. We have analyzed both genetic (mutations of BRAF, KRAS, and p53 and microsatellite instability) and epigenetic alterations (DNA methylation of 27 CpG island promoter regions) in 97 primary colorectal cancer patients. Two clustering analyses on the basis of either epigenetic profiling or a combination of genetic and epigenetic profiling were performed to identify subclasses with distinct molecular signatures. Unsupervised hierarchical clustering of the DNA methylation data identified three distinct groups of colon cancers named CpG island methylator phenotype (CIMP) 1, CIMP2, and CIMP negative. Genetically, these three groups correspond to very distinct profiles. CIMP1 are characterized by MSI (80%) and BRAF mutations (53%) and rare KRAS and p53 mutations (16% and 11%, respectively). CIMP2 is associated with 92% KRAS mutations and rare MSI, BRAF, or p53 mutations (0, 4, and 31% respectively). CIMP-negative cases have a high rate of p53 mutations (71%) and lower rates of MSI (12%) or mutations of BRAF (2%) or KRAS (33%). Clustering based on both genetic and epigenetic parameters also identifies three distinct (and homogeneous) groups that largely overlap with the previous classification. The three groups are independent of age, gender, or stage, but CIMP1 and 2 are more common in proximal tumors. Together, our integrated genetic and epigenetic analysis reveals that colon cancers correspond to three molecularly distinct subclasses of disease. PMID:18003927

Association of height and pubertal timing with lipoprotein subclass profile: exploring the role of genetic and environmental effects.

PubMed

Jelenkovic, Aline; Bogl, Leonie H; Rose, Richard J; Kangas, Antti J; Soininen, Pasi; Ala-Korpela, Mika; Kaprio, Jaakko; Silventoinen, Karri

2013-01-01

Little is known about the relationship between growth and lipoprotein profile. We aimed to analyze common genetic and environmental factors in the association of height from late childhood to adulthood and pubertal timing with serum lipid and lipoprotein subclass profile. A longitudinal cohort of Finnish twin pairs (FinnTwin12) was analyzed using self-reported height at 11-12, 14, 17 years and measured stature at adult age (21-24 years). Data were available for 719 individual twins including 298 complete pairs. Serum lipids and lipoprotein subclasses were measured by proton nuclear magnetic resonance spectroscopy. Multivariate variance component models for twin data were fitted. Cholesky decomposition was used to partition the phenotypic covariation among traits into additive genetic and unique environmental correlations. In men, the strongest associations for both adult height and puberty were observed with total cholesterol, low-density lipoprotein cholesterol, intermediate-density lipoprotein cholesterol, and low-density lipoprotein particle subclasses (max. r = -0.19). In women, the magnitude of the correlations was weaker (max. r = -0.13). Few associations were detected between height during adolescence and adult lipid profile. Early onset of puberty was related to an adverse lipid profile, but delayed pubertal development in girls was associated with an unfavorable profile, as well. All associations were mediated mainly by additive genetic factors, but unique environmental effects cannot be disregarded. Early puberty and shorter adult height relate to higher concentrations of atherogenic lipids and lipoprotein particles in early adulthood. Common genetic effects behind these phenotypes substantially contribute to the observed associations. Copyright © 2013 Wiley Periodicals, Inc.

Search for Type Ia supernova NUV-optical subclasses

NASA Astrophysics Data System (ADS)

Cinabro, David; Scolnic, Daniel; Kessler, Richard; Li, Ashley; Miller, Jake

2017-04-01

In response to a recently reported observation of evidence for two classes of Type Ia supernovae (SNe Ia) distinguished by their brightness in the rest-frame near-ultraviolet (NUV), we search for the phenomenon in publicly available light-curve data. We use the SNANA supernova analysis package to simulate SN Ia light curves in the Sloan Digital Sky Survey (SDSS) Supernova Search and the Supernova Legacy Survey (SNLS) with a model of two distinct ultraviolet classes of SNe Ia and a conventional model with a single broad distribution of SN-Ia ultraviolet brightnesses. We compare simulated distributions of rest-frame colours with these two models to those observed in 158 SNe Ia in the SDSS and SNLS data. The SNLS sample of 99 SNe Ia is in clearly better agreement with a model with one class of SN Ia light curves and shows no evidence for distinct NUV sub-classes. The SDSS sample of 59 SNe Ia with poorer colour resolution does not distinguish between the two models.

A subclass of plant heat shock cognate 70 chaperones carries a motif that facilitates trafficking through plasmodesmata

PubMed Central

Aoki, Koh; Kragler, Friedrich; Xoconostle-Cázares, Beatriz; Lucas, William J.

2002-01-01

Plasmodesmata establish a pathway for the trafficking of non-cell-autonomously acting proteins and ribonucleoprotein complexes. Plasmodesmal enriched cell fractions and the contents of enucleate sieve elements, in the form of phloem sap, were used to isolate and characterize heat shock cognate 70 (Hsc70) chaperones associated with this cell-to-cell transport pathway. Three Cucurbita maxima Hsc70 chaperones were cloned and functional and sequence analysis led to the identification of a previously uncharacterized subclass of non-cell-autonomous chaperones. The highly conserved nature of the heat shock protein 70 (Hsp70) family, in conjunction with mutant analysis, permitted the characterization of a motif that allows these Hsc70 chaperones to engage the plasmodesmal non-cell-autonomous translocation machinery. Proof of concept that this motif is necessary for Hsp70 gain-of-movement function was obtained through the engineering of a human Hsp70 that acquired the capacity to traffic through plasmodesmata. These results are discussed in terms of the roles likely played by this subclass of Hsc70 chaperones in the trafficking of non-cell-autonomous proteins. PMID:12456884

Effect of transmission intensity and age on subclass antibody responses to Plasmodium falciparum pre-erythrocytic and blood-stage antigens.

PubMed

Noland, Gregory S; Jansen, Paul; Vulule, John M; Park, Gregory S; Ondigo, Bartholomew N; Kazura, James W; Moormann, Ann M; John, Chandy C

2015-02-01

Cytophilic immunoglobulin (IgG) subclass responses (IgG1 and IgG3) to Plasmodium falciparum antigens have been associated with protection from malaria, yet the relative importance of transmission intensity and age in generation of subclass responses to pre-erythrocytic and blood-stage antigens have not been clearly defined. We analyzed IgG subclass responses to the pre-erythrocytic antigens CSP, LSA-1, and TRAP and the blood-stage antigens AMA-1, EBA-175, and MSP-1 in asymptomatic residents age 2 years or older in stable (n=116) and unstable (n=96) transmission areas in Western Kenya. In the area of stable malaria transmission, a high prevalence of cytophilic (IgG1 and IgG3) antibodies to each antigen was seen in all age groups. Prevalence and levels of cytophilic antibodies to pre-erythrocytic and blood-stage P. falciparum antigens increased with age in the unstable transmission area, yet IgG1 and IgG3 responses to most antigens for all ages in the unstable transmission area were less prevalent and lower in magnitude than even the youngest age group from the stable transmission area. The dominance of cytophilic responses over non-cytophilic (IgG2 and IgG4) was more pronounced in the stable transmission area, and the ratio of IgG3 over IgG1 generally increased with age. In the unstable transmission area, the ratio of cytophilic to non-cytophilic antibodies did not increase with age, and tended to be IgG3-biased for pre-erythrocytic antigens yet IgG1-biased for blood-stage antigens. The differences between areas could not be attributed to active parasitemia status, as there were minimal differences in antibody responses between those positive and negative for Plasmodium infection by microscopy in the stable transmission area. Individuals in areas of unstable transmission have low cytophilic to non-cytophilic IgG subclass ratios and low IgG3:IgG1 ratios to P. falciparum antigens. These imbalances could contribute to the persistent risk of clinical malaria in these

[Serum immunoglobulin IgG subclass distribution of antibody responses to pertussis toxin and filamentous hemagglutinin of Bordetella pertussis in patients with whooping cough].

PubMed

Rastawicki, Waldemar; Smietańska, Karolina; Rokosz-Chudziak, Natalia; Jagielski, Marek

2013-01-01

The present study was aimed at determining the IgG subclass distribution against pertussis toxin (PT) and filamentous hemagglutinin (FHA) of Bordetella pertussis in patients with whooping cough. The total number of 222 serum samples obtained from patients suspected in clinical investigation for pertussis were tested separately by in-house ELISA for the presence of IgG antibodies to pertussis toxin and filamentous hemagglutinin. The percentage distribution of specific anti-PT and anti-FHA IgG subclass response was calculated only on the basis of group of sera confirmed in the present study as positive for total IgG antibodies (183 sera to PT antigen and 129 to FHA antigen). Paired serum specimens were obtained from 36 patients. Based on the results of determining the level of antibodies in the sera of 40 blood donors, the cut-off limit of serum antibodies for each subclass was set at arithmetic mean plus two standard deviations. Antibodies of IgG1 to pertussis toxin and filamentous hemagglutinin were diagnosed in 151 (82.5%) and 99 (76.7%), IgG2 in 72 (39.0%) and 50 (38.8%), IgG3 in 17 (9.3%) and 43 (33.3%), IgG4 in 55 (30.1%) and 53 (41.1%) serum samples, respectively. There were no significant differences in percentage of sera with IgG1, IgG2 and IgG3 in relation to age of the patients. However, the frequency of occurrence of IgG4 antibodies was highest in the group of the youngest children to the age of 6 years old (61.8% for PT and 68.0% for FHA), and decrease with age, reaching the minimum in the group of patients above 40 years old (13.2% and 4.2% for PT and FHA, respectively). We also found significantly higher frequency of IgG4 to PT and FHA antigens in men than in women. Statistically significant, essential changes in the pattern of IgG subclass during the course of infection were not found. In conclusion, this study showed that all four subclasses of IgG antibodies to pertussis toxin and filamentous hemagglutinin are produced during whooping cough.

47 CFR 97.205 - Repeater station.

Code of Federal Regulations, 2013 CFR

2013-10-01

... case, the licensee of the non-coordinated repeater has primary responsibility to resolve the interference. (d) A repeater may be automatically controlled. (e) Ancillary functions of a repeater that are available to users on the input channel are not considered remotely controlled functions of the station...

47 CFR 97.205 - Repeater station.

Code of Federal Regulations, 2014 CFR

2014-10-01

... case, the licensee of the non-coordinated repeater has primary responsibility to resolve the interference. (d) A repeater may be automatically controlled. (e) Ancillary functions of a repeater that are available to users on the input channel are not considered remotely controlled functions of the station...

47 CFR 97.205 - Repeater station.

Code of Federal Regulations, 2012 CFR

2012-10-01

... case, the licensee of the non-coordinated repeater has primary responsibility to resolve the interference. (d) A repeater may be automatically controlled. (e) Ancillary functions of a repeater that are available to users on the input channel are not considered remotely controlled functions of the station...

47 CFR 97.205 - Repeater station.

Code of Federal Regulations, 2011 CFR

2011-10-01

... case, the licensee of the non-coordinated repeater has primary responsibility to resolve the interference. (d) A repeater may be automatically controlled. (e) Ancillary functions of a repeater that are available to users on the input channel are not considered remotely controlled functions of the station...

47 CFR 97.205 - Repeater station.

Code of Federal Regulations, 2010 CFR

2010-10-01

... case, the licensee of the non-coordinated repeater has primary responsibility to resolve the interference. (d) A repeater may be automatically controlled. (e) Ancillary functions of a repeater that are available to users on the input channel are not considered remotely controlled functions of the station...

E-motif formed by extrahelical cytosine bases in DNA homoduplexes of trinucleotide and hexanucleotide repeats

PubMed Central

Pan, Feng; Zhang, Yuan; Man, Viet Hoang; Roland, Christopher

2018-01-01

Abstract Atypical DNA secondary structures play an important role in expandable trinucleotide repeat (TR) and hexanucleotide repeat (HR) diseases. The cytosine mismatches in C-rich homoduplexes and hairpin stems are weakly bonded; experiments show that for certain sequences these may flip out of the helix core, forming an unusual structure termed an ‘e-motif’. We have performed molecular dynamics simulations of C-rich TR and HR DNA homoduplexes in order to characterize the conformations, stability and dynamics of formation of the e-motif, where the mismatched cytosines symmetrically flip out in the minor groove, pointing their base moieties towards the 5′-direction in each strand. TRs have two non-equivalent reading frames, (GCC)n and (CCG)n; while HRs have three: (CCCGGC)n, (CGGCCC)n, (CCCCGG)n. We define three types of pseudo basepair steps related to the mismatches and show that the e-motif is only stable in (GCC)n and (CCCGGC)n homoduplexes due to the favorable stacking of pseudo GpC steps (whose nature depends on whether TRs or HRs are involved) and the formation of hydrogen bonds between the mismatched cytosine at position i and the cytosine (TRs) or guanine (HRs) at position i − 2 along the same strand. We also characterize the extended e-motif, where all mismatched cytosines are extruded, their extra-helical stacking additionally stabilizing the homoduplexes. PMID:29190385

Comparison of the Specificities of IgG, IgG-Subclass, IgA and IgM Reactivities in African and European HIV-Infected Individuals with an HIV-1 Clade C Proteome-Based Array

PubMed Central

Gallerano, Daniela; Ndlovu, Portia; Makupe, Ian; Focke-Tejkl, Margarete; Fauland, Kerstin; Wollmann, Eva; Puchhammer-Stöckl, Elisabeth; Keller, Walter; Sibanda, Elopy; Valenta, Rudolf

2015-01-01

A comprehensive set of recombinant proteins and peptides of the proteome of HIV-1 clade C was prepared and purified and used to measure IgG, IgG-subclass, IgA and IgM responses in HIV-infected patients from Sub-Saharan Africa, where clade C is predominant. As a comparison group, HIV-infected patients from Europe were tested. African and European patients showed an almost identical antibody reactivity profile in terms of epitope specificity and involvement of IgG, IgG subclass, IgA and IgM responses. A V3-peptide of gp120 was identified as major epitope recognized by IgG1>IgG2 = IgG4>IgG3, IgA>IgM antibodies and a C-terminal peptide represented another major peptide epitope for the four IgG subclasses. By contrast, gp41-derived-peptides were mainly recognized by IgG1 but not by the other IgG subclasses, IgA or IgM. Among the non-surface proteins, protease, reverse transcriptase+RNAseH, integrase, as well as the capsid and matrix proteins were the most frequently and strongly recognized antigens which showed broad IgG subclass and IgA reactivity. Specificities and magnitudes of antibody responses in African patients were stable during disease and antiretroviral treatment, and persisted despite severe T cell loss. Using a comprehensive panel of gp120, gp41 peptides and recombinant non-surface proteins of HIV-1 clade C we found an almost identical antibody recognition profile in African and European patients regarding epitopes and involved IgG-sublass, IgA- and IgM-responses. Immune recognition of gp120 peptides and non-surface proteins involved all four IgG subclasses and was indicative of a mixed Th1/Th2 immune response. The HIV-1 clade C proteome-based test allowed diagnosis and monitoring of antibody responses in the course of HIV-infections and assessment of isotype and subclass responses. PMID:25658330

The Mitochondrion-Targeted PENTATRICOPEPTIDE REPEAT78 Protein Is Required for nad5 Mature mRNA Stability and Seed Development in Maize.

PubMed

Zhang, Ya-Feng; Suzuki, Masaharu; Sun, Feng; Tan, Bao-Cai

2017-10-09

Pentatricopepetide repeat (PPR) proteins are a large family of RNA-binding proteins involved in RNA metabolism in plant organelles. Although many PPR proteins have been functionally studied, few of them are identified with a function in mitochondrial RNA stability. By using a reverse genetic approach, we characterized the role of the mitochondrion-targeted PPR78 protein in nad5 mature mRNA stability and maize (Zea mays) seed development. Loss of PPR78 function leads to a dramatic reduction in the steady-state level of mitochondrial nad5 mature mRNA, blocks the assembly of complex I in the electron transport chain, and causes an arrest in embryogenesis and endosperm development. Characterization of a second strong allele confirms the function of PPR78 in nad5 mRNA accumulation and maize seed development. The generation of mature nad5 requires the assembly of three distinct precursor RNAs via trans-splicing reactions, and the accumulation of nad5T1 precursor is reduced in the ppr78 mutants. However, it is the instability of mature nad5 rather than nad5T1 causing loss of the full-length nad5 transcript, and degradation of nad5 losing both translation start and stop codons is enriched in the mutant. Our data imply the assembly of mature nad5 mRNA precedes the protection of PPR78. Copyright © 2017 The Author. Published by Elsevier Inc. All rights reserved.

On subclasses of opioid analgesics.

PubMed

Raffa, Robert B

2014-12-01

The history of discovery of analgesic drugs has followed a trajectory from original serendipitous discovery of plant-derived substances to laboratory creation of customized molecules that are intentionally designed to interact with specific receptors of neurotransmitters involved in either the transmission of the pain signal or the attenuation of such a signal. The drugs most recently developed have been designed to provide incremental greater separation between pain relief and adverse effects. The result has been drugs that have individualized pharmacodynamic and pharmacokinetic characteristics that represent specific advances in basic science and translate into unique clinical profiles. Several of the drugs include non-opioid components. They retain some of the features of opioids, but have distinct clinical characteristics that differentiate them from traditional opioids. Thus they defy simple classification as opioids. A summary is provided of the development of the modern view of multi-mechanistic pain and its treatment using analgesics that have multi-mechanisms of action (consisting of both opioid and non-opioid components). Descriptions of examples of such current analgesics and of those that have pharmacokinetic characteristics that result in atypical opioid clinical profiles are given. By serendipity or design, several current strong analgesics have opioid components of action, but have an additional non-opioid mechanism of action or some pharmacokinetic feature that gives them an atypical opioid clinical profile and renders them not easily classified as classical opioids. An appreciation that there are now opioid analgesics that differentiate from classical opioids in ways that defy their simplistic classification as opioids suggests that recognition of subclasses of opioid analgesics would be more accurate scientifically and would be more informative for healthcare providers and regulators. This would likely lead to positive outcomes for the clinical

[Distribution of IgG subclasses of TgAb and TPOAb in sera from patients with Graves' disease, Graves' disease plus Hashimoto's thyroiditis and Hashimoto's thyrotoxicosis].

PubMed

Yuan, Shanshan; Yu, Nan; Gao, Ying; Huang, Wei; He, Yifan; Dong, Bin; Lu, Guizhi; Li, Maorong; Cai, Xiaopin; Peng, Dingqiong; Wang, Yunhong; Li, Ting; Huang, Youyuan; Gao, Yanming; Guo, Xiaohui; Shi, Bingyin

2014-01-14

To evaluate the distribution of IgG subclasses of TgAb and TPOAb in sera from patients with Graves' disease (GD), Graves' disease plus Hashimoto's thyroiditis (GH) and Hashimoto's thyrotoxicosis. Patients with GD (n = 33), GH (n = 31) or Hashimoto's thyrotoxicosis (n = 18) diagnosed by fine needle aspiration cytology at Department of Endocrinology of Peking University First Hospital, Beijing Haidian Hospital, China-Japan Friendship Hospital and Civil Aviation General Hospital during the period from January 2010 to May 2013 were enrolled. All of them had TgAb and TPOAb. The total serum IgG and IgG subclasses of TgAb and TPOAb were detected by antigen-specific enzyme-linked immunosorbent assay (ELISA). The prevalence and relative amount of IgG subclasses were calculated and compared among three groups. The levels of TRAb in GD group (21.80(7.53, 40) U/L) were significantly higher than those in GH (7.30(3.10, 25.40) U/L) (P = 0.000) and Hashimoto's thyrotoxicosis groups (4.90(1.69, 16.43) U/L) (P = 0.003). And no significant differences were found in the levels of TgAb and TPOAb. The prevalence of TgAb IgG3 subclass in Hashimoto's thyrotoxicosis group (66.7%) was higher than GD group (35.5%) and GH group (36.4%) and the difference was close to significance (P = 0.066). There were significant differences of relative amount of TgAb IgG2 and TgAb IgG4 among three groups (P = 0.039 and 0.013), and GD patients had higher relative amounts of TgAb IgG2 (0.59(0.34, 0.94)) and TgAb IgG4 (0.57(0.28, 0.97)) than GH patients (TgAb IgG2, 0.31(0.23, 0.34); TgAb IgG4, 0.26(0.09, 0.48)) or patients with Hashimoto's thyrotoxicosis (TgAb IgG2, 0.32(0.24, 0.83); TgAb IgG4, 0.33(0.10, 0.65)) (for TgAb IgG2, P = 0.009 and 0.167; for TgAb IgG4, P = 0.005 and 0.041 respectively). No significant difference was found in the prevalence of each TPOAb IgG subclass. The difference of relative amount of TPOAb IgG2 among three groups was close to significance (P = 0.069). And the relative amount

Comparison of a reduced carbohydrate and reduced fat diet for LDL, HDL, and VLDL subclasses during 9-months of weight maintenance subsequent to weight loss.

PubMed

LeCheminant, James D; Smith, Bryan K; Westman, Eric C; Vernon, Mary C; Donnelly, Joseph E

2010-06-01

This study compared LDL, HDL, and VLDL subclasses in overweight or obese adults consuming either a reduced carbohydrate (RC) or reduced fat (RF) weight maintenance diet for 9 months following significant weight loss. Thirty-five (21 RC; 14 RF) overweight or obese middle-aged adults completed a 1-year weight management clinic. Participants met weekly for the first six months and bi-weekly thereafter. Meetings included instruction for diet, physical activity, and behavior change related to weight management. Additionally, participants followed a liquid very low-energy diet of approximately 2092 kJ per day for the first three months of the study. Subsequently, participants followed a dietary plan for nine months that targeted a reduced percentage of carbohydrate (approximately 20%) or fat (approximately 30%) intake and an energy intake level calculated to maintain weight loss. Lipid subclasses using NMR spectroscopy were analyzed prior to weight loss and at multiple intervals during weight maintenance. Body weight change was not significantly different within or between groups during weight maintenance (p>0.05). The RC group showed significant increases in mean LDL size, large LDL, total HDL, large and small HDL, mean VLDL size, and large VLDL during weight maintenance while the RF group showed increases in total HDL, large and small HDL, total VLDL, and large, medium, and small VLDL (p<0.05). Group*time interactions were significant for large and medium VLDL (p>0.05). Some individual lipid subclasses improved in both dietary groups. Large and medium VLDL subclasses increased to a greater extent across weight maintenance in the RF group.

A direct repeat of E-box-like elements is required for cell-autonomous circadian rhythm of clock genes

PubMed Central

Nakahata, Yasukazu; Yoshida, Mayumi; Takano, Atsuko; Soma, Haruhiko; Yamamoto, Takuro; Yasuda, Akio; Nakatsu, Toru; Takumi, Toru

2008-01-01

Background The circadian expression of the mammalian clock genes is based on transcriptional feedback loops. Two basic helix-loop-helix (bHLH) PAS (for Period-Arnt-Sim) domain-containing transcriptional activators, CLOCK and BMAL1, are known to regulate gene expression by interacting with a promoter element termed the E-box (CACGTG). The non-canonical E-boxes or E-box-like sequences have also been reported to be necessary for circadian oscillation. Results We report a new cis-element required for cell-autonomous circadian transcription of clock genes. This new element consists of a canonical E-box or a non-canonical E-box and an E-box-like sequence in tandem with the latter with a short interval, 6 base pairs, between them. We demonstrate that both E-box or E-box-like sequences are needed to generate cell-autonomous oscillation. We also verify that the spacing nucleotides with constant length between these 2 E-elements are crucial for robust oscillation. Furthermore, by in silico analysis we conclude that several clock and clock-controlled genes possess a direct repeat of the E-box-like elements in their promoter region. Conclusion We propose a novel possible mechanism regulated by double E-box-like elements, not to a single E-box, for circadian transcriptional oscillation. The direct repeat of the E-box-like elements identified in this study is the minimal required element for the generation of cell-autonomous transcriptional oscillation of clock and clock-controlled genes. PMID:18177499

Sel1 repeat protein LpnE is a Legionella pneumophila virulence determinant that influences vacuolar trafficking.

PubMed

Newton, Hayley J; Sansom, Fiona M; Dao, Jenny; McAlister, Adrian D; Sloan, Joan; Cianciotto, Nicholas P; Hartland, Elizabeth L

2007-12-01

The environmental pathogen Legionella pneumophila possesses five proteins with Sel1 repeats (SLRs) from the tetratricopeptide repeat protein family. Three of these proteins, LpnE, EnhC, and LidL, have been implicated in the ability of L. pneumophila to efficiently establish infection and/or manipulate host cell trafficking events. Previously, we showed that LpnE is important for L. pneumophila entry into macrophages and epithelial cells. In further virulence studies here, we show that LpnE is also required for efficient infection of Acanthamoeba castellanii by L. pneumophila and for replication of L. pneumophila in the lungs of A/J mice. In addition, we found that the role of LpnE in host cell invasion is dependent on the eight SLR regions of the protein. A truncated form of LpnE lacking the two C-terminal SLR domains was unable to complement the invasion defect of an lpnE mutant of L. pneumophila 130b in both the A549 and THP-1 cell lines. The lpnE mutant displayed impaired avoidance of LAMP-1 association, suggesting that LpnE influenced trafficking of the L. pneumophila vacuole, similar to the case for EnhC and LidL. We also found that LpnE was present in L. pneumophila culture supernatants and that its export was independent of both the Lsp type II secretion system and the Dot/Icm type IV secretion system. The fact that LpnE was exported suggested that the protein may interact with a eukaryotic protein. Using LpnE as bait, we screened a HeLa cell cDNA library for interacting partners, using the yeast two-hybrid system. Examination of the protein-protein interaction between LpnE and a eukaryotic protein, obscurin-like protein 1, suggested that LpnE can interact with eukaryotic proteins containing immunoglobulin-like folds via the SLR regions. This investigation has further characterized the contribution of LpnE to L. pneumophila virulence and, more specifically, the importance of the SLR regions to LpnE function.

R-loops: targets for nuclease cleavage and repeat instability.

PubMed

Freudenreich, Catherine H

2018-01-11

R-loops form when transcribed RNA remains bound to its DNA template to form a stable RNA:DNA hybrid. Stable R-loops form when the RNA is purine-rich, and are further stabilized by DNA secondary structures on the non-template strand. Interestingly, many expandable and disease-causing repeat sequences form stable R-loops, and R-loops can contribute to repeat instability. Repeat expansions are responsible for multiple neurodegenerative diseases, including Huntington's disease, myotonic dystrophy, and several types of ataxias. Recently, it was found that R-loops at an expanded CAG/CTG repeat tract cause DNA breaks as well as repeat instability (Su and Freudenreich, Proc Natl Acad Sci USA 114, E8392-E8401, 2017). Two factors were identified as causing R-loop-dependent breaks at CAG/CTG tracts: deamination of cytosines and the MutLγ (Mlh1-Mlh3) endonuclease, defining two new mechanisms for how R-loops can generate DNA breaks (Su and Freudenreich, Proc Natl Acad Sci USA 114, E8392-E8401, 2017). Following R-loop-dependent nicking, base excision repair resulted in repeat instability. These results have implications for human repeat expansion diseases and provide a paradigm for how RNA:DNA hybrids can cause genome instability at structure-forming DNA sequences. This perspective summarizes mechanisms of R-loop-induced fragility at G-rich repeats and new links between DNA breaks and repeat instability.

Growth of chitinolytic dune soil beta-subclass Proteobacteria in response to invading fungal hyphae.

PubMed

De Boer, W; Klein Gunnewiek, P J; Kowalchuk, G A; Van Veen, J A

2001-08-01

It has frequently been reported that chitinolytic soil bacteria, in particular biocontrol strains, can lyse living fungal hyphae, thereby releasing potential growth substrate. However, the conditions used in such assays (high bacterial density, rich media, fragmented hyphae) make it difficult to determine whether mycolytic activity is actually of importance for the growth and survival of chitinolytic bacteria in soils. An unidentified group of beta-subclass Proteobacteria (CbetaPs) was most dominant among the culturable nonfilamentous chitinolytic bacteria isolated from Dutch sand dune soils. Here we demonstrate that the CbetaPs grew at the expense of extending fungal mycelium of three dune soil fungi (Chaetomium globosum, Fusarium culmorum, and Mucor hiemalis) under nutrient-limiting, soil-like conditions. Aggregates of CbetaPs were also often found attached to fungal hyphae. The growth of a control group of dominant nonchitinolytic dune soil bacteria (beta- and gamma-subclass Proteobacteria) was not stimulated in the mycelial zone, indicating that growth-supporting materials were not independently released in appreciable amounts by the extending hyphae. Therefore, mycolytic activities of CbetaPs have apparently been involved in allowing them to grow after exposure to living hyphae. The chitinase inhibitor allosamidin did not, in the case of Mucor, or only partially, in the cases of Chaetomium and Fusarium, repress mycolytic growth of the CbetaPs, indicating that chitinase activity alone could not explain the extent of bacterial proliferation. Chitinolytic Stenotrophomonas-like and Cytophaga-like bacteria, isolated from the same dune soils, were only slightly stimulated by exposure to fungal hyphae.

“One code to find them all”: a perl tool to conveniently parse RepeatMasker output files

PubMed Central

2014-01-01

library with incomplete TE class/subclass information was used with RepeatMasker. We hope that this tool will be helpful for people working on the distribution and evolution of TEs within genomes.

Small high-density lipoprotein (HDL) subclasses are increased with decreased activity of HDL-associated phospholipase A₂ in subjects with prediabetes.

PubMed

Filippatos, Theodosios D; Rizos, Evangelos C; Tsimihodimos, Vasilios; Gazi, Irene F; Tselepis, Alexandros D; Elisaf, Moses S

2013-06-01

Alterations in high-density lipoprotein (HDL) subclass distribution, as well as in the activities of HDL-associated enzymes, have been associated with increased cardiovascular disease (CVD) risk. HDL subclass distribution and the activities of HDL-associated enzymes remain unknown in prediabetic patients, a condition also associated with increased CVD risk. The aim of the present study was to assess any differences in HDL subclass distribution (using polyacrylamide gel electrophoresis) and in activities of HDL-associated enzymes between prediabetic (impaired fasting glucose, IFG, n = 80) and non-prediabetic subjects (n = 105). Subjects with prediabetes had significantly increased waist circumference, blood pressure and triacylglycerol (TAG) levels compared with subjects with fasting glucose levels <100 mg/dL (all p < 0.05). The proportion of small HDL3 over HDL cholesterol (HDL-C) was significantly increased in prediabetic subjects compared with their controls (p < 0.05). The activity of the anti-atherogenic HDL-associated lipoprotein-associated phospholipase A₂ (HDL-LpPLA₂) was significantly lower in subjects with prediabetes (p < 0.05), whereas the activity of paraoxonase 1 (using both paraoxon and phenyl acetate as substrates) did not significantly differ between subjects with or without prediabetes. In a stepwise linear regression analysis, the proportion of small HDL3 over HDL-C concentration was independently associated with the presence of prediabetes and with total cholesterol and TAG concentration (positively), as well as with HDL-C levels (negatively). We also observed a trend of increased small dense low-density lipoprotein cholesterol levels in prediabetic subjects compared with their controls. Subjects with IFG exhibit increased proportion of small HDL3 particles combined with decreased activity of the anti-atherogenic HDL-LpPLA₂.

Repeatability of Cryogenic Multilayer Insulation

NASA Technical Reports Server (NTRS)

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

2017-01-01

Due to the variety of requirements across aerospace platforms, and one off projects, the repeatability of cryogenic multilayer insulation has never been fully established. The objective of this test program is to provide a more basic understanding of the thermal performance repeatability of MLI systems that are applicable to large scale tanks. There are several different types of repeatability that can be accounted for: these include repeatability between multiple identical blankets, repeatability of installation of the same blanket, and repeatability of a test apparatus. The focus of the work in this report is on the first two types of repeatability. Statistically, repeatability can mean many different things. In simplest form, it refers to the range of performance that a population exhibits and the average of the population. However, as more and more identical components are made (i.e. the population of concern grows), the simple range morphs into a standard deviation from an average performance. Initial repeatability testing on MLI blankets has been completed at Florida State University. Repeatability of five GRC provided coupons with 25 layers was shown to be +/- 8.4 whereas repeatability of repeatedly installing a single coupon was shown to be +/- 8.0. A second group of 10 coupons have been fabricated by Yetispace and tested by Florida State University, through the first 4 tests, the repeatability has been shown to be +/- 16. Based on detailed statistical analysis, the data has been shown to be statistically significant.

Repeatability of Cryogenic Multilayer Insulation

NASA Technical Reports Server (NTRS)

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

2017-01-01

Due to the variety of requirements across aerospace platforms, and one off projects, the repeatability of cryogenic multilayer insulation has never been fully established. The objective of this test program is to provide a more basic understanding of the thermal performance repeatability of MLI systems that are applicable to large scale tanks. There are several different types of repeatability that can be accounted for: these include repeatability between multiple identical blankets, repeatability of installation of the same blanket, and repeatability of a test apparatus. The focus of the work in this report is on the first two types of repeatability. Statistically, repeatability can mean many different things. In simplest form, it refers to the range of performance that a population exhibits and the average of the population. However, as more and more identical components are made (i.e. the population of concern grows), the simple range morphs into a standard deviation from an average performance. Initial repeatability testing on MLI blankets has been completed at Florida State University. Repeatability of five GRC provided coupons with 25 layers was shown to be +/- 8.4% whereas repeatability of repeatedly installing a single coupon was shown to be +/- 8.0%. A second group of 10 coupons have been fabricated by Yetispace and tested by Florida State University, through the first 4 tests, the repeatability has been shown to be +/- 15-25%. Based on detailed statistical analysis, the data has been shown to be statistically significant.

Repeatability of Cryogenic Multilayer Insulation

NASA Astrophysics Data System (ADS)

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

2017-12-01

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

Production of monoclonal antibody, PR81, recognizing the tandem repeat region of MUC1 mucin.

PubMed

Paknejad, M; Rasaee, M J; Tehrani, F Karami; Kashanian, S; Mohagheghi, M A; Omidfar, K; Bazl, M Rajabi

2003-06-01

A monoclonal antibody (MAb) was generated by immunizing BALB/c mice with homogenized breast cancerous tissues. This antibody (PR81) was found to be of IgG(1) class and subclass, containing kappa light chain. PR81 reacted with either the membrane extracts of several breast cancerous tissues or the cell surface of some MUC1 positive cell lines (MCF-7, BT-20 and T-47D) tested by enzyme immunoassay and for MCF-7 by immunofluorescence method. PR81 also reacted with two synthetic 27 and 16-amino acid peptides, TSA-P1-24 and A-P1-15, respectively, which included the core tandem repeat sequence of MUC1. However, this antibody did not react with a synthetic 14 amino acid peptide that has no similarity with tandem repeat found in MUC1. The generated antibody had good and similar affinities (2.19 x 10(8) M(-1)) toward TSA-P1-24 and A-P1-15, which are mainly shared in the hydrophilic sequence of PDTRPAP. Through Western blot analysis of homogenized breast tissues, PR81 recognized only a major band of 250 kDa. This band is stronger in malignant tissue than benign and normal tissues.

A novel structural tree for wrap-proteins, a subclass of (α+β)-proteins.

PubMed

Boshkova, Eugenia A; Gordeev, Alexey B; Efimov, Alexander V

2014-01-01

In this paper, a novel structural subclass of (α+β)-proteins is presented. A characteristic feature of these proteins and domains is that they consist of strongly twisted and coiled β-sheets wrapped around one or two α-helices, so they are referred to here as wrap-proteins. It is shown that overall folds of the wrap-proteins can be obtained by stepwise addition of α-helices and/or β-strands to the strongly twisted and coiled β-hairpin taken as the starting structure in modeling. As a result of modeling, a structural tree for the wrap-proteins was constructed that includes 201 folds of which 49 occur in known nonhomologous proteins.

IGG Subclass and Isotype Specific Immunoglobulin Responses to Lassa Fever and Venezuelan Equine Encephalomyelitis: Natural Infection and Immunization

DTIC Science & Technology

1991-12-30

AD-A246 912 AD ARMY PROJECT ORDER 88PP8804 TITLE: IGG SUBCLASS AND ISOTYPE SPECIFIC IMMUNOGLOBULIN RESPONSES TO LASSA FEVER AND VENEZUELAN EQUINE ...and Isotype Specific Immunoglobulin responses Army Project Order to Lassa Fever and Venezuelan Equine Encephalitis: 88PP8804 Natual...unlimited 13. ABSTRACT (Maximum 200 words) Venezuelan Equine Encephalitis (VEE) specific inimunoglobulin responses to the two vaccines, TC-83 (A live

Whole-cell or acellular pertussis vaccination in infancy determines IgG subclass profiles to DTaP booster vaccination.

PubMed

van der Lee, Saskia; Sanders, Elisabeth A M; Berbers, Guy A M; Buisman, Anne-Marie

2018-01-04

Duration of protection against pertussis is shorter in adolescents who have been immunized with acellular pertussis (aP) in infancy compared with adolescents who received whole-cell pertussis (wP) vaccines in infancy, which is related to immune responses elicited by these priming vaccines. To better understand differences in vaccine induced immunity, we determined pertussis, diphtheria, and tetanus (DTaP) vaccine antigen-specific IgG subclass responses in wP- and aP-primed children before and after two successive DTaP booster vaccinations. Blood samples were collected in a cross-sectional study from wP- or aP-primed children before and 1 month after the pre-school DTaP booster vaccination at age 4 years. Blood samples were collected from two different wP- and aP-primed groups of children before, 1 month and 1 year after an additional pre-adolescent Tdap booster at age 9 years. IgG subclass levels against the antigens included in the DTaP vaccine have been determined with fluorescent-bead-based multiplex immunoassays. At 4 years of age, the IgG4 proportion and concentration for pertussis, diphtheria and tetanus vaccine antigens were significantly higher in aP-primed children compared with wP-primed children. IgG4 concentrations further increased upon the two successive booster vaccinations at 4 and 9 years of age in both wP- and aP-primed children, but remained significantly higher in aP-primed children. The pertussis vaccinations administered in the primary series at infancy determine the vaccine antigen-specific IgG subclass profiles, not only against the pertussis vaccine antigens, but also against the co-administered diphtheria and tetanus vaccine antigens. These profiles did not change after DTaP booster vaccinations later in childhood. The different immune response with high proportions of specific IgG4 in some aP-primed children may contribute to a reduced protection against pertussis. ISRCTN65428640; ISRCTN64117538; NTR4089. Copyright © 2017

Skin-transmitted pathogens and the heebie jeebies: evidence for a subclass of disgust stimuli that evoke a qualitatively unique emotional response.

PubMed

Blake, Khandis R; Yih, Jennifer; Zhao, Kun; Sung, Billy; Harmon-Jones, Cindy

2017-09-01

Skin-transmitted pathogens have threatened humans since ancient times. We investigated whether skin-transmitted pathogens were a subclass of disgust stimuli that evoked an emotional response that was related to, but distinct from, disgust and fear. We labelled this response "the heebie jeebies". In Study 1, coding of 76 participants' experiences of disgust, fear, and the heebie jeebies showed that the heebie jeebies was elicited by unique stimuli which produced skin-crawling sensations and an urge to protect the skin. In Experiment 2,350 participants' responses to skin-transmitted pathogen, fear-inducing, and disgust-inducing vignettes showed that the vignettes elicited sensations and urges which loaded onto heebie jeebies, fear, and disgust factors, respectively. Experiment 3 largely replicated findings from Experiment 2 using video stimuli (178 participants). Results are consistent with the notion that skin-transmitted pathogens are a subclass of disgust stimuli which motivate behaviours that are functionally consistent with disgust yet qualitatively distinct.

Genetic and biochemical characterization of HMB-1, a novel subclass B1 metallo-β-lactamase found in a Pseudomonas aeruginosa clinical isolate.

PubMed

Pfennigwerth, Niels; Lange, Felix; Belmar Campos, Cristina; Hentschke, Moritz; Gatermann, Sören G; Kaase, Martin

2017-04-01

To characterize a novel subclass B1 metallo-β-lactamase (MBL) found in an MDR Pseudomonas aeruginosa clinical isolate. The isolate P. aeruginosa NRZ-03096 was recovered in 2012 from an anal swab from a patient hospitalized in Northern Germany and showed high MICs of carbapenems. MBL production was analysed by several phenotypic tests. Genetic characterization of the novel bla gene and MLST was performed by WGS. The novel bla gene was expressed in Escherichia coli TOP10 and the enzyme was subjected to biochemical characterization to determine the kinetic parameters K m and k cat . P. aeruginosa NRZ-03096 was resistant to all tested β-lactams and showed an MBL phenotype. Shotgun cloning experiments yielded a clone producing a novel subclass B1 enzyme with only 74.3% identity to the next nearest relative, KHM-1. The novel MBL was named HMB-1 (for Hamburg MBL). Analysis of WGS data showed that the bla HMB-1 gene was chromosomally located as part of a Tn 3 family transposon that was named Tn 6345 . Expression of bla HMB-1 in E. coli TOP10 led to increased resistance to β-lactams. Determination of K m and k cat revealed that HMB-1 had different hydrolytic characteristics compared with KHM-1, with lower hydrolytic rates for cephalosporins and a higher rate for imipenem. The identification of HMB-1 further underlines the ongoing spread and diversification of carbapenemases in Gram-negative human pathogens and especially in P. aeruginosa . © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Time-dependent transition of the immunoglobulin G subclass and immunoglobulin E response in cancer patients vaccinated with cholesteryl pullulan-melanoma antigen gene-A4 nanogel

PubMed Central

Kyogoku, Noriaki; Ikeda, Hiroaki; Tsuchikawa, Takahiro; Abiko, Takehiro; Fujiwara, Aki; Maki, Takehiro; Yamamura, Yoshiyuki; Ichinokawa, Masaomi; Tanaka, Kimitaka; Imai, Naoko; Miyahara, Yoshihiro; Kageyama, Shinichi; Shiku, Hiroshi; Hirano, Satoshi

2016-01-01

A phase I+II clinical trial of vaccination with MAGE-A4 protein complexed with cholesteryl pullulan melanoma antigen gene-A4 nanogel (CHP-MAGE-A4) is currently underway in patients with MAGE-A4-expressing cancer. In the present study, the primary phase I endpoint was to test the safety of the administration of 300 µg CHP-MAGE-A4 with and without OK-432. Another aim of the study was to clarify the details of the specific humoral immune response to vaccination. The 9 patients enrolled for phase I were vaccinated 6 times, once every 2 weeks: 3 patients with 100 µg and 3 patients with 300 µg CHP-MAGE-A4, and 3 patients with 300 µg CHP-MAGE-A4 plus 0.5 clinical units of OK-432. Toxicities were assessed using Common Terminology Criteria for Adverse Events v3.0. Clinical response was evaluated by modified Response Evaluation Criteria in Solid Tumours. Immunological monitoring of anti-MAGE-A4-specific antibodies was performed by ELISA of pre- and post-vaccination patient sera. The 6 vaccinations produced no severe adverse events. Stable disease was assessed in 4/9 patients. Anti-MAGE-A4 total immunoglobulin (Ig)G titers increased in 7/9 patients. Efficacious anti-MAGE-A4 IgG1, 2 and 3 antibody responses were observed in 7/9 patients. Among them, positive conversions to T helper 2 (Th2)-type antibody responses (IgG4 and IgE) were observed after frequent vaccination in 4/7 patients. The Th2 conversion was possibly associated with undesirable clinical observations, including progressive disease and the appearance of a new relapse lesion. The present study suggested that frequent vaccinations activated a Th2-dominant status in the cancer patients. The identification of a time-dependent IgG subclass and IgE antibody production during vaccination protocols may be a useful surrogate marker indicating a potentially undesirable change of the immunological environment for an effective antitumor immune response in cancer patients. PMID:28105158

Impact of liver fat on the differential partitioning of hepatic triacylglycerol into VLDL subclasses on high and low sugar diets.

PubMed

Umpleby, A Margot; Shojaee-Moradie, Fariba; Fielding, Barbara; Li, Xuefei; Marino, Andrea; Alsini, Najlaa; Isherwood, Cheryl; Jackson, Nicola; Ahmad, Aryati; Stolinski, Michael; Lovegrove, Julie A; Johnsen, Sigurd; Jeewaka R Mendis, A S; Wright, John; Wilinska, Malgorzata E; Hovorka, Roman; Bell, Jimmy D; Thomas, E Louise; Frost, Gary S; Griffin, Bruce A

2017-11-01

Dietary sugars are linked to the development of non-alcoholic fatty liver disease (NAFLD) and dyslipidaemia, but it is unknown if NAFLD itself influences the effects of sugars on plasma lipoproteins. To study this further, men with NAFLD ( n = 11) and low liver fat 'controls' ( n = 14) were fed two iso-energetic diets, high or low in sugars (26% or 6% total energy) for 12 weeks, in a randomised, cross-over design. Fasting plasma lipid and lipoprotein kinetics were measured after each diet by stable isotope trace-labelling.There were significant differences in the production and catabolic rates of VLDL subclasses between men with NAFLD and controls, in response to the high and low sugar diets. Men with NAFLD had higher plasma concentrations of VLDL 1 -triacylglycerol (TAG) after the high ( P <0.02) and low sugar ( P <0.0002) diets, a lower VLDL 1 -TAG fractional catabolic rate after the high sugar diet ( P <0.01), and a higher VLDL 1 -TAG production rate after the low sugar diet ( P <0.01), relative to controls. An effect of the high sugar diet, was to channel hepatic TAG into a higher production of VLDL 1 -TAG ( P <0.02) in the controls, but in contrast, a higher production of VLDL 2 -TAG ( P <0.05) in NAFLD. These dietary effects on VLDL subclass kinetics could be explained, in part, by differences in the contribution of fatty acids from intra-hepatic stores, and de novo lipogenesis. The present study provides new evidence that liver fat accumulation leads to a differential partitioning of hepatic TAG into large and small VLDL subclasses, in response to high and low intakes of sugars. © 2017 The Author(s).

The cytidine deaminase signature HxE(x)n CxxC of DYW1 binds zinc and is necessary for RNA editing of ndhD-1.

PubMed

Boussardon, Clément; Avon, Alexandra; Kindgren, Peter; Bond, Charles S; Challenor, Michael; Lurin, Claire; Small, Ian

2014-09-01

In flowering plants, RNA editing involves deamination of specific cytidines to uridines in both mitochondrial and chloroplast transcripts. Pentatricopeptide repeat (PPR) proteins and multiple organellar RNA editing factor (MORF) proteins have been shown to be involved in RNA editing but none have been shown to possess cytidine deaminase activity. The DYW domain of some PPR proteins contains a highly conserved signature resembling the zinc-binding active site motif of known nucleotide deaminases. We modified these highly conserved amino acids in the DYW motif of DYW1, an editing factor required for editing of the ndhD-1 site in Arabidopsis chloroplasts. We demonstrate that several amino acids of this signature motif are required for RNA editing in vivo and for zinc binding in vitro. We conclude that the DYW domain of DYW1 has features in common with cytidine deaminases, reinforcing the hypothesis that this domain forms part of the active enzyme that carries out RNA editing in plants. © 2014 The Authors. New Phytologist © 2014 New Phytologist Trust.

Antibody-Mediated Internalization of Infectious HIV-1 Virions Differs among Antibody Isotypes and Subclasses.

PubMed

Tay, Matthew Zirui; Liu, Pinghuang; Williams, LaTonya D; McRaven, Michael D; Sawant, Sheetal; Gurley, Thaddeus C; Xu, Thomas T; Dennison, S Moses; Liao, Hua-Xin; Chenine, Agnès-Laurence; Alam, S Munir; Moody, M Anthony; Hope, Thomas J; Haynes, Barton F; Tomaras, Georgia D

2016-08-01

Emerging data support a role for antibody Fc-mediated antiviral activity in vaccine efficacy and in the control of HIV-1 replication by broadly neutralizing antibodies. Antibody-mediated virus internalization is an Fc-mediated function that may act at the portal of entry whereby effector cells may be triggered by pre-existing antibodies to prevent HIV-1 acquisition. Understanding the capacity of HIV-1 antibodies in mediating internalization of HIV-1 virions by primary monocytes is critical to understanding their full antiviral potency. Antibody isotypes/subclasses differ in functional profile, with consequences for their antiviral activity. For instance, in the RV144 vaccine trial that achieved partial efficacy, Env IgA correlated with increased risk of HIV-1 infection (i.e. decreased vaccine efficacy), whereas V1-V2 IgG3 correlated with decreased risk of HIV-1 infection (i.e. increased vaccine efficacy). Thus, understanding the different functional attributes of HIV-1 specific IgG1, IgG3 and IgA antibodies will help define the mechanisms of immune protection. Here, we utilized an in vitro flow cytometric method utilizing primary monocytes as phagocytes and infectious HIV-1 virions as targets to determine the capacity of Env IgA (IgA1, IgA2), IgG1 and IgG3 antibodies to mediate HIV-1 infectious virion internalization. Importantly, both broadly neutralizing antibodies (i.e. PG9, 2G12, CH31, VRC01 IgG) and non-broadly neutralizing antibodies (i.e. 7B2 mAb, mucosal HIV-1+ IgG) mediated internalization of HIV-1 virions. Furthermore, we found that Env IgG3 of multiple specificities (i.e. CD4bs, V1-V2 and gp41) mediated increased infectious virion internalization over Env IgG1 of the same specificity, while Env IgA mediated decreased infectious virion internalization compared to IgG1. These data demonstrate that antibody-mediated internalization of HIV-1 virions depends on antibody specificity and isotype. Evaluation of the phagocytic potency of vaccine

Antibody-Mediated Internalization of Infectious HIV-1 Virions Differs among Antibody Isotypes and Subclasses

PubMed Central

McRaven, Michael D; Sawant, Sheetal; Gurley, Thaddeus C; Xu, Thomas T.; Dennison, S. Moses; Liao, Hua-Xin; Chenine, Agnès-Laurence; Alam, S. Munir; Haynes, Barton F.; Tomaras, Georgia D.

2016-01-01

Emerging data support a role for antibody Fc-mediated antiviral activity in vaccine efficacy and in the control of HIV-1 replication by broadly neutralizing antibodies. Antibody-mediated virus internalization is an Fc-mediated function that may act at the portal of entry whereby effector cells may be triggered by pre-existing antibodies to prevent HIV-1 acquisition. Understanding the capacity of HIV-1 antibodies in mediating internalization of HIV-1 virions by primary monocytes is critical to understanding their full antiviral potency. Antibody isotypes/subclasses differ in functional profile, with consequences for their antiviral activity. For instance, in the RV144 vaccine trial that achieved partial efficacy, Env IgA correlated with increased risk of HIV-1 infection (i.e. decreased vaccine efficacy), whereas V1-V2 IgG3 correlated with decreased risk of HIV-1 infection (i.e. increased vaccine efficacy). Thus, understanding the different functional attributes of HIV-1 specific IgG1, IgG3 and IgA antibodies will help define the mechanisms of immune protection. Here, we utilized an in vitro flow cytometric method utilizing primary monocytes as phagocytes and infectious HIV-1 virions as targets to determine the capacity of Env IgA (IgA1, IgA2), IgG1 and IgG3 antibodies to mediate HIV-1 infectious virion internalization. Importantly, both broadly neutralizing antibodies (i.e. PG9, 2G12, CH31, VRC01 IgG) and non-broadly neutralizing antibodies (i.e. 7B2 mAb, mucosal HIV-1+ IgG) mediated internalization of HIV-1 virions. Furthermore, we found that Env IgG3 of multiple specificities (i.e. CD4bs, V1-V2 and gp41) mediated increased infectious virion internalization over Env IgG1 of the same specificity, while Env IgA mediated decreased infectious virion internalization compared to IgG1. These data demonstrate that antibody-mediated internalization of HIV-1 virions depends on antibody specificity and isotype. Evaluation of the phagocytic potency of vaccine

Immunological studies on bee-keepers: specific IgG and subclass typing IgG against bee venom and bee venom components.

PubMed

Urbanek, R; Forster, J; Ziupa, J; Karitzky, D

1980-11-17

Specific IgE antibodies against bee venom and its components were studied in 23 bee-keepers. The highest IgG serum levels were observed for whole bee venom followed by phospholipase A. The serum levels of specific IgG antibodies against melittin and MCD-peptide were lower, the lowest serum levels being observed for apamin. After a 5 month absence from bee-keeping a fall in the serum levels of IgG antibodies was observed in all the bee-keepers studied. The investigation of the IgG subclass antibodies 1-4 against bee venom and phospholipase A demonstrated the highest serum levels for IgG 4 and IgG 2, the lowest levels were observed for IgG 1. The lowest IgG serum levels were associated with the least effective protection to bee stings. These findings support the concept that specific IgG antibodies prevent the development of allergic symptoms after bee sting.

[Human IgG subclass study. II. The levels of the individual IgG subclasses in paired sera from mothers and newborn infants as well as in the blood sera of inhabitants of an isolated northern village].

PubMed

Basova, E N; Stefani, D V; Kazantseva, L Z

1979-07-01

The levels of the first 3 subclasses of IgG, as determined by the radial immunodiffusion test, proved to be similar in the blood sera obtained from mothers and newborns in Moscow. The concentration of IgG4 was 0.64 +/- 0.02 g/l iently indicative of a limited passage of IgG4 molecules through the placenta. The inhabitants of an isolated northern village were found to have the inheritable combined deficit of IfG2 and IgG3 synthesis in their blood sera, which was probably due to the prolonged processes of inbreeding and the progenitor effect.

Effect of e-learning and repeated performance feedback on spirometry test quality in family practice: a cluster trial.

PubMed

Schermer, Tjard R; Akkermans, Reinier P; Crockett, Alan J; van Montfort, Marian; Grootens-Stekelenburg, Joke; Stout, Jim W; Pieters, Willem

2011-01-01

Spirometry has become an indispensable tool in primary care to exclude, diagnose, and monitor chronic respiratory conditions, but the quality of spirometry tests in family practices is a reason for concern. Aim of this study was to investigate whether a combination of e-learning and bimonthly performance feedback would improve spirometry test quality in family practices in the course of 1 year. Our study was a cluster trial with 19 family practices allocated to intervention or control conditions through minimization. Intervention consisted of e-learning and bimonthly feedback reports to practice nurses. Control practices received only the joint baseline workshop. Spirometry quality was assessed by independent lung function technicians. Two outcomes were defined, with the difference between rates of tests with 2 acceptable and repeatable blows being the primary outcome and the difference between rates of tests with 2 acceptable blows being the secondary outcome. We used multilevel logistic regression analysis to calculate odds ratios (ORs) for an adequate test in intervention group practices. We analyzed 1,135 tests. Rate of adequate tests was 33% in intervention and 30% in control group practices (OR = 1.3; P=.605). Adequacy of tests did not differ between groups but tended to increase with time: OR = 2.2 (P = .057) after 3 and OR = 2.0 (P = .086) in intervention group practices after 4 feedback reports. When ignoring test repeatability, these differences between the groups were slightly more pronounced: OR = 2.4 (P = .033) after 3 and OR=2.2 (P = .051) after 4 feedback reports. In the course of 1 year, we observed a small and late effect of e-learning and repeated feedback on the quality of spirometry as performed by family practice nurses. This intervention does not seem to compensate the lack of rigorous training and experience in performing spirometry tests in most practices.

CYP2E1 immunoglobulin G4 subclass antibodies after desflurane anesthesia

PubMed Central

Batistaki, Chrysanthi; Michalopoulos, George; Matsota, Paraskevi; Nomikos, Tzortzis; Kalimeris, Konstantinos; Riga, Maria; Nakou, Maria; Kostopanagiotou, Georgia

2014-01-01

AIM: To investigate CYP2E1 IgG4 autoantibody levels and liver biochemical markers in adult patients after anesthesia with desflurane. METHODS: Forty patients who were > 18 years old and undergoing elective surgery under general anesthesia with desflurane were studied. Alpha-glutathione-S-transferase (αGST) and IgG4 antibodies against CYP2E1 were measured preoperatively and 96 h postoperatively, as well as complete blood count, prothrombin time (PT), activated partial thromboplastin time (aPTT), international normalized ratio (INR), aspartate aminotransferase (SGOT), alanine aminotransferase (SGPT), g-glutamyl-transpeptidase (gGT), alkaline phosphatase, total serum proteins, albumin and bilirubin. A separate group of 8 patients who received regional anesthesia was also studied for calibration of the methodology used for CYP2E1 IgG4 and αGST measurements. Student’s t-test and the Mann-Whitney U test were used for comparison of the continuous variables, and Fisher’s exact test was used for the categorical variables. All tests were two-tailed, with statistical significance set as P < 0.05. RESULTS: None of the patients developed postoperative liver dysfunction, and all patients were successfully discharged from the hospital. No statistically significant difference was observed regarding liver function tests (SGOT, SGPT, γGT, bilirubin, INR), αGST and CYP2E1 IgG4, before and after exposure to desflurane. After dividing patients into two subgroups based on whether or not they had received general anesthesia in the past, no significant difference in the levels of CYP2E1 IgG4 was observed at baseline or 96 h after desflurane administration (P = 0.099 and P = 0.051, respectively). Alpha-GST baseline levels and levels after the intervention also did not differ significantly between these two subgroups (P > 0.1). The mean αGST differences were statistically elevated in men by 2.15 ng/mL compared to women when adjusted for BMI, duration of anesthesia, number of times

Genome-Wide Analyses and Functional Classification of Proline Repeat-Rich Proteins: Potential Role of eIF5A in Eukaryotic Evolution

PubMed Central

Mandal, Ajeet; Mandal, Swati; Park, Myung Hee

2014-01-01

The eukaryotic translation factor, eIF5A has been recently reported as a sequence-specific elongation factor that facilitates peptide bond formation at consecutive prolines in Saccharomyces cerevisiae, as its ortholog elongation factor P (EF-P) does in bacteria. We have searched the genome databases of 35 representative organisms from six kingdoms of life for PPP (Pro-Pro-Pro) and/or PPG (Pro-Pro-Gly)-encoding genes whose expression is expected to depend on eIF5A. We have made detailed analyses of proteome data of 5 selected species, Escherichia coli, Saccharomyces cerevisiae, Drosophila melanogaster, Mus musculus and Homo sapiens. The PPP and PPG motifs are low in the prokaryotic proteomes. However, their frequencies markedly increase with the biological complexity of eukaryotic organisms, and are higher in newly derived proteins than in those orthologous proteins commonly shared in all species. Ontology classifications of S. cerevisiae and human genes encoding the highest level of polyprolines reveal their strong association with several specific biological processes, including actin/cytoskeletal associated functions, RNA splicing/turnover, DNA binding/transcription and cell signaling. Previously reported phenotypic defects in actin polarity and mRNA decay of eIF5A mutant strains are consistent with the proposed role for eIF5A in the translation of the polyproline-containing proteins. Of all the amino acid tandem repeats (≥3 amino acids), only the proline repeat frequency correlates with functional complexity of the five organisms examined. Taken together, these findings suggest the importance of proline repeat-rich proteins and a potential role for eIF5A and its hypusine modification pathway in the course of eukaryotic evolution. PMID:25364902

Repeatability and Reproducibility of Compression Strength Measurements Conducted According to ASTM E9

NASA Technical Reports Server (NTRS)

Luecke, William E.; Ma, Li; Graham, Stephen M.; Adler, Matthew A.

