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Sample records for 3-year efs rate

  1. Impairment in Occupational Functioning and Adult ADHD: The Predictive Utility of Executive Function (EF) Ratings Versus EF Tests

    PubMed Central

    Barkley, Russell A.; Murphy, Kevin R.

    2010-01-01

    Attention deficit hyperactivity disorder (ADHD) is associated with deficits in executive functioning (EF). ADHD in adults is also associated with impairments in major life activities, particularly occupational functioning. We investigated the extent to which EF deficits assessed by both tests and self-ratings contributed to the degree of impairment in 11 measures involving self-reported occupational problems, employer reported workplace adjustment, and clinician rated occupational adjustment. Three groups of adults were recruited as a function of their severity of ADHD: ADHD diagnosis (n = 146), clinical controls self-referring for ADHD but not diagnosed with it (n = 97), and community controls (n = 109). Groups were combined and regression analyses revealed that self-ratings of EF were significantly predictive of impairments in all 11 measures of occupational adjustment. Although several tests of EF also did so, they contributed substantially less than did the EF ratings, particularly when analyzed jointly with the ratings. We conclude that EF deficits contribute to the impairments in occupational functioning that occur in conjunction with adult ADHD. Ratings of EF in daily life contribute more to such impairments than do EF tests, perhaps because, as we hypothesize, each assesses a different level in the hierarchical organization of EF as a meta-construct. PMID:20197297

  2. Articulation Rate in Preschool Children: A 3-Year Longitudinal Study

    ERIC Educational Resources Information Center

    Walker, Jean F.; Archibald, Lisa M. D.

    2006-01-01

    Background: Speaking rate has implications for both clinical practice and an understanding of normal and disordered communication processes. Fundamental information on speaking rate is required by the clinician for the appropriate management of those disorders with disturbances of rate or those in which rate modification strategies are applied.…

  3. Rates of mutation and host transmission for an Escherichia coli clone over 3 years.

    PubMed

    Reeves, Peter R; Liu, Bin; Zhou, Zhemin; Li, Dan; Guo, Dan; Ren, Yan; Clabots, Connie; Lan, Ruiting; Johnson, James R; Wang, Lei

    2011-01-01

    Although over 50 complete Escherichia coli/Shigella genome sequences are available, it is only for closely related strains, for example the O55:H7 and O157:H7 clones of E. coli, that we can assign differences to individual evolutionary events along specific lineages. Here we sequence the genomes of 14 isolates of a uropathogenic E. coli clone that persisted for 3 years within a household, including a dog, causing a urinary tract infection (UTI) in the dog after 2 years. The 20 mutations observed fit a single tree that allows us to estimate the mutation rate to be about 1.1 per genome per year, with minimal evidence for adaptive change, including in relation to the UTI episode. The host data also imply at least 6 host transfer events over the 3 years, with 2 lineages present over much of that period. To our knowledge, these are the first direct measurements for a clone in a well-defined host community that includes rates of mutation and host transmission. There is a concentration of non-synonymous mutations associated with 2 transfers to the dog, suggesting some selection pressure from the change of host. However, there are no changes to which we can attribute the UTI event in the dog, which suggests that this occurrence after 2 years of the clone being in the household may have been due to chance, or some unknown change in the host or environment. The ability of a UTI strain to persist for 2 years and also to transfer readily within a household has implications for epidemiology, diagnosis, and clinical intervention.

  4. Success Rate of MTA Pulpotomy on Vital Pulp of Primary Molars: A 3-Year Observational Study

    PubMed Central

    Tyagi, Rishi

    2016-01-01

    Introduction Vital pulp therapy is a major contributor in the preservation of primary dentition after caries affliction. Introduction of mineral trioxide aggregate (MTA) has revolutionized such treatment. Aim The aim of our study was to evaluate and correlate the effects of MTA clinically and radiographically on pulpotomized primary molars till their exfoliation or extraction followed by histological evaluation. Study design This is an observational study. Materials and methods A total of 25 teeth were selected from 5- to 8-year-old children requiring pulp therapy on the basis of inclusion and exclusion criterion. The teeth were treated by conventional pulpotomy technique under aseptic conditions using MTA and were immediately restored with stainless steel crown. The teeth were assessed postoperatively till 36 months. The exfoliated or extracted teeth were examined histologically. Results The pulpotomized teeth were vital with no adverse clinical findings during the observation period. After 3 months, one tooth showed internal resorption, but the same was not observed after 12 months. Pulp canal obliteration was seen in three cases. At the end of the study, five teeth were exfoliated and one tooth was extracted for maintaining arch symmetry. The histological examination of extracted tooth revealed the presence of healthy pulp and the area of true calcification. Remaining exfoliated teeth presented dentin bridge formation. Statistics Frequencies and percentages were used for descriptive statistics. Fisher’s exact tests were used to see the difference between clinical and radiological findings. The probability value was fixed at 5% level of significance. Conclusion The response of pulp in primary teeth to MTA was favorable in all cases from clinical and radiographic perspective, and histological evaluation confirmed the observation. How to cite this article Godhi B, Tyagi R. Success Rate of MTA Pulpotomy on Vital Pulp of Primary Molars: A 3-Year Observational Study

  5. Soil ingestion rates for children under 3 years old in Taiwan

    EPA Science Inventory

    Soil and dust ingestion rates by children are among the most critical exposure factors in determining risks to children from exposures to environmental contaminants in soil and dust. This is the first published soil ingestion study for children in Taiwan using tracer element meth...

  6. Cumulative success rates following mild IVF in unselected infertile patients: a 3-year, single-centre cohort study.

    PubMed

    Bodri, Daniel; Kawachiya, Satoshi; De Brucker, Michaël; Tournaye, Herman; Kondo, Masae; Kato, Ryutaro; Matsumoto, Tsunekazu

    2014-05-01

    A 3-year, retrospective, single-centre cohort study was conducted in a private infertility centre to determine cumulative live birth rates (LBR) per scheduled oocyte retrieval following minimal ovarian stimulation/natural-cycle IVF in unselected infertile patients. A total of 727 consecutive infertile patients were analysed who underwent 2876 (median 4) cycles with scheduled oocyte retrieval from November 2008 to December 2011. Natural-cycle IVF or clomiphene-based minimal ovarian stimulation was coupled with single-embryo transfer and increased use of delayed vitrified-warmed blastocyst transfer. Main outcome measures were crude and expected age-specific cumulative LBR per scheduled oocyte retrieval. Crude cumulative LBR were 65%, 60%, 39%, 15% and 5% in patients aged 26-34, 35-37, 38-40, 41-42 and 43-44 years, respectively. No live births occurred in patients aged ⩾ 45 years. Dropout rates per cycle were 13-25%. Success rates gradually reached a plateau, with few additional live births after six cycles. Most of the expected success rate was reached within 6 months with almost maximal rates within 15 months of the first oocyte retrieval. Acceptable cumulative LBR are reached with an exclusive minimal ovarian stimulation/single-embryo transfer policy especially in patients aged <38 years but also in intermediate aged patients (38-40 years).

  7. Mechanism and rates of exchange of L7/L12 between ribosomes and the effects of binding EF-G.

    PubMed

    Deroo, Stéphanie; Hyung, Suk-Joon; Marcoux, Julien; Gordiyenko, Yuliya; Koripella, Ravi Kiran; Sanyal, Suparna; Robinson, Carol V

    2012-06-15

    The ribosomal stalk complex binds and recruits translation factors to the ribosome during protein biosynthesis. In Escherichia coli the stalk is composed of protein L10 and four copies of L7/L12. Despite the crucial role of the stalk, mechanistic details of L7/L12 subunit exchange are not established. By incubating isotopically labeled intact ribosomes with their unlabeled counterparts we monitored the exchange of the labile stalk proteins by recording mass spectra as a function of time. On the basis of kinetic analysis, we proposed a mechanism whereby exchange proceeds via L7/L12 monomers and dimers. We also compared exchange of L7/L12 from free ribosomes with exchange from ribosomes in complex with elongation factor G (EF-G), trapped in the posttranslocational state by fusidic acid. Results showed that binding of EF-G reduces the L7/L12 exchange reaction of monomers by ~27% and of dimers by ~47% compared with exchange from free ribosomes. This is consistent with a model in which binding of EF-G does not modify interactions between the L7/L12 monomers but rather one of the four monomers, and as a result one of the two dimers, become anchored to the ribosome-EF-G complex preventing their free exchange. Overall therefore our results not only provide mechanistic insight into the exchange of L7/L12 monomers and dimers and the effects of EF-G binding but also have implications for modulating stability in response to environmental and functional stimuli within the cell.

  8. Recurrence rate of stress urinary incontinence in females with initial cure after transobturator tape procedure at 3-year follow-up

    PubMed Central

    Jun, Taeyong; Yoon, Hyun Sik; Kim, Hyung Suk; Lee, Jeong Woo; Bae, Jungbum

    2017-01-01

    Purpose To assess recurrence rates of urinary incontinence in women with initial cure after transobturator tape (TOT) procedure at 3-year follow-up. Materials and Methods Between June 2006 and May 2013, a total of 402 consecutive patients underwent the TOT procedure for female stress urinary incontinence (SUI) at Dongguk University Ilsan Hospital. Of the 402 patients, 223 had sufficient medical records for analysis. Therefore, they were followed-up for 3 years postoperatively. Patient characteristics, urinary symptoms, physical examination, and urodynamic parameters were evaluated. The primary end point of “cure” was defined as the absence of any complaint of urinary leakage without needing pads for usual activities. Results Of the 223 patients, 196 patients (87.9%) were initially cured within 6 months postoperatively. Of the 196 patients, 70 (35.7%) had recurrent urinary incontinence at 3 years postoperatively, 51 (26.0%) had SUI, 16 (8.2%) had urgency urinary incontinence, and 3 (1.5%) had mixed urinary incontinence. In univariate analysis, preoperative urinary obstructive symptom was found to significant contributor to the recurrence of urinary incontinence at 3-year postoperatively (p=0.004). Conclusions In our study, 35.7% of the women with initial cure after TOT experienced the recurrence of urinary leakage during the 3-year follow-up. The cure rate of TOT was decreased as time went by, although the initial cure rate was high. PMID:28097269

  9. Rate of deaths due to child abuse and neglect in children 0-3 years of age in Germany.

    PubMed

    Banaschak, Sibylle; Janßen, Katharina; Schulte, Babette; Rothschild, Markus A

    2015-09-01

    In recent years, increasing attention has been paid to the issue of (fatal) child abuse and neglect, largely due to the media attention garnered by some headline-grabbing cases. If media statements are to be believed, such cases may be an increasing phenomenon. With these published accounts in mind, publicly available statistics should be analysed with respect to the question of whether reliable statements can be formulated based on these figures. It is hypothesised that certain data, e.g., the Innocenti report published by UNICEF in 2003, may be based on unreliable data sources. For this reason, the generation of such data, and the reliability of the data itself, should also be discussed. Our focus was on publicly available German mortality and police crime statistics (Polizeiliche Kriminalstatistik). These data were classified with respect to child age, data origin, and cause of death (murder, culpable homicide, etc.). In our opinion, the available data could not be considered in formulating reliable scientific statements about fatal child abuse and neglect, given the lack of detail and the flawed nature of the basic data. Increasing the number of autopsies of children 0-3 years of age should be considered as a means to ensure the capture of valid, practical, and reliable data. This could bring about some enlightenment and assist in the development of preemptive strategies to decrease the incidence of (fatal) child abuse and neglect.

  10. The structure of executive function in 3-year-olds.

    PubMed

    Wiebe, Sandra A; Sheffield, Tiffany; Nelson, Jennifer Mize; Clark, Caron A C; Chevalier, Nicolas; Espy, Kimberly Andrews

    2011-03-01

    Although the structure of executive function (EF) during adulthood is characterized by both unity and diversity, recent evidence suggests that preschool EF may be best described by a single factor. The latent structure of EF was examined in 228 3-year-olds using confirmatory factor analysis. Children completed a battery of executive tasks that differed in format and response requirements and in putative working memory and inhibitory control demands. Tasks appeared to be age appropriate, with adequate sensitivity across the range of performance and without floor or ceiling effects. Tests of the relative fit of several alternative models supported a single latent EF construct. Measurement invariance testing revealed less proficient EF in children at higher sociodemographic risk relative to those at lower risk and no differences between boys and girls. At 3years of age, when EF skills are emerging, EF appears to be a unitary, more domain-general process.

  11. Teacher Ratings Predict Peer Ratings of Aggression at 3-Year Follow-Up in Boys with Attention Deficit Disorder with Hyperactivity.

    ERIC Educational Resources Information Center

    Johnston, Charlotte; Pelham, William E.

    1986-01-01

    Initial and follow-up peer ratings of boys with attention deficit disorder with hyperactivity (ADDH) were compared. Peer ratings of aggression improved for boys whom teachers rated below the median on the Iowa Conners Aggression scale but not for boys rated above the median. Subgroups reflecting other teacher and peer ratings were less effective…

  12. Changes in cortisol release and heart rate and heart rate variability during the initial training of 3-year-old sport horses.

    PubMed

    Schmidt, Alice; Aurich, Jörg; Möstl, Erich; Müller, Jürgen; Aurich, Christine

    2010-09-01

    Based on cortisol release, a variety of situations to which domestic horses are exposed have been classified as stressors but studies on the stress during equestrian training are limited. In the present study, Warmblood stallions (n=9) and mares (n=7) were followed through a 9 respective 12-week initial training program in order to determine potentially stressful training steps. Salivary cortisol concentrations, beat-to-beat (RR) interval and heart rate variability (HRV) were determined. The HRV variables standard deviation of the RR interval (SDRR), RMSSD (root mean square of successive RR differences) and the geometric means standard deviation 1 (SD1) and 2 (SD2) were calculated. Nearly each training unit was associated with an increase in salivary cortisol concentrations (p<0.01). Cortisol release varied between training units and occasionally was more pronounced in mares than in stallions (p<0.05). The RR interval decreased slightly in response to lunging before mounting of the rider. A pronounced decrease occurred when the rider was mounting, but before the horse showed physical activity (p<0.001). The HRV variables SDRR, RMSSD and SD1 decreased in response to training and lowest values were reached during mounting of a rider (p<0.001). Thereafter RR interval and HRV variables increased again. In contrast, SD2 increased with the beginning of lunging (p<0.05) and no changes in response to mounting were detectable. In conclusion, initial training is a stressor for horses. The most pronounced reaction occurred in response to mounting by a rider, a situation resembling a potentially lethal threat under natural conditions.

  13. Developmental milestones record - 3 years

    MedlinePlus

    ... years; Growth milestones for children - 3 years; Childhood growth milestones - 3 years; Well child - 3 years ... activities related to your child's interests. Encourage your child to use words to express feelings (rather than acting out).

  14. A 3-year continuous record on the influence of daytime, season, and fertilizer treatment on methane emission rates from an Italian rice paddy

    SciTech Connect

    Schuetz, H.; Holzapfel-Pschorn, A.; Conrad, R.; Rennenberg, H.; Seiler, W. )

    1989-11-20

    CH{sub 4} emission rates have been measured in an Italian rice paddy between 1984 and 1986, covering three vegetation periods. For these measurements a fully automated, computerized sampling and analyzing system was developed which allowed the simultaneous determination of CH{sub 4} emission rates at 16 different field plots. CH{sub 4} emission rates showed strong diurnal and seasonal variations. Diurnal changes correlated with changes in soil temperature. During the season, CH{sub 4} emission rates showed a first maximum in May--June before tillering and a second maximum in July during the reproductive stage of the rice plants. In 1985 and 1986 two maxima were observed during summer in addition to the first maximum in the rate of CH{sub 4} emission during spring. Application of mineral and/or organic fertilizer application. Thus the rates decreased by at most 40% and 60% after fertilization by deep incorporation with 200 kg N/ha urea and 200 kg N/ha ammonium sulfate, respectively. Application of 200 kg N/ha calcium cyanamide led to a reduction of the first maximum of CH{sub 4} emission but caused the second maximum to increase, the overall result being that the seasonally averaged CH{sub 4} emission rate was comparable to that observed in unfertilized fields. Application of rice straw at a rate of 12t/ha enhanced the rate of CH{sub 4} emission by a factor of 2 compared with the control. Higher application rates of rice straw did not cause a further increase in CH{sub 4} emission.

  15. Education for Sustainability (EfS): Practice and Practice Architectures

    ERIC Educational Resources Information Center

    Kemmis, Stephen; Mutton, Rebecca

    2012-01-01

    This paper reports some findings from an investigation of educational practice in ten (formal and informal) education for sustainability (EfS) initiatives, to characterise exemplary practice in school and community education for sustainability, considered crucial to Australia's future. The study focused on rural/regional Australia, specifically…

  16. Assessment of Uncertainty in Cloud Radiative Effects and Heating Rates through Retrieval Algorithm Differences: Analysis using 3-years of ARM data at Darwin, Australia

    SciTech Connect

    Comstock, Jennifer M.; Protat, Alain; McFarlane, Sally A.; Delanoe, Julien; Deng, Min

    2013-05-22

    Ground-based radar and lidar observations obtained at the Department of Energy’s Atmospheric Radiation Measurement Program’s Tropical Western Pacific site located in Darwin, Australia are used to retrieve ice cloud properties in anvil and cirrus clouds. Cloud microphysical properties derived from four different retrieval algorithms (two radar-lidar and two radar only algorithms) are compared by examining mean profiles and probability density functions of effective radius (Re), ice water content (IWC), extinction, ice number concentration, ice crystal fall speed, and vertical air velocity. Retrieval algorithm uncertainty is quantified using radiative flux closure exercises. The effect of uncertainty in retrieved quantities on the cloud radiative effect and radiative heating rates are presented. Our analysis shows that IWC compares well among algorithms, but Re shows significant discrepancies, which is attributed primarily to assumptions of particle shape. Uncertainty in Re and IWC translates into sometimes-large differences in cloud radiative effect (CRE) though the majority of cases have a CRE difference of roughly 10 W m-2 on average. These differences, which we believe are primarily driven by the uncertainty in Re, can cause up to 2 K/day difference in the radiative heating rates between algorithms.

  17. Your Child's Development: 3 Years

    MedlinePlus

    ... Feeding Your 1- to 2-Year-Old Your Child’s Development: 3 Years KidsHealth > For Parents > Your Child’s Development: 3 Years A A A Kids this age ... but certain signs could indicate a delay in development. Talk to your doctor if your child: doesn't speak, or can't speak in ...

  18. Your Child's Development: 3 Years

    MedlinePlus

    ... Feeding Your 1- to 2-Year-Old Your Child’s Development: 3 Years KidsHealth > For Parents > Your Child’s Development: 3 Years Print A A A en español ... but certain signs could indicate a delay in development. Talk to your doctor if your child: doesn't speak, or can't speak in ...

  19. The Development of Core Cognitive Skills in Autism: A 3-Year Prospective Study

    ERIC Educational Resources Information Center

    Pellicano, Elizabeth

    2010-01-01

    This longitudinal study tested the veracity of one candidate multiple-deficits account of autism by assessing 37 children with autism (M age = 67.9 months) and 31 typical children (M age = 65.2 months) on tasks tapping components of theory of mind (ToM), executive function (EF), and central coherence (CC) at intake and again 3 years later. As a…

  20. Concentrator E-F11 water test

    SciTech Connect

    Ethington, P.R.

    1994-02-25

    This document is the Process Test Report for performing operation testing with water of the modified E-F11 concentrator in PUREX on water. The test was performed to determine the effects of the following concentrator modifications; routing concentrator off-gasses via the PUREX air tunnel to the main stack, blanking of condenser cooling water, blanking of process condensate route to a crib, restricting flow to steam tube bundles, and routing of steam condensate to TK-F12. The test was successful. Concentrator boil-off rates of 6--7 gpm were achieved while the overheads exited the PUREX plant in vapor form. With minor recommended modifications, this process is recommended for use in processing PUREX deactivation flush solutions and other miscellaneous wastes accumulated during the completion of the deactivation project.

  1. Green fluorescence induced by EF-hand assembly in a split GFP system.

    PubMed

    Lindman, Stina; Johansson, Ida; Thulin, Eva; Linse, Sara

    2009-06-01

    The affinity between the 1-157 and 158-238 fragments of green fluorescent protein (GFP) is too low for spontaneous in vivo reassembly of the protein upon co-expression of the two fragments. This prevents chromophore maturation and the cells lack GFP fluorescence. We have utilized the very high affinity between the two EF-hands of calbindin D(9k) to facilitate GFP assembly from its fragments and to introduce a calcium dependent molecular switch. In GFPN-EF1, residues 1-157 of GFP are fused to residues 1-43 of calbindin, and in EF2-GFPC, residues 44-75 of calbindin are fused to residues 158-238 of GFP. When co-expressed, GFPN-EF1 and EF2-GFPC associate spontaneously and rapidly resulting in a folded reconstituted protein with bright GFP fluorescence. The high affinity of GFPN-EF1 for EF2-GFPC leads to brighter fluorescence of the cells compared to cells with a control constructs carrying leucine zippers (Wilson et al., Nature Methods 2004;3:255). The complex of GFPN-EF1 and EF2-GFPC was purified from cells using metal-ion chelate chromatography and the temperature dependence of GFP fluorescence was found to be calcium dependent. The GFPN-EF1 and EF2-GFPC fragments were separated by ion exchange chromatography. The assembly of the fragments was found to be reversible and the complex was regained upon mixing, as evidenced by surface plasmon resonance (SPR) data. The affinity between GFPN-EF1 and EF2-GFPC as well as rates of association and dissociation were found to be Ca(2+)-dependent.