2010-01-01

Ten commercial laboratories participated in an interlaboratory study to establish the repeatability and reproducibility of compression strength tests conducted according to ASTM International Standard Test Method E9. The test employed a cylindrical aluminum AA2024-T351 test specimen. Participants measured elastic modulus and 0.2 % offset yield strength, YS(0.2 % offset), using an extensometer attached to the specimen. The repeatability and reproducibility of the yield strength measurement, expressed as coefficient of variations were cv(sub r)= 0.011 and cv(sub R)= 0.020 The reproducibility of the test across the laboratories was among the best that has been reported for uniaxial tests. The reported data indicated that using diametrically opposed extensometers, instead of a single extensometer doubled the precision of the test method. Laboratories that did not lubricate the ends of the specimen measured yield stresses and elastic moduli that were smaller than those measured in laboratories that lubricated the specimen ends. A finite element analysis of the test specimen deformation for frictionless and perfect friction could not explain the discrepancy, however. The modulus measured from stress-strain data were reanalyzed using a technique that finds the optimal fit range, and applies several quality checks to the data. The error in modulus measurements from stress-strain curves generally increased as the fit range decreased to less than 40 % of the stress range.

MicroRNA Superfamilies Descended from miR390 and Their Roles in Secondary Small Interfering RNA Biogenesis in Eudicots[W

PubMed Central

Xia, Rui; Meyers, Blake C.; Liu, Zhongchi; Beers, Eric P.; Ye, Songqing; Liu, Zongrang

2013-01-01

Trans-acting small interfering RNAs (tasiRNAs) are a major class of small RNAs performing essential biological functions in plants. The first reported tasiRNA pathway, that of miR173-TAS1/2, produces tasiRNAs regulating a set of pentatricopeptide repeat (PPR) genes and has been characterized only in Arabidopsis thaliana to date. Here, we demonstrate that the microRNA (miRNA)-trans-acting small interfering RNA gene (TAS)-pentatricopeptide repeat-containing gene (PPR)-small interfering RNA pathway is a highly dynamic and widespread feature of eudicots. Nine eudicot plants, representing six different plant families, have evolved similar tasiRNA pathways to initiate phased small interfering RNA (phasiRNA) production from PPR genes. The PPR phasiRNA production is triggered by different 22-nucleotide miRNAs, including miR7122, miR1509, and fve-PPRtri1/2, and through distinct mechanistic strategies exploiting miRNA direct targeting or indirect targeting through TAS-like genes (TASL), one-hit or two-hit, or even two layers of tasiRNA–TASL interactions. Intriguingly, although those miRNA triggers display high sequence divergence caused by the occurrence of frequent point mutations and splicing shifts, their corresponding MIRNA genes show pronounced identity to the Arabidopsis MIR173, implying a common origin of this group of miRNAs (super-miR7122). Further analyses reveal that super-miR7122 may have evolved from a newly defined miR4376 superfamily, which probably originated from the widely conserved miR390. The elucidation of this evolutionary path expands our understanding of the course of miRNA evolution, especially for relatively conserved miRNA families. PMID:23695981

Pentatricopeptide repeat 336 as the candidate gene for paternal sorting of mitochondria (Psm) in cucumber

USDA-ARS?s Scientific Manuscript database

Cucumber (Cucumis sativus L.) is a useful plant to study organellar-nuclear interactions because its three genomes show differential transmission: bi-parental nuclear, maternal chloroplast and paternal mitochondrial (mt). The mt DNA of cucumber is relatively large due in part to accumulation of rep...

COMMON PATTERNS IN THE EVOLUTION BETWEEN THE LUMINOUS NEUTRON STAR LOW-MASS X-RAY BINARY SUBCLASSES

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

Fridriksson, Joel K.; Homan, Jeroen; Remillard, Ronald A., E-mail: J.K.Fridriksson@uva.nl

2015-08-10

The X-ray transient XTE J1701–462 was the first source observed to evolve through all known subclasses of low-magnetic-field neutron star low-mass X-ray binaries (NS-LMXBs), as a result of large changes in its mass accretion rate. To investigate to what extent similar evolution is seen in other NS-LMXBs we have performed a detailed study of the color–color and hardness–intensity diagrams (CDs and HIDs) of Cyg X-2, Cir X-1, and GX 13+1—three luminous X-ray binaries, containing weakly magnetized neutron stars, known to exhibit strong secular changes in their CD/HID tracks. Using the full set of Rossi X-ray Timing Explorer Proportional Counter Arraymore » data collected for the sources over the 16 year duration of the mission, we show that Cyg X-2 and Cir X-1 display CD/HID evolution with close similarities to XTE J1701–462. Although GX 13+1 shows behavior that is in some ways unique, it also exhibits similarities to XTE J1701–462, and we conclude that its overall CD/HID properties strongly indicate that it should be classified as a Z source, rather than as an atoll source. We conjecture that the secular evolution of Cyg X-2, Cir X-1, and GX 13+1—illustrated by sequences of CD/HID tracks we construct—arises from changes in the mass accretion rate. Our results strengthen previous suggestions that within single sources Cyg-like Z source behavior takes place at higher luminosities and mass accretion rates than Sco-like Z behavior, and lend support to the notion that the mass accretion rate is the primary physical parameter distinguishing the various NS-LMXB subclasses.« less

The binding of human and guinea-pig IgG subclasses to homologous macrophage and monocyte Fc receptors.

PubMed Central

Alexander, M D; Andrews, J A; Leslie, R G; Wood, N J

1978-01-01

Guinea-pig IgG2 and IgT1 bind to contiguous Fc receptors on homologous peritoneal macrophages. Equilibrium association constants determined for the binding of human IgG subclasses to homologous peripheral blood monocytes show that the order of binding is IgG1 greater than IgG3 greater than IgG4 greater than IgG2. Direct binding and rosette assay techniques independently established that both guinea-pig IgG2 and human IgG bind to homologous macrophage-monocyte Fc receptors through a site present in whole Fc (CH2. CH3)2, but absent in pFc' subfragments (CH3)2. PMID:680795

Whole-animal metabolic rate is a repeatable trait: a meta-analysis.

PubMed

Nespolo, Roberto F; Franco, Marcela

2007-06-01

Repeatability studies are gaining considerable interest among physiological ecologists, particularly in traits affected by high environmental/residual variance, such as whole-animal metabolic rate (MR). The original definition of repeatability, known as the intraclass correlation coefficient, is computed from the components of variance obtained in a one-way ANOVA on several individuals from which two or more measurements are performed. An alternative estimation of repeatability, popular among physiological ecologists, is the Pearson product-moment correlation between two consecutive measurements. However, despite the more than 30 studies reporting repeatability of MR, so far there is not a definite synthesis indicating: (1) whether repeatability changes in different types of animals; (2) whether some kinds of metabolism are more repeatable than others; and most important, (3) whether metabolic rate is significantly repeatable. We performed a meta-analysis to address these questions, as well as to explore the historical trend in repeatability studies. Our results show that metabolic rate is significantly repeatable and its effect size is not statistically affected by any of the mentioned factors (i.e. repeatability of MR does not change in different species, type of metabolism, time between measurements, and number of individuals). The cumulative meta-analysis revealed that repeatability studies in MR have already reached an asymptotical effect size with no further change either in its magnitude and/or variance (i.e. additional studies will not contribute significantly to the estimator). There was no evidence of strong publication bias.

Strong linkage disequilibrium of a HbE variant with the (AT)9(T)5 repeat in the BP1 binding site upstream of the beta-globin gene in the Thai population.

PubMed

Ohashi, Jun; Naka, Izumi; Patarapotikul, Jintana; Hananantachai, Hathairad; Brittenham, Gary; Looareesuwan, Sornchai; Clark, Andrew G; Tokunaga, Katsushi

2005-01-01

A binding site for the repressor protein BP1, which contains a tandem (AT)x(T)y repeat, is located approximately 530 bp 5' to the human beta-globin gene (HBB). There is accumulating evidence that BP1 binds to the (AT)9(T)5 allele more strongly than to other alleles, thereby reducing the expression of HBB. In this study, we investigated polymorphisms in the (AT)x(T)y repeat in 57 individuals living in Thailand, including three homozygotes for the hemoglobin E variant (HbE; beta26Glu-->Lys), 22 heterozygotes, and 32 normal homozygotes. We found that (AT)9(T)5 and (AT)7(T)7 alleles were predominant in the studied population and that the HbE variant is in strong linkage disequilibrium with the (AT)9(T)5 allele, which can explain why the betaE chain is inefficiently synthesized compared to the normal betaA chain. Moreover, the mildness of the HbE disease compared to other hemoglobinopathies in Thai may be due, in part, to the presence of the (AT)9(T)5 repeat on the HbE chromosome. In addition, a novel (AC)n polymorphism adjacent to the (AT)x(T)y repeat (i.e., (AC)3(AT)7(T)5) was found through the variation screening in this study.

The production and characterization of novel heavy-chain antibodies against the tandem repeat region of MUC1 mucin.

PubMed

Rahbarizadeh, Fatemeh; Rasaee, Mohammad J; Forouzandeh, Mehdi; Allameh, Abdolamir; Sarrami, Ramin; Nasiry, Habib; Sadeghizadeh, Majid

2005-01-01

Camelidae are known to produce immunoglobulins (Igs) devoid of light chains and constant heavy-chain domains (CH1). Antigen-specific fragments of these heavy-chain IgGs (VHH) are of great interest in biotechnology applications. This paper describes the first example of successfully raised heavy-chain antibodies in Camelus dromedarius (single-humped camel) and Camelus bactrianus (two-humped camel) against a MUC1 related peptide that is found to be an important epitope expressed in cancerous tissue. Camels were immunized against a synthetic peptide corresponding to the tandem repeat region of MUC1 mucin and cancerous tissue preparation obtained from patients suffering from breast carcinoma. Three IgG subclasses with different binding properties to protein A and G were purified by affinity chromatography. Both conventional and heavy-chain IgG antibodies were produced in response to MUC1-related peptide. The elicited antibodies could react specifically with the tandem repeat region of MUC1 mucin in an enzyme linked immunosorbant assay (ELISA). Anti-peptide antibodies were purified after passing antiserum over two affinity chromatography columns. Using ELISA, immunocytochemistry and Western blotting, the interaction of purified antibodies with different antigens was evaluated. The antibodies were observed to be selectively bound to antigens namely: MUC1 peptide (tandem repeat region), human milk fat globule membrane (HMFG), deglycosylated human milk fat globule membrane (D-HMFG), homogenized cancerous breast tissue and a native MUC1 purified from ascitic fluid. Ka values of specific polyclonal antipeptide antibodies were estimated in C. dromedarius and C. bactrianus, as 7 x 10(10) M(-1) and 1.4 x 10(10) M(-1) respectively.

Absence of bacterial resistance following repeat exposure to photodynamic therapy

NASA Astrophysics Data System (ADS)

Pedigo, Lisa A.; Gibbs, Aaron J.; Scott, Robert J.; Street, Cale N.

2009-06-01

The prevalence of antibiotic resistant bacteria necessitates exploration of alternative approaches to treat hospital and community acquired infections. The aim of this study was to determine whether bacterial pathogens develop resistance to antimicrobial photodynamic therapy (aPDT) during repeated sub-lethal challenge. Antibiotic sensitive and resistant strains of S. aureus and antibiotic sensitive E. coli were subjected to repeat PDT treatments using a methylene blue photosensitizer formulation and 670 nm illumination from a non-thermal diode laser. Parameters were adjusted such that kills were <100% so that surviving colonies could be passaged for subsequent exposures. With each repeat, kills were compared to those using non-exposed cultures of the same strain. Oxacillin resistance was induced in S. aureus using a disc diffusion method. For each experiment, "virgin" and "repeat" cultures were exposed to methylene blue at 0.01% w/v and illuminated with an energy dose of 20.6 J/cm2. No significant difference in killing of E. coli (repeat vs. virgin culture) was observed through 11 repeat exposures. Similar results were seen using MSSA and MRSA, wherein kill rate did not significantly differ from control over 25 repeat exposures. In contrast, complete oxacillin resistance could be generated in S. aureus over a limited number of exposures. PDT is effective in the eradication of pathogens including antibiotic resistance strains. Furthermore, repeated sub-lethal exposure does not induce resistance to subsequent PDT treatments. The absence of resistance formation represents a significant advantage of PDT over traditional antibiotics.

Role of memory errors in quantum repeaters

NASA Astrophysics Data System (ADS)

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

2007-03-01

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

Can non-cholesterol sterols and lipoprotein subclasses distribution predict different patterns of cholesterol metabolism and statin therapy response?

PubMed

Gojkovic, Tamara; Vladimirov, Sandra; Spasojevic-Kalimanovska, Vesna; Zeljkovic, Aleksandra; Vekic, Jelena; Kalimanovska-Ostric, Dimitra; Djuricic, Ivana; Sobajic, Sladjana; Jelic-Ivanovic, Zorana

2017-03-01

Cholesterol homeostasis disorders may cause dyslipidemia, atherosclerosis progression and coronary artery disease (CAD) development. Evaluation of non-cholesterol sterols (NCSs) as synthesis and absorption markers, and lipoprotein particles quality may indicate the dyslipidemia early development. This study investigates associations of different cholesterol homeostasis patterns with low-density (LDL) and high-density lipoproteins (HDL) subclasses distribution in statin-treated and statin-untreated CAD patients, and potential use of aforementioned markers for CAD treatment optimization. The study included 78 CAD patients (47 statin-untreated and 31 statin-treated) and 31 controls (CG). NCSs concentrations were quantified using gas chromatography- flame ionization detection (GC-FID). Lipoprotein subclasses were separated by gradient gel electrophoresis. In patients, cholesterol-synthesis markers were significantly higher comparing to CG. Cholesterol-synthesis markers were inversely associated with LDL size in all groups. For cholesterol homeostasis estimation, each group was divided to good and/or poor synthetizers and/or absorbers according to desmosterol and β-sitosterol median values. In CG, participants with reduced cholesterol absorption, the relative proportion of small, dense LDL was higher in those with increased cholesterol synthesis compared to those with reduced synthesis (p<0.01). LDL I fraction was significantly higher in poor synthetizers/poor absorbers subgroup compared to poor synthetizers/good absorbers (p<0.01), and good synthetizers/poor absorbers (p<0.01). Statin-treated patients with increased cholesterol absorption had increased proportion of LDL IVB (p<0.05). The results suggest the existence of different lipoprotein abnormalities according to various patterns of cholesterol homeostasis. Desmosterol/β-sitosterol ratio could be used for estimating individual propensity toward dyslipidemia development and direct the future treatment.

Carbon-enhanced metal-poor stars: CEMP-s and CEMP-no subclasses in the halo system of the Milky Way

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

Carollo, Daniela; Freeman, Ken; Beers, Timothy C.

2014-06-20

We explore the kinematics and orbital properties of a sample of 323 very metal-poor stars in the halo system of the Milky Way, selected from the high-resolution spectroscopic follow-up studies of Aoki et al. and Yong et al. The combined sample contains a significant fraction of carbon-enhanced metal-poor (CEMP) stars (22% or 29%, depending on whether a strict or relaxed criterion is applied for this definition). Barium abundances (or upper limits) are available for the great majority of the CEMP stars, allowing for their separation into the CEMP-s and CEMP-no subclasses. A new method to assign membership to the inner-more » and outer-halo populations of the Milky Way is developed, making use of the integrals of motion, and applied to determine the relative fractions of CEMP stars in these two subclasses for each halo component. Although limited by small-number statistics, the data suggest that the inner halo of the Milky Way exhibits a somewhat higher relative number of CEMP-s stars than CEMP-no stars (57% versus 43%), while the outer halo possesses a clearly higher fraction of CEMP-no stars than CEMP-s stars (70% versus 30%). Although larger samples of CEMP stars with known Ba abundances are required, this result suggests that the dominant progenitors of CEMP stars in the two halo components were different; massive stars for the outer halo, and intermediate-mass stars in the case of the inner halo.« less

A Repeat Look at Repeating Patterns

ERIC Educational Resources Information Center

Markworth, Kimberly A.

2016-01-01

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

Intra-session repeatability of lower limb muscles activation pattern during pedaling.

PubMed

Dorel, Sylvain; Couturier, Antoine; Hug, François

2008-10-01

Assessment of intra-session repeatability of muscle activation pattern is of considerable relevance for research settings, especially when used to determine changes over time. However, the repeatability of lower limb muscles activation pattern during pedaling is not fully established. Thus, we tested the intra-session repeatability of the activation pattern of 10 lower limb muscles during a sub-maximal cycling exercise. Eleven triathletes participated to this study. The experimental session consisted in a reference sub-maximal cycling exercise (i.e. 150 W) performed before and after a 53-min simulated training session (mean power output=200+/-12 W). Repeatability of EMG patterns was assessed in terms of muscle activity level (i.e. RMS of the mean pedaling cycle and burst) and muscle activation timing (i.e. onset and offset of the EMG burst) for the 10 following lower limb muscles: gluteus maximus (GMax), semimembranosus (SM), Biceps femoris (BF), vastus medialis (VM), rectus femoris (RF), vastus lateralis (VL), gastrocnemius medianus (GM) and lateralis (GL), soleus (SOL) and tibialis anterior (TA). No significant differences concerning the muscle activation level were found between test and retest for all the muscles investigated. Only VM, SOL and TA showed significant differences in muscle activation timing parameters. Whereas ICC and SEM values confirmed this weak repeatability, cross-correlation coefficients suggest a good repeatability of the activation timing parameters for all the studied muscles. Overall, the main finding of this work is the good repeatability of the EMG pattern during pedaling both in term of muscle activity level and muscle activation timing.

Overcoming fixation with repeated memory suppression.

PubMed

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

2015-01-01

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

Isoelectric focusing-affinity immunoblot analysis of mouse monoclonal antibodies to the four human IgG subclasses

NASA Technical Reports Server (NTRS)

Hamilton, Robert G.; Roebber, Marianne; Rodkey, L. Scott; Reimer, Charles B.

1987-01-01

Isoelectric focusing (IEF)/affinity immunoblotting and enzyme-linked immunosorbent assay (ELISA) were used for parallel analysis of murine monoclonal antihuman IgG-subclass antisera (MoAbs). Coomassie Blue-stained protein bands in the pH region 5.5-8.0 were shown to be murine IgG by direct blotting onto nitrocellulose followed by detection with conjugated antimouse IgG. Use of IgG myeloma antigen-coated nitrocellulose in the IEF-affinity immunoblot allowed detection of the charge microheterogeneity of MoAbs. The MoAb group contained one to five major dense bands flanked by up to four minor fainter bands, all with pIs ranging from 6.1 to 7.8. Semiquantitative estimates of binding specificity in the IEF-affinity blot compared well with cross-reactivity data obtained from a quantitative ELISA.

Reward modulation of contextual cueing: Repeated context overshadows repeated target location.

PubMed

Sharifian, Fariba; Contier, Oliver; Preuschhof, Claudia; Pollmann, Stefan

2017-10-01

Contextual cueing can be enhanced by reward. However, there is a debate if reward is associated with the repeated target-distractor configurations or with the repeated target locations that occur in both repeated and new displays. Based on neuroimaging evidence, we hypothesized that reward becomes associated with the target location only in new displays, but not in repeated displays, where the repeated target location is overshadowed by the more salient repeated target-distractor configuration. To test this hypothesis, we varied the reward value associated with the same target location in repeated and new displays. The results confirmed the overshadowing hypothesis in that search facilitation in repeated target-distractor configurations was modulated by the variable value associated with the target location. This effect was observed mainly in early learning.

Production of double repeated B subunit of Shiga toxin 2e at high levels in transgenic lettuce plants as vaccine material for porcine edema disease.

PubMed

Matsui, Takeshi; Takita, Eiji; Sato, Toshio; Aizawa, Michie; Ki, Misa; Kadoyama, Yumiko; Hirano, Kenji; Kinjo, Satoko; Asao, Hiroshi; Kawamoto, Keiko; Kariya, Haruko; Makino, Sou-Ichi; Hamabata, Takashi; Sawada, Kazutoshi; Kato, Ko

2011-08-01

Pig edema disease is a bacterial disease caused by enterohemorrhagic Escherichia coli. E. coli produces Shiga toxin 2e (Stx2e), which is composed of one A subunit (Stx2eA) and five B subunits (Stx2eB). We previously reported production of Stx2eB in lettuce plants as a potential edible vaccine (Matsui et al. in Biosci Biotechnol Biochem 73:1628-1634, 2009). However, the accumulation level was very low, and it was necessary to improve expression of Stx2eB for potential use of this plant-based vaccine. Therefore, in this study, we optimized the Stx2eB expression cassette and found that a double repeated Stx2eB (2× Stx2eB) accumulates to higher levels than a single Stx2eB in cultured tobacco cells. Furthermore, a linker peptide between the two Stx2eB moieties played an important role in maximizing the effects of the double repeat. Finally, we generated transgenic lettuce plants expressing 2× Stx2eB with a suitable linker peptide that accumulate as much as 80 mg per 100 g fresh weight, a level that will allow us to use these transgenic lettuce plants practically to generate vaccine material.

IgG subclass antibodies to human and bacterial HSP60 are not associated with disease activity and progression over time in axial spondyloarthritis

PubMed Central

2013-01-01

Introduction Spondyloarthritis (SpA), an interrelated group of rheumatic diseases, has been suggested to be triggered by bacterial infections prior to the development of an autoimmune response that causes inflammation of the spinal and peripheral joints. Because human heat shock protein 60 (HSP60), recently renamed HSPD1, and bacterial HSP60 are highly homologous, immunological cross-reactivity has been proposed as a mechanism of disease initiation. However, previous investigations of the humoral immune response to HSP60 in SpA patients have lacked determination of immunoglobulin G (IgG) subclasses and patient follow-up. In this study, we have focused on these parameters in a cohort of axial SpA patients with a well-established set of clinical characteristics, including MRI changes and human leukocyte antigen B27. Methods IgG subclass antibodies (IgG1, IgG2, IgG3 and IgG4) against recombinant HSP60 of three reactive arthritis-related bacteria; human HSP60; and the microorganisms Chlamydia trachomatis and C. pneumoniae were determined by ELISA. Serum samples collected from 2004 to 2006 and in 2010 and 2011 from 39 axial SpA patients were analyzed and compared with samples from 39 healthy controls. The Mann-Whitney U test and Wilcoxon matched pairs test were used to compare the antibody levels in different and paired groups, respectively. P < 0.01 was considered significant. The Spearman nonparametric correlation was used to determine correlation between antibody levels and between antibody levels and the disease parameters. Results Elevated levels of IgG1 and IgG3 to human HSP60 and IgG1 to HSP60 of Salmonella enterica Enteritidis were observed in SpA patients compared with healthy controls at both time points. The antibody levels were almost constant over time for IgG1, whereas high levels of IgG3 to human HSP60 tended to decrease over time. The antibody response to human HSP60 was predominantly of the IgG3 subclass, and patients with high levels of IgG3 to this

Color distributions in E-S0 galaxies. I. Frequency and importance of dust patterns for various brands of E classified galaxies

NASA Astrophysics Data System (ADS)

Michard, R.

1998-06-01

From the consideration of a sample of color distributions in 67 E classified objects of the Local Supercluster, it is found that local dust features are much more frequent and important in disky E's than boxy E's. The subclass of undeterminate objects, those which cannot be assigned to the diE or boE groups, is intermediate. Subsets of objects of common properties are considered from the point of view of local dust features occurrence: giant boxy E's; minor boxy E's with rotational support; compact dwarfs; SB0-like E's. It is noted that the detection of dust features is more than twice less frequent in Virgo cluster ellipticals than in the full sample, but the significance of this result is not clear. Based on observations collected at the Canada-France-Hawaii Telescope and at the Observatoire du Pic du Midi

IgG4 subclass antibodies impair antitumor immunity in melanoma

PubMed Central

Karagiannis, Panagiotis; Gilbert, Amy E.; Josephs, Debra H.; Ali, Niwa; Dodev, Tihomir; Saul, Louise; Correa, Isabel; Roberts, Luke; Beddowes, Emma; Koers, Alexander; Hobbs, Carl; Ferreira, Silvia; Geh, Jenny L.C.; Healy, Ciaran; Harries, Mark; Acland, Katharine M.; Blower, Philip J.; Mitchell, Tracey; Fear, David J.; Spicer, James F.; Lacy, Katie E.; Nestle, Frank O.; Karagiannis, Sophia N.

2013-01-01

Host-induced antibodies and their contributions to cancer inflammation are largely unexplored. IgG4 subclass antibodies are present in IL-10–driven Th2 immune responses in some inflammatory conditions. Since Th2-biased inflammation is a hallmark of tumor microenvironments, we investigated the presence and functional implications of IgG4 in malignant melanoma. Consistent with Th2 inflammation, CD22+ B cells and IgG4+-infiltrating cells accumulated in tumors, and IL-10, IL-4, and tumor-reactive IgG4 were expressed in situ. When compared with B cells from patient lymph nodes and blood, tumor-associated B cells were polarized to produce IgG4. Secreted B cells increased VEGF and IgG4, and tumor cells enhanced IL-10 secretion in cocultures. Unlike IgG1, an engineered tumor antigen-specific IgG4 was ineffective in triggering effector cell–mediated tumor killing in vitro. Antigen-specific and nonspecific IgG4 inhibited IgG1-mediated tumoricidal functions. IgG4 blockade was mediated through reduction of FcγRI activation. Additionally, IgG4 significantly impaired the potency of tumoricidal IgG1 in a human melanoma xenograft mouse model. Furthermore, serum IgG4 was inversely correlated with patient survival. These findings suggest that IgG4 promoted by tumor-induced Th2-biased inflammation may restrict effector cell functions against tumors, providing a previously unexplored aspect of tumor-induced immune escape and a basis for biomarker development and patient-specific therapeutic approaches. PMID:23454746

Low density lipoprotein subclasses in Asian and Caucasian adolescent boys.

PubMed

Raschke, Verena; Elmadfa, Ibrahim; Bermingham, Margaret A; Steinbeck, Kate

2006-01-01

South Asian adults are known to have very high rates of Coronary heart disease (CHD) and insulin resistance and, even as adolescents, may show higher risk factors for CHD. The aim of this study was to investigate the prevalence of small, dense low density lipoprotein (sdLDL) subclasses in a cohort of adolescent boys. The specific objective was to investigate the relationship between measures of fatness, ethnicity and LDL diameter in this cohort. Preformed native (non-denaturing) polyacrylamide 3-13% gradient gels and a multipurpose vertical electrophoresis system were used for the separation of LDL sub-fractions in a single school year cohort of boys aged 15-16 years (n=135). Latex beads and thyroglobulin standards were used to construct a calibration curve in order to calculate LDL particle diameters by regression (Total Lab Software v1.11). ANOVA was used to compare LDL size among different ethnic groups (SPSS and Stat View). The study sample was comprised of 45.2% Caucasians, 41.5% East Asians and 13.3% from the Indian subcontinent (South Asians). There was a non-significant trend for South Asians to have a lower LDL diameter than either Caucasians or East Asian boys which was independent of % total body fat (%TBF) and body mass index (BMI). This is the first adolescent cohort to examine sdLDL which included Caucasians, East and South Asians. It appears that the higher risk profile for CHD and diabetes noted in South Asian adults may be evident even during adolescence.

Psychological and physiological responses following repeated peer death.

PubMed

Andersen, Judith Pizarro; Silver, Roxane Cohen; Stewart, Brandon; Koperwas, Billie; Kirschbaum, Clemens

2013-01-01

Undergraduates at a university in the United States were exposed - directly and indirectly - to 14 peer deaths during one academic year. We examined how individual and social factors were associated with psychological (e.g., anxiety, depression, somatization) and physiological (i.e., cortisol) distress responses following this unexpected and repeated experience with loss. Two to three months after the final peer death, respondents (N = 122, 61% female, 18-23 years, M = 20.13, SD = 1.14) reported prior adverse experiences, degree of closeness with the deceased, acute responses to the peer deaths, ongoing distress responses, social support, support seeking, and media viewing. A subset (n = 24) returned hair samples for evaluation of cortisol responses during the previous 3 months. Ongoing psychological distress was associated with a) prior interpersonal trauma, b) fewer social supports, and c) media exposure to news of the deaths (p's<.05). Participants who had no prior bereavements showed, on average, high cortisol (>25 p/mg) compared to individuals with one or two prior bereavement experiences (who were, on average, within the normal range, 10 to 25 p/mg) (p<.05). Only 8% of the sample utilized available university psychological or physical health resources and support groups. Limited research has examined the psychological and physiological impact of exposure to chronic, repeated peer loss, despite the fact that there are groups of individuals (e.g., police, military soldiers) that routinely face such exposures. Prior adversity appears to play a role in shaping psychological and physiological responses to repeated loss. This topic warrants further research given the health implications of repeated loss for individuals in high-risk occupations and university settings.

A Monograph of the Polish Oxfordian Echinoids: Part 2, Subclass Euechinoidea Bronn, 1860

NASA Astrophysics Data System (ADS)

Radwańska, Urszula

2014-12-01

The non-cidaroid echinoids (subclass Euechinoidea Bronn, 1860) from the Oxfordian epicontinental sequence of Poland (Polish Jura, Holy Cross Mountains, Mid-Polish Anticlinorium) are assigned to the genera Hemipedina Wright, 1855, Hemicidaris L. Agassiz, 1838, Hemitiaris Pomel, 1883, Pseudocidaris Étallon, 1859, Stomechinus Desor, 1856, Eucosmus L. Agassiz in Agassiz and Desor, 1846, Glypticus L. Agassiz, 1840, Pleurodiadema de Loriol, 1870, Diplopodia McCoy, 1848, Trochotiara Lambert, 1901, Desorella Cotteau, 1855, and Heterocidaris Cotteau, 1860, plus one acropeltid taxon, and one taxon left in open nomenclature. Within the genus Hemicidaris L. Agassiz, 1838, the relationship between Hemicidaris intermedia (Fleming, 1828), Hemicidaris crenularis L. Agassiz, 1839 [non Lamarck, nec Goldfuss] and Hemicidaris quenstedti Mérian, 1855, all with confused taxonomy, is discussed. Based on test structure, the genera Polydiadema Lambert, 1883, and Trochotiara Lambert, 1901, of the family Emiratiidae Ali, 1990, are proved to be separate; the common species mamillana of F.A. Roemer (1836) is a typical Trochotiara. An attention is paid to the morphology of the tiny, juvenile specimens, common in Eucosmus decoratus L. Agassiz in L. Agassiz and Desor, 1846, and in Pleurodiadema stutzi (Moesch, 1867).

Phylogenetic Information Content of Copepoda Ribosomal DNA Repeat Units: ITS1 and ITS2 Impact

PubMed Central

Zagoskin, Maxim V.; Lazareva, Valentina I.; Grishanin, Andrey K.; Mukha, Dmitry V.

2014-01-01

The utility of various regions of the ribosomal repeat unit for phylogenetic analysis was examined in 16 species representing four families, nine genera, and two orders of the subclass Copepoda (Crustacea). Fragments approximately 2000 bp in length containing the ribosomal DNA (rDNA) 18S and 28S gene fragments, the 5.8S gene, and the internal transcribed spacer regions I and II (ITS1 and ITS2) were amplified and analyzed. The DAMBE (Data Analysis in Molecular Biology and Evolution) software was used to analyze the saturation of nucleotide substitutions; this test revealed the suitability of both the 28S gene fragment and the ITS1/ITS2 rDNA regions for the reconstruction of phylogenetic trees. Distance (minimum evolution) and probabilistic (maximum likelihood, Bayesian) analyses of the data revealed that the 28S rDNA and the ITS1 and ITS2 regions are informative markers for inferring phylogenetic relationships among families of copepods and within the Cyclopidae family and associated genera. Split-graph analysis of concatenated ITS1/ITS2 rDNA regions of cyclopoid copepods suggested that the Mesocyclops, Thermocyclops, and Macrocyclops genera share complex evolutionary relationships. This study revealed that the ITS1 and ITS2 regions potentially represent different phylogenetic signals. PMID:25215300

[Cholesterol of the high-density lipoprotein subclasses in the native inhabitants of the Chukchi National Autonomous Okrug].

PubMed

Polesskiĭ, V A; Chepurnenko, N V; Koshechkin, V A; Morozov, V V; Gerasimova, E N

1980-12-01

The authors studied the content of total cholesterol (Ch), triglycerides (TG), CS of high density lipoprotein (HDL2 and HDL3) subclasses and testosterone in blood plasma of 30-59-year-old males, natives or newcomers of Chukotsk, and compared the results with the corresponding values determined in the male population of Moscow. It was established that the mean HDL Ch concentration in blood plasma was higher and the content of TG and to a lesser degree that of total CS, was lower in the Chukchi males than in the male Moscow population and in the newcomers who were examined. It was also shown that in hypo- and hyper-alphalipoproteinemia in all groups examined, the content of HDL2 Ch changed for the most part (decreased or increased, respectively) while the level of HDL3 Ch remained relatively stable.

HLA class I antibodies trigger increased adherence of monocytes to endothelial cells by eliciting an increase in endothelial P-selectin and, depending on subclass, by engaging FcγRs.

PubMed

Valenzuela, Nicole M; Mulder, Arend; Reed, Elaine F

2013-06-15

Ab-mediated rejection (AMR) of solid organ transplants is characterized by intragraft macrophages. It is incompletely understood how donor-specific Ab binding to graft endothelium promotes monocyte adhesion, and what, if any, contribution is made by the Fc region of the Ab. We investigated the mechanisms underlying monocyte recruitment by HLA class I (HLA I) Ab-activated endothelium. We used a panel of murine mAbs of different subclasses to crosslink HLA I on human aortic, venous, and microvascular endothelial cells and measured the binding of human monocytic cell lines and peripheral blood monocytes. Both anti-HLA I murine (m)IgG1 and mIgG2a induced endothelial P-selectin, which was required for monocyte adhesion to endothelium irrespective of subclass. mIgG2a but not mIgG1 could bind human FcγRs. Accordingly, HLA I mIgG2a but not mIgG1 treatment of endothelial cells significantly augmented recruitment, predominantly through FcγRI, and, to a lesser extent, FcγRIIa. Moreover, HLA I mIgG2a promoted firm adhesion of monocytes to ICAM-1 through Mac-1, which may explain the prominence of monocytes during AMR. We confirmed these observations using human HLA allele-specific mAbs and IgG purified from transplant patient sera. HLA I Abs universally elicit endothelial exocytosis leading to monocyte adherence, implying that P-selectin is a putative therapeutic target to prevent macrophage infiltration during AMR. Importantly, the subclass of donor-specific Ab may influence its pathogenesis. These results imply that human IgG1 and human IgG3 should have a greater capacity to trigger monocyte infiltration into the graft than IgG2 or IgG4 due to enhancement by FcγR interactions.

To Repeat or Not to Repeat a Course

ERIC Educational Resources Information Center

Armstrong, Michael J.; Biktimirov, Ernest N.

2013-01-01

The difficult transition from high school to university means that many students need to repeat (retake) 1 or more of their university courses. The authors examine the performance of students repeating first-year core courses in an undergraduate business program. They used data from university records for 116 students who took a total of 232…

Importance of IgG subclasses of anti-Rh antibodies for the detection of Fc-receptor-bearing human lymphocytes.

PubMed

Zupańska, B; Maślanka, K; van Loghem, E

1982-11-01

13 anti-Rh sera were compared for their usefulness in the detection of Fc-receptor-bearing lymphocytes (EAhum test). IgG subclasses of anti-Rh antibodies were determined by the antiglobulin test with monospecific sera and by the detection of Gm allotypic markers in the haemagglutination inhibition test. Six sera with IgG1 + IgG3 or IgG1 + IgG2 + IgG3 antibodies and one with pure IgG3 antibodies were found to be useful, whereas six other sera with only IgG1 were unsuitable for the EAhum test. G3m markers were detected only on the anti-Rh antibodies which were capable of forming rosettes with lymphocytes. The data show that human peripheral lymphocytes possess Fc receptors for IgG3 immunoglobulins.

PASTA repeats of the protein kinase StkP interconnect cell constriction and separation of Streptococcus pneumoniae.

PubMed

Zucchini, Laure; Mercy, Chryslène; Garcia, Pierre Simon; Cluzel, Caroline; Gueguen-Chaignon, Virginie; Galisson, Frédéric; Freton, Céline; Guiral, Sébastien; Brochier-Armanet, Céline; Gouet, Patrice; Grangeasse, Christophe

2018-02-01

Eukaryotic-like serine/threonine kinases (eSTKs) with extracellular PASTA repeats are key membrane regulators of bacterial cell division. How PASTA repeats govern eSTK activation and function remains elusive. Using evolution- and structural-guided approaches combined with cell imaging, we disentangle the role of each PASTA repeat of the eSTK StkP from Streptococcus pneumoniae. While the three membrane-proximal PASTA repeats behave as interchangeable modules required for the activation of StkP independently of cell wall binding, they also control the septal cell wall thickness. In contrast, the fourth and membrane-distal PASTA repeat directs StkP localization at the division septum and encompasses a specific motif that is critical for final cell separation through interaction with the cell wall hydrolase LytB. We propose a model in which the extracellular four-PASTA domain of StkP plays a dual function in interconnecting the phosphorylation of StkP endogenous targets along with septal cell wall remodelling to allow cell division of the pneumococcus.

VizieR Online Data Catalog: Abundances of 8 RR Lyrae subclass C variable stars (Govea+, 2014)

NASA Astrophysics Data System (ADS)

Govea, J.; Gomez, T.; Preston, G. W.; Sneden, C.

2016-02-01

We chose 10 candidate RR Lyrae variable stars of subclass c (RRc) stars for spectroscopic observation. Many of these stars were first identified as RRc variables by the All Sky Automated Survey (ASAS) of Pojmanski 2003 (cat. II/264). The target star list included ASAS 144154-0324.7 and ASAS 204440-2402.7. But our spectroscopic study suggest that these two stars are probably W UMa binaries instead of RR Lyrae stars Our spectra were obtained with the echelle spectrograph of the du Pont 2.5m telescope at the Las Campanas Observatory. Four observing runs during 2009-2010 were partly devoted to this project. The spectrograph was used with the 1.5*4'' entrance slit, which translates to a resolving power of R=λ/Δλ~27000 at the MgI b lines near 5180Å. The total continuous wavelength coverage of the spectra was 3500-9000Å. (6 data files).

Subclass distribution of IgG antibodies to the rat oesophagus stratum corneum (so-called anti-keratin antibodies) in rheumatoid arthritis.

PubMed Central

Vincent, C; Serre, G; Basile, J P; Lestra, H C; Girbal, E; Sebbag, M; Soleilhavoup, J P

1990-01-01

Serum IgG, labelling the stratum corneum of the rat oesophagus epithelium, so-called anti-keratin antibodies (AKA) constitute the most specific marker for the diagnosis of rheumatoid arthritis. In this study, we investigated 31 IgG AKA-positive rheumatoid sera and 21 control sera from patients with non-rheumatoid inflammatory rheumatic diseases. The serum level of IgG1,2,3 and 4 was determined by radial immunodiffusion and the subclass distribution of IgG AKA by a three-step semi-quantitative immunofluorescence assay using standard monoclonal antibodies specific for each of the four human IgG subclasses. In the rheumatoid sera, the serum level of IgG1 was found to be significantly increased and the level of IgG2 significantly decreased with regard to the control sera, while the levels of IgG3 and 4 as well as total IgG were in the normal range. IgG1,2,3, and 4 AKA were detected in 27 (87%), 6 (19%), 4 (13%) and 11 (35%) of the 31 rheumatoid sera, respectively, and were found to be independent of the clinical and biological indices of the disease. In spite of inter-individual heterogeneity, two predominant profiles were distinguished: IgG1 (alone) and IgG(1 + 4), which together represented 18 sera (58%). The large predominance of IgG1 AKA and the quasi-absence of IgG2 AKA suggest that the recognized antigen may be partly comprised of protein. Moreover, the high frequency of occurrence of IgG4 AKA might result from chronic exposure to the eliciting antigen, which could be a genuine autoantigen since we demonstrated that it is also present in the stratum corneum of human epidermis. Images Fig. 1 PMID:1696185

Antibody repertoire development in fetal and neonatal piglets. XVII. IgG subclass transcription revisited with emphasis on new IgG3.

PubMed

Butler, John E; Wertz, Nancy

2006-10-15

Fetal piglets offer an in vivo model for determining whether Ag-independent IgG subclass transcription proceeds in a manner that differs from subclass transcription in pigs exposed to environmental Ags and TLR ligands. Our data from approximately 12,000 Cgamma clones from > 60 piglets provide the first report on the relative usage of all known porcine Cgamma genes in fetal and young pigs. Studies revealed that among the six Cgamma genes, allelic variants of IgG1 comprised 50-80% of the repertoire, and IgG2 alleles comprised < 10% in nearly all tissues. However, relative transcription of allelic variants of IgG1 randomly deviate from the 1:1 ratio expected in heterozygotes. Most surprising was the finding that IgG3 accounted for half of all Cgamma transcripts in the ileal Peyer's patches (IPPs) and mesenteric lymph nodes but on average only approximately 5% of the clones from the thymus, tonsil, spleen, peripheral blood, and bone marrow of newborns. Lymphoid tissues from late term fetuses revealed a similar expression pattern. Except for IgG3 in the IPPs and mesenteric lymph nodes, no stochastic pattern of Cgamma expression during development was seen in animals from mid-gestation through 5 mo. The age and tissue dependence of IgG3 transcription paralleled the developmental persistence of the IPP, and its near disappearance corresponds to the diversification of the preimmune VDJ repertoire in young piglets. We hypothesize that long-hinged porcine IgG3 may be important in preadaptive responses to T cell-independent Ags similar to those described for its murine namesake.

A comparative study of the N-linked oligosaccharide structures of human IgG subclass proteins.

PubMed Central

Jefferis, R; Lund, J; Mizutani, H; Nakagawa, H; Kawazoe, Y; Arata, Y; Takahashi, N

1990-01-01

Quantitative oligosaccharide profiles were determined for each of 18 human IgG paraproteins representing the four subclasses. Each paraprotein exhibits a unique profile that may be substantially different from that observed for polyclonal IgG. The IgG2 and some IgG3 proteins analysed exhibit a predominance of oligosaccharide moieties having galactose on the Man(alpha 1----3) arm rather than the Man(alpha 1----6) arm; it was previously held that galactosylation of the Man(alpha 1----6) arm is preferred, as observed for IgG1, IgG4 and polyclonal IgG. An IgG4 protein is reported that has galactosylated Man(alpha 1----3) and Man(alpha 1----6) arms on both Fc-localized carbohydrate moieties; previous findings suggested that such fully glycosylated structures could not be accommodated within the internal space of the C gamma 2 domains. Unusual monoantennary oligosaccharides present in IgG2 and IgG3 proteins were isolated and their structures determined. Images Fig. 1. PMID:2363690

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

NASA Astrophysics Data System (ADS)

Yamasaki, Shotaro; Totani, Tomonori; Kiuchi, Kenta

2018-04-01

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

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

NASA Astrophysics Data System (ADS)

Yamasaki, Shotaro; Totani, Tomonori; Kiuchi, Kenta

2018-06-01

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

Effect of Repeat Copy Number on Variable-Number Tandem Repeat Mutations in Escherichia coli O157:H7

PubMed Central

Vogler, Amy J.; Keys, Christine; Nemoto, Yoshimi; Colman, Rebecca E.; Jay, Zack; Keim, Paul

2006-01-01

Variable-number tandem repeat (VNTR) loci have shown a remarkable ability to discriminate among isolates of the recently emerged clonal pathogen Escherichia coli O157:H7, making them a very useful molecular epidemiological tool. However, little is known about the rates at which these sequences mutate, the factors that affect mutation rates, or the mechanisms by which mutations occur at these loci. Here, we measure mutation rates for 28 VNTR loci and investigate the effects of repeat copy number and mismatch repair on mutation rate using in vitro-generated populations for 10 E. coli O157:H7 strains. We find single-locus rates as high as 7.0 × 10−4 mutations/generation and a combined 28-locus rate of 6.4 × 10−4 mutations/generation. We observed single- and multirepeat mutations that were consistent with a slipped-strand mispairing mutation model, as well as a smaller number of large repeat copy number mutations that were consistent with recombination-mediated events. Repeat copy number within an array was strongly correlated with mutation rate both at the most mutable locus, O157-10 (r2 = 0.565, P = 0.0196), and across all mutating loci. The combined locus model was significant whether locus O157-10 was included (r2 = 0.833, P < 0.0001) or excluded (r2 = 0.452, P < 0.0001) from the analysis. Deficient mismatch repair did not affect mutation rate at any of the 28 VNTRs with repeat unit sizes of >5 bp, although a poly(G) homomeric tract was destabilized in the mutS strain. Finally, we describe a general model for VNTR mutations that encompasses insertions and deletions, single- and multiple-repeat mutations, and their relative frequencies based upon our empirical mutation rate data. PMID:16740932

Effect of repeat copy number on variable-number tandem repeat mutations in Escherichia coli O157:H7.

PubMed

Vogler, Amy J; Keys, Christine; Nemoto, Yoshimi; Colman, Rebecca E; Jay, Zack; Keim, Paul

2006-06-01

Variable-number tandem repeat (VNTR) loci have shown a remarkable ability to discriminate among isolates of the recently emerged clonal pathogen Escherichia coli O157:H7, making them a very useful molecular epidemiological tool. However, little is known about the rates at which these sequences mutate, the factors that affect mutation rates, or the mechanisms by which mutations occur at these loci. Here, we measure mutation rates for 28 VNTR loci and investigate the effects of repeat copy number and mismatch repair on mutation rate using in vitro-generated populations for 10 E. coli O157:H7 strains. We find single-locus rates as high as 7.0 x 10(-4) mutations/generation and a combined 28-locus rate of 6.4 x 10(-4) mutations/generation. We observed single- and multirepeat mutations that were consistent with a slipped-strand mispairing mutation model, as well as a smaller number of large repeat copy number mutations that were consistent with recombination-mediated events. Repeat copy number within an array was strongly correlated with mutation rate both at the most mutable locus, O157-10 (r2= 0.565, P = 0.0196), and across all mutating loci. The combined locus model was significant whether locus O157-10 was included (r2= 0.833, P < 0.0001) or excluded (r2= 0.452, P < 0.0001) from the analysis. Deficient mismatch repair did not affect mutation rate at any of the 28 VNTRs with repeat unit sizes of >5 bp, although a poly(G) homomeric tract was destabilized in the mutS strain. Finally, we describe a general model for VNTR mutations that encompasses insertions and deletions, single- and multiple-repeat mutations, and their relative frequencies based upon our empirical mutation rate data.

HLA class I antibodies trigger increased adherence of monocytes to endothelial cells by eliciting an increase in endothelial P-selectin and, depending on subclass, by engaging FcγRs1

PubMed Central

Valenzuela, Nicole M; Mulder, Arend; Reed, Elaine F

2013-01-01

Antibody-mediated rejection of solid organ transplants is characterized by intragraft macrophages. It is incompletely understood how donor specific antibody binding to graft endothelium promotes monocyte adhesion, and what, if any, contribution is made by the Fc region of the antibody. We investigated the mechanisms underlying monocyte recruitment by HLA class I antibody-activated endothelium. We used a panel of murine monoclonal antibodies of different subclasses to crosslink HLA I on human aortic, venous and microvascular endothelial cells, and measured the binding of human monocytic cell lines and peripheral blood monocytes. Both anti-HLA I murine IgG1 and mIgG2a induced endothelial P-selectin, which was required for monocyte adhesion to endothelium irrespective of subclass. Mouse IgG2a but not mIgG1 could bind human FcγRs. Accordingly, HLA I mIgG2a but not mIgG1 treatment of endothelial cells significantly augmented recruitment, predominantly through FcγRI, and, to a lesser extent, FcγRIIa. Moreover, HLA I mIgG2a promoted firm adhesion of monocytes to ICAM-1 through Mac-1, which may explain the prominence of monocytes during antibody mediated rejection. We confirmed these observations using human HLA allele specific monoclonal antibodies and IgG purified from transplant patient sera. HLA I antibodies universally elicit endothelial exocytosis leading to monocyte adherence, implying that P-selectin is a putative therapeutic target to prevent macrophage infiltration during antibody-mediated rejection. Importantly, the subclass of donor specific antibody may influence its pathogenesis. These results imply that hIgG1 and hIgG3 should have a greater capacity to trigger monocyte infiltration into the graft than IgG2 or IgG4 due to enhancement by FcγR interactions. PMID:23690477

The Influence of Relational Knowledge and Executive Function on Preschoolers' Repeating Pattern Knowledge

ERIC Educational Resources Information Center

Miller, Michael R.; Rittle-Johnson, Bethany; Loehr, Abbey M.; Fyfe, Emily R.

2016-01-01

Children's knowledge of repeating patterns (e.g., ABBABB) is a central component of early mathematics, but the developmental mechanisms underlying this knowledge are currently unknown. We sought clarity on the importance of relational knowledge and executive function (EF) to preschoolers' understanding of repeating patterns. One hundred…

Comparative Chloroplast Genomics of Gossypium Species: Insights Into Repeat Sequence Variations and Phylogeny

PubMed Central

Wu, Ying; Liu, Fang; Yang, Dai-Gang; Li, Wei; Zhou, Xiao-Jian; Pei, Xiao-Yu; Liu, Yan-Gai; He, Kun-Lun; Zhang, Wen-Sheng; Ren, Zhong-Ying; Zhou, Ke-Hai; Ma, Xiong-Feng; Li, Zhong-Hu

2018-01-01

Cotton is one of the most economically important fiber crop plants worldwide. The genus Gossypium contains a single allotetraploid group (AD) and eight diploid genome groups (A–G and K). However, the evolution of repeat sequences in the chloroplast genomes and the phylogenetic relationships of Gossypium species are unclear. Thus, we determined the variations in the repeat sequences and the evolutionary relationships of 40 cotton chloroplast genomes, which represented the most diverse in the genus, including five newly sequenced diploid species, i.e., G. nandewarense (C1-n), G. armourianum (D2-1), G. lobatum (D7), G. trilobum (D8), and G. schwendimanii (D11), and an important semi-wild race of upland cotton, G. hirsutum race latifolium (AD1). The genome structure, gene order, and GC content of cotton species were similar to those of other higher plant plastid genomes. In total, 2860 long sequence repeats (>10 bp in length) were identified, where the F-genome species had the largest number of repeats (G. longicalyx F1: 108) and E-genome species had the lowest (G. stocksii E1: 53). Large-scale repeat sequences possibly enrich the genetic information and maintain genome stability in cotton species. We also identified 10 divergence hotspot regions, i.e., rpl33-rps18, psbZ-trnG (GCC), rps4-trnT (UGU), trnL (UAG)-rpl32, trnE (UUC)-trnT (GGU), atpE, ndhI, rps2, ycf1, and ndhF, which could be useful molecular genetic markers for future population genetics and phylogenetic studies. Site-specific selection analysis showed that some of the coding sites of 10 chloroplast genes (atpB, atpE, rps2, rps3, petB, petD, ccsA, cemA, ycf1, and rbcL) were under protein sequence evolution. Phylogenetic analysis based on the whole plastomes suggested that the Gossypium species grouped into six previously identified genetic clades. Interestingly, all 13 D-genome species clustered into a strong monophyletic clade. Unexpectedly, the cotton species with C, G, and K-genomes were admixed and

Exceptionally long 5' UTR short tandem repeats specifically linked to primates.

PubMed

Namdar-Aligoodarzi, P; Mohammadparast, S; Zaker-Kandjani, B; Talebi Kakroodi, S; Jafari Vesiehsari, M; Ohadi, M

2015-09-10

We have previously reported genome-scale short tandem repeats (STRs) in the core promoter interval (i.e. -120 to +1 to the transcription start site) of protein-coding genes that have evolved identically in primates vs. non-primates. Those STRs may function as evolutionary switch codes for primate speciation. In the current study, we used the Ensembl database to analyze the 5' untranslated region (5' UTR) between +1 and +60 of the transcription start site of the entire human protein-coding genes annotated in the GeneCards database, in order to identify "exceptionally long" STRs (≥5-repeats), which may be of selective/adaptive advantage. The importance of this critical interval is its function as core promoter, and its effect on transcription and translation. In order to minimize ascertainment bias, we analyzed the evolutionary status of the human 5' UTR STRs of ≥5-repeats in several species encompassing six major orders and superorders across mammals, including primates, rodents, Scandentia, Laurasiatheria, Afrotheria, and Xenarthra. We introduce primate-specific STRs, and STRs which have expanded from mouse to primates. Identical co-occurrence of the identified STRs of rare average frequency between 0.006 and 0.0001 in primates supports a role for those motifs in processes that diverged primates from other mammals, such as neuronal differentiation (e.g. APOD and FGF4), and craniofacial development (e.g. FILIP1L). A number of the identified STRs of ≥5-repeats may be human-specific (e.g. ZMYM3 and DAZAP1). Future work is warranted to examine the importance of the listed genes in primate/human evolution, development, and disease. Copyright © 2015 Elsevier B.V. All rights reserved.

Duct Leakage Repeatability Testing

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

Walker, Iain; Sherman, Max

2014-08-01

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

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

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

Bagchi, Manjari, E-mail: manjari@imsc.res.in

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

Socioeconomic and clinical characteristics associated with repeat suicide attempts among young people.

PubMed

Chen, Chuan-Yu; Yeh, Hsueh-Han; Huang, Nicole; Lin, Yun-Chen

2014-05-01

Repeat suicidal behaviors in young people are a critical public health concern. The study investigates individual socioeconomic and episode-dependent clinical factors predicting repeat suicide attempts among youth by gender. Using a retrospective cohort study, we identified a total of 4,094 male and 3,219 female youths who had the index suicide episode at the ages of 15-24 years from the 1996-2007 National Health Insurance Research Database in Taiwan. The recurrence of suicide attempt was assessed within 1 year after the index suicide. Information pertaining to suicide management and postsuicide treatment was obtained from healthcare records. Repeated event survival analyses were used to estimate episode-dependent risk of suicide attempt. The occurrence of repeat suicide attempts was more common in males, yet the phenomenon of risk aggravation appears more prominent in females. The estimate for peak hazard of the second repeat attempt was 2-fold higher than that of the first repeat event in males, and approximately 6-fold in females. Socioeconomic (e.g., labor market participation: adjusted Hazard Ratio [aHR] = 1.14, 95% CI = 1.01-1.28) and index suicide management characteristics (e.g., receiving treatment at clinic, aHR = 1.54, 95% CI = 1.19-1.99) were found to play important roles for repeat suicide attempts in males. For females, postsuicide treatment of mental disorders appears more influential. The relationships between socioeconomic and clinical factors with repeat suicide attempts in young people vary by gender. School/workplace-based post suicide attempt consultation and clinical management for youth may be planned and delivered on a gender-appropriate basis. Copyright © 2014 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

Examining Repeaters' Performance on Second Language Proficiency Tests: A Review and a Call for Research

ERIC Educational Resources Information Center

Barkaoui, Khaled

2017-01-01

As the number of candidates who repeat English language proficiency tests more than once to meet a certain cutscore (e.g., for university admission) or to demonstrate progress (e.g., after instruction) continues to increase dramatically, there is a need for more research on the attributes and test performance of test repeaters. This article…

Distinct Immunoglobulin Class and Immunoglobulin G Subclass Patterns against Ganglioside GQ1b in Miller Fisher Syndrome following Different Types of Infection

PubMed Central

Schwerer, Beatrix; Neisser, Andrea; Bernheimer, Hanno

1999-01-01

We studied serum antibodies against gangliosides GQ1b and GM1 in 13 patients with Miller Fisher syndrome (MFS) and in 18 patients with Guillain-Barré syndrome (GBS) with cranial nerve involvement. Anti-GQ1b titers were elevated in all patients with MFS cases (immunoglobulin G [IgG] > IgA, IgM), and in 8 of the 18 with GBS. Lower frequencies of increased anti-GM1 titers were observed in MFS patients (3 of 13), as well as in GBS patients (5 of 18). During the course of MFS, anti-GQ1b titers of all Ig classes decreased within 3 weeks after onset. By contrast, anti-GM1 titers (mainly IgM) transiently increased during the course of MFS in five of six patients, suggesting a nonspecific secondary immune response. In patients with MFS following respiratory infections, IgG was the major anti-GQ1b Ig class (six of six patients) and IgG3 was the major subclass (five of six). In contrast, four of five patients with MFS following gastrointestinal infections showed predominance of anti-GQ1b IgA or IgM over IgG and predominance of the IgG2 subclass; anti-GQ1b IgG (IgG3) prevailed in one patient only. These distinct Ig patterns strongly suggest that different infections may trigger different mechanisms of anti-GQ1b production, such as via T-cell-dependent as opposed to T-cell-independent pathways. Thus, the origin of antibodies against GQ1b in MFS may be determined by the type of infectious agent that precipitates the disease. PMID:10225903

Drosophila fragile X mental retardation protein and metabotropic glutamate receptor A convergently regulate the synaptic ratio of ionotropic glutamate receptor subclasses.

PubMed

Pan, Luyuan; Broadie, Kendal S

2007-11-07

A current hypothesis proposes that fragile X mental retardation protein (FMRP), an RNA-binding translational regulator, acts downstream of glutamatergic transmission, via metabotropic glutamate receptor (mGluR) G(q)-dependent signaling, to modulate protein synthesis critical for trafficking ionotropic glutamate receptors (iGluRs) at synapses. However, direct evidence linking FMRP and mGluR function with iGluR synaptic expression is limited. In this study, we use the Drosophila fragile X model to test this hypothesis at the well characterized glutamatergic neuromuscular junction (NMJ). Two iGluR classes reside at this synapse, each containing common GluRIIC (III), IID and IIE subunits, and variable GluRIIA (A-class) or GluRIIB (B-class) subunits. In Drosophila fragile X mental retardation 1 (dfmr1) null mutants, A-class GluRs accumulate and B-class GluRs are lost, whereas total GluR levels do not change, resulting in a striking change in GluR subclass ratio at individual synapses. The sole Drosophila mGluR, DmGluRA, is also expressed at the NMJ. In dmGluRA null mutants, both iGluR classes increase, resulting in an increase in total synaptic GluR content at individual synapses. Targeted postsynaptic dmGluRA overexpression causes the exact opposite GluR phenotype to the dfmr1 null, confirming postsynaptic GluR subtype-specific regulation. In dfmr1; dmGluRA double null mutants, there is an additive increase in A-class GluRs, and a similar additive impact on B-class GluRs, toward normal levels in the double mutants. These results show that both dFMRP and DmGluRA differentially regulate the abundance of different GluR subclasses in a convergent mechanism within individual postsynaptic domains.

Slipped-strand mispairing at noncontiguous repeats in Poecilia reticulata: a model for minisatellite birth.

PubMed Central

Taylor, J S; Breden, F

2000-01-01

The standard slipped-strand mispairing (SSM) model for the formation of variable number tandem repeats (VNTRs) proposes that a few tandem repeats, produced by chance mutations, provide the "raw material" for VNTR expansion. However, this model is unlikely to explain the formation of VNTRs with long motifs (e.g., minisatellites), because the likelihood of a tandem repeat forming by chance decreases rapidly as the length of the repeat motif increases. Phylogenetic reconstruction of the birth of a mitochondrial (mt) DNA minisatellite in guppies suggests that VNTRs with long motifs can form as a consequence of SSM at noncontiguous repeats. VNTRs formed in this manner have motifs longer than the noncontiguous repeat originally formed by chance and are flanked by one unit of the original, noncontiguous repeat. SSM at noncontiguous repeats can therefore explain the birth of VNTRs with long motifs and the "imperfect" or "short direct" repeats frequently observed adjacent to both mtDNA and nuclear VNTRs. PMID:10880490

Suppression of synthesis of an IgG subclass in a persistent viral infection.

PubMed Central

McGuire, T C

1976-01-01

Comparison of immunoglobulin levels of nine horses before and after infection with equine infectious anaemia (EIA) virus demonstrated a significant depression of serum IgG(T) at 2 months (P less than 0-001) and at 1 year (P less than 0-01) after infection. In contrast, the levels of IgGa were significantly increased at both times after infection. Another sixteen horses with EIA for 1-4 months were examined and there was also significant depression (P less than 0-001) of IgG(T) when compared to pre-infection levels. No significant changes in IgG(T), IgGa and IgM were noted in fourteen normal horses housed for 2-7 months in the same manner as infected horses. Following DNP immunization there was a significant (P less than 0-02) decrease in the amount of IgG(T) antibody produced in five horses with EIA when compared to five normal horses. Metabolism studies with iodinated IgG(T) showed a significant (P less than 0-001) decrease in synthesis of this immunoglobulin in EIA-infected horses when compared to normal horses. Amounts of IgGa synthesized were similar in the two groups. Thus, persistent EIA viral infection suppresses the synthesis of IgG(T), an IgG subclass, without suppressing IgGa. PMID:814077

Discovery of a New Photometric Sub-class of Faint and Fast Classical Novae

NASA Astrophysics Data System (ADS)

Kasliwal, M. M.; Cenko, S. B.; Kulkarni, S. R.; Ofek, E. O.; Quimby, R.; Rau, A.

2011-07-01

We present photometric and spectroscopic follow-up of a sample of extragalactic novae discovered by the Palomar 60 inch telescope during a search for "Fast Transients In Nearest Galaxies" (P60-FasTING). Designed as a fast cadence (1 day) and deep (g < 21 mag) survey, P60-FasTING was particularly sensitive to short-lived and faint optical transients. The P60-FasTING nova sample includes 10 novae in M 31, 6 in M 81, 3 in M 82, 1 in NGC 2403, and 1 in NGC 891. This significantly expands the known sample of extragalactic novae beyond the Local Group, including the first discoveries in a starburst environment. Surprisingly, our photometry shows that this sample is quite inconsistent with the canonical maximum-magnitude-rate-of-decline (MMRD) relation for classical novae. Furthermore, the spectra of the P60-FasTING sample are indistinguishable from classical novae. We suggest that we have uncovered a sub-class of faint and fast classical novae in a new phase space in luminosity-timescale of optical transients. Thus, novae span two orders of magnitude in both luminosity and time. Perhaps the MMRD, which is characterized only by the white dwarf mass, was an oversimplification. Nova physics appears to be characterized by a relatively rich four-dimensional parameter space in white dwarf mass, temperature, composition, and accretion rate.

Reconfigurable multiport EPON repeater

NASA Astrophysics Data System (ADS)

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

2009-11-01

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

Interstitial telomere-like repeats in the Arabidopsis thaliana genome.

PubMed

Uchida, Wakana; Matsunaga, Sachihiro; Sugiyama, Ryuji; Kawano, Shigeyuki

2002-02-01

Eukaryotic chromosomal ends are protected by telomeres, which are thought to play an important role in ensuring the complete replication of chromosomes. On the other hand, non-functional telomere-like repeats in the interchromosomal regions (interstitial telomeric repeats; ITRs) have been reported in several eukaryotes. In this study, we identified eight ITRs in the Arabidopsis thaliana genome, each consisting of complete and degenerate 300- to 1200-bp sequences. The ITRs were grouped into three classes (class IA-B, class II, and class IIIA-E) based on the degeneracy of the telomeric repeats in ITRs. The telomeric repeats of the two ITRs in class I were conserved for the most part, whereas the single ITR in class II, and the five ITRs in class III were relatively degenerated. In addition, degenerate ITRs were surrounded by common sequences that shared 70-100% homology to each other; these are named ITR-adjacent sequences (IAS). Although the genomic regions around ITRs in class I lacked IAS, those around ITRs in class II contained IAS (IASa), and those around five ITRs in class III had nine types of IAS (IASb, c, d, e, f, g, h, i, and j). Ten IAS types in classes II and III showed no significant homology to each other. The chromosomal locations of ITRs and IAS were not category-related, but most of them were adjacent to, or part of, a centromere. These results show that the A. thaliana genome has undergone chromosomal rearrangements, such as end-fusions and segmental duplications.

Ehrlichia chaffeensis Tandem Repeat Proteins and Ank200 are Type 1 Secretion System Substrates Related to the Repeats-in-Toxin Exoprotein Family

PubMed Central

Wakeel, Abdul; den Dulk-Ras, Amke; Hooykaas, Paul J. J.; McBride, Jere W.

2011-01-01

Ehrlichia chaffeensis has type 1 and 4 secretion systems (T1SS and T4SS), but the substrates have not been identified. Potential substrates include secreted tandem repeat protein (TRP) 47, TRP120, and TRP32, and the ankyrin repeat protein, Ank200, that are involved in molecular host–pathogen interactions including DNA binding and a network of protein–protein interactions with host targets associated with signaling, transcriptional regulation, vesicle trafficking, and apoptosis. In this study we report that E. chaffeensis TRP47, TRP32, TRP120, and Ank200 were not secreted in the Agrobacterium tumefaciens Cre recombinase reporter assay routinely used to identify T4SS substrates. In contrast, all TRPs and the Ank200 proteins were secreted by the Escherichia coli complemented with the hemolysin secretion system (T1SS), and secretion was reduced in a T1SS mutant (ΔTolC), demonstrating that these proteins are T1SS substrates. Moreover, T1SS secretion signals were identified in the C-terminal domains of the TRPs and Ank200, and a detailed bioinformatic analysis of E. chaffeensis TRPs and Ank200 revealed features consistent with those described in the repeats-in-toxins (RTX) family of exoproteins, including glycine- and aspartate-rich tandem repeats, homology with ATP-transporters, a non-cleavable C-terminal T1SS signal, acidic pIs, and functions consistent with other T1SS substrates. Using a heterologous E. coli T1SS, this investigation has identified the first Ehrlichia T1SS substrates supporting the conclusion that the T1SS and corresponding substrates are involved in molecular host–pathogen interactions that contribute to Ehrlichia pathobiology. Further investigation of the relationship between Ehrlichia TRPs, Ank200, and the RTX exoprotein family may lead to a greater understanding of the importance of T1SS substrates and specific functions of T1SS in the pathobiology of obligately intracellular bacteria. PMID:22919588

Decrease of selective immunoglobulin E response to amoxicillin despite repeated administration of benzylpenicillin and penicillin V.

PubMed

Fernandez, T; Torres, M J; R-Pena, R; Fuentes, M S; Robles, S; Mayorga, C; Blanca, M

2005-12-01

Subjects with IgE responses to betalactams can develop selective or cross-reactive responses after the administration of penicillin derivatives. After the reaction, however, the hapten induces a boosting phenomenon, which may increase the titre and the affinity of the antibody, with the resulting risk of developing allergic reactions to other penicillins. To determine in subjects with selective responses to amoxicillin (AX) and good tolerance to benzylpenicillin (BP) and penicillin V (PV) whether the administration of these compounds induced any change in specificity, measured by either skin or in vitro testing, which could predict the appearance of cross-reactivity. Ten subjects with a selective response to AX were followed-up for 2 years with the periodic administration of penicillin G and V (Group A) and compared with another group composed of 10 persons with identical clinical characteristics but without repeated penicillin administration (Group B). Periodic in vitro and in vivo measurements of specific IgE antibodies were performed at 6-month intervals. Patients were randomized to Group A or B according to their order of inclusion. In both groups, skin test reactivity tended to decrease, and although greater in Group A, the difference was not significant compared with Group B. Median RAST values also decreased over time and showed no differences in the exposed group compared with the controls. One patient in Group A became positive to benzylpenicilloyl (BPO), despite becoming negative to AX. Subjects with selective IgE responses to side-chain-specific determinants seem to become negative, with no influence from subsequent administration of a closely related penicillin.

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

PubMed

Yu, Zhenming; Zhu, Yongqing; Chen-Plotkin, Alice S; Clay-Falcone, Dana; McCluskey, Leo; Elman, Lauren; Kalb, Robert G; Trojanowski, John Q; Lee, Virginia M-Y; Van Deerlin, Vivianna M; Gitler, Aaron D; Bonini, Nancy M

2011-03-29

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

Relationship of baseline HDL subclasses, small dense LDL and LDL triglyceride to cardiovascular events in the AIM-HIGH clinical trial

PubMed Central

Albers, John J; Slee, April; Fleg, Jerome L; O’Brien, Kevin D; Marcovina, Santica M

2016-01-01

Background and aims Previous results of the AIM-HIGH trial showed that baseline levels of the conventional lipid parameters were not predictive of future cardiovascular (CV) outcomes. The aims of this secondary analysis were to examine the levels of cholesterol in high density lipoprotein (HDL) subclasses (HDL2-C and HDL3-C), small dense low density lipoprotein (sdLDL-C), and LDL triglyceride (LDL-TG) at baseline, as well as the relationship between these levels and CV outcomes. Methods Individuals with CV disease and low baseline HDL-C levels were randomized to simvastatin plus placebo or simvastatin plus extended release niacin (ERN), 1,500 to 2,000 mg/day, with ezetimibe added as needed in both groups to maintain an on-treatment LDL-C in the range of 40 to 80 mg/dL. The primary composite endpoint was death from coronary disease, nonfatal myocardial infarction, ischemic stroke, hospitalization for acute coronary syndrome, or symptom-driven coronary or cerebrovascular revascularization. HDL-C, HDL3-C, sdLDL-C and LDL-TG were measured at baseline by detergent-based homogeneous assays. HDL2-C was computed by the difference between HDL-C and HDL3-C. Analyses were performed on 3,094 study participants who were already on statin therapy prior to enrollment in the trial. Independent contributions of lipoprotein fractions to CV events were determined by Cox proportional hazards modeling. Results Baseline HDL3-C was protective against CV events (HR: 0.84, p=0.043) while HDL-C, HDL2-C, sdLDL-C and LDL-TG were not event-related (HR: 0.96, p=0.369; HR: 1.07, p=0.373; HR: 1.05, p=0.492; HR: 1.03, p=0.554, respectively). Conclusions The results of this secondary analysis of the AIM-HIGH Study indicate that levels of HDL3-C, but not other lipoprotein fractions, are predictive of CV events, suggesting that the HDL3 subclass may be primarily responsible for the inverse association of HDL-C and CV disease. PMID:27320173

Risks of repeated miscarriage.

PubMed

George, Lena; Granath, Fredrik; Johansson, Anna L V; Olander, Bodil; Cnattingius, Sven

2006-03-01

There is a lack of well-designed epidemiological studies of possible risk factors for repeated miscarriage. In this Swedish population-based case-control study, we investigated the association between sociodemographic and anthropometric factors, obstetric history and life-style factors, with respect to the risks of first-trimester repeated miscarriage. Information on maternal characteristics was collected through in-person interviews. Plasma blood samples were analysed for cotinine and folate concentrations. Adjusted odds ratios (OR) with 95% confidence interval [CI] were used to estimate the relative risk of repeated miscarriage. The risks of repeated miscarriage were increased for women aged > or = 35 years (adjusted OR 2.9 [95% CI 1.4, 5.8]), as well as for women aged < or = 24 years (OR 2.8 [95% CI 1.1, 6.8]). Women with a history of at least one preceding miscarriage prior to the two index pregnancies, women reporting prolonged time to conceive, and women with a history of myoma, faced a more than fourfold increased risk of repeated miscarriage. Smokers were at an increased risk of repeated miscarriage (OR 2.1 [95% CI 1.1, 4.1]). Among non-smoking women with high caffeine intake, there was an increased risk of repeated miscarriage, whereas there was no such association among smokers. Low plasma folate levels were not associated with increased risks.

Repeating Earthquakes on the Queen Charlotte Plate Boundary

NASA Astrophysics Data System (ADS)

Hayward, T. W.; Bostock, M. G.

2015-12-01

The Queen Charlotte Fault (QCF) is a major plate boundary located off the northwest coast of North America that has produced large earthquakes in 1949 (M8.1) and more recently in October, 2012 (M7.8). The 2012 event was dominated by thrusting despite the fact that plate motions at the boundary are nearly transcurrent. It is now widely believed that the plate boundary comprises the QCF (i.e., a dextral strike-slip fault) as well as an element of subduction of the Pacific Plate beneath the North American Plate. Repeating earthquakes and seismic tremor have been observed in the vicinity of the QCF; providing insight into the spatial and temporal characteristics of repeating earthquakes is the goal of this research. Due to poor station coverage and data quality, traditional methods of locating earthquakes are not applicable to these events. Instead, we have implemented an algorithm to locate local (i.e., < 100 km distance to epicenter) earthquakes using a single, three-component seismogram. This algorithm relies on the P-wave polarization and, through comparison with larger local events in the Geological Survey of Canada catalogue, is shown to yield epicentral locations accurate to within 5-10 km. A total of 24 unique families of repeating earthquakes has been identified, and 4 of these families have been located with high confidence. Their epicenters locate directly on the trace of the QCF and their depths are shallow (i.e., 5-15 km), consistent with the proposed depth of the QCF. Analysis of temporal recurrence leading up to the 2012 M7.8 event reveals a non-random pattern, with an approximately 15 day periodicity. Further analysis is planned to study whether this behaviour persists after the 2012 event and to gain insight into the effects of the 2012 event on the stress field and frictional properties of the plate boundary.

Repeated batch fermentation of immobilized E. coli expressing Vitreoscilla hemoglobin for long-term use

PubMed Central

Sar, Taner; Seker, Gamze; Erman, Ayse Gokce; Stark, Benjamin C.; Yesilcimen Akbas, Meltem

2017-01-01

ABSTRACT This study describes an efficient and reusable process for ethanol production from medium containing whey powder, using alginate immobilized ethanologenic E. coli strains either expressing (TS3) or not expressing (FBR5) Vitreoscilla hemoglobin. Reuseabilities of the FBR5 and TS3 strains were investigated regarding their ethanol production capacities over the course of 15 successive 96-h batch fermentations. The ethanol production was fairly stable over the entire duration of the experiment, with strain TS3 maintaining a substantial advantage over strain FBR5. Storage of both strains in 2 different solutions for up to 60 d resulted in only a modest loss of ethanol production, with strain TS3 consistently outperforming strain FBR5 by a substantial amount. Strains stored for 15 or 30 d maintained their abilities to produce ethanol without dimunition over the course of 8 successive batch fermentations; again strain TS3 maintained a substantial advantage over strain FBR5 throughout the entire experiment. Thus, immobilization is a useful strategy to maintain the advantage in ethanol productivity afforded by expression of Vitreoscilla hemoglobin over long periods of time and large numbers of repeated batch fermentations, including, as in this case, using media with food processing wastes as the carbon source. PMID:28394725

Repeated batch fermentation of immobilized E. coli expressing Vitreoscilla hemoglobin for long-term use.

PubMed

Sar, Taner; Seker, Gamze; Erman, Ayse Gokce; Stark, Benjamin C; Yesilcimen Akbas, Meltem

2017-09-03

This study describes an efficient and reusable process for ethanol production from medium containing whey powder, using alginate immobilized ethanologenic E. coli strains either expressing (TS3) or not expressing (FBR5) Vitreoscilla hemoglobin. Reuseabilities of the FBR5 and TS3 strains were investigated regarding their ethanol production capacities over the course of 15 successive 96-h batch fermentations. The ethanol production was fairly stable over the entire duration of the experiment, with strain TS3 maintaining a substantial advantage over strain FBR5. Storage of both strains in 2 different solutions for up to 60 d resulted in only a modest loss of ethanol production, with strain TS3 consistently outperforming strain FBR5 by a substantial amount. Strains stored for 15 or 30 d maintained their abilities to produce ethanol without dimunition over the course of 8 successive batch fermentations; again strain TS3 maintained a substantial advantage over strain FBR5 throughout the entire experiment. Thus, immobilization is a useful strategy to maintain the advantage in ethanol productivity afforded by expression of Vitreoscilla hemoglobin over long periods of time and large numbers of repeated batch fermentations, including, as in this case, using media with food processing wastes as the carbon source.

Rapid and high resolution genotyping of all Escherichia coli serotypes using 10 genomic repeat-containing loci.

PubMed

Løbersli, Inger; Haugum, Kjersti; Lindstedt, Bjørn-Arne

2012-01-01

Our laboratory has previously published two multiple-locus variable-number tandem-repeats analysis (MLVA) methods for rapid genotyping of Escherichia coli (E. coli), which are now in routine use for surveillance and outbreak detection. The first assay developed was specific for E. coli O157:H7; however this assay was not suitable for genotyping other E. coli serotypes. A new generic MLVA-assay was then developed with the capability of genotyping all E. coli serotypes. This generic E. coli MLVA (GECM7) was based on polymorphism in seven variable number of tandem repeats (VNTR) loci. GECM7 worked well with the majority of E. coli serotypes; however we wanted to increase the resolution for this method based in part of comparison with PFGE typing of E. coli O26:H11, where PFGE appeared to display higher resolution. The GECM7 method was improved by adding three new repeat-loci to a total of ten (GECM10), and a considerable increase in resolution was observed (from 296 to 507 genotypes on the same set of strains). Copyright © 2011 Elsevier B.V. All rights reserved.

Revisiting the TALE repeat.

PubMed

Deng, Dong; Yan, Chuangye; Wu, Jianping; Pan, Xiaojing; Yan, Nieng

2014-04-01

Transcription activator-like (TAL) effectors specifically bind to double stranded (ds) DNA through a central domain of tandem repeats. Each TAL effector (TALE) repeat comprises 33-35 amino acids and recognizes one specific DNA base through a highly variable residue at a fixed position in the repeat. Structural studies have revealed the molecular basis of DNA recognition by TALE repeats. Examination of the overall structure reveals that the basic building block of TALE protein, namely a helical hairpin, is one-helix shifted from the previously defined TALE motif. Here we wish to suggest a structure-based re-demarcation of the TALE repeat which starts with the residues that bind to the DNA backbone phosphate and concludes with the base-recognition hyper-variable residue. This new numbering system is consistent with the α-solenoid superfamily to which TALE belongs, and reflects the structural integrity of TAL effectors. In addition, it confers integral number of TALE repeats that matches the number of bound DNA bases. We then present fifteen crystal structures of engineered dHax3 variants in complex with target DNA molecules, which elucidate the structural basis for the recognition of bases adenine (A) and guanine (G) by reported or uncharacterized TALE codes. Finally, we analyzed the sequence-structure correlation of the amino acid residues within a TALE repeat. The structural analyses reported here may advance the mechanistic understanding of TALE proteins and facilitate the design of TALEN with improved affinity and specificity.

All-photonic quantum repeaters

PubMed Central

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

2015-01-01

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

Two-Hierarchy Entanglement Swapping for a Linear Optical Quantum Repeater

NASA Astrophysics Data System (ADS)

Xu, Ping; Yong, Hai-Lin; Chen, Luo-Kan; Liu, Chang; Xiang, Tong; Yao, Xing-Can; Lu, He; Li, Zheng-Da; Liu, Nai-Le; Li, Li; Yang, Tao; Peng, Cheng-Zhi; Zhao, Bo; Chen, Yu-Ao; Pan, Jian-Wei

2017-10-01

Quantum repeaters play a significant role in achieving long-distance quantum communication. In the past decades, tremendous effort has been devoted towards constructing a quantum repeater. As one of the crucial elements, entanglement has been created in different memory systems via entanglement swapping. The realization of j -hierarchy entanglement swapping, i.e., connecting quantum memory and further extending the communication distance, is important for implementing a practical quantum repeater. Here, we report the first demonstration of a fault-tolerant two-hierarchy entanglement swapping with linear optics using parametric down-conversion sources. In the experiment, the dominant or most probable noise terms in the one-hierarchy entanglement swapping, which is on the same order of magnitude as the desired state and prevents further entanglement connections, are automatically washed out by a proper design of the detection setting, and the communication distance can be extended. Given suitable quantum memory, our techniques can be directly applied to implementing an atomic ensemble based quantum repeater, and are of significant importance in the scalable quantum information processing.

Two-Hierarchy Entanglement Swapping for a Linear Optical Quantum Repeater.

PubMed

Xu, Ping; Yong, Hai-Lin; Chen, Luo-Kan; Liu, Chang; Xiang, Tong; Yao, Xing-Can; Lu, He; Li, Zheng-Da; Liu, Nai-Le; Li, Li; Yang, Tao; Peng, Cheng-Zhi; Zhao, Bo; Chen, Yu-Ao; Pan, Jian-Wei

2017-10-27

Quantum repeaters play a significant role in achieving long-distance quantum communication. In the past decades, tremendous effort has been devoted towards constructing a quantum repeater. As one of the crucial elements, entanglement has been created in different memory systems via entanglement swapping. The realization of j-hierarchy entanglement swapping, i.e., connecting quantum memory and further extending the communication distance, is important for implementing a practical quantum repeater. Here, we report the first demonstration of a fault-tolerant two-hierarchy entanglement swapping with linear optics using parametric down-conversion sources. In the experiment, the dominant or most probable noise terms in the one-hierarchy entanglement swapping, which is on the same order of magnitude as the desired state and prevents further entanglement connections, are automatically washed out by a proper design of the detection setting, and the communication distance can be extended. Given suitable quantum memory, our techniques can be directly applied to implementing an atomic ensemble based quantum repeater, and are of significant importance in the scalable quantum information processing.

Multiple transcriptional regulatory domains in the human immunodeficiency virus type 1 long terminal repeat are involved in basal and E1A/E1B-induced promoter activity.

PubMed Central

Kliewer, S; Garcia, J; Pearson, L; Soultanakis, E; Dasgupta, A; Gaynor, R

1989-01-01

The human immunodeficiency virus (HIV) type 1 long terminal repeat (LTR) is the site of activation of the HIV tat protein. However, additional transactivators, such as the adenovirus E1A and herpesvirus ICPO proteins, have also been shown to be capable of activating the HIV LTR. Analysis of adenovirus mutants indicated that complete transactivation of the HIV LTR was dependent on both the E1A and E1B proteins. To determine which regions of the HIV LTR were important for complete E1A/E1B activation, a variety of oligonucleotide-directed mutations in HIV transcriptional regulatory domains were assayed both in vivo and in vitro. S1 nuclease analysis of RNA prepared after transfection of these HIV constructs into HeLa cells infected with wild-type adenovirus indicated that the enhancer, SP1, TATA, and a portion of the transactivation-responsive element were each required for complete E1A/E1B-mediated activation of the HIV LTR. These same promoter elements were required for both basal and E1A/E1B-induced levels of transcription in in vitro transcription reactions performed with cellular extracts prepared from cells infected with dl434, an E1A/E1B deletion mutant, or wild-type adenovirus. No mutations were found that reduced only E1A/E1B-induced expression without proportionally reducing basal levels of transcription, suggesting that E1A/E1B-mediated induction of the HIV LTR requires multiple promoter elements which are also required for basal transcriptional levels. Unlike activation by the tat protein, there was not a rigid dependence on maintenance of the transactivation-responsive stem base pairing for E1A/E1B-mediated activation either in vivo or in vitro, indicating that activation occurs by a mechanism distinct from that of tat induction. Images PMID:2529378

Effect of gender on fatigue and recovery following maximal intensity repeated sprint performance.

PubMed

Laurent, C M; Green, J M; Bishop, P A; Sjökvist, J; Schumacker, R E; Richardson, M T; Curtner-Smith, M

2010-09-01

This study investigated the effects of gender on repeated, maximal-intensity intermittent sprint exercise following variable day-to-day recovery periods. Sixteen volunteers (8 men, 8 women) performed four trials of high-intensity intermittent sprint exercise consisting of three bouts of eight 30 m sprints (total of 24 sprints). Following completion of the baseline trial, in repeated-measures design, participants were assigned, in counter-balanced order, variable recovery periods of 24, 48, and 72 h whereupon they repeated an identical exercise trial. Results from a series of 4 (trial) x 3 (bout) repeated measures ANOVAs revealed men produced significantly (P < 0.01) faster times throughout all bouts and trials of repeated sprint exercise. Additionally, women exhibited significantly lower (P < 0.05) blood lactate concentration and significantly lower (P < 0.05) decrement in performance, indicating increased resistance to fatigue during repeated exercise sessions. There were no significant differences (P > 0.05) between genders for heart rate or rating of perceived exertion during or following trials. There were no significant differences for overall sprint performance within either gender among trials. These results indicate men, while able to produce higher absolute power outputs (i.e., lower sprint time), demonstrate higher decrement scores within a trial compared to women, thus suggesting women may recover faster and fatigue less. Also, gender differences affecting recovery within in a trial were observed to be diminished between trials (i.e., day-to-day recovery) of maximal intermittent sprint work evidenced by the observed stability of performance between trials following various recovery durations.

RepeatsDB-lite: a web server for unit annotation of tandem repeat proteins.

PubMed

Hirsh, Layla; Paladin, Lisanna; Piovesan, Damiano; Tosatto, Silvio C E

2018-05-09

RepeatsDB-lite (http://protein.bio.unipd.it/repeatsdb-lite) is a web server for the prediction of repetitive structural elements and units in tandem repeat (TR) proteins. TRs are a widespread but poorly annotated class of non-globular proteins carrying heterogeneous functions. RepeatsDB-lite extends the prediction to all TR types and strongly improves the performance both in terms of computational time and accuracy over previous methods, with precision above 95% for solenoid structures. The algorithm exploits an improved TR unit library derived from the RepeatsDB database to perform an iterative structural search and assignment. The web interface provides tools for analyzing the evolutionary relationships between units and manually refine the prediction by changing unit positions and protein classification. An all-against-all structure-based sequence similarity matrix is calculated and visualized in real-time for every user edit. Reviewed predictions can be submitted to RepeatsDB for review and inclusion.

Deciding the liveness for a subclass of weighted Petri nets based on structurally circular wait

NASA Astrophysics Data System (ADS)

Liu, GuanJun; Chen, LiJing

2016-05-01

Weighted Petri nets as a kind of formal language are widely used to model and verify discrete event systems related to resource allocation like flexible manufacturing systems. System of Simple Sequential Processes with Multi-Resources (S3PMR, a subclass of weighted Petri nets and an important extension to the well-known System of Simple Sequential Processes with Resources, can model many discrete event systems in which (1) multiple processes may run in parallel and (2) each execution step of each process may use multiple units from multiple resource types. This paper gives a necessary and sufficient condition for the liveness of S3PMR. A new structural concept called Structurally Circular Wait (SCW) is proposed for S3PMR. Blocking Marking (BM) associated with an SCW is defined. It is proven that a marked S3PMR is live if and only if each SCW has no BM. We use an example of multi-processor system-on-chip to show that SCW and BM can precisely characterise the (partial) deadlocks for S3PMR. Simultaneously, two examples are used to show the advantages of SCW in preventing deadlocks of S3PMR. These results are significant for the further research on dealing with the deadlock problem.

The value of the repeated examination of BRAF V600E mutation status in diagnostics of papillary thyroid cancer.

PubMed

Beiša, Augustas; Beiša, Virgilijus; Stoškus, Mindaugas; Ostanevičiūtė, Elvyra; Griškevičius, Laimonas; Strupas, Kęstutis

2016-01-01

Nodular thyroid disease is one of the most frequently diagnosed pathologies of the adult population in iodine-deficient regions. Approximately 30% of thyroid aspirates are classified as nondiagnostic/unsatisfactory or indeterminate. However, patients with indeterminate cytology still undergo surgery. The object of this study was to determine the diagnostic value of re-examining the BRAF V600E mutation in papillary thyroid carcinoma patients. All patients underwent ultrasound guided fine-needle aspiration of a thyroid nodule. They were assigned to one of the four groups (indeterminate or positive for malignant cells) of the Bethesda System for Reporting Thyroid Cytopathology. Genetic investigation of the BRAF V600E mutation was performed for all of the fine-needle aspiration cytology specimens. All of the patients underwent surgery. Subsequently, histological investigation of the removed tissues was performed. Additional analysis of the BRAF V600E mutation from the histology specimen was then performed for the initially BRAF-negative cases. Two hundred and fourteen patients were involved in the study. One hundred and six (49.53%) patients were diagnosed with thyroid cancer. Of these 106 patients, 95 (89.62%) patients were diagnosed with papillary thyroid cancer. The BRAF V600E mutation was positive in 62 (65.26%) and negative in 33 (34.74%) histologically confirmed papillary thyroid cancer cases. After the genetic investigation, a total of 74 (77.89%) papillary thyroid cancer cases were positive for the BRAF V600E mutation and 21 (22.11%) were negative. Repeated examination of the BRAF V600E mutation status in the fine-needle aspiration may potentially increase the sensitivity of papillary thyroid cancer diagnostics.

BEHAVIORAL AND NEUROCHEMICAL CHANGES IN RATS DOSED REPEATEDLY WITH DIISOPROPYLFLUOROPHOSPHATE (DFP)

EPA Science Inventory

Behavioral effects of organophosphates (OPs) typically decrease with repeated exposure, despite persistence of OP-induced inhibition of acetylcholinesterase (AChE) and downregulation of muscarinic acetylcholine (ACh) receptors. o characterize this tolerance phenomenon, rats were ...

Highly diverse variable number tandem repeat loci in the E. coli O157:H7 and O55:H7 genomes for high-resolution molecular typing.

PubMed

Keys, C; Kemper, S; Keim, P

2005-01-01

Evaluation of the Escherichia coli genome for variable number tandem repeat (VNTR) loci in order to provide a subtyping tool with greater discrimination and more efficient capacity. Twenty-nine putative VNTR loci were identified from the E. coli genomic sequence. Their variability was validated by characterizing the number of repeats at each locus in a set of 56 E. coli O157:H7/HN and O55:H7 isolates. An optimized multiplex assay system was developed to facility high capacity analysis. Locus diversity values ranged from 0.23 to 0.95 while the number of alleles ranged from two to 29. This multiple-locus VNTR analysis (MLVA) data was used to describe genetic relationships among these isolates and was compared with PFGE (pulse field gel electrophoresis) data from a subset of the same strains. Genetic similarity values were highly correlated between the two approaches, through MLVA was capable of discrimination amongst closely related isolates when PFGE similar values were equal to 1.0. Highly variable VNTR loci exist in the E. coli O157:H7 genome and are excellent estimators of genetic relationships, in particular for closely related isolates. Escherichia coli O157:H7 MLVA offers a complimentary analysis to the more traditional PFGE approach. Application of MLVA to an outbreak cluster could generate superior molecular epidemiology and result in a more effective public health response.

Sex differences in acute translational repressor 4E-BP1 activity and sprint performance in response to repeated-sprint exercise in team sport athletes.

PubMed

Dent, Jessica R; Edge, Johann A; Hawke, Emma; McMahon, Christopher; Mündel, Toby

2015-11-01

The physiological requirements underlying soccer-specific exercise are incomplete and sex-based comparisons are sparse. The aim of this study was to determine the effects of a repeated-sprint protocol on the translational repressor 4E-BP1 and sprint performance in male and female soccer players. Cross-over design involving eight female and seven male university soccer players. Participants performed four bouts of 6 × 30-m maximal sprints spread equally over 40 min. Heart rate, sprint time and sprint decrement were measured for each sprint and during the course of each bout. Venous blood samples and muscle biopsies from the vastus lateralis were taken at rest, at 15 min and 2h post-exercise. While males maintained a faster mean sprint time for each bout (P < 0.05) females exhibited a greater decrement in sprint performance for each bout (P < 0.05), indicating a superior maintenance of sprint performance in males, with no sex differences for heart rate or lactate. Muscle analyses revealed sex differences in resting total (P < 0.05) and phosphorylated (P < 0.05) 4E-BP1 Thr37/46, and 15 min post-exercise the 4E-BP1 Thr37/46 ratio decreased below resting levels in males only (P < 0.05), indicative of a decreased translation initiation following repeated sprints. We show that females have a larger sprint decrement indicating that males have a superior ability to recover sprint performance. Sex differences in resting 4E-BP1 Thr37/46 suggest diversity in the training-induced phenotype of the muscle of males and females competing in equivalent levels of team-sport competition. Copyright © 2014 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Sequence repeats and protein structure

NASA Astrophysics Data System (ADS)

Hoang, Trinh X.; Trovato, Antonio; Seno, Flavio; Banavar, Jayanth R.; Maritan, Amos

2012-11-01

Repeats are frequently found in known protein sequences. The level of sequence conservation in tandem repeats correlates with their propensities to be intrinsically disordered. We employ a coarse-grained model of a protein with a two-letter amino acid alphabet, hydrophobic (H) and polar (P), to examine the sequence-structure relationship in the realm of repeated sequences. A fraction of repeated sequences comprises a distinct class of bad folders, whose folding temperatures are much lower than those of random sequences. Imperfection in sequence repetition improves the folding properties of the bad folders while deteriorating those of the good folders. Our results may explain why nature has utilized repeated sequences for their versatility and especially to design functional proteins that are intrinsically unstructured at physiological temperatures.

A new estimator for VLBI baseline length repeatability

NASA Astrophysics Data System (ADS)

Titov, O.

2009-11-01

The goal of this paper is to introduce a more effective technique to approximate for the “repeatability-baseline length” relationship that is used to evaluate the quality of geodetic VLBI results. Traditionally, this relationship is approximated by a quadratic function of baseline length over all baselines. The new model incorporates the mean number of observed group delays of the reference radio sources (i.e. estimated as global parameters) used in the estimation of each baseline. It is shown that the new method provides a better approximation of the “repeatability-baseline length” relationship than the traditional model. Further development of the new approach comes down to modeling the repeatability as a function of two parameters: baseline length and baseline slewing rate. Within the framework of this new approach the station vertical and horizontal uncertainties can be treated as a function of baseline length. While the previous relationship indicated that the station vertical uncertainties are generally 4-5 times larger than the horizontal uncertainties, the vertical uncertainties as determined by the new method are only larger by a factor of 1.44 over all baseline lengths.

Repeat Customer Success in Extension

ERIC Educational Resources Information Center

Bess, Melissa M.; Traub, Sarah M.

2013-01-01

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

Repeated ischaemic preconditioning: a novel therapeutic intervention and potential underlying mechanisms.

PubMed

Thijssen, Dick H J; Maxwell, Joseph; Green, Daniel J; Cable, N Timothy; Jones, Helen

2016-06-01

What is the topic of this review? This review discusses the effects of repeated exposure of tissue to ischaemic preconditioning on cardiovascular function, the attendant adaptations and their potential clinical relevance. What advances does it highlight? We discuss the effects of episodic exposure to ischaemic preconditioning to prevent and/or attenuate ischaemic injury and summarize evidence pertaining to improvements in cardiovascular function and structure. Discussion is provided regarding the potential mechanisms that contribute to both local and systemic adaptation. Findings suggest that clinical benefits result from both the prevention of ischaemic events and the attenuation of their consequences. Ischaemic preconditioning (IPC) refers to the phenomenon whereby short periods of cyclical tissue ischaemia confer subsequent protection against ischaemia-induced injury. As a consequence, IPC can ameliorate the myocardial damage following infarction and can reduce infarct size. The ability of IPC to confer remote protection makes IPC a potentially feasible cardioprotective strategy. In this review, we discuss the concept that repeated exposure of tissue to IPC may increase the 'dose' of protection and subsequently lead to enhanced protection against ischaemia-induced myocardial injury. This may be relevant for clinical populations, who demonstrate attenuated efficacy of IPC to prevent or attenuate ischaemic injury (and therefore myocardial infarct size). Furthermore, episodic IPC facilitates repeated exposure to local (e.g. shear stress) and systemic stimuli (e.g. hormones, cytokines, blood-borne substances), which may induce improvement in vascular function and health. Such adaptation may contribute to prevention of cardio- and cerebrovascular events. The clinical benefits of repeated IPC may, therefore, result from both the prevention of ischaemic events and the attenuation of their consequences. We provide an overview of the literature pertaining to the impact

Repeat migration and disappointment.

PubMed

Grant, E K; Vanderkamp, J

1986-01-01

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

Rf8-mediated T-urf13 transcript accumulation coincides with a pentatricopeptide repeat cluster on maize chromosome 2L

USDA-ARS?s Scientific Manuscript database

Cytoplasmic male sterility (CMS) is a maternally inherited inability to produce functional pollen. In T-cytoplasm maize, CMS results from the action of the URF13 mitochondrial pore-forming protein, encoded by the unique T-urf13 mitochondrial gene. Full or partial restoration of fertility to T-cyto...

Antibody classes & subclasses induced by mucosal immunization of mice with Streptococcus pyogenes M6 protein & oligodeoxynucleotides containing CpG motifs.

PubMed

Teloni, R; von Hunolstein, C; Mariotti, S; Donati, S; Orefici, G; Nisini, R

2004-05-01

Type-specific antibodies against M protein are critical for human protection as they enhance phagocytosis and are protective. An ideal vaccine for the protection against Streptococcus pyogenes would warrant mucosal immunity, but mucosally administered M-protein has been shown to be poorly immunogenic in animals. We used a recombinant M type 6 protein to immunize mice in the presence of synthetic oligodeoxynucleotides containing CpG motifs (immunostimulatory sequences: ISS) or cholera toxin (CT) to explore its possible usage in a mucosal vaccine. Mice were immunized by intranasal (in) or intradermal (id) administration with four doses at weekly intervals of M6-protein (10 microg/mouse) with or without adjuvant (ISS, 10 microg/mouse or CT, 0,5 microg/mouse). M6 specific antibodies were measured by enzyme linked immunosorbent assay using class and subclass specific monoclonal antibodies. The use of ISS induced an impressive anti M-protein serum IgG response but when id administered was not detectable in the absence of adjuvant. When used in, M-protein in the presence of both ISS and CT induced anti M-protein IgA in the bronchoalveolar lavage, as well as specific IgG in the serum. IgG were able to react with serotype M6 strains of S. pyogenes. The level of antibodies obtained by immunizing mice in with M-protein and CT was higher in comparison to M-protein and ISS. The analysis of anti-M protein specific IgG subclasses showed high levels of IgG1, IgG2a and IgG2b, and low levels of IgG3 when ISS were used as adjuvant. Thus, in the presence of ISS, the ratio IgG2a/IgG1 and (IgG2a+IgG3)/IgG1 >1 indicated a type 1-like response obtained both in mucosally or systemically vaccinated mice. Our study offers a reproducible model of anti-M protein vaccination that could be applied to test new antigenic formulations to induce an anti-group A Streptococcus (GAS) vaccination suitable for protection against the different diseases caused by this bacterium.

Relationship of baseline HDL subclasses, small dense LDL and LDL triglyceride to cardiovascular events in the AIM-HIGH clinical trial.

PubMed

Albers, John J; Slee, April; Fleg, Jerome L; O'Brien, Kevin D; Marcovina, Santica M

2016-08-01

Previous results of the AIM-HIGH trial showed that baseline levels of the conventional lipid parameters were not predictive of future cardiovascular (CV) outcomes. The aims of this secondary analysis were to examine the levels of cholesterol in high density lipoprotein (HDL) subclasses (HDL2-C and HDL3-C), small dense low density lipoprotein (sdLDL-C), and LDL triglyceride (LDL-TG) at baseline, as well as the relationship between these levels and CV outcomes. Individuals with CV disease and low baseline HDL-C levels were randomized to simvastatin plus placebo or simvastatin plus extended release niacin (ERN), 1500 to 2000 mg/day, with ezetimibe added as needed in both groups to maintain an on-treatment LDL-C in the range of 40-80 mg/dL. The primary composite endpoint was death from coronary disease, nonfatal myocardial infarction, ischemic stroke, hospitalization for acute coronary syndrome, or symptom-driven coronary or cerebrovascular revascularization. HDL-C, HDL3-C, sdLDL-C and LDL-TG were measured at baseline by detergent-based homogeneous assays. HDL2-C was computed by the difference between HDL-C and HDL3-C. Analyses were performed on 3094 study participants who were already on statin therapy prior to enrollment in the trial. Independent contributions of lipoprotein fractions to CV events were determined by Cox proportional hazards modeling. Baseline HDL3-C was protective against CV events (HR: 0.84, p = 0.043) while HDL-C, HDL2-C, sdLDL-C and LDL-TG were not event-related (HR: 0.96, p = 0.369; HR: 1.07, p = 0.373; HR: 1.05, p = 0.492; HR: 1.03, p = 0.554, respectively). The results of this secondary analysis of the AIM-HIGH Study indicate that levels of HDL3-C, but not other lipoprotein fractions, are predictive of CV events, suggesting that the HDL3 subclass may be primarily responsible for the inverse association of HDL-C and CV disease. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Cytology of the minor-vein phloem in 320 species from the subclass Asteridae suggests a high diversity of phloem-loading modes†

PubMed Central

Batashev, Denis R.; Pakhomova, Marina V.; Razumovskaya, Anna V.; Voitsekhovskaja, Olga V.; Gamalei, Yuri V.

2013-01-01

The discovery of abundant plasmodesmata at the bundle sheath/phloem interface in Oleaceae (Gamalei, 1974) and Cucurbitaceae (Turgeon et al., 1975) raised the questions as to whether these plasmodesmata are functional in phloem loading and how widespread symplasmic loading would be. Analysis of over 800 dicot species allowed the definition of “open” and “closed” types of the minor vein phloem depending on the abundance of plasmodesmata between companion cells and bundle sheath (Gamalei, 1989, 1990). These types corresponded to potential symplasmic and apoplasmic phloem loaders, respectively; however, this definition covered a spectrum of diverse structures of phloem endings. Here, a review of detailed cytological analyses of minor veins in 320 species from the subclass Asteridae is presented, including data on companion cell types and their combinations which have not been reported previously. The percentage of Asteridae species with “open” minor vein cytology which also contain sieve-element-companion cell complexes with “closed” cytology, i.e., that show specialization for both symplasmic and apoplasmic phloem loading, was determined. Along with recent data confirming the dissimilar functional specialization of structurally different parts of minor vein phloem in the stachyose-translocating species Alonsoa meridionalis (Voitsekhovskaja et al., 2009), these findings suggest that apoplasmic loading is indispensable in a large group of species previously classified as putative symplasmic loaders. Altogether, this study provides formal classifications of companion cells and of minor veins, respectively, in 24 families of the Asteridae based on their structural features, opening the way to a close investigation of the relationship between structure and function in phloem loading. PMID:23970890

Origin of a folded repeat protein from an intrinsically disordered ancestor

PubMed Central

Zhu, Hongbo; Sepulveda, Edgardo; Hartmann, Marcus D; Kogenaru, Manjunatha; Ursinus, Astrid; Sulz, Eva; Albrecht, Reinhard; Coles, Murray; Martin, Jörg; Lupas, Andrei N

2016-01-01

Repetitive proteins are thought to have arisen through the amplification of subdomain-sized peptides. Many of these originated in a non-repetitive context as cofactors of RNA-based replication and catalysis, and required the RNA to assume their active conformation. In search of the origins of one of the most widespread repeat protein families, the tetratricopeptide repeat (TPR), we identified several potential homologs of its repeated helical hairpin in non-repetitive proteins, including the putatively ancient ribosomal protein S20 (RPS20), which only becomes structured in the context of the ribosome. We evaluated the ability of the RPS20 hairpin to form a TPR fold by amplification and obtained structures identical to natural TPRs for variants with 2–5 point mutations per repeat. The mutations were neutral in the parent organism, suggesting that they could have been sampled in the course of evolution. TPRs could thus have plausibly arisen by amplification from an ancestral helical hairpin. DOI: http://dx.doi.org/10.7554/eLife.16761.001 PMID:27623012

Repeated partial endoscopic resections as treatment for two patients with inoperable tracheal tumours

PubMed Central

Nakratzas, G.; Wagenaar, J. P. M.; Reintjes, M.; Scheffer, E.; Swierenga, J.

1974-01-01

Nakratzas, G., Wagenaar, J. P. M., Reintjes, M., Scheffer, E., and Swierenga, J. (1974).Thorax, 29, 125-131. Repeated partial endoscopic resections as treatment for two patients with inoperable tracheal tumours. Two cases of tracheal tumour are described, one a carcinoid and the other an adenoid cystic carcinoma (cylindroma). Both patients were treated by repeated partial bronchoscopic resections. The patients are in good health nine and three years respectively after treatment. Images PMID:4363463

Single molecule study of the intrinsically disordered FG-repeat nucleoporin 153.

PubMed

Milles, Sigrid; Lemke, Edward A

2011-10-05

Nucleoporins (Nups), which are intrinsically disordered, form a selectivity filter inside the nuclear pore complex, taking a central role in the vital nucleocytoplasmic transport mechanism. These Nups display a complex and nonrandom amino-acid architecture of phenylalanine glycine (FG)-repeat clusters and intra-FG linkers. How such heterogeneous sequence composition relates to function and could give rise to a transport mechanism is still unclear. Here we describe a combined chemical biology and single-molecule fluorescence approach to study the large human Nup153 FG-domain. In order to obtain insights into the properties of this domain beyond the average behavior, we probed the end-to-end distance (R(E)) of several ∼50-residues long FG-repeat clusters in the context of the whole protein domain. Despite the sequence heterogeneity of these FG-clusters, we detected a reoccurring and consistent compaction from a relaxed coil behavior under denaturing conditions (R(E)/R(E,RC) = 0.99 ± 0.15 with R(E,RC) corresponding to ideal relaxed coil behavior) to a collapsed state under native conditions (R(E)/R(E,RC) = 0.79 ± 0.09). We then analyzed the properties of this protein on the supramolecular level, and determined that this human FG-domain was in fact able to form a hydrogel with physiological permeability barrier properties. Copyright © 2011 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Expanded complexity of unstable repeat diseases

PubMed Central

Polak, Urszula; McIvor, Elizabeth; Dent, Sharon Y.R.; Wells, Robert D.; Napierala, Marek

2015-01-01

Unstable Repeat Diseases (URDs) share a common mutational phenomenon of changes in the copy number of short, tandemly repeated DNA sequences. More than 20 human neurological diseases are caused by instability, predominantly expansion, of microsatellite sequences. Changes in the repeat size initiate a cascade of pathological processes, frequently characteristic of a unique disease or a small subgroup of the URDs. Understanding of both the mechanism of repeat instability and molecular consequences of the repeat expansions is critical to developing successful therapies for these diseases. Recent technological breakthroughs in whole genome, transcriptome and proteome analyses will almost certainly lead to new discoveries regarding the mechanisms of repeat instability, the pathogenesis of URDs, and will facilitate development of novel therapeutic approaches. The aim of this review is to give a general overview of unstable repeats diseases, highlight the complexities of these diseases, and feature the emerging discoveries in the field. PMID:23233240

Fostering repeat donations in Ghana.

PubMed

Owusu-Ofori, S; Asenso-Mensah, K; Boateng, P; Sarkodie, F; Allain, J-P

2010-01-01

Most African countries are challenged in recruiting and retaining voluntary blood donors by cost and other complexities and in establishing and implementing national blood policies. The availability of replacement donors who are a cheaper source of blood has not enhanced repeat voluntary donor initiatives. An overview of activities for recruiting and retaining voluntary blood donors was carried out. Donor records from mobile sessions were reviewed from 2002 to 2008. A total of 71,701 blood donations; 45,515 (63.5%) being voluntary donations with 11,680 (25%) repeat donations were collected during the study period. Donations from schools and colleges contributed a steady 60% of total voluntary whilst radio station blood drives increased contribution from 10 to 27%. Though Muslim population is less than 20%, blood collection was above the 30-donation cost-effectiveness threshold with a repeat donation trend reaching 60%. In contrast Christian worshippers provided <25 unit/session and 30% repeat donations. Repeat donation trends amongst school donors and radio blood drives were 20% and 70% respectively. Repeat donations rates have been variable amongst different blood donor groups in Kumasi, Ghana. The impact of community leaders in propagating altruism cannot be overemphasized. Programs aiming at motivating replacement donors to be repeat donors should be developed and assessed. Copyright 2009 The International Association for Biologicals. All rights reserved.

Multiple subclasses of Purkinje cells in the primate floccular complex provide similar signals to guide learning in the vestibulo-ocular reflex

NASA Technical Reports Server (NTRS)

Raymond, J. L.; Lisberger, S. G.

1997-01-01

The neural "learning rules" governing the induction of plasticity in the cerebellum were analyzed by recording the patterns of neural activity in awake, behaving animals during stimuli that induce a form of cerebellum-dependent learning. We recorded the simple- and complex-spike responses of a broad sample of Purkinje cells in the floccular complex during a number of stimulus conditions that induce motor learning in the vestibulo-ocular reflex (VOR). Each subclass of Purkinje cells carried essentially the same information about required changes in the gain of the VOR. The correlation of simple-spike activity in Purkinje cells with activity in vestibular pathways could guide learning during low-frequency but not high-frequency stimuli. Climbing fiber activity could guide learning during all stimuli tested but only if compared with the activity present approximately 100 msec earlier in either vestibular pathways or Purkinje cells.

[Color stability of porcelain-fused-to-titanium restorations after repeated firings].

PubMed

Wu, Xiao-min; Zhou, Zheng

2004-08-01

To study the effect of repeated firings on color of porcelain-fused-to-titanium restorations. Twenty standard porcelain-fused-to-titanium specimens were made with Dentsply DETREY TiBond C3 and Dentaurum rematitan Til. Then they were fired 1, 2, 4, 7, and 10 times. Color measurement was done after each firing. Most of the color parameters had no significant difference after firing except for a* and Hab. All the color difference among groups were smaller than 1.0 (deltaE < 1.0). Repeated firings will not affect the color stability of porcelain-fused-to-titanium restorations.

Evolution of Protein Domain Repeats in Metazoa

PubMed Central

Schüler, Andreas; Bornberg-Bauer, Erich

2016-01-01

Repeats are ubiquitous elements of proteins and they play important roles for cellular function and during evolution. Repeats are, however, also notoriously difficult to capture computationally and large scale studies so far had difficulties in linking genetic causes, structural properties and evolutionary trajectories of protein repeats. Here we apply recently developed methods for repeat detection and analysis to a large dataset comprising over hundred metazoan genomes. We find that repeats in larger protein families experience generally very few insertions or deletions (indels) of repeat units but there is also a significant fraction of noteworthy volatile outliers with very high indel rates. Analysis of structural data indicates that repeats with an open structure and independently folding units are more volatile and more likely to be intrinsically disordered. Such disordered repeats are also significantly enriched in sites with a high functional potential such as linear motifs. Furthermore, the most volatile repeats have a high sequence similarity between their units. Since many volatile repeats also show signs of recombination, we conclude they are often shaped by concerted evolution. Intriguingly, many of these conserved yet volatile repeats are involved in host-pathogen interactions where they might foster fast but subtle adaptation in biological arms races. Key Words: protein evolution, domain rearrangements, protein repeats, concerted evolution. PMID:27671125

Joint modelling of repeated measurement and time-to-event data: an introductory tutorial.

PubMed

Asar, Özgür; Ritchie, James; Kalra, Philip A; Diggle, Peter J

2015-02-01

The term 'joint modelling' is used in the statistical literature to refer to methods for simultaneously analysing longitudinal measurement outcomes, also called repeated measurement data, and time-to-event outcomes, also called survival data. A typical example from nephrology is a study in which the data from each participant consist of repeated estimated glomerular filtration rate (eGFR) measurements and time to initiation of renal replacement therapy (RRT). Joint models typically combine linear mixed effects models for repeated measurements and Cox models for censored survival outcomes. Our aim in this paper is to present an introductory tutorial on joint modelling methods, with a case study in nephrology. We describe the development of the joint modelling framework and compare the results with those obtained by the more widely used approaches of conducting separate analyses of the repeated measurements and survival times based on a linear mixed effects model and a Cox model, respectively. Our case study concerns a data set from the Chronic Renal Insufficiency Standards Implementation Study (CRISIS). We also provide details of our open-source software implementation to allow others to replicate and/or modify our analysis. The results for the conventional linear mixed effects model and the longitudinal component of the joint models were found to be similar. However, there were considerable differences between the results for the Cox model with time-varying covariate and the time-to-event component of the joint model. For example, the relationship between kidney function as measured by eGFR and the hazard for initiation of RRT was significantly underestimated by the Cox model that treats eGFR as a time-varying covariate, because the Cox model does not take measurement error in eGFR into account. Joint models should be preferred for simultaneous analyses of repeated measurement and survival data, especially when the former is measured with error and the association

Repeatability in Color Measurements of a Spectrophotometer using Different Positioning Devices.

PubMed

Hemming, Michael; Kwon, So Ran; Qian, Fang

2015-12-01

This study aimed to evaluate the repeatability of color measurements of an intraoral spectrophotometer with the use of three different methods by two operators. A total of 60 teeth were obtained, comprising 30 human maxillary teeth [central incisors (n = 10); canines (n = 10); molars (n = 10)] and 30 artificial teeth [lateral incisors (n = 10); premolar (n = 20)]. Multiple repeated color measurements were obtained from each tooth using three measuring methods by each of the two operators. Five typodonts with alternating artificial and human teeth were made. Measurements were taken by two operators with the Vita EasyShade spectrophotometer using the custom tray (CT), custom jig (CJ) and free hand (FH) method, twice, at an interval of 2 to 7 days. Friedman test was used to detect difference among the three color measuring methods. Post hoc Wilcoxon signed-rank test with Bonferroni correction applied was used for pair-wise comparison of color measurements among the three methods. Additionally, a paired-sample t-test was used to assess a significant difference between the two duplicated measurements made on the same tooth by the same operator for each color parameter and measuring method. For operator A, mean (SD) overall color change-ΔE* (SD) perceived for FH, CT and CJ were 2.21(2.00), 2.39 (1.58) and 2.86 (1.92), respectively. There was statistically significant difference in perceived ΔE* in FH vs CJ (p = 0.0107). However, there were no significant differences between FH and CT (p = 0.2829) or between CT and CJ (p = 0.1159). For operator B mean ΔE* (SD) for FH, CT and CJ were 3.24 (3.46), 1.95 (1.19) and 2.45 (1.56), respectively. There was a significant difference between FH and CT (p = 0.0031). However, there were no statistically significant differences in ΔE* in FH vs CJ (p = 0.3696) or CT vs CJ (p = 0.0809). The repeatability of color measurements was different among the three measuring methods by operators. Overall, the CT method worked well for both

Topological characteristics of helical repeat proteins.