  2. Impaired Myocardial Bioenergetics in HFpEF and the Role of Antioxidants.

    PubMed

    Hiebert, John B; Shen, Qiuhua; Thimmesch, Amanda; Pierce, Janet

    2016-01-01

    Heart failure with preserved ejection fraction (HFpEF) is a significant cardiovascular condition for more than 50% of patients with heart failure. Currently, there is no effective treatment to decrease morbidity and mortality rates associated with HFpEF because of its pathophysiological heterogeneity. Recent evidence shows that deficiency in myocardial bioenergetics is one of the key pathophysiological factors contributing to diastolic dysfunction in HFpEF. Another known mechanism for HFpEF is an overproduction of free radicals, specifically reactive oxygen species. To reduce free radical formation, antioxidants are often used. This article is a summative review of the recent relevant literature that addresses cardiac bioenergetics, deficiency in myocardial bioenergetics, and increased reactive oxygen species associated with HFpEF and the promising potential use of antioxidants in managing this condition.

  3. How Grammatical Are 3-Year-Olds?

    ERIC Educational Resources Information Center

    Eisenberg, Sarita L.; Guo, Ling-Yu; Germezia, Mor

    2012-01-01

    Purpose: This study investigated the level of grammatical accuracy in typically developing 3-year-olds and the types of errors they produce. Method: Twenty-two 3-year-olds participated in a picture description task. The percentage of grammatical utterances was computed and error types were analyzed. Results: The mean level of grammatical accuracy…

  4. Antibacterial activity of synthetic curcumin derivatives: 3,5-bis(benzylidene)-4-piperidone (EF24) and EF24-dimer linked via diethylenetriaminepentacetic acid (EF2DTPA).

    PubMed

    Vilekar, Prachi; King, Catherine; Lagisetty, Pallavi; Awasthi, Vibhudutta; Awasthi, Shanjana

    2014-04-01

    Curcumin is well known for its antimicrobial and anti-inflammatory properties. However, since systemic absorption and bioavailability of curcumin from gastrointestinal tract is considerably poor, synthetic curcuminoids are being developed as better alternatives. Two curcumin derivatives: 3,5-bis(benzylidene)-4-piperidone (EF24) and EF24-dimer linked via diethylenetriaminepentacetic acid (EF2DTPA), were included in this study. We investigated the antibacterial activity of EF24 and EF2DTPA against Gram-negative (Escherichia coli) and Gram-positive (Enterococcus faecalis, Staphylococcus aureus) bacteria. We also studied the effects of EF24 and EF2DTPA on uptake and localization of pHrodo-labeled E. coli in the acidic compartments (phagolysosomes) of dendritic cells (DCs) under in vitro conditions. Our results demonstrate that treatment with EF24 and EF2DTPA directly suppresses the bacterial growth. However, these compounds do not affect the bacterial uptake or localization in the DCs.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  6. Structural Consequences of Calmodulin EF Hand Mutations.

    PubMed

    Piazza, Michael; Taiakina, Valentina; Dieckmann, Thorsten; Guillemette, J Guy

    2017-02-21

    Calmodulin (CaM) is a cytosolic Ca(2+)-binding protein that serves as a control element for many enzymes. It consists of two globular domains, each containing two EF hand pairs capable of binding Ca(2+), joined by a flexible central linker region. CaM is able to bind and activate its target proteins in the Ca(2+)-replete and Ca(2+)-deplete forms. To study the Ca(2+)-dependent/independent properties of binding and activation of target proteins by CaM, CaM constructs with Ca(2+)-binding disrupting mutations of Asp to Ala at position one of each EF hand have been used. These CaM mutant proteins are deficient in binding Ca(2+) in either the N-lobe EF hands (CaM12), C-lobe EF hands (CaM34), or all four EF hands (CaM1234). To investigate potential structural changes these mutations may cause, we performed detailed NMR studies of CaM12, CaM34, and CaM1234 including determining the solution structure of CaM1234. We then investigated if these CaM mutants affected the interaction of CaM with a target protein known to interact with apoCaM by determining the solution structure of CaM34 bound to the iNOS CaM binding domain peptide. The structures provide direct structural evidence of changes that are present in these Ca(2+)-deficient CaM mutants and show these mutations increase the hydrophobic exposed surface and decrease the electronegative surface potential throughout each lobe of CaM. These Ca(2+)-deficient CaM mutants may not be a true representation of apoCaM and may not allow for native-like interactions of apoCaM with its target proteins.

  7. Evolution of translational elongation factor (EF) sequences: reliability of global phylogenies inferred from EF-1 alpha(Tu) and EF-2(G) proteins.

    PubMed Central

    Creti, R; Ceccarelli, E; Bocchetta, M; Sanangelantoni, A M; Tiboni, O; Palm, P; Cammarano, P

    1994-01-01

    The EF-2 coding genes of the Archaea Pyrococcus woesei and Desulfurococcus mobilis were cloned and sequenced. Global phylogenies were inferred by alternative tree-making methods from available EF-2(G) sequence data and contrasted with phylogenies constructed from the more conserved but shorter EF-1 alpha(Tu) sequences. Both the monophyly (sensu Hennig) of Archaea and their subdivision into the kingdoms Crenarchaeota and Euryarchaeota are consistently inferred by analysis of EF-2(G) sequences, usually at a high bootstrap confidence level. In contrast, EF-1 alpha(Tu) phylogenies tend to be inconsistent with one another and show low bootstrap confidence levels. While evolutionary distance and DNA maximum parsimony analyses of EF-1 alpha(Tu) sequences do show archaeal monophyly, protein parsimony and DNA maximum-likelihood analyses of these data do not. In no case, however, do any of the tree topologies inferred from EF-1 alpha(Tu) sequence analyses receive significant bootstrap support. PMID:8159735

  8. Class E/F switching power amplifiers

    NASA Technical Reports Server (NTRS)

    Hajimiri, Seyed-Ali (Inventor); Aoki, Ichiro (Inventor); Rutledge, David B. (Inventor); Kee, Scott David (Inventor)

    2004-01-01

    The present invention discloses a new family of switching amplifier classes called class E/F amplifiers. These amplifiers are generally characterized by their use of the zero-voltage-switching (ZVS) phase correction technique to eliminate of the loss normally associated with the inherent capacitance of the switching device as utilized in class-E amplifiers, together with a load network for improved voltage and current wave-shaping by presenting class-F.sup.-1 impedances at selected overtones and class-E impedances at the remaining overtones. The present invention discloses a several topologies and specific circuit implementations for achieving such performance.

  9. AID awards 3-year Guatemala contract.

    PubMed

    1984-01-01

    The US Agency for International Development (USAID) has awarded a 3-year US$593,036 grant to the Los Angeles firm of Juarez and Associates, Inc. to help implement a contraceptive social marketing project in Guatemala. The firm will provide marketing assistance to the for-profit organization. Importadora de Productos Farmaceuticos (PROFA), an offshoot of the nonprofit International Planned Parenthood Federation affiliate, Asociacion Pro-Bienestar de la Familia de Guatemala (APROFAM), created specifically to conduct the social marketing project. Juarez and Associates has previous market research experience in family planning in Guatemala. Contraceptive social marketing sales are projected to begin in early 1985.

  10. Algerian Eddies lifetime can near 3 years

    NASA Astrophysics Data System (ADS)

    Puillat, I.; Taupier-Letage, I.; Millot, C.

    2002-01-01

    The Algerian Current (AC) is unstable and generates mesoscale meanders and eddies. Only anticyclonic eddies can develop and reach diameters over 200 km with vertical extents down to the bottom (˜3000 m). Algerian Eddies (AEs) first propagate eastward along the Algerian slope at few kilometers per day. In the vicinity of the Channel of Sardinia, a few AEs detach from the Algerian slope and propagate along the Sardinian one. It was hypothesized that AEs then followed a counter-clockwise circuit in the eastern part of the basin. Maximum recorded lifetimes were known to exceed 9 months. Within the framework of the 1-year Eddies and Leddies Interdisciplinary Study off Algeria (ELISA) experiment (1997-1998), we exhaustively tracked two AEs, using mainly an ˜3-year time series of NOAA/AVHRR satellite images. We show that AEs lifetimes can near 3 years, exceeding 33 months at least. We also confirm the long-lived AEs preferential circuit in the eastern part of the Algerian Basin, and specify that it may include several loops (at least three).

  11. Inflammation in HFpEF: Key or circumstantial?

    PubMed

    van Empel, Vanessa; Brunner-La Rocca, Hans-Peter

    2015-01-01

    Heart failure (HF) can be split into HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF). Currently the pathophysiologic mechanisms involved in HFpEF remain largely unknown. The neurohumoral and sympathetic nervous systems seem not to play a crucial role in HFpEF, as treatments targeting these pathways do not show beneficial effects in HFpEF patients, in contrast to HFrEF patients. A better understanding of the pathophysiological processes involved in HFpEF is needed, as there is no proven treatment for this disease at the moment. Recent data have yielded growing attention to the role of inflammation in HFpEF. In this review we discuss increased inflammation in HFpEF as demonstrated in translational animal models and human studies. This review evaluates whether inflammation plays a key role in HFpEF or is just a by-product of various comorbidities. Additionally, we analyze the involvement of oxidative stress and endothelial dysfunction and lastly we outline potential therapeutic targets.

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

    SciTech Connect

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

    2014-07-18

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

  13. The Eroding Foil Switch (EFS) model

    NASA Astrophysics Data System (ADS)

    Brandenburg, John E.; Terry, Robert E.

    1986-01-01

    An analysis of the results of two experiments, the Los Alamos Foil Switch Experiment and the Magnetic Gate Experiment, reveals evidence of mass loss and unexpectedly high temperatures in strongly accelerated aluminum foils. Nonlinear magnetic diffusion theory is analyzed both analytically and numerically and found to give strong concentrations of current density, in a propagating front, for foils thicker than a classical skin depth. This concentrated current front is found to lead to mass erosion and high temperatures in foils undergoing strong acceleration. These results are used to formulate a new model of foil kinematics called the EFS model that features both a rocket (or mass loss) phase, and a snowplow (shock wave) phase after foil disassembly. This model is shown to give good agreement with experimental results.

  14. Effects of effluent organic matter (EfOM) on the removal of emerging contaminants by ozonation.

    PubMed

    Cai, Ming-Jhih; Lin, Yi-Pin

    2016-05-01

    Removal of emerging contaminants in wastewater treatment is essential to ensure the ecological health of the receiving water bodies. Ozonation is a promising technology to achieve this purpose but important wastewater characteristics affecting the optimal removal efficiency need to be elucidated. Secondary effluents contain effluent organic matter (EfOM), which can react directly with ozone as well as react as the initiator, promoter and inhibitor in the hydroxyl radical (.OH) chain reactions resulting from ozone decomposition. These different reaction modes of EfOM, coupled with alkalinity and pH value, collectively determine the ozone and .OH exposures and the degradation of pharmaceutical compounds by ozonation. In this study, we determined the rate constants of EfOM collected from two municipal wastewater treatment plants in terms of direct ozone reaction, initiation, promotion and inhibition at various pH values (pH 6.0-7.5) and temperatures (10-30 °C). The rate constants of direct reaction and initiation generally increased with the increasing pH value while the rate constants of promotion and inhibition did not vary significantly. All rate constants increased with the increasing temperature. The removal of ibuprofen, acetylsulfamethoxazole and metoprolol in diluted secondary effluent by ozonation can be fairly-well modeled by using the determined rate constants of EfOM.

  15. Cell- and molecular-level mechanisms contributing to diastolic dysfunction in HFpEF.

    PubMed

    Campbell, Kenneth S; Sorrell, Vincent L

    2015-11-15

    Heart failure with preserved ejection fraction (HFpEF) is the default diagnosis for patients who have symptoms of heart failure, an ejection fraction >0.5, and evidence of diastolic dysfunction. The clinical condition, which was largely unrecognized 30 years ago, is now a major health problem and currently accounts for 50% of all patients with heart failure. Clinical studies show that patients with HFpEF exhibit increased passive stiffness of the ventricles and a slower rate of pressure decline during diastole. This review discusses some of the cell- and molecular-level mechanisms that contribute to these effects and focuses on data obtained using human samples. Collagen cross linking, modulation of protein kinase G-related pathways, Ca(2+) handling, and strain-dependent detachment of cross bridges are highlighted as potential factors that could be modulated to improve ventricular function in patients with HFpEF.

  16. EF-Tu from the enacyloxin producing Frateuria W-315 strain: Structure/activity relationship and antibiotic resistance.

    PubMed

    Créchet, Jean-Bernard; Malosse, Christian; Hountondji, Codjo

    2016-08-01

    In this report, we have demonstrated that the poly(U)-dependent poly(Phe) synthesis activity of elongator factor Tu (EF-Tu) from the enacyloxin producing strain Frateuria sp. W-315 is inhibited by the antibiotic similarly to that of Escherichia coli EF-Tu. The inhibitory effect of enacyloxin observed in a purified system was the same as that obtained with an S30 extract from E. coli or Frateuria sp. W-315, respectively, suggesting that antibiotic resistance of enacyloxin producing Frateuria sp. W-315 is not due neither to EF-Tu nor to other components of the translation machinery but to a still unknown mechanism. The EF-Tu gene, as PCR amplified from Frateuria W-315 genomic DNA and sequenced represented an ORF of 1191 nucleotides corresponding to 396 amino acids. This protein is larger than the product of tufA from E. coli by only two amino acid residues. Alignment of the amino acid sequence of EF-Tu from E. coli with those of Frateuria and Ralstonia solanacearum indicates on average 80% identical amino acid residues and 9.7% conservative replacements between EF-Tu Frateuria and EF-Tu E. coli, on one hand, and 97% identity and 1.7% conservative replacement between EF-Tu Frateuria and EF-Tu Ralstonia solanacearum, on the other hand. These strong primary structure similarities between EF-Tu from different origins are consistent with the fact that this factor is essential for the translation process in all kingdoms of life. Comparison of the effects of antibiotics on EF-Tu Frateuria and EF-Tu E. coli revealed that enacyloxin, kirromycin and pulvomycin exert a stronger stimulation of the GDP dissociation rate on EF-Tu Frateuria, while the effects of the antibiotics on the GDP association rate were comparable for the two EF-Tu species. Different mutants of EF-Tu E. coli were constructed with the help of site directed mutagenesis by changing one or several residues of EF-Tu E. coli by the corresponding residues of EF-Tu Frateuria. The single A45K substitution did

  17. 9 CFR 205.209 - Amendment or continuation of EFS.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Amendment or continuation of EFS. 205.209 Section 205.209 Animals and Animal Products GRAIN INSPECTION, PACKERS AND STOCKYARDS... OF FARM PRODUCTS Interpretive Opinions § 205.209 Amendment or continuation of EFS. (a) The...

  18. 23 CFR Appendixes E-F to Subpart A... - [Reserved

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 23 Highways 1 2010-04-01 2010-04-01 false E Appendixes E-F to Subpart A of Part 230 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION CIVIL RIGHTS EXTERNAL PROGRAMS Equal...) Appendixes E-F to Subpart A of Part 230...

  19. Targeting elongation factor-2 kinase (eEF-2K) induces apoptosis in human pancreatic cancer cells.

    PubMed

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

    2014-01-01

    Pancreatic cancer (PaCa) is one of the most aggressive, apoptosis-resistant and currently incurable cancers with a poor survival rate. Eukaryotic elongation factor-2 kinase (eEF-2K) is an atypical kinase, whose role in PaCa survival is not yet known. Here, we show that eEF-2K is overexpressed in PaCa cells and its down-regulation induces apoptotic cell death. Rottlerin (ROT), a polyphenolic compound initially identified as a PKC-δ inhibitor, induces apoptosis and autophagy in a variety of cancer cells including PaCa cells. We demonstrated that ROT induces intrinsic apoptosis, with dissipation of mitochondrial membrane potential (ΔΨm), and stimulates extrinsic apoptosis with concomitant induction of TNF-related apoptosis inducing ligand (TRAIL) receptors, DR4 and DR5, with caspase-8 activation, in PANC-1 and MIAPaCa-2 cells. Notably, while none of these effects were dependent on PKC-δ inhibition, ROT down-regulates eEF-2K at mRNA level, and induce eEF-2K protein degradation through ubiquitin-proteasome pathway. Down-regulation of eEF-2K recapitulates the events observed after ROT treatment, while its over-expression suppressed the ROT-induced apoptosis. Furthermore, eEF-2K regulates the expression of tissue transglutaminase (TG2), an enzyme previously implicated in proliferation, drug resistance and survival of cancer cells. Inhibition of eEF-2K/TG2 axis leads to caspase-independent apoptosis which is associated with induction of apoptosis-inducing factor (AIF). Collectively, these results indicate, for the first time, that the down-regulation of eEF-2K leads to induction of intrinsic, extrinsic as well as AIF-dependent apoptosis in PaCa cells, suggesting that eEF-2K may represent an attractive therapeutic target for the future anticancer agents in PaCa.

  20. Mineralocorticoid receptor antagonists in heart failure with preserved ejection fraction (HFpEF).

    PubMed

    Capuano, Annalisa; Scavone, Cristina; Vitale, Cristiana; Sportiello, Liberata; Rossi, Francesco; Rosano, Giuseppe M C; Coats, Andrew J Stewart

    2015-12-01

    The role of spironolactone and eplerenone in patients with Heart Failure with preserved Ejection Fraction (HFpEF) is not well defined. Since a growing medical literature has suggested that mineralocorticoid receptor antagonists may be beneficial for patients with HFpEF, this review gives an in-depth update on the role of spironolactone and eplerenone and their implications for therapy in the setting of HFpEF. Eleven clinical studies, including seven randomized trials, were reviewed. Two randomized controlled trials evaluated the effect of eplerenone on different end-points, including 6 minute walk distance (6 MWD), cardiovascular mortality, non-fatal reinfarction, hospitalization for unstable angina and congestive heart failure. Eplerenone did not affect either 6 MWD or event-free survival rates in the overall study population in these two reports. The effects of spironolactone on similar composite endpoints were evaluated in 7 studies in patients with HFpEF. Compared to placebo, hospitalization for heart failure was significantly lower in the spironolactone group and spironolactone was also shown to improve diastolic function and induced beneficial remodeling through a reduction in myocardial fibrosis. The safety profile of spironolactone and eplerenone has been assessed in two recent studies. Data showed that eplerenone and spironolactone are both associated with the occurrence of gynecomastia, mastodynia, and abnormal vaginal bleeding and in addition, they can increase natriuresis and cause renal retention of potassium; furthermore, eplerenone may cause hyperkalemia and promote the onset of metabolic acidosis or hyponatremia. In conclusion although the mineralocorticoid receptor antagonists eplerenone and spironolactone improve clinical outcomes in patients with HFrEF, additional data will be necessary to better define their risk-benefit profile, especially for eplerenone, in the treatment of HFpEF.

  1. Embedding EfS in Teacher Education through a Multi-Level Systems Approach: Lessons from Queensland

    ERIC Educational Resources Information Center

    Evans, Neus; Ferreira, Jo-Anne; Davis, Julie; Stevenson, Robert B.

    2016-01-01

    This article reports on the fourth stage of an evolving study to develop a systems model for embedding education for sustainability (EfS) into preservice teacher education. The fourth stage trialled the extension of the model to a comprehensive state-wide systems approach involving representatives from all eight Queensland teacher education…

  2. The Atlas E/F launch vehicle - An unsung workhorse

    NASA Astrophysics Data System (ADS)

    Powell, J. W.; Richards, G. R.

    1991-05-01

    Over the 22 years ending in April 1990, the USAF and NASA used the 'E/F' version of the venerable Atlas ICBM for 39 launches, using 11 different upper-stage combinations. Beginning in 1983, a number of the Atlas E/F payloads were assigned to the Atlas H launch vehicle derived from the SLV-3D version of the NASA Atlas-Centaur. A complete Atlas E/F and H chronology is presented, in conjunction with a historical account of some of the most significant satellite payloads lofted by these launch vehicles.

  3. Protein synthesis alongation factors EF-Tu and eEF1A: biosynthesis, functions and application in the improvement of heat tolerance in plants

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Protein synthesis elongation factors EF-Tu and eEF1A (EFs) represent a group of highly conserved and abundant GTPases with an important role in transporting the aminoacyl-tRNA complex to the A site of the ribosome during elongation phase of translation. EF-Tu proteins are located in bacteria and, du...

  4. When Policy and Infrastructure Provisions Are Exemplary but Still Insufficient: Paradoxes Affecting Education for Sustainability (EfS) in a Custom-Designed Sustainability School

    ERIC Educational Resources Information Center

    Kuzich, Sonja; Taylor, Elisabeth; Taylor, Peter Charles

    2015-01-01

    Schools willing to implement education for sustainability (EfS) commonly find themselves confronted with curricula, school grounds and buildings and teaching practices that do not lend themselves easily to best practice EfS. In this article, we present what we learned about some of the challenges confronted daily by the staff of a purpose-built…

  5. Design and properties of efficient tRNA:EF-Tu FRET system for studies of ribosomal translation.

    PubMed

    Chudaev, Maxim; Poruri, Kiran; Goldman, Emanuel; Jakubowski, Hieronim; Jain, Mohit Raja; Chen, Wei; Li, Hong; Tyagi, Sanjay; Mandecki, Wlodek

    2013-05-01

    Formation of the ternary complex between GTP-bound form of elongation factor Tu (EF-Tu) and aminoacylated transfer RNA (aa-tRNA) is a key event in protein biosynthesis. Here we show that fluorescently modified Escherichia coli EF-Tu carrying three mutations, C137A, C255V and E348C, and fluorescently modified Phe-tRNA(Phe) form functionally active ternary complex that has properties similar to those of the naturally occurring (unmodified) complex. Similarities include the binding and binding rate constants, behavior in gel retardation assay, as well as activities in tRNA protection and in vitro translation assays. Proper labeling of EF-Tu was demonstrated in MALDI mass spectroscopy experiments. To generate the mutant EF-Tu, a series of genetic constructions were performed. Two native cysteine residues in the wild-type EF-Tu at positions 137 and 255 were replaced by Ala and Val, respectively, and an additional cysteine was introduced either in position 324 or 348. The assembly FRET assay showed a 5- to 7-fold increase of Cy5-labeled EF-Tu E348C mutant fluorescence upon formation of ternary complex with charged tRNA(Phe)(Cy3-labeled) when the complex was excited at 532 nm and monitored at 665 nm. In a control experiment, we did not observe FRET using uncharged tRNA(Phe)(Cy3), nor with wild-type EF-Tu preparation that was allowed to react with Cy5 maleimide, nor in the absence of GTP. The results obtained demonstrate that the EF-Tu:tRNA FRET system described can be used for investigations of ribosomal translation in many types of experiments.

  6. A tRNA body with high affinity for EF-Tu hastens ribosomal incorporation of unnatural amino acids.

    PubMed

    Ieong, Ka-Weng; Pavlov, Michael Y; Kwiatkowski, Marek; Ehrenberg, Måns; Forster, Anthony C

    2014-05-01

    There is evidence that tRNA bodies have evolved to reduce differences between aminoacyl-tRNAs in their affinity to EF-Tu. Here, we study the kinetics of incorporation of L-amino acids (AAs) Phe, Ala allyl-glycine (aG), methyl-serine (mS), and biotinyl-lysine (bK) using a tRNA(Ala)-based body (tRNA(AlaB)) with a high affinity for EF-Tu. Results are compared with previous data on the kinetics of incorporation of the same AAs using a tRNA(PheB) body with a comparatively low affinity for EF-Tu. All incorporations exhibited fast and slow phases, reflecting the equilibrium fraction of AA-tRNA in active ternary complex with EF-Tu:GTP before the incorporation reaction. Increasing the concentration of EF-Tu increased the amplitude of the fast phase and left its rate unaltered. This allowed estimation of the affinity of each AA-tRNA to EF-Tu:GTP during translation, showing about a 10-fold higher EF-Tu affinity for AA-tRNAs formed from the tRNA(AlaB) body than from the tRNA(PheB) body. At ∼1 µM EF-Tu, tRNA(AlaB) conferred considerably faster incorporation kinetics than tRNA(PheB), especially in the case of the bulky bK. In contrast, the swap to the tRNA(AlaB) body did not increase the fast phase fraction of N-methyl-Phe incorporation, suggesting that the slow incorporation of N-methyl-Phe had a different cause than low EF-Tu:GTP affinity. The total time for AA-tRNA release from EF-Tu:GDP, accommodation, and peptidyl transfer on the ribosome was similar for the tRNA(AlaB) and tRNA(PheB) bodies. We conclude that a tRNA body with high EF-Tu affinity can greatly improve incorporation of unnatural AAs in a potentially generalizable manner.

  7. A tRNA body with high affinity for EF-Tu hastens ribosomal incorporation of unnatural amino acids

    PubMed Central

    Ieong, Ka-Weng; Pavlov, Michael Y.; Kwiatkowski, Marek; Ehrenberg, Måns; Forster, Anthony C.

    2014-01-01

    There is evidence that tRNA bodies have evolved to reduce differences between aminoacyl-tRNAs in their affinity to EF-Tu. Here, we study the kinetics of incorporation of L-amino acids (AAs) Phe, Ala allyl-glycine (aG), methyl-serine (mS), and biotinyl-lysine (bK) using a tRNAAla-based body (tRNAAlaB) with a high affinity for EF-Tu. Results are compared with previous data on the kinetics of incorporation of the same AAs using a tRNAPheB body with a comparatively low affinity for EF-Tu. All incorporations exhibited fast and slow phases, reflecting the equilibrium fraction of AA-tRNA in active ternary complex with EF-Tu:GTP before the incorporation reaction. Increasing the concentration of EF-Tu increased the amplitude of the fast phase and left its rate unaltered. This allowed estimation of the affinity of each AA-tRNA to EF-Tu:GTP during translation, showing about a 10-fold higher EF-Tu affinity for AA-tRNAs formed from the tRNAAlaB body than from the tRNAPheB body. At ∼1 µM EF-Tu, tRNAAlaB conferred considerably faster incorporation kinetics than tRNAPheB, especially in the case of the bulky bK. In contrast, the swap to the tRNAAlaB body did not increase the fast phase fraction of N-methyl-Phe incorporation, suggesting that the slow incorporation of N-methyl-Phe had a different cause than low EF-Tu:GTP affinity. The total time for AA-tRNA release from EF-Tu:GDP, accommodation, and peptidyl transfer on the ribosome was similar for the tRNAAlaB and tRNAPheB bodies. We conclude that a tRNA body with high EF-Tu affinity can greatly improve incorporation of unnatural AAs in a potentially generalizable manner. PMID:24671767

  8. Induction of eEF2-specific antitumor CTL responses in vivo by vaccination with eEF2-derived 9mer-peptides.

    PubMed

    Nakajima, Hiroko; Murakami, Yui; Morii, Eiichi; Akao, Toshiki; Tatsumi, Naoya; Odajima, Satoko; Fukuda, Mari; Machitani, Takao; Iwai, Miki; Kawata, Sayo; Hojo, Nozomi; Oka, Yoshihiro; Sugiyama, Haruo; Oji, Yusuke

    2016-04-01

    Eukaryotic elongation factor 2 (eEF2) is an essential factor for protein synthesis. Previous studies have shown that the eEF2 gene was overexpressed and plays an oncogenic role in various types of cancers and that eEF2 gene product elicited both humoral immune responses to produce eEF2-specific IgG autoantibody in cancer-bearing individuals and cellular immune responses to induce eEF2 peptide-specific cytotoxic T lymphocytes (CTLs) in vitro. The purpose of the present study was to induce eEF2-specific, antitumor CTL responses in vivo by vaccination with MHC class I-binding eEF2-derived peptide. First, two mouse MHC class I-restricted eEF2‑derived, 9-mer peptides, EF17 (17-25 aa, ANIRNMSVI) and EF180 (180-188 aa, RIVENVNVI) were identified as eEF2-specific CTL peptides, and mice were vaccinated intradermally eight times with either EF17 or EF180 peptide emulsified with Montanide ISA51 adjuvant. Cytotoxicity assay showed that eEF2-specific CTLs were induced in both EF17‑and EF180‑vaccinated mice, and histological study showed no detectable damage in the organs of these mice. Next, to examine in vivo antitumor effects of eEF2 peptide vaccination in a therapeutic model, mice were vaccinated four times with one each of the two eEF2 peptides at weekly intervals after implantation of eEF2-expressing leukemia cells. The vaccination with eEF2 peptides induced eEF2-specific CTLs and suppressed tumor growth, and disease-free survival was significantly longer in EF180-vaccinated mice compared to control mice. The survival was associated with the robustness of eEF2-specific CTL induction. These results indicate that vaccination with MHC class I-binding eEF2 peptide induced eEF2-targeting, antitumor CTL responses in vivo without damage to normal organs, which provided us a rationale for eEF2 peptide-based cancer immunotherapy.

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

    PubMed Central

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

    2016-01-01

    ABSTRACT EF-G, EF4, and BipA are members of the translation factor family of GTPases with a common ribosome binding mode and GTPase activation mechanism. However, topological variations of shared as well as unique domains ensure different roles played by these proteins during translation. Recent X-ray crystallography and cryo-electron microscopy studies have revealed the structural basis for the involvement of EF-G domain IV in securing the movement of tRNAs and mRNA during translocation as well as revealing how the unique C-terminal domains of EF4 and BipA interact with the ribosome and tRNAs contributing to the regulation of translation under certain conditions. EF-G, EF-4, and BipA are intriguing examples of structural variations on a common theme that results in diverse behavior and function. Structural studies of translational GTPase factors have been greatly facilitated by the use of antibiotics, which have revealed their mechanism of action. PMID:27325008

  10. Request to Monitor EF Eri for Hubble Space Telescope Observations

    NASA Astrophysics Data System (ADS)

    Templeton, Matthew R.

    2008-01-01

    Request to Monitor EF Eri for Hubble Space Telescope Observations January 6, 2008 Dr. Paula Szkody (University of Washington) has requested our help in monitoring the magnetic cataclysmic variable (intermediate polar) EF Eri for upcoming Hubble Space Telescope observations. Confirming observations are requested to ensure that EF Eri is fainter than the safe observing threshold during the HST observing window on 2008 January 17 UT. Time-resolved spectroscopy with the Hubble Space Telescope will be used to investigate the physical origin of ultraviolet variability observed with the GALEX satellite in 2004 (also by Szkody et al). HST can only observe objects fainter than 14th magnitude due to the sensitivity of its instruments, and so observations of EF Eri can only be made if it is known that the star is fainter than those limits. AAVSO observers are asked to begin monitoring this star nightly beginning immediately, and to monitor this object intensely immediately prior to and during the observing window beginning 2008 January 17 01:30 UT and continuing th! rough the closing of the observing window at 2008 January 17 16:15 UT. Both positive and "fainter-than" observations are useful for this campaign. Visual observers are asked to report the faintest comparison star they can reliably detect, with the two nearby stars at m(V) = 14.5 and m(V) = 14.8 being ideal. CCD observers should observe such that they obtain a signal to noise of 10 in the faintest comparison star they can reliably detect in reasonable time. EF Eri is currently around m(V) = 18.1; if you are able to detect EF Eri with S/N of 10 in reasonable time using a CCD, please do so. Filtered CCD observations are not required, but please indicate which if any filters you are using when submitting observations. Please report all observations promptly via WebObs. Please note that EF Eri is approximately 20 arcseconds East of the m(V) = 14.8 comparison star, so please make sure you are measuring (and reporting

  11. Classification and evolution of EF-hand proteins

    NASA Technical Reports Server (NTRS)

    Kawasaki, H.; Nakayama, S.; Kretsinger, R. H.

    1998-01-01

    Forty-five distinct subfamilies of EF-hand proteins have been identified. They contain from two to eight EF-hands that are recognizable by amino acid sequence as being statistically similar to other EF-hand domains. All proteins within one subfamily are congruent to one another, i.e. the dendrogram computed from one of the EF-hand domains is similar, within statistical error, to the dendrogram computed from another(s) domain. Thirteen subfamilies--including Calmodulin, Troponin C, Essential light chain, Regulatory light chain--referred to collectively as CTER, are congruent with one another. They appear to have evolved from a single ur-domain by two cycles of gene duplication and fusion. The subfamilies of CTER subsequently evolved by gene duplications and speciations. The remaining 32 subfamilies do not show such general patterns of congruence; however, some--such as S100, intestinal calcium binding protein (calbindin 9 kd), and trichohylin--do not form congruent clusters of subfamilies. Nearly all of the domains 1, 3, 5, and 7 are most similar to other ODD domains. Correspondingly the EVEN numbered domains of all 45 subfamilies most closely resemble EVEN domains of other subfamilies. Many sequence and chemical characteristics do not show systemic trends by subfamily or species of host organisms; such homoplasy is widespread. Eighteen of the subfamilies are heterochimeric; in addition to multiple EF-hands they contain domains of other evolutionary origins.

  12. Growth and Your 2- to 3-Year-Old

    MedlinePlus

    ... 1- to 2-Year-Old Growth and Your 2- to 3-Year-Old KidsHealth > For Parents > Growth and Your 2- to 3-Year-Old Print A A A ... 4 pounds (1.8 kilograms) and grow about 2 to 3 inches (5 to 8 centimeters). They' ...

  13. Fitness and Your 2- to 3-Year-Old

    MedlinePlus

    ... 1- to 2-Year-Old Fitness and Your 2- to 3-Year-Old KidsHealth > For Parents > Fitness and Your 2- to 3-Year-Old A A A Kids ... skills are appropriate for this age. By age 2, toddlers should be able to walk and run ...

  14. An unusual mechanism for EF-Tu activation during tmRNA-mediated ribosome rescue.

    PubMed

    Miller, Mickey R; Buskirk, Allen R

    2014-02-01

    In bacteria, ribosomes stalled on truncated mRNAs are rescued by transfer-messenger RNA (tmRNA) and its protein partner SmpB. Acting like tRNA, the aminoacyl-tmRNA/SmpB complex is delivered to the ribosomal A site by EF-Tu and accepts the transfer of the nascent polypeptide. Although SmpB binding within the decoding center is clearly critical for licensing tmRNA entry into the ribosome, it is not known how activation of EF-Tu occurs in the absence of a codon-anticodon interaction. A recent crystal structure revealed that SmpB residue His136 stacks on 16S rRNA nucleotide G530, a critical player in the canonical decoding mechanism. Here we use pre-steady-state kinetic methods to probe the role of this interaction in ribosome rescue. We find that although mutation of His136 does not reduce SmpB's affinity for the ribosomal A-site, it dramatically reduces the rate of GTP hydrolysis by EF-Tu. Surprisingly, the same mutation has little effect on the apparent rate of peptide-bond formation, suggesting that release of EF-Tu from the tmRNA/SmpB complex on the ribosome may occur prior to GTP hydrolysis. Consistent with this idea, we find that peptidyl transfer to tmRNA is relatively insensitive to the antibiotic kirromycin. Taken together, our studies provide a model for the initial stages of ribosomal rescue by tmRNA.

  15. An unusual mechanism for EF-Tu activation during tmRNA-mediated ribosome rescue

    PubMed Central

    Miller, Mickey R.; Buskirk, Allen R.

    2014-01-01

    In bacteria, ribosomes stalled on truncated mRNAs are rescued by transfer-messenger RNA (tmRNA) and its protein partner SmpB. Acting like tRNA, the aminoacyl-tmRNA/SmpB complex is delivered to the ribosomal A site by EF-Tu and accepts the transfer of the nascent polypeptide. Although SmpB binding within the decoding center is clearly critical for licensing tmRNA entry into the ribosome, it is not known how activation of EF-Tu occurs in the absence of a codon–anticodon interaction. A recent crystal structure revealed that SmpB residue His136 stacks on 16S rRNA nucleotide G530, a critical player in the canonical decoding mechanism. Here we use pre-steady-state kinetic methods to probe the role of this interaction in ribosome rescue. We find that although mutation of His136 does not reduce SmpB's affinity for the ribosomal A-site, it dramatically reduces the rate of GTP hydrolysis by EF-Tu. Surprisingly, the same mutation has little effect on the apparent rate of peptide-bond formation, suggesting that release of EF-Tu from the tmRNA/SmpB complex on the ribosome may occur prior to GTP hydrolysis. Consistent with this idea, we find that peptidyl transfer to tmRNA is relatively insensitive to the antibiotic kirromycin. Taken together, our studies provide a model for the initial stages of ribosomal rescue by tmRNA. PMID:24345396

  16. 75 FR 27986 - Electronic Filing System-Web (EFS-Web) Contingency Option

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-19

    ... United States Patent and Trademark Office Electronic Filing System--Web (EFS-Web) Contingency Option..., Electronic Filing System--Web (EFS-Web) by providing a new contingency option when the primary portal to EFS-Web has an unscheduled outage. Previously, the entire EFS-Web system is not available to the...

  17. The Development of Inhibitory Control in Early Childhood: A Twin Study from 2-3 Years

    ERIC Educational Resources Information Center

    Gagne, Jeffrey R.; Saudino, Kimberly J.

    2016-01-01

    Parent- and lab-based observer ratings were employed to examine genetic and environmental influences on continuity and change in inhibitory control (IC) in over 300 twin-pairs assessed longitudinally at 2 and 3 years of age. Genetic influences accounted for approximately 60% of the variance in parent-rated IC at both ages. Although many of the…

  18. Evolution of EF-hand calcium-modulated proteins. II. Domains of several subfamilies have diverse evolutionary histories

    NASA Technical Reports Server (NTRS)

    Nakayama, S.; Moncrief, N. D.; Kretsinger, R. H.

    1992-01-01

    In the first report in this series we described the relationships and evolution of 152 individual proteins of the EF-hand subfamilies. Here we add 66 additional proteins and define eight (CDC, TPNV, CLNB, LPS, DGK, 1F8, VIS, TCBP) new subfamilies and seven (CAL, SQUD, CDPK, EFH5, TPP, LAV, CRGP) new unique proteins, which we assume represent new subfamilies. The main focus of this study is the classification of individual EF-hand domains. Five subfamilies--calmodulin, troponin C, essential light chain, regulatory light chain, CDC31/caltractin--and three uniques--call, squidulin, and calcium-dependent protein kinase--are congruent in that all evolved from a common four-domain precursor. In contrast calpain and sarcoplasmic calcium-binding protein (SARC) each evolved from its own one-domain precursor. The remaining 19 subfamilies and uniques appear to have evolved by translocation and splicing of genes encoding the EF-hand domains that were precursors to the congruent eight and to calpain and to SARC. The rates of evolution of the EF-hand domains are slower following formation of the subfamilies and establishment of their functions. Subfamilies are not readily classified by patterns of calcium coordination, interdomain linker stability, and glycine and proline distribution. There are many homoplasies indicating that similar variants of the EF-hand evolved by independent pathways.

  19. Structural proteins of Enterococcus faecalis bacteriophage ϕEf11

    PubMed Central

    Stevens, Roy H.; Zhang, Hongming; Hsiao, Chaiwing; Kachlany, Scott; Tinoco, Eduardo M. B.; DePew, Jessica; Fouts, Derrick E.

    2016-01-01

    ABSTRACT ϕEf11, a temperate Siphoviridae bacteriophage, was isolated by induction from a root canal isolate of Enterococcus faecalis. Sequence analysis suggested that the ϕEf11 genome included a contiguous 8 gene module whose function was related to head structure assembly and another module of 10 contiguous genes whose products were responsible for tail structure assembly. SDS-PAGE analysis of virions of a ϕEf11 derivative revealed 11 well-resolved protein bands. To unify the deduced functional gene assignments emanating from the DNA sequence data, with the structural protein analysis of the purified virus, 6 of the SDS-PAGE bands were subjected to mass spectrometry analysis. 5 of the 6 protein bands analyzed by mass spectrometry displayed identical amino acid sequences to those predicted to be specified by 4 of the ORFs identified in the ϕEf11 genome. These included: ORF8 (predicted scaffold protein), ORF10 (predicted major head protein), ORF15 (predicted major tail protein), and ORF23 (presumptive antireceptor). PMID:28090386

  20. 9 CFR 205.103 - EFS-minimum information.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false EFS-minimum information. 205.103 Section 205.103 Animals and Animal Products GRAIN INSPECTION, PACKERS AND STOCKYARDS ADMINISTRATION (PACKERS AND STOCKYARDS PROGRAMS), DEPARTMENT OF AGRICULTURE CLEAR TITLE-PROTECTION FOR PURCHASERS OF...

  1. 9 CFR 205.203 - Place of filing EFS.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Place of filing EFS. 205.203 Section 205.203 Animals and Animal Products GRAIN INSPECTION, PACKERS AND STOCKYARDS ADMINISTRATION (PACKERS AND STOCKYARDS PROGRAMS), DEPARTMENT OF AGRICULTURE CLEAR TITLE-PROTECTION FOR PURCHASERS OF...

  2. Growth and Your 2- to 3-Year-Old

    MedlinePlus

    ... effective in significantly increasing their final adult height. Constitutional growth delay (delayed puberty). Although they are usually ... about age 2 or 3 years, kids with constitutional growth delay will grow at a normal childhood ...