PubMed

Groves, M R; Barford, D

1999-06-01

The recent elucidation of protein structures based upon repeating amino acid motifs, including the armadillo motif, the HEAT motif and tetratricopeptide repeats, reveals that they belong to the class of helical repeat proteins. These proteins share the common property of being assembled from tandem repeats of an alpha-helical structural unit, creating extended superhelical structures that are ideally suited to create a protein recognition interface.

SSRscanner: a program for reporting distribution and exact location of simple sequence repeats.

PubMed

Anwar, Tamanna; Khan, Asad U

2006-02-20

Simple sequence repeats (SSRs) have become important molecular markers for a broad range of applications, such as genome mapping and characterization, phenotype mapping, marker assisted selection of crop plants and a range of molecular ecology and diversity studies. These repeated DNA sequences are found in both prokaryotes and eukaryotes. They are distributed almost at random throughout the genome, ranging from mononucleotide to trinucleotide repeats. They are also found at longer lengths (> 6 repeating units) of tracts. Most of the computer programs that find SSRs do not report its exact position. A computer program SSRscanner was written to find out distribution, frequency and exact location of each SSR in the genome. SSRscanner is user friendly. It can search repeats of any length and produce outputs with their exact position on chromosome and their frequency of occurrence in the sequence. This program has been written in PERL and is freely available for non-commercial users by request from the authors. Please contact the authors by E-mail: huzzi99@hotmail.com.

SSRscanner: a program for reporting distribution and exact location of simple sequence repeats

PubMed Central

Anwar, Tamanna; Khan, Asad U

2006-01-01

Simple sequence repeats (SSRs) have become important molecular markers for a broad range of applications, such as genome mapping and characterization, phenotype mapping, marker assisted selection of crop plants and a range of molecular ecology and diversity studies. These repeated DNA sequences are found in both prokaryotes and eukaryotes. They are distributed almost at random throughout the genome, ranging from mononucleotide to trinucleotide repeats. They are also found at longer lengths (> 6 repeating units) of tracts. Most of the computer programs that find SSRs do not report its exact position. A computer program SSRscanner was written to find out distribution, frequency and exact location of each SSR in the genome. SSRscanner is user friendly. It can search repeats of any length and produce outputs with their exact position on chromosome and their frequency of occurrence in the sequence. Availability This program has been written in PERL and is freely available for non-commercial users by request from the authors. Please contact the authors by E-mail: huzzi99@hotmail.com PMID:17597863

Supplemented vaccination with tandem repeat M2e virus-like particles enhances protection against homologous and heterologous HPAI H5 viruses in chickens.

PubMed

Song, Byung-Min; Kang, Hyun-Mi; Lee, Eun-Kyoung; Jung, Suk Chan; Kim, Min-Chul; Lee, Yu-Na; Kang, Sang-Moo; Lee, Youn-Jeong

2016-01-27

Highly pathogenic avian influenza (HPAI) H5 viruses derived from A/Goose/Guangdong/1/96 have been continuously circulating globally, severely affecting the public health and poultry industries. The matrix 2 protein ectodomain (M2e) is considered a promising candidate for a universal cross-protective influenza vaccine that provides more effective control over HPAI H5 viruses harboring variant hemagglutinin (HA)-antigens. Here, we evaluated the protective efficacy of a tandem repeat construct of heterologous M2e presented on virus-like particles (M2e5x VLPs) either alone or as a supplement against HPAI H5 viruses in a chicken model. Chickens immunized with M2e5x VLPs alone induced M2e-specific antibodies but were not protected against HPAI H5. The homo- and cross-protective efficacy of M2e5x VLP-supplemented vaccination of chickens was also examined. Importantly, supplementation with M2e5x VLPs induced significantly higher levels of antibodies specific for M2e and different viruses as well as provided improved protection against homologous and heterologous HPAI H5 viruses. Considering the limited efficacy of inactivated vaccines, supplement vaccination with M2e5x VLPs may be an effective measure for preventing outbreaks of HPAI viruses that have the ability to constantly change their antigenic properties in poultry. Copyright © 2015 Elsevier Ltd. All rights reserved.

Repeatability of in vitro measurements of the ultraviolet protection factor (UPF) by spectrophotometry with automatic sampling.

PubMed

Hoffmann, K; Kesners, P; Bader, A; Avermaete, A; Altmeyer, P; Gambichler, T

2001-11-01

Spectrophotometric assessment (in vitro) is the most established method for determining the ultraviolet protection factor (UPF) of textiles. Apart from stringent requirements for measurement precision, practical methods are required for the routine determination of the UPF. We report here spectrophotometric measurements of textiles using a newly developed autosampler. Measurement precision was evaluated under repeatable conditions. Fifteen different textiles were spectrophotometrically assessed for the determination of the UPF. Sample handling inside the spectrophotometer was performed with a computer-controlled sampling device, capable of loading and unloading a textile sample from a magazine as well as rotating the sample perpendicular to the spectrometer beam. In order to evaluate the repeatability of measurements, one sample of each textile was assessed eight times under the same conditions in the same laboratory. A mean percentage of the standard error of 1% [E(UPF)] was calculated for the UPF measurements. For UPFs >30, a significantly higher E(UPF) was found (r=0.78; P<0.001). E(UV) (3.9%) of ultraviolet A (UVA) transmission differed significantly from E(UV) (1.1 %) of ultraviolet B (UVB) transmission (P<0.05). Though a slight decrease of repeatability was observed for UVA transmission measurements and UPFs higher than 30, our data indicate a high measurement precision under repeatable conditions. In conclusion, spectrophotometric measurements of textiles with the aid of the autosampler presented have been shown to be highly practical, time saving and precise.

Repeated imitation makes human vocalizations more word-like.

PubMed

Edmiston, Pierce; Perlman, Marcus; Lupyan, Gary

2018-03-14

People have long pondered the evolution of language and the origin of words. Here, we investigate how conventional spoken words might emerge from imitations of environmental sounds. Does the repeated imitation of an environmental sound gradually give rise to more word-like forms? In what ways do these forms resemble the original sounds that motivated them (i.e. exhibit iconicity)? Participants played a version of the children's game 'Telephone'. The first generation of participants imitated recognizable environmental sounds (e.g. glass breaking, water splashing). Subsequent generations imitated the previous generation of imitations for a maximum of eight generations. The results showed that the imitations became more stable and word-like, and later imitations were easier to learn as category labels. At the same time, even after eight generations, both spoken imitations and their written transcriptions could be matched above chance to the category of environmental sound that motivated them. These results show how repeated imitation can create progressively more word-like forms while continuing to retain a resemblance to the original sound that motivated them, and speak to the possible role of human vocal imitation in explaining the origins of at least some spoken words. © 2018 The Author(s).

Fox gene loci in Takifugu rubripes and Tetraodon nigroviridis genomes and comparison with those of medaka and zebrafish genomes.

PubMed

Shen, Xueyan; Cui, Jianzhou; Gong, Qingli

2011-12-01

Members of the Fox gene family of transcriptional regulators are essential for animal development and have been extensively studied in vertebrates. The mouse and human genomes contain at least 40 FOX genes which are divided into 19 subclasses based on the sequence similarity of the highly conserved forkhead domain. Using the genome sequence of the Takifugu rubripes and Tetraodon nigroviridis , we examined the genomic complement of fox genes in these organisms to gain insight into the evolutionary relationship of this gene family. We identified 53 fox genes in Tetraodon nigroviridis and Takifugu rubripes genome by searching the forkhead domain. These genes are divided into 18 subclasses as follows: 8 fox genes in subclass O; 6 in subclass P ; 4 in subclasses D, J, and N; 3 in subclasses A, B, C, E, F, and I; 2 in subclasses K, L, and Q; and 1 in subclasses G, H, M, and R. Together with the forkhead domain sequences of human, chicken, frog, zebrafish, medaka, and Caenorhabditis elegans, the phylogenetic relationship of the fox genes in Takifugu rubripes and Tetraodon nigroviridis were analyzed and compared. The genes structure, general features, and the three-dimensional model of these genes were also discussed.

Repeated nightmares

MedlinePlus

Nightmares - repeated; Dream anxiety disorder ... Arnulf I, Nightmares and dream disturbances. In: Kryger M, Roth T, Dement WC, eds. Principles and Practice of Sleep Medicine . 6th ed. Philadelphia, PA: Elsevier; ...

Yeast eIF4B binds to the head of the 40S ribosomal subunit and promotes mRNA recruitment through its N-terminal and internal repeat domains.

PubMed

Walker, Sarah E; Zhou, Fujun; Mitchell, Sarah F; Larson, Victoria S; Valasek, Leos; Hinnebusch, Alan G; Lorsch, Jon R

2013-02-01

Eukaryotic translation initiation factor (eIF)4B stimulates recruitment of mRNA to the 43S ribosomal pre-initiation complex (PIC). Yeast eIF4B (yeIF4B), shown previously to bind single-stranded (ss) RNA, consists of an N-terminal domain (NTD), predicted to be unstructured in solution; an RNA-recognition motif (RRM); an unusual domain comprised of seven imperfect repeats of 26 amino acids; and a C-terminal domain. Although the mechanism of yeIF4B action has remained obscure, most models have suggested central roles for its RRM and ssRNA-binding activity. We have dissected the functions of yeIF4B's domains and show that the RRM and its ssRNA-binding activity are dispensable in vitro and in vivo. Instead, our data indicate that the 7-repeats and NTD are the most critical domains, which mediate binding of yeIF4B to the head of the 40S ribosomal subunit via interaction with Rps20. This interaction induces structural changes in the ribosome's mRNA entry channel that could facilitate mRNA loading. We also show that yeIF4B strongly promotes productive interaction of eIF4A with the 43S•mRNA PIC in a manner required for efficient mRNA recruitment.

Yeast eIF4B binds to the head of the 40S ribosomal subunit and promotes mRNA recruitment through its N-terminal and internal repeat domains

PubMed Central

Walker, Sarah E.; Zhou, Fujun; Mitchell, Sarah F.; Larson, Victoria S.; Valasek, Leos; Hinnebusch, Alan G.; Lorsch, Jon R.

2013-01-01

Eukaryotic translation initiation factor (eIF)4B stimulates recruitment of mRNA to the 43S ribosomal pre-initiation complex (PIC). Yeast eIF4B (yeIF4B), shown previously to bind single-stranded (ss) RNA, consists of an N-terminal domain (NTD), predicted to be unstructured in solution; an RNA-recognition motif (RRM); an unusual domain comprised of seven imperfect repeats of 26 amino acids; and a C-terminal domain. Although the mechanism of yeIF4B action has remained obscure, most models have suggested central roles for its RRM and ssRNA-binding activity. We have dissected the functions of yeIF4B’s domains and show that the RRM and its ssRNA-binding activity are dispensable in vitro and in vivo. Instead, our data indicate that the 7-repeats and NTD are the most critical domains, which mediate binding of yeIF4B to the head of the 40S ribosomal subunit via interaction with Rps20. This interaction induces structural changes in the ribosome’s mRNA entry channel that could facilitate mRNA loading. We also show that yeIF4B strongly promotes productive interaction of eIF4A with the 43S•mRNA PIC in a manner required for efficient mRNA recruitment. PMID:23236192

Phenotypic characterization of individuals with 30-40 CAG repeats in the Huntington disease (HD) gene reveals HD cases with 36 repeats and apparently normal elderly individuals with 36-39 repeats

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

Rubinsztein, D.C.; Leggo, J.; Whittaker, J.L.

1996-07-01

Abnormal CAG expansions in the IT-15 gene are associated with Huntington disease (HD). In the diagnostic setting it is necessary to define the limits of the CAG size ranges on normal and HD-associated chromosomes. Most large analyses that defined the limits of the normal and pathological size ranges employed PCR assays, which included the CAG repeats and a CCG repeat tract that was thought to be invariant. Many of these experiments found an overlap between the normal and disease size ranges. Subsequent findings that the CCG repeats vary by 9 trinucleotide lengths suggested that the limits of the normal andmore » disease size ranges should be reevaluated with assays that exclude the CCG polymorphism. Since patients with between 30 and 40 repeats are rare, a consortium was assembled to collect such individuals. All 178 samples were reanalyzed in Cambridge by using assays specific for the CAG repeats. We have optimized methods for reliable sizing of CAG repeats and show cases that demonstrate the dangers of using PCR assays that include both the CAG and CCG polymorphisms. Seven HD patients had 36 repeats, which confirms that this allele is associated with disease. Individuals without apparent symptoms or signs of HD were found at 36 repeats (aged 74, 78, 79, and 87 years), 37 repeats (aged 69 years), 38 repeats (aged 69 and 90 years), and 39 repeats (aged 67, 90, and 95 years). The detailed case histories of an exceptional case from this series will be presented: a 95-year-old man with 39 repeats who did not have classical features of HD. The apparently healthy survival into old age of some individuals with 36-39 repeats suggests that the HD mutation may not always be fully penetrant. 26 refs., 3 figs., 1 tab.« less

Correlation between the Amount of Anti-D Antibodies and IgG Subclasses with Severity of Haemolytic Disease of Foetus and Newborn.

PubMed

Velkova, Emilija

2015-06-15

The aim of this study was to investigate the influence of subclasses to IgG anti-D on the intensity of hemolytic disease of fetus and newborn (HDFN) at 45 fetuses/newborns with symptoms of mild and severe HDFN in Republic of Macedonia. In retrospective and prospective studies, in a period of 10 years, from 2004 to 2014, there have been immunohemathology tests performed on 22 009 samples on serums of pregnant women. At 37.78% of the total number of tested patients, IgG1 and IgG3 was the reason for severe HDFN. At 17.77% of the total number of tested patients, which had only IgG1detected, was the reason for serious intensity of HDFN. The correlation of the titer to anti-D antibodies in the mother's serum and the intensity of HDFN were researched in 48 newborns. The titers between 1:8 and 1:32 resulted in 3 cases of HDFN with symptoms of severe disease and in 4 cases there were no signs of HDFN. At 12 women that had a titre between 1:32 and 1:512, five of the newborns developed severe HDFN, and seven had symptoms of mild and weak intensity form. In 3 cases the titer was higher than 512, and out of them one newborn had weak symptoms of HDFN, one developed severe HDFN and one ended with foetal death. Only in one case the titer reached a value higher than 1000, and it ended with a fetal death. The titers of the pregnant women serum those are lower than 32 and those higher than 1000 can well predict HDFN. The titers of anti-D antibodies between 64 and 512 have no exact predictive value. IgG1 and IgG3 subclasses of anti-D have no predictive value by themselves, and cannot foresee the outcome of HDFN. The research study results suggest that IgG1 and IgG3 should be included in a multi - parameter protocol for evaluation of the HDFN intensity. They can give a real assessment of the expected HDFN intensity in combination with the titer hight and the significance of the antibodies.

The profile of repeat-associated histone lysine methylation states in the mouse epigenome

PubMed Central

Martens, Joost H A; O'Sullivan, Roderick J; Braunschweig, Ulrich; Opravil, Susanne; Radolf, Martin; Steinlein, Peter; Jenuwein, Thomas

2005-01-01

Histone lysine methylation has been shown to index silenced chromatin regions at, for example, pericentric heterochromatin or of the inactive X chromosome. Here, we examined the distribution of repressive histone lysine methylation states over the entire family of DNA repeats in the mouse genome. Using chromatin immunoprecipitation in a cluster analysis representing repetitive elements, our data demonstrate the selective enrichment of distinct H3-K9, H3-K27 and H4-K20 methylation marks across tandem repeats (e.g. major and minor satellites), DNA transposons, retrotransposons, long interspersed nucleotide elements and short interspersed nucleotide elements. Tandem repeats, but not the other repetitive elements, give rise to double-stranded (ds) RNAs that are further elevated in embryonic stem (ES) cells lacking the H3-K9-specific Suv39h histone methyltransferases. Importantly, although H3-K9 tri- and H4-K20 trimethylation appear stable at the satellite repeats, many of the other repeat-associated repressive marks vary in chromatin of differentiated ES cells or of embryonic trophoblasts and fibroblasts. Our data define a profile of repressive histone lysine methylation states for the repetitive complement of four distinct mouse epigenomes and suggest tandem repeats and dsRNA as primary triggers for more stable chromatin imprints. PMID:15678104

Spiculated Bladder Calculi: The Culprit for Repeated Catheter Failure

PubMed Central

Wek, C.; Fox, T. P.; Muir, G. H.

2013-01-01

We report on the case of a frustrated 90-year-old gentleman who was seen in the Accident and Emergency department for the third time in four days with failure of his long-term urethral catheter. He reported that the catheter simply “fell out” with the balloon deflated. On each occasion previously, the catheter had been reinserted in A&E and the patient discharged home. These repeated visits to A&E were understandably a source of much frustration for the patient and his family. On the third presentation, plain abdominal radiography demonstrated a large spiculated bladder calculus. PMID:23984173

Repeatability and Heritability of Behavioural Types in a Social Cichlid

PubMed Central

Chervet, Noémie; Zöttl, Markus; Schürch, Roger; Taborsky, Michael; Heg, Dik

2011-01-01

Aim. The quantitative genetics underlying correlated behavioural traits (‘‘animal personality”) have hitherto been studied mainly in domesticated animals. Here we report the repeatability (R) and heritability (h2) of behavioural types in the highly social cichlid fish Neolamprologus pulcher. Methods. We tested 1779 individuals repeatedly and calculated the h2 of behavioural types by variance components estimation (GLMM REML), using 1327 offspring from 162 broods from 74 pairs. Results. Repeatability of behavioural types was significant and considerable (0.546), but declined from 0.83 between tests conducted on the same day, to 0.19 on tests conducted up to 1201 days apart. All h2 estimates were significant but low (e.g., pair identity h2 = 0.15 ± 0.03 SE). Additionally, we found significant variation between broods nested within the parent(s), but these were not related to several environmental factors tested. Conclusions. We conclude that despite a considerable R, h2 in this cichlid species is low, and variability in behavioural type appears to be strongly affected by other (non)genetic effects. PMID:21716729

Sel1-like repeat proteins in signal transduction.

PubMed

Mittl, Peer R E; Schneider-Brachert, Wulf

2007-01-01

Solenoid proteins, which are distinguished from general globular proteins by their modular architectures, are frequently involved in signal transduction pathways. Proteins from the tetratricopeptide repeat (TPR) and Sel1-like repeat (SLR) families share similar alpha-helical conformations but different consensus sequence lengths and superhelical topologies. Both families are characterized by low sequence similarity levels, rendering the identification of functional homologous difficult. Therefore current knowledge of the molecular and cellular functions of the SLR proteins Sel1, Hrd3, Chs4, Nif1, PodJ, ExoR, AlgK, HcpA, Hsp12, EnhC, LpnE, MotX, and MerG has been reviewed. Although SLR proteins possess different cellular functions they all seem to serve as adaptor proteins for the assembly of macromolecular complexes. Sel1, Hrd3, Hsp12 and LpnE are activated under cellular stress. The eukaryotic Sel1 and Hrd3 proteins are involved in the ER-associated protein degradation, whereas the bacterial LpnE, EnhC, HcpA, ExoR, and AlgK proteins mediate the interactions between bacterial and eukaryotic host cells. LpnE and EnhC are responsible for the entry of L. pneumophila into epithelial cells and macrophages. ExoR from the symbiotic microorganism S. melioti and AlgK from the pathogen P. aeruginosa regulate exopolysaccaride synthesis. Nif1 and Chs4 from yeast are responsible for the regulation of mitosis and septum formation during cell division, respectively, and PodJ guides the cellular differentiation during the cell cycle of the bacterium C. crescentus. Taken together the SLR motif establishes a link between signal transduction pathways from eukaryotes and bacteria. The SLR motif is so far absent from archaea. Therefore the SLR could have developed in the last common ancestor between eukaryotes and bacteria.

Marginal versus joint Box-Cox transformation with applications to percentile curve construction for IgG subclasses and blood pressures.

PubMed

He, Xuming; Ng, K W; Shi, Jian

2003-02-15

When age-specific percentile curves are constructed for several correlated variables, the marginal method of handling one variable at a time has typically been used. We address the question, frequently asked by practitioners, of whether we can achieve efficiency gains by joint estimation. We focus on a simple but common method of Box-Cox transformation and assess the statistical impact of a joint transformation to multivariate normality on the percentile curve estimation for correlated variables. We find that there is little gain from the joint transformation for estimating percentiles around the median but a noticeable reduction in variances is possible for estimating extreme percentiles that are usually of main interest in medical and biological applications. Our study is motivated by problems in constructing percentile charts for IgG subclasses of children and for blood pressures in adult populations, both of which are discussed in the paper as examples, and yet our general findings are applicable to a wide range of other problems. Copyright 2003 John Wiley & Sons, Ltd.

Instance-Based Learning: Integrating Sampling and Repeated Decisions from Experience

ERIC Educational Resources Information Center

Gonzalez, Cleotilde; Dutt, Varun

2011-01-01

In decisions from experience, there are 2 experimental paradigms: sampling and repeated-choice. In the sampling paradigm, participants sample between 2 options as many times as they want (i.e., the stopping point is variable), observe the outcome with no real consequences each time, and finally select 1 of the 2 options that cause them to earn or…

Isolation and growth characteristics of an EDTA-degrading member of the alpha-subclass of Proteobacteria.

PubMed

Weilenmann, Hans-Ueli; Engeli, Barbara; Bucheli-Witschel, Margarete; Egli, Thomas

2004-10-01

A Gram-negative, ethylenediaminetetraacetic acid (EDTA)-degrading bacterium (deposited at the German Culture Collection as strain DSM 9103) utilising EDTA as the only source of carbon, energy and nitrogen was isolated from a mixed EDTA-degrading population that was originally enriched in a column system from a mixture of activated sludge and soil. Chemotaxonomic analysis of quinones, polar lipids and fatty acids allowed allocation of the isolate to the alpha-subclass of Proteobacteria. 16S rDNA sequencing and phylogenetic analysis revealed highest similarity to the Mesorhizobium genus followed by the Aminobacter genus. However, the EDTA-degrading strain apparently forms a new branch within the Phyllobacteriaceae/Mesorhizobia family. Growth of the strain was rather slow not only on EDTA (micro(max) = 0.05 h(-1)) but also on other substrates. Classical substrate utilisation testing in batch culture suggested a quite restricted carbon source spectrum with only lactate, glutamate, and complexing agents chemically related to EDTA (nitrilotriacetate, iminodiacetate and ethylenediaminedisuccinate) supporting growth. However, when EDTA-limited continuous cultures of strain DSM 9103 were pulsed with fumarate, succinate, glucose or acetate, these substrates were assimilated immediately. Apparently, the strain can use a broader spectrum than indicated by traditional substrate testing techniques. The EDTA species CaEDTA and MgEDTA served as growth substrates of the strain because in the mineral medium employed EDTA was predicted to be mainly present in the form of these two complexes. The bacterium was not able to degrade Fe3+-complexed EDTA.

Fatigue in repeated-sprint exercise is related to muscle power factors and reduced neuromuscular activity.

PubMed

Mendez-Villanueva, Alberto; Hamer, Peter; Bishop, David

2008-07-01

The purpose of this study was (1) to determine the relationship between each individual's anaerobic power reserve (APR) [i.e., the difference between the maximum anaerobic (Pana) and aerobic power (Paer)] and fatigability during repeated-sprint exercise and (2) to examine the acute effects of repeated sprints on neuromuscular activity, as evidenced by changes in the surface electromyogram (EMG) signals. Eight healthy males carried out tests to determine Pana (defined as the highest power output attained during a 6-s cycling sprint), Paer (defined as the highest power output achieved during a progressive, discontinuous cycling test to failure) and a repeated cycling sprint test (10 x 6-s max sprints with 30 s rest). Peak power output (PPO) and mean power output (MPO) were calculated for each maximal 6-s cycling bout. Root mean square (RMS) was utilized to quantify EMG activity from the vastus lateralis (VL) muscle of the right leg. Over the ten sprints, PPO and MPO decreased by 24.6 and 28.3% from the maximal value (i.e., sprint 1), respectively. Fatigue index during repeated sprints was significantly correlated with APR (R = 0.87; P < 0.05). RMS values decreased over the ten sprints by 14.6% (+/-6.3%). There was a strong linear relationship (R2 = 0.97; P < 0.05) between the changes in MPO and EMG RMS from the vastus lateralis muscle during the ten sprints. The individual advantage in fatigue-resistance when performing a repeated sprint task was related with a lower anaerobic power reserve. Additionally, a suboptimal net motor unit activity might also impair the ability to repeatedly generate maximum power outputs.

Igg Subclasses Targeting the Flagella of Salmonella enterica Serovar Typhimurium Can Mediate Phagocytosis and Bacterial Killing

PubMed Central

Goh, Yun Shan; Armour, Kathryn L; Clark, Michael R; Grant, Andrew J; Mastroeni, Pietro

2016-01-01

Invasive non-typhoidal Salmonella are a common cause of invasive disease in immuno-compromised individuals and in children. Multi-drug resistance poses challenges to disease control, with a critical need for effective vaccines. Flagellin is an attractive vaccine candidate due to surface exposure and high epitope copy number, but its potential as a target for opsonophacytic antibodies is unclear. We examined the effect of targeting flagella with different classes of IgG on the interaction between Salmonella Typhimurium and a human phagocyte-like cell line, THP-1. We tagged the FliC flagellar protein with a foreign CD52 mimotope (TSSPSAD) and bacteria were opsonized with a panel of humanised CD52 antibodies with the same antigen-binding V-region, but different constant regions. We found that IgG binding to flagella increases bacterial phagocytosis and reduces viable intracellular bacterial numbers. Opsonisation with IgG3, followed by IgG1, IgG4, and IgG2, resulted in the highest level of bacterial uptake and in the highest reduction in the intracellular load of viable bacteria. Taken together, our data provide proof-of-principle evidence that targeting flagella with antibodies can increase the antibacterial function of host cells, with IgG3 being the most potent subclass. These data will assist the rational design of urgently needed, optimised vaccines against iNTS disease. PMID:27366588

Repeated mild closed head injury impairs short-term visuospatial memory and complex learning.

PubMed

Hylin, Michael J; Orsi, Sara A; Rozas, Natalia S; Hill, Julia L; Zhao, Jing; Redell, John B; Moore, Anthony N; Dash, Pramod K

2013-05-01

Concussive force can cause neurocognitive and neurobehavioral dysfunction by inducing functional, electrophysiological, and/or ultrastructural changes within the brain. Although concussion-triggered symptoms typically subside within days to weeks in most people, in 15%-20% of the cases, symptomology can continue beyond this time point. Problems with memory, attention, processing speed, and cognitive flexibility (e.g., problem solving, conflict resolution) are some of the prominent post-concussive cognitive symptoms. Repeated concussions (with loss or altered consciousness), which are common to many contact sports, can exacerbate these symptoms. The pathophysiology of repeated concussions is not well understood, nor is an effective treatment available. In order to facilitate drug discovery to treat post-concussive symptoms (PCSs), there is a need to determine if animal models of repeated mild closed head injury (mCHI) can mimic the neurocognitive and histopathological consequences of repeated concussions. To this end, we employed a controlled cortical impact (CCI) device to deliver a mCHI directly to the skull of mice daily for 4 days, and examined the ensuing neurological and neurocognitive functions using beam balance, foot-fault, an abbreviated Morris water maze test, context discrimination, and active place avoidance tasks. Repeated mCHI exacerbated vestibulomotor, motor, short-term memory and conflict learning impairments as compared to a single mCHI. Learning and memory impairments were still observed in repeated mCHI mice when tested 3 months post-injury. Repeated mCHI also reduced cerebral perfusion, prolonged the inflammatory response, and in some animals, caused hippocampal neuronal loss. Our results show that repeated mCHI can reproduce some of the deficits seen after repeated concussions in humans and may be suitable for drug discovery studies and translational research.

AtNG1 encodes a protein that is required for seed germination.

PubMed

Yang, Libo; Peng, Xiongbo; Sun, Meng-xiang

2011-10-01

The pentatricopeptide repeat (PPR) family of eukaryotic proteins has numerous members in plants and is important for plant development. In the present study, we cloned a novel PPR gene, designated AtNG1, and characterized the ng1 Arabidopsis mutant. Morphological and structural observation of an ng1 mutant revealed that its sexual reproduction and seed formation processes are essentially normal. The mature embryonic root of ng1 is fully developed and has a well-differentiated structure; however, ng1 seeds cannot germinate, even when supplied with supplemental hormones and nutrition. Further investigation showed that embryo expansion and root cell elongation fails to occur after water imbibitions. Transient gene expression analysis indicated that AtNG1 localizes in mitochondrion. This implies that the deficiency of mitochondrion function might be the reason for the failed seed germination. Thus, our finding confirmed that AtNG1 plays a critical role in the early process of seed germination. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Development of Genome Engineering Tools from Plant-Specific PPR Proteins Using Animal Cultured Cells.

PubMed

Kobayashi, Takehito; Yagi, Yusuke; Nakamura, Takahiro

2016-01-01

The pentatricopeptide repeat (PPR) motif is a sequence-specific RNA/DNA-binding module. Elucidation of the RNA/DNA recognition mechanism has enabled engineering of PPR motifs as new RNA/DNA manipulation tools in living cells, including for genome editing. However, the biochemical characteristics of PPR proteins remain unknown, mostly due to the instability and/or unfolding propensities of PPR proteins in heterologous expression systems such as bacteria and yeast. To overcome this issue, we constructed reporter systems using animal cultured cells. The cell-based system has highly attractive features for PPR engineering: robust eukaryotic gene expression; availability of various vectors, reagents, and antibodies; highly efficient DNA delivery ratio (>80 %); and rapid, high-throughput data production. In this chapter, we introduce an example of such reporter systems: a PPR-based sequence-specific translational activation system. The cell-based reporter system can be applied to characterize plant genes of interested and to PPR engineering.

Mechanical unfolding of an ankyrin repeat protein.

PubMed

Serquera, David; Lee, Whasil; Settanni, Giovanni; Marszalek, Piotr E; Paci, Emanuele; Itzhaki, Laura S

2010-04-07

Ankryin repeat proteins comprise tandem arrays of a 33-residue, predominantly alpha-helical motif that stacks roughly linearly to produce elongated and superhelical structures. They function as scaffolds mediating a diverse range of protein-protein interactions, and some have been proposed to play a role in mechanical signal transduction processes in the cell. Here we use atomic force microscopy and molecular-dynamics simulations to investigate the natural 7-ankyrin repeat protein gankyrin. We find that gankyrin unfolds under force via multiple distinct pathways. The reactions do not proceed in a cooperative manner, nor do they always involve fully stepwise unfolding of one repeat at a time. The peeling away of half an ankyrin repeat, or one or more ankyrin repeats, occurs at low forces; however, intermediate species are formed that are resistant to high forces, and the simulations indicate that in some instances they are stabilized by nonnative interactions. The unfolding of individual ankyrin repeats generates a refolding force, a feature that may be more easily detected in these proteins than in globular proteins because the refolding of a repeat involves a short contraction distance and incurs a low entropic cost. We discuss the origins of the differences between the force- and chemical-induced unfolding pathways of ankyrin repeat proteins, as well as the differences between the mechanics of natural occurring ankyrin repeat proteins and those of designed consensus ankyin repeat and globular proteins. Copyright (c) 2010 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Combined roles of human IgG subclass, alternative complement pathway activation, and epitope density in the bactericidal activity of antibodies to meningococcal factor h binding protein.

PubMed

Giuntini, Serena; Reason, Donald C; Granoff, Dan M

2012-01-01

Meningococcal vaccines containing factor H binding protein (fHbp) are in clinical development. fHbp binds human fH, which enables the meningococcus to resist complement-mediated bacteriolysis. Previously, we found that chimeric human IgG1 mouse anti-fHbp monoclonal antibodies (MAbs) had human complement-mediated bactericidal activity only if the MAb inhibited fH binding. Since IgG subclasses differ in their ability to activate complement, we investigated the role of human IgG subclasses on antibody functional activity. We constructed chimeric MAbs in which three different murine fHbp-specific binding domains were each paired with human IgG1, IgG2, or IgG3. Against a wild-type group B isolate, all three IgG3 MAbs, irrespective of their ability to inhibit fH binding, had bactericidal activity that was >5-fold higher than the respective IgG1 MAbs, while the IgG2 MAbs had the least activity. Against a mutant with increased fHbp expression, the anti-fHbp MAbs elicited greater C4b deposition (classical pathway) and greater bactericidal activity than against the wild-type strain, and the IgG1 MAbs had similar or greater activity than the respective IgG3 MAbs. The bactericidal activity against both wild-type and mutant strains also was dependent, in part, on activation of the alternative complement pathway. Thus, at lower epitope density in the wild-type strain, the IgG3 anti-fHbp MAbs had the greatest bactericidal activity. At a higher epitope density in the mutant, the IgG1 MAbs had similar or greater bactericidal activity than the IgG3 MAbs, and the activity was less dependent on the inhibition of fH binding than at a lower epitope density.

Repeated vitrification/warming of human sperm gives better results than repeated slow programmable freezing

PubMed Central

Vutyavanich, Teraporn; Lattiwongsakorn, Worashorn; Piromlertamorn, Waraporn; Samchimchom, Sudarat

2012-01-01

In this study, we compared the effects of repeated freezing/thawing of human sperm by our in-house method of rapid freezing with slow programmable freezing. Sperm samples from 11 normozoospermic subjects were processed through density gradients and divided into three aliquots: non-frozen, rapid freezing and slow programmable freezing. Sperm in the rapid freezing group had better motility and viability than those in the slow freezing group (P<0.01) after the first, second and third cycles of freezing/thawing, but there was no difference in morphology. In the second experiment, rapid freezing was repeated three times in 20 subjects. The samples from each thawing cycle were evaluated for DNA fragmentation using the alkaline comet assay. DNA fragmentation began to increase considerably after the second cycle of freezing/thawing, but to a level that was not clinically important. In the third experiment, rapid freezing was done repeatedly in 10 subjects, until no motile sperm were observed after thawing. The median number of repeated freezing/thawing that yielded no motile sperm was seven (range: 5–8, mean: 6.8). In conclusion, we demonstrated that repeated freezing/thawing of processed semen using our rapid freezing method gave better results than standard slow programmable freezing. This method can help maximize the usage of precious cryopreserved sperm samples in assisted reproduction technology. PMID:23064685

Effect of repeated immersion solution cycles on the color stability of denture tooth acrylic resins

PubMed Central

da SILVA, Paulo Maurício Batista; ACOSTA, Emílio José Tabaré Rodríguez; JACOBINA, Matheus; PINTO, Luciana de Rezende; PORTO, Vinícius Carvalho

2011-01-01

Objective Chemical solutions have been widely used for disinfection of dentures, but their effect on color stability of denture tooth acrylic resins after repeated procedures is still unclear. The aim of this in vitro study was to evaluate whether repeated cycles of chemical disinfectants affected the color stability of two denture tooth acrylic resins. Material and Methods Sixty disc-shaped specimens (40 mm x 3 mm) were fabricated from two different brands (Artiplus and Trilux) of denture tooth acrylic resin. The specimens from each brand (n=30) were randomly divided into 6 groups (n=5) and immersed in the following solutions: distilled water (control group) and 5 disinfecting solutions (1% sodium hypochlorite, 2% sodium hypochlorite, 5.25% sodium hypochlorite, 2% glutaraldehyde, and 4% chlorhexidine gluconate). Tooth color measurements were made by spectrophotometry. Before disinfection, the initial color of each tooth was recorded. Further color measurements were determined after subjecting the specimens to 7, 21, 30, 45, 60, and 90 immersion cycles in each tested solution. Color differences (ΔE*) were determined using the CIE L*a*b* color system. Data were analyzed using two-way repeated measures analysis of variance (ANOVA) followed by Tukey tests. The significance level was set at 5%. Results There were statistically significant differences in ΔE* among the 5 disinfectants and water during the 90 cycles of immersion for both denture tooth acrylic resins. Distilled water promoted the greatest color change in both denture tooth acrylic resins, nevertheless none of tested disinfectants promoted ΔE* values higher than 1.0 on these acrylic materials during the 90 cycles of disinfection. Conclusions Repeated immersion cycles in disinfecting solutions alter ∆E* values, however these values do not compromise the color of the tested denture tooth acrylic resins because they are imperceptible to the human eye. PMID:22230997

The Dark Side of Testing Memory: Repeated Retrieval Can Enhance Eyewitness Suggestibility

ERIC Educational Resources Information Center

Chan, Jason C. K.; LaPaglia, Jessica A.

2011-01-01

Eyewitnesses typically recount their experiences many times before trial. Such repeated retrieval can enhance memory retention of the witnessed event. However, recent studies (e.g., Chan, Thomas, & Bulevich, 2009) have found that initial retrieval can exacerbate eyewitness suggestibility to later misleading information--a finding termed…

Repeated allergen exposure enhances excitatory nonadrenergic noncholinergic nerve-mediated bronchoconstriction in sensitized guinea-pigs.

PubMed

Kageyama, N; Ichinose, M; Igarashi, A; Miura, M; Yamauchi, H; Sasaki, Y; Ishikawa, J; Tomaki, M; Shirato, K

1996-07-01

The effect of repeated allergen inhalation challenge on the airway excitatory nonadrenergic noncholinergic (e-NANC) nerve-mediated bronchoconstrictor response was studied in ovalbumin (OA) sensitized guinea-pigs. Three weeks after sensitization, OA inhalation, 0.03% for 3 min (challenged group), or saline inhalation (control group) was repeated every day for 4 weeks. The e-NANC nerve function was examined in vitro by means of isometric tension measurement of main bronchi. After pretreatment with atropine (10(-6) M) and propranolol (10(-6) M), we performed electrical field stimulation (EFS) or exogenous neurokinin A (NKA) administration. In the challenged group, EFS-induced main bronchial contraction was significantly greater than that of the control group (p < 0.05 or p < 0.01), but exogenous NKA-mediated responses were almost the same in both groups. The e-NANC-induced main bronchial contractions after EFS were enhanced by pretreatment with the neutral endopeptidase inhibitor, phosphoramidon, to the same degree in the control and challenged groups, indicating that the peptide degradation mechanisms were not impaired even in the challenged group. Substance P immunoreactivities in the lung of the challenged group were significantly higher than those of the control group. These results suggest that chronic airway inflammation after repeated allergen challenge increases excitatory nonadrenergic noncholinergic nerve function, possibly by enhancing sensory neuropeptide production and/or release.

ACCUMULATION AND METABOLISM OF ARSENIC IN MICE AFTER REPEATED ADMINISTRATION OF ARSENATE

EPA Science Inventory

Accumulation and metabolism of arsenic in mice after repeated oral administration of arsenate, Hughes, M. F., Kenyon, E. M., Edwards, B. C., Mitchell, C. T., Del Razo, L. M., and Thomas,
D. J.

The human carcinogen inorganic arsenic (iAs) is a pervasive environmental ...

SCA8 Repeat Expansion: Large CTA/CTG Repeat Alleles Are More Common in Ataxic Patients, Including Those with SCA6

PubMed Central

Izumi, Yuishin; Maruyama, Hirofumi; Oda, Masaya; Morino, Hiroyuki; Okada, Takayuki; Ito, Hidefumi; Sasaki, Iwao; Tanaka, Hiroyasu; Komure, Osamu; Udaka, Fukashi; Nakamura, Shigenobu; Kawakami, Hideshi

2003-01-01

We analyzed the SCA8 CTA/CTG repeat in a large group of Japanese subjects. The frequency of large alleles (85–399 CTA/CTG repeats) was 1.9% in spinocerebellar ataxia (SCA), 0.4% in Parkinson disease, 0.3% in Alzheimer disease, and 0% in a healthy control group; the frequency was significantly higher in the group with SCA than in the control group. Homozygotes for large alleles were observed only in the group with SCA. In five patients with SCA from two families, a large SCA8 CTA/CTG repeat and a large SCA6 CAG repeat coexisted. Age at onset was correlated with SCA8 repeats rather than SCA6 repeats in these five patients. In one of these families, at least one patient showed only a large SCA8 CTA/CTG repeat allele, with no large SCA6 CAG repeat allele. We speculate that the presence of a large SCA8 CTA/CTG repeat allele influences the function of channels such as α1A-voltage–dependent calcium channel through changing or aberrant splicing, resulting in the development of cerebellar ataxia, especially in homozygous patients. PMID:12545428

SCA8 repeat expansion: large CTA/CTG repeat alleles are more common in ataxic patients, including those with SCA6.

PubMed

Izumi, Yuishin; Maruyama, Hirofumi; Oda, Masaya; Morino, Hiroyuki; Okada, Takayuki; Ito, Hidefumi; Sasaki, Iwao; Tanaka, Hiroyasu; Komure, Osamu; Udaka, Fukashi; Nakamura, Shigenobu; Kawakami, Hideshi

2003-03-01

We analyzed the SCA8 CTA/CTG repeat in a large group of Japanese subjects. The frequency of large alleles (85-399 CTA/CTG repeats) was 1.9% in spinocerebellar ataxia (SCA), 0.4% in Parkinson disease, 0.3% in Alzheimer disease, and 0% in a healthy control group; the frequency was significantly higher in the group with SCA than in the control group. Homozygotes for large alleles were observed only in the group with SCA. In five patients with SCA from two families, a large SCA8 CTA/CTG repeat and a large SCA6 CAG repeat coexisted. Age at onset was correlated with SCA8 repeats rather than SCA6 repeats in these five patients. In one of these families, at least one patient showed only a large SCA8 CTA/CTG repeat allele, with no large SCA6 CAG repeat allele. We speculate that the presence of a large SCA8 CTA/CTG repeat allele influences the function of channels such as alpha(1A)-voltage-dependent calcium channel through changing or aberrant splicing, resulting in the development of cerebellar ataxia, especially in homozygous patients.

Comparison of simple sequence repeats in 19 Archaea.

PubMed

Trivedi, S

2006-12-05

All organisms that have been studied until now have been found to have differential distribution of simple sequence repeats (SSRs), with more SSRs in intergenic than in coding sequences. SSR distribution was investigated in Archaea genomes where complete chromosome sequences of 19 Archaea were analyzed with the program SPUTNIK to find di- to penta-nucleotide repeats. The number of repeats was determined for the complete chromosome sequences and for the coding and non-coding sequences. Different from what has been found for other groups of organisms, there is an abundance of SSRs in coding regions of the genome of some Archaea. Dinucleotide repeats were rare and CG repeats were found in only two Archaea. In general, trinucleotide repeats are the most abundant SSR motifs; however, pentanucleotide repeats are abundant in some Archaea. Some of the tetranucleotide and pentanucleotide repeat motifs are organism specific. In general, repeats are short and CG-rich repeats are present in Archaea having a CG-rich genome. Among the 19 Archaea, SSR density was not correlated with genome size or with optimum growth temperature. Pentanucleotide density had an inverse correlation with the CG content of the genome.

Short Tandem Repeat DNA Internet Database

National Institute of Standards and Technology Data Gateway

SRD 130 Short Tandem Repeat DNA Internet Database (Web, free access)   Short Tandem Repeat DNA Internet Database is intended to benefit research and application of short tandem repeat DNA markers for human identity testing. Facts and sequence information on each STR system, population data, commonly used multiplex STR systems, PCR primers and conditions, and a review of various technologies for analysis of STR alleles have been included.

Triage of women with low-grade cervical lesions--HPV mRNA testing versus repeat cytology.

PubMed

Sørbye, Sveinung Wergeland; Arbyn, Marc; Fismen, Silje; Gutteberg, Tore Jarl; Mortensen, Elin Synnøve

2011-01-01

In Norway, women with low-grade squamous intraepithelial lesions (LSIL) are followed up after six months in order to decide whether they should undergo further follow-up or be referred back to the screening interval of three years. A high specificity and positive predictive value (PPV) of the triage test is important to avoid unnecessary diagnostic and therapeutic procedures. At the University Hospital of North Norway, repeat cytology and the HPV mRNA test PreTect HPV-Proofer, detecting E6/E7 mRNA from HPV types 16, 18, 31, 33 and 45, are used in triage of women with ASC-US and LSIL. In this study, women with LSIL cytology in the period 2005-2008 were included (n = 522). Two triage methods were evaluated in two separate groups: repeat cytology only (n = 225) and HPV mRNA testing in addition to repeat cytology (n = 297). Histologically confirmed cervical intraepithelial neoplasia of grade 2 or worse (CIN2+) was used as the study endpoint. Of 522 women with LSIL, 207 had biopsies and 125 of them had CIN2+. The sensitivity and specificity of repeat cytology (ASC-US or worse) were 85.7% (95% confidence interval (CI): 72.1, 92.2) and 54.4 % (95% CI: 46.9, 61.9), respectively. The sensitivity and specificity of the HPV mRNA test were 94.2% (95% CI: 88.7, 99.7) and 86.0% (95% CI: 81.5, 90.5), respectively. The PPV of repeat cytology was 38.4% (95% CI: 29.9, 46.9) compared to 67.0% (95% CI: 57.7, 76.4) of the HPV mRNA test. HPV mRNA testing was more sensitive and specific than repeat cytology in triage of women with LSIL cytology. In addition, the HPV mRNA test showed higher PPV. These data indicate that the HPV mRNA test is a better triage test for women with LSIL than repeat cytology.

Triage of Women with Low-Grade Cervical Lesions - HPV mRNA Testing versus Repeat Cytology

PubMed Central

Sørbye, Sveinung Wergeland; Arbyn, Marc; Fismen, Silje; Gutteberg, Tore Jarl; Mortensen, Elin Synnøve

2011-01-01

Background In Norway, women with low-grade squamous intraepithelial lesions (LSIL) are followed up after six months in order to decide whether they should undergo further follow-up or be referred back to the screening interval of three years. A high specificity and positive predictive value (PPV) of the triage test is important to avoid unnecessary diagnostic and therapeutic procedures. Materials and Methods At the University Hospital of North Norway, repeat cytology and the HPV mRNA test PreTect HPV-Proofer, detecting E6/E7 mRNA from HPV types 16, 18, 31, 33 and 45, are used in triage of women with ASC-US and LSIL. In this study, women with LSIL cytology in the period 2005–2008 were included (n = 522). Two triage methods were evaluated in two separate groups: repeat cytology only (n = 225) and HPV mRNA testing in addition to repeat cytology (n = 297). Histologically confirmed cervical intraepithelial neoplasia of grade 2 or worse (CIN2+) was used as the study endpoint. Results Of 522 women with LSIL, 207 had biopsies and 125 of them had CIN2+. The sensitivity and specificity of repeat cytology (ASC-US or worse) were 85.7% (95% confidence interval (CI): 72.1, 92.2) and 54.4 % (95% CI: 46.9, 61.9), respectively. The sensitivity and specificity of the HPV mRNA test were 94.2% (95% CI: 88.7, 99.7) and 86.0% (95% CI: 81.5, 90.5), respectively. The PPV of repeat cytology was 38.4% (95% CI: 29.9, 46.9) compared to 67.0% (95% CI: 57.7, 76.4) of the HPV mRNA test. Conclusion HPV mRNA testing was more sensitive and specific than repeat cytology in triage of women with LSIL cytology. In addition, the HPV mRNA test showed higher PPV. These data indicate that the HPV mRNA test is a better triage test for women with LSIL than repeat cytology. PMID:21918682

Repeated irradiations with gamma-rays at a Dose of 0.5 Gy may exacerbate asthma.

PubMed

Fang, Su-ping; Tago, Fumitoshi; Tanaka, Takashi; Simura, Noriko; Muto, Yasuko; Goto, Resuke; Kojima, Shuji

2005-06-01

We previously showed that 0.5 Gy whole-body gamma-ray irradiation with a single or small number of repeated exposures inhibits tumor growth in mice, via elevation of the IFN-gamma/IL-4 ratio concomitantly with a decrease in the percentage of B cells. Here we examined whether repeated 0.5 Gy gamma-rays irradiation can improve asthma in an OVA-induced asthmatic mouse model. We found that repeated irradiation (10 times) with 0.5 Gy of gamma-rays significantly increased total IgE in comparison with the disease-control group. The levels of IL-4 and IL-5 were also significantly higher in the gamma-ray-irradiated group, while that of IFN-gamma was significantly lower, resulting in a further decrease of the IFN-gamma/IL-4 ratio from the normal value. These results indicate that the repeated irradiation with gamma-rays may exacerbate asthma, and may have opposite effects on different immune reactions unlike the irradiation with a single or small number of repeated exposures.

RNA Editing and Its Molecular Mechanism in Plant Organelles

PubMed Central

Ichinose, Mizuho; Sugita, Mamoru

2016-01-01

RNA editing by cytidine (C) to uridine (U) conversions is widespread in plant mitochondria and chloroplasts. In some plant taxa, “reverse” U-to-C editing also occurs. However, to date, no instance of RNA editing has yet been reported in green algae and the complex thalloid liverworts. RNA editing may have evolved in early land plants 450 million years ago. However, in some plant species, including the liverwort, Marchantia polymorpha, editing may have been lost during evolution. Most RNA editing events can restore the evolutionarily conserved amino acid residues in mRNAs or create translation start and stop codons. Therefore, RNA editing is an essential process to maintain genetic information at the RNA level. Individual RNA editing sites are recognized by plant-specific pentatricopeptide repeat (PPR) proteins that are encoded in the nuclear genome. These PPR proteins are characterized by repeat elements that bind specifically to RNA sequences upstream of target editing sites. In flowering plants, non-PPR proteins also participate in multiple RNA editing events as auxiliary factors. C-to-U editing can be explained by cytidine deamination. The proteins discovered to date are important factors for RNA editing but a bona fide RNA editing enzyme has yet to be identified. PMID:28025543

Nifty Nines and Repeating Decimals

ERIC Educational Resources Information Center

Brown, Scott A.

2016-01-01

The traditional technique for converting repeating decimals to common fractions can be found in nearly every algebra textbook that has been published, as well as in many precalculus texts. However, students generally encounter repeating decimal numerals earlier than high school when they study rational numbers in prealgebra classes. Therefore, how…

Repeated Prescribed Burning in Aspen

Treesearch

Donald A. Perala

1974-01-01

Infrequent burning weather, low flammability of the aspen-hardwood association, and prolific sprouting and seeding of shrubs and hardwoods made repeated dormant season burning a poor tool to convert good site aspen to conifers. Repeat fall burns for wildlife habitat maintenance is workable if species composition changes are not important.

Taxonomic resolutions based on 18S rRNA genes: a case study of subclass copepoda.

PubMed

Wu, Shu; Xiong, Jie; Yu, Yuhe

2015-01-01

Biodiversity studies are commonly conducted using 18S rRNA genes. In this study, we compared the inter-species divergence of variable regions (V1-9) within the copepod 18S rRNA gene, and tested their taxonomic resolutions at different taxonomic levels. Our results indicate that the 18S rRNA gene is a good molecular marker for the study of copepod biodiversity, and our conclusions are as follows: 1) 18S rRNA genes are highly conserved intra-species (intra-species similarities are close to 100%); and could aid in species-level analyses, but with some limitations; 2) nearly-whole-length sequences and some partial regions (around V2, V4, and V9) of the 18S rRNA gene can be used to discriminate between samples at both the family and order levels (with a success rate of about 80%); 3) compared with other regions, V9 has a higher resolution at the genus level (with an identification success rate of about 80%); and 4) V7 is most divergent in length, and would be a good candidate marker for the phylogenetic study of Acartia species. This study also evaluated the correlation between similarity thresholds and the accuracy of using nuclear 18S rRNA genes for the classification of organisms in the subclass Copepoda. We suggest that sample identification accuracy should be considered when a molecular sequence divergence threshold is used for taxonomic identification, and that the lowest similarity threshold should be determined based on a pre-designated level of acceptable accuracy.

Taxonomic Resolutions Based on 18S rRNA Genes: A Case Study of Subclass Copepoda

PubMed Central

Wu, Shu; Xiong, Jie; Yu, Yuhe

2015-01-01

Biodiversity studies are commonly conducted using 18S rRNA genes. In this study, we compared the inter-species divergence of variable regions (V1–9) within the copepod 18S rRNA gene, and tested their taxonomic resolutions at different taxonomic levels. Our results indicate that the 18S rRNA gene is a good molecular marker for the study of copepod biodiversity, and our conclusions are as follows: 1) 18S rRNA genes are highly conserved intra-species (intra-species similarities are close to 100%); and could aid in species-level analyses, but with some limitations; 2) nearly-whole-length sequences and some partial regions (around V2, V4, and V9) of the 18S rRNA gene can be used to discriminate between samples at both the family and order levels (with a success rate of about 80%); 3) compared with other regions, V9 has a higher resolution at the genus level (with an identification success rate of about 80%); and 4) V7 is most divergent in length, and would be a good candidate marker for the phylogenetic study of Acartia species. This study also evaluated the correlation between similarity thresholds and the accuracy of using nuclear 18S rRNA genes for the classification of organisms in the subclass Copepoda. We suggest that sample identification accuracy should be considered when a molecular sequence divergence threshold is used for taxonomic identification, and that the lowest similarity threshold should be determined based on a pre-designated level of acceptable accuracy. PMID:26107258

E622, a miniature, virulence-associated mobile element.

PubMed

Stavrinides, John; Kirzinger, Morgan W B; Beasley, Federico C; Guttman, David S

2012-01-01

Miniature inverted terminal repeat elements (MITEs) are nonautonomous mobile elements that have a significant impact on bacterial evolution. Here we characterize E622, a 611-bp virulence-associated MITE from Pseudomonas syringae, which contains no coding region but has almost perfect 168-bp inverted repeats. Using an antibiotic coupling assay, we show that E622 is transposable and can mobilize an antibiotic resistance gene contained between its borders. Its predicted parent element, designated TnE622, has a typical transposon structure with a three-gene operon, consisting of resolvase, integrase, and exeA-like genes, which is bounded by the same terminal inverted repeats as E622. A broader genome level survey of the E622/TnE622 inverted repeats identified homologs in Pseudomonas, Salmonella, Shewanella, Erwinia, Pantoea, and the cyanobacteria Nostoc and Cyanothece, many of which appear to encompass known virulence genes, including genes encoding toxins, enzymes, and type III secreted effectors. Its association with niche-specific genetic determinants, along with its persistence and evolutionary diversification, indicates that this mobile element family has played a prominent role in the evolution of many agriculturally and clinically relevant pathogenic bacteria.

Disease-associated repeat instability and mismatch repair.

PubMed

Schmidt, Monika H M; Pearson, Christopher E

2016-02-01

Expanded tandem repeat sequences in DNA are associated with at least 40 human genetic neurological, neurodegenerative, and neuromuscular diseases. Repeat expansion can occur during parent-to-offspring transmission, and arise at variable rates in specific tissues throughout the life of an affected individual. Since the ongoing somatic repeat expansions can affect disease age-of-onset, severity, and progression, targeting somatic expansion holds potential as a therapeutic target. Thus, understanding the factors that regulate this mutation is crucial. DNA repair, in particular mismatch repair (MMR), is the major driving force of disease-associated repeat expansions. In contrast to its anti-mutagenic roles, mammalian MMR curiously drives the expansion mutations of disease-associated (CAG)·(CTG) repeats. Recent advances have broadened our knowledge of both the MMR proteins involved in disease repeat expansions, including: MSH2, MSH3, MSH6, MLH1, PMS2, and MLH3, as well as the types of repeats affected by MMR, now including: (CAG)·(CTG), (CGG)·(CCG), and (GAA)·(TTC) repeats. Mutagenic slipped-DNA structures have been detected in patient tissues, and the size of the slip-out and their junction conformation can determine the involvement of MMR. Furthermore, the formation of other unusual DNA and R-loop structures is proposed to play a key role in MMR-mediated instability. A complex correlation is emerging between tissues showing varying amounts of repeat instability and MMR expression levels. Notably, naturally occurring polymorphic variants of DNA repair genes can have dramatic effects upon the levels of repeat instability, which may explain the variation in disease age-of-onset, progression and severity. An increasing grasp of these factors holds prognostic and therapeutic potential. Copyright © 2015 Elsevier B.V. All rights reserved.

The Effects of Repeated Writing and Repeated Revision Strategies on Composing Fluency of Learning Disabled Adolescents. Final Report.

ERIC Educational Resources Information Center

Harriman, Nancy E.; Gajar, Anna H.

The study investigated the use of repeated writings as a means of increasing written language fluency with 48 learning disabled students in senior high school resource room English classes. Subjects received one of four treatments for 4 days: repeated writing with structural cues, repeated revision with structural cues, writing on a new topic with…

Global Seismic Cross-Correlation Results: Characterizing Repeating Seismic Events

NASA Astrophysics Data System (ADS)

Vieceli, R.; Dodge, D. A.; Walter, W. R.

2016-12-01

Increases in seismic instrument quality and coverage have led to increased knowledge of earthquakes, but have also revealed the complex and diverse nature of earthquake ruptures. Nonetheless, some earthquakes are sufficiently similar to each other that they produce correlated waveforms. Such repeating events have been used to investigate interplate coupling of subduction zones [e.g. Igarashi, 2010; Yu, 2013], study spatio-temporal changes in slip rate at plate boundaries [e.g. Igarashi et al., 2003], observe variations in seismic wave propagation velocities in the crust [e.g. Schaff and Beroza, 2004; Sawazaki et al., 2015], and assess inner core rotation [e.g. Yu, 2016]. The characterization of repeating events on a global scale remains a very challenging problem. An initial global seismic cross-correlation study used over 310 million waveforms from nearly 3.8 million events recorded between 1970 and 2013 to determine an initial look at global correlated seismicity [Dodge and Walter, 2015]. In this work, we analyze the spatial and temporal distribution of the most highly correlated event clusters or "multiplets" from the Dodge and Walter [2015] study. We examine how the distributions and characteristics of multiplets are effected by tectonic environment, source-station separation, and frequency band. Preliminary results suggest that the distribution of multiplets does not correspond to the tectonic environment in any obvious way, nor do they always coincide with the occurrence of large earthquakes. Future work will focus on clustering correlated pairs and working to reduce the bias introduced by non-uniform seismic station coverage and data availability. This work performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under Contract DE-AC52-07NA27344.