  3. Parallel re-modeling of EF-1α function: divergent EF-1α genes co-occur with EFL genes in diverse distantly related eukaryotes

    PubMed Central

    2013-01-01

    Background Elongation factor-1α (EF-1α) and elongation factor-like (EFL) proteins are functionally homologous to one another, and are core components of the eukaryotic translation machinery. The patchy distribution of the two elongation factor types across global eukaryotic phylogeny is suggestive of a ‘differential loss’ hypothesis that assumes that EF-1α and EFL were present in the most recent common ancestor of eukaryotes followed by independent differential losses of one of the two factors in the descendant lineages. To date, however, just one diatom and one fungus have been found to have both EF-1α and EFL (dual-EF-containing species). Results In this study, we characterized 35 new EF-1α/EFL sequences from phylogenetically diverse eukaryotes. In so doing we identified 11 previously unreported dual-EF-containing species from diverse eukaryote groups including the Stramenopiles, Apusomonadida, Goniomonadida, and Fungi. Phylogenetic analyses suggested vertical inheritance of both genes in each of the dual-EF lineages. In the dual-EF-containing species we identified, the EF-1α genes appeared to be highly divergent in sequence and suppressed at the transcriptional level compared to the co-occurring EFL genes. Conclusions According to the known EF-1α/EFL distribution, the differential loss process should have occurred independently in diverse eukaryotic lineages, and more dual-EF-containing species remain unidentified. We predict that dual-EF-containing species retain the divergent EF-1α homologues only for a sub-set of the original functions. As the dual-EF-containing species are distantly related to each other, we propose that independent re-modelling of EF-1α function took place in multiple branches in the tree of eukaryotes. PMID:23800323

  4. One-Year Outcomes of Acute Decompensated Systolic Heart Failure in Taiwan: Lessons from TSOC-HFrEF Registry

    PubMed Central

    Chang, Hung-Yu; Wang, Chun-Chieh; Wu, Yen-Wen; Chu, Pao-Hsien; Wu, Chih-Cheng; Hsu, Chih-Hsin; Wen, Ming-Shien; Voon, Wen-Chol; Lin, Wei-Shiang; Huang, Jin-Long; Chen, Shyh-Ming; Yang, Ning-I; Chang, Heng-Chia; Chang, Kuan-Cheng; Sung, Shih-Hsien; Shyu, Kou-Gi; Lin, Jiunn-Lee; Mar, Guang-Yuan; Chan, Kuei-Chuan; Kuo, Jen-Yuan; Wang, Ji-Hung; Chen, Zhih-Cherng; Tseng, Wei-Kung; Cherng, Wen-Jin; Yin, Wei-Hsian

    2017-01-01

    Background Heart failure (HF) is a global health problem. The Taiwan Society of Cardiology-Heart Failure with reduced Ejection Fraction (TSOC-HFrEF) registry was a multicenter, observational survey of patients admitted with HFrEF in Taiwan. The aim of this study was to report the one-year outcome in this large-cohort of hospitalized patients presenting with acute decompensated HFrEF. Methods Patients hospitalized for acute HFrEF were recruited in 21 hospitals in Taiwan. A total of 1509 patients were enrolled into the registry by the end of October 2014. Clinical status, readmission rates and dispensed medications were collected and analyzed 1 year after patient index hospitalization. Results Our study indicated that re-hospitalization rates after HFrEF were 31.9% and 38.5% at 6 and 12 months after index hospitalization, respectively. Of these patients, 9.7% of them were readmitted more than once. At 6 and 12 months after hospital discharge, all-cause mortality rates were 9.5% and 15.9%, respectively, and cardiovascular mortality rates were 6.8% and 10.5%, respectively. Twenty-three patients (1.5%) underwent heart transplantation. During a follow-up period of 1 year, 46.4% of patients were free from mortality, HF re-hospitalization, left ventricular assist device use and heart transplantation. At the conclusion of follow-up, 57.5% of patients were prescribed either with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers; also, 66.3% were prescribed with beta-blockers and 40.8% were prescribed with mineralocorticoid receptor antagonists. Conclusions The TSOC-HFrEF registry showed evidence of suboptimal practice of guideline-directed medical therapy and high HF re-hospitalization rate in Taiwan. The one-year mortality rate of the TSOC-HFrEF registry remained high. Ultimately, our data indicated a need for further improvement in HF care. PMID:28344416

  5. EF-Tu dynamics during pre-translocation complex formation: EF-Tu·GDP exits the ribosome via two different pathways.

    PubMed

    Liu, Wei; Chen, Chunlai; Kavaliauskas, Darius; Knudsen, Charlotte R; Goldman, Yale E; Cooperman, Barry S

    2015-10-30

    The G-protein EF-Tu, which undergoes a major conformational change when EF-Tu·GTP is converted to EF-Tu·GDP, forms part of an aminoacyl(aa)-tRNA·EF-Tu·GTP ternary complex (TC) that accelerates the binding of aa-tRNA to the ribosome during peptide elongation. Such binding, placing a portion of EF-Tu in contact with the GTPase Associated Center (GAC), is followed by GTP hydrolysis and Pi release, and results in formation of a pretranslocation (PRE) complex. Although tRNA movement through the ribosome during PRE complex formation has been extensively studied, comparatively little is known about the dynamics of EF-Tu interaction with either the ribosome or aa-tRNA. Here we examine these dynamics, utilizing ensemble and single molecule assays employing fluorescent labeled derivatives of EF-Tu, tRNA, and the ribosome to measure changes in either FRET efficiency or fluorescence intensity during PRE complex formation. Our results indicate that ribosome-bound EF-Tu separates from the GAC prior to its full separation from aa-tRNA, and suggest that EF-Tu·GDP dissociates from the ribosome by two different pathways. These pathways correspond to either reversible EF-Tu·GDP dissociation from the ribosome prior to the major conformational change in EF-Tu that follows GTP hydrolysis, or irreversible dissociation after or concomitant with this conformational change.

  6. Elucidating the Role of Injury-Induced Electric Fields (EFs) in Regulating the Astrocytic Response to Injury in the Mammalian Central Nervous System.

    PubMed

    Baer, Matthew L; Henderson, Scott C; Colello, Raymond J

    2015-01-01

    Injury to the vertebrate central nervous system (CNS) induces astrocytes to change their morphology, to increase their rate of proliferation, and to display directional migration to the injury site, all to facilitate repair. These astrocytic responses to injury occur in a clear temporal sequence and, by their intensity and duration, can have both beneficial and detrimental effects on the repair of damaged CNS tissue. Studies on highly regenerative tissues in non-mammalian vertebrates have demonstrated that the intensity of direct-current extracellular electric fields (EFs) at the injury site, which are 50-100 fold greater than in uninjured tissue, represent a potent signal to drive tissue repair. In contrast, a 10-fold EF increase has been measured in many injured mammalian tissues where limited regeneration occurs. As the astrocytic response to CNS injury is crucial to the reparative outcome, we exposed purified rat cortical astrocytes to EF intensities associated with intact and injured mammalian tissues, as well as to those EF intensities measured in regenerating non-mammalian vertebrate tissues, to determine whether EFs may contribute to the astrocytic injury response. Astrocytes exposed to EF intensities associated with uninjured tissue showed little change in their cellular behavior. However, astrocytes exposed to EF intensities associated with injured tissue showed a dramatic increase in migration and proliferation. At EF intensities associated with regenerating non-mammalian vertebrate tissues, these cellular responses were even more robust and included morphological changes consistent with a regenerative phenotype. These findings suggest that endogenous EFs may be a crucial signal for regulating the astrocytic response to injury and that their manipulation may be a novel target for facilitating CNS repair.

  7. Elucidating the Role of Injury-Induced Electric Fields (EFs) in Regulating the Astrocytic Response to Injury in the Mammalian Central Nervous System

    PubMed Central

    Baer, Matthew L.; Henderson, Scott C.; Colello, Raymond J.

    2015-01-01

    Injury to the vertebrate central nervous system (CNS) induces astrocytes to change their morphology, to increase their rate of proliferation, and to display directional migration to the injury site, all to facilitate repair. These astrocytic responses to injury occur in a clear temporal sequence and, by their intensity and duration, can have both beneficial and detrimental effects on the repair of damaged CNS tissue. Studies on highly regenerative tissues in non-mammalian vertebrates have demonstrated that the intensity of direct-current extracellular electric fields (EFs) at the injury site, which are 50–100 fold greater than in uninjured tissue, represent a potent signal to drive tissue repair. In contrast, a 10-fold EF increase has been measured in many injured mammalian tissues where limited regeneration occurs. As the astrocytic response to CNS injury is crucial to the reparative outcome, we exposed purified rat cortical astrocytes to EF intensities associated with intact and injured mammalian tissues, as well as to those EF intensities measured in regenerating non-mammalian vertebrate tissues, to determine whether EFs may contribute to the astrocytic injury response. Astrocytes exposed to EF intensities associated with uninjured tissue showed little change in their cellular behavior. However, astrocytes exposed to EF intensities associated with injured tissue showed a dramatic increase in migration and proliferation. At EF intensities associated with regenerating non-mammalian vertebrate tissues, these cellular responses were even more robust and included morphological changes consistent with a regenerative phenotype. These findings suggest that endogenous EFs may be a crucial signal for regulating the astrocytic response to injury and that their manipulation may be a novel target for facilitating CNS repair. PMID:26562295

  8. The multidrug efflux pump MdtEF protects against nitrosative damage during the anaerobic respiration in Escherichia coli.

    PubMed

    Zhang, Yiliang; Xiao, Minfeng; Horiyama, Tsukasa; Zhang, Yinfeng; Li, Xuechen; Nishino, Kunihiko; Yan, Aixin

    2011-07-29

    Drug efflux represents an important protection mechanism in bacteria to withstand antibiotics and environmental toxic substances. Efflux genes constitute 6-18% of all transporters in bacterial genomes, yet the expression and functions of only a handful of them have been studied. Among the 20 efflux genes encoded in the Escherichia coli K-12 genome, only the AcrAB-TolC system is constitutively expressed. The expression, activities, and physiological functions of the remaining efflux genes are poorly understood. In this study we identified a dramatic up-regulation of an additional efflux pump, MdtEF, under the anaerobic growth condition of E. coli, which is independent of antibiotic exposure. We found that expression of MdtEF is up-regulated more than 20-fold under anaerobic conditions by the global transcription factor ArcA, resulting in increased efflux activity and enhanced drug tolerance in anaerobically grown E. coli. Cells lacking mdtEF display a significantly decreased survival rate under the condition of anaerobic respiration of nitrate. Deletion of the genes responsible for the biosynthesis of indole, tnaAB, or replacing nitrate with fumarate as the terminal electron acceptor during the anaerobic respiration restores the decreased survival of ΔmdtEF cells. Moreover, ΔmdtEF cells are susceptible to indole nitrosative derivatives, a class of toxic byproducts formed and accumulated within E. coli when the bacterium respires nitrate under anaerobic conditions. Taken together, we conclude that the multidrug efflux pump MdtEF is up-regulated during the anaerobic physiology of E. coli to protect the bacterium from nitrosative damage through expelling the nitrosyl indole derivatives out of the cells.

  9. Draft Whole-Genome Sequences of Escherichia fergusonii Strains Isolated from Beef Trim (GTA-EF02), Ground Beef (GTA-EF03), and Chopped Kale (GTA-EF04).

    PubMed

    Manninger, Paul; Koziol, Adam; Carrillo, Catherine D

    2016-04-14

    Escherichia fergusoniiis a Gram-negative, rod-shaped, non-spore-forming member of theEnterobacteriaceaefamily and is a bacterium with both biotechnological applications and implication in human clinical disease. Here, we report the draft genome sequences of three isolates ofE. fergusoniifrom beef trim (GTA-EF02), ground beef (GTA-EF03), and chopped kale (GTA-EF04).

  10. Trajectories of Maternal Harsh Parenting in the First 3 Years of Life

    ERIC Educational Resources Information Center

    Kim, Hyoun K.; Pears, Katherine C.; Fisher, Philip A.; Connelly, Cynthia D.; Landsverk, John A.

    2010-01-01

    Objective: Despite the high prevalence rates of harsh parenting, the nature of developmental change in this domain early in life and the factors that contribute to changes in harsh parenting over time are not well understood. The present study examined developmental patterns in maternal harsh parenting behavior from birth to age 3 years and their…

  11. After the storm: personal experiences following an EF4 tornado.

    PubMed

    May, Olivia W; Bigham, Amy B

    2012-08-01

    In April of 2011, an EF4 tornado ripped through the city of Tuscaloosa, AL, leaving in its wake thousands of destroyed homes and businesses. In the hours and days that followed, the health care community of this city, as well as the entire state of Alabama and the southeastern United States, came together to provide care to hundreds of victims, recovery workers, and volunteers.

  12. Similarity Predicts Liking in 3-Year-Old Children

    ERIC Educational Resources Information Center

    Fawcett, Christine A.; Markson, Lori

    2010-01-01

    Two studies examined the influence of similarity on 3-year-old children's initial liking of their peers. Children were presented with pairs of childlike puppets who were either similar or dissimilar to them on a specified dimension and then were asked to choose one of the puppets to play with as a measure of liking. Children selected the puppet…

  13. Developing Dialogic Argumentation Skills: A 3-Year Intervention Study

    ERIC Educational Resources Information Center

    Crowell, Amanda; Kuhn, Deanna

    2014-01-01

    Argumentation is increasingly recognized as a fundamental intellectual skill, but evidence suggests that few adolescents or adults are skilled arguers. This article reports on an extended (3-year, twice weekly) intervention designed to afford dense practice in dialogic argumentation to middle-school students from traditionally academically…

  14. Comparison of the Hypoxia PET Tracer 18F-EF5 to Immunohistochemical Marker EF5 in 3 Different Human Tumor Xenograft Models

    PubMed Central

    Chitneni, Satish K.; Bida, Gerald T.; Zalutsky, Michael R.; Dewhirst, Mark W.

    2014-01-01

    The availability of 18F-labeled and unlabeled 2-(2-nitro-1H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl)-acetamide (EF5) allows for a comparative assessment of tumor hypoxia by PET and immunohistochemistry; however, the combined use of these 2 approaches has not been fully assessed in vivo. The aim of this study was to evaluate 18F-EF5 tumor uptake versus EF5 binding and hypoxia as determined from immunohistochemistry at both macroscopic and microregional levels. Methods Three tumor models— PC3, HCT116, and H460—were evaluated. Tumor-bearing animals were coinjected with 18F-EF5 and EF5 (30 mg/kg), and PET imaging was performed at 2.5 h after injection. After PET imaging and 2 min after Hoechst 33342 injection, the tumors were excised and evaluated for 18F-EF5 distribution by autoradiography and EF5 binding by immunohistochemistry. Additionally, the effects of nonradioactive EF5 (30 mg/kg) on the hypoxia-imaging characteristics of 18F-EF5 were evaluated by comparing the PET data for H460 tumors with those from animals injected with 18F-EF5 alone. Results The uptake of 18F-EF5 in hypoxic tumor regions and the spatial relationship between 18F-EF5 uptake and EF5 binding varied among tumors. H460 tumors showed higher tumor-to-muscle contrast in PET imaging; however, the distribution and uptake of the tracer was less specific for hypoxia in H460 than in HCT116 and PC3 tumors. Correlation analyses revealed that the highest spatial correlation between 18F-EF5 uptake and EF5 binding was in PC3 tumors (r = 0.73 ± 0.02) followed by HCT116 (r = 0.60 ± 0.06) and H460 (r = 0.53 ± 0.10). Uptake and binding of 18F-EF5 and EF5 correlated negatively with Hoechst 33342 perfusion marker distribution in the 3 tumor models. Image contrast and heterogeneous uptake of 18F-EF5 in H460 tumors was significantly higher when the radiotracer was used alone versus in combination with unlabeled EF5 (tumor-to-muscle ratio of 2.51 ± 0.33 vs. 1.71 ± 0.17, P , 0.001). Conclusion The uptake

  15. Assessing functional divergence in EF-1alpha and its paralogs in eukaryotes and archaebacteria.

    PubMed

    Inagaki, Yuji; Blouin, Christian; Susko, Edward; Roger, Andrew J

    2003-07-15

    A number of methods have recently been published that use phylogenetic information extracted from large multiple sequence alignments to detect sites that have changed properties in related protein families. In this study we use such methods to assess functional divergence between eukaryotic EF-1alpha (eEF-1alpha), archaebacterial EF-1alpha (aEF-1alpha) and two eukaryote-specific EF-1alpha paralogs-eukaryotic release factor 3 (eRF3) and Hsp70 subfamily B suppressor 1 (HBS1). Overall, the evolutionary modes of aEF-1alpha, HBS1 and eRF3 appear to significantly differ from that of eEF-1alpha. However, functionally divergent (FD) sites detected between aEF-1alpha and eEF-1alpha only weakly overlap with sites implicated as putative EF-1beta or aminoacyl-tRNA (aa-tRNA) binding residues in EF-1alpha, as expected based on the shared ancestral primary translational functions of these two orthologs. In contrast, FD sites detected between eEF-1alpha and its paralogs significantly overlap with the putative EF-1beta and/or aa-tRNA binding sites in EF-1alpha. In eRF3 and HBS1, these sites appear to be released from functional constraints, indicating that they bind neither eEF-1beta nor aa-tRNA. These results are consistent with experimental observations that eRF3 does not bind to aa-tRNA, but do not support the 'EF-1alpha-like' function recently proposed for HBS1. We re-assess the available genetic data for HBS1 in light of our analyses, and propose that this protein may function in stop codon-independent peptide release.

  16. Assessing functional divergence in EF-1α and its paralogs in eukaryotes and archaebacteria

    PubMed Central

    Inagaki, Yuji; Blouin, Christian; Susko, Edward; Roger, Andrew J.

    2003-01-01

    A number of methods have recently been published that use phylogenetic information extracted from large multiple sequence alignments to detect sites that have changed properties in related protein families. In this study we use such methods to assess functional divergence between eukaryotic EF-1α (eEF-1α), archaebacterial EF-1α (aEF-1α) and two eukaryote-specific EF-1α paralogs—eukaryotic release factor 3 (eRF3) and Hsp70 subfamily B suppressor 1 (HBS1). Overall, the evolutionary modes of aEF-1α, HBS1 and eRF3 appear to significantly differ from that of eEF-1α. However, functionally divergent (FD) sites detected between aEF-1α and eEF-1α only weakly overlap with sites implicated as putative EF-1β or aminoacyl-tRNA (aa-tRNA) binding residues in EF-1α, as expected based on the shared ancestral primary translational functions of these two orthologs. In contrast, FD sites detected between eEF-1α and its paralogs significantly overlap with the putative EF-1β and/or aa-tRNA binding sites in EF-1α. In eRF3 and HBS1, these sites appear to be released from functional constraints, indicating that they bind neither eEF-1β nor aa-tRNA. These results are consistent with experimental observations that eRF3 does not bind to aa-tRNA, but do not support the ‘EF-1α-like’ function recently proposed for HBS1. We re-assess the available genetic data for HBS1 in light of our analyses, and propose that this protein may function in stop codon-independent peptide release. PMID:12853641

  17. Biodistribution and dosimetry of 18F-EF5 in cancer patients with preliminary comparison of 18F-EF5 uptake versus EF5 binding in human glioblastoma

    PubMed Central

    Koch, Cameron J.; Scheuermann, Joshua S.; Divgi, Chaitanya; Judy, Kevin D.; Kachur, Alexander V.; Freifelder, Richard; Reddin, Janet S.; Karp, Joel; Stubbs, James B.; Hahn, Stephen M.; Driesbaugh, Jason; Smith, Deborah; Prendergast, Susan; Evans, Sydney M.

    2010-01-01

    Purpose The primary purpose of this study was to assess the biodistribution and radiation dose resulting from administration of 18F-EF5, a lipophilic 2-nitroimidazole hypoxia marker in ten cancer patients. For three of these patients (with glioblastoma) unlabeled EF5 was additionally administered to allow the comparative assessment of 18F-EF5 tumor uptake with EF5 binding, the latter measured in tumor biopsies by fluorescent anti-EF5 monoclonal antibodies. Methods 18F-EF5 was synthesized by electrophilic addition of 18F2 gas, made by deuteron bombardment of a neon/fluorine mixture in a high-pressure gas target, to an allyl precursor in trifluoroacetic acid at 0° then purified and administered by intravenous bolus. Three whole-body images were collected for each of ten patients using an Allegro (Philips) scanner. Gamma counts were determined in blood, drawn during each image, and urine, pooled as a single sample. PET images were analyzed to determine radiotracer uptake in several tissues and the resulting radiation dose calculated using OLINDA software and standard phantom. For three patients, 21 mg/kg unlabeled EF5 was administered after the PET scans, and tissue samples obtained the next day at surgery to determine EF5 binding using immunohistochemistry techniques (IHC). Results EF5 distributes evenly throughout soft tissue within minutes of injection. Its concentration in blood over the typical time frame of the study (~3.5 h) was nearly constant, consistent with a previously determined EF5 plasma half-life of ~13 h. Elimination was primarily via urine and bile. Radiation exposure from labeled EF5 is similar to other 18F-labeled imaging agents (e.g., FDG and FMISO). In a de novo glioblastoma multiforme patient, focal uptake of 18F-EF5 was confirmed by IHC. Conclusion These results confirm predictions of biodistribution and safety based on EF5's characteristics (high biological stability, high lipophilicity). EF5 is a novel hypoxia marker with unique

  18. Health Blogging and Social Support: A 3-Year Panel Study.

    PubMed

    Keating, David M; Rains, Stephen A

    2015-01-01

    The reported study explored the implications of informal computer-mediated social support for the well-being of individuals coping with illness over the course of 3 years. A panel study was conducted in which respondents--bloggers writing about their experiences living with a health condition--reported on their perceptions of social support and well-being during 2010 and again during 2013. Among respondents who completed both questionnaires (n = 49), increases in support availability from family and friends were related to improvements in bloggers' health self-efficacy as well as improvements in bloggers' loneliness, particularly among those who also experienced increased support availability from blog readers. Increased blog reader support availability was associated with improvements in bloggers' health-related uncertainty. Among respondents who completed the initial questionnaire (N = 121), a survival analysis showed that neither support available from family and friends nor support from blog readers predicted continued health blogging over the 3-year period.

  19. [Dermatobia hominis infection in a 3-year-old child].

    PubMed

    Meissner, M; Kippenberger, S; Valesky, E M; Kaufmann, R

    2012-04-01

    In the context of increasing travel to the tropics, outpatient services are more frequently confronted with non-domestic diseases in Europe. A 3-year old child presented with a painful tumor of the scalp. After incision of the furuncle-like lesion, we extracted a larva of the botfly Dermatobia hominis. Botflies are mainly encountered in Central and South America; they should be considered if patients demonstrate a furuncle-like lesion and have returned from a holiday in these endemic regions.

  20. Multicenter study on the long-term (3-year) efficacy of lanthanum carbonate in dialysis patients.

    PubMed

    Ando, Ryoichi; Yama, Satomi; Ohnishi, Tsuyoshi; Iwamoto, Shunsuke; Kimura, Hitoshi; Chida, Yoshiko; Ishida, Yuji; Yamada, Kouei; Inagaki, Yuichiro; Takayama, Masanobu; Tachibana, Ken; Kikuchi, Kan; Inoue, Atsushi; Ohtsuka, Masakazu

    2014-06-01

    We previously conducted a multicenter study enrolling 101 dialysis patients with hyperphosphatemia in which lanthanum carbonate (LC) was administered for 2 years. In this study, the administration has been continued for an additional year, and we have evaluated the long-term (a total of 3 years) effects of LC. The average serum phosphorus (P) level was 6.05 mg/dL at the start and decreased to 5.84 mg/dL after 3 years, but no significant differences were observed at both points. The average serum corrected calcium (Ca) level significantly reduced after 3 years (P < 0.001). As results of evaluating the achievement rates with the management target values of serum P, Ca and intact parathyroid hormone (PTH) stated in the Japanese guideline, the achievement rates increased after 3 years. From these results, LC is considered to be a useful P binder that can be used for long-term treatment of hyperphosphatemia, without causing a Ca load.

  1. Mapping the human translation elongation factor eEF1H complex using the yeast two-hybrid system.

    PubMed Central

    Mansilla, Francisco; Friis, Irene; Jadidi, Mandana; Nielsen, Karen M; Clark, Brian F C; Knudsen, Charlotte R

    2002-01-01

    In eukaryotes, the eukaryotic translation elongation factor eEF1A responsible for transporting amino-acylated tRNA to the ribosome forms a higher-order complex, eEF1H, with its guanine-nucleotide-exchange factor eEF1B. In metazoans, eEF1B consists of three subunits: eEF1B alpha, eEF1B eta and eEF1B gamma. The first two subunits possess the nucleotide-exchange activity, whereas the role of the last remains poorly defined. In mammals, two active tissue-specific isoforms of eEF1A have been identified. The reason for this pattern of differential expression is unknown. Several models on the basis of in vitro experiments have been proposed for the macromolecular organization of the eEF1H complex. However, these models differ in various aspects. This might be due to the difficulties of handling, particularly the eEF1B beta and eEF1B gamma subunits in vitro. Here, the human eEF1H complex is for the first time mapped using the yeast two-hybrid system, which is a powerful in vivo technique for analysing protein-protein interactions. The following complexes were observed: eEF1A1:eEF1B alpha, eEF1A1:eEF1B beta, eEF1B beta:eEF1B beta, eEF1B alpha:eEF1B gamma, eEF1B beta:eEF1B gamma and eEF1B alpha:eEF1B gamma:eEF1B beta, where the last was observed using a three-hybrid approach. Surprisingly, eEF1A2 showed no or only little affinity for the guanine-nucleotide-exchange factors. Truncated versions of the subunits of eEF1B were used to orientate these subunits within the resulting model. The model unit is a pentamer composed of two molecules of eEF1A, each interacting with either eEF1B alpha or eEF1B beta held together by eEF1B gamma. These units can dimerize via eEF1B beta. Our model is compared with other models, and structural as well as functional aspects of the model are discussed. PMID:11985494

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

    PubMed

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

    1993-04-26

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

  3. [The EFS metrology: From the production to the reason].

    PubMed

    Reifenberg, J-M; Riout, E; Leroy, A; Begue, S

    2014-06-01

    In order to answer statutory requirements and to anticipate the future needs and standards, the EFS is committed, since a few years, in a process of harmonization of its metrology function. In particular, the institution has opted for the skills development by internalizing the metrological traceability of the main critical quantities (temperature, volumetric) measurements. The development of metrology so resulted in a significant increase in calibration and testing activities. Methods are homogenized and improved through accreditations. The investment strategies are based on more and more demanding specifications. The performance of the equipments is better known and mastered. Technical expertise and maturity of the national metrology function today are assets to review in more informed ways the appropriateness of the applied periodicities. Analysis of numerous information and data in the calibration and testing reports could be pooled and operated on behalf of the unique establishment. The objective of this article is to illustrate these reflections with a few examples from of a feedback of the EFS Pyrénées Méditerranée. The analysis of some methods of qualification, the exploitation of the historical metrology in order to quantify the risk of non-compliance, and to adapt the control strategy, analysis of the criticality of an instrument in a measurement process, risk analyses are tools that deserve to be more widely exploited for that discipline wins in efficiency at the national level.

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

    PubMed

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

    2016-03-21

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

  5. Blowout Fracture in a 3-Year-Old

    PubMed Central

    Pluijmers, Britt I.; Koudstaal, Maarten J.; Paridaens, Dion; van der Wal, Karel G.H.

    2013-01-01

    A 3-year-old patient was referred to the oral and maxillofacial department with a fracture of the orbital floor. Due to the lack of clinical symptoms, a conservative approach was chosen. After 3 weeks, an enophthalmos developed. The orbital floor reconstruction was successfully performed through a transconjunctival approach. This case highlights the rarity of pure blowout fractures in young children. The specific presentation and diagnostics of orbital floor fractures in children and the related surgical planning and intervention are discussed. PMID:24436749

  6. Pulmonary nocardiosis in a 3-year-old child

    PubMed Central

    Holdaway, M. D.; Kennedy, J.; Ashcroft, T.; Kay-Butler, J. J.

    1967-01-01

    Until 1960, 179 cases of infection with Nocardia asteroides had been described in the world literature. Seventeen cases in children were reported by 1963. The organism is a common saprophyte in nature with probably a world-wide distribution. Infection can be primary but is more common in patients with underlying malignancy, auto-immune disease or preceding tuberculosis. Sulphonamides, particularly sulphadiazine, are the drugs of choice in treatment; the value of antibiotics is less clearly established. The indications for surgical treatment have not yet been defined. We record a further case of primary pulmonary nocardiosis in a 3-year-old child. Images PMID:6035802

  7. Cryoplasty Versus Conventional Angioplasty in Femoropopliteal Arterial Recanalization: 3-Year Analysis of Reintervention-Free Survival by Treatment Received

    SciTech Connect

    Diaz, Maria Lourdes; Urtasun, Fermin Barberena, Javier; Aranzadi, Carlos; Guillen-Grima, Francisco; Bilbao, Jose Ignacio

    2011-10-15

    Purpose: To compare long-term efficacy of cryoplasty therapy versus conventional angioplasty in the treatment of peripheral arterial atherosclerotic stenosis on the basis of our 3-year clinical experience. Materials and Methods: From January 2006 to December 2008, a total of 155 patients with 192 lesions of the femoropopliteal sector were randomized to receive either cryoplasty or conventional balloon angioplasty. The primary study end point was lesion target patency. Follow-up with clinical evaluation of patient's symptoms, ankle-brachial index, and Doppler ultrasound was scheduled at 1, 6, 9, 12, 24, and 36 months. Results: For the cryoplasty group (n = 86), technical immediate success was achieved in 74.4% of lesions. Rate of significant dissection was 13.5% and rate of stent placement of 22%. In the long term, target lesion patency rate at 6 months was 59.4%, with rates of 55.9, 52.6, and 49.1% at 1, 2, and 3 years, respectively. For the conventional angioplasty group (n = 69), the immediate technical success rate was 83.7%. Rate of significant dissection was 19%, and rate of stent placement was 72.9%. Patency rates at 6 months and at 1, 2, and 3 years were 71.5, 61.2, 60, and 56%, respectively. Conclusion: Compared with conventional angioplasty, cryoplasty showed good immediate success rates with lower stent placement rates. During the 3-year follow-up, patency rates tended to equalize between the two modalities.

  8. Differential Responses of Post-Exercise Recovery of Leg Blood Flow and Oxygen Uptake Kinetics in HFpEF versus HFrEF

    PubMed Central

    Thompson, Richard B.; Pagano, Joseph J.; Mathewson, Kory W.; Paterson, Ian; Dyck, Jason R.; Kitzman, Dalane W.; Haykowsky, Mark J.

    2016-01-01

    The goals of the current study were to compare leg blood flow, oxygen extraction and oxygen uptake (VO2) after constant load sub-maximal unilateral knee extension (ULKE) exercise in patients with heart failure with reduced ejection fraction (HFrEF) compared to those with preserved ejection fraction (HFpEF). Previously, it has been shown that prolonged whole body VO2 recovery kinetics are directly related to disease severity and all-cause mortality in HFrEF patients. To date, no study has simultaneously measured muscle-specific blood flow and oxygen extraction post exercise recovery kinetics in HFrEF or HFpEF patients; therefore it is unknown if muscle VO2 recovery kinetics, and more specifically, the recovery kinetics of blood flow and oxygen extraction at the level of the muscle, differ between HF phenotypes. Ten older (68±10yrs) HFrEF (n = 5) and HFpEF (n = 5) patients performed sub-maximal (85% of maximal weight lifted during an incremental test) ULKE exercise for 4 minutes. Femoral venous blood flow and venous O2 saturation were measured continuously from the onset of end-exercise, using a novel MRI method, to determine off-kinetics (mean response times, MRT) for leg VO2 and its determinants. HFpEF and HFrEF patients had similar end-exercise leg blood flow (1.1±0.6 vs. 1.2±0.6 L/min, p>0.05), venous saturation (42±12 vs. 41±11%, p>0.05) and VO2 (0.13±0.08 vs. 0.11±0.05 L/min, p>0.05); however HFrEF had significantly delayed recovery MRT for flow (292±135sec. vs 105±63sec., p = 0.004) and VO2 (95±37sec. vs. 47±15sec., p = 0.005) compared to HFpEF. Impaired muscle VO2 recovery kinetics following ULKE exercise differentiated HFrEF from HFpEF patients and suggests distinct underlying pathology and potential therapeutic approaches in these populations. PMID:27701422

  9. Differential Responses of Post-Exercise Recovery of Leg Blood Flow and Oxygen Uptake Kinetics in HFpEF versus HFrEF.

    PubMed

    Thompson, Richard B; Pagano, Joseph J; Mathewson, Kory W; Paterson, Ian; Dyck, Jason R; Kitzman, Dalane W; Haykowsky, Mark J

    2016-01-01

    The goals of the current study were to compare leg blood flow, oxygen extraction and oxygen uptake (VO2) after constant load sub-maximal unilateral knee extension (ULKE) exercise in patients with heart failure with reduced ejection fraction (HFrEF) compared to those with preserved ejection fraction (HFpEF). Previously, it has been shown that prolonged whole body VO2 recovery kinetics are directly related to disease severity and all-cause mortality in HFrEF patients. To date, no study has simultaneously measured muscle-specific blood flow and oxygen extraction post exercise recovery kinetics in HFrEF or HFpEF patients; therefore it is unknown if muscle VO2 recovery kinetics, and more specifically, the recovery kinetics of blood flow and oxygen extraction at the level of the muscle, differ between HF phenotypes. Ten older (68±10yrs) HFrEF (n = 5) and HFpEF (n = 5) patients performed sub-maximal (85% of maximal weight lifted during an incremental test) ULKE exercise for 4 minutes. Femoral venous blood flow and venous O2 saturation were measured continuously from the onset of end-exercise, using a novel MRI method, to determine off-kinetics (mean response times, MRT) for leg VO2 and its determinants. HFpEF and HFrEF patients had similar end-exercise leg blood flow (1.1±0.6 vs. 1.2±0.6 L/min, p>0.05), venous saturation (42±12 vs. 41±11%, p>0.05) and VO2 (0.13±0.08 vs. 0.11±0.05 L/min, p>0.05); however HFrEF had significantly delayed recovery MRT for flow (292±135sec. vs 105±63sec., p = 0.004) and VO2 (95±37sec. vs. 47±15sec., p = 0.005) compared to HFpEF. Impaired muscle VO2 recovery kinetics following ULKE exercise differentiated HFrEF from HFpEF patients and suggests distinct underlying pathology and potential therapeutic approaches in these populations.

  10. α-HCH enantiomer fraction (EF): A novel approach to calculate the ventilation age of water in the Arctic Ocean?

    NASA Astrophysics Data System (ADS)

    Pućko, Monika; Macdonald, Robie W.; Barber, David G.; Rosenberg, Bruno; Gratton, Yves; Stern, Gary A.

    2012-08-01

    α-HCH (hexachlorocyclohexane) and the enantiomeric fraction (EF) of its mirror-image isomers have been determined for water column profiles in the southern Beaufort Sea in 2004 and 2007. Using estimated rates of metabolic degradation, we have applied a simple kinetic model to convert the observed EFs to apparent ventilation ages of the water masses in the study region. We found an age of 1.7 ± 0.1 years for the Polar Mixed Layer (PML), 6.6 ± 0.6 for the core of the Pacific Layer centered at salinity 33.1, and 21.7 ± 0.5 years for the core of the Atlantic Layer identified by a Tmax of ˜0.5°C. These ages are in reasonable accord with other methods used to date water masses in the Arctic Ocean suggesting that α-HCH has an unexploited potential as a dating tool.

  11. The NIMH Child Emotional Faces Picture Set (NIMH-ChEFS): a new set of children's facial emotion stimuli.

    PubMed

    Egger, Helen Link; Pine, Daniel S; Nelson, Eric; Leibenluft, Ellen; Ernst, Monique; Towbin, Kenneth E; Angold, Adrian

    2011-09-01

    With the emergence of new technologies, there has been an explosion of basic and clinical research on the affective and cognitive neuroscience of face processing and emotion perception. Adult emotional face stimuli are commonly used in these studies. For developmental research, there is a need for a validated set of child emotional faces. This paper describes the development of the National Institute of Mental Health Child Emotional Faces Picture Set (NIMH-ChEFS), a relatively large stimulus set with high quality, color images of the emotional faces of children. The set includes 482 photographs of fearful, angry, happy, sad and neutral child faces with two gaze conditions: direct and averted gaze. In this paper we describe the development of the NIMH-ChEFS and data on the set's validity based on ratings by 20 healthy adult raters. Agreement between the a priori emotion designation and the raters' labels was high and comparable with values reported for commonly used adult picture sets. Intensity, representativeness, and composite "goodness" ratings are also presented to guide researchers in their choice of specific stimuli for their studies. These data should give researchers confidence in the NIMH-ChEFS's validity for use in affective and social neuroscience research.

  12. An extracellular glucoamylase produced by endophytic fungus EF6.

    PubMed

    Tangngamsakul, P; Karnchanatat, A; Sihanonth, P; Sangvanich, P

    2011-01-01

    A strain of endophytic fungus EF6 isolated from Thai medicinal plants was found to produce higher levels of extracellular glucoamylase. This strain produced glucoamylase of culture filtrate when grown on 1% soluble starch. The enzyme was purified and characterized. Purification steps involved (NH4)2SO4 precipitation, anion exchange, and gel filtration chromatography. Final purification fold was 14.49 and the yield obtained was 9.15%. The enzyme is monomeric with a molecular mass of 62.2 kDa as estimated by SDS-PAGE, and with a molecular mass of 62.031 kDa estimated by MALDI-TOF spectrometry. The temperature for maximum activity was 60 degrees C. After 30 min for incubation, glucoamylase was found to be stable lower than 50 degrees C. The activity decrease rapidly when residual activity was retained about 45% at 55 degrees C. The pH optimum of the enzyme activity was 6.0, and it was stable over a pH range of 4.0-7.0 at 50 degrees C. The activity of glucoamylase was stimulated by Ca2+, Co2+, Mg2+, Mn2+, glycerol, DMSO, DTT and EDTA, and strongly inhibited by Hg2+. Various types of starch were test, soluble starch proved to be the best substrate for digestion process. The enzyme catalyzes the hydrolysis of soluble starch and maltose as the substrate, the enzyme had Km values of 2.63, and 1.88 mg/ml and Vmax, values of 1.25, and 2.54 U/min/mg protein, and Vmax/Km values of 0.48 and 1.35, respectively. The internal amino acid sequences of endophytic fungus EF6 glucoamylase; RALAN HKQVV DSFRS have similarity to the sequence of the glucoamylase purified form Thermomyces lanuginosus. From all results indicated that this enzyme is a glucoamylase (1,4-alpha-D-glucan glucanohydrolase).

  13. GRB 030329: 3 years of radio afterglow monitoring.

    PubMed

    van der Horst, A J; Kamble, A; Wijers, R A M J; Resmi, L; Bhattacharya, D; Rol, E; Strom, R; Kouveliotou, C; Oosterloo, T; Ishwara-Chandra, C H

    2007-05-15

    Radio observations of gamma-ray burst (GRB) afterglows are essential for our understanding of the physics of relativistic blast waves, as they enable us to follow the evolution of GRB explosions much longer than the afterglows in any other wave band. We have performed a 3-year monitoring campaign of GRB 030329 with the Westerbork Synthesis Radio Telescopes and the Giant Metrewave Radio Telescope. Our observations, combined with observations at other wavelengths, have allowed us to determine the GRB blast wave physical parameters, such as the total burst energy and the ambient medium density, as well as to investigate the jet nature of the relativistic outflow. Further, by modelling the late-time radio light curve of GRB 030329, we predict that the Low-Frequency Array (30-240 MHz) will be able to observe afterglows of similar GRBs, and constrain the physics of the blast wave during its non-relativistic phase.

  14. ISS ECLSS: 3 Years of Logistics for Maintenance

    NASA Technical Reports Server (NTRS)

    Shkedi, Brienne; Thompson, Dean

    2004-01-01

    The International Space Station (ISS) Environmental Control and Life Support System (ECLSS) is designed to be maintainable. During the 3 years since the ISS US Lab became operational, there have been numerous ECLSS Orbital Replacement Units (ORUs) launched and returned to Maintain the ECLSS operation in the US segments. The maintenance logistics have provided tools for maintenance, replaced limited life ORUs and failed ORUs, upgraded ECLSS hardware to improve reliability and placed critical spares onboard prior to need. In most cases, the removed ORUs have been returned for either failure analysis and repair or refurbishment. This paper describes the ECLSS manifesting history and maintenance events and quantifies the numbers of ECLSS items, weights, and volumes.

  15. Extrinsic Rewards Diminish Costly Sharing in 3-Year-Olds.

    PubMed

    Ulber, Julia; Hamann, Katharina; Tomasello, Michael

    2016-07-01

    Two studies investigated the influence of external rewards and social praise in young children's fairness-related behavior. The motivation of ninety-six 3-year-olds' to equalize unfair resource allocations was measured in three scenarios (collaboration, windfall, and dictator game) following three different treatments (material reward, verbal praise, and neutral response). In all scenarios, children's willingness to engage in costly sharing was negatively influenced when they had received a reward for equal sharing during treatment than when they had received praise or no reward. The negative effect of material rewards was not due to subjects responding in kind to their partner's termination of rewards. These results provide new evidence for the intrinsic motivation of prosociality-in this case, costly sharing behavior-in preschool children.

  16. Pipeline for uncoilable or failed aneurysms: 3-year follow-up results.

    PubMed

    Becske, Tibor; Potts, Matthew B; Shapiro, Maksim; Kallmes, David F; Brinjikji, Waleed; Saatci, Isil; McDougall, Cameron G; Szikora, István; Lanzino, Giuseppe; Moran, Christopher J; Woo, Henry H; Lopes, Demetrius K; Berez, Aaron L; Cher, Daniel J; Siddiqui, Adnan H; Levy, Elad I; Albuquerque, Felipe C; Fiorella, David J; Berentei, Zsolt; Marosföi, Miklós; Cekirge, Saruhan H; Nelson, Peter K

    2016-10-14

    OBJECTIVE The long-term effectiveness of endovascular treatment of large and giant wide-neck aneurysms using traditional endovascular techniques has been disappointing, with high recanalization and re-treatment rates. Flow diversion with the Pipeline Embolization Device (PED) has been recently used as a stand-alone therapy for complex aneurysms, showing significant improvement in effectiveness while demonstrating a similar safety profile to stent-supported coil treatment. However, relatively little is known about its long-term safety and effectiveness. Here the authors report on the 3-year safety and effectiveness of flow diversion with the PED in a prospective cohort of patients with large and giant internal carotid artery aneurysms enrolled in the Pipeline for Uncoilable or Failed Aneurysms (PUFS) trial. METHODS The PUFS trial is a prospective study of 107 patients with 109 aneurysms treated with the PED. Primary effectiveness and safety end points were demonstrated based on independently monitored 180-day clinical and angiographic data. Patients were enrolled in a long-term follow-up protocol including 1-, 3-, and 5-year clinical and imaging follow-up. In this paper, the authors report the midstudy (3-year) effectiveness and safety data. RESULTS At 3 years posttreatment, 74 subjects with 76 aneurysms underwent catheter angiography as required per protocol. Overall, complete angiographic aneurysm occlusion was observed in 71 of these 76 aneurysms (93.4% cure rate). Five aneurysms were re-treated, using either coils or additional PEDs, for failure to occlude, and 3 of these 5 were cured by the 3-year follow-up. Angiographic cure with one or two treatments of Pipeline embolization alone was therefore achieved in 92.1%. No recanalization of a previously completely occluded aneurysm was noted on the 3-year angiograms. There were 3 (2.6%) delayed device- or aneurysm-related serious adverse events, none of which led to permanent neurological sequelae. No major or minor

  17. Protein synthesis elongation factor EF-1 alpha expression and longevity in Drosophila melanogaster.

    PubMed Central

    Shikama, N; Ackermann, R; Brack, C

    1994-01-01

    It has been proposed that the decline in protein synthesis observed in aging organisms may result from a decrease in elongation factor EF-1 alpha. Transgenic Drosophila melanogaster flies carrying an additional copy of the EF-1 alpha gene under control of a heat-inducible promoter have an extended lifespan, further indicating that the EF-1 alpha gene may play an important role in determining longevity. To test this hypothesis, we have quantitated EF-1 alpha mRNA, EF-1 alpha protein, and the EF-1 alpha complex-formation activity in these transgenic flies. Furthermore, we have tested whether the transgene construct is functional--i.e., whether transgenic mRNA is induced when flies are grown at higher temperature. The results show that although there is a clear difference in mean lifespan between the EF-1 alpha transgenic (E) flies and the control transgenic (C) flies, E flies do not express more EF-1 alpha protein or mRNA than C flies kept at the same experimental conditions. Although the transgene can be induced when E flies are heat-shocked at 37 degrees C, transgenic mRNA is not detectable in E flies aged at 29 degrees C. In both lines, the loss in catalytic activity with age is the same. We conclude that the E flies examined here do not live longer because of overexpressing the EF-1 alpha gene. Images PMID:8183891

  18. Inhibition by Elongation Factor EF G of Aminoacyl-tRNA Binding to Ribosomes

    PubMed Central

    Cabrer, Bartolomé; Vázquez, David; Modolell, Juan

    1972-01-01

    Elongation factor G (EF G), bound to ribosomes either with GMPPCP or with fusidic acid and GDP, inhibits elongation factor Tu (EF Tu)-dependent binding of Phe-tRNA on the ribosome-poly(U) complex and binding of Ala-tRNA on the initiation complex formed with RNA from bacteriophage R17; GTP hydrolysis associated with Phe-tRNA binding is also inhibited. Moreover, nonenzymic binding of Phe-tRNA at high Mg++ concentration is completely blocked by EF G. Thus, EF G appears to bind at a site that overlaps or interacts with the ribosomal A-site. PMID:4551985

  19. Heart failure preserved ejection fraction (HFpEF): an integrated and strategic review.

    PubMed

    Lekavich, Carolyn L; Barksdale, Debra J; Neelon, Virginia; Wu, Jia-Rong

    2015-11-01

    In the USA, 5.7 million Americans ≥20 years have heart failure (HF) and heart failure preserved ejection fraction (HFpEF) accounts for at least 50 % of all hospital admissions for HF. HFpEF has no single guideline for diagnosis or treatment, the patient population is heterogeneously and inconsistently described, and longitudinal studies are lacking. The primary aims of this manuscript were to present an integrated review of the current state of the science on HFpEF, demonstrate gaps in the literature and provide the rationale for the design and implementation of future research to yield insights into the syndrome of HFpEF. The scientific literature was comprehensively reviewed on HFpEF pathophysiology, patient characteristics, diagnostic criteria, echocardiography biomarkers, treatment approaches and outcomes. Discrepancies in patient characteristics, diagnostic criteria, study methods and echocardiographic biomarkers were identified. This review indicates that no single test or guideline exists for diagnosis or treatment for HFpEF; heterogeneity of the population is complicated by multiple comorbidities that factor into etiology, race and age are likely important factors that define the phenotype, and limited information is available that designates early markers of impending HFpEF. Studies designed and adequately powered to study the impact of race and age along with consistent use of HFpEF diagnostic criteria are critically needed to further incident HFpEF research.