WD-repeat instability and diversification of the Podospora anserina hnwd non-self recognition gene family.

PubMed

Chevanne, Damien; Saupe, Sven J; Clavé, Corinne; Paoletti, Mathieu

2010-05-06

Genes involved in non-self recognition and host defence are typically capable of rapid diversification and exploit specialized genetic mechanism to that end. Fungi display a non-self recognition phenomenon termed heterokaryon incompatibility that operates when cells of unlike genotype fuse and leads to the cell death of the fusion cell. In the fungus Podospora anserina, three genes controlling this allorecognition process het-d, het-e and het-r are paralogs belonging to the same hnwd gene family. HNWD proteins are STAND proteins (signal transduction NTPase with multiple domains) that display a WD-repeat domain controlling recognition specificity. Based on genomic sequence analysis of different P. anserina isolates, it was established that repeat regions of all members of the gene family are extremely polymorphic and undergoing concerted evolution arguing for frequent recombination within and between family members. Herein, we directly analyzed the genetic instability and diversification of this allorecognition gene family. We have constituted a collection of 143 spontaneous mutants of the het-R (HNWD2) and het-E (hnwd5) genes with altered recognition specificities. The vast majority of the mutants present rearrangements in the repeat arrays with deletions, duplications and other modifications as well as creation of novel repeat unit variants. We investigate the extreme genetic instability of these genes and provide a direct illustration of the diversification strategy of this eukaryotic allorecognition gene family.

Analysis of sequence repeats of proteins in the PDB.

PubMed

Mary Rajathei, David; Selvaraj, Samuel

2013-12-01

Internal repeats in protein sequences play a significant role in the evolution of protein structure and function. Applications of different bioinformatics tools help in the identification and characterization of these repeats. In the present study, we analyzed sequence repeats in a non-redundant set of proteins available in the Protein Data Bank (PDB). We used RADAR for detecting internal repeats in a protein, PDBeFOLD for assessing structural similarity, PDBsum for finding functional involvement and Pfam for domain assignment of the repeats in a protein. Through the analysis of sequence repeats, we found that identity of the sequence repeats falls in the range of 20-40% and, the superimposed structures of the most of the sequence repeats maintain similar overall folding. Analysis sequence repeats at the functional level reveals that most of the sequence repeats are involved in the function of the protein through functionally involved residues in the repeat regions. We also found that sequence repeats in single and two domain proteins often contained conserved sequence motifs for the function of the domain. Copyright © 2013 Elsevier Ltd. All rights reserved.

Structural studies of CNG repeats

PubMed Central

Kiliszek, Agnieszka; Rypniewski, Wojciech

2014-01-01

CNG repeats (where N denotes one of the four natural nucleotides) are abundant in the human genome. Their tendency to undergo expansion can lead to hereditary diseases known as TREDs (trinucleotide repeat expansion disorders). The toxic factor can be protein, if the abnormal gene is expressed, or the gene transcript, or both. The gene transcripts have attracted much attention in the biomedical community, but their molecular structures have only recently been investigated. Model RNA molecules comprising CNG repeats fold into long hairpins whose stems generally conform to an A-type helix, in which the non-canonical N-N pairs are flanked by C-G and G-C pairs. Each homobasic pair is accommodated in the helical context in a unique manner, with consequences for the local helical parameters, solvent structure, electrostatic potential and potential to interact with ligands. The detailed three-dimensional profiles of RNA CNG repeats can be used in screening of compound libraries for potential therapeutics and in structure-based drug design. Here is a brief survey of the CNG structures published to date. PMID:24939898

Effects of Repeated Reading and Listening Passage Preview on Oral Reading Fluency

ERIC Educational Resources Information Center

Swain, Kristine D.; Leader-Janssen, Elizabeth M.; Conley, Perry

2017-01-01

This case study examined the effectiveness of three fluency interventions (i.e., repeated reading, audio listening passage preview and teacher modeled listening passage preview) with a fifth grade student struggling with fluency skills. When compared to baseline, each intervention increased oral reading fluency by the end of the 7 weeks of…

A Complete and Accurate Ab Initio Repeat Finding Algorithm.

PubMed

Lian, Shuaibin; Chen, Xinwu; Wang, Peng; Zhang, Xiaoli; Dai, Xianhua

2016-03-01

It has become clear that repetitive sequences have played multiple roles in eukaryotic genome evolution including increasing genetic diversity through mutation, changes in gene expression and facilitating generation of novel genes. However, identification of repetitive elements can be difficult in the ab initio manner. Currently, some classical ab initio tools of finding repeats have already presented and compared. The completeness and accuracy of detecting repeats of them are little pool. To this end, we proposed a new ab initio repeat finding tool, named HashRepeatFinder, which is based on hash index and word counting. Furthermore, we assessed the performances of HashRepeatFinder with other two famous tools, such as RepeatScout and Repeatfinder, in human genome data hg19. The results indicated the following three conclusions: (1) The completeness of HashRepeatFinder is the best one among these three compared tools in almost all chromosomes, especially in chr9 (8 times of RepeatScout, 10 times of Repeatfinder); (2) in terms of detecting large repeats, HashRepeatFinder also performed best in all chromosomes, especially in chr3 (24 times of RepeatScout and 250 times of Repeatfinder) and chr19 (12 times of RepeatScout and 60 times of Repeatfinder); (3) in terms of accuracy, HashRepeatFinder can merge the abundant repeats with high accuracy.

Repeated Reading. What Works Clearinghouse Intervention Report

ERIC Educational Resources Information Center

What Works Clearinghouse, 2014

2014-01-01

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

Effects of rearing environment and population origin on responses to repeated behavioural trials in cane toads (Rhinella marina).

PubMed

Gruber, Jodie; Whiting, Martin J; Brown, Gregory; Shine, Richard

2018-05-02

Behavioural response to repeated trials in captivity can be driven by many factors including rearing environment, population of origin, habituation to captivity/trial conditions and an individual's behavioural type (e.g., bold versus shy). We tested the effect of rearing environment (captive raised common-garden versus wild-caught) and population origin (range-edge versus range-front) on the responses of invasive cane toads (Rhinella marina) to repeated exploration and risk-taking assays in captivity. We found that behavioural responses to identical assays performed on two occasions were complex and showed few consistent patterns based on rearing environment or population of origin. However, behavioural traits were repeatable across Trial Blocks when all sample populations were grouped together, indicating general consistency in individual toad behaviour across repeated behavioural assays. Our findings exemplify the complexity and unpredictability of behavioural responses and their effects on the repeatability and interpretation of behavioural traits across repeated behavioural assays in captivity. To meaningfully interpret the results from repeated behavioural assays, we need to consider how multiple factors may affect behavioural responses to these tests and importantly, how these responses may affect the repeatability of behavioural traits across time. Copyright © 2018. Published by Elsevier B.V.

Repeat Radiosurgery for Trigeminal Neuralgia.

PubMed

Helis, Corbin A; Lucas, John T; Bourland, J Daniel; Chan, Michael D; Tatter, Stephen B; Laxton, Adrian W

2015-11-01

Repeat Gamma Knife radiosurgery (GKRS) is an established option for patients whose pain has recurred after the initial procedure, with reported success rates varying from 68% to 95%. Predictive factors for response to the repeat GKRS are ill-defined. This cohort study aimed to report the outcomes and factors predictive of success for patients who have undergone repeated GKRS for trigeminal neuralgia at Wake Forest University Baptist Medical Center. Between 1999 and 2013, 152 patients underwent repeat GKRS at Wake Forest, 125 of whom were available for long-term follow-up. A retrospective chart review and telephone interviews were conducted to determine background medical history, dosimetric data, outcomes, and adverse effects of the procedure. Eighty-four percent of patients achieved at least Barrow Neurological Institute (BNI) IIIb pain relief, with 46% achieving BNI I. The 1-, 3-, and 5-year rates of BNI I pain relief were 63%, 50%, and 37%, respectively. The 1-, 3-, and 5-year rates of BNI IIIb or better pain relief were 74%, 59%, and 46%, respectively. One patient experienced bothersome numbness and 2 patients developed anesthesia dolorosa. The dominant predictive factors for pain relief were facial numbness after the first GKRS and a positive pain response to the first GKRS. Repeat GKRS is an effective method of treating recurrent trigeminal neuralgia. Patients who have facial numbness after the first treatment and a positive pain response to the first GKRS are significantly more likely to respond well to the second treatment.

Repeat surfactant therapy for postsurfactant slump.

PubMed

Katz, L A; Klein, J M

2006-07-01

To evaluate repeat surfactant therapy for the treatment of respiratory failure associated with postsurfactant slump in extremely low birth weight infants (ELBW) by characterizing the population of premature infants who develop postsurfactant slump and measuring their response to a secondary course of surfactant therapy. A retrospective analysis of a cohort of all patients admitted over a 3-year period with birth weights <1000 g (ELBW infants). Information was collected by chart review and the patients were categorized into three distinct groups for analysis. Initial surfactant only, patients who received surfactant replacement therapy only for respiratory distress syndrome (RDS); repeat surfactant, patients who received both initial surfactant replacement for RDS and repeat surfactant therapy for postsurfactant slump (defined as respiratory failure after 6 days of age), and no surfactant, patients in whom no surfactant was ever administered. A respiratory severity score (RSS) was used to measure the severity of lung disease and response to surfactant therapy. Over 3 years, there were 165 ELBW infants who could develop postsurfactant slump and be eligible for repeat surfactant therapy. There were 39 infants who never received any surfactant therapy estimated gestational age (EGA) 27.7 +/- 1.7, birth weight 856 +/- 109 g) either at birth or after 6 days of life. There were 126 patients treated for RDS with initial surfactant replacement therapy (EGA 25.6 +/- 1.9 weeks, birth weight 713 +/- 179 g). Out of these RDS patients, 101 improved with an initial course of surfactant therapy (EGA 26 +/- 1.8, birth weight 751 +/- 143 g), but 25 (20% of the patients with RDS) developed postsurfactant slump and received a repeat course of surfactant therapy (EGA 24.7 +/- 1.2, birth weight 647 +/- 120 g). The repeat surfactant group (postsurfactant slump) was significantly more premature and had significantly lower birth weights compared to both the initial surfactant only group

Increased levels of IgE and autoreactive, polyreactive IgG in wild rodents: implications for the hygiene hypothesis

USGS Publications Warehouse

Devalapalli, A.P.; Lesher, A.; Shieh, K.; Solow, J.S.; Everett, M.L.; Edala, A.S.; Whitt, P.; Long, Renee R.; Newton, N.; Parker, W.

2006-01-01

To probe the potential role of Th1 versus Th2 reactivity underlying the hygiene hypothesis, intrinsic levels of Th1-associated and Th2-associated antibodies in the serum of wild rodents were compared with that in various strains of laboratory rodents. Studies using rat lung antigens as a target indicated that wild rats have substantially greater levels of autoreactive, polyreactive immunoglobulin G (IgG), but not autoreactive, polyreactive IgM than do laboratory rats, both on a quantitative and qualitative basis. Increased levels of serum IgG and IgE were observed in both wild rats and wild mice relative to their laboratory-raised counterparts, with the effect being most pronounced for IgE levels. Further, wild rats had greater intrinsic levels of both Th1- and Th2-associated IgG subclasses than did lab rats. The habitat (wild versus laboratory raised) had a more substantial impact on immunoglobulin concentration than did age, strain or gender in the animals studied. The presence in wild rodents of increased intrinsic, presumably protective, non-pathogenic responses similar to both autoimmune (autoreactive IgG, Th1-associated) and allergic (IgE, Th2-associated) reactions as well as increased levels of Th1-associated and Th2-associated IgG subclasses points toward a generally increased stimulation of the immune system in these animals rather than a shift in the nature of the immunoreactivity. It is concluded that, at least to the extent that feedback inhibition is a controlling element of immunoreactivity, an overly hygienic environment may affect the threshold of both types of immune responses more so than the balance between the different responses.

Increased levels of IgE and autoreactive, polyreactive IgG in wild rodents: implications for the hygiene hypothesis.

PubMed

Devalapalli, A P; Lesher, A; Shieh, K; Solow, J S; Everett, M L; Edala, A S; Whitt, P; Long, R R; Newton, N; Parker, W

2006-08-01

To probe the potential role of Th1 versus Th2 reactivity underlying the hygiene hypothesis, intrinsic levels of Th1-associated and Th2-associated antibodies in the serum of wild rodents were compared with that in various strains of laboratory rodents. Studies using rat lung antigens as a target indicated that wild rats have substantially greater levels of autoreactive, polyreactive immunoglobulin G (IgG), but not autoreactive, polyreactive IgM than do laboratory rats, both on a quantitative and qualitative basis. Increased levels of serum IgG and IgE were observed in both wild rats and wild mice relative to their laboratory-raised counterparts, with the effect being most pronounced for IgE levels. Further, wild rats had greater intrinsic levels of both Th1- and Th2-associated IgG subclasses than did lab rats. The habitat (wild versus laboratory raised) had a more substantial impact on immunoglobulin concentration than did age, strain or gender in the animals studied. The presence in wild rodents of increased intrinsic, presumably protective, non-pathogenic responses similar to both autoimmune (autoreactive IgG, Th1-associated) and allergic (IgE, Th2-associated) reactions as well as increased levels of Th1-associated and Th2-associated IgG subclasses points toward a generally increased stimulation of the immune system in these animals rather than a shift in the nature of the immunoreactivity. It is concluded that, at least to the extent that feedback inhibition is a controlling element of immunoreactivity, an overly hygienic environment may affect the threshold of both types of immune responses more so than the balance between the different responses.

Long interspersed repeated DNA (LINE) causes polymorphism at the rat insulin 1 locus.

PubMed

Lakshmikumaran, M S; D'Ambrosio, E; Laimins, L A; Lin, D T; Furano, A V

1985-09-01

The insulin 1, but not the insulin 2, locus is polymorphic (i.e., exhibits allelic variation) in rats. Restriction enzyme analysis and hybridization studies showed that the polymorphic region is 2.2 kilobases upstream of the insulin 1 coding region and is due to the presence or absence of an approximately 2.7-kilobase repeated DNA element. DNA sequence determination showed that this DNA element is a member of a long interspersed repeated DNA family (LINE) that is highly repeated (greater than 50,000 copies) and highly transcribed in the rat. Although the presence or absence of LINE sequences at the insulin 1 locus occurs in both the homozygous and heterozygous states, LINE-containing insulin 1 alleles are more prevalent in the rat population than are alleles without LINEs. Restriction enzyme analysis of the LINE-containing alleles indicated that at least two versions of the LINE sequence may be present at the insulin 1 locus in different rats. Either repeated transposition of LINE sequences or gene conversion between the resident insulin 1 LINE and other sequences in the genome are possible explanations for this.

Long interspersed repeated DNA (LINE) causes polymorphism at the rat insulin 1 locus.

PubMed Central

Lakshmikumaran, M S; D'Ambrosio, E; Laimins, L A; Lin, D T; Furano, A V

1985-01-01

The insulin 1, but not the insulin 2, locus is polymorphic (i.e., exhibits allelic variation) in rats. Restriction enzyme analysis and hybridization studies showed that the polymorphic region is 2.2 kilobases upstream of the insulin 1 coding region and is due to the presence or absence of an approximately 2.7-kilobase repeated DNA element. DNA sequence determination showed that this DNA element is a member of a long interspersed repeated DNA family (LINE) that is highly repeated (greater than 50,000 copies) and highly transcribed in the rat. Although the presence or absence of LINE sequences at the insulin 1 locus occurs in both the homozygous and heterozygous states, LINE-containing insulin 1 alleles are more prevalent in the rat population than are alleles without LINEs. Restriction enzyme analysis of the LINE-containing alleles indicated that at least two versions of the LINE sequence may be present at the insulin 1 locus in different rats. Either repeated transposition of LINE sequences or gene conversion between the resident insulin 1 LINE and other sequences in the genome are possible explanations for this. Images PMID:3016521

Out of sight, out of mind: Do repeating students overlook online course components?

PubMed

Holland, Jane; Clarke, Eric; Glynn, Mark

2016-11-01

E-Learning is becoming an integral part of undergraduate medicine, with many curricula incorporating a number of online activities and resources, in addition to more traditional teaching methods. This study examines physical attendance, online activity, and examination outcomes in a first-year undergraduate medical program. All 358 students who completed the Alimentary System module within the first semester of the program were included, 30 of whom were repeating the year, and thus the module. This systems-based, multidisciplinary module incorporated didactic lectures, cadaveric small group tutorials and additional e-Learning resources such as online histology tutorials. Significant differences were demonstrated in physical attendance and utilization of online resources between repeating students and those participating in the module for the first time. Subsequent analyses confirmed that physical attendance, access of online lecture resources, and utilization of online histology tutorials were all significantly correlated. In addition, both physical attendance and utilization of online resources significantly correlated with summative examination performance. While nonattendance may be due to a variety of factors, our data confirm that significant differences exist in both physical attendance and online activity between new entrants and repeating students, such that all students repeating a module or academic year should be routinely interviewed and offered appropriate supports to ensure that they continue to engage with the program. While the development of complex algorithmic models may be resource intensive, using readily available indices from virtual learning environments is a straightforward, albeit less powerful, means to identify struggling students prior to summative examinations. Anat Sci Educ 9: 555-564. © 2016 American Association of Anatomists. © 2016 American Association of Anatomists.

[Study on causes and treatment of repeated vulvovaginitis in girlhood].

PubMed

Zhang, Di-kai; Li, Xiu-yun; Yang, Dong-zi; Kuang, Jian-quan

2006-07-01

To explore the causes and treatment of repeated vulvovaginitis in girlhood in order to improve its prevention and treatment. Fifty-one girls with repeated vulvovaginitis (age < or = 10 years) admitted to The Second Affiliated Hospital of Sun Yat-sen University from Jan. 1990 to Nov. 2004 were reviewed retrospectively. We found 28 girls (55%) suffering from non-specific vulvovaginitis and 14 ones (27%) suffering from posterior recto-vaginal fistula with in 51 patients. Five girls (10%) were smitten with vulval ulcer and 3 ones (6%) had been were found with vaginal foreign bodies. One girl (2%) was smitten with adhesion of labia minora. The vaginal discharges taken from 21 girls were cultured. Seventeen cases found bacteria. The positive rate of bacteria culture in the 21 cases reached 81%, in which, E.coli accounted for 5 cases (24%), staphylococcus and streptococcus accounted for 3 cases (14%) respectively. Patients suffering from non-specific vulvovaginitis and vulval ulcer accepted external lotion, antibiotic ointment or combining with antibiotics. Patients suffering from posterior recto-vaginal fistula accepted fistulectomy. Three girls who found vaginal foreign bodies took out of foreign bodies by hysteroscope. Fifty-one girls all were cured after appropriate therapy. Vulvovaginitis is the most common gynecologic diagnosis in girlhood. The principal cause of repeated invasion is non-specific vulvovaginitis and the secondly one is posterior recto-vaginal fistula. It need overhaul during the diagnosis. It is very availability to use hysteroscopy and do bacteria culture + antibiotic sensitivity test for repeated pediatric vulvovaginitis.

Structural studies of CNG repeats.

PubMed

Kiliszek, Agnieszka; Rypniewski, Wojciech

2014-07-01

CNG repeats (where N denotes one of the four natural nucleotides) are abundant in the human genome. Their tendency to undergo expansion can lead to hereditary diseases known as TREDs (trinucleotide repeat expansion disorders). The toxic factor can be protein, if the abnormal gene is expressed, or the gene transcript, or both. The gene transcripts have attracted much attention in the biomedical community, but their molecular structures have only recently been investigated. Model RNA molecules comprising CNG repeats fold into long hairpins whose stems generally conform to an A-type helix, in which the non-canonical N-N pairs are flanked by C-G and G-C pairs. Each homobasic pair is accommodated in the helical context in a unique manner, with consequences for the local helical parameters, solvent structure, electrostatic potential and potential to interact with ligands. The detailed three-dimensional profiles of RNA CNG repeats can be used in screening of compound libraries for potential therapeutics and in structure-based drug design. Here is a brief survey of the CNG structures published to date. © Published by Oxford University Press on behalf of Nucleic Acids Research.

Distribution and Evolution of Yersinia Leucine-Rich Repeat Proteins

PubMed Central

Hu, Yueming; Huang, He; Hui, Xinjie; Cheng, Xi; White, Aaron P.

2016-01-01

Leucine-rich repeat (LRR) proteins are widely distributed in bacteria, playing important roles in various protein-protein interaction processes. In Yersinia, the well-characterized type III secreted effector YopM also belongs to the LRR protein family and is encoded by virulence plasmids. However, little has been known about other LRR members encoded by Yersinia genomes or their evolution. In this study, the Yersinia LRR proteins were comprehensively screened, categorized, and compared. The LRR proteins encoded by chromosomes (LRR1 proteins) appeared to be more similar to each other and different from those encoded by plasmids (LRR2 proteins) with regard to repeat-unit length, amino acid composition profile, and gene expression regulation circuits. LRR1 proteins were also different from LRR2 proteins in that the LRR1 proteins contained an E3 ligase domain (NEL domain) in the C-terminal region or an NEL domain-encoding nucleotide relic in flanking genomic sequences. The LRR1 protein-encoding genes (LRR1 genes) varied dramatically and were categorized into 4 subgroups (a to d), with the LRR1a to -c genes evolving from the same ancestor and LRR1d genes evolving from another ancestor. The consensus and ancestor repeat-unit sequences were inferred for different LRR1 protein subgroups by use of a maximum parsimony modeling strategy. Structural modeling disclosed very similar repeat-unit structures between LRR1 and LRR2 proteins despite the different unit lengths and amino acid compositions. Structural constraints may serve as the driving force to explain the observed mutations in the LRR regions. This study suggests that there may be functional variation and lays the foundation for future experiments investigating the functions of the chromosomally encoded LRR proteins of Yersinia. PMID:27217422

Prospective, randomized comparison of OM-85 BV and a prophylactic antibiotic in children with recurrent infections and immunoglobulin A and/or G subclass deficiency☆

PubMed Central

Genel, Ferah; Kutukculer, Necil

2003-01-01

Background Patients with immunoglobulin (Ig)A and/or IgG subclass deficiency may be asymptomatic or may have recurrent, mainly respiratory infections. Objective This study compared the clinical efficacy and tolerability of prophylactic therapy with either the oral immunomodulator bacterial extract OM-85 BV or benzathine penicillin G (BPG) in the prevention of recurrent infections in symptomatic patients. Methods In this 26-month, prospective, randomized study conducted at the Department of Pediatric Immunology, Ege University (Izmir, Turkey), children aged 1 to 12 years with recurrent infections and IgA and/or IgG subclass deficiency were enrolled. After an initial 12-month control period, patients were randomized to receive OM-85 BV or BPG. OM-85 BV (3.5-mg capsule) was given once daily for the first 10 days of each month for the first 3 months of the study. IM injections of BPG were given at a dose of 1.2 million units (for patients with body weight > 27 kg) or at a half-dose (for patients with body weight ≤27 kg) every 3 weeks for 12 months. In nonresponders (ie, those who continued to have recurrent infections at 12-month follow-up), IV immunoglobulin (IVIG) replacement therapy at 400 mg/kg body weight was given every 4 weeks for an additional 12 months. The results of IVIG therapy were assessed by the authors using clinical observation. Adverse effects and adverse drug reactions were documented by the authors for each vaccine, prophylactic therapy, and IVIG. Results A total of 91 children (56 boys, 35 girls; mean [SD] age at the start of the control period, 46.4 [31.0] months) were enrolled. Of these, 44 were randomized to the OM-85 BV group and 47 to the BPG group. The year before prophylactic therapy, the mean (SD) number of reported infections was 10.7 (3.6) and the mean (SD) number of antibiotic courses was 9.7 (3.6) (OM-85 BV group: mean [SD] number of reported infections, 10.5 [3.3]; mean (SD) number of antibiotic courses, 9.3 [3.3]; BPG group: mean

Intraindividual variability of boldness is repeatable across contexts in a wild lizard.

PubMed

Highcock, Laura; Carter, Alecia J

2014-01-01

Animals do not behave in exactly the same way when repeatedly tested in the same context or situation, even once systematic variation, such as habituation, has been controlled for. This unpredictability is called intraindividual variability (IIV) and has been little studied in animals. Here we investigated how IIV in boldness (estimated by flight initiation distances) changed across two seasons--the dry, non-breeding season and the wet, breeding season--in a wild population of the Namibian rock agama, Agama planiceps. We found significant differences in IIV both between individuals and seasons, and IIV was higher in the wet season, suggesting plasticity in IIV. Further, IIV was highly repeatable (r = 0.61) between seasons and we found strong negative correlations between consistent individual differences in flight initiation distances, i.e. their boldness, and individuals' IIVs. We suggest that to understand personality in animals, researchers should generate a personality 'profile' that includes not only the relative level of a trait (i.e. its personality), but also its plasticity and variability under natural conditions.

Some characteristics of repeated sickness absence

PubMed Central

Ferguson, David

1972-01-01

Ferguson, D. (1972).Brit. J. industr. Med.,29, 420-431. Some characteristics of repeated sickness absence. Several studies have shown that frequency of absence attributed to sickness is not distributed randomly but tends to follow the negative binomial distribution, and this has been taken to support the concept of `proneness' to such absence. Thus, the distribution of sickness absence resembles that of minor injury at work demonstrated over 50 years ago. Because the investigation of proneness to absence does not appear to have been reported by others in Australia, the opportunity was taken, during a wider study of health among telegraphists in a large communications undertaking, to analyse some characteristics of repeated sickness absence. The records of medically certified and uncertified sickness absence of all 769 telegraphists continuously employed in all State capitals over a two-and-a-half-year period were compared with those of 411 clerks and 415 mechanics and, in Sydney, 380 mail sorters and 80 of their supervisors. All telegraphists in Sydney, Melbourne, and Brisbane, and all mail sorters in Sydney, who were available and willing were later medically examined. From their absence pattern repeaters (employees who had had eight or more certified absences in two and a half years) were separated into three types based on a presumptive origin in chance, recurrent disease and symptomatic non-specific disorder. The observed distribution of individual frequency of certified absence over the full two-and-a-half-year period of study followed that expected from the univariate negative binomial, using maximum likelihood estimators, rather than the poisson distribution, in three of the four occupational groups in Sydney. Limited correlational and bivariate analysis supported the interpretation of proneness ascribed to the univariate fit. In the two groups studied, frequency of uncertified absence could not be fitted by the negative binomial, although the numbers of

Deletion of internal structured repeats increases the stability of a leucine-rich repeat protein, YopM

PubMed Central

Barrick, Doug

2011-01-01

Mapping the stability distributions of proteins in their native folded states provides a critical link between structure, thermodynamics, and function. Linear repeat proteins have proven more amenable to this kind of mapping than globular proteins. C-terminal deletion studies of YopM, a large, linear leucine-rich repeat (LRR) protein, show that stability is distributed quite heterogeneously, yet a high level of cooperativity is maintained [1]. Key components of this distribution are three interfaces that strongly stabilize adjacent sequences, thereby maintaining structural integrity and promoting cooperativity. To better understand the distribution of interaction energy around these critical interfaces, we studied internal (rather than terminal) deletions of three LRRs in this region, including one of these stabilizing interfaces. Contrary to our expectation that deletion of structured repeats should be destabilizing, we find that internal deletion of folded repeats can actually stabilize the native state, suggesting that these repeats are destabilizing, although paradoxically, they are folded in the native state. We identified two residues within this destabilizing segment that deviate from the consensus sequence at a position that normally forms a stacked leucine ladder in the hydrophobic core. Replacement of these nonconsensus residues with leucine is stabilizing. This stability enhancement can be reproduced in the context of nonnative interfaces, but it requires an extended hydrophobic core. Our results demonstrate that different LRRs vary widely in their contribution to stability, and that this variation is context-dependent. These two factors are likely to determine the types of rearrangements that lead to folded, functional proteins, and in turn, are likely to restrict the pathways available for the evolution of linear repeat proteins. PMID:21764506

Identification and Characterization of Functionally Critical, Conserved Motifs in the Internal Repeats and N-terminal Domain of Yeast Translation Initiation Factor 4B (yeIF4B)*

PubMed Central

Zhou, Fujun; Walker, Sarah E.; Mitchell, Sarah F.; Lorsch, Jon R.; Hinnebusch, Alan G.

2014-01-01

eIF4B has been implicated in attachment of the 43 S preinitiation complex (PIC) to mRNAs and scanning to the start codon. We recently determined that the internal seven repeats (of ∼26 amino acids each) of Saccharomyces cerevisiae eIF4B (yeIF4B) compose the region most critically required to enhance mRNA recruitment by 43 S PICs in vitro and stimulate general translation initiation in yeast. Moreover, although the N-terminal domain (NTD) of yeIF4B contributes to these activities, the RNA recognition motif is dispensable. We have now determined that only two of the seven internal repeats are sufficient for wild-type (WT) yeIF4B function in vivo when all other domains are intact. However, three or more repeats are needed in the absence of the NTD or when the functions of eIF4F components are compromised. We corroborated these observations in the reconstituted system by demonstrating that yeIF4B variants with only one or two repeats display substantial activity in promoting mRNA recruitment by the PIC, whereas additional repeats are required at lower levels of eIF4A or when the NTD is missing. These findings indicate functional overlap among the 7-repeats and NTD domains of yeIF4B and eIF4A in mRNA recruitment. Interestingly, only three highly conserved positions in the 26-amino acid repeat are essential for function in vitro and in vivo. Finally, we identified conserved motifs in the NTD and demonstrate functional overlap of two such motifs. These results provide a comprehensive description of the critical sequence elements in yeIF4B that support eIF4F function in mRNA recruitment by the PIC. PMID:24285537

Repeat microearthquakes observed in western Nagano, Japan and implications to rupture dynamics

NASA Astrophysics Data System (ADS)

Cheng, X.; Niu, F.; Silver, P.; Horiuchi, S.; Takai, K.

2005-12-01

the first rupture, (i.e., no intermediate repeaters), similar to those observed by Rubin and Gillard (2000). Stress drop seems to be independent to earthquake size, and is estimated to be a few tens of mega-Pascal, which is slightly higher than those observed at the San Andreas Fault.

Children's False Memory and True Disclosure in the Face of Repeated Questions

ERIC Educational Resources Information Center

Schaaf, Jennifer M.; Alexander, Kristen Weede; Goodman, Gail S.

2008-01-01

The current study was designed to investigate children's memory and suggestibility for events differing in valence (positive or negative) and veracity (true or false). A total of 82 3- and 5-year-olds were asked repeated questions about true and false events, either in a grouped order (i.e., all questions about a certain event asked consecutively)…

Digital repeat analysis; setup and operation.

PubMed

Nol, J; Isouard, G; Mirecki, J

2006-06-01

Since the emergence of digital imaging, there have been questions about the necessity of continuing reject analysis programs in imaging departments to evaluate performance and quality. As a marketing strategy, most suppliers of digital technology focus on the supremacy of the technology and its ability to reduce the number of repeats, resulting in less radiation doses given to patients and increased productivity in the department. On the other hand, quality assurance radiographers and radiologists believe that repeats are mainly related to positioning skills, and repeat analysis is the main tool to plan training needs to up-skill radiographers. A comparative study between conventional and digital imaging was undertaken to compare outcomes and evaluate the need for reject analysis. However, digital technology still being at its early development stages, setting a credible reject analysis program became the major task of the study. It took the department, with the help of the suppliers of the computed radiography reader and the picture archiving and communication system, over 2 years of software enhancement to build a reliable digital repeat analysis system. The results were supportive of both philosophies; the number of repeats as a result of exposure factors was reduced dramatically; however, the percentage of repeats as a result of positioning skills was slightly on the increase for the simple reason that some rejects in the conventional system qualifying for both exposure and positioning errors were classified as exposure error. The ability of digitally adjusting dark or light images reclassified some of those images as positioning errors.

High-speed and low-power repeater for VLSI interconnects

NASA Astrophysics Data System (ADS)

Karthikeyan, A.; Mallick, P. S.

2017-10-01

This paper proposes a repeater for boosting the speed of interconnects with low power dissipation. We have designed and implemented at 45 and 32 nm technology nodes. Delay and power dissipation performances are analyzed for various voltage levels at these technology nodes using Spice simulations. A significant reduction in delay and power dissipation are observed compared to a conventional repeater. The results show that the proposed high-speed low-power repeater has a reduced delay for higher load capacitance. The proposed repeater is also compared with LPTG CMOS repeater, and the results shows that the proposed repeater has reduced delay. The proposed repeater can be suitable for high-speed global interconnects and has the capacity to drive large loads.

Demonstration of IgG Subclass (IgG1 and IgG3) in Immuno-Related Hemocytopenia.

PubMed

Shao, Yuanyuan; Qi, Xiao; Fu, Rong; Liu, Hui; Wang, Yihao; Ding, Shaoxue; Wang, Huaquan; Li, Lijuan; Shao, Zonghong

2018-06-01

Immuno-related hemocytopenia (IRH) is defined as idiopathic cytopenia of undetermined significance (ICUS) patients with autoantibodies. In our previous studies, we found that IgG1 levels were increased in IRH patients and might cause the destruction of hematopoietic cells. In this study, we analyzed IgG subclasses in 30 IRH patients (male:female = 13:17, median age 32 years, range 18 - 56), 15 IRH remission patients (IRH-R) (male:female = 6:9, median age 34, range 20 - 52) and 20 normal controls (male:female = 8:12, median age 27, range 24 - 36) by Cytometric Bead Array, Flow Cytometry and Immunohistochemical staining. Levels of IgG1/IgG3 in the bone marrow supernatant of IRH patents, as well as the proportion of CD5+ B lymphocytes and Th2 cells (CD3+CD8-IL-4+) were higher than those of IRH-R patients and normal controls, and IgG1 levels had a positive correlation with the proportion of Th2 cells. In IRH patients, IgG1 and IgG3 were positive on nucleated erythrocytes and granulocytes, which were negative in IRH-R patients and healthy controls and had inverse correlations with hematopoietic function. Using immunohistochemical staining, IgG1 were also detected on bone marrow biopsies of IRH patients. The results indicated that IgG1 and IgG3 autoantibodies in IRH patients might play a key role in the IRH pathogenesis and in the abnormal immune function of IRH patients.

Repeated quick hot-and-chilling treatments for the inactivation of Escherichia coli O157:H7 in mung bean and radish seeds.

PubMed

Bari, Md Latiful; Sugiyama, Jun; Kawamoto, Shinnichi

2009-01-01

The majority of the seed sprout-related outbreaks have been associated with Escherichia coli O157:H7. Therefore, it is necessary to find an effective method to inactivate these organisms on the seeds prior to sprouting. This study was conducted to assess the effectiveness of repeated quick hot-and-chilling treatments with various chemicals to inactivate E. coli O157:H7 populations inoculated onto mung bean and radish seeds intended for sprout production and to determine the effect of these treatments on seed germination. The treatment time was 20 sec for quick hot and 20 sec for quick chilling in one repeat. Likewise up to five repeats were done throughout the experiments. The chemicals used for this study were electrolyzed acidic (EO) water, phytic acid (0.05%), oxalic acid (3%), surfcera(R), and alpha-torino water(R), and distilled water was used as control. The quick hot treatment was done with 75 degrees C, 70 degrees C, and 60 degrees C, and the chilling temperature was 0 degrees C. The treated seeds were then assessed for the efficacy of this treatment in reducing populations of the pathogens and the effects of repeated quick hot-and-chilling treatments on germination yield. It was found that repeating treatment at 75 degrees C for two or three repeats with phytic acid and oxalic acid could reduce 4.38-log colony-forming unit (CFU)/g of E. coli O157:H7 in mung bean seeds. EO water and distilled water were found equally effective at 75 degrees C for four or five repeats to inactivate E. coli O157:H7 in mung bean seeds. However, alpha-torino water(R) and surfcera(R) were not found effective in comparison to other sanitizers used in this experiment. Irrespective of sanitizer used, the germination yield of the mung bean seed was not affected significantly. On the other hand, distilled water, EO water, and alpha-torino water(R) at 75 degrees C for five repeats were found effective in reducing 5.80-log CFU/g of E. coli O157:H7 in radish seeds; however, the

Coexistence of 3G repeaters with LTE base stations.

PubMed

Yeo, Woon-Young; Lee, Sang-Min; Hwang, Gyung-Ho; Kim, Jae-Hoon

2013-01-01

Repeaters have been an attractive solution for mobile operators to upgrade their wireless networks at low cost and to extend network coverage effectively. Since the first LTE commercial deployment in 2009, many mobile operators have launched LTE networks by upgrading their 3G and legacy networks. Because all 3G frequency bands are shared with the frequency bands for LTE deployment and 3G mobile operators have an enormous number of repeaters, reusing 3G repeaters in LTE networks is definitely a practical and cost-efficient solution. However, 3G repeaters usually do not support spatial multiplexing with multiple antennas, and thus it is difficult to reuse them directly in LTE networks. In order to support spatial multiplexing of LTE, the role of 3G repeaters should be replaced with small LTE base stations or MIMO-capable repeaters. In this paper, a repeater network is proposed to reuse 3G repeaters in LTE deployment while still supporting multilayer transmission of LTE. Interestingly, the proposed network has a higher cluster throughput than an LTE network with MIMO-capable repeaters.

Coexistence of 3G Repeaters with LTE Base Stations

PubMed Central

Yeo, Woon-Young

2013-01-01

Repeaters have been an attractive solution for mobile operators to upgrade their wireless networks at low cost and to extend network coverage effectively. Since the first LTE commercial deployment in 2009, many mobile operators have launched LTE networks by upgrading their 3G and legacy networks. Because all 3G frequency bands are shared with the frequency bands for LTE deployment and 3G mobile operators have an enormous number of repeaters, reusing 3G repeaters in LTE networks is definitely a practical and cost-efficient solution. However, 3G repeaters usually do not support spatial multiplexing with multiple antennas, and thus it is difficult to reuse them directly in LTE networks. In order to support spatial multiplexing of LTE, the role of 3G repeaters should be replaced with small LTE base stations or MIMO-capable repeaters. In this paper, a repeater network is proposed to reuse 3G repeaters in LTE deployment while still supporting multilayer transmission of LTE. Interestingly, the proposed network has a higher cluster throughput than an LTE network with MIMO-capable repeaters. PMID:24459420

FRB 121102: A Starquake-induced Repeater?

NASA Astrophysics Data System (ADS)

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

2018-01-01

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

Repeated exposure of the developing rat brain to magnetic resonance imaging did not affect neurogenesis, cell death or memory function

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

Zhu, Changlian; Department of Pediatrics, The Third Affiliated Hospital, Zhengzhou University; Gao, Jianfeng

2011-01-07

Research highlights: {yields} The effect of MRI on the developing brain is a matter of debate. {yields} Repeated exposure to MRI did not affect neurogenesis. {yields} Memory function was not affected by repeated MRI during development. {yields} Neither late gestation nor young postnatal brains were affected by MRI. {yields} Repeated MRI did not cause cell death in the neurogenic region of the hippocampus. -- Abstract: The effect of magnetic fields on the brain is a matter of debate. The objective of this study was to investigate whether repeated exposure to strong magnetic fields, such as during magnetic resonance imaging (MRI),more » could elicit changes in the developing rat brain. Embryonic day 15 (E15) and postnatal day 14 (P14) rats were exposed to MRI using a 7.05 T MR system. The animals were anesthetized and exposed for 35 min per day for 4 successive days. Control animals were anesthetized but no MRI was performed. Body temperature was maintained at 37 {sup o}C. BrdU was injected after each session (50 mg/kg). One month later, cell proliferation, neurogenesis and astrogenesis in the dentate gyrus were evaluated, revealing no effects of MRI, neither in the E15, nor in the P14 group. DNA damage in the dentate gyrus in the P14 group was evaluated on P18, 1 day after the last session, using TUNEL staining. There was no difference in the number of TUNEL-positive cells after MRI compared with controls, neither in mature neurons, nor in newborn progenitors (BrdU/TUNEL double-labeled cells). Novel object recognition was performed to assess memory function 1 month after MRI. There was no difference in the recognition index observed after MRI compared with the control rats, neither for the E15, nor for the P14 group. In conclusion, repeated exposure to MRI did not appear to affect neurogenesis, cell death or memory function in rats, neither in late gestation (E15-E18) nor in young postnatal (P14-P17) rats.« less

Effect of Chitosan and Liposome Nanoparticles as Adjuvant Codelivery on the Immunoglobulin G Subclass Distribution in a Mouse Model.

PubMed

Haryono, Agus; Salsabila, Korrie; Restu, Witta Kartika; Harmami, Sri Budi; Safari, Dodi

2017-01-01

We investigate the immunogenic properties of chitosan and liposome nanoparticles as adjuvant codelivery against a commercial pneumococcal conjugate vaccine (PCV) in an animal model. The chitosan and liposome nanoparticles were prepared by ionic gelation and dry methods, respectively. The PCV immunization was performed intradermally in the presence of adjuvants and booster injections which were given without an adjuvant. The Quil-A® was used as a control adjuvant. The ELISA was performed to measure the antibodies against pneumococcal type 14 polysaccharide (Pn14PS). The level of total antibodies against Pn14PS antigen was no different between the mouse groups with or without adjuvant codelivery. Codelivery of the PCV with chitosan nanoparticles as well as the Quil-A adjuvant elicited IgG1, IgG2a, IgG2b, and IgG3 antibodies. Meanwhile, codelivery of liposome nanoparticles elicited mainly IgG1 antibodies against the Pn14PS. The chitosan and liposome nanoparticles as adjuvant codelivery were successfully synthesized. These nanoparticles have different shapes in particle formation, liposome nanoparticle with their unilamellar shape and chitosan nanoparticles in large shape due to the aggregation of small-size particles. Codelivery of chitosan nanoparticles has more effect on the IgG subclass antibody production than that of liposome nanoparticles in a mouse model.

Small leucine-rich repeat proteoglycans associated with mature insoluble elastin serve as binding sites for galectins.

PubMed

Itoh, Aiko; Nonaka, Yasuhiro; Ogawa, Takashi; Nakamura, Takanori; Nishi, Nozomu

2017-11-01

We previously reported that galectin-9 (Gal-9), an immunomodulatory animal lectin, could bind to insoluble collagen preparations and exerted direct cytocidal effects on immune cells. In the present study, we found that mature insoluble elastin is capable of binding Gal-9 and other members of the human galectin family. Lectin blot analysis of a series of commercial water-soluble elastin preparations, PES-(A) ~ PES-(E), revealed that only PES-(E) contained substances recognized by Gal-9. Gal-9-interacting substances in PES-(E) were affinity-purified, digested with trypsin and then analyzed by reversed-phase HPLC. Peptide fragments derived from five members of the small leucine-rich repeat proteoglycan family, versican, lumican, osteoglycin/mimecan, prolargin, and fibromodulin, were identified by N-terminal amino acid sequence analysis. The results indicate that Gal-9 and possibly other galectins recognize glycans attached to small leucine-rich repeat proteoglycans associated with insoluble elastin and also indicate the possibility that mature insoluble elastin serves as an extracellular reservoir for galectins.

Acute exercise attenuates negative affect following repeated sad mood inductions in persons who have recovered from depression.

PubMed

Mata, Jutta; Hogan, Candice L; Joormann, Jutta; Waugh, Christian E; Gotlib, Ian H

2013-02-01

Identifying factors that may protect individuals from developing Major Depressive Disorder (MDD) in the face of stress is critical. In the current study we experimentally tested whether such a potentially protective factor, engaging in acute exercise, reduces the adverse effects of repeated sad mood inductions in individuals who have recovered from depression. We hypothesized that recovered depressed participants who engage in acute exercise report a smaller increase in negative affect (NA) and a smaller decrease in positive affect (PA) when exposed to a repeated sad mood induction (i.e., habituation), whereas participants who do not exercise show sensitization (i.e., increased NA and decreased PA in response to a repeated adverse stimulus). Forty-one women recovered from MDD and 40 healthy control women were randomly assigned to either exercise for 15 minutes or quiet rest. Afterward, participants were exposed to two sad mood inductions and reported their levels of affect throughout the study. Recovered depressed participants who had not exercised exhibited higher NA after the second sad mood induction, a finding consistent with sensitization. In contrast, both recovered depressed participants who had engaged in acute exercise and healthy control participants showed no increase in NA in response to the repeated sad mood induction. Participants who exercised reported higher PA after the exercise bout; however, our hypothesis concerning reported PA trajectories following the sad mood inductions was not supported. Results suggest that exercise can serve as a protective factor in the face of exposure to repeated emotional stressors, particularly concerning NA in individuals who have recovered from depression. 2013 APA, all rights reserved

Do gamma-ray burst sources repeat?

NASA Technical Reports Server (NTRS)

Meegan, C. A.; Hartmann, D. H.; Brainerd, J. J.; Briggs, M.; Paciesas, W. S.; Pendleton, G.; Kouveliotou, C.; Fishman, G.; Blumenthal, G.; Brock, M.

1994-01-01

The demonstration of repeated gamma-ray bursts from an individual source would severely constrain burst source models. Recent reports of evidence for repetition in the first BATSE burst catalog have generated renewed interest in this issue. Here, we analyze the angular distribution of 585 bursts of the second BATSE catalog (Meegan et al. 1994). We search for evidence of burst recurrence using the nearest and farthest neighbor statistic ad the two-point angular correlation function. We find the data to be consistent with the hypothesis that burst sources do not repeat; however, a repeater fraction of up to about 20% of the bursts cannot be excluded.

Test–retest repeatability of human speech biomarkers from static and real-time dynamic magnetic resonance imaging

PubMed Central

Töger, Johannes; Sorensen, Tanner; Somandepalli, Krishna; Toutios, Asterios; Lingala, Sajan Goud; Narayanan, Shrikanth; Nayak, Krishna

2017-01-01

Static anatomical and real-time dynamic magnetic resonance imaging (RT-MRI) of the upper airway is a valuable method for studying speech production in research and clinical settings. The test–retest repeatability of quantitative imaging biomarkers is an important parameter, since it limits the effect sizes and intragroup differences that can be studied. Therefore, this study aims to present a framework for determining the test–retest repeatability of quantitative speech biomarkers from static MRI and RT-MRI, and apply the framework to healthy volunteers. Subjects (n = 8, 4 females, 4 males) are imaged in two scans on the same day, including static images and dynamic RT-MRI of speech tasks. The inter-study agreement is quantified using intraclass correlation coefficient (ICC) and mean within-subject standard deviation (σe). Inter-study agreement is strong to very strong for static measures (ICC: min/median/max 0.71/0.89/0.98, σe: 0.90/2.20/6.72 mm), poor to strong for dynamic RT-MRI measures of articulator motion range (ICC: 0.26/0.75/0.90, σe: 1.6/2.5/3.6 mm), and poor to very strong for velocities (ICC: 0.21/0.56/0.93, σe: 2.2/4.4/16.7 cm/s). In conclusion, this study characterizes repeatability of static and dynamic MRI-derived speech biomarkers using state-of-the-art imaging. The introduced framework can be used to guide future development of speech biomarkers. Test–retest MRI data are provided free for research use. PMID:28599561

Based Upon Repeat Pattern (BURP): an algorithm to characterize the long-term evolution of Staphylococcus aureus populations based on spa polymorphisms.

PubMed

Mellmann, Alexander; Weniger, Thomas; Berssenbrügge, Christoph; Rothgänger, Jörg; Sammeth, Michael; Stoye, Jens; Harmsen, Dag

2007-10-29

For typing of Staphylococcus aureus, DNA sequencing of the repeat region of the protein A (spa) gene is a well established discriminatory method for outbreak investigations. Recently, it was hypothesized that this region also reflects long-term epidemiology. However, no automated and objective algorithm existed to cluster different repeat regions. In this study, the Based Upon Repeat Pattern (BURP) implementation that is a heuristic variant of the newly described EDSI algorithm was investigated to infer the clonal relatedness of different spa types. For calibration of BURP parameters, 400 representative S. aureus strains with different spa types were characterized by MLST and clustered using eBURST as "gold standard" for their phylogeny. Typing concordance analysis between eBURST and BURP clustering (spa-CC) were performed using all possible BURP parameters to determine their optimal combination. BURP was subsequently evaluated with a strain collection reflecting the breadth of diversity of S. aureus (JCM 2002; 40:4544). In total, the 400 strains exhibited 122 different MLST types. eBURST grouped them into 23 clonal complexes (CC; 354 isolates) and 33 singletons (46 isolates). BURP clustering of spa types using all possible parameter combinations and subsequent comparison with eBURST CCs resulted in concordances ranging from 8.2 to 96.2%. However, 96.2% concordance was reached only if spa types shorter than 8 repeats were excluded, which resulted in 37% excluded spa types. Therefore, the optimal combination of the BURP parameters was "exclude spa types shorter than 5 repeats" and "cluster spa types into spa-CC if cost distances are less than 4" exhibiting 95.3% concordance to eBURST. This algorithm identified 24 spa-CCs, 40 singletons, and excluded only 7.8% spa types. Analyzing the natural population with these parameters, the comparison of whole-genome micro-array groupings (at the level of 0.31 Pearson correlation index) and spa-CCs gave a concordance of 87

Repeated short presentations of morphed facial expressions change recognition and evaluation of facial expressions.

PubMed

Moriya, Jun; Tanno, Yoshihiko; Sugiura, Yoshinori

2013-11-01

This study investigated whether sensitivity to and evaluation of facial expressions varied with repeated exposure to non-prototypical facial expressions for a short presentation time. A morphed facial expression was presented for 500 ms repeatedly, and participants were required to indicate whether each facial expression was happy or angry. We manipulated the distribution of presentations of the morphed facial expressions for each facial stimulus. Some of the individuals depicted in the facial stimuli expressed anger frequently (i.e., anger-prone individuals), while the others expressed happiness frequently (i.e., happiness-prone individuals). After being exposed to the faces of anger-prone individuals, the participants became less sensitive to those individuals' angry faces. Further, after being exposed to the faces of happiness-prone individuals, the participants became less sensitive to those individuals' happy faces. We also found a relative increase in the social desirability of happiness-prone individuals after exposure to the facial stimuli.

The network impact of hijacking a quantum repeater

NASA Astrophysics Data System (ADS)

Satoh, Takahiko; Nagayama, Shota; Oka, Takafumi; Van Meter, Rodney

2018-07-01

In quantum networking, repeater hijacking menaces the security and utility of quantum applications. To deal with this problem, it is important to take a measure of the impact of quantum repeater hijacking. First, we quantify the work of each quantum repeater with regards to each quantum communication. Based on this, we show the costs for repeater hijacking detection using distributed quantum state tomography and the amount of work loss and rerouting penalties caused by hijacking. This quantitative evaluation covers both purification-entanglement swapping and quantum error correction repeater networks. Naive implementation of the checks necessary for correct network operation can be subverted by a single hijacker to bring down an entire network. Fortunately, the simple fix of randomly assigned testing can prevent such an attack.

LPA gene: interaction between the apolipoprotein(a) size ('kringle IV' repeat) polymorphism and a pentanucleotide repeat polymorphism influences Lp(a) lipoprotein level.

PubMed

Røsby, O; Berg, K

2000-01-01

In order to search for factors influencing the Lp(a) lipoprotein level, we have examined the apolipoprotein(a) (apo(a)) size polymorphism as well as a pentanucleotide (TTTTA) repeat polymorphism in the 5' control region of the LPA gene. Lp(a) lipoprotein levels were compared between individuals with different genotypes as defined by pulsed field gel electrophoresis of DNA plugs, and PCR of DNA samples followed by polyacrylamide gel electrophoresis. DNA plugs and DNA were prepared from blood samples collected from blood donors. Twenty-seven different K IV repeat alleles were observed in the 71 women and 92 men from which apo(a) size polymorphism results were obtained. Alleles encoding 26-32 Kringle IV repeats were the most frequent. Alleles encoding seven to 11 TTTTA repeats were detected in the 84 women and 122 men included in the pentanucleotide polymorphism study, and homozygosity for eight TTTTA repeats was the most common genotype. The eight TTTTA repeat allele occurred with almost any apo(a) allele. An inverse relationship between number of K IV repeats and Lp(a) concentration was confirmed. The contributions of the apo(a) size polymorphism and the pentanucleotide repeat polymorphism to the interindividual variance of Lp(a) lipoprotein concentrations were 9.7 and 3.5%, respectively (type IV sum of squares). Nineteen per cent of the variance in Lp(a) lipoprotein level appeared to be the result of the multiplication product (interaction) between the apo(a) size polymorphism and the pentanucleotide repeat polymorphism. The contribution of the apo(a) size polymorphism alone to the variation in Lp(a) lipoprotein level was lower than previously reported. However, the multiplicative interaction effect between the K IV repeat polymorphism and the pentanucleotide repeat polymorphism may be an important factor explaining the variation in Lp(a) lipoprotein levels among the populations.

Type-IVC Secretion System: A Novel Subclass of Type IV Secretion System (T4SS) Common Existing in Gram-Positive Genus Streptococcus

PubMed Central

Chen, Chen; Gao, George F.

2012-01-01

A growing number of pathogens are being found to possess specialized secretion systems which they use in various ways to subvert host defenses. Type IV secretion system (T4SS) is one of versatile secretion systems essential for the virulence and even survival of some bacteria species, and they enable the secretion of protein and DNA substrates across the cell envelope. T4SS was once believed to be present only in Gram-negative bacteria. In this study, we present evidence of a new subclass of T4SS, Type-IVC secretion system and indicate its common existence in the Gram-positive bacterial genus Streptococcus. We further identified that VirB1, VirB4, VirB6 and VirD4 are the minimal key components of this system. Using genome comparisons and evolutionary relationship analysis, we proposed that Type-IVC secretion system is movable via transposon factors and mediates the conjugative transfer of DNA, enhances bacterial pathogenicity, and could cause large-scale outbreaks of infections in humans. PMID:23056296

Deployment Repeatability

DTIC Science & Technology

2016-04-01

environment. Modeling is suitable for well- characterized parts, and stochastic modeling techniques can be used for sensitivity analysis and generating a...large cohort of trials to spot unusual cases. However, deployment repeatability is inherently a nonlinear phenomenon, which makes modeling difficult...recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the U.S. Air Force. 1. Test the flight model

Determination of repeatability of kinect sensor.

PubMed

Bonnechère, Bruno; Sholukha, Victor; Jansen, Bart; Omelina, Lubos; Rooze, Marcel; Van Sint Jan, Serge

2014-05-01

The Kinect™ (Microsoft™, Redmond, WA) sensor, originally developed for gaming purposes, may have interesting possibilities for other fields such as posture and motion assessment. The ability of the Kinect sensor to perform biomechanical measurements has previously been studied and shows promising results. However, interday repeatability of the device is still not known. This study assessed the intra- and interday repeatability of the Kinect sensor compared with a standard stereophotogrammetric device during posture assessment for measuring segment lengths. Forty subjects took part in the study. Five motionless captures were performed in one session to assess posture. Data were simultaneously recorded with both devices. Similar intraclass correlations coefficient (ICC) values were found for intraday (ICC=0.94 for the Kinect device and 0.98 for the stereophotogrammetric device) and interday (ICC=0.88 and 0.87, respectively) repeatability. Results of this study suggest that a cost-effective, easy-to-use, and portable single markerless camera offers the same repeatability during posture assessment as an expensive, time-consuming, and nontransportable marker-based device.

Do gamma-ray burst sources repeat?

NASA Technical Reports Server (NTRS)

Meegan, Charles A.; Hartmann, Dieter H.; Brainerd, J. J.; Briggs, Michael S.; Paciesas, William S.; Pendleton, Geoffrey; Kouveliotou, Chryssa; Fishman, Gerald; Blumenthal, George; Brock, Martin

1995-01-01

The demonstration of repeated gamma-ray bursts from an individual source would severely constrain burst source models. Recent reports (Quashnock and Lamb, 1993; Wang and Lingenfelter, 1993) of evidence for repetition in the first BATSE burst catalog have generated renewed interest in this issue. Here, we analyze the angular distribution of 585 bursts of the second BATSE catalog (Meegan et al., 1994). We search for evidence of burst recurrence using the nearest and farthest neighbor statistic and the two-point angular correlation function. We find the data to be consistent with the hypothesis that burst sources do not repeat; however, a repeater fraction of up to about 20% of the observed bursts cannot be excluded.

Digital Photoplethysmography for Assessment of Arterial Stiffness: Repeatability and Comparison with Applanation Tonometry

PubMed Central

Östling, Gerd; Nilsson, Peter M.

2015-01-01

Introduction Arterial stiffness is an independent risk factor for cardiovascular morbidity and can be assessed by applanation tonometry by measuring pulse wave velocity (PWV) and augmentation index (AIX) by pressure pulse wave analysis (PWA). As an inexpensive and operator independent alternative, photoelectric plethysmography (PPG) has been introduced with analysis of the digital volume pulse wave (DPA) and its second derivatives of wave reflections. Objective The objective was to investigate the repeatability of arterial stiffness parameters measured by digital pulse wave analysis (DPA) and the associations to applanation tonometry parameters. Methods and Results 112 pregnant and non-pregnant individuals of different ages and genders were examined with SphygmoCor arterial wall tonometry and Meridian DPA finger photoplethysmography. Coefficients of repeatability, Bland-Altman plots, intraclass correlation coefficients and correlations to heart rate (HR) and body height were calculated for DPA variables, and the DPA variables were compared to tonometry variables left ventricular ejection time (LVET), PWV and AIX. No DPA variable showed any systematic measurement error or excellent repeatability, but dicrotic index (DI), dicrotic dilatation index (DDI), cardiac ejection elasticity index (EEI), aging index (AI) and second derivatives of the crude pulse wave curve, b/a and e/a, showed good repeatability. Overall, the correlations to AIX were better than to PWV, with correlations coefficients >0.70 for EEI, AI and b/a. Considering the level of repeatability and the correlations to tonometry, the overall best DPA parameters were EEI, AI and b/a. The two pansystolic time parameters, ejection time compensated (ETc) by DPA and LVET by tonometry, showed a significant but weak correlation. Conclusion For estimation of the LV function, ETc, EEI and b/a are suitable, for large artery stiffness EEI, and for small arteries DI and DDI. The only global parameter, AI, showed a high

Dental Fear in Children with Repeated Tooth Injuries.

PubMed

Negovetić Vranić, Dubravka; Ivančić Jokić, Nataša; Bakarčić, Danko; Carek, Andreja; Rotim, Željko; Verzak, Željko

2016-06-01

Tooth injuries are serious clinical conditions. Some children experience dental trauma only once, while others are more prone to repeated tooth injuries. Repeated dental trauma occurs in 19.4% to 30% of patients. Pain and dental trauma are the most common reasons for fear and anxiety. The main objective of this study was to investigate how dental trauma, as well as repeated dental trauma affects the occurrence and development of dental fear in children. The study was conducted on a random sample of 147 subjects (88 boys and 59 girls) aged 5-8 and 9-12 years. Subjects in both age groups were divided into subroups without dental trauma, with one dental trauma and with repeated dental trauma. The validated Children’s Fear Survey Schedule – Dental Subscale was used on fear assessment. Results showed that only 12.2% of children without trauma, 33.3% with one trauma and 51.7% with repeated trauma were not afraid of injection. Older children had a significantly lower fear of injections, touch of an unknown person, choking, going to the hospital and people in white uniforms. Dentist was not the cause of fear in 65.5% of patients with repeated trauma. With each repeated injury of teeth, the degree of their fear of dental treatment was lower.

Erroneous Memories Arising from Repeated Attempts to Remember

ERIC Educational Resources Information Center

Henkel, Linda A.

2004-01-01

The impact of repeated and prolonged attempts at remembering on false memory rates was assessed in three experiments. Participants saw and imagined pictures and then made repeated recall attempts before taking a source memory test. Although the number of items recalled increased with repeated tests, the net gains were associated with more source…

Effects of acute versus repeated cocaine exposure on the expression of endocannabinoid signaling-related proteins in the mouse cerebellum.

PubMed

Palomino, Ana; Pavón, Francisco-Javier; Blanco-Calvo, Eduardo; Serrano, Antonia; Arrabal, Sergio; Rivera, Patricia; Alén, Francisco; Vargas, Antonio; Bilbao, Ainhoa; Rubio, Leticia; Rodríguez de Fonseca, Fernando; Suárez, Juan

2014-01-01

Growing awareness of cerebellar involvement in addiction is based on the cerebellum's intermediary position between motor and reward, potentially acting as an interface between motivational and cognitive functions. Here, we examined the impact of acute and repeated cocaine exposure on the two main signaling systems in the mouse cerebellum: the endocannabinoid (eCB) and glutamate systems. To this end, we investigated whether eCB signaling-related gene and protein expression {cannabinoid receptor type 1 receptors and enzymes that produce [diacylglycerol lipase alpha/beta (DAGLα/β) and N-acyl phosphatidylethanolamine phospholipase D (NAPE-PLD)] and degrade [monoacylglycerol lipase (MAGL) and fatty acid amino hydrolase (FAAH)] eCB} were altered. In addition, we analyzed the gene expression of relevant components of the glutamate signaling system [glutamate synthesizing enzymes liver-type glutaminase isoform (LGA) and kidney-type glutaminase isoform (KGA), metabotropic glutamatergic receptor (mGluR3/5), NMDA-ionotropic glutamatergic receptor (NR1/2A/2B/2C) and AMPA-ionotropic receptor subunits (GluR1/2/3/4)] and the gene expression of tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine biosynthesis, because noradrenergic terminals innervate the cerebellar cortex. Results indicated that acute cocaine exposure decreased DAGLα expression, suggesting a down-regulation of 2-arachidonylglycerol (2-AG) production, as well as gene expression of TH, KGA, mGluR3 and all ionotropic receptor subunits analyzed in the cerebellum. The acquisition of conditioned locomotion and sensitization after repeated cocaine exposure were associated with an increased NAPE-PLD/FAAH ratio, suggesting enhanced anandamide production, and a decreased DAGLβ/MAGL ratio, suggesting decreased 2-AG generation. Repeated cocaine also increased LGA gene expression but had no effect on glutamate receptors. These findings indicate that acute cocaine modulates the expression of the eCB and

Effects of acute versus repeated cocaine exposure on the expression of endocannabinoid signaling-related proteins in the mouse cerebellum

PubMed Central

Palomino, Ana; Pavón, Francisco-Javier; Blanco-Calvo, Eduardo; Serrano, Antonia; Arrabal, Sergio; Rivera, Patricia; Alén, Francisco; Vargas, Antonio; Bilbao, Ainhoa; Rubio, Leticia; Rodríguez de Fonseca, Fernando; Suárez, Juan

2014-01-01

Growing awareness of cerebellar involvement in addiction is based on the cerebellum’s intermediary position between motor and reward, potentially acting as an interface between motivational and cognitive functions. Here, we examined the impact of acute and repeated cocaine exposure on the two main signaling systems in the mouse cerebellum: the endocannabinoid (eCB) and glutamate systems. To this end, we investigated whether eCB signaling-related gene and protein expression {cannabinoid receptor type 1 receptors and enzymes that produce [diacylglycerol lipase alpha/beta (DAGLα/β) and N-acyl phosphatidylethanolamine phospholipase D (NAPE-PLD)] and degrade [monoacylglycerol lipase (MAGL) and fatty acid amino hydrolase (FAAH)] eCB} were altered. In addition, we analyzed the gene expression of relevant components of the glutamate signaling system [glutamate synthesizing enzymes liver-type glutaminase isoform (LGA) and kidney-type glutaminase isoform (KGA), metabotropic glutamatergic receptor (mGluR3/5), NMDA-ionotropic glutamatergic receptor (NR1/2A/2B/2C) and AMPA-ionotropic receptor subunits (GluR1/2/3/4)] and the gene expression of tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine biosynthesis, because noradrenergic terminals innervate the cerebellar cortex. Results indicated that acute cocaine exposure decreased DAGLα expression, suggesting a down-regulation of 2-arachidonylglycerol (2-AG) production, as well as gene expression of TH, KGA, mGluR3 and all ionotropic receptor subunits analyzed in the cerebellum. The acquisition of conditioned locomotion and sensitization after repeated cocaine exposure were associated with an increased NAPE-PLD/FAAH ratio, suggesting enhanced anandamide production, and a decreased DAGLβ/MAGL ratio, suggesting decreased 2-AG generation. Repeated cocaine also increased LGA gene expression but had no effect on glutamate receptors. These findings indicate that acute cocaine modulates the expression of the eCB and

Limitations on quantum key repeaters.

PubMed

Bäuml, Stefan; Christandl, Matthias; Horodecki, Karol; Winter, Andreas

2015-04-23

A major application of quantum communication is the distribution of entangled particles for use in quantum key distribution. Owing to noise in the communication line, quantum key distribution is, in practice, limited to a distance of a few hundred kilometres, and can only be extended to longer distances by use of a quantum repeater, a device that performs entanglement distillation and quantum teleportation. The existence of noisy entangled states that are undistillable but nevertheless useful for quantum key distribution raises the question of the feasibility of a quantum key repeater, which would work beyond the limits of entanglement distillation, hence possibly tolerating higher noise levels than existing protocols. Here we exhibit fundamental limits on such a device in the form of bounds on the rate at which it may extract secure key. As a consequence, we give examples of states suitable for quantum key distribution but unsuitable for the most general quantum key repeater protocol.

Neisseria meningitidis Group A IgG1 and IgG2 Subclass Immune Response in African Children Aged 12–23 Months Following Meningococcal Vaccination

PubMed Central

Holme, Daniel; Findlow, Helen; Sow, Samba O.; Idoko, Olubukola T.; Preziosi, Marie-Pierre; Carlone, George; Plikaytis, Brian D.; Borrow, Ray

2015-01-01

Background. A group A meningococcal conjugate vaccine, PsA-TT, was licensed in 2010 and was previously studied in a phase 2 clinical trial to evaluate its safety and immunogenicity in African children 12–23 months of age. Methods. Subjects received either PsA-TT; meningococcal group A, C, W, Y polysaccharide vaccine (PsACWY); or Haemophilus influenzae type b conjugate vaccine (Hib-TT). Forty weeks following primary vaccination, the 3 groups were further randomized to receive either PsA-TT, one-fifth dose of PsACWY, or Hib-TT. Group A–specific immunoglobulin G (IgG) subclass response was characterized using an enzyme-linked immunosorbent assay. Results. The predominant IgG subclass response, regardless of vaccine, was IgG1. One month following primary vaccination, the geometric mean concentrations (GMCs) of IgG1 and IgG2 in the PsA-TT group were 21.73 µg/mL and 6.27 µg/mL, whereas in the PsACWY group the mean GMCs were 2.01 µg/mL and 0.97 µg/mL, respectively (P < .0001). Group A–specific IgG1 and IgG2 GMCs remained greater in the PsA-TT group than in the PsACWY group 40 weeks following primary vaccination (P < .0001). One week following revaccination, those given 2 doses of PsA-TT had the greatest IgG1 and IgG2 GMCs of 125.23 µg/mL and 36.12 µg/mL, respectively (P = .0008), and demonstrated a significant increase in IgG1:IgG2 mean ratio, indicative of the T-cell–dependent response associated with conjugate vaccines. Conclusions. Vaccination of African children aged 12–24 months with either PsA-TT or PsACWY elicited a predominantly IgG1 response. The IgG1:IgG2 mean ratio decreased following successive vaccination with PsACWY, indicating a shift toward IgG2, suggestive of the T-cell–independent immune response commonly associated with polysaccharide antigens. Clinical Trials Registration. SRCTN78147026. PMID:26553689

Identification, variation and transcription of pneumococcal repeat sequences

PubMed Central

2011-01-01

Background Small interspersed repeats are commonly found in many bacterial chromosomes. Two families of repeats (BOX and RUP) have previously been identified in the genome of Streptococcus pneumoniae, a nasopharyngeal commensal and respiratory pathogen of humans. However, little is known about the role they play in pneumococcal genetics. Results Analysis of the genome of S. pneumoniae ATCC 700669 revealed the presence of a third repeat family, which we have named SPRITE. All three repeats are present at a reduced density in the genome of the closely related species S. mitis. However, they are almost entirely absent from all other streptococci, although a set of elements related to the pneumococcal BOX repeat was identified in the zoonotic pathogen S. suis. In conjunction with information regarding their distribution within the pneumococcal chromosome, this suggests that it is unlikely that these repeats are specialised sequences performing a particular role for the host, but rather that they constitute parasitic elements. However, comparing insertion sites between pneumococcal sequences indicates that they appear to transpose at a much lower rate than IS elements. Some large BOX elements in S. pneumoniae were found to encode open reading frames on both strands of the genome, whilst another was found to form a composite RNA structure with two T box riboswitches. In multiple cases, such BOX elements were demonstrated as being expressed using directional RNA-seq and RT-PCR. Conclusions BOX, RUP and SPRITE repeats appear to have proliferated extensively throughout the pneumococcal chromosome during the species' past, but novel insertions are currently occurring at a relatively slow rate. Through their extensive secondary structures, they seem likely to affect the expression of genes with which they are co-transcribed. Software for annotation of these repeats is freely available from ftp://ftp.sanger.ac.uk/pub/pathogens/strep_repeats/. PMID:21333003

Dispersion Measure Variation of Repeating Fast Radio Burst Sources

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

Yang, Yuan-Pei; Zhang, Bing, E-mail: yypspore@gmail.com, E-mail: zhang@physics.unlv.edu

The repeating fast radio burst (FRB) 121102 was recently localized in a dwarf galaxy at a cosmological distance. The dispersion measure (DM) derived for each burst from FRB 121102 so far has not shown significant evolution, even though an apparent increase was recently seen with newly detected VLA bursts. It is expected that more repeating FRB sources may be detected in the future. In this work, we investigate a list of possible astrophysical processes that might cause DM variation of a particular FRB source. The processes include (1) cosmological scale effects such as Hubble expansion and large-scale structure fluctuations; (2)more » FRB local effects such as gas density fluctuation, expansion of a supernova remnant (SNR), a pulsar wind nebula, and an H ii region; and (3) the propagation effect due to plasma lensing. We find that the DM variations contributed by the large-scale structure are extremely small, and any observable DM variation is likely caused by the plasma local to the FRB source. In addition to mechanisms that decrease DM over time, we suggest that an FRB source in an expanding SNR around a nearly neutral ambient medium during the deceleration (Sedov–Taylor and snowplow) phases or in a growing H ii region can increase DM. Some effects (e.g., an FRB source moving in an H ii region or plasma lensing) can produce either positive or negative DM variations. Future observations of DM variations of FRB 121102 and other repeating FRB sources can provide important clues regarding the physical origin of these sources.« less

Reasons sought for repeat drinking and driving

DOT National Transportation Integrated Search

1996-06-01

This document summarizes the results of a study about why some individuals repeatedly drive while under the influence or intoxicated, even after being convicted of DWI and after experiencing sanctions. Qualified interviewers asked repeat offenders di...

Multi-locus variable number tandem repeat analysis for Escherichia coli causing extraintestinal infections.

PubMed

Manges, Amee R; Tellis, Patricia A; Vincent, Caroline; Lifeso, Kimberley; Geneau, Geneviève; Reid-Smith, Richard J; Boerlin, Patrick

2009-11-01

Discriminatory genotyping methods for the analysis of Escherichia coli other than O157:H7 are necessary for public health-related activities. A new multi-locus variable number tandem repeat analysis protocol is presented; this method achieves an index of discrimination of 99.5% and is reproducible and valid when tested on a collection of 836 diverse E. coli.

A Gammaherpesviral Internal Repeat Contributes to Latency Amplification

PubMed Central

Thakur, Nagendra N.; El-Gogo, Susanne; Steer, Beatrix; Freimüller, Klaus; Waha, Andreas; Adler, Heiko

2007-01-01

Background Gammaherpesviruses cause important infections of humans, in particular in immunocompromised patients. The genomes of gammaherpesviruses contain variable numbers of internal repeats whose precise role for in vivo pathogenesis is not well understood. Methodology/Principal Findings We used infection of laboratory mice with murine gammaherpesvirus 68 (MHV-68) to explore the biological role of the 40 bp internal repeat of MHV-68. We constructed several mutant viruses partially or completely lacking this repeat. Both in vitro and in vivo, the loss of the repeat did not substantially affect lytic replication of the mutant viruses. However, the extent of splenomegaly, which is associated with the establishment of latency, and the number of ex vivo reactivating and genome positive splenocytes were reduced. Since the 40 bp repeat is part of the hypothetical open reading frame (ORF) M6, it might function as part of M6 or as an independent structure. To differentiate between these two possibilities, we constructed an N-terminal M6STOP mutant, leaving the repeat structure intact but rendering ORF M6 unfunctional. Disruption of ORF M6 did neither affect lytic nor latent infection. In contrast to the situation in lytically infected NIH3T3 cells, the expression of the latency-associated genes K3 and ORF72 was reduced in the latently infected murine B cell line Ag8 in the absence of the 40 bp repeat. Conclusions/Significance These data suggest that the 40 bp repeat contributes to latency amplification and might be involved in the regulation of viral gene expression. PMID:17710133

Small RNA Deep Sequencing and the Effects of microRNA408 on Root Gravitropic Bending in Arabidopsis

NASA Astrophysics Data System (ADS)

Li, Huasheng; Lu, Jinying; Sun, Qiao; Chen, Yu; He, Dacheng; Liu, Min

2015-11-01

MicroRNA (miRNA) is a non-coding small RNA composed of 20 to 24 nucleotides that influences plant root development. This study analyzed the miRNA expression in Arabidopsis root tip cells using Illumina sequencing and real-time PCR before (sample 0) and 15 min after (sample 15) a 3-D clinostat rotational treatment was administered. After stimulation was performed, the expression levels of seven miRNA genes, including Arabidopsis miR160, miR161, miR394, miR402, miR403, miR408, and miR823, were significantly upregulated. Illumina sequencing results also revealed two novel miRNAsthat have not been previously reported, The target genes of these miRNAs included pentatricopeptide repeat-containing protein and diadenosine tetraphosphate hydrolase. An overexpression vector of Arabidopsis miR408 was constructed and transferred to Arabidopsis plant. The roots of plants over expressing miR408 exhibited a slower reorientation upon gravistimulation in comparison with those of wild-type. This result indicate that miR408 could play a role in root gravitropic response.

Impaired complex IV activity in response to loss of LRPPRC function can be compensated by mitochondrial hyperfusion

PubMed Central

Rolland, Stéphane G.; Motori, Elisa; Memar, Nadin; Hench, Jürgen; Frank, Stephan; Winklhofer, Konstanze F.; Conradt, Barbara

2013-01-01

Mitochondrial morphology changes in response to various stimuli but the significance of this is unclear. In a screen for mutants with abnormal mitochondrial morphology, we identified MMA-1, the Caenorhabditis elegans homolog of the French Canadian Leigh Syndrome protein LRPPRC (leucine-rich pentatricopeptide repeat containing). We demonstrate that reducing mma-1 or LRPPRC function causes mitochondrial hyperfusion. Reducing mma-1/LRPPRC function also decreases the activity of complex IV of the electron transport chain, however without affecting cellular ATP levels. Preventing mitochondrial hyperfusion in mma-1 animals causes larval arrest and embryonic lethality. Furthermore, prolonged LRPPRC knock-down in mammalian cells leads to mitochondrial fragmentation and decreased levels of ATP. These findings indicate that in a mma-1/LRPPRC–deficient background, hyperfusion allows mitochondria to maintain their functions despite a reduction in complex IV activity. Our data reveal an evolutionary conserved mechanism that is triggered by reduced complex IV function and that induces mitochondrial hyperfusion to transiently compensate for a drop in the activity of the electron transport chain. PMID:23878239

Translation of dipeptide repeat proteins from the C9ORF72 expanded repeat is associated with cellular stress.

PubMed

Sonobe, Yoshifumi; Ghadge, Ghanashyam; Masaki, Katsuhisa; Sendoel, Ataman; Fuchs, Elaine; Roos, Raymond P

2018-08-01

Expansion of a hexanucleotide repeat (HRE), GGGGCC, in the C9ORF72 gene is recognized as the most common cause of familial amyotrophic lateral sclerosis (FALS), frontotemporal dementia (FTD) and ALS-FTD, as well as 5-10% of sporadic ALS. Despite the location of the HRE in the non-coding region (with respect to the main C9ORF72 gene product), dipeptide repeat proteins (DPRs) that are thought to be toxic are translated from the HRE in all three reading frames from both the sense and antisense transcript. Here, we identified a CUG that has a good Kozak consensus sequence as the translation initiation codon. Mutation of this CTG significantly suppressed polyglycine-alanine (GA) translation. GA was translated when the G 4 C 2 construct was placed as the second cistron in a bicistronic construct. CRISPR/Cas9-induced knockout of a non-canonical translation initiation factor, eIF2A, impaired GA translation. Transfection of G 4 C 2 constructs induced an integrated stress response (ISR), while triggering the ISR led to a continuation of translation of GA with a decline in conventional cap-dependent translation. These in vitro observations were confirmed in chick embryo neural cells. The findings suggest that DPRs translated from an HRE in C9ORF72 aggregate and lead to an ISR that then leads to continuing DPR production and aggregation, thereby creating a continuing pathogenic cycle. Copyright © 2018 Elsevier Inc. All rights reserved.

SkyRepeater

DTIC Science & Technology

2005-01-01

MUSIC.consultant, Doug Lewis, host of WVGN’s Doug Lewis Show, cddick@viaccess.net Being For The Benefit of Mr. Kite, Beatles , Writer, lead vocal...and in the case of a repeater failure. Tested on both VHF and UHF bands, one person can setup in 15 minutes. Cost is approximately $2,000.00. Minimum...This was originally written as a term paper for the Center for Homeland Defense and Security at the Naval Postgraduate

The effect of emotional design and online customer review on customer repeat purchase intention in online stores

NASA Astrophysics Data System (ADS)

Dewi, D. S.; Sudiarno, A.; Saputra, H.; Dewi, R. S.

2018-04-01

The internet users in Indonesia has increased rapidly over the last decade. A survey conducted by Association of Internet Service Providers Indonesia shows that the internet users has reached 34.9% of total population in Indonesia. The increase of internet users has led to a shift in trading practice from conventional trade to online trade. It is predicted in the next years the number of online consumers in Indonesia will continue to increase, provide many opportunity for online business. The huge number of internet users is not necesarily followed by the high number of e-purchase. It is therefore become the interest of many researchers to investigate factors that influence the decision on online purchasing.This research proposes a model that assess the effect of emotional design and customer review to customer intention on e-repeat purchase. Online questionnaire is designed and is distributed randomly through google forms. There are 187 respondent filled the questionnaire from which only 162 respondents actually have experience in online purchase. These data are then processed by using statistical analysis. A model is developed by applying structural equation modeling (SEM) approach. This study revealed that customer reviews especially objective reviews has a significant effect toward repeat purchase. Whereas emotional design particularly visual attractiveness also shows a significant effect toward e-repeat purchase.

Subtypes of the Type II Pit Pattern Reflect Distinct Molecular Subclasses in the Serrated Neoplastic Pathway.

PubMed

Aoki, Hironori; Yamamoto, Eiichiro; Yamano, Hiro-O; Sugai, Tamotsu; Kimura, Tomoaki; Tanaka, Yoshihito; Matsushita, Hiro-O; Yoshikawa, Kenjiro; Takagi, Ryo; Harada, Eiji; Nakaoka, Michiko; Yoshida, Yuko; Harada, Taku; Sudo, Gota; Eizuka, Makoto; Yorozu, Akira; Kitajima, Hiroshi; Niinuma, Takeshi; Kai, Masahiro; Nojima, Masanori; Suzuki, Hiromu; Nakase, Hiroshi

2018-03-15

Colorectal serrated lesions (SLs) are important premalignant lesions whose clinical and biological features are not fully understood. We aimed to establish accurate colonoscopic diagnosis and treatment of SLs through evaluation of associations among the morphological, pathological, and molecular characteristics of SLs. A total of 388 premalignant and 18 malignant colorectal lesions were studied. Using magnifying colonoscopy, microsurface structures were assessed based on Kudo's pit pattern classification system, and the Type II pit pattern was subcategorized into classical Type II, Type II-Open (Type II-O) and Type II-Long (Type II-L). BRAF/KRAS mutations and DNA methylation of CpG island methylator phenotype (CIMP) markers (MINT1, - 2, - 12, - 31, p16, and MLH1) were analyzed through pyrosequencing. Type II-O was tightly associated with sessile serrated adenoma/polyps (SSA/Ps) with BRAF mutation and CIMP-high. Most lesions with simple Type II or Type II-L were hyperplastic polyps, while mixtures of Type II or Type II-L plus more advanced pit patterns (III/IV) were characteristic of traditional serrated adenomas (TSAs). Type II-positive TSAs frequently exhibited BRAF mutation and CIMP-low, while Type II-L-positive TSAs were tightly associated with KRAS mutation and CIMP-low. Analysis of lesions containing both premalignant and cancerous components suggested Type II-L-positive TSAs may develop into KRAS-mutated/CIMP-low/microsatellite stable cancers, while Type II-O-positive SSA/Ps develop into BRAF-mutated/CIMP-high/microsatellite unstable cancers. These results suggest that Type II subtypes reflect distinct molecular subclasses in the serrated neoplasia pathway and that they could be useful hallmarks for identifying SLs at high risk of developing into CRC.

Evolution of genes and repeats in the Nimrod superfamily.

PubMed

Somogyi, Kálmán; Sipos, Botond; Pénzes, Zsolt; Kurucz, Eva; Zsámboki, János; Hultmark, Dan; Andó, István

2008-11-01

The recently identified Nimrod superfamily is characterized by the presence of a special type of EGF repeat, the NIM repeat, located right after a typical CCXGY/W amino acid motif. On the basis of structural features, nimrod genes can be divided into three types. The proteins encoded by Draper-type genes have an EMI domain at the N-terminal part and only one copy of the NIM motif, followed by a variable number of EGF-like repeats. The products of Nimrod B-type and Nimrod C-type genes (including the eater gene) have different kinds of N-terminal domains, and lack EGF-like repeats but contain a variable number of NIM repeats. Draper and Nimrod C-type (but not Nimrod B-type) proteins carry a transmembrane domain. Several members of the superfamily were claimed to function as receptors in phagocytosis and/or binding of bacteria, which indicates an important role in the cellular immunity and the elimination of apoptotic cells. In this paper, the evolution of the Nimrod superfamily is studied with various methods on the level of genes and repeats. A hypothesis is presented in which the NIM repeat, along with the EMI domain, emerged by structural reorganizations at the end of an EGF-like repeat chain, suggesting a mechanism for the formation of novel types of repeats. The analyses revealed diverse evolutionary patterns in the sequences containing multiple NIM repeats. Although in the Nimrod B and Nimrod C proteins show characteristics of independent evolution, many internal NIM repeats in Eater sequences seem to have undergone concerted evolution. An analysis of the nimrod genes has been performed using phylogenetic and other methods and an evolutionary scenario of the origin and diversification of the Nimrod superfamily is proposed. Our study presents an intriguing example how the evolution of multigene families may contribute to the complexity of the innate immune response.

Repeated Reading of CD-ROM Storybook as a Support for Emergent Literacy: A Developmental Perspective in Two SES Groups

ERIC Educational Resources Information Center

Korat, Ofra; Blau, Hila

2010-01-01

We investigated the effect of repeated readings of an electronic book (e-book) on pre-kindergarten and kindergarten children from low (n = 127) and middle (n = 120) SES groups. Children were randomly assigned to one of three options: reading an e-book in five sessions, reading an e-book in three sessions, or receiving the regular kindergarten…

Hypoxic Repeat Sprint Training Improves Rugby Player's Repeated Sprint but Not Endurance Performance

PubMed Central

Hamlin, Michael J.; Olsen, Peter D.; Marshall, Helen C.; Lizamore, Catherine A.; Elliot, Catherine A.

2017-01-01

This study aims to investigate the performance changes in 19 well-trained male rugby players after repeat-sprint training (six sessions of four sets of 5 × 5 s sprints with 25 s and 5 min of active recovery between reps and sets, respectively) in either normobaric hypoxia (HYP; n = 9; FIO2 = 14.5%) or normobaric normoxia (NORM; n = 10; FIO2 = 20.9%). Three weeks after the intervention, 2 additional repeat-sprint training sessions in hypoxia (FIO2 = 14.5%) was investigated in both groups to gauge the efficacy of using “top-up” sessions for previously hypoxic-trained subjects and whether a small hypoxic dose would be beneficial for the previously normoxic-trained group. Repeated sprint (8 × 20 m) and Yo-Yo Intermittent Recovery Level 1 (YYIR1) performances were tested twice at baseline (Pre 1 and Pre 2) and weekly after (Post 1–3) the initial intervention (intervention 1) and again weekly after the second “top-up” intervention (Post 4–5). After each training set, heart rate, oxygen saturation, and rate of perceived exertion were recorded. Compared to baseline (mean of Pre 1 and Pre 2), both the hypoxic and normoxic groups similarly lowered fatigue over the 8 sprints 1 week after the intervention (Post 1: −1.8 ± 1.6%, −1.5 ± 1.4%, mean change ± 90% CI in HYP and NORM groups, respectively). However, from Post 2 onwards, only the hypoxic group maintained the performance improvement compared to baseline (Post 2: −2.1 ± 1.8%, Post 3: −2.3 ± 1.7%, Post 4: −1.9 ± 1.8%, and Post 5: −1.2 ± 1.7%). Compared to the normoxic group, the hypoxic group was likely to have substantially less fatigue at Post 3–5 (−2.0 ± 2.4%, −2.2 ± 2.4%, −1.6 ± 2.4% Post 3, Post 4, Post 5, respectively). YYIR1 performances improved throughout the recovery period in both groups (13–37% compared to baseline) with unclear differences found between groups. The addition of two sessions of “top-up” training after intervention 1, had little effect on either

Swarms of repeating long-period earthquakes at Shishaldin Volcano, Alaska, 2001-2004

USGS Publications Warehouse

Petersen, Tanja

2007-01-01

During 2001–2004, a series of four periods of elevated long-period seismic activity, each lasting about 1–2 months, occurred at Shishaldin Volcano, Aleutian Islands, Alaska. The time periods are termed swarms of repeating events, reflecting an abundance of earthquakes with highly similar waveforms that indicate stable, non-destructive sources. These swarms are characterized by increased earthquake amplitudes, although the seismicity rate of one event every 0.5–5 min has remained more or less constant since Shishaldin last erupted in 1999. A method based on waveform cross-correlation is used to identify highly repetitive events, suggestive of spatially distinct source locations. The waveform analysis shows that several different families of similar events co-exist during a given swarm day, but generally only one large family dominates. A network of hydrothermal fractures may explain the events that do not belong to a dominant repeating event group, i.e. multiple sources at different locations exist next to a dominant source. The dominant waveforms exhibit systematic changes throughout each swarm, but some of these waveforms do reappear over the course of 4 years indicating repeatedly activated source locations. The choked flow model provides a plausible trigger mechanism for the repeating events observed at Shishaldin, explaining the gradual changes in waveforms over time by changes in pressure gradient across a constriction within the uppermost part of the conduit. The sustained generation of Shishaldin's long-period events may be attributed to complex dynamics of a multi-fractured hydrothermal system: the pressure gradient within the main conduit may be regulated by temporarily sealing and reopening of parallel flow pathways, by the amount of debris within the main conduit and/or by changing gas influx into the hydrothermal system. The observations suggest that Shishaldin's swarms of repeating events represent time periods during which a dominant source

Photometric Repeatability of Scanned Imagery: UVIS

NASA Astrophysics Data System (ADS)

Shanahan, Clare E.; McCullough, Peter; Baggett, Sylvia

2017-08-01

We provide the preliminary results of a study on the photometric repeatability of spatial scans of bright, isolated white dwarf stars with the UVIS channel of the Wide Field Camera 3 (WFC3) on the Hubble Space Telescope (HST). We analyze straight-line scans from the first pair of identical orbits of HST program 14878 to assess if sub 0.1% repeatability can be attained with WFC3/UVIS. This study is motivated by the desire to achieve better signal-to-noise in the UVIS contamination and stability monitor, in which observations of standard stars in staring mode have been taken from the installation of WFC3 in 2009 to the present to assess temporal photometric stability. Higher signal to noise in this program would greatly benefit the sensitivity to detect contamination, and to better characterize the observed small throughput drifts over time. We find excellent repeatability between identical visits of program 14878, with sub 0.1% repeatability achieved in most filters. These! results support the initiative to transition the staring mode UVIS contamination and photometric stability monitor from staring mode images to spatial scans.

Combined effects of repeated oral hygiene motivation and type of toothbrush on orthodontic patients: a blind randomized clinical trial.

PubMed

Marini, Ida; Bortolotti, Francesco; Parenti, Serena Incerti; Gatto, Maria Rosaria; Bonetti, Giulio Alessandri

2014-09-01

To investigate the effects on plaque index (PI) scores of manual or electric toothbrush with or without repeated oral hygiene instructions (OHI) and motivation on patients wearing fixed orthodontic appliances. One month after the orthodontic fixed appliance bonding on both arches, 60 patients were randomly assigned to four groups; groups E1 (n  =  15) and E2 (n  =  15) received a powered rotating-oscillating toothbrush, and groups M1 (n  =  15) and M2 (n  =  15) received a manual toothbrush. Groups E1 and M1 received OHI and motivation at baseline (T0) and after 4, 8, 12, 16, and 20 weeks (T4, T8, T12, T16, and T20, respectively) by a Registered Dental Hygienist; groups E2 and M2 received OHI and motivation only at baseline. At each time point a blinded examiner scored plaque of all teeth using the modified Quigley-Hein PI. In all groups the PI score decreased significantly over time, and there were differences among groups at T8, T12, T16, and T20. At T8, PI scores of group E1 were lower than those of group E2, and at T12, T16, and T20, PI scores of groups M1 and E1 were lower compared to those of groups M2 and E2. A linear mixed model showed that the effect of repeated OHI and motivation during time was statistically significant, independently from the use of manual or electric toothbrush. The present results showed that repeated OHI and motivation are crucial in reducing PI score in orthodontic patients, independent of the type of toothbrush used.

Deployment Repeatability

DTIC Science & Technology

2016-08-31

photogrammetry to track a set of LEDS in two dimensions, a method that was able to resolve 2.2-mm lateral displacements of a 40-meter boom. This method... displacements . Sub-milliradian repeatability in MOIRE [This is a stand-in section for the MOIRE case study, which Dave Waller is getting through...The structure will most likely be under this stowed state for a long time under displacement paths and put this data into a computationally cheap 1

Androgen receptor CAG repeat polymorphisms in canine prostate cancer.

PubMed

Lai, C-L; L'Eplattenier, H; van den Ham, R; Verseijden, F; Jagtenberg, A; Mol, J A; Teske, E

2008-01-01

Relatively shorter lengths of the polymorphic polyglutamine repeat-1 of the androgen receptor (AR) have been associated with an increased risk of prostate cancer (PC) in humans. In the dog, there are 2 polymorphic CAG repeat (CAGr) regions. To investigate the relationship of CAGr length of the canine AR-gene and the development of PC. Thirty-two dogs with PC and 172 control dogs were used. DNA was extracted from blood. Both CAG repeats were amplified by polymerase chain reaction (PCR) and PCR products were sequenced. In dogs with PC, CAG-1 repeat length was shorter (P = .001) by an increased proportion of 10 repeats (P = .011) and no 12 repeats (P = .0017) than in the control dogs. No significant changes were found in CAG-3 length distribution. CAG-1 and CAG-3 polymorphisms proved not to be in linkage disequilibrium. Breed difference in allelic distribution was found in the control group. Of the prostate-disease sensitive breeds, a high percentage (64.5%) of the shortest haplotype 10/11 was found in the Doberman, whereas Beagles and German Pointers had higher haplotype 12/11 (47.1 and 50%). Bernese Mountain dogs and Bouvier dogs both shared a high percentage of 11 CAG-1 repeats and 13 CAG-3 repeats. Differences in (combined) allelic distributions among breeds were not significant. In this preliminary study, short CAG-1 repeats in the AR-gene were associated with an increased risk of developing canine PC. Although breed-specific differences in allelic distribution of CAG-1 and CAG-3 repeats were found, these could not be related to PC risk.

Roles of CUB and LDL receptor class A domain repeats of a transmembrane serine protease matriptase in its zymogen activation

PubMed Central

Inouye, Kuniyo; Tomoishi, Marie; Yasumoto, Makoto; Miyake, Yuka; Kojima, Kenji; Tsuzuki, Satoshi; Fushiki, Tohru

2013-01-01

Matriptase is a type II transmembrane serine protease containing two complement proteases C1r/C1s–urchin embryonic growth factor–bone morphogenetic protein domains (CUB repeat) and four low-density lipoprotein receptor class A domains (LDLRA repeat). The single-chain zymogen of matriptase has been found to exhibit substantial protease activity, possibly causing its own activation (i.e. conversion to a disulfide-linked two-chain fully active form), although the activation seems to be mediated predominantly by two-chain molecules. Our aim was to assess the roles of CUB and LDLRA repeats in zymogen activation. Transient expression studies of soluble truncated constructs of recombinant matriptase in COS-1 cells showed that the CUB repeat had an inhibitory effect on zymogen activation, possibly because it facilitated the interaction of two-chain molecules with a matriptase inhibitor, hepatocyte growth factor activator inhibitor type-1. By contrast, the LDLRA repeat had a promoting effect on zymogen activation. The effect of the LDLRA repeat seems to reflect its ability to increase zymogen activity. The proteolytic activities were higher in pseudozymogen forms of recombinant matriptase containing the LDLRA repeat than in a pseudozymogen without the repeat. Our findings provide new insights into the roles of these non-catalytic domains in the generation of active matriptase. PMID:23038671

The Effects of Repeaters on Test Equating.

ERIC Educational Resources Information Center

Andrulis, Richard S.; And Others

1978-01-01

The effects of repeaters (testees included in both administrations of two forms of a test) on the test equating process are examined. It is shown that repeaters do effect test equating and tend to lower the cutoff point for passing the test. (JKS)

Effect of Chitosan and Liposome Nanoparticles as Adjuvant Codelivery on the Immunoglobulin G Subclass Distribution in a Mouse Model

PubMed Central

Haryono, Agus; Salsabila, Korrie; Restu, Witta Kartika; Harmami, Sri Budi

2017-01-01

Background We investigate the immunogenic properties of chitosan and liposome nanoparticles as adjuvant codelivery against a commercial pneumococcal conjugate vaccine (PCV) in an animal model. Methods The chitosan and liposome nanoparticles were prepared by ionic gelation and dry methods, respectively. The PCV immunization was performed intradermally in the presence of adjuvants and booster injections which were given without an adjuvant. The Quil-A® was used as a control adjuvant. The ELISA was performed to measure the antibodies against pneumococcal type 14 polysaccharide (Pn14PS). Results The level of total antibodies against Pn14PS antigen was no different between the mouse groups with or without adjuvant codelivery. Codelivery of the PCV with chitosan nanoparticles as well as the Quil-A adjuvant elicited IgG1, IgG2a, IgG2b, and IgG3 antibodies. Meanwhile, codelivery of liposome nanoparticles elicited mainly IgG1 antibodies against the Pn14PS. Conclusions The chitosan and liposome nanoparticles as adjuvant codelivery were successfully synthesized. These nanoparticles have different shapes in particle formation, liposome nanoparticle with their unilamellar shape and chitosan nanoparticles in large shape due to the aggregation of small-size particles. Codelivery of chitosan nanoparticles has more effect on the IgG subclass antibody production than that of liposome nanoparticles in a mouse model. PMID:28758135

Comparison of Two Types of Warm-Up Upon Repeated-Sprint Performance in Experienced Soccer Players.

PubMed

van den Tillaar, Roland; von Heimburg, Erna

2016-08-01

van den Tillaar, R and von Heimburg, E. Comparison of two types of warm-up upon repeated-sprint performance in experienced soccer players. J Strength Cond Res 30(8): 2258-2265, 2016-The aim of the study was to compare the effects of a long warm-up and a short warm-up upon repeated-sprint performance in soccer players. Ten male soccer players (age, 21.9 ± 1.9 years; body mass, 77.7 ± 8.3 kg; body height, 1.85 ± 0.03 m) conducted 2 types of warm-ups with 1 week in between: a long warm-up (20 minutes: LWup) and a short warm-up (10 minutes: SWup). Each warm-up was followed by a repeated-sprint test consisting of 8 × 30 m sprints with a new start every 30th second. The best sprint time, total sprinting time, and % decrease in time together with heart rate, lactate, and rate of perceived exertion (RPE) were measured. No significant differences in performance were found for the repeated-sprint test parameters (total sprint time: 35.99 ± 1.32 seconds [LWup] and 36.12 ± 0.96 seconds [SWup]; best sprint time: 4.32 ± 0.13 seconds [LWup] and 4.30 ± 0.10 seconds [SWup]; and % sprint decrease: 4.16 ± 2.15% [LWup] and 5.02 ± 2.07% [SWup]). No differences in lactate concentration after the warm-up and after the repeated-sprint test were found. However, RPE and heart rate were significantly higher after the long warm-up and the repeated-sprint test compared with the short warm-up. It was concluded that a short warm-up is as effective as a long warm-up for repeated sprints in soccer. Therefore, in regular training, less warm-up time is needed; the extra time could be used for important soccer skill training.

Pentatricopeptide 336 and mitochondrial sorting in cucumber

USDA-ARS?s Scientific Manuscript database

Cucumber is a unique model plant for organellar genetics because its three genomes show differential transmission: maternal for chloroplast, paternal for mitochondrial and bi-parental for nuclear. A cucumber line has been selected showing a paternally transmitted, strongly mosaic (MSC) phenotype as...

Development of analog watch with minute repeater

NASA Astrophysics Data System (ADS)

Okigami, Tomio; Aoyama, Shigeru; Osa, Takashi; Igarashi, Kiyotaka; Ikegami, Tomomi

A complementary metal oxide semiconductor with large scale integration was developed for an electronic minute repeater. It is equipped with the synthetic struck sound circuit to generate natural struck sound necessary for the minute repeater. This circuit consists of an envelope curve drawing circuit, frequency mixer, polyphonic mixer, and booster circuit made by using analog circuit technology. This large scale integration is a single chip microcomputer with motor drivers and input ports in addition to the synthetic struck sound circuit, and it is possible to make an electronic system of minute repeater at a very low cost in comparison with the conventional type.

Zero-determinant strategies in finitely repeated games.

PubMed

Ichinose, Genki; Masuda, Naoki

2018-02-07

Direct reciprocity is a mechanism for sustaining mutual cooperation in repeated social dilemma games, where a player would keep cooperation to avoid being retaliated by a co-player in the future. So-called zero-determinant (ZD) strategies enable a player to unilaterally set a linear relationship between the player's own payoff and the co-player's payoff regardless of the strategy of the co-player. In the present study, we analytically study zero-determinant strategies in finitely repeated (two-person) prisoner's dilemma games with a general payoff matrix. Our results are as follows. First, we present the forms of solutions that extend the known results for infinitely repeated games (with a discount factor w of unity) to the case of finitely repeated games (0 < w < 1). Second, for the three most prominent ZD strategies, the equalizers, extortioners, and generous strategies, we derive the threshold value of w above which the ZD strategies exist. Third, we show that the only strategies that enforce a linear relationship between the two players' payoffs are either the ZD strategies or unconditional strategies, where the latter independently cooperates with a fixed probability in each round of the game, proving a conjecture previously made for infinitely repeated games. Copyright © 2017 Elsevier Ltd. All rights reserved.

Mission design for NISAR repeat-pass Interferometric SAR

NASA Astrophysics Data System (ADS)

Alvarez-Salazar, Oscar; Hatch, Sara; Rocca, Jennifer; Rosen, Paul; Shaffer, Scott; Shen, Yuhsyen; Sweetser, Theodore; Xaypraseuth, Peter

2014-10-01

The proposed spaceborne NASA-ISRO SAR (NISAR) mission would use the repeat-pass interferometric Synthetic Aperture Radar (InSAR) technique to measure the changing shape of Earth's surface at the centimeter scale in support of investigations in solid Earth and cryospheric sciences. Repeat-pass InSAR relies on multiple SAR observations acquired from nearly identical positions of the spacecraft as seen from the ground. Consequently, there are tight constraints on the repeatability of the orbit, and given the narrow field of view of the radar antenna beam, on the repeatability of the beam pointing. The quality and accuracy of the InSAR data depend on highly precise control of both orbital position and observatory pointing throughout the science observation life of the mission. This paper describes preliminary NISAR requirements and rationale for orbit repeatability and attitude control in order to meet science requirements. A preliminary error budget allocation and an implementation approach to meet these allocations are also discussed.

RTEL1 Inhibits Trinucleotide Repeat Expansions and Fragility

PubMed Central

Frizzell, Aisling; Nguyen, Jennifer H.G.; Petalcorin, Mark I.R.; Turner, Katherine D.; Boulton, Simon J.; Freudenreich, Catherine H.; Lahue, Robert S.

2018-01-01

SUMMARY Human RTEL1 is an essential, multifunctional helicase that maintains telomeres, regulates homologous recombination, and helps prevent bone marrow failure. Here, we show that RTEL1 also blocks trinucleotide repeat expansions, the causal mutation for 17 neurological diseases. Increased expansion frequencies of (CTG·CAG) repeats occurred in human cells following knockdown of RTEL1, but not the alternative helicase Fbh1, and purified RTEL1 efficiently unwound triplet repeat hairpins in vitro. The expansion-blocking activity of RTEL1 also required Rad18 and HLTF, homologs of yeast Rad18 and Rad5. These findings are reminiscent of budding yeast Srs2, which inhibits expansions, unwinds hairpins, and prevents triplet-repeat-induced chromosome fragility. Accordingly, we found expansions and fragility were suppressed in yeast srs2 mutants expressing RTEL1, but not Fbh1. We propose that RTEL1 serves as a human analog of Srs2 to inhibit (CTG·CAG) repeat expansions and fragility, likely by unwinding problematic hairpins. PMID:24561255

Isolation of human simple repeat loci by hybridization selection.

PubMed

Armour, J A; Neumann, R; Gobert, S; Jeffreys, A J

1994-04-01

We have isolated short tandem repeat arrays from the human genome, using a rapid method involving filter hybridization to enrich for tri- or tetranucleotide tandem repeats. About 30% of clones from the enriched library cross-hybridize with probes containing trimeric or tetrameric tandem arrays, facilitating the rapid isolation of large numbers of clones. In an initial analysis of 54 clones, 46 different tandem arrays were identified. Analysis of these tandem repeat loci by PCR showed that 24 were polymorphic in length; substantially higher levels of polymorphism were displayed by the tetrameric repeat loci isolated than by the trimeric repeats. Primary mapping of these loci by linkage analysis showed that they derive from 17 chromosomes, including the X chromosome. We anticipate the use of this strategy for the efficient isolation of tandem repeats from other sources of genomic DNA, including DNA from flow-sorted chromosomes, and from other species.

Ligand binding by repeat proteins: natural and designed

PubMed Central

Grove, Tijana Z; Cortajarena, Aitziber L; Regan, Lynne

2012-01-01

Repeat proteins contain tandem arrays of small structural motifs. As a consequence of this architecture, they adopt non-globular, extended structures that present large, highly specific surfaces for ligand binding. Here we discuss recent advances toward understanding the functional role of this unique modular architecture. We showcase specific examples of natural repeat proteins interacting with diverse ligands and also present examples of designed repeat protein–ligand interactions. PMID:18602006

Tandem-repeat protein domains across the tree of life.

PubMed

Jernigan, Kristin K; Bordenstein, Seth R

2015-01-01

Tandem-repeat protein domains, composed of repeated units of conserved stretches of 20-40 amino acids, are required for a wide array of biological functions. Despite their diverse and fundamental functions, there has been no comprehensive assessment of their taxonomic distribution, incidence, and associations with organismal lifestyle and phylogeny. In this study, we assess for the first time the abundance of armadillo (ARM) and tetratricopeptide (TPR) repeat domains across all three domains in the tree of life and compare the results to our previous analysis on ankyrin (ANK) repeat domains in this journal. All eukaryotes and a majority of the bacterial and archaeal genomes analyzed have a minimum of one TPR and ARM repeat. In eukaryotes, the fraction of ARM-containing proteins is approximately double that of TPR and ANK-containing proteins, whereas bacteria and archaea are enriched in TPR-containing proteins relative to ARM- and ANK-containing proteins. We show in bacteria that phylogenetic history, rather than lifestyle or pathogenicity, is a predictor of TPR repeat domain abundance, while neither phylogenetic history nor lifestyle predicts ARM repeat domain abundance. Surprisingly, pathogenic bacteria were not enriched in TPR-containing proteins, which have been associated within virulence factors in certain species. Taken together, this comparative analysis provides a newly appreciated view of the prevalence and diversity of multiple types of tandem-repeat protein domains across the tree of life. A central finding of this analysis is that tandem repeat domain-containing proteins are prevalent not just in eukaryotes, but also in bacterial and archaeal species.

The effectiveness of repeat lumbar transforaminal epidural steroid injections.

PubMed

Murthy, Naveen S; Geske, Jennifer R; Shelerud, Randy A; Wald, John T; Diehn, Felix E; Thielen, Kent R; Kaufmann, Timothy J; Morris, Jonathan M; Lehman, Vance T; Amrami, Kimberly K; Carter, Rickey E; Maus, Timothy P

2014-10-01

The aim of this study was to determine 1) if repeat lumbar transforaminal epidural steroid injections (TFESIs) resulted in recovery of pain relief, which has waned since an index injection, and 2) if cumulative benefit could be achieved by repeat injections within 3 months of the index injection. Retrospective observational study with statistical modeling of the response to repeat TFESI. Academic radiology practice. Two thousand eighty-seven single-level TFESIs were performed for radicular pain on 933 subjects. Subjects received repeat TFESIs >2 weeks and <1 year from the index injection. Hierarchical linear modeling was performed to evaluate changes in continuous and categorical pain relief outcomes after repeat TFESI. Subgroup analyses were performed on patients with <3 months duration of pain (acute pain), patients receiving repeat injections within 3 months (clustered injections), and in patients with both acute pain and clustered injections. Repeat TFESIs achieved pain relief in both continuous and categorical outcomes. Relative to the index injection, there was a minimal but statistically significant decrease in pain relief in modeled continuous outcome measures with subsequent injections. Acute pain patients recovered all prior benefit with a statistically significant cumulative benefit. Patients receiving clustered injections achieved statistically significant cumulative benefit, of greater magnitude in acute pain patients. Repeat TFESI may be performed for recurrence of radicular pain with the expectation of recovery of most or all previously achieved benefit; acute pain patients will likely recover all prior benefit. Repeat TFESIs within 3 months of the index injection can provide cumulative benefit. Wiley Periodicals, Inc.

Tandem-repeat protein domains across the tree of life

PubMed Central

Jernigan, Kristin K.

2015-01-01

Tandem-repeat protein domains, composed of repeated units of conserved stretches of 20–40 amino acids, are required for a wide array of biological functions. Despite their diverse and fundamental functions, there has been no comprehensive assessment of their taxonomic distribution, incidence, and associations with organismal lifestyle and phylogeny. In this study, we assess for the first time the abundance of armadillo (ARM) and tetratricopeptide (TPR) repeat domains across all three domains in the tree of life and compare the results to our previous analysis on ankyrin (ANK) repeat domains in this journal. All eukaryotes and a majority of the bacterial and archaeal genomes analyzed have a minimum of one TPR and ARM repeat. In eukaryotes, the fraction of ARM-containing proteins is approximately double that of TPR and ANK-containing proteins, whereas bacteria and archaea are enriched in TPR-containing proteins relative to ARM- and ANK-containing proteins. We show in bacteria that phylogenetic history, rather than lifestyle or pathogenicity, is a predictor of TPR repeat domain abundance, while neither phylogenetic history nor lifestyle predicts ARM repeat domain abundance. Surprisingly, pathogenic bacteria were not enriched in TPR-containing proteins, which have been associated within virulence factors in certain species. Taken together, this comparative analysis provides a newly appreciated view of the prevalence and diversity of multiple types of tandem-repeat protein domains across the tree of life. A central finding of this analysis is that tandem repeat domain-containing proteins are prevalent not just in eukaryotes, but also in bacterial and archaeal species. PMID:25653910

Repeated, but Not Acute, Stress Suppresses Inflammatory Plasma Extravasation

NASA Astrophysics Data System (ADS)

Strausbaugh, Holly J.; Dallman, Mary F.; Levine, Jon D.

1999-12-01

Clinical findings suggest that inflammatory disease symptoms are aggravated by ongoing, repeated stress, but not by acute stress. We hypothesized that, compared with single acute stressors, chronic repeated stress may engage different physiological mechanisms that exert qualitatively different effects on the inflammatory response. Because inhibition of plasma extravasation, a critical component of the inflammatory response, has been associated with increased disease severity in experimental arthritis, we tested for a potential repeated stress-induced inhibition of plasma extravasation. Repeated, but not single, exposures to restraint stress produced a profound inhibition of bradykinin-induced synovial plasma extravasation in the rat. Experiments examining the mechanism of inhibition showed that the effect of repeated stress was blocked by adrenalectomy, but not by adrenal medullae denervation, suggesting that the adrenal cortex mediates this effect. Consistent with known effects of stress and with mediation by the adrenal cortex, restraint stress evoked repeated transient elevations of plasma corticosterone levels. This elevated corticosterone was necessary and sufficient to produce inhibition of plasma extravasation because the stress-induced inhibition was blocked by preventing corticosterone synthesis and, conversely, induction of repeated transient elevations in plasma corticosterone levels mimicked the effects of repeated stress. These data suggest that repetition of a mild stressor can induce changes in the physiological state of the animal that enable a previously innocuous stressor to inhibit the inflammatory response. These findings provide a potential explanation for the clinical association between repeated stress and aggravation of inflammatory disease symptoms and provide a model for study of the biological mechanisms underlying the stress-induced aggravation of chronic inflammatory diseases.

Glutamate quantification by PRESS or MEGA-PRESS: Validation, repeatability, and concordance.

PubMed

van Veenendaal, Tamar M; Backes, Walter H; van Bussel, Frank C G; Edden, Richard A E; Puts, Nicolaas A J; Aldenkamp, Albert P; Jansen, Jacobus F A

2018-05-01

While PRESS is often employed to measure glutamate concentrations, MEGA-PRESS enables simultaneous Glx (glutamate and glutamine) and GABA measurements. This study aimed to compare validation, repeatability, and concordance of different approaches for glutamate quantification at 3T to aid future studies in their selection of the appropriate sequence and quantification method. Nine phantoms with different glutamate and glutamine concentrations and five healthy participants were scanned twice to assess respectively the validation and repeatability of measurements with PRESS and MEGA-PRESS. To assess concordance between the different methods, results from 95 human participants were compared. PRESS, MEGA-PRESS (i.e. difference), and the MEGA-PRESS OFF spectra were analyzed with both LCModel and Gannet. In vitro, excellent agreement was shown between actual and measured glutamate concentrations for all measurements (r>0.98). In vivo CVs were better for PRESS (2.9%) than MEGA-PRESS (4.9%) and MEGA-PRESS OFF (4.2%). However, the concordance between the sequences was low (PRESS and MEGA-PRESS OFF, r=0.3) to modest (MEGA-PRESS versus MEGA-PRESS OFF, r=0.8). Both PRESS and MEGA-PRESS can be employed to measure in vivo glutamate concentrations, although PRESS shows a better repeatability. Comparisons between in vivo glutamate measures of different sequences however need to be interpreted cautiously. Copyright © 2018 Elsevier Inc. All rights reserved.

Study of repeater technology for advanced multifunctional communications satellites

NASA Technical Reports Server (NTRS)

1972-01-01

Investigations are presented concerning design concepts and implementation approaches for the satellite communication repeater subsystems of advanced multifunctional satellites. In such systems the important concepts are the use of multiple antenna beams, repeater switching (routing), and efficient spectrum utilization through frequency reuse. An information base on these techniques was developed and tradeoff analyses were made of repeater design concepts, with the work design taken in a broad sense to include modulation beam coverage patterns. There were five major areas of study: requirements analysis and processing; study of interbeam interference in multibeam systems; characterization of multiple-beam switching repeaters; estimation of repeater weight and power for a number of alternatives; and tradeoff analyses based on these weight and power data.

The dark side of testing memory: repeated retrieval can enhance eyewitness suggestibility.

PubMed

Chan, Jason C K; Lapaglia, Jessica A

2011-12-01

Eyewitnesses typically recount their experiences many times before trial. Such repeated retrieval can enhance memory retention of the witnessed event. However, recent studies (e.g., Chan, Thomas, & Bulevich, 2009) have found that initial retrieval can exacerbate eyewitness suggestibility to later misleading information--a finding termed retrieval-enhanced suggestibility (RES). Here we examined the influence of multiple retrieval attempts on eyewitness suggestibility to subsequent misinformation. In four experiments, we systematically varied the number of initial tests taken (between zero and six), the delay between initial testing and misinformation exposure (~30 min or 1 week), and whether initial testing was manipulated between- or within-subjects. University undergraduate students were used as participants. Overall, we found that eyewitness suggestibility increased as the number of initial tests increased, but this RES effect was qualified by the delay and by whether initial testing occurred in a within- or between-subjects manner. Specifically, the within-subjects RES effect was smaller than the between-subjects RES effect, possibly because of the influence of retrieval-induced forgetting/facilitation (Chan, 2009) when initial testing was manipulated within subjects. Moreover, consistent with the testing effect literature (Roediger & Karpicke, 2006), the benefits of repeated testing on later memory were stronger after a 1-week delay than after a 30-min delay, thus reducing the negative impact of RES in long-term situations. These findings suggest that conditions that are likely to occur in criminal investigations can either increase (repeated testing) or reduce (delay) the influence of RES, thus further demonstrating the complex relationship between eyewitness memory and repeated retrieval.

Parameter regimes for a single sequential quantum repeater

NASA Astrophysics Data System (ADS)

Rozpędek, F.; Goodenough, K.; Ribeiro, J.; Kalb, N.; Caprara Vivoli, V.; Reiserer, A.; Hanson, R.; Wehner, S.; Elkouss, D.

2018-07-01

Quantum key distribution allows for the generation of a secret key between distant parties connected by a quantum channel such as optical fibre or free space. Unfortunately, the rate of generation of a secret key by direct transmission is fundamentally limited by the distance. This limit can be overcome by the implementation of so-called quantum repeaters. Here, we assess the performance of a specific but very natural setup called a single sequential repeater for quantum key distribution. We offer a fine-grained assessment of the repeater by introducing a series of benchmarks. The benchmarks, which should be surpassed to claim a working repeater, are based on finite-energy considerations, thermal noise and the losses in the setup. In order to boost the performance of the studied repeaters we introduce two methods. The first one corresponds to the concept of a cut-off, which reduces the effect of decoherence during the storage of a quantum state by introducing a maximum storage time. Secondly, we supplement the standard classical post-processing with an advantage distillation procedure. Using these methods, we find realistic parameters for which it is possible to achieve rates greater than each of the benchmarks, guiding the way towards implementing quantum repeaters.