  20. EF24 induces ROS-mediated apoptosis via targeting thioredoxin reductase 1 in gastric cancer cells

    PubMed Central

    Chen, Weiqian; Chen, Xi; Ying, Shilong; Feng, Zhiguo; Chen, Tongke; Ye, Qingqing; Wang, Zhe; Qiu, Chenyu; Yang, Shulin; Liang, Guang

    2016-01-01

    Gastric cancer (GC) is one of the leading causes of cancer mortality in the world, and finding novel agents for the treatment of advanced gastric cancer is of urgent need. Diphenyl difluoroketone (EF24), a molecule having structural similarity to curcumin, exhibits potent anti-tumor activities by arresting cell cycle and inducing apoptosis. Although EF24 demonstrates potent anticancer efficacy in numerous types of human cancer cells, the cellular targets of EF24 have not been fully defined. We report here that EF24 may interact with the thioredoxin reductase 1 (TrxR1), an important selenocysteine (Sec)-containing antioxidant enzyme, to induce reactive oxygen species (ROS)-mediated apoptosis in human gastric cancer cells. By inhibiting TrxR1 activity and increasing intracellular ROS levels, EF24 induces a lethal endoplasmic reticulum stress in human gastric cancer cells. Importantly, knockdown of TrxR1 sensitizes cells to EF24 treatment. In vivo, EF24 treatment markedly reduces the TrxR1 activity and tumor cell burden, and displays synergistic lethality with 5-FU against gastric cancer cells. Targeting TrxR1 with EF24 thus discloses a previously unrecognized mechanism underlying the biological activity of EF24, and reveals that TrxR1 is a good target for gastric cancer therapy. PMID:26919110

  1. Characterization of a helix-loop-helix (EF hand) motif of silver hake parvalbumin isoform B.

    PubMed

    Revett, S P; King, G; Shabanowitz, J; Hunt, D F; Hartman, K L; Laue, T M; Nelson, D J

    1997-11-01

    Parvalbumins are a class of calcium-binding proteins characterized by the presence of several helix-loop-helix (EF-hand) motifs. It is suspected that these proteins evolved via intragene duplication from a single EF-hand. Silver hake parvalbumin (SHPV) consists of three EF-type helix-loop-helix regions, two of which have the ability to bind calcium. The three helix-loop-helix motifs are designated AB, CD, and EF, respectively. In this study, native silver hake parvalbumin isoform B (SHPV-B) has been sequenced by mass spectrometry. The sequence indicates that this parvalbumin is a beta-lineage parvalbumin. SHPV-B was cleaved into two major fragments, consisting of the ABCD and EF regions of the native protein. The 33-amino acid EF fragment (residues 76-108), containing one of the calcium ion binding sites in native SHPV-B, has been isolated and studied for its structural characteristics, ability to bind divalent and trivalent cations, and for its propensity to undergo metal ion-induced self-association. The presence of Ca2+ does not induce significant secondary structure in the EF fragment. However, NMR and CD results indicate significant secondary structure promotion in the EF fragment in the presence of the higher charge-density trivalent cations. Sedimentation equilibrium analysis results show that the EF fragment exists in a monomer-dimer equilibrium when complexed with La3+.

  2. SMOS Instrument Performance and Calibration after 3 Years in Orbit

    NASA Astrophysics Data System (ADS)

    Martin-Neira, Manuel; Corbella, Ignasi; Torres, Francesc; Kainulainen, Juha; Oliva, Roger; Closa, Josep; Cabot, François; Castro, Rita; Barbosa, Jose; Gutierrez, Antonio; Anterrieu, Eric; Tenerelli, Joe; Martin-Porqueras, Fernando; Buenadicha, Guillermo; Delwart, Steven; Crapolicchio, Raffaele; Suess, Martin

    2013-04-01

    ESA's Soil Moisture and Ocean Salinity (SMOS) mission has been in orbit for already over 3 years which has allowed the calibration and data processing team consolidating both the calibration strategy and the Level-1 processor which transforms the raw visibility samples into polarimetric brightness temperature images. The payload on board SMOS, MIRAS, is quite unique in that it is the first microwave radiometer in space ever capable to generate wide field of view images at every snapshot measurement. This means that most of the calibration as well as image processing techniques are being developed for the first time with little heritage from any previous space mission. Issues intrinsically attached to its wide field of view such as spatial ripples across the snapshot images are particular to MIRAS and to no other earlier radiometer. Even the fundamental theory behind the instrument was put at test, first on ground inside an electromagnetic compatibility chamber, and now in orbit when imaging the Cosmic Microwave Background Radiation of the cold sky. A groundbreaking effort is being carried out by the SMOS project team to understand and master all calibration and image reconstruction issues of this novel microwave interferometer payload. MIRAS in-orbit performance is driven by the amplitude of spatial ripples across the image and orbital and seasonal radiometer stability. Spatial ripples are unique to interferometric radiometers and are produced by (a) a limited knowledge of the antenna patterns and, in general, of the model of the instrument, (b) some fundamental limitations related to the inverse problem of image reconstruction in undetermined conditions and (c) subtle data processing inconsistencies which are discovered and corrected. To reduce the spatial ripples sea surface salinity retrievals are performed by first removing the brightness temperature spatial errors using a uniform region of the Pacific Ocean. However soil moisture retrievals cannot benefit of

  3. Spontaneous analog number representations in 3-year-old children.

    PubMed

    Cantlon, Jessica F; Safford, Kelley E; Brannon, Elizabeth M

    2010-03-01

    When enumerating small sets of elements nonverbally, human infants often show a set-size limitation whereby they are unable to represent sets larger than three elements. This finding has been interpreted as evidence that infants spontaneously represent small numbers with an object-file system instead of an analog magnitude system (Feigenson, Dehaene & Spelke, 2004). In contrast, non-human animals and adult humans have been shown to rely on analog magnitudes for representing both small and large numbers (Brannon & Terrace, 1998; Cantlon & Brannon, 2007; Cordes, Gelman, Gallistel & Whalen, 2001). Here we demonstrate that, like adults and non-human animals, children as young as 3 years of age spontaneously employ analog magnitude representations to enumerate both small and large sets. Moreover, we show that children spontaneously attend to numerical value in lieu of cumulative surface area. These findings provide evidence of young children's greater sensitivity to number relative to other quantities and demonstrate continuity in the process they spontaneously recruit to judge small and large values.

  4. A 3-year follow-up of hypertension in Delhi.

    PubMed Central

    Gopinath, N.; Chadha, S. L.; Shekhawat, S.; Tandon, R.

    1994-01-01

    A follow-up study of hypertension was carried out among adults in Delhi 3 years after an initial community-based epidemiological survey of the same population. The treatment and the severity status of 1115 out of 1749 individuals with hypertension detected in the initial survey were compared with those observed in the follow-up. The proportion of treated cases with controlled blood pressure rose from 10.8% to 60.8%. Among the cohort of 3611 subjects aged 25-64 years who were normotensive in the initial survey, 132 new cases of hypertension, were detected. The annual incidence of hypertension was the same in men and women (12.2 per 1000). Diabetes and regular alcohol consumption were significant risk factors for hypertension, being present in 13 and 7 cases, respectively. Electrocardiograms (ECGs) were recorded for 871 of the 1115 cases of hypertension. Abnormal ECGs were exhibited by 307 cases (35.2%), of which 24 (2.7%) had had myocardial infarction, 133 (15.3%) had ischaemic ST-T changes, 54 (6.2%) had left ventricular hypertrophy, and 96 (11.0%) had conduction defects and arrhythmias. PMID:7955019

  5. Acute epididymitis in Greek children: a 3-year retrospective study.

    PubMed

    Sakellaris, George S; Charissis, Giorgos C

    2008-07-01

    The aim of the study was to compare historical features, physical examination findings, and testicular color Doppler ultrasound in pediatric patients with epididymitis compared to testicular torsion and torsion of the appendix testes. A retrospective review of the medical records of 66 boys presenting with clinical aspects of acute scrotum over a 3-year period was performed. Sixty-six patients were included in the study (29 with epididymitis, 8 with testicular torsion and 12 with torsion of the appendix testis, 4 with scrotal abscesses, 5 with scrotal swelling, and 1 with inflamed epididymal cyst). The duration of symptoms ranged from 6 h to 4 days with a peak on the second day. Urine cultures and viral testes were negative in all patients. Color Doppler ultrasound was diagnostic for epididymitis in 28 patients (96.6%). Systemic intravenous antibiotics were given in all 29 patients with epididymitis. No patient showed signs of testicular atrophy in the follow-up. The increasing incidence of epididymitis should question the policy of routine exploration of the acute scrotum in children. The history and physical examination cannot reliably identify those boys who can be managed conservatively. Color Doppler ultrasound is a useful adjunct in the evaluation of the acute scrotum when physical findings are equivocal but it can also be misleading.

  6. TSOC-HFrEF Registry: A Registry of Hospitalized Patients with Decompensated Systolic Heart Failure: Description of Population and Management

    PubMed Central

    Wang, Chun-Chieh; Chang, Hung-Yu; Yin, Wei-Hsian; Wu, Yen-Wen; Chu, Pao-Hsien; Wu, Chih-Cheng; Hsu, Chih-Hsin; Wen, Ming-Shien; Voon, Wen-Chol; Lin, Wei-Shiang; Huang, Jin-Long; Chen, Shyh-Ming; Yang, Ning-I; Chang, Heng-Chia; Chang, Kuan-Cheng; Sung, Shih-Hsien; Shyu, Kou-Gi; Lin, Jiunn-Lee; Mar, Guang-Yuan; Chan, Kuei-Chuan; Kuo, Jen-Yuan; Wang, Ji-Hung; Chen, Zhih-Cherng; Tseng, Wei-Kung; Cherng, Wen-Jin

    2016-01-01

    Introduction Heart failure (HF) is a medical condition with a rapidly increasing incidence both in Taiwan and worldwide. The objective of the TSOC-HFrEF registry was to assess epidemiology, etiology, clinical management, and outcomes in a large sample of hospitalized patients presenting with acute decompensated systolic HF. Methods The TSOC-HFrEF registry was a prospective, multicenter, observational survey of patients presenting to 21 medical centers or teaching hospitals in Taiwan. Hospitalized patients with either acute new-onset HF or acute decompensation of chronic HFrEF were enrolled. Data including demographic characteristics, medical history, primary etiology of HF, precipitating factors for HF hospitalization, presenting symptoms and signs, diagnostic and treatment procedures, in-hospital mortality, length of stay, and discharge medications, were collected and analyzed. Results A total of 1509 patients were enrolled into the registry by the end of October 2014, with a mean age of 64 years (72% were male). Ischemic cardiomyopathy and dilated cardiomyopathy were diagnosed in 44% and 33% of patients, respectively. Coronary artery disease, hypertension, diabetes, and chronic renal insufficiency were the common comorbid conditions. Acute coronary syndrome, non-compliant to treatment, and concurrent infection were the major precipitating factors for acute decompensation. The median length of hospital stay was 8 days, and the in-hospital mortality rate was 2.4%. At discharge, 62% of patients were prescribed either angiotensin-converting enzyme-inhibitors or angiotensin receptor blockers, 60% were prescribed beta-blockers, and 49% were prescribed mineralocorticoid receptor antagonists. Conclusions The TSOC-HFrEF registry provided important insights into the current clinical characteristics and management of hospitalized decompensated systolic HF patients in Taiwan. One important observation was that adherence to guideline-directed medical therapy was suboptimal

  7. Effects of Stimulant Medication on Growth Rates across 3 Years in the MTA Follow-up

    ERIC Educational Resources Information Center

    Swanson, James M.; Elliott, Glen R.; Greenhill, Laurence L.; Wigal, Timothy; Arnold, L. Eugene; Vitiello, Benedetto; Hechtman, Lily; Epstein, Jeffery N.; Pelham, William E.; Abikoff, Howard B.; Newcorn, Jeffrey H.; Molina, Brooke S. G.; Hinshaw, Stephen P.; Wells, Karen C.; Hoza, Betsy; Jensen, Peter S.; Gibbons, Robert D.; Hur, Kwan; Stehli, Annamarie; Davies, Mark; March, John S.; Conners, C. Keith; Caron, Mark; Volkow, Nora D.

    2007-01-01

    Objective: To evaluate the hypothesis of stimulant medication effect on physical growth in the follow-up phase of the Multimodal Treatment Study of Children With ADHD. Method: Naturalistic subgroups were established based on patterns of treatment with stimulant medication at baseline, 14-, 24-, and 36-month assessments: not medicated (n = 65),…

  8. The development of inhibitory control in early childhood: A twin study from 2-3 years

    PubMed Central

    Gagne, Jeffrey R.; Saudino, Kimberly J.

    2015-01-01

    Parent and lab-based observer ratings were employed to examine genetic and environmental influences on continuity and change in inhibitory control (IC) in over 300 twin-pairs assessed longitudinally at 2 and 3 years of age. Genetic influences accounted for approximately 60% of the variance in parent-rated IC at both ages. Although many of the same genetic effects on parent-rated IC were stable across age, there were also novel genetic effects that emerged at age 3 (i.e., genetic factors contributed to both continuity and change in parent ratings of IC). Observed IC displayed a different developmental pattern. Genetic influences were moderate at age 2 (38%) and nonsignificant at age 3 (6%). Change in observed IC across early childhood was due to shared and nonshared environmental factors. Findings indicate that it is important to consider the measurement of IC when interpreting developmental and etiological findings. PMID:26784384

  9. Cercozoa comprises both EF-1α-containing and EFL-containing members.

    PubMed

    Kamikawa, Ryoma; Yabuki, Akinori; Nakayama, Takuro; Ishida, Ken-ichiro; Hashimoto, Tetsuo; Inagaki, Yuji

    2011-01-01

    Elongation factor 1α (EF-1α) and elongation factor-like protein (EFL) are considered to be functionally equivalent proteins involved in peptide synthesis. Eukaryotes can be fundamentally divided into 'EF-1α-containing' and 'EFL-containing' types. Recently, EF-1α and EFL genes have been surveyed across the diversity of eukaryotes to explore the origin and evolution of EFL genes. Although the phylum Cercozoa is a diverse group, gene data for either EFL or EF-1α are absent from all cercozoans except chlorarachniophytes which were previously defined as EFL-containing members. Our survey revealed that two members of the cercozoan subphylum Filosa (Thaumatomastix sp. and strain YPF610) are EFL-containing members. Importantly, we identified EF-1α genes from two members of Filosa (Paracercomonas marina and Paulinella chromatophora) and a member of the other subphylum Endomyxa (Filoreta japonica). All cercozoan EFL homologues could not be recovered as a monophyletic group in maximum-likelihood and Bayesian analyses, suggesting that lateral gene transfer was involved in the EFL evolution in this protist assemblage. In contrast, EF-1α analysis successfully recovered a monophyly of three homologues sampled from the two cercozoan subphyla. Based on the results, we postulate that cercozoan EF-1α genes have been vertically inherited, and the current EFL-containing species may have secondarily lost their EF-1α genes.

  10. Education for Sustainability (EFS): Citizenship Education for Radical Resistance or Cultural Conformity?

    ERIC Educational Resources Information Center

    Tulloch, Lynley

    2009-01-01

    There is little doubt that the use of EFS curricula, resources, and programmes in publicly provided education has been controversial. This paper will examine the dilemmas, for educators involved in EFS, relating to the politics and conservative forces underpinning national curriculum development in a free market capitalist economy such as…

  11. Fruit flies with additional expression of the elongation factor EF-1 alpha live longer.

    PubMed Central

    Shepherd, J C; Walldorf, U; Hug, P; Gehring, W J

    1989-01-01

    In Drosophila melanogaster, the decrease in protein synthesis that accompanies aging is preceded by a decrease in elongation factor EF-1 alpha protein and mRNA. Here we show that Drosophila transformed with a P-element vector containing an EF-1 alpha gene under control of hsp70 regulatory sequences have a longer life-span than control flies. Images PMID:2508089

  12. EF-1[alpha] Is Associated with a Cytoskeletal Network Surrounding Protein Bodies in Maize Endosperm Cells.

    PubMed Central

    Clore, A. M.; Dannenhoffer, J. M.; Larkins, B. A.

    1996-01-01

    By using indirect immunofluorescence and confocal microscopy, we documented changes in the distribution of elongation factor-1[alpha] (EF-1[alpha]), actin, and microtubules during the development of maize endosperm cells. In older interphase cells actively forming starch grains and protein bodies, the protein bodies are enmeshed in EF-1[alpha] and actin and are found juxtaposed with a multidirectional array of microtubules. Actin and EF-1[alpha] appear to exist in a complex, because we observed that the two are colocalized, and treatment with cytochalasin D resulted in the redistribution of EF-1[alpa]. These data suggest that EF-1[alpha] and actin are associated in maize endosperm cells and may help to explain the basis of the correlation we found between the concentration of EF-1[alpha] and lysine content. The data also support the hypothesis that the cytoskeleton plays a role in storage protein deposition. The distributions of EF-1[alpha] actin, and microtubules change during development. We observed that in young cells before the accumulation of starch and storage protein, EF-1[alpha], actin, and microtubules are found mainly in the cell cortex or in association with nuclei. PMID:12239373

  13. 9 CFR 205.202 - “Effective financing statement” or EFS.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false âEffective financing statementâ or EFS. 205.202 Section 205.202 Animals and Animal Products GRAIN INSPECTION, PACKERS AND STOCKYARDS... OF FARM PRODUCTS Interpretive Opinions § 205.202 “Effective financing statement” or EFS. (a) An...

  14. 9 CFR 205.210 - Effect of EFS outside State in which filed.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Effect of EFS outside State in which filed. 205.210 Section 205.210 Animals and Animal Products GRAIN INSPECTION, PACKERS AND STOCKYARDS... OF FARM PRODUCTS Interpretive Opinions § 205.210 Effect of EFS outside State in which filed. (a)...

  15. Borrelia burgdorferi elongation factor EF-Tu is an immunogenic protein during Lyme borreliosis.

    PubMed

    Carrasco, Sebastian E; Yang, Youyun; Troxell, Bryan; Yang, Xiuli; Pal, Utpal; Yang, X Frank

    2015-09-02

    Borrelia burgdorferi, the etiological agent of Lyme disease, does not produce lipopolysaccharide but expresses a large number of lipoproteins on its cell surface. These outer membrane lipoproteins are highly immunogenic and have been used for serodiagnosis of Lyme disease. Recent studies have shown that highly conserved cytosolic proteins such as enolase and elongation factor Tu (EF-Tu) unexpectedly localized on the surface of bacteria including B. burgdorferi, and surface-localized enolase has shown to contribute to the enzootic cycle of B. burgdorferi. In this study, we studied the immunogenicity, surface localization, and function of B. burgdorferi EF-Tu. We found that EF-Tu is highly immunogenic in mice, and EF-Tu antibodies were readily detected in Lyme disease patients. On the other hand, active immunization studies showed that EF-Tu antibodies did not protect mice from infection when challenged with B. burgdorferi via either needle inoculation or tick bites. Borrelial mouse-tick cycle studies showed that EF-Tu antibodies also did not block B. burgdorferi migration and survival in ticks. Consistent with these findings, we found that EF-Tu primarily localizes in the protoplasmic cylinder of spirochetes and is not on the surface of B. burgdorferi. Taken together, our studies suggest that B. burgdorferi EF-Tu is not surfaced exposed, but it is highly immunogenic and is a potential serodiagnostic marker for Lyme borreliosis.