ATXN2 trinucleotide repeat length correlates with risk of ALS.

PubMed

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

2017-03-01

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

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

PubMed

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

2018-02-01

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

Large Polyglutamine Repeats Cause Muscle Degeneration in SCA17 Mice

PubMed Central

Huang, Shanshan; Yang, Su; Guo, Jifeng; Yan, Sen; Gaertig, Marta A.; Li, Shihua; Li, Xiao-Jiang

2015-01-01

SUMMARY In polyglutamine (polyQ) diseases, large polyQ repeats cause juvenile cases with different symptoms than adult-onset patients, who carry smaller expanded polyQ repeats. The mechanisms behind the differential pathology mediated by different polyQ repeat lengths remain unknown. By studying knock-in mouse models of spinal cerebellar ataxia-17 (SCA17), we found that a large polyQ (105 glutamines) in the TATA box-binding protein (TBP) preferentially causes muscle degeneration and reduces the expression of muscle-specific genes. Direct expression of TBP with different polyQ repeats in mouse muscle revealed that muscle degeneration is mediated only by the large polyQ repeats. Different polyQ repeats differentially alter TBP’s interaction with neuronal and muscle-specific transcription factors. As a result, the large polyQ repeat decreases the association of MyoD with TBP and DNA promoters. Our findings suggest that specific alterations in protein interactions by large polyQ repeats may account for the unique pathology in juvenile polyQ diseases. PMID:26387956

Eccentricity and argument of perigee control for orbits with repeat ground tracks

NASA Technical Reports Server (NTRS)

Vincent, Mark A.

1992-01-01

In order to gain an understanding into the problem of eccentricity (e) and argument of perigee (omega) control for TOPEX/Poseidon, the two cases where the highest latitude crossing time and one of the equator crossings are held constant are investigated. Variations in e and omega cause a significant effect on the satellite's ground-track repeatability. Maintaining e and omega near their frozen values will minimize this variation. Analytical expressions are found to express this relationship while keeping an arbitrary point of the ground track fixed. The initial offset of the ground track from its nominal path determines the subsequent evolution of e and omega about their frozen values. This long-term behavior is numerically determined using an earth gravitational field including the first 17 zonal harmonics. The numerical results are plotted together with the analytical constraints to see if the later values of e and omega cause unacceptable deviation in the ground track.

47 CFR 90.247 - Mobile repeater stations.

Code of Federal Regulations, 2010 CFR

2010-10-01

... of the mobile unit and an automatic time-delay device that de-activates the transmitter after any... 47 Telecommunication 5 2010-10-01 2010-10-01 false Mobile repeater stations. 90.247 Section 90.247... MOBILE RADIO SERVICES Non-Voice and Other Specialized Operations § 90.247 Mobile repeater stations. A...

Repeat HIV-testing is associated with an increase in behavioral risk among men who have sex with men: a cohort study.

PubMed

Hoenigl, Martin; Anderson, Christy M; Green, Nella; Mehta, Sanjay R; Smith, Davey M; Little, Susan J

2015-09-11

The Center for Disease Control and Prevention recommends that high-risk groups, like sexually active men who have sex with men (MSM), receive HIV testing and counseling at least annually. The objective of this study was to investigate the relationship between voluntary repeat HIV testing and sexual risk behavior in MSM receiving rapid serologic and nucleic acid amplification testing. We performed a cohort study to analyze reported risk behavior among MSM receiving the "Early Test", a community-based, confidential acute and early HIV infection screening program in San Diego, California, between April 2008 and July 2014. The study included 8,935 MSM receiving 17,333 "Early Tests". A previously published risk behavior score for HIV acquisition in MSM (i.e. Menza score) was chosen as an outcome to assess associations between risk behaviors and number of repeated tests. At baseline, repeat-testers (n = 3,202) reported more male partners and more condomless receptive anal intercourse (CRAI) when compared to single-testers (n = 5,405, all P <0.001). In 2,457 repeat testers there was a strong association observed between repeated HIV tests obtained and increased risk behavior, with number of male partners, CRAI with high risk persons, non-injection stimulant drug use, and sexually transmitted infections all increasing between the first and last test. There was also a linear increase of risk (i.e. high Menza scores) with number of tests up to the 17th test. In the multivariable mixed effects model, more HIV tests (OR = 1.18 for each doubling of the number of tests, P <0.001) and younger age (OR = 0.95 per 5-year increase, P = 0.006) had significant associations with high Menza scores. This study found that the highest risk individuals for acquiring HIV (e.g. candidates for antiretroviral pre-exposure prophylaxis) can be identified by their testing patterns. Future studies should delineate causation versus association to improve prevention messages delivered to repeat

Large Torque Variations in Two Soft Gamma Repeaters

NASA Technical Reports Server (NTRS)

Woods, Peter M.; Kouveliotou, Chryssa; Gogus, Ersin; Finger, Mark H.; Swank, Jean; Markwardt, Craig B.; Hurley, Kevin; vanderKlis, Michiel

2002-01-01

We have monitored the pulse frequencies of the two soft gamma repeaters SGR 1806-20 and SGR 1900+14 through the beginning of year 2001 using primarily Rossi X-Ray Timing Explorer Proportional Counter Array observations. In both sources, we observe large changes in the spin-down torque up to a factor of approximately 4, which persist for several months. Using long-baseline phase-connected timing solutions as well as the overall frequency histories, we construct torque noise power spectra for each SGR (Soft Gamma Repeater). The power spectrum of each source is very red (power-law slope is approximately -3.5). The torque noise power levels are consistent with some accreting systems on timescales of approximately 1 yr, yet the full power spectrum is much steeper in frequency than any known accreting source. To the best of our knowledge, torque noise power spectra with a comparably steep frequency dependence have been seen only in young, glitching radio pulsars (e.g., Vela). The observed changes in spin-down rate do not correlate with burst activity; therefore, the physical mechanisms behind each phenomenon are also likely unrelated. Within the context of the magnetar model, seismic activity can not account for both the bursts and the long-term torque changes unless the seismically active regions are decoupled from one another.

Brokering as a framework for hydrological model repeatability

NASA Astrophysics Data System (ADS)

Fuka, Daniel; Collick, Amy; MacAlister, Charlotte; Braeckel, Aaron; Wright, Dawn; Jodha Khalsa, Siri; Boldrini, Enrico; Easton, Zachary

2015-04-01

Data brokering aims to provide those in the the sciences with quick and repeatable access to data that represents physical, biological, and chemical characteristics; specifically to accelerate scientific discovery. Environmental models are useful tools to understand the behavior of hydrological systems. Unfortunately, parameterization of these hydrological models requires many different data, from different sources, and from different disciplines (e.g., atmospheric, geoscience, ecology). In basin scale hydrological modeling, the traditional procedure for model initialization starts with obtaining elevation models, land-use characterizations, soils maps, and weather data. It is often the researcher's past experience with these datasets that determines which datasets will be used in a study, and often newer, or more suitable data products will exist. An added complexity is that various science communities have differing data formats, storage protocols, and manipulation methods, which makes use by a non native user exceedingly difficult and time consuming. We demonstrate data brokering as a means to address several of these challenges. We present two test case scenarios in which researchers attempt to reproduce hydrological model results using 1) general internet based data gathering techniques, and 2) a scientific data brokering interface. We show that data brokering can increase the efficiency with which data are obtained, models are initialized, and results are analyzed. As an added benefit, it appears brokering can significantly increase the repeatability of a given study.

A repeating fast radio burst

NASA Astrophysics Data System (ADS)

Spitler, L. G.; Scholz, P.; Hessels, J. W. T.; Bogdanov, S.; Brazier, A.; Camilo, F.; Chatterjee, S.; Cordes, J. M.; Crawford, F.; Deneva, J.; Ferdman, R. D.; Freire, P. C. C.; Kaspi, V. M.; Lazarus, P.; Lynch, R.; Madsen, E. C.; McLaughlin, M. A.; Patel, C.; Ransom, S. M.; Seymour, A.; Stairs, I. H.; Stappers, B. W.; van Leeuwen, J.; Zhu, W. W.

2016-03-01

Fast radio bursts are millisecond-duration astronomical radio pulses of unknown physical origin that appear to come from extragalactic distances. Previous follow-up observations have failed to find additional bursts at the same dispersion measure (that is, the integrated column density of free electrons between source and telescope) and sky position as the original detections. The apparent non-repeating nature of these bursts has led to the suggestion that they originate in cataclysmic events. Here we report observations of ten additional bursts from the direction of the fast radio burst FRB 121102. These bursts have dispersion measures and sky positions consistent with the original burst. This unambiguously identifies FRB 121102 as repeating and demonstrates that its source survives the energetic events that cause the bursts. Additionally, the bursts from FRB 121102 show a wide range of spectral shapes that appear to be predominantly intrinsic to the source and which vary on timescales of minutes or less. Although there may be multiple physical origins for the population of fast radio bursts, these repeat bursts with high dispersion measure and variable spectra specifically seen from the direction of FRB 121102 support an origin in a young, highly magnetized, extragalactic neutron star.

A repeating fast radio burst.

PubMed

Spitler, L G; Scholz, P; Hessels, J W T; Bogdanov, S; Brazier, A; Camilo, F; Chatterjee, S; Cordes, J M; Crawford, F; Deneva, J; Ferdman, R D; Freire, P C C; Kaspi, V M; Lazarus, P; Lynch, R; Madsen, E C; McLaughlin, M A; Patel, C; Ransom, S M; Seymour, A; Stairs, I H; Stappers, B W; van Leeuwen, J; Zhu, W W

2016-03-10

Fast radio bursts are millisecond-duration astronomical radio pulses of unknown physical origin that appear to come from extragalactic distances. Previous follow-up observations have failed to find additional bursts at the same dispersion measure (that is, the integrated column density of free electrons between source and telescope) and sky position as the original detections. The apparent non-repeating nature of these bursts has led to the suggestion that they originate in cataclysmic events. Here we report observations of ten additional bursts from the direction of the fast radio burst FRB 121102. These bursts have dispersion measures and sky positions consistent with the original burst. This unambiguously identifies FRB 121102 as repeating and demonstrates that its source survives the energetic events that cause the bursts. Additionally, the bursts from FRB 121102 show a wide range of spectral shapes that appear to be predominantly intrinsic to the source and which vary on timescales of minutes or less. Although there may be multiple physical origins for the population of fast radio bursts, these repeat bursts with high dispersion measure and variable spectra specifically seen from the direction of FRB 121102 support an origin in a young, highly magnetized, extragalactic neutron star.

RTEL1 inhibits trinucleotide repeat expansions and fragility.

PubMed

Frizzell, Aisling; Nguyen, Jennifer H G; Petalcorin, Mark I R; Turner, Katherine D; Boulton, Simon J; Freudenreich, Catherine H; Lahue, Robert S

2014-03-13

Human RTEL1 is an essential, multifunctional helicase that maintains telomeres, regulates homologous recombination, and helps prevent bone marrow failure. Here, we show that RTEL1 also blocks trinucleotide repeat expansions, the causal mutation for 17 neurological diseases. Increased expansion frequencies of (CTG⋅CAG) repeats occurred in human cells following knockdown of RTEL1, but not the alternative helicase Fbh1, and purified RTEL1 efficiently unwound triplet repeat hairpins in vitro. The expansion-blocking activity of RTEL1 also required Rad18 and HLTF, homologs of yeast Rad18 and Rad5. These findings are reminiscent of budding yeast Srs2, which inhibits expansions, unwinds hairpins, and prevents triplet-repeat-induced chromosome fragility. Accordingly, we found expansions and fragility were suppressed in yeast srs2 mutants expressing RTEL1, but not Fbh1. We propose that RTEL1 serves as a human analog of Srs2 to inhibit (CTG⋅CAG) repeat expansions and fragility, likely by unwinding problematic hairpins. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

[Convergent origin of repeats in genes coding for globular proteins. An analysis of the factors determining the presence of inverted and symmetrical repeats].

PubMed

Solov'ev, V V; Kel', A E; Kolchanov, N A

1989-01-01

The factors, determining the presence of inverted and symmetrical repeats in genes coding for globular proteins, have been analysed. An interesting property of genetical code has been revealed in the analysis of symmetrical repeats: the pairs of symmetrical codons corresponded to pairs of amino acids with mostly similar physical-chemical parameters. This property may explain the presence of symmetrical repeats and palindromes only in genes coding for beta-structural proteins-polypeptides, where amino acids with similar physical-chemical properties occupy symmetrical positions. A stochastic model of evolution of polynucleotide sequences has been used for analysis of inverted repeats. The modelling demonstrated that only limiting of sequences (uneven frequencies of used codons) is enough for arising of nonrandom inverted repeats in genes.

47 CFR 90.247 - Mobile repeater stations.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 47 Telecommunication 5 2014-10-01 2014-10-01 false Mobile repeater stations. 90.247 Section 90.247... MOBILE RADIO SERVICES Non-Voice and Other Specialized Operations § 90.247 Mobile repeater stations. A mobile station authorized to operate on a mobile service frequency above 25 MHz may be used as a mobile...

47 CFR 90.247 - Mobile repeater stations.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 47 Telecommunication 5 2013-10-01 2013-10-01 false Mobile repeater stations. 90.247 Section 90.247... MOBILE RADIO SERVICES Non-Voice and Other Specialized Operations § 90.247 Mobile repeater stations. A mobile station authorized to operate on a mobile service frequency above 25 MHz may be used as a mobile...

47 CFR 90.247 - Mobile repeater stations.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 47 Telecommunication 5 2011-10-01 2011-10-01 false Mobile repeater stations. 90.247 Section 90.247... MOBILE RADIO SERVICES Non-Voice and Other Specialized Operations § 90.247 Mobile repeater stations. A mobile station authorized to operate on a mobile service frequency above 25 MHz may be used as a mobile...

47 CFR 90.247 - Mobile repeater stations.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 47 Telecommunication 5 2012-10-01 2012-10-01 false Mobile repeater stations. 90.247 Section 90.247... MOBILE RADIO SERVICES Non-Voice and Other Specialized Operations § 90.247 Mobile repeater stations. A mobile station authorized to operate on a mobile service frequency above 25 MHz may be used as a mobile...

Oxidative stress adaptation with acute, chronic, and repeated stress.

PubMed

Pickering, Andrew M; Vojtovich, Lesya; Tower, John; A Davies, Kelvin J

2013-02-01

Oxidative stress adaptation, or hormesis, is an important mechanism by which cells and organisms respond to, and cope with, environmental and physiological shifts in the level of oxidative stress. Most studies of oxidative stress adaption have been limited to adaptation induced by acute stress. In contrast, many if not most environmental and physiological stresses are either repeated or chronic. In this study we find that both cultured mammalian cells and the fruit fly Drosophila melanogaster are capable of adapting to chronic or repeated stress by upregulating protective systems, such as their proteasomal proteolytic capacity to remove oxidized proteins. Repeated stress adaptation resulted in significant extension of adaptive responses. Repeated stresses must occur at sufficiently long intervals, however (12-h or more for MEF cells and 7 days or more for flies), for adaptation to be successful, and the levels of both repeated and chronic stress must be lower than is optimal for adaptation to acute stress. Regrettably, regimens of adaptation to both repeated and chronic stress that were successful for short-term survival in Drosophila nevertheless also caused significant reductions in life span for the flies. Thus, although both repeated and chronic stress can be tolerated, they may result in a shorter life. Copyright © 2012 Elsevier Inc. All rights reserved.

Childhood remembered: Reports of both unique and repeated events.

PubMed

Peterson, Carole; Baker-Ward, Lynne; Grovenstein, Tiffany N

2016-01-01

To explore the significance of repeated memories for individuals' personal histories, we compared the characteristics of young adults' unique and repeated memories of childhood experiences. Memory type (unique vs. repeated) was a within-participant variable. In Experiment 1, college-age participants generated as many early memories as possible in 4 minutes; in Experiment 2, another sample provided complete reports of five early memories in each condition. In both experiments, participants rated the vividness, biographical importance and personal meaning of each memory and labelled the accompanying emotion. Unique memories were more vivid than repeated memories as well as more likely to include negative emotion, regardless of the method of reporting. Most importantly, college students rated their memories for unique and repeated events as equivalently infused with personal meaning. Analysis of the content of the memories reported in Experiment 2 established that unique and repeated memories did not differ in word count or percentages of perceptual terms or words indicating positive affect, although unique memories contained a greater percentage of negative affect. Additional analyses of content provided evidence for differences in the functions served by unique and repeated memories. The results have implications for the study of autobiographical memory and for identifying over-general memories.

Environmental stress induces trinucleotide repeat mutagenesis in human cells.

PubMed

Chatterjee, Nimrat; Lin, Yunfu; Santillan, Beatriz A; Yotnda, Patricia; Wilson, John H

2015-03-24

The dynamic mutability of microsatellite repeats is implicated in the modification of gene function and disease phenotype. Studies of the enhanced instability of long trinucleotide repeats (TNRs)-the cause of multiple human diseases-have revealed a remarkable complexity of mutagenic mechanisms. Here, we show that cold, heat, hypoxic, and oxidative stresses induce mutagenesis of a long CAG repeat tract in human cells. We show that stress-response factors mediate the stress-induced mutagenesis (SIM) of CAG repeats. We show further that SIM of CAG repeats does not involve mismatch repair, nucleotide excision repair, or transcription, processes that are known to promote TNR mutagenesis in other pathways of instability. Instead, we find that these stresses stimulate DNA rereplication, increasing the proportion of cells with >4 C-value (C) DNA content. Knockdown of the replication origin-licensing factor CDT1 eliminates both stress-induced rereplication and CAG repeat mutagenesis. In addition, direct induction of rereplication in the absence of stress also increases the proportion of cells with >4C DNA content and promotes repeat mutagenesis. Thus, environmental stress triggers a unique pathway for TNR mutagenesis that likely is mediated by DNA rereplication. This pathway may impact normal cells as they encounter stresses in their environment or during development or abnormal cells as they evolve metastatic potential.

Security of Quantum Repeater Network Operation

DTIC Science & Technology

2016-10-03

readily in quantum networks than in classical networks. Our presentation at the SENT workshop attracted the attention of computer and network researchers...AFRL-AFOSR-JP-TR-2016-0079 Security of Quantum Repeater Network Operation Rodney Van Meter KEIO UNIVERSITY Final Report 10/03/2016 DISTRIBUTION A...To)  29 May 2014 to 28 May 2016 4. TITLE AND SUBTITLE Security of Quantum Repeater Network Operation 5a.  CONTRACT NUMBER 5b.  GRANT NUMBER FA2386

Repeatability of DTI-based skeletal muscle fiber tracking

PubMed Central

Heemskerk, Anneriet M.; Sinha, Tuhin K.; Wilson, Kevin J.; Ding, Zhaohua; Damon, Bruce M.

2015-01-01

Diffusion tensor imaging (DTI)-based muscle fiber tracking enables the measurement of muscle architectural parameters, such as pennation angle (θ) and fiber tract length (Lft), throughout the entire muscle. Little is known, however, about the repeatability of either the muscle architectural measures or the underlying diffusion measures. Therefore, the goal of this study was to investigate the repeatability of DTI fiber tracking-based measurements and θ and Lft. Four DTI acquisitions were performed on two days that allowed for between acquisition, within day, and between day analyses. The eigenvalues and fractional anisotropy were calculated at the maximum cross-sectional area of, and fiber tracking was performed in, the tibialis anterior muscle of nine healthy subjects. The between acquisitions condition had the highest repeatability for the DTI indices and the architectural parameters. The overall inter class correlation coefficients (ICC’s) were greater than 0.6 for both θ and Lft and the repeatability coefficients were θ <10.2° and Lft < 50 mm. In conclusion, under the experimental and data analysis conditions used, the repeatability of the diffusion measures is very good and repeatability of the architectural measurements is acceptable. Therefore, this study demonstrates the feasibility for longitudinal studies of alterations in muscle architecture using DTI-based fiber tracking, under similar noise conditions and with similar diffusion characteristics. PMID:20099372

Algorithm to find distant repeats in a single protein sequence

PubMed Central

Banerjee, Nirjhar; Sarani, Rangarajan; Ranjani, Chellamuthu Vasuki; Sowmiya, Govindaraj; Michael, Daliah; Balakrishnan, Narayanasamy; Sekar, Kanagaraj

2008-01-01

Distant repeats in protein sequence play an important role in various aspects of protein analysis. A keen analysis of the distant repeats would enable to establish a firm relation of the repeats with respect to their function and three-dimensional structure during the evolutionary process. Further, it enlightens the diversity of duplication during the evolution. To this end, an algorithm has been developed to find all distant repeats in a protein sequence. The scores from Point Accepted Mutation (PAM) matrix has been deployed for the identification of amino acid substitutions while detecting the distant repeats. Due to the biological importance of distant repeats, the proposed algorithm will be of importance to structural biologists, molecular biologists, biochemists and researchers involved in phylogenetic and evolutionary studies. PMID:19052663

Repeated rat-forced swim test: reducing the number of animals to evaluate gradual effects of antidepressants.

PubMed

Mezadri, T J; Batista, G M; Portes, A C; Marino-Neto, J; Lino-de-Oliveira, C

2011-02-15

The forced swim test (FST) is a pre-clinical test to short and long term treatment with antidepressant drugs (ADT), which requires between-subject designs. Herein a modified protocol of the FST using within-subject design (repeated rat-FST) was evaluated. Male Wistar rats were submitted to 15 min of swimming (Day 1: pretest) followed by three subsequent 5 min-swimming tests one week apart (Day 2: test, Day 7: retest 1, Day 14: retest 2). To determine the temporal and factorial characteristics of the variables scored in the repeated rat-FST, the protocol was carried out in untreated animals (E1). To validate the method, daily injections of Fluoxetine (FLX, 2.5mg/kg, i.p.) or saline were given over a 2-week period (E2). Tests and retests have been videotaped for further register of the latency, frequency and duration of behaviors. Over retesting the latency to immobility decreased whereas duration of immobility tended to increase. Factorial analysis revealed that the test, the retest 1 as well as the retest 2 have variables suitable to detection of antidepressant-like effects of ADT. Compared to saline, FLX chronically administrated reduced duration of immobility whereas increased duration of swimming in retest 2. The data suggest that repeated rat-FST detected the gradual increase in the efficacy of low doses of FLX over time. Therefore, repeated rat-FST seemed suitable to detect short and long term effects of selective serotonin reuptake inhibitors, or other ADT, thus reducing the number of animals used in the screenings of this type of compounds. © 2010 Elsevier B.V. All rights reserved.

GFP-based fluorescence assay for CAG repeat instability in cultured human cells.

PubMed

Santillan, Beatriz A; Moye, Christopher; Mittelman, David; Wilson, John H

2014-01-01

Trinucleotide repeats can be highly unstable, mutating far more frequently than point mutations. Repeats typically mutate by addition or loss of units of the repeat. CAG repeat expansions in humans trigger neurological diseases that include myotonic dystrophy, Huntington disease, and several spinocerebellar ataxias. In human cells, diverse mechanisms promote CAG repeat instability, and in mice, the mechanisms of instability are varied and tissue-dependent. Dissection of mechanistic complexity and discovery of potential therapeutics necessitates quantitative and scalable screens for repeat mutation. We describe a GFP-based assay for screening modifiers of CAG repeat instability in human cells. The assay exploits an engineered intronic CAG repeat tract that interferes with expression of an inducible GFP minigene. Like the phenotypes of many trinucleotide repeat disorders, we find that GFP function is impaired by repeat expansion, in a length-dependent manner. The intensity of fluorescence varies inversely with repeat length, allowing estimates of repeat tract changes in live cells. We validate the assay using transcription through the repeat and engineered CAG-specific nucleases, which have previously been reported to induce CAG repeat instability. The assay is relatively fast and should be adaptable to large-scale screens of chemical and shRNA libraries.

ICAO helicopter noise measurement repeatability program : U.S. test report, Bell 206L-1, noise measurement flight test

DOT National Transportation Integrated Search

1985-09-30

This document reports the findings of the U.S. test team's participation in the Helicopter Noise Measurement Repeatability Program (HNMRP) conducted under the direction of the International Civil Aviation Organization's (ICAO) Committee on Aviation E...

Repeated human leukocyte antigen mismatches in lung re-transplantation.

PubMed

Sommer, Wiebke; Hallensleben, Michael; Ius, Fabio; Kühn, Christian; Tudorache, Igor; Avsar, Murat; Salman, Jawad; Siemeni, Thierry; Greer, Mark; Gottlieb, Jens; Boethig, Dietmar; Blasczyk, Rainer; Haverich, Axel; Warnecke, Gregor

2017-02-01

The role of HLA-sensitization in the absence of detectable DSA in lung re-transplantation is unclear. Antigens of the second donor matching the HLA typing of the first donor are considered 'unacceptable', by some tissue typing laboratories, especially in kidney re-transplantation. Thus, we performed a retrospective analysis of all lung re-transplantations focussing on the impact of HLA-homologies between the first and the second donor ('unacceptable' antigens; repeated HLA mismatch) on patient and graft survival. A total of 132 lung re-transplantations were performed at our centre between 1985 and 2014, of which 120 with complete HLA data were analysed. 55.8% of the recipients received re-transplants with repeated HLA mismatched antigens whereas 43.2% of the re-transplants were transplanted without repeated HLA mismatched antigens. Postoperative survival showed no difference between re-transplant procedures with or without repeated HLA mismatches (p=0.99). While neither homologies on the HLA-A, -B, -C, or -DR locus, nor the addition of several locus homologies (p=0.72) had an impact on survival, unexpectedly, repeated HLA mismatching on the HLA-DQ locus was correlated with better survival. Re-transplantations with repeated HLA mismatches did not result in more development of CLAD as compared to recipients without repeated HLA mismatches (p=0.99). Neither the number of repeated HLA mismatched antigens (p=0.52) nor the HLA locus (HLA-A(p=0.34), HLA-B(p=0.97), HLA-C (p=0.80), HLA-DR(p=0.49) and HLA-DQ(p=0.07)) had an impact on the development of CLAD after re-transplantation. Transplantation with repeated HLA mismatches due to sensitization by a previous transplantation in the absence of detectable HLA-antibodies does not have a negative impact on patient or graft survival. Copyright © 2016 Elsevier B.V. All rights reserved.

Repeat Gamma Knife Radiosurgery for Trigeminal Neuralgia

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

Aubuchon, Adam C., E-mail: acaubuchon@gmail.com; Chan, Michael D.; Lovato, James F.

2011-11-15

Purpose: Repeat gamma knife stereotactic radiosurgery (GKRS) for recurrent or persistent trigeminal neuralgia induces an additional response but at the expense of an increased incidence of facial numbness. The present series summarized the results of a repeat treatment series at Wake Forest University Baptist Medical Center, including a multivariate analysis of the data to identify the prognostic factors for treatment success and toxicity. Methods and Materials: Between January 1999 and December 2007, 37 patients underwent a second GKRS application because of treatment failure after a first GKRS treatment. The mean initial dose in the series was 87.3 Gy (range, 80-90).more » The mean retreatment dose was 84.4 Gy (range, 60-90). The dosimetric variables recorded included the dorsal root entry zone dose, pons surface dose, and dose to the distal nerve. Results: Of the 37 patients, 81% achieved a >50% pain relief response to repeat GKRS, and 57% experienced some form of trigeminal dysfunction after repeat GKRS. Two patients (5%) experienced clinically significant toxicity: one with bothersome numbness and one with corneal dryness requiring tarsorraphy. A dorsal root entry zone dose at repeat treatment of >26.6 Gy predicted for treatment success (61% vs. 32%, p = .0716). A cumulative dorsal root entry zone dose of >84.3 Gy (72% vs. 44%, p = .091) and a cumulative pons surface dose of >108.5 Gy (78% vs. 44%, p = .018) predicted for post-GKRS numbness. The presence of any post-GKRS numbness predicted for a >50% decrease in pain intensity (100% vs. 60%, p = .0015). Conclusion: Repeat GKRS is a viable treatment option for recurrent trigeminal neuralgia, although the patient assumes a greater risk of nerve dysfunction to achieve maximal pain relief.« less

Diversity and evolution of centromere repeats in the maize genome.

PubMed

Bilinski, Paul; Distor, Kevin; Gutierrez-Lopez, Jose; Mendoza, Gabriela Mendoza; Shi, Jinghua; Dawe, R Kelly; Ross-Ibarra, Jeffrey

2015-03-01

Centromere repeats are found in most eukaryotes and play a critical role in kinetochore formation. Though centromere repeats exhibit considerable diversity both within and among species, little is understood about the mechanisms that drive centromere repeat evolution. Here, we use maize as a model to investigate how a complex history involving polyploidy, fractionation, and recent domestication has impacted the diversity of the maize centromeric repeat CentC. We first validate the existence of long tandem arrays of repeats in maize and other taxa in the genus Zea. Although we find considerable sequence diversity among CentC copies genome-wide, genetic similarity among repeats is highest within these arrays, suggesting that tandem duplications are the primary mechanism for the generation of new copies. Nonetheless, clustering analyses identify similar sequences among distant repeats, and simulations suggest that this pattern may be due to homoplasious mutation. Although the two ancestral subgenomes of maize have contributed nearly equal numbers of centromeres, our analysis shows that the majority of all CentC repeats derive from one of the parental genomes, with an even stronger bias when examining the largest assembled contiguous clusters. Finally, by comparing maize with its wild progenitor teosinte, we find that the abundance of CentC likely decreased after domestication, while the pericentromeric repeat Cent4 has drastically increased.

The evolution of filamin-a protein domain repeat perspective.

PubMed

Light, Sara; Sagit, Rauan; Ithychanda, Sujay S; Qin, Jun; Elofsson, Arne

2012-09-01

Particularly in higher eukaryotes, some protein domains are found in tandem repeats, performing broad functions often related to cellular organization. For instance, the eukaryotic protein filamin interacts with many proteins and is crucial for the cytoskeleton. The functional properties of long repeat domains are governed by the specific properties of each individual domain as well as by the repeat copy number. To provide better understanding of the evolutionary and functional history of repeating domains, we investigated the mode of evolution of the filamin domain in some detail. Among the domains that are common in long repeat proteins, sushi and spectrin domains evolve primarily through cassette tandem duplications while scavenger and immunoglobulin repeats appear to evolve through clustered tandem duplications. Additionally, immunoglobulin and filamin repeats exhibit a unique pattern where every other domain shows high sequence similarity. This pattern may be the result of tandem duplications, serve to avert aggregation between adjacent domains or it is the result of functional constraints. In filamin, our studies confirm the presence of interspersed integrin binding domains in vertebrates, while invertebrates exhibit more varied patterns, including more clustered integrin binding domains. The most notable case is leech filamin, which contains a 20 repeat expansion and exhibits unique dimerization topology. Clearly, invertebrate filamins are varied and contain examples of similar adjacent integrin-binding domains. Given that invertebrate integrin shows more similarity to the weaker filamin binder, integrin β3, it is possible that the distance between integrin-binding domains is not as crucial for invertebrate filamins as for vertebrates. Copyright © 2012 Elsevier Inc. All rights reserved.

Repeatability and Reproducibility of Decisions by Latent Fingerprint Examiners

PubMed Central

Ulery, Bradford T.; Hicklin, R. Austin; Buscaglia, JoAnn; Roberts, Maria Antonia

2012-01-01

The interpretation of forensic fingerprint evidence relies on the expertise of latent print examiners. We tested latent print examiners on the extent to which they reached consistent decisions. This study assessed intra-examiner repeatability by retesting 72 examiners on comparisons of latent and exemplar fingerprints, after an interval of approximately seven months; each examiner was reassigned 25 image pairs for comparison, out of total pool of 744 image pairs. We compare these repeatability results with reproducibility (inter-examiner) results derived from our previous study. Examiners repeated 89.1% of their individualization decisions, and 90.1% of their exclusion decisions; most of the changed decisions resulted in inconclusive decisions. Repeatability of comparison decisions (individualization, exclusion, inconclusive) was 90.0% for mated pairs, and 85.9% for nonmated pairs. Repeatability and reproducibility were notably lower for comparisons assessed by the examiners as “difficult” than for “easy” or “moderate” comparisons, indicating that examiners' assessments of difficulty may be useful for quality assurance. No false positive errors were repeated (n = 4); 30% of false negative errors were repeated. One percent of latent value decisions were completely reversed (no value even for exclusion vs. of value for individualization). Most of the inter- and intra-examiner variability concerned whether the examiners considered the information available to be sufficient to reach a conclusion; this variability was concentrated on specific image pairs such that repeatability and reproducibility were very high on some comparisons and very low on others. Much of the variability appears to be due to making categorical decisions in borderline cases. PMID:22427888

Security of Quantum Repeater Network Operation

DTIC Science & Technology

2016-10-03

AFRL-AFOSR-JP-TR-2016-0079 Security of Quantum Repeater Network Operation Rodney Van Meter KEIO UNIVERSITY Final Report 10/03/2016 DISTRIBUTION A...To)  29 May 2014 to 28 May 2016 4. TITLE AND SUBTITLE Security of Quantum Repeater Network Operation 5a.  CONTRACT NUMBER 5b.  GRANT NUMBER FA2386...ABSTRACT Much of the work on quantum networks , both entangled and unentangled, has been about the uses of quantum networks to enhance end- host security

Repeat-swap homology modeling of secondary active transporters: updated protocol and prediction of elevator-type mechanisms

PubMed Central

Vergara-Jaque, Ariela; Fenollar-Ferrer, Cristina; Kaufmann, Desirée; Forrest, Lucy R.

2015-01-01

Secondary active transporters are critical for neurotransmitter clearance and recycling during synaptic transmission and uptake of nutrients. These proteins mediate the movement of solutes against their concentration gradients, by using the energy released in the movement of ions down pre-existing concentration gradients. To achieve this, transporters conform to the so-called alternating-access hypothesis, whereby the protein adopts at least two conformations in which the substrate binding sites are exposed to one or other side of the membrane, but not both simultaneously. Structures of a bacterial homolog of neuronal glutamate transporters, GltPh, in several different conformational states have revealed that the protein structure is asymmetric in the outward- and inward-open states, and that the conformational change connecting them involves a elevator-like movement of a substrate binding domain across the membrane. The structural asymmetry is created by inverted-topology repeats, i.e., structural repeats with similar overall folds whose transmembrane topologies are related to each other by two-fold pseudo-symmetry around an axis parallel to the membrane plane. Inverted repeats have been found in around three-quarters of secondary transporter folds. Moreover, the (a)symmetry of these systems has been successfully used as a bioinformatic tool, called “repeat-swap modeling” to predict structural models of a transporter in one conformation using the known structure of the transporter in the complementary conformation as a template. Here, we describe an updated repeat-swap homology modeling protocol, and calibrate the accuracy of the method using GltPh, for which both inward- and outward-facing conformations are known. We then apply this repeat-swap homology modeling procedure to a concentrative nucleoside transporter, VcCNT, which has a three-dimensional arrangement related to that of GltPh. The repeat-swapped model of VcCNT predicts that nucleoside transport

Phylogeny and strain typing of Escherichia coli, inferred from variation at mononucleotide repeat loci.

PubMed

Diamant, Eran; Palti, Yniv; Gur-Arie, Riva; Cohen, Helit; Hallerman, Eric M; Kashi, Yechezkel

2004-04-01

Multilocus sequencing of housekeeping genes has been used previously for bacterial strain typing and for inferring evolutionary relationships among strains of Escherichia coli. In this study, we used shorter intergenic sequences that contained simple sequence repeats (SSRs) of repeating mononucleotide motifs (mononucleotide repeats [MNRs]) to infer the phylogeny of pathogenic and commensal E. coli strains. Seven noncoding loci (four MNRs and three non-SSRs) were sequenced in 27 strains, including enterohemorrhagic (six isolates of O157:H7), enteropathogenic, enterotoxigenic, B, and K-12 strains. The four MNRs were also sequenced in 20 representative strains of the E. coli reference (ECOR) collection. Sequence polymorphism was significantly higher at the MNR loci, including the flanking sequences, indicating a higher mutation rate in the sequences flanking the MNR tracts. The four MNR loci were amplifiable by PCR in the standard ECOR A, B1, and D groups, but only one (yaiN) in the B2 group was amplified, which is consistent with previous studies that suggested that B2 is the most ancient group. High sequence compatibility was found between the four MNR loci, indicating that they are in the same clonal frame. The phylogenetic trees that were constructed from the sequence data were in good agreement with those of previous studies that used multilocus enzyme electrophoresis. The results demonstrate that MNR loci are useful for inferring phylogenetic relationships and provide much higher sequence variation than housekeeping genes. Therefore, the use of MNR loci for multilocus sequence typing should prove efficient for clinical diagnostics, epidemiology, and evolutionary study of bacteria.

Phylogeny and Strain Typing of Escherichia coli, Inferred from Variation at Mononucleotide Repeat Loci

PubMed Central

Diamant, Eran; Palti, Yniv; Gur-Arie, Riva; Cohen, Helit; Hallerman, Eric M.; Kashi, Yechezkel

2004-01-01

Multilocus sequencing of housekeeping genes has been used previously for bacterial strain typing and for inferring evolutionary relationships among strains of Escherichia coli. In this study, we used shorter intergenic sequences that contained simple sequence repeats (SSRs) of repeating mononucleotide motifs (mononucleotide repeats [MNRs]) to infer the phylogeny of pathogenic and commensal E. coli strains. Seven noncoding loci (four MNRs and three non-SSRs) were sequenced in 27 strains, including enterohemorrhagic (six isolates of O157:H7), enteropathogenic, enterotoxigenic, B, and K-12 strains. The four MNRs were also sequenced in 20 representative strains of the E. coli reference (ECOR) collection. Sequence polymorphism was significantly higher at the MNR loci, including the flanking sequences, indicating a higher mutation rate in the sequences flanking the MNR tracts. The four MNR loci were amplifiable by PCR in the standard ECOR A, B1, and D groups, but only one (yaiN) in the B2 group was amplified, which is consistent with previous studies that suggested that B2 is the most ancient group. High sequence compatibility was found between the four MNR loci, indicating that they are in the same clonal frame. The phylogenetic trees that were constructed from the sequence data were in good agreement with those of previous studies that used multilocus enzyme electrophoresis. The results demonstrate that MNR loci are useful for inferring phylogenetic relationships and provide much higher sequence variation than housekeeping genes. Therefore, the use of MNR loci for multilocus sequence typing should prove efficient for clinical diagnostics, epidemiology, and evolutionary study of bacteria. PMID:15066845

GFP-Based Fluorescence Assay for CAG Repeat Instability in Cultured Human Cells

PubMed Central

Santillan, Beatriz A.; Moye, Christopher; Mittelman, David; Wilson, John H.

2014-01-01

Trinucleotide repeats can be highly unstable, mutating far more frequently than point mutations. Repeats typically mutate by addition or loss of units of the repeat. CAG repeat expansions in humans trigger neurological diseases that include myotonic dystrophy, Huntington disease, and several spinocerebellar ataxias. In human cells, diverse mechanisms promote CAG repeat instability, and in mice, the mechanisms of instability are varied and tissue-dependent. Dissection of mechanistic complexity and discovery of potential therapeutics necessitates quantitative and scalable screens for repeat mutation. We describe a GFP-based assay for screening modifiers of CAG repeat instability in human cells. The assay exploits an engineered intronic CAG repeat tract that interferes with expression of an inducible GFP minigene. Like the phenotypes of many trinucleotide repeat disorders, we find that GFP function is impaired by repeat expansion, in a length-dependent manner. The intensity of fluorescence varies inversely with repeat length, allowing estimates of repeat tract changes in live cells. We validate the assay using transcription through the repeat and engineered CAG-specific nucleases, which have previously been reported to induce CAG repeat instability. The assay is relatively fast and should be adaptable to large-scale screens of chemical and shRNA libraries. PMID:25423602

Immunoglobulin G (IgG) Subclass Distribution and IgG1 Avidity of Antibodies in Human Immunodeficiency Virus-Infected Individuals after Revaccination with Tetanus Toxoid

PubMed Central

Kroon, F. P.; van Tol, M. J. D.; Jol-van der Zijde, C. M.; van Furth, R.; van Dissel, J. T.

1999-01-01

In human immunodeficiency virus (HIV)-infected individuals the amount of antibodies formed after vaccination with T-cell-dependent recall antigens such as tetanus toxoid is proportional to the peripheral blood CD4+ T-lymphocyte counts. To investigate whether the immunoglobulin G (IgG) subclass distribution and avidity of the antibodies produced after vaccination are affected as well, we gave 13 HIV-infected adults with low CD4+ T-lymphocyte counts (<200 × 106/liter; group I), 11 HIV-infected adults with intermediate CD4+ T-lymphocyte counts (≥200 × 106/liter; group II), and 5 healthy controls booster immunizations with tetanus toxoid. The prevaccination antibody concentrations against tetanus toxoid were similar in the HIV-infected and healthy adults. After vaccination the total IgG and the IgG1 anti-tetanus toxoid antibody concentrations were significantly lower in group I than in group II and the controls. The avidity of the IgG1 anti-tetanus toxoid antibodies formed by HIV-infected adults was within the range for healthy controls, irrespective of their CD4+ T-lymphocyte counts. PMID:10225835

Exploring the repeat protein universe through computational protein design

DOE PAGES

Brunette, TJ; Parmeggiani, Fabio; Huang, Po-Ssu; ...

2015-12-16

A central question in protein evolution is the extent to which naturally occurring proteins sample the space of folded structures accessible to the polypeptide chain. Repeat proteins composed of multiple tandem copies of a modular structure unit are widespread in nature and have critical roles in molecular recognition, signalling, and other essential biological processes. Naturally occurring repeat proteins have been re-engineered for molecular recognition and modular scaffolding applications. In this paper, we use computational protein design to investigate the space of folded structures that can be generated by tandem repeating a simple helix–loop–helix–loop structural motif. Eighty-three designs with sequences unrelatedmore » to known repeat proteins were experimentally characterized. Of these, 53 are monomeric and stable at 95 °C, and 43 have solution X-ray scattering spectra consistent with the design models. Crystal structures of 15 designs spanning a broad range of curvatures are in close agreement with the design models with root mean square deviations ranging from 0.7 to 2.5 Å. Finally, our results show that existing repeat proteins occupy only a small fraction of the possible repeat protein sequence and structure space and that it is possible to design novel repeat proteins with precisely specified geometries, opening up a wide array of new possibilities for biomolecular engineering.« less

Environmental stress induces trinucleotide repeat mutagenesis in human cells

PubMed Central

Chatterjee, Nimrat; Lin, Yunfu; Santillan, Beatriz A.; Yotnda, Patricia; Wilson, John H.

2015-01-01

The dynamic mutability of microsatellite repeats is implicated in the modification of gene function and disease phenotype. Studies of the enhanced instability of long trinucleotide repeats (TNRs)—the cause of multiple human diseases—have revealed a remarkable complexity of mutagenic mechanisms. Here, we show that cold, heat, hypoxic, and oxidative stresses induce mutagenesis of a long CAG repeat tract in human cells. We show that stress-response factors mediate the stress-induced mutagenesis (SIM) of CAG repeats. We show further that SIM of CAG repeats does not involve mismatch repair, nucleotide excision repair, or transcription, processes that are known to promote TNR mutagenesis in other pathways of instability. Instead, we find that these stresses stimulate DNA rereplication, increasing the proportion of cells with >4 C-value (C) DNA content. Knockdown of the replication origin-licensing factor CDT1 eliminates both stress-induced rereplication and CAG repeat mutagenesis. In addition, direct induction of rereplication in the absence of stress also increases the proportion of cells with >4C DNA content and promotes repeat mutagenesis. Thus, environmental stress triggers a unique pathway for TNR mutagenesis that likely is mediated by DNA rereplication. This pathway may impact normal cells as they encounter stresses in their environment or during development or abnormal cells as they evolve metastatic potential. PMID:25775519

A smart way to identify and extract repeated patterns of a layout

NASA Astrophysics Data System (ADS)

Wei, Fang; Gu, Tingting; Chu, Zhihao; Zhang, Chenming; Chen, Han; Zhu, Jun; Hu, Xinyi; Du, Chunshan; Wan, Qijian; Liu, Zhengfang

2018-03-01

As integrated circuits (IC) technology moves forward, manufacturing process is facing more and more challenges. Optical proximity correction (OPC) has been playing an important role in the whole manufacturing process. In the deep sub-micron technology, OPC engineers not only need to guarantee the layout designs to be manufacturable but also take a more precise control of the critical patterns to ensure a high performance circuit. One of the tasks that would like to be performed is the consistency checking as the identical patterns under identical context should have identical OPC results in theory, like SRAM regions. Consistency checking is essentially a technique of repeated patterns identification, extraction and derived patterns (i.e. OPC results) comparison. The layout passing to the OPC team may not have enough design hierarchical information either because the original designs may have undergone several layout processing steps or some other unknown reasons. This paper presents a generic way to identify and extract repeated layout structures in SRAM regions purely based on layout pattern analysis through Calibre Pattern Matching and Calibre equation-based DRC (eqDRC). Without Pattern Matching and eqDRC, it will take lots of effort to manually get it done by trial and error, it is almost impossible to automate the pattern analysis process. Combining Pattern Matching and eqDRC opens a new way to implement this flow. The repeated patterns must have some fundamental features for measurement of pitches in the horizontal and vertical direction separately by Calibre eqDRC and meanwhile can be a helper to generate some anchor points which will be the starting points for Pattern Matching to capture patterns. The informative statistical report from the pattern search tells the match counts individually for each patterns captured. Experiment shows that this is a smart way of identifying and extracting repeated structures effectively. The OPC results are the derived

TRStalker: an efficient heuristic for finding fuzzy tandem repeats.

PubMed

Pellegrini, Marco; Renda, M Elena; Vecchio, Alessio

2010-06-15

Genomes in higher eukaryotic organisms contain a substantial amount of repeated sequences. Tandem Repeats (TRs) constitute a large class of repetitive sequences that are originated via phenomena such as replication slippage and are characterized by close spatial contiguity. They play an important role in several molecular regulatory mechanisms, and also in several diseases (e.g. in the group of trinucleotide repeat disorders). While for TRs with a low or medium level of divergence the current methods are rather effective, the problem of detecting TRs with higher divergence (fuzzy TRs) is still open. The detection of fuzzy TRs is propaedeutic to enriching our view of their role in regulatory mechanisms and diseases. Fuzzy TRs are also important as tools to shed light on the evolutionary history of the genome, where higher divergence correlates with more remote duplication events. We have developed an algorithm (christened TRStalker) with the aim of detecting efficiently TRs that are hard to detect because of their inherent fuzziness, due to high levels of base substitutions, insertions and deletions. To attain this goal, we developed heuristics to solve a Steiner version of the problem for which the fuzziness is measured with respect to a motif string not necessarily present in the input string. This problem is akin to the 'generalized median string' that is known to be an NP-hard problem. Experiments with both synthetic and biological sequences demonstrate that our method performs better than current state of the art for fuzzy TRs and that the fuzzy TRs of the type we detect are indeed present in important biological sequences. TRStalker will be integrated in the web-based TRs Discovery Service (TReaDS) at bioalgo.iit.cnr.it. Supplementary data are available at Bioinformatics online.

Repeated high-intensity exercise in professional rugby union.

PubMed

Austin, Damien; Gabbett, Tim; Jenkins, David

2011-07-01

The aim of the present study was to describe the frequency, duration, and nature of repeated high-intensity exercise in Super 14 rugby union. Time-motion analysis was used during seven competition matches over the 2008 and 2009 Super 14 seasons; five players from each of four positional groups (front row forwards, back row forwards, inside backs, and outside backs) were assessed (20 players in total). A repeated high-intensity exercise bout was considered to involve three or more sprints, and/or tackles and/or scrum/ruck/maul activities within 21 s during the same passage of play. The range of repeated high-intensity exercise bouts for each group in a match was as follows: 11-18 for front row forwards, 11-21 for back row forwards, 13-18 for inside backs, and 2-11 for outside backs. The durations of the most intense repeated high-intensity exercise bouts for each position ranged from 53 s to 165 s and the minimum recovery periods between repeated high-intensity exercise bouts ranged from 25 s for the back row forwards to 64 s for the front row forwards. The present results show that repeated high-intensity exercise bouts vary in duration and activities relative to position but all players in a game will average at least 10 changes in activity in the most demanding bouts and complete at least one tackle and two sprints. The most intense periods of activity are likely to last as long as 120 s and as little as 25 s recovery may separate consecutive repeated high-intensity exercise bouts. The present findings can be used by coaches to prepare their players for the most demanding passages of play likely to be experienced in elite rugby union.

Strategy When Faced with Failure: Persistence and Degree Attainment of Course Repeaters versus Non-Repeaters. AIR 2002 Forum Paper.

ERIC Educational Resources Information Center

Fenton, Kathleen S.

Graduation and persistence rates were compared for 184 students, 92 of whom had repeated multiple courses or at least 1 course 3 times. A control group of 92 nonrepeating students was drawn from the remaining 303 students of the entire 1996 cohort. There was no difference between the graduation rate of repeaters and nonrepeaters. The persistence…

Alu repeats: A source for the genesis of primate microsatellites

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

Arcot, S.S.; Batzer, M.A.; Wang, Zhenyuan

1995-09-01

As a result of their abundance, relatively uniform distribution, and high degree of polymorphism, microsatellites and minisatellites have become valuable tools in genetic mapping, forensic identity testing, and population studies. In recent years, a number of microsatellite repeats have been found to be associated with Alu interspersed repeated DNA elements. The association of an Alu element with a microsatellite repeat could result from the integration of an Alu element within a preexisting microsatellite repeat. Alternatively, Alu elements could have a direct role in the origin of microsatellite repeats. Errors introduced during reverse transcription of the primary transcript derived from anmore » Alu {open_quotes}master{close_quote} gene or the accumulation of random mutations in the middle A-rich regions and oligo(dA)-rich tails of Alu elements after insertion and subsequent expansion and contraction of these sequences could result in the genesis of a microsatellite repeat. We have tested these hypotheses by a direct evolutionary comparison of the sequences of some recent Alu elements that are found only in humans and are absent from nonhuman primates, as well as some older Alu elements that are present at orthologous positions in a number of nonhuman primates. The origin of {open_quotes}young{close_quotes} Alu insertions, absence of sequences that resemble microsatellite repeats at the orthologous loci in chimpanzees, and the gradual expansion of microsatellite repeats in some old Alu repeats at orthologous positions within the genomes of a number of nonhuman primates suggest that Alu elements are a source for the genesis of primate microsatellite repeats. 48 refs., 5 figs., 3 tabs.« less

Repeated annual influenza vaccination and vaccine effectiveness: review of evidence.

PubMed

Belongia, Edward A; Skowronski, Danuta M; McLean, Huong Q; Chambers, Catharine; Sundaram, Maria E; De Serres, Gaston

2017-07-01

Studies in the 1970s and 1980s signaled concern that repeated influenza vaccination could affect vaccine protection. The antigenic distance hypothesis provided a theoretical framework to explain variability in repeat vaccination effects based on antigenic similarity between successive vaccine components and the epidemic strain. Areas covered: A meta-analysis of vaccine effectiveness studies from 2010-11 through 2014-15 shows substantial heterogeneity in repeat vaccination effects within and between seasons and subtypes. When negative effects were observed, they were most pronounced for H3N2, especially in 2014-15 when vaccine components were unchanged and antigenically distinct from the epidemic strain. Studies of repeated vaccination across multiple seasons suggest that vaccine effectiveness may be influenced by more than one prior season. In immunogenicity studies, repeated vaccination blunts the hemagglutinin antibody response, particularly for H3N2. Expert commentary: Substantial heterogeneity in repeated vaccination effects is not surprising given the variation in study populations and seasons, and the variable effects of antigenic distance and immunological landscape in different age groups and populations. Caution is required in the interpretation of pooled results across multiple seasons, since this can mask important variation in repeat vaccination effects between seasons. Multi-season clinical studies are needed to understand repeat vaccination effects and guide recommendations.

Clinical oversight and the avoidance of repeat induced abortion.

PubMed

Jacovetty, Erica L; Clare, Camille A; Squire, Mary-Beatrice; Kubal, Keshar P; Liou, Sherry; Inchiosa, Mario A

2018-06-03

To evaluate the impact of patient counseling, demographics, and contraceptive methods on repeat induced abortion in women attending family planning clinics. A retrospective chart review of repeat induced abortions was performed. The analysis included patients with an initial induced abortion obtained between January 1, 2001, and March 31, 2014, at New York City Health + Hospitals/Metropolitan. The duration of involvement in the family planning program, the use of contraceptive interventions, and 18 patient factors were analyzed for their correlation with the incidence of repeat induced abortions per year of follow-up. A decreased rate of repeat induced abortions was associated with a longer duration of clinical oversight (r 2 =0.449, P<0.001), a higher contraceptive efficacy score (r=0.280, P=0.025), and a larger number of clinic visits for contraception (r=0.333, P=0.007). A continuum of contact with all of the services of a family planning clinic demonstrated a strong efficacy to limit repeat induced abortions. By determining the patient characteristics that most influence repeat induced abortion rates, providers can best choose the most efficacious method of contraception available. © 2018 International Federation of Gynecology and Obstetrics.

Microevolution of Pandemic Vibrio parahaemolyticus Assessed by the Number of Repeat Units in Short Sequence Tandem Repeat Regions

PubMed Central

García, Katherine; Gavilán, Ronnie G.; Höfle, Manfred G.; Martínez-Urtaza, Jaime; Espejo, Romilio T.

2012-01-01

The emergence of the pandemic strain Vibrio parahaemolyticus O3:K6 in 1996 caused a large increase of diarrhea outbreaks related to seafood consumption in Southeast Asia, and later worldwide. Isolates of this strain constitutes a clonal complex, and their effectual differentiation is possible by comparison of their variable number tandem repeats (VNTRs). The differentiation of the isolates by the differences in VNTRs will allow inferring the population dynamics and microevolution of this strain but this requires knowing the rate and mechanism of VNTRs' variation. Our study of mutants obtained after serial cultivation of clones showed that mutation rates of the six VNTRs examined are on the order of 10−4 mutant per generation and that difference increases by stepwise addition of single mutations. The single stepwise mutation (SSM) was deduced because mutants with 1, 2, 3, or more repeat unit deletions or insertions follow a geometric distribution. Plausible phylogenetic trees are obtained when, according to SSM, the genetic distance between clusters with different number of repeats is assessed by the absolute differences in repeats. Using this approach, mutants originated from different isolates of pandemic V. parahaemolyticus after serial cultivation are clustered with their parental isolates. Additionally, isolates of pandemic V. parahaemolyticus from Southeast Asia, Tokyo, and northern and southern Chile are clustered according their geographical origin. The deepest split in these four populations is observed between the Tokyo and southern Chile populations. We conclude that proper phylogenetic relations and successful tracing of pandemic V. parahaemolyticus requires measuring the differences between isolates by the absolute number of repeats in the VNTRs considered. PMID:22292049

In Vitro Expansion of CAG, CAA, and Mixed CAG/CAA Repeats.

PubMed

Figura, Grzegorz; Koscianska, Edyta; Krzyzosiak, Wlodzimierz J

2015-08-11

Polyglutamine diseases, including Huntington's disease and a number of spinocerebellar ataxias, are caused by expanded CAG repeats that are located in translated sequences of individual, functionally-unrelated genes. Only mutant proteins containing polyglutamine expansions have long been thought to be pathogenic, but recent evidence has implicated mutant transcripts containing long CAG repeats in pathogenic processes. The presence of two pathogenic factors prompted us to attempt to distinguish the effects triggered by mutant protein from those caused by mutant RNA in cellular models of polyglutamine diseases. We used the SLIP (Synthesis of Long Iterative Polynucleotide) method to generate plasmids expressing long CAG repeats (forming a hairpin structure), CAA-interrupted CAG repeats (forming multiple unstable hairpins) or pure CAA repeats (not forming any secondary structure). We successfully modified the original SLIP protocol to generate repeats of desired length starting from constructs containing short repeat tracts. We demonstrated that the SLIP method is a time- and cost-effective approach to manipulate the lengths of expanded repeat sequences.