  16. Centers of motion associated with EF-Tu binding to the ribosome.

    PubMed

    Paci, Maxim; Fox, George E

    2016-05-03

    Structural centers of motion (pivot points) in the ribosome have recently been identified by measurement of conformational changes in rRNA resulting from EF-G GTP hydrolysis. This series of measurements is extended here to the ribosome's interactions with the cofactor EF-Tu. Four recent EF-Tu bound ribosome structures were compared to unbound structures. A total of 16 pivots were identified, of which 4 are unique to the EF-Tu interaction. Pivots in the GTPase associated center and the sarcin-ricin loop omitted previously, are found to be mobile in response to both EF-Tu and EF-G binding. Pivots in the intersubunit bridge rRNAs are found to be cofactor specific. Head swiveling motions in the small subunit are observed in the EF-Tu bound structures that were trapped post GTP hydrolysis. As in the case of pivots associated with EF-G, the additional pivots described here are associated with weak points in the rRNA structures such as non-canonical pairs and bulge loops. The combined set of pivots should be regarded as a minimal set. Only several states available to the ribosome have been presented in this work. Future, precise crystal structures in conjunction with experimental data will likely show additional functional pivoting elements in the rRNA.

  17. Two-peptide bacteriocin PlnEF causes cell membrane damage to Lactobacillus plantarum.

    PubMed

    Zhang, Xu; Wang, Yang; Liu, Lei; Wei, Yunlu; Shang, Nan; Zhang, Xiangmei; Li, Pinglan

    2016-02-01

    Biologically active, artificially synthesized two-peptide bacteriocin PlnEF was used to study its mode of action on sensitive bacteria Lactobacillus plantarum pl2. The data obtained showed that PlnEF induced membrane permeabilization, allowing for the efflux of electrolytes, which was evidenced by the increased extracellular conductivity, the dissipation of transmembrane electrical potential and pH gradient, and rapid intracellular ATP depletion after L. plantarum pl2 cells were treated with PlnEF for minutes. Laser confocal microscopy showed that PlnEF accumulated very quickly in L. plantarum pl2 cells and the accumulation of PlnEF caused damage to cell membrane. Scanning electron microscopy and transmission electron microscopy further showed that PlnEF induced morphological changes and structure disruption to L. plantarum pl2 cells, such as the formation of blebs, microspheres, membrane deformation and cell lysis. In summary, the data obtained show that PlnEF caused cell membrane damage to L. plantarum pl2 cells. Our study reveals the antimicrobial mechanism of two-peptide bacteriocin PlnEF against L. plantarum.

  18. Soothing the sleeping giant: improving skeletal muscle oxygen kinetics and exercise intolerance in HFpEF.

    PubMed

    Sarma, Satyam; Levine, Benjamin D

    2015-09-15

    Patients with heart failure with preserved ejection fraction (HFpEF) have similar degrees of exercise intolerance and dyspnea as patients with heart failure with reduced EF (HFrEF). The underlying pathophysiology leading to impaired exertional ability in the HFpEF syndrome is not completely understood, and a growing body of evidence suggests "peripheral," i.e., noncardiac, factors may play an important role. Changes in skeletal muscle function (decreased muscle mass, capillary density, mitochondrial volume, and phosphorylative capacity) are common findings in HFrEF. While cardiac failure and decreased cardiac reserve account for a large proportion of the decline in oxygen consumption in HFrEF, impaired oxygen diffusion and decreased skeletal muscle oxidative capacity can also hinder aerobic performance, functional capacity and oxygen consumption (V̇o2) kinetics. The impact of skeletal muscle dysfunction and abnormal oxidative capacity may be even more pronounced in HFpEF, a disease predominantly affecting the elderly and women, two demographic groups with a high prevalence of sarcopenia. In this review, we 1) describe the basic concepts of skeletal muscle oxygen kinetics and 2) evaluate evidence suggesting limitations in aerobic performance and functional capacity in HFpEF subjects may, in part, be due to alterations in skeletal muscle oxygen delivery and utilization. Improving oxygen kinetics with specific training regimens may improve exercise efficiency and reduce the tremendous burden imposed by skeletal muscle upon the cardiovascular system.

  19. Cloning, expression and functional study of translation elongation factor 2 (EF-2) in zebrafish.

    PubMed

    Zhang, Shu-Hong; Yao, Ji-Hua; Song, Huai-Dong; Wang, Lu; Xue, Jing-Lun

    2006-01-01

    We have identified translation elongation factor 2 (EF-2) in zebrafish (GenBank Accession No. AAQ91234). Analysis of the DNA sequence of zebrafish EF-2 shows that the 2826 bp cDNA spans an open reading frame between nucleotide 55 to 2631 and encodes a protein of 858 amino acids. Zebrafish EF-2 protein shares 92%, 93%, 93% and 92% identity with the corresponding amino acid sequence in human, mouse, Chinese hamster and Gallus EF-2, respectively. Whole-mount in situ hybridization showed that zebrafish EF-2 was a developmentally regulated gene and might play important roles during the early development of zebrafish embryos. Therefore, we further studied the function of EF-2 during early embryogenesis. Using morpholino antisense oligo knockdown assays, anti-MO injected embryos were found to display abnormal development. The yolk balls were larger than normal and the melanophores spreading on their bodies became fewer. Furthermore, their tails were incurvate and their lenses were much smaller than those of the normal embryos. However the EF-2 overexpression data showed that extra EF-2 protein had no obvious effect on zebrafish embryonic development.

  20. Model of EF4-induced ribosomal state transitions and mRNA translocation

    NASA Astrophysics Data System (ADS)

    Xie, Ping

    2014-08-01

    EF4, a highly conserved protein present in bacteria, mitochondria and chloroplasts, can bind to both the posttranslocation and pretranslocation ribosomal complexes. When binding to the posttranslocation state, it catalyzes backward translocation to a pretranslocation state. When binding to the pretranslocation state, it catalyzes transition to another pretranslocation state that is similar and possibly identical to that resulting from the posttranslocation state bound by EF4, and competes with EF-G to regulate the elongation cycle. However, the molecular mechanism on how EF4 induces state transitions and mRNA translocation remains unclear. Here, we present both the model for state transitions induced by EF4 binding to the posttranslocation state and that by EF4 binding to the pretranslocation state, based on which we study the kinetics of EF4-induced state transitions and mRNA translocation, giving quantitative explanations of the available experimental data. Moreover, we present some predicted results on state transitions and mRNA translocation induced by EF4 binding to the pretranslocation state complexed with the mRNA containing a duplex region.

  1. Acute dapsone poisoning in a 3-year-old child: Case report with review of literature

    PubMed Central

    Sunilkumar, Menon Narayanankutty; Ajith, Thekkuttuparambil Ananthanarayanan; Parvathy, Vadakut Krishnan

    2015-01-01

    Dapsone (DDS-diamino diphenyl sulphone) is a sulfone antibiotic being used for a variety of clinical conditions. Poisoning in children by DDS is rarely reported. Poisoning in acute cases will be frequently unrecognized due to relative lack of severe signs and symptoms. Methemoglobinemia is the major life-threatening situation associated with poisoning of DDS. Hence, any delay for medical attention can lead to increased rate of mortality. In this case, we describe acute DDS poisoning in a 3-year-old child and the successful management using intravenous methylene blue. PMID:26488029

  2. Preventing Pregnancy in High School Students: Observations From a 3-Year Longitudinal, Quasi-Experimental Study

    PubMed Central

    Dierschke, Nicole; Lowe, Diana; Plastino, Kristen

    2016-01-01

    Objectives. To assess whether a sexual health education intervention reduces pregnancy rates in high school students. Methods. We performed a secondary analysis of a 3-year quasi-experimental study performed in South Texas from 2011 to 2015 in which 1437 students without a history of pregnancy at baseline were surveyed each fall and spring. Potentially confounding risk factors considered included sexual behaviors, intentions, and demographics. The outcome measure was self-reported pregnancy status for male and female students. We performed analyses for male and female students using separate discrete time-to-event models. Results. We found no difference in pregnancy rates between intervention and comparison students within the first 3 years of high school. Female and male students in the intervention groups had pregnancy hazard ratios of, respectively, 1.62 (95% CI = 0.9, 2.61; P = .1) and 0.78 (95% CI = 0.44, 1.48; P = .4) relative to the comparison groups. Conclusions. The educational intervention had no impact on the pregnancy rate. Social media tools in pregnancy prevention programs should be adaptive to new technologies and rapidly changing adolescent preferences for these services. PMID:27689503

  3. Vascular Calcification in Patients with Nondialysis CKD over 3 Years

    PubMed Central

    Molina, Pablo; Cerverón, M. Jesús; Vila, Rocío; Bover, Jordi; Nieto, Javier; Barril, Guillermina; Martínez-Castelao, Alberto; Fernández, Elvira; Escudero, Verónica; Piñera, Celestino; Adragao, Teresa; Navarro-Gonzalez, Juan F.; Molinero, Luis M.; Castro-Alonso, Cristina; Pallardó, Luis M.; Jamal, Sophie A.

    2015-01-01

    Background and objectives Vascular calcification (VC) is common in CKD, but little is known about its prognostic effect on patients with nondialysis CKD. The prevalence of VC and its ability to predict death, time to hospitalization, and renal progression were assessed. Design, setting, participants, & measurements The Study of Mineral and Bone Disorders in CKD in Spain is a prospective, observational, 3-year follow-up study of 742 patients with nondialysis CKD stages 3–5 from 39 centers in Spain from April to May 2009. VC was assessed using Adragao (AS; x-ray pelvis and hands) and Kauppila (KS; x-ray lateral lumbar spine) scores from 572 and 568 patients, respectively. The primary end point was death. Secondary outcomes were hospital admissions and appearance of a combined renal end point (beginning of dialysis or drop >30% in eGFR). Factors related to VC were assessed by logistic regression analysis. Survival analysis was assessed by Cox proportional models. Results VC was present in 79% of patients and prominent in 47% (AS≥3 or KS>6). Age (odds ratio [OR], 1.05; 95% confidence interval [95% CI], 1.02 to 1.07; P<0.001), phosphorous (OR, 1.68; 95% CI, 1.28 to 2.20; P<0.001), and diabetes (OR, 2.11; 95% CI, 1.32 to 3.35; P=0.002) were independently related to AS≥3. After a median follow-up of 35 months (interquartile range=17–36), there were 70 deaths (10%). After multivariate adjustment for age, smoking, diabetes, comorbidity, renal function, and level of phosphorous, AS≥3 but not KS>6 was independently associated with all-cause (hazard ratio [HR], 2.07; 95% CI, 1.07 to 4.01; P=0.03) and cardiovascular (HR, 3.46; 95% CI, 1.27 to 9.45; P=0.02) mortality as well as a shorter hospitalization event–free period (HR, 1.14; 95% CI, 1.06 to 1.22; P<0.001). VC did not predict renal progression. Conclusions VC is highly prevalent in patients with CKD. VC assessment using AS independently predicts death and time to hospitalization. Therefore, it could be a useful

  4. Deep Space 1 Ion Engine Completed a 3-Year Journey

    NASA Technical Reports Server (NTRS)

    Sovey, James S.; Patterson, Michael J.; Rawlin, Vincent K.; Hamley, John A.

    2001-01-01

    A xenon ion engine and power processor system, which was developed by the NASA Glenn Research Center in partnership with the Jet Propulsion Laboratory and Boeing Electron Dynamic Devices, completed nearly 3 years of operation aboard the Deep Space 1 spacecraft. The 2.3-kW ion engine, which provided primary propulsion and two-axis attitude control, thrusted for more than 16,000 hr and consumed more than 70 kg of xenon propellant. The Deep Space 1 spacecraft was launched on October 24, 1998, to validate 12 futuristic technologies, including the ion-propulsion system. After the technology validation process was successfully completed, the Deep Space 1 spacecraft flew by the small asteroid Braille on July 29, 1999. The final objective of this mission was to encounter the active comet Borrelly, which is about 6 miles long. The ion engine was on a thrusting schedule to navigate the Deep Space 1 spacecraft to within 1400 miles of the comet. Since the hydrazine used for spacecraft attitude control was in short supply, the ion engine also provided two-axis attitude control to conserve the hydrazine supply for the Borrelly encounter. The comet encounter took place on September 22, 2001. Dr. Marc Rayman, project manager of Deep Space 1 at the Jet Propulsion Laboratory said, "Deep Space 1 plunged into the heart of the comet Borrelly and has lived to tell every detail of its spinetingling adventure! The images are even better than the impressive images of comet Halley taken by Europe's Giotto spacecraft in 1986." The Deep Space 1 mission, which successfully tested the 12 high-risk, advanced technologies and captured the best images ever taken of a comet, was voluntarily terminated on December 18, 2001. The successful demonstration of the 2-kW-class ion propulsion system technology is now providing mission planners with off-the-shelf flight hardware. Higher power, next generation ion propulsion systems are being developed for large flagship missions, such as outer planet

  5. A randomized study on migration of the Spectron EF and the Charnley flanged 40 cemented femoral components using radiostereometric analysis at 2 years

    PubMed Central

    2011-01-01

    Background and purpose We performed a randomized study to determine the migration patterns of the Spectron EF femoral stem and to compare them with those of the Charnley stem, which is regarded by many as the gold standard for comparison of implants due to its extensive documentation. Patients and methods 150 patients with a mean age of 70 years were randomized, single-blinded, to receive either a cemented Charnley flanged 40 monoblock, stainless steel, vaquasheen surface femoral stem with a 22.2-mm head (n = 30) or a cemented Spectron EF modular, matte, straight, collared, cobalt-chrome femoral stem with a 28-mm femoral head and a roughened proximal third of the stem (n = 120). The patients were followed with repeated radiostereometric analysis for 2 years to assess migration. Results At 2 years, stem retroversion was 2.3° and 0.7° (p < 0.001) and posterior translation was 0.44 mm and 0.17 mm (p = 0.002) for the Charnley group (n = 26) and the Spectron EF group (n = 74), respectively. Subsidence was 0.26 mm for the Charnley and 0.20 mm for the Spectron EF (p = 0.5). Interpretation The Spectron EF femoral stem was more stable than the Charnley flanged 40 stem in our study when evaluated at 2 years. In a report from the Norwegian arthroplasty register, the Spectron EF stem had a higher revision rate due to aseptic loosening beyond 5 years than the Charnley. Initial stability is not invariably related to good long-term results. Our results emphasize the importance of prospective long-term follow-up of prosthetic implants in clinical trials and national registries and a stepwise introduction of implants. PMID:21895504

  6. A bioactive dental luting cement--its retentive properties and 3-year clinical findings.

    PubMed

    Jefferies, Steven R; Pameijer, Cornelis H; Appleby, David C; Boston, Daniel; Lööf, Jesper

    2013-02-01

    A clinical validation study was conducted to determine the performance of a new bioactive dental cement (Ceramir C&B, Doxa Dental AB) for permanent cementation. The cement is a new formulation class, which is a hybrid material comprised of calcium aluminate and glass-ionomer components. A total of 38 crowns and bridges were cemented in 17 patients; 31 of the abutment teeth were vital and seven were non-vital. Six restorations were bridges with a total of 14 abutment teeth (12 vital/ two non-vital). One fixed splint comprising two abutment teeth was also included. Preparation parameters were recorded, as well as cement characteristics such as working time, setting time, seating characteristics, and ease of cement removal. Baseline data were recorded for the handling of the cement, gingival inflammation, and pre-cementation sensitivity. Post-cementation parameters included post-cementation sensitivity, gingival tissue reaction, marginal integrity, and discoloration. All patients were seen for recall examinations at 30 days and 6 months. Fifteen of 17 subjects and 13 of 17 patients were also available for subsequent comprehensive 1- and 2-year recall examination, and 13 patients were available for a 3-year recall examination. Restorations available for the 3-year recall examination included 14 single-unit full-coverage crown restorations, four three-unit bridges comprising eight abutments, and one two-unit splint. Three-year recall data yielded no loss of retention, no secondary caries, no marginal discolorations, and no subjective sensitivity. All restorations rated excellent for marginal integrity. Average visual analogue scale (VAS) score for tooth sensitivity decreased from 7.63 mm at baseline to 0.44 mm at 6-month recall, 0.20 mm at 1-year recall, and 0.00 mm at 2- and 3-year recall. Average gingival index (GI) score for gingival inflammation decreased from 0.56 at baseline to 0.11 at 6-month recall, 0.16 at 1-year recall, 0.21 at 2-year recall, and 0.07 at 3

  7. [3-year results of clinical and immunological monitoring of patients with multiple sclerosis treated by copaxone].

    PubMed

    Orlova, Iu Iu; Alifirova, V M; Cherdyntseva, N V; Zagrebina, I A; Bychkova, I V

    2005-01-01

    Tipe 1 T-helper cells are of importance in development of multiple sclerosis (MS). Copaxone (TEVA, Israel) is one of the preventive drugs, which modifies T-helpers activity. Thirty-three patients with MS were treated by copaxone for 2 years and 13 patients--for 3 years. Clinical and immunological parameters were examined: amount of CD3+, CD4+, CD8+, CD16+, CD22+, CD95+, CD25+ lymphocytes, HLA-D+ cells, IgG, IgA, IgM and phagocytosis. During the treatment course, mean rate of relapses decreased from the pretreatment value from 1.26 +/- 0.11 to 0.59 +/- 0.11 in the first year and 0.28 +/- 0.07 in the second one. After 3 years no relapses were observed in 13 patients. Relapse rate was the highest in the first 3-6 months. But after 3 months there was an increase of CD22+ cells that persisted for all the period of the study. After a year of the treatment, a level of IgM, IgG, IgA and CD95+ cells has raised significantly, with decreasing of a number of CD4+ and CD8+ cells. The authors suggest that immunological shift is related to mechanism of copaxone action determining its positive effect i.e. reducing of frequency of MS relapses.

  8. Understanding the EF-hand closing pathway using non-biased interatomic potentials.

    PubMed

    Dupuis, L; Mousseau, Normand

    2012-01-21

    The EF-hand superfamily of proteins is characterized by the presence of calcium binding helix-loop-helix structures. Many of these proteins undergo considerable motion responsible for a wide range of properties upon binding but the exact mechanism at the root of this motion is not fully understood. Here, we use an unbiased accelerated multiscale simulation scheme, coupled with two force fields - CHARMM-EEF1 and the extended OPEP - to explore in details the closing pathway, from the unbound holo state to the closed apo state, of two EF-hand proteins, the Calmodulin and Troponin C N-terminal nodules. Based on a number of closing simulations for these two sequences, we show that the EF-hand β-scaffold, identified as crucial by Grabarek for the EF-hand opening driven by calcium binding, is also important in closing the EF-hand. We also show the crucial importance of the phenylalanine situated at the end of first EF-hand helix, and identify an intermediate state modulating its behavior, providing a detailed picture of the closing mechanism for these two representatives of EF-hand proteins.

  9. Understanding the EF-hand closing pathway using non-biased interatomic potentials

    NASA Astrophysics Data System (ADS)

    Dupuis, L.; Mousseau, Normand

    2012-01-01

    The EF-hand superfamily of proteins is characterized by the presence of calcium binding helix-loop-helix structures. Many of these proteins undergo considerable motion responsible for a wide range of properties upon binding but the exact mechanism at the root of this motion is not fully understood. Here, we use an unbiased accelerated multiscale simulation scheme, coupled with two force fields — CHARMM-EEF1 and the extended OPEP — to explore in details the closing pathway, from the unbound holo state to the closed apo state, of two EF-hand proteins, the Calmodulin and Troponin C N-terminal nodules. Based on a number of closing simulations for these two sequences, we show that the EF-hand β-scaffold, identified as crucial by Grabarek for the EF-hand opening driven by calcium binding, is also important in closing the EF-hand. We also show the crucial importance of the phenylalanine situated at the end of first EF-hand helix, and identify an intermediate state modulating its behavior, providing a detailed picture of the closing mechanism for these two representatives of EF-hand proteins.

  10. Dual-Polarimetric Radar-Based Tornado Debris Paths Associated with EF-4 and EF-5 Tornadoes over Northern Alabama During the Historic Outbreak of 27 April 2011

    NASA Technical Reports Server (NTRS)

    Carey, Lawrence D.; Schultz, Christopher J.; Schultz, Elise V.; Petersen, Walter A.; Gatlin, Patrick N.; Knupp, Kevin R.; Molthan, Andrew L.; Darden, Christopher B.

    2011-01-01

    An historic tornado and severe weather outbreak devastated much of the southeastern United States between 25 and 28 April 2011. On 27 April 2011, northern Alabama was particularly hard hit by a large number of tornadoes, including several that reached EF-4 and EF-5 on the Enhanced Fujita damage scale. In northern Alabama alone, there were approximately 100 fatalities and hundreds of more people who were injured or lost their homes during the havoc caused by these violent tornadic storms. Two long-track and violent (EF-4 and EF-5) tornadoes occurred within range of the University of Alabama in Huntsville (UAHuntsville) Advanced Radar for Meteorological and Operational Research (ARMOR, C-band dual-polarimetric). A unique capability of dual-polarimetric radar is the near-real time identification of lofted debris associated with ongoing tornadoes on the ground. The focus of this paper is to analyze the dual-polarimetric radar-inferred tornado debris signatures and identify the associated debris paths of the long-track EF-4 and EF-5 tornadoes near ARMOR. The relative locations of the debris and damage paths for each tornado will be ascertained by careful comparison of the ARMOR analysis with NASA MODIS (Moderate Resolution Imaging Spectroradiometer) and ASTER (Advanced Spaceborne Thermal Emission and Reflection Radiometer) satellite imagery of the tornado damage scenes and the National Weather Service tornado damage surveys. With the ongoing upgrade of the WSR-88D (Weather Surveillance Radar - 1988 Doppler) operational network to dual-polarimetry and a similar process having already taken place or ongoing for many private sector radars, dual-polarimetric radar signatures of tornado debris promise the potential to assist in the situational awareness of government and private sector forecasters and emergency managers during tornadic events. As such, a companion abstract (Schultz et al.) also submitted to this conference explores "The use of dual-polarimetric tornadic

  11. Dual-Polarimetric Radar-Based Tornado Debris Paths Associated with EF-4 and EF-5 Tornadoes over Northern Alabama During the Historic Outbreak of 27 April 2011

    NASA Technical Reports Server (NTRS)

    Carey, Lawrence D.; Schultz, Chrstopher J.; Schultz, Elise V.; Petersen, Walter A.; Gatlin, Patrick N.; Knupp, Kevin R.; Molthan, Andrew L.; Jedlovec, Gary J.; Darden, Christopher B.

    2012-01-01

    An historic tornado and severe weather outbreak devastated much of the southeastern United States between 25 and 28 April 2011. On 27 April 2011, northern Alabama was particularly hard hit by a large number of tornadoes, including several that reached EF-4 and EF-5 on the Enhanced Fujita damage scale. In northern Alabama alone, there were approximately 100 fatalities and hundreds of more people who were injured or lost their homes during the havoc caused by these violent tornadic storms. Two long-track and violent (EF-4 and EF-5) tornadoes occurred within range of the University of Alabama in Huntsville (UAHuntsville) Advanced Radar for Meteorological and Operational Research (ARMOR, C-band dual-polarimetric). A unique capability of dual-polarimetric radar is the near-real time identification of lofted debris associated with ongoing tornadoes on the ground. The focus of this paper is to analyze the dual-polarimetric radar-inferred tornado debris signatures and identify the associated debris paths of the long-track EF-4 and EF-5 tornadoes near ARMOR. The relative locations of the debris and damage paths for each tornado will be ascertained by careful comparison of the ARMOR analysis with NASA MODIS (Moderate Resolution Imaging Spectroradiometer) and ASTER (Advanced Spaceborne Thermal Emission and Reflection Radiometer) satellite imagery of the tornado damage scenes and the National Weather Service tornado damage surveys. With the ongoing upgrade of the WSR-88D (Weather Surveillance Radar 1988 Doppler) operational network to dual-polarimetry and a similar process having already taken place or ongoing for many private sector radars, dual-polarimetric radar signatures of tornado debris promise the potential to assist in the situational awareness of government and private sector forecasters and emergency managers during tornadic events. As such, a companion abstract (Schultz et al.) also submitted to this conference explores The use of dual-polarimetric tornadic debris

  12. Neurodevelopment of children under 3 years of age with Smith-Magenis syndrome.

    PubMed

    Wolters, Pamela L; Gropman, Andrea L; Martin, Staci C; Smith, Michaele R; Hildenbrand, Hanna L; Brewer, Carmen C; Smith, Ann C M

    2009-10-01

    Systematic data regarding early neurodevelopmental functioning in Smith-Magenis syndrome are limited. Eleven children with Smith-Magenis syndrome less than 3 years of age (mean, 19 months; range, 5-34 months) received prospective multidisciplinary assessments using standardized measures. The total sample scored in the moderately to severely delayed range in cognitive functioning, expressive language, and motor skills and exhibited generalized hypotonia, oral-motor abnormalities, and middle ear dysfunction. Socialization skills were average, and significantly higher than daily living, communication, and motor abilities, which were below average. Mean behavior ratings were in the nonautistic range. According to exploratory analyses, the toddler subgroup scored significantly lower than the infant subgroup in cognition, expressive language, and adaptive behavior, suggesting that the toddlers were more delayed than the infants relative to their respective peers. Infants aged approximately 1 year or younger exhibited cognitive, language, and motor skills that ranged from average to delayed, but with age-appropriate social skills and minimal maladaptive behaviors. At ages 2 to 3 years, the toddlers consistently exhibited cognitive, expressive language, adaptive behavior, and motor delays and mildly to moderately autistic behaviors. Combining age groups in studies may mask developmental and behavioral differences. Increased knowledge of these early neurodevelopmental characteristics should facilitate diagnosis and appropriate intervention.

  13. 1-Benzyl-3-cetyl-2-methylimidazolium iodide (NH125) induces phosphorylation of eukaryotic elongation factor-2 (eEF2): a cautionary note on the anticancer mechanism of an eEF2 kinase inhibitor.

    PubMed

    Chen, Zehan; Gopalakrishnan, Sujatha M; Bui, Mai-Ha; Soni, Niru B; Warrior, Usha; Johnson, Eric F; Donnelly, Jennifer B; Glaser, Keith B

    2011-12-23

    Eukaryotic elongation factor-2 kinase (eEF2K) relays growth and stress signals to protein synthesis through phosphorylation and inactivation of eukaryotic elongation factor 2 (eEF2). 1-Benzyl-3-cetyl-2-methylimidazolium iodide (NH125) is a widely accepted inhibitor of mammalian eEF2K and an efficacious anti-proliferation agent against different cancer cells. It implied that eEF2K could be an efficacious anticancer target. However, eEF2K siRNA was ineffective against cancer cells including those sensitive to NH125. To test if pharmacological intervention differs from siRNA interference, we identified a highly selective small molecule eEF2K inhibitor A-484954. Like siRNA, A-484954 had little effect on cancer cell growth. We carefully examined the effect of NH125 and A-484954 on phosphorylation of eEF2, the known cellular substrate of eEF2K. Surprisingly, NH125 increased eEF2 phosphorylation, whereas A-484954 inhibited the phosphorylation as expected for an eEF2K inhibitor. Both A-484954 and eEF2K siRNA inhibited eEF2K and reduced eEF2 phosphorylation with little effect on cancer cell growth. These data demonstrated clearly that the anticancer activity of NH125 was more correlated with induction of eEF2 phosphorylation than inhibition of eEF2K. Actually, induction of eEF2 phosphorylation was reported to correlate with inhibition of cancer cell growth. We compared several known inducers of eEF2 phosphorylation including AMPK activators and an mTOR inhibitor. Interestingly, stronger induction of eEF2 phosphorylation correlated with more effective growth inhibition. We also explored signal transduction pathways leading to NH125-induced eEF2 phosphorylation. Preliminary data suggested that NH125-induced eEF2 phosphorylation was likely mediated through multiple pathways. These observations identified an opportunity for a new multipathway approach to anticancer therapies.

  14. 2ND EF Conference in Turbulent Heat Transfer

    DTIC Science & Technology

    1998-01-01

    Dry test vO0 f? f f’ f _ B. (e) Water...deg C 180 170 180 150 140 130 120 »11° -100 I 80 ; so 70 - Water flow rate: 13 g/s Water flow rate: 27 g/s Dry test f d* .ET 20...Water flow rate: 13 g/s Water flow rate: 27 g/s Dry test -B-GG ^’ .rf*’ BO 80 40 20 0 ’- ?■ (c) Water Injection temperature: 55 dag

  15. Inhibition of eEF2-K by thieno[2,3-b]pyridine analogues.

    PubMed

    Lockman, Jeffrey W; Reeder, Matthew D; Suzuki, Kazuyuki; Ostanin, Kirill; Hoff, Ryan; Bhoite, Leena; Austin, Harry; Baichwal, Vijay; Adam Willardsen, J

    2010-04-01

    Several series of thieno[2-3-b]pyridine analogues were synthesized and screened for inhibitory activity against eukaryotic elongation factor-2 kinase (eEF2-K). Modifications around several regions of the lead molecules were made, with a ring fusion adjacent to the nitrogen on the thienopyridine core being critical for activity. The most active compound 34 shows an IC(50) of 170 nM against eEF2-K in vitro.

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

    PubMed Central

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

    2008-01-01

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

  17. Cleavage of the sarcin–ricin loop of 23S rRNA differentially affects EF-G and EF-Tu binding

    PubMed Central

    García-Ortega, Lucía; Álvarez-García, Elisa; Gavilanes, José G.; Martínez-del-Pozo, Álvaro; Joseph, Simpson

    2010-01-01

    Ribotoxins are potent inhibitors of protein biosynthesis and inactivate ribosomes from a variety of organisms. The ribotoxin α-sarcin cleaves the large 23S ribosomal RNA (rRNA) at the universally conserved sarcin–ricin loop (SRL) leading to complete inactivation of the ribosome and cellular death. The SRL interacts with translation factors that hydrolyze GTP, and it is important for their binding to the ribosome, but its precise role is not yet understood. We studied the effect of α-sarcin on defined steps of translation by the bacterial ribosome. α-Sarcin-treated ribosomes showed no defects in mRNA and tRNA binding, peptide-bond formation and sparsomycin-dependent translocation. Cleavage of SRL slightly affected binding of elongation factor Tu ternary complex (EF-Tu•GTP•tRNA) to the ribosome. In contrast, the activity of elongation factor G (EF-G) was strongly impaired in α-sarcin-treated ribosomes. Importantly, cleavage of SRL inhibited EF-G binding, and consequently GTP hydrolysis and mRNA–tRNA translocation. These results suggest that the SRL is more critical in EF-G than ternary complex binding to the ribosome implicating different requirements in this region of the ribosome during protein elongation. PMID:20215430

  18. A complex distribution of elongation family GTPases EF1A and EFL in basal alveolate lineages.

    PubMed

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

    2014-09-01

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

  19. Dityromycin and GE82832 bind protein S12 and block EF-G catalyzed translocation

    PubMed Central

    Bulkley, David; Brandi, Letizia; Polikanov, Yury S.; Fabbretti, Attilio; O’Connor, Michael; Gualerzi, Claudio O.; Steitz, Thomas A.

    2017-01-01

    Summary The translocation of messenger RNA and transfer RNA through the ribosome is catalyzed by EF-G, a universally conserved GTPase. The mechanism by which the closely related decapeptide antibiotics dityromycin and GE82832 inhibit EF-G-catalyzed translocation is elucidated in this study. Using crystallographic and biochemical experiments we demonstrate that these antibiotics bind to ribosomal protein S12 in solution as well as within the small ribosomal subunit, inducing long-range effects on the ribosomal head. The crystal structure of the antibiotic in complex with the 70S ribosome reveals that the binding involves conserved amino acid residues of S12 whose mutations result in in vitro and in vivo antibiotic resistance and loss of antibiotic binding. The data also suggest that GE82832/dityromycin inhibits EF-G-catalyzed translocation by disrupting a critical contact between EF-G and S12 that is required to stabilize the post-translocational conformation of EF-G, thereby preventing the ribosome-EF-G complex from entering a conformation productive for translocation. PMID:24412368

  20. Molecular Approaches in HFpEF: MicroRNAs and iPSC-Derived Cardiomyocytes.

    PubMed

    Kriegel, Alison J; Gartz, Melanie; Afzal, Muhammad Z; de Lange, Willem J; Ralphe, J Carter; Strande, Jennifer L

    2016-12-28

    Heart failure with preserved left ventricular ejection fraction (HFpEF) has emerged as one of the largest unmet needs in cardiovascular medicine. HFpEF is increasing in prevalence and causes significant morbidity, mortality, and health care resource utilization. Patients have multiple co-morbidities which contribute to the disease complexity. To date, no effective treatment for HFpEF has been identified. The paucity of cardiac biopsies from this patient population and the absence of well-accepted animal models limit our understanding of the underlying molecular mechanisms of HFpEF. In this review, we discuss combining state-of-the-art technologies of microRNA profiling and human induced pluripotent cell-derived cardiomyocytes (iPSC-CMs) in order to uncover novel molecular pathways that may contribute to the development of HFpEF. Here, we focus the advantages and limitations of microRNA profiling and iPSC-CMs as a disease model system to discover molecular mechanisms in HFpEF.

  1. Heat-Killed Enterococcus faecalis EF-2001 Ameliorates Atopic Dermatitis in a Murine Model

    PubMed Central

    Choi, Eun-Ju; Iwasa, Masahiro; Han, Kwon-Il; Kim, Wan-Jae; Tang, Yujiao; Hwang, Young Joung; Chae, Jeong Ryong; Han, Weon Cheol; Shin, Yu-Su; Kim, Eun-Kyung

    2016-01-01

    Recent reports have shown the immunomodulatory effect of heat-killed lactic acid bacteria. Atopic dermatitis (AD) is an allergic skin disease, caused by immune dysregulation among other factors. The aim of this study was to assess the effect of heat-killed Enterococcus faecalis EF-2001 (EF-2001) on AD. We established an in vivo AD model by repeated local exposure of Dermatophagoides farinae extract (DFE; house dust mite extract) and 2,4-dinitrochlorobenzene (DNCB) to the ears of mice. After oral administration of EF-2001 for four weeks, the epidermal and dermal ear thickness, mast cell infiltration, and serum immunoglobulin levels were measured. In addition, the gene expression levels of pathogenic cytokines in the ears, lymph nodes, and splenocytes were assayed. EF-2001 attenuated AD symptoms based on the ear thickness, histopathological analysis, and serum immunoglobulin levels. Moreover, EF-2001 decreased the DFE/DNCB-induced expression of various pathogenic cytokines in the ears, lymph nodes, and splenocytes. These results suggest that EF-2001 has therapeutic potential in the treatment of AD owing to its immunomodulatory effects. PMID:26959058

  2. Heat-Killed Enterococcus faecalis EF-2001 Ameliorates Atopic Dermatitis in a Murine Model.

    PubMed

    Choi, Eun-Ju; Iwasa, Masahiro; Han, Kwon-Il; Kim, Wan-Jae; Tang, Yujiao; Hwang, Young Joung; Chae, Jeong Ryong; Han, Weon Cheol; Shin, Yu-Su; Kim, Eun-Kyung

    2016-03-05

    Recent reports have shown the immunomodulatory effect of heat-killed lactic acid bacteria. Atopic dermatitis (AD) is an allergic skin disease, caused by immune dysregulation among other factors. The aim of this study was to assess the effect of heat-killed Enterococcus faecalis EF-2001 (EF-2001) on AD. We established an in vivo AD model by repeated local exposure of Dermatophagoides farinae extract (DFE; house dust mite extract) and 2,4-dinitrochlorobenzene (DNCB) to the ears of mice. After oral administration of EF-2001 for four weeks, the epidermal and dermal ear thickness, mast cell infiltration, and serum immunoglobulin levels were measured. In addition, the gene expression levels of pathogenic cytokines in the ears, lymph nodes, and splenocytes were assayed. EF-2001 attenuated AD symptoms based on the ear thickness, histopathological analysis, and serum immunoglobulin levels. Moreover, EF-2001 decreased the DFE/DNCB-induced expression of various pathogenic cytokines in the ears, lymph nodes, and splenocytes. These results suggest that EF-2001 has therapeutic potential in the treatment of AD owing to its immunomodulatory effects.

  3. mazEF-mediated programmed cell death in bacteria: "what is this?".

    PubMed

    Ramisetty, Bhaskar Chandra Mohan; Natarajan, Bhargavi; Santhosh, Ramachandran Sarojini

    2015-02-01

    Toxin-antitoxin (TA) systems consist of a bicistronic operon, encoding a toxin and an antitoxin. They are widely distributed in the prokaryotic kingdom, often in multiple numbers. TAs are implicated in contradicting phenomena of persistence and programmed cell death (PCD) in bacteria. mazEF TA system, one of the widely distributed type II toxin-antitoxin systems, is particularly implicated in PCD of Escherichia coli. Nutrient starvation, antibiotic stress, heat shock, DNA damage and other kinds of stresses are shown to elicit mazEF-mediated-PCD. ppGpp and extracellular death factor play a central role in regulating mazEF-mediated PCD. The activation of mazEF system is achieved through inhibition of transcription or translation of mazEF loci. Upon activation, MazF cleaves RNA in a ribosome-independent fashion and subsequent processes result in cell death. It is hypothesized that PCD aids in perseverance of the population during stress; the surviving minority of the cells can scavenge the nutrients released by the dead cells, a kind of "nutritional-altruism." Issues regarding the strains, reproducibility of experimental results and ecological plausibility necessitate speculation. We review the molecular mechanisms of the activation of mazEF TA system, the consequences leading to cell death and the pros and cons of the altruism hypothesis from an ecological perspective.

  4. 1-Benzyl-3-cetyl-2-methylimidazolium iodide (NH125) Induces Phosphorylation of Eukaryotic Elongation Factor-2 (eEF2)

    PubMed Central

    Chen, Zehan; Gopalakrishnan, Sujatha M.; Bui, Mai-Ha; Soni, Niru B.; Warrior, Usha; Johnson, Eric F.; Donnelly, Jennifer B.; Glaser, Keith B.

    2011-01-01

    Eukaryotic elongation factor-2 kinase (eEF2K) relays growth and stress signals to protein synthesis through phosphorylation and inactivation of eukaryotic elongation factor 2 (eEF2). 1-Benzyl-3-cetyl-2-methylimidazolium iodide (NH125) is a widely accepted inhibitor of mammalian eEF2K and an efficacious anti-proliferation agent against different cancer cells. It implied that eEF2K could be an efficacious anticancer target. However, eEF2K siRNA was ineffective against cancer cells including those sensitive to NH125. To test if pharmacological intervention differs from siRNA interference, we identified a highly selective small molecule eEF2K inhibitor A-484954. Like siRNA, A-484954 had little effect on cancer cell growth. We carefully examined the effect of NH125 and A-484954 on phosphorylation of eEF2, the known cellular substrate of eEF2K. Surprisingly, NH125 increased eEF2 phosphorylation, whereas A-484954 inhibited the phosphorylation as expected for an eEF2K inhibitor. Both A-484954 and eEF2K siRNA inhibited eEF2K and reduced eEF2 phosphorylation with little effect on cancer cell growth. These data demonstrated clearly that the anticancer activity of NH125 was more correlated with induction of eEF2 phosphorylation than inhibition of eEF2K. Actually, induction of eEF2 phosphorylation was reported to correlate with inhibition of cancer cell growth. We compared several known inducers of eEF2 phosphorylation including AMPK activators and an mTOR inhibitor. Interestingly, stronger induction of eEF2 phosphorylation correlated with more effective growth inhibition. We also explored signal transduction pathways leading to NH125-induced eEF2 phosphorylation. Preliminary data suggested that NH125-induced eEF2 phosphorylation was likely mediated through multiple pathways. These observations identified an opportunity for a new multipathway approach to anticancer therapies. PMID:22020937

  5. Analysis of transgenic wheat (Triticum aestivum L.) harboring a maize (Zea mays L.) gene for plastid EF-Tu: segregation pattern, expression and effects of the transgene.

    PubMed

    Fu, Jianming; Ristic, Zoran

    2010-06-01

    We previously reported that transgenic wheat (Triticum aestivum L.) carrying a maize (Zea mays L.) gene (Zmeftu1) for chloroplast protein synthesis elongation factor, EF-Tu, displays reduced thermal aggregation of leaf proteins, reduced injury to photosynthetic membranes (thylakoids), and enhanced rate of CO(2) fixation following exposure to heat stress (18 h at 45 degrees C) [Fu et al. in Plant Mol Biol 68:277-288, 2008]. In the current study, we investigated the segregation pattern and expression of the transgene Zmeftu1 and determined the grain yield of transgenic plants after exposure to a brief heat stress (18 h at 45 degrees C). We also assessed thermal aggregation of soluble leaf proteins in transgenic plants, testing the hypothesis that increased levels of EF-Tu will lead to a non-specific protection of leaf proteins against thermal aggregation. The transgenic wheat displayed a single-gene pattern of segregation of Zmeftu1. Zmeftu1 was expressed, and the transgenic plants synthesized and accumulated three anti-EF-Tu cross-reacting polypeptides of similar molecular mass but different pI, suggesting the possibility of posttranslational modification of this protein. The transgenic plants also showed better grain yield after exposure to heat stress compared with their non-transgenic counterparts. Soluble leaf proteins of various molecular masses displayed lower thermal aggregation in transgenic than in non-transgenic wheat. The results suggest that overexpression of chloroplast EF-Tu can be beneficial to wheat tolerance to heat stress. Moreover, the results also support the hypothesis that EF-Tu contributes to heat tolerance by acting as a molecular chaperone and protecting heat-labile proteins from thermal aggregation in a non-specific manner.

  6. Circadian clock regulation of mRNA translation through eukaryotic elongation factor eEF-2

    PubMed Central

    Caster, Stephen Z.; Castillo, Kathrina; Sachs, Matthew S.; Bell-Pedersen, Deborah

    2016-01-01

    The circadian clock has a profound effect on gene regulation, controlling rhythmic transcript accumulation for up to half of expressed genes in eukaryotes. Evidence also exists for clock control of mRNA translation, but the extent and mechanisms for this regulation are not known. In Neurospora crassa, the circadian clock generates daily rhythms in the activation of conserved mitogen-activated protein kinase (MAPK) pathways when cells are grown in constant conditions, including rhythmic activation of the well-characterized p38 osmosensing (OS) MAPK pathway. Rhythmic phosphorylation of the MAPK OS-2 (P-OS-2) leads to temporal