CAG repeat expansion in Huntington disease determines age at onset in a fully dominant fashion

PubMed Central

Lee, J.-M.; Ramos, E.M.; Lee, J.-H.; Gillis, T.; Mysore, J.S.; Hayden, M.R.; Warby, S.C.; Morrison, P.; Nance, M.; Ross, C.A.; Margolis, R.L.; Squitieri, F.; Orobello, S.; Di Donato, S.; Gomez-Tortosa, E.; Ayuso, C.; Suchowersky, O.; Trent, R.J.A.; McCusker, E.; Novelletto, A.; Frontali, M.; Jones, R.; Ashizawa, T.; Frank, S.; Saint-Hilaire, M.H.; Hersch, S.M.; Rosas, H.D.; Lucente, D.; Harrison, M.B.; Zanko, A.; Abramson, R.K.; Marder, K.; Sequeiros, J.; Paulsen, J.S.; Landwehrmeyer, G.B.; Myers, R.H.; MacDonald, M.E.; Durr, Alexandra; Rosenblatt, Adam; Frati, Luigi; Perlman, Susan; Conneally, Patrick M.; Klimek, Mary Lou; Diggin, Melissa; Hadzi, Tiffany; Duckett, Ayana; Ahmed, Anwar; Allen, Paul; Ames, David; Anderson, Christine; Anderson, Karla; Anderson, Karen; Andrews, Thomasin; Ashburner, John; Axelson, Eric; Aylward, Elizabeth; Barker, Roger A.; Barth, Katrin; Barton, Stacey; Baynes, Kathleen; Bea, Alexandra; Beall, Erik; Beg, Mirza Faisal; Beglinger, Leigh J.; Biglan, Kevin; Bjork, Kristine; Blanchard, Steve; Bockholt, Jeremy; Bommu, Sudharshan Reddy; Brossman, Bradley; Burrows, Maggie; Calhoun, Vince; Carlozzi, Noelle; Chesire, Amy; Chiu, Edmond; Chua, Phyllis; Connell, R.J.; Connor, Carmela; Corey-Bloom, Jody; Craufurd, David; Cross, Stephen; Cysique, Lucette; Santos, Rachelle Dar; Davis, Jennifer; Decolongon, Joji; DiPietro, Anna; Doucette, Nicholas; Downing, Nancy; Dudler, Ann; Dunn, Steve; Ecker, Daniel; Epping, Eric A.; Erickson, Diane; Erwin, Cheryl; Evans, Ken; Factor, Stewart A.; Farias, Sarah; Fatas, Marta; Fiedorowicz, Jess; Fullam, Ruth; Furtado, Sarah; Garde, Monica Bascunana; Gehl, Carissa; Geschwind, Michael D.; Goh, Anita; Gooblar, Jon; Goodman, Anna; Griffith, Jane; Groves, Mark; Guttman, Mark; Hamilton, Joanne; Harrington, Deborah; Harris, Greg; Heaton, Robert K.; Helmer, Karl; Henneberry, Machelle; Hershey, Tamara; Herwig, Kelly; Howard, Elizabeth; Hunter, Christine; Jankovic, Joseph; Johnson, Hans; Johnson, Arik; Jones, Kathy; Juhl, Andrew; Kim, Eun Young; Kimble, Mycah; King, Pamela; Klimek, Mary Lou; Klöppel, Stefan; Koenig, Katherine; Komiti, Angela; Kumar, Rajeev; Langbehn, Douglas; Leavitt, Blair; Leserman, Anne; Lim, Kelvin; Lipe, Hillary; Lowe, Mark; Magnotta, Vincent A.; Mallonee, William M.; Mans, Nicole; Marietta, Jacquie; Marshall, Frederick; Martin, Wayne; Mason, Sarah; Matheson, Kirsty; Matson, Wayne; Mazzoni, Pietro; McDowell, William; Miedzybrodzka, Zosia; Miller, Michael; Mills, James; Miracle, Dawn; Montross, Kelsey; Moore, David; Mori, Sasumu; Moser, David J.; Moskowitz, Carol; Newman, Emily; Nopoulos, Peg; Novak, Marianne; O'Rourke, Justin; Oakes, David; Ondo, William; Orth, Michael; Panegyres, Peter; Pease, Karen; Perlman, Susan; Perlmutter, Joel; Peterson, Asa; Phillips, Michael; Pierson, Ron; Potkin, Steve; Preston, Joy; Quaid, Kimberly; Radtke, Dawn; Rae, Daniela; Rao, Stephen; Raymond, Lynn; Reading, Sarah; Ready, Rebecca; Reece, Christine; Reilmann, Ralf; Reynolds, Norm; Richardson, Kylie; Rickards, Hugh; Ro, Eunyoe; Robinson, Robert; Rodnitzky, Robert; Rogers, Ben; Rosenblatt, Adam; Rosser, Elisabeth; Rosser, Anne; Price, Kathy; Price, Kathy; Ryan, Pat; Salmon, David; Samii, Ali; Schumacher, Jamy; Schumacher, Jessica; Sendon, Jose Luis Lópenz; Shear, Paula; Sheinberg, Alanna; Shpritz, Barnett; Siedlecki, Karen; Simpson, Sheila A.; Singer, Adam; Smith, Jim; Smith, Megan; Smith, Glenn; Snyder, Pete; Song, Allen; Sran, Satwinder; Stephan, Klaas; Stober, Janice; Sü?muth, Sigurd; Suter, Greg; Tabrizi, Sarah; Tempkin, Terry; Testa, Claudia; Thompson, Sean; Thomsen, Teri; Thumma, Kelli; Toga, Arthur; Trautmann, Sonja; Tremont, Geoff; Turner, Jessica; Uc, Ergun; Vaccarino, Anthony; van Duijn, Eric; Van Walsem, Marleen; Vik, Stacie; Vonsattel, Jean Paul; Vuletich, Elizabeth; Warner, Tom; Wasserman, Paula; Wassink, Thomas; Waterman, Elijah; Weaver, Kurt; Weir, David; Welsh, Claire; Werling-Witkoske, Chris; Wesson, Melissa; Westervelt, Holly; Weydt, Patrick; Wheelock, Vicki; Williams, Kent; Williams, Janet; Wodarski, Mary; Wojcieszek, Joanne; Wood, Jessica; Wood-Siverio, Cathy; Wu, Shuhua; Yastrubetskaya, Olga; de Yebenes, Justo Garcia; Zhao, Yong Qiang; Zimbelman, Janice; Zschiegner, Roland; Aaserud, Olaf; Abbruzzese, Giovanni; Andrews, Thomasin; Andrich, Jurgin; Antczak, Jakub; Arran, Natalie; Artiga, Maria J. Saiz; Bachoud-Lévi, Anne-Catherine; Banaszkiewicz, Krysztof; di Poggio, Monica Bandettini; Bandmann, Oliver; Barbera, Miguel A.; Barker, Roger A.; Barrero, Francisco; Barth, Katrin; Bas, Jordi; Beister, Antoine; Bentivoglio, Anna Rita; Bertini, Elisabetta; Biunno, Ida; Bjørgo, Kathrine; Bjørnevoll, Inga; Bohlen, Stefan; Bonelli, Raphael M.; Bos, Reineke; Bourne, Colin; Bradbury, Alyson; Brockie, Peter; Brown, Felicity; Bruno, Stefania; Bryl, Anna; Buck, Andrea; Burg, Sabrina; Burgunder, Jean-Marc; Burns, Peter; Burrows, Liz; Busquets, Nuria; Busse, Monica; Calopa, Matilde; Carruesco, Gemma T.; Casado, Ana Gonzalez; Catena, Judit López; Chu, Carol; Ciesielska, Anna; Clapton, Jackie; Clayton, Carole; Clenaghan, Catherine; Coelho, Miguel; Connemann, Julia; Craufurd, David; Crooks, Jenny; Cubillo, Patricia Trigo; Cubo, Esther; Curtis, Adrienne; De Michele, Giuseppe; De Nicola, A.; de Souza, Jenny; de Weert, A. Marit; de Yébenes, Justo Garcia; Dekker, M.; Descals, A. Martínez; Di Maio, Luigi; Di Pietro, Anna; Dipple, Heather; Dose, Matthias; Dumas, Eve M.; Dunnett, Stephen; Ecker, Daniel; Elifani, F.; Ellison-Rose, Lynda; Elorza, Marina D.; Eschenbach, Carolin; Evans, Carole; Fairtlough, Helen; Fannemel, Madelein; Fasano, Alfonso; Fenollar, Maria; Ferrandes, Giovanna; Ferreira, Jaoquim J.; Fillingham, Kay; Finisterra, Ana Maria; Fisher, K.; Fletcher, Amy; Foster, Jillian; Foustanos, Isabella; Frech, Fernando A.; Fullam, Robert; Fullham, Ruth; Gago, Miguel; García, RocioGarcía-Ramos; García, Socorro S.; Garrett, Carolina; Gellera, Cinzia; Gill, Paul; Ginestroni, Andrea; Golding, Charlotte; Goodman, Anna; Gørvell, Per; Grant, Janet; Griguoli, A.; Gross, Diana; Guedes, Leonor; BascuñanaGuerra, Monica; Guerra, Maria Rosalia; Guerrero, Rosa; Guia, Dolores B.; Guidubaldi, Arianna; Hallam, Caroline; Hamer, Stephanie; Hammer, Kathrin; Handley, Olivia J.; Harding, Alison; Hasholt, Lis; Hedge, Reikha; Heiberg, Arvid; Heinicke, Walburgis; Held, Christine; Hernanz, Laura Casas; Herranhof, Briggitte; Herrera, Carmen Durán; Hidding, Ute; Hiivola, Heli; Hill, Susan; Hjermind, Lena. E.; Hobson, Emma; Hoffmann, Rainer; Holl, Anna Hödl; Howard, Liz; Hunt, Sarah; Huson, Susan; Ialongo, Tamara; Idiago, Jesus Miguel R.; Illmann, Torsten; Jachinska, Katarzyna; Jacopini, Gioia; Jakobsen, Oda; Jamieson, Stuart; Jamrozik, Zygmunt; Janik, Piotr; Johns, Nicola; Jones, Lesley; Jones, Una; Jurgens, Caroline K.; Kaelin, Alain; Kalbarczyk, Anna; Kershaw, Ann; Khalil, Hanan; Kieni, Janina; Klimberg, Aneta; Koivisto, Susana P.; Koppers, Kerstin; Kosinski, Christoph Michael; Krawczyk, Malgorzata; Kremer, Berry; Krysa, Wioletta; Kwiecinski, Hubert; Lahiri, Nayana; Lambeck, Johann; Lange, Herwig; Laver, Fiona; Leenders, K.L.; Levey, Jamie; Leythaeuser, Gabriele; Lezius, Franziska; Llesoy, Joan Roig; Löhle, Matthias; López, Cristobal Diez-Aja; Lorenza, Fortuna; Loria, Giovanna; Magnet, Markus; Mandich, Paola; Marchese, Roberta; Marcinkowski, Jerzy; Mariotti, Caterina; Mariscal, Natividad; Markova, Ivana; Marquard, Ralf; Martikainen, Kirsti; Martínez, Isabel Haro; Martínez-Descals, Asuncion; Martino, T.; Mason, Sarah; McKenzie, Sue; Mechi, Claudia; Mendes, Tiago; Mestre, Tiago; Middleton, Julia; Milkereit, Eva; Miller, Joanne; Miller, Julie; Minster, Sara; Möller, Jens Carsten; Monza, Daniela; Morales, Blas; Moreau, Laura V.; Moreno, Jose L. López-Sendón; Münchau, Alexander; Murch, Ann; Nielsen, Jørgen E.; Niess, Anke; Nørremølle, Anne; Novak, Marianne; O'Donovan, Kristy; Orth, Michael; Otti, Daniela; Owen, Michael; Padieu, Helene; Paganini, Marco; Painold, Annamaria; Päivärinta, Markku; Partington-Jones, Lucy; Paterski, Laurent; Paterson, Nicole; Patino, Dawn; Patton, Michael; Peinemann, Alexander; Peppa, Nadia; Perea, Maria Fuensanta Noguera; Peterson, Maria; Piacentini, Silvia; Piano, Carla; Càrdenas, Regina Pons i; Prehn, Christian; Price, Kathleen; Probst, Daniela; Quarrell, Oliver; Quiroga, Purificacion Pin; Raab, Tina; Rakowicz, Maryla; Raman, Ashok; Raymond, Lucy; Reilmann, Ralf; Reinante, Gema; Reisinger, Karin; Retterstol, Lars; Ribaï, Pascale; Riballo, Antonio V.; Ribas, Guillermo G.; Richter, Sven; Rickards, Hugh; Rinaldi, Carlo; Rissling, Ida; Ritchie, Stuart; Rivera, Susana Vázquez; Robert, Misericordia Floriach; Roca, Elvira; Romano, Silvia; Romoli, Anna Maria; Roos, Raymond A.C.; Røren, Niini; Rose, Sarah; Rosser, Elisabeth; Rosser, Anne; Rossi, Fabiana; Rothery, Jean; Rudzinska, Monika; Ruíz, Pedro J. García; Ruíz, Belan Garzon; Russo, Cinzia Valeria; Ryglewicz, Danuta; Saft, Carston; Salvatore, Elena; Sánchez, Vicenta; Sando, Sigrid Botne; Šašinková, Pavla; Sass, Christian; Scheibl, Monika; Schiefer, Johannes; Schlangen, Christiane; Schmidt, Simone; Schöggl, Helmut; Schrenk, Caroline; Schüpbach, Michael; Schuierer, Michele; Sebastián, Ana Rojo; Selimbegovic-Turkovic, Amina; Sempolowicz, Justyna; Silva, Mark; Sitek, Emilia; Slawek, Jaroslaw; Snowden, Julie; Soleti, Francesco; Soliveri, Paola; Sollom, Andrea; Soltan, Witold; Sorbi, Sandro; Sorensen, Sven Asger; Spadaro, Maria; Städtler, Michael; Stamm, Christiane; Steiner, Tanja; Stokholm, Jette; Stokke, Bodil; Stopford, Cheryl; Storch, Alexander; Straßburger, Katrin; Stubbe, Lars; Sulek, Anna; Szczudlik, Andrzej; Tabrizi, Sarah; Taylor, Rachel; Terol, Santiago Duran-Sindreu; Thomas, Gareth; Thompson, Jennifer; Thomson, Aileen; Tidswell, Katherine; Torres, Maria M. Antequera; Toscano, Jean; Townhill, Jenny; Trautmann, Sonja; Tucci, Tecla; Tuuha, Katri; Uhrova, Tereza; Valadas, Anabela; van Hout, Monique S.E.; van Oostrom, J.C.H.; van Vugt, Jeroen P.P.; vanm, Walsem Marleen R.; Vandenberghe, Wim; Verellen-Dumoulin, Christine; Vergara, Mar Ruiz; Verstappen, C.C.P.; Verstraelen, Nichola; Viladrich, Celia Mareca; Villanueva, Clara; Wahlström, Jan; Warner, Thomas; Wehus, Raghild; Weindl, Adolf; Werner, Cornelius J.; Westmoreland, Leann; Weydt, Patrick; Wiedemann, Alexandra; Wild, Edward; Wild, Sue; Witjes-Ané, Marie-Noelle; Witkowski, Grzegorz; Wójcik, Magdalena; Wolz, Martin; Wolz, Annett; Wright, Jan; Yardumian, Pam; Yates, Shona; Yudina, Elizaveta; Zaremba, Jacek; Zaugg, Sabine W.; Zdzienicka, Elzbieta; Zielonka, Daniel; Zielonka, Euginiusz; Zinzi, Paola; Zittel, Simone; Zucker, Birgrit; Adams, John; Agarwal, Pinky; Antonijevic, Irina; Beck, Christopher; Chiu, Edmond; Churchyard, Andrew; Colcher, Amy; Corey-Bloom, Jody; Dorsey, Ray; Drazinic, Carolyn; Dubinsky, Richard; Duff, Kevin; Factor, Stewart; Foroud, Tatiana; Furtado, Sarah; Giuliano, Joe; Greenamyre, Timothy; Higgins, Don; Jankovic, Joseph; Jennings, Dana; Kang, Un Jung; Kostyk, Sandra; Kumar, Rajeev; Leavitt, Blair; LeDoux, Mark; Mallonee, William; Marshall, Frederick; Mohlo, Eric; Morgan, John; Oakes, David; Panegyres, Peter; Panisset, Michel; Perlman, Susan; Perlmutter, Joel; Quaid, Kimberly; Raymond, Lynn; Revilla, Fredy; Robertson, Suzanne; Robottom, Bradley; Sanchez-Ramos, Juan; Scott, Burton; Shannon, Kathleen; Shoulson, Ira; Singer, Carlos; Tabbal, Samer; Testa, Claudia; van, Kammen Dan; Vetter, Louise; Walker, Francis; Warner, John; Weiner, illiam; Wheelock, Vicki; Yastrubetskaya, Olga; Barton, Stacey; Broyles, Janice; Clouse, Ronda; Coleman, Allison; Davis, Robert; Decolongon, Joji; DeLaRosa, Jeanene; Deuel, Lisa; Dietrich, Susan; Dubinsky, Hilary; Eaton, Ken; Erickson, Diane; Fitzpatrick, Mary Jane; Frucht, Steven; Gartner, Maureen; Goldstein, Jody; Griffith, Jane; Hickey, Charlyne; Hunt, Victoria; Jaglin, Jeana; Klimek, Mary Lou; Lindsay, Pat; Louis, Elan; Loy, Clemet; Lucarelli, Nancy; Malarick, Keith; Martin, Amanda; McInnis, Robert; Moskowitz, Carol; Muratori, Lisa; Nucifora, Frederick; O'Neill, Christine; Palao, Alicia; Peavy, Guerry; Quesada, Monica; Schmidt, Amy; Segro, Vicki; Sperin, Elaine; Suter, Greg; Tanev, Kalo; Tempkin, Teresa; Thiede, Curtis; Wasserman, Paula; Welsh, Claire; Wesson, Melissa; Zauber, Elizabeth

2012-01-01

Objective: Age at onset of diagnostic motor manifestations in Huntington disease (HD) is strongly correlated with an expanded CAG trinucleotide repeat. The length of the normal CAG repeat allele has been reported also to influence age at onset, in interaction with the expanded allele. Due to profound implications for disease mechanism and modification, we tested whether the normal allele, interaction between the expanded and normal alleles, or presence of a second expanded allele affects age at onset of HD motor signs. Methods: We modeled natural log-transformed age at onset as a function of CAG repeat lengths of expanded and normal alleles and their interaction by linear regression. Results: An apparently significant effect of interaction on age at motor onset among 4,068 subjects was dependent on a single outlier data point. A rigorous statistical analysis with a well-behaved dataset that conformed to the fundamental assumptions of linear regression (e.g., constant variance and normally distributed error) revealed significance only for the expanded CAG repeat, with no effect of the normal CAG repeat. Ten subjects with 2 expanded alleles showed an age at motor onset consistent with the length of the larger expanded allele. Conclusions: Normal allele CAG length, interaction between expanded and normal alleles, and presence of a second expanded allele do not influence age at onset of motor manifestations, indicating that the rate of HD pathogenesis leading to motor diagnosis is determined by a completely dominant action of the longest expanded allele and as yet unidentified genetic or environmental factors. Neurology® 2012;78:690–695 PMID:22323755

Supplementation of H1N1pdm09 split vaccine with heterologous tandem repeat M2e5x virus-like particles confers improved cross-protection in ferrets.

PubMed

Music, Nedzad; Reber, Adrian J; Kim, Min-Chul; York, Ian A; Kang, Sang-Moo

2016-01-20

Current influenza vaccines induce strain-specific immunity to the highly variable hemagglutinin (HA) protein. It is therefore a high priority to develop vaccines that induce broadly cross-protective immunity to different strains of influenza. Since influenza A M2 proteins are highly conserved among different strains, five tandem repeats of the extracellular peptide of M2 in a membrane-anchored form on virus-like particles (VLPs) have been suggested to be a promising candidate for universal influenza vaccine. In this study, ferrets were intramuscularly immunized with 2009 H1N1 split HA vaccine ("Split") alone, influenza split vaccine supplemented with M2e5x VLP ("Split+M2e5x"), M2e5x VLP alone ("M2e5x"), or mock immunized. Vaccine efficacy was measured serologically and by protection against a serologically distinct viral challenge. Ferrets immunized with Split+M2e5x induced HA strain specific and conserved M2e immunity. Supplementation of M2e5x VLP to split vaccination significantly increased the immunogenicity of split vaccine compared to split alone. The Split+M2e5x ferret group showed evidence of cross-reactive protection, including faster recovery from weight loss, and reduced inflammation, as inferred from changes in peripheral leukocyte subsets, compared to mock-immunized animals. In addition, ferrets immunized with Split+M2e5x shed lower viral nasal-wash titers than the other groups. Ferrets immunized with M2e5x alone also show some protective effects, while those immunized with split vaccine alone induced no protective effects compared to mock-immunized ferrets. These studies suggest that supplementation of split vaccine with M2e5x-VLP may provide broader and improved cross-protection than split vaccine alone. Published by Elsevier Ltd.

Supplementation of H1N1pdm09 split vaccine with heterologous tandem repeat M2e5x virus-like particles confers improved cross-protection in ferrets

PubMed Central

Music, Nedzad; Reber, Adrian J.; Kim, Min-Chul; York, Ian A.; Kang, Sang-Moo

2015-01-01

Current influenza vaccines induce strain-specific immunity to the highly variable hemagglutinin (HA) protein. It is therefore a high priority to develop vaccines that induce broadly cross-protective immunity to different strains of influenza. Since influenza A M2 proteins are highly conserved among different strains, five tandem repeats of the extracellular peptide of M2 in a membrane-anchored form on virus-like particles (VLPs) have been suggested to be a promising candidate for universal influenza vaccine. In this study, ferrets were intramuscularly immunized with 2009 H1N1 split HA vaccine (“Split”) alone, influenza split vaccine supplemented with M2e5x VLP (“Split+M2e5x”), M2e5x VLP alone (“M2e5x”), or mock immunized. Vaccine efficacy was measured serologically and by protection against a serologically distinct viral challenge. Ferrets immunized with Split+M2e5x induced HA strain specific and conserved M2e immunity. Supplementation of M2e5x VLP to split vaccination significantly increased the immunogenicity of split vaccine compared to split alone. The Split+M2e5x ferret group showed evidence of cross-reactive protection, including faster recovery from weight loss, and reduced inflammation, as inferred from changes in peripheral leukocyte subsets, compared to mock-immunized animals. In addition, ferrets immunized with Split+M2e5x shed lower viral nasal-wash titers than the other groups. Ferrets immunized with M2e5x alone also show some protective effects, while those immunized with split vaccine alone induced no protective effects compared to mock-immunized ferrets. These studies suggest that supplementation of split vaccine with M2e5x-VLP may provide broader and improved cross-protection than split vaccine alone. PMID:26709639

Palmprint and Face Multi-Modal Biometric Recognition Based on SDA-GSVD and Its Kernelization

PubMed Central

Jing, Xiao-Yuan; Li, Sheng; Li, Wen-Qian; Yao, Yong-Fang; Lan, Chao; Lu, Jia-Sen; Yang, Jing-Yu

2012-01-01

When extracting discriminative features from multimodal data, current methods rarely concern themselves with the data distribution. In this paper, we present an assumption that is consistent with the viewpoint of discrimination, that is, a person's overall biometric data should be regarded as one class in the input space, and his different biometric data can form different Gaussians distributions, i.e., different subclasses. Hence, we propose a novel multimodal feature extraction and recognition approach based on subclass discriminant analysis (SDA). Specifically, one person's different bio-data are treated as different subclasses of one class, and a transformed space is calculated, where the difference among subclasses belonging to different persons is maximized, and the difference within each subclass is minimized. Then, the obtained multimodal features are used for classification. Two solutions are presented to overcome the singularity problem encountered in calculation, which are using PCA preprocessing, and employing the generalized singular value decomposition (GSVD) technique, respectively. Further, we provide nonlinear extensions of SDA based multimodal feature extraction, that is, the feature fusion based on KPCA-SDA and KSDA-GSVD. In KPCA-SDA, we first apply Kernel PCA on each single modal before performing SDA. While in KSDA-GSVD, we directly perform Kernel SDA to fuse multimodal data by applying GSVD to avoid the singular problem. For simplicity two typical types of biometric data are considered in this paper, i.e., palmprint data and face data. Compared with several representative multimodal biometrics recognition methods, experimental results show that our approaches outperform related multimodal recognition methods and KSDA-GSVD achieves the best recognition performance. PMID:22778600

Palmprint and face multi-modal biometric recognition based on SDA-GSVD and its kernelization.

PubMed

Jing, Xiao-Yuan; Li, Sheng; Li, Wen-Qian; Yao, Yong-Fang; Lan, Chao; Lu, Jia-Sen; Yang, Jing-Yu

2012-01-01

When extracting discriminative features from multimodal data, current methods rarely concern themselves with the data distribution. In this paper, we present an assumption that is consistent with the viewpoint of discrimination, that is, a person's overall biometric data should be regarded as one class in the input space, and his different biometric data can form different Gaussians distributions, i.e., different subclasses. Hence, we propose a novel multimodal feature extraction and recognition approach based on subclass discriminant analysis (SDA). Specifically, one person's different bio-data are treated as different subclasses of one class, and a transformed space is calculated, where the difference among subclasses belonging to different persons is maximized, and the difference within each subclass is minimized. Then, the obtained multimodal features are used for classification. Two solutions are presented to overcome the singularity problem encountered in calculation, which are using PCA preprocessing, and employing the generalized singular value decomposition (GSVD) technique, respectively. Further, we provide nonlinear extensions of SDA based multimodal feature extraction, that is, the feature fusion based on KPCA-SDA and KSDA-GSVD. In KPCA-SDA, we first apply Kernel PCA on each single modal before performing SDA. While in KSDA-GSVD, we directly perform Kernel SDA to fuse multimodal data by applying GSVD to avoid the singular problem. For simplicity two typical types of biometric data are considered in this paper, i.e., palmprint data and face data. Compared with several representative multimodal biometrics recognition methods, experimental results show that our approaches outperform related multimodal recognition methods and KSDA-GSVD achieves the best recognition performance.

Repeatability study of replicate crash tests: A signal analysis approach.

PubMed

Seppi, Jeremy; Toczyski, Jacek; Crandall, Jeff R; Kerrigan, Jason

2017-10-03

To provide an objective basis on which to evaluate the repeatability of vehicle crash test methods, a recently developed signal analysis method was used to evaluate correlation of sensor time history data between replicate vehicle crash tests. The goal of this study was to evaluate the repeatability of rollover crash tests performed with the Dynamic Rollover Test System (DRoTS) relative to other vehicle crash test methods. Test data from DRoTS tests, deceleration rollover sled (DRS) tests, frontal crash tests, frontal offset crash tests, small overlap crash tests, small overlap impact (SOI) crash tests, and oblique crash tests were obtained from the literature and publicly available databases (the NHTSA vehicle database and the Insurance Institute for Highway Safety TechData) to examine crash test repeatability. Signal analysis of the DRoTS tests showed that force and deformation time histories had good to excellent repeatability, whereas vehicle kinematics showed only fair repeatability due to the vehicle mounting method for one pair of tests and slightly dissimilar mass properties (2.2%) in a second pair of tests. Relative to the DRS, the DRoTS tests showed very similar or higher levels of repeatability in nearly all vehicle kinematic data signals with the exception of global X' (road direction of travel) velocity and displacement due to the functionality of the DRoTS fixture. Based on the average overall scoring metric of the dominant acceleration, DRoTS was found to be as repeatable as all other crash tests analyzed. Vertical force measures showed good repeatability and were on par with frontal crash barrier forces. Dynamic deformation measures showed good to excellent repeatability as opposed to poor repeatability seen in SOI and oblique deformation measures. Using the signal analysis method as outlined in this article, the DRoTS was shown to have the same or better repeatability of crash test methods used in government regulatory and consumer evaluation test

Evolution of vulnerability of communities facing repeated hazards

PubMed Central

Guikema, Seth D.; Zhu, Laiyin; Igusa, Takeru

2017-01-01

The decisions that individuals make when recovering from and adapting to repeated hazards affect a region’s vulnerability in future hazards. As such, community vulnerability is not a static property but rather a dynamic property dependent on behavioral responses to repeated hazards and damage. This paper is the first of its kind to build a framework that addresses the complex interactions between repeated hazards, regional damage, mitigation decisions, and community vulnerability. The framework enables researchers and regional planners to visualize and quantify how a community could evolve over time in response to repeated hazards under various behavioral scenarios. An illustrative example using parcel-level data from Anne Arundel County, Maryland—a county that experiences fairly frequent hurricanes—is presented to illustrate the methodology and to demonstrate how the interplay between individual choices and regional vulnerability is affected by the region’s hurricane experience. PMID:28953893

Heralded high-efficiency quantum repeater with atomic ensembles assisted by faithful single-photon transmission

NASA Astrophysics Data System (ADS)

Li, Tao; Deng, Fu-Guo

2015-10-01

Quantum repeater is one of the important building blocks for long distance quantum communication network. The previous quantum repeaters based on atomic ensembles and linear optical elements can only be performed with a maximal success probability of 1/2 during the entanglement creation and entanglement swapping procedures. Meanwhile, the polarization noise during the entanglement distribution process is harmful to the entangled channel created. Here we introduce a general interface between a polarized photon and an atomic ensemble trapped in a single-sided optical cavity, and with which we propose a high-efficiency quantum repeater protocol in which the robust entanglement distribution is accomplished by the stable spatial-temporal entanglement and it can in principle create the deterministic entanglement between neighboring atomic ensembles in a heralded way as a result of cavity quantum electrodynamics. Meanwhile, the simplified parity-check gate makes the entanglement swapping be completed with unity efficiency, other than 1/2 with linear optics. We detail the performance of our protocol with current experimental parameters and show its robustness to the imperfections, i.e., detuning and coupling variation, involved in the reflection process. These good features make it a useful building block in long distance quantum communication.

Heralded high-efficiency quantum repeater with atomic ensembles assisted by faithful single-photon transmission.

PubMed

Li, Tao; Deng, Fu-Guo

2015-10-27

Quantum repeater is one of the important building blocks for long distance quantum communication network. The previous quantum repeaters based on atomic ensembles and linear optical elements can only be performed with a maximal success probability of 1/2 during the entanglement creation and entanglement swapping procedures. Meanwhile, the polarization noise during the entanglement distribution process is harmful to the entangled channel created. Here we introduce a general interface between a polarized photon and an atomic ensemble trapped in a single-sided optical cavity, and with which we propose a high-efficiency quantum repeater protocol in which the robust entanglement distribution is accomplished by the stable spatial-temporal entanglement and it can in principle create the deterministic entanglement between neighboring atomic ensembles in a heralded way as a result of cavity quantum electrodynamics. Meanwhile, the simplified parity-check gate makes the entanglement swapping be completed with unity efficiency, other than 1/2 with linear optics. We detail the performance of our protocol with current experimental parameters and show its robustness to the imperfections, i.e., detuning and coupling variation, involved in the reflection process. These good features make it a useful building block in long distance quantum communication.

Criminal Behavior and Repeat Violent Trauma: A Case-Control Study.

PubMed

Nanney, John T; Conrad, Erich J; McCloskey, Michael; Constans, Joseph I

2015-09-01

Repeat violent injury is common among young urban men and is increasingly a focus of trauma center-based injury prevention efforts. Though understanding risk factors for repeat violent injury may be critical in designing such interventions, this knowledge is limited. This study aims to determine which criminal behaviors, both before and after the initial trauma, predict repeat violent trauma. Gun, violent, and drug crimes are expected to increase risk of subsequent violent injury among victims of violence. A case-control design examined trauma registry and publicly available criminal data for all male patients aged <40 years presenting for violent trauma between April 2006 and December 2011 (N=1,142) to the sole Level 1 trauma center in a city with high rates of violence. Logistic regression was used to determine criminal behaviors predictive of repeat violent injury. Data were obtained and analyzed between January 2013 and June 2014. Regarding crimes committed before the first injury, only drug crime (OR=5.32) predicted repeat violent trauma. With respect to crimes committed after the initial injury, illegal gun possession (OR=2.70) predicted repeat victimization. Initiating gun (OR=3.53) or drug crime (OR=5.12) was associated with increased risk. Prior drug involvement may identify young male victims of violence as at high risk of repeat violent injury. Gun carrying and initiating drug involvement after the initial injury may increase risk of repeat injury and may be important targets for interventions aimed at preventing repeat violent trauma. Published by Elsevier Inc.

ACCA phosphopeptide recognition by the BRCT repeats of BRCA1.

PubMed

Ray, Hind; Moreau, Karen; Dizin, Eva; Callebaut, Isabelle; Venezia, Nicole Dalla

2006-06-16

The tumour suppressor gene BRCA1 encodes a 220 kDa protein that participates in multiple cellular processes. The BRCA1 protein contains a tandem of two BRCT repeats at its carboxy-terminal region. The majority of disease-associated BRCA1 mutations affect this region and provide to the BRCT repeats a central role in the BRCA1 tumour suppressor function. The BRCT repeats have been shown to mediate phospho-dependant protein-protein interactions. They recognize phosphorylated peptides using a recognition groove that spans both BRCT repeats. We previously identified an interaction between the tandem of BRCA1 BRCT repeats and ACCA, which was disrupted by germ line BRCA1 mutations that affect the BRCT repeats. We recently showed that BRCA1 modulates ACCA activity through its phospho-dependent binding to ACCA. To delineate the region of ACCA that is crucial for the regulation of its activity by BRCA1, we searched for potential phosphorylation sites in the ACCA sequence that might be recognized by the BRCA1 BRCT repeats. Using sequence analysis and structure modelling, we proposed the Ser1263 residue as the most favourable candidate among six residues, for recognition by the BRCA1 BRCT repeats. Using experimental approaches, such as GST pull-down assay with Bosc cells, we clearly showed that phosphorylation of only Ser1263 was essential for the interaction of ACCA with the BRCT repeats. We finally demonstrated by immunoprecipitation of ACCA in cells, that the whole BRCA1 protein interacts with ACCA when phosphorylated on Ser1263.

Automated quality checks on repeat prescribing.

PubMed Central

Rogers, Jeremy E; Wroe, Christopher J; Roberts, Angus; Swallow, Angela; Stables, David; Cantrill, Judith A; Rector, Alan L

2003-01-01

BACKGROUND: Good clinical practice in primary care includes periodic review of repeat prescriptions. Markers of prescriptions that may need review have been described, but manually checking all repeat prescriptions against the markers would be impractical. AIM: To investigate the feasibility of computerising the application of repeat prescribing quality checks to electronic patient records in United Kingdom (UK) primary care. DESIGN OF STUDY: Software performance test against benchmark manual analysis of cross-sectional convenience sample of prescribing documentation. SETTING: Three general practices in Greater Manchester, in the north west of England, during a 4-month period in 2001. METHOD: A machine-readable drug information resource, based on the British National Formulary (BNF) as the 'gold standard' for valid drug indications, was installed in three practices. Software raised alerts for each repeat prescribed item where the electronic patient record contained no valid indication for the medication. Alerts raised by the software in two practices were analysed manually. Clinical reaction to the software was assessed by semi-structured interviews in three practices. RESULTS: There was no valid indication in the electronic medical records for 14.8% of repeat prescribed items. Sixty-two per cent of all alerts generated were incorrect. Forty-three per cent of all incorrect alerts were as a result of errors in the drug information resource, 44% to locally idiosyncratic clinical coding, 8% to the use of the BNF without adaptation as a gold standard, and 5% to the inability of the system to infer diagnoses that, although unrecorded, would be 'obvious' to a clinical reading the record. The interviewed clinicians supported the goals of the software. CONCLUSION: Using electronic records for secondary decision support purposes will benefit from (and may require) both more consistent electronic clinical data collection across multiple sites, and reconciling clinicians

Design, production and molecular structure of a new family of artificial alpha-helicoidal repeat proteins (αRep) based on thermostable HEAT-like repeats.

PubMed

Urvoas, Agathe; Guellouz, Asma; Valerio-Lepiniec, Marie; Graille, Marc; Durand, Dominique; Desravines, Danielle C; van Tilbeurgh, Herman; Desmadril, Michel; Minard, Philippe

2010-11-26

Repeat proteins have a modular organization and a regular architecture that make them attractive models for design and directed evolution experiments. HEAT repeat proteins, although very common, have not been used as a scaffold for artificial proteins, probably because they are made of long and irregular repeats. Here, we present and validate a consensus sequence for artificial HEAT repeat proteins. The sequence was defined from the structure-based sequence analysis of a thermostable HEAT-like repeat protein. Appropriate sequences were identified for the N- and C-caps. A library of genes coding for artificial proteins based on this sequence design, named αRep, was assembled using new and versatile methodology based on circular amplification. Proteins picked randomly from this library are expressed as soluble proteins. The biophysical properties of proteins with different numbers of repeats and different combinations of side chains in hypervariable positions were characterized. Circular dichroism and differential scanning calorimetry experiments showed that all these proteins are folded cooperatively and are very stable (T(m) >70 °C). Stability of these proteins increases with the number of repeats. Detailed gel filtration and small-angle X-ray scattering studies showed that the purified proteins form either monomers or dimers. The X-ray structure of a stable dimeric variant structure was solved. The protein is folded with a highly regular topology and the repeat structure is organized, as expected, as pairs of alpha helices. In this protein variant, the dimerization interface results directly from the variable surface enriched in aromatic residues located in the randomized positions of the repeats. The dimer was crystallized both in an apo and in a PEG-bound form, revealing a very well defined binding crevice and some structure flexibility at the interface. This fortuitous binding site could later prove to be a useful binding site for other low molecular mass

Instability of expanded CAG/CAA repeats in spinocerebellar ataxia type 17.

PubMed

Gao, Rui; Matsuura, Tohru; Coolbaugh, Mary; Zühlke, Christine; Nakamura, Koichiro; Rasmussen, Astrid; Siciliano, Michael J; Ashizawa, Tetsuo; Lin, Xi

2008-02-01

Trinucleotide repeat expansions are dynamic mutations causing many neurological disorders, and their instability is influenced by multiple factors. Repeat configuration seems particularly important, and pure repeats are thought to be more unstable than interrupted repeats. But direct evidence is still lacking. Here, we presented strong support for this hypothesis from our studies on spinocerebellar ataxia type 17 (SCA17). SCA17 is a typical polyglutamine disease caused by CAG repeat expansion in TBP (TATA binding protein), and is unique in that the pure expanded polyglutamine tract is coded by either a simple configuration with long stretches of pure CAGs or a complex configuration containing CAA interruptions. By small pool PCR (SP-PCR) analysis of blood DNA from SCA17 patients of distinct racial backgrounds, we quantitatively assessed the instability of these two types of expanded alleles coding similar length of polyglutamine expansion. Mutation frequency in patients harboring pure CAG repeats is 2-3 folds of those with CAA interruptions. Interestingly, the pure CAG repeats showed both expansion and deletion while the interrupted repeats exhibited mostly deletion at a significantly lower frequency. These data strongly suggest that repeat configuration is a critical determinant for instability, and CAA interruptions might serve as a limiting element for further expansion of CAG repeats in SCA17 locus, suggesting a molecular basis for lack of anticipation in SCA17 families with interrupted CAG expansion.

Repeatless and repeat-based centromeres in potato: implications for centromere evolution.

PubMed

Gong, Zhiyun; Wu, Yufeng; Koblízková, Andrea; Torres, Giovana A; Wang, Kai; Iovene, Marina; Neumann, Pavel; Zhang, Wenli; Novák, Petr; Buell, C Robin; Macas, Jirí; Jiang, Jiming

2012-09-01

Centromeres in most higher eukaryotes are composed of long arrays of satellite repeats. By contrast, most newly formed centromeres (neocentromeres) do not contain satellite repeats and instead include DNA sequences representative of the genome. An unknown question in centromere evolution is how satellite repeat-based centromeres evolve from neocentromeres. We conducted a genome-wide characterization of sequences associated with CENH3 nucleosomes in potato (Solanum tuberosum). Five potato centromeres (Cen4, Cen6, Cen10, Cen11, and Cen12) consisted primarily of single- or low-copy DNA sequences. No satellite repeats were identified in these five centromeres. At least one transcribed gene was associated with CENH3 nucleosomes. Thus, these five centromeres structurally resemble neocentromeres. By contrast, six potato centromeres (Cen1, Cen2, Cen3, Cen5, Cen7, and Cen8) contained megabase-sized satellite repeat arrays that are unique to individual centromeres. The satellite repeat arrays likely span the entire functional cores of these six centromeres. At least four of the centromeric repeats were amplified from retrotransposon-related sequences and were not detected in Solanum species closely related to potato. The presence of two distinct types of centromeres, coupled with the boom-and-bust cycles of centromeric satellite repeats in Solanum species, suggests that repeat-based centromeres can rapidly evolve from neocentromeres by de novo amplification and insertion of satellite repeats in the CENH3 domains.

Optimization of incubation conditions of Plasmodium falciparum antibody multiplex assays to measure IgG, IgG1-4, IgM and IgE using standard and customized reference pools for sero-epidemiological and vaccine studies.

PubMed

Ubillos, Itziar; Jiménez, Alfons; Vidal, Marta; Bowyer, Paul W; Gaur, Deepak; Dutta, Sheetij; Gamain, Benoit; Coppel, Ross; Chauhan, Virander; Lanar, David; Chitnis, Chetan; Angov, Evelina; Beeson, James; Cavanagh, David; Campo, Joseph J; Aguilar, Ruth; Dobaño, Carlota

2018-06-01

The quantitative suspension array technology (qSAT) is a useful platform for malaria immune marker discovery. However, a major challenge for large sero-epidemiological and malaria vaccine studies is the comparability across laboratories, which requires the access to standardized control reagents for assay optimization, to monitor performance and improve reproducibility. Here, the Plasmodium falciparum antibody reactivities of the newly available WHO reference reagent for anti-malaria human plasma (10/198) and of additional customized positive controls were examined with seven in-house qSAT multiplex assays measuring IgG, IgG 1-4 subclasses, IgM and IgE against a panel of 40 antigens. The different positive controls were tested at different incubation times and temperatures (4 °C overnight, 37 °C 2 h, room temperature 1 h) to select the optimal conditions. Overall, the WHO reference reagent had low IgG2, IgG4, IgM and IgE, and also low anti-CSP antibody levels, thus this reagent was enriched with plasmas from RTS,S-vaccinated volunteers to be used as standard for CSP-based vaccine studies. For the IgM assay, another customized plasma pool prepared with samples from malaria primo-infected adults with adequate IgM levels proved to be more adequate as a positive control. The range and magnitude of IgG and IgG 1-4 responses were highest when the WHO reference reagent was incubated with antigen-coupled beads at 4 °C overnight. IgG levels measured in the negative control did not vary between incubations at 37 °C 2 h and 4 °C overnight, indicating no difference in unspecific binding. With this study, the immunogenicity profile of the WHO reference reagent, including seven immunoglobulin isotypes and subclasses, and more P. falciparum antigens, also those included in the leading RTS,S malaria vaccine, was better characterized. Overall, incubation of samples at 4 °C overnight rendered the best performance for antibody measurements against the antigens tested

Short intronic repeat sequences facilitate circular RNA production.

PubMed

Liang, Dongming; Wilusz, Jeremy E

2014-10-15

Recent deep sequencing studies have revealed thousands of circular noncoding RNAs generated from protein-coding genes. These RNAs are produced when the precursor messenger RNA (pre-mRNA) splicing machinery "backsplices" and covalently joins, for example, the two ends of a single exon. However, the mechanism by which the spliceosome selects only certain exons to circularize is largely unknown. Using extensive mutagenesis of expression plasmids, we show that miniature introns containing the splice sites along with short (∼ 30- to 40-nucleotide) inverted repeats, such as Alu elements, are sufficient to allow the intervening exons to circularize in cells. The intronic repeats must base-pair to one another, thereby bringing the splice sites into close proximity to each other. More than simple thermodynamics is clearly at play, however, as not all repeats support circularization, and increasing the stability of the hairpin between the repeats can sometimes inhibit circular RNA biogenesis. The intronic repeats and exonic sequences must collaborate with one another, and a functional 3' end processing signal is required, suggesting that circularization may occur post-transcriptionally. These results suggest detailed and generalizable models that explain how the splicing machinery determines whether to produce a circular noncoding RNA or a linear mRNA. © 2014 Liang and Wilusz; Published by Cold Spring Harbor Laboratory Press.

Short intronic repeat sequences facilitate circular RNA production

PubMed Central

Liang, Dongming

2014-01-01

Recent deep sequencing studies have revealed thousands of circular noncoding RNAs generated from protein-coding genes. These RNAs are produced when the precursor messenger RNA (pre-mRNA) splicing machinery “backsplices” and covalently joins, for example, the two ends of a single exon. However, the mechanism by which the spliceosome selects only certain exons to circularize is largely unknown. Using extensive mutagenesis of expression plasmids, we show that miniature introns containing the splice sites along with short (∼30- to 40-nucleotide) inverted repeats, such as Alu elements, are sufficient to allow the intervening exons to circularize in cells. The intronic repeats must base-pair to one another, thereby bringing the splice sites into close proximity to each other. More than simple thermodynamics is clearly at play, however, as not all repeats support circularization, and increasing the stability of the hairpin between the repeats can sometimes inhibit circular RNA biogenesis. The intronic repeats and exonic sequences must collaborate with one another, and a functional 3′ end processing signal is required, suggesting that circularization may occur post-transcriptionally. These results suggest detailed and generalizable models that explain how the splicing machinery determines whether to produce a circular noncoding RNA or a linear mRNA. PMID:25281217

Pathways and intermediates in forced unfolding of spectrin repeats.

PubMed

Altmann, Stephan M; Grünberg, Raik G; Lenne, Pierre-François; Ylänne, Jari; Raae, Arnt; Herbert, Kristina; Saraste, Matti; Nilges, Michael; Hörber, J K Heinrich

2002-08-01

Spectrin repeats are triple-helical coiled-coil domains found in many proteins that are regularly subjected to mechanical stress. We used atomic force microscopy technique and steered molecular dynamics simulations to study the behavior of a wild-type spectrin repeat and two mutants. The experiments indicate that spectrin repeats can form stable unfolding intermediates when subjected to external forces. In the simulations the unfolding proceeded via a variety of pathways. Stable intermediates were associated to kinking of the central helix close to a proline residue. A mutant stabilizing the central helix showed no intermediates in experiments, in agreement with simulation. Spectrin repeats may thus function as elastic elements, extendable to intermediate states at various lengths.

Genome-Wide Characterization and Linkage Mapping of Simple Sequence Repeats in Mei (Prunus mume Sieb. et Zucc.)

PubMed Central

Sun, Lidan; Yang, Weiru; Zhang, Qixiang; Cheng, Tangren; Pan, Huitang; Xu, Zongda; Zhang, Jie; Chen, Chuguang

2013-01-01

Because of its popularity as an ornamental plant in East Asia, mei (Prunus mume Sieb. et Zucc.) has received increasing attention in genetic and genomic research with the recent shotgun sequencing of its genome. Here, we performed the genome-wide characterization of simple sequence repeats (SSRs) in the mei genome and detected a total of 188,149 SSRs occurring at a frequency of 794 SSR/Mb. Mononucleotide repeats were the most common type of SSR in genomic regions, followed by di- and tetranucleotide repeats. Most of the SSRs in coding sequences (CDS) were composed of tri- or hexanucleotide repeat motifs, but mononucleotide repeats were always the most common in intergenic regions. Genome-wide comparison of SSR patterns among the mei, strawberry (Fragaria vesca), and apple (Malus×domestica) genomes showed mei to have the highest density of SSRs, slightly higher than that of strawberry (608 SSR/Mb) and almost twice as high as that of apple (398 SSR/Mb). Mononucleotide repeats were the dominant SSR motifs in the three Rosaceae species. Using 144 SSR markers, we constructed a 670 cM-long linkage map of mei delimited into eight linkage groups (LGs), with an average marker distance of 5 cM. Seventy one scaffolds covering about 27.9% of the assembled mei genome were anchored to the genetic map, depending on which the macro-colinearity between the mei genome and Prunus T×E reference map was identified. The framework map of mei constructed provides a first step into subsequent high-resolution genetic mapping and marker-assisted selection for this ornamental species. PMID:23555708

47 CFR 95.1311 - Repeater operations and signal boosters prohibited.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 47 Telecommunication 5 2012-10-01 2012-10-01 false Repeater operations and signal boosters... § 95.1311 Repeater operations and signal boosters prohibited. MURS stations are prohibited from operating as a repeater station or as a signal booster. This prohibition includes store-and-forward packet...

47 CFR 95.1311 - Repeater operations and signal boosters prohibited.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 47 Telecommunication 5 2011-10-01 2011-10-01 false Repeater operations and signal boosters... § 95.1311 Repeater operations and signal boosters prohibited. MURS stations are prohibited from operating as a repeater station or as a signal booster. This prohibition includes store-and-forward packet...

47 CFR 95.1311 - Repeater operations and signal boosters prohibited.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 47 Telecommunication 5 2013-10-01 2013-10-01 false Repeater operations and signal boosters... § 95.1311 Repeater operations and signal boosters prohibited. MURS stations are prohibited from operating as a repeater station or as a signal booster. This prohibition includes store-and-forward packet...

47 CFR 95.1311 - Repeater operations and signal boosters prohibited.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 47 Telecommunication 5 2014-10-01 2014-10-01 false Repeater operations and signal boosters... § 95.1311 Repeater operations and signal boosters prohibited. MURS stations are prohibited from operating as a repeater station or as a signal booster. This prohibition includes store-and-forward packet...

47 CFR 95.1311 - Repeater operations and signal boosters prohibited.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 5 2010-10-01 2010-10-01 false Repeater operations and signal boosters... § 95.1311 Repeater operations and signal boosters prohibited. MURS stations are prohibited from operating as a repeater station or as a signal booster. This prohibition includes store-and-forward packet...

Two tandemly repeated telomere-associated sequences in Nicotiana plumbaginifolia.

PubMed

Chen, C M; Wang, C T; Wang, C J; Ho, C H; Kao, Y Y; Chen, C C

1997-12-01

Two tandemly repeated telomere-associated sequences, NP3R and NP4R, have been isolated from Nicotiana plumbaginifolia. The length of a repeating unit for NP3R and NP4R is 165 and 180 nucleotides respectively. The abundance of NP3R, NP4R and telomeric repeats is, respectively, 8.4 x 10(4), 6 x 10(3) and 1.5 x 10(6) copies per haploid genome of N. plumbaginifolia. Fluorescence in situ hybridization revealed that NP3R is located at the ends and/or in interstitial regions of all 10 chromosomes and NP4R on the terminal regions of three chromosomes in the haploid genome of N. plumbaginifolia. Sequence homology search revealed that not only are NP3R and NP4R homologous to HRS60 and GRS, respectively, two tandem repeats isolated from N. tabacum, but that NP3R and NP4R are also related to each other, suggesting that they originated from a common ancestral sequence. The role of these repeated sequences in chromosome healing is discussed based on the observation that two to three copies of a telomere-similar sequence were present in each repeating unit of NP3R and NP4R.

Rational design of alpha-helical tandem repeat proteins with closed architectures

PubMed Central

Doyle, Lindsey; Hallinan, Jazmine; Bolduc, Jill; Parmeggiani, Fabio; Baker, David; Stoddard, Barry L.; Bradley, Philip

2015-01-01

Tandem repeat proteins, which are formed by repetition of modular units of protein sequence and structure, play important biological roles as macromolecular binding and scaffolding domains, enzymes, and building blocks for the assembly of fibrous materials1,2. The modular nature of repeat proteins enables the rapid construction and diversification of extended binding surfaces by duplication and recombination of simple building blocks3,4. The overall architecture of tandem repeat protein structures – which is dictated by the internal geometry and local packing of the repeat building blocks – is highly diverse, ranging from extended, super-helical folds that bind peptide, DNA, and RNA partners5–9, to closed and compact conformations with internal cavities suitable for small molecule binding and catalysis10. Here we report the development and validation of computational methods for de novo design of tandem repeat protein architectures driven purely by geometric criteria defining the inter-repeat geometry, without reference to the sequences and structures of existing repeat protein families. We have applied these methods to design a series of closed alpha-solenoid11 repeat structures (alpha-toroids) in which the inter-repeat packing geometry is constrained so as to juxtapose the N- and C-termini; several of these designed structures have been validated by X-ray crystallography. Unlike previous approaches to tandem repeat protein engineering12–20, our design procedure does not rely on template sequence or structural information taken from natural repeat proteins and hence can produce structures unlike those seen in nature. As an example, we have successfully designed and validated closed alpha-solenoid repeats with a left-handed helical architecture that – to our knowledge – is not yet present in the protein structure database21. PMID:26675735

Genomic Repeat Abundances Contain Phylogenetic Signal

PubMed Central

Dodsworth, Steven; Chase, Mark W.; Kelly, Laura J.; Leitch, Ilia J.; Macas, Jiří; Novák, Petr; Piednoël, Mathieu; Weiss-Schneeweiss, Hanna; Leitch, Andrew R.

2015-01-01

A large proportion of genomic information, particularly repetitive elements, is usually ignored when researchers are using next-generation sequencing. Here we demonstrate the usefulness of this repetitive fraction in phylogenetic analyses, utilizing comparative graph-based clustering of next-generation sequence reads, which results in abundance estimates of different classes of genomic repeats. Phylogenetic trees are then inferred based on the genome-wide abundance of different repeat types treated as continuously varying characters; such repeats are scattered across chromosomes and in angiosperms can constitute a majority of nuclear genomic DNA. In six diverse examples, five angiosperms and one insect, this method provides generally well-supported relationships at interspecific and intergeneric levels that agree with results from more standard phylogenetic analyses of commonly used markers. We propose that this methodology may prove especially useful in groups where there is little genetic differentiation in standard phylogenetic markers. At the same time as providing data for phylogenetic inference, this method additionally yields a wealth of data for comparative studies of genome evolution. PMID:25261464

PRELP (proline/arginine-rich end leucine-rich repeat protein) promotes osteoblastic differentiation of preosteoblastic MC3T3-E1 cells by regulating the β-catenin pathway

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

Li, Haiying; Cui, Yazhou; Luan, Jing

Proline/arginine-rich end leucine-rich repeat protein (PRELP) is a collagen-binding proteoglycan highly expressed in the developing bones. Recent studies indicated that PRELP could inhibit osteoclastogenesis as a NF-κB inhibitor. However, its role during osteoblast differentiation is still unclear. In this study, we confirmed that the expression of PRELP increased with the osteogenesis induction of preosteoblastic MC3T3-E1 cells. Down-regulation of PRELP expression by shRNA reduced ALP activity, mineralization and expression of osteogenic marker gene Runx2. Our microarray analysis data suggested that β-catenin may act as a hub gene in the PRELP-mediated gene network. We validated furtherly that PRELP knockdown could inhibit themore » level of connexin43, a key regulator of osteoblast differentiation by affecting β-catenin protein expression, and its nuclear translocation in MC3T3-E1 preosteoblasts. Therefore, this study established a new role of PRELP in modulating β-catenin/connexin43 pathway and osteoblast differentiation.« less

47 CFR 80.469 - Maritime mobile repeater stations in Alaska.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 5 2010-10-01 2010-10-01 false Maritime mobile repeater stations in Alaska. 80... RADIO SERVICES STATIONS IN THE MARITIME SERVICES Public Coast Stations Use of Telephony § 80.469 Maritime mobile repeater stations in Alaska. (a) Maritime mobile repeater stations are authorized to extend...

Use of the Counseling Center Assessment of Psychological Symptoms 62 (CCAPS-62) as a Repeated Measure

ERIC Educational Resources Information Center

Ghosh, Arpita; Rieder Bennett, Sara; Martin, Juanita K.

2018-01-01

The purpose of this initial, exploratory study was to examine the utility of the Counseling Center Assessment of Psychological Symptoms-62 (CCAPS-62) as a repeated measure tool at one university counseling center. This study investigated whether clients engaged in individual counseling changed in symptomology while in treatment and when (e.g.,…

StaRProtein, A Web Server for Prediction of the Stability of Repeat Proteins

PubMed Central

Xu, Yongtao; Zhou, Xu; Huang, Meilan

2015-01-01

Repeat proteins have become increasingly important due to their capability to bind to almost any proteins and the potential as alternative therapy to monoclonal antibodies. In the past decade repeat proteins have been designed to mediate specific protein-protein interactions. The tetratricopeptide and ankyrin repeat proteins are two classes of helical repeat proteins that form different binding pockets to accommodate various partners. It is important to understand the factors that define folding and stability of repeat proteins in order to prioritize the most stable designed repeat proteins to further explore their potential binding affinities. Here we developed distance-dependant statistical potentials using two classes of alpha-helical repeat proteins, tetratricopeptide and ankyrin repeat proteins respectively, and evaluated their efficiency in predicting the stability of repeat proteins. We demonstrated that the repeat-specific statistical potentials based on these two classes of repeat proteins showed paramount accuracy compared with non-specific statistical potentials in: 1) discriminate correct vs. incorrect models 2) rank the stability of designed repeat proteins. In particular, the statistical scores correlate closely with the equilibrium unfolding free energies of repeat proteins and therefore would serve as a novel tool in quickly prioritizing the designed repeat proteins with high stability. StaRProtein web server was developed for predicting the stability of repeat proteins. PMID:25807112

Contagion and Repeat Offending among Urban Juvenile Delinquents

ERIC Educational Resources Information Center

Mennis, Jeremy; Harris, Philip

2011-01-01

This research investigates the role of repeat offending and spatial contagion in juvenile delinquency recidivism using a database of 7166 male juvenile offenders sent to community-based programs by the Family Court of Philadelphia. Results indicate evidence of repeat offending among juvenile delinquents, particularly for drug offenders. The…

47 CFR 22.573 - Use of base transmitters as repeaters.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 47 Telecommunication 2 2013-10-01 2013-10-01 false Use of base transmitters as repeaters. 22.573... of base transmitters as repeaters. As an additional function, base transmitters may be used as repeaters. Licensees must be able to turn the base transmitter on or off from the control point regardless...

47 CFR 22.573 - Use of base transmitters as repeaters.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 47 Telecommunication 2 2011-10-01 2011-10-01 false Use of base transmitters as repeaters. 22.573... of base transmitters as repeaters. As an additional function, base transmitters may be used as repeaters. Licensees must be able to turn the base transmitter on or off from the control point regardless...

47 CFR 22.573 - Use of base transmitters as repeaters.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 47 Telecommunication 2 2012-10-01 2012-10-01 false Use of base transmitters as repeaters. 22.573... of base transmitters as repeaters. As an additional function, base transmitters may be used as repeaters. Licensees must be able to turn the base transmitter on or off from the control point regardless...

47 CFR 22.573 - Use of base transmitters as repeaters.

Code of Federal Regulations, 2010 CFR

2010-10-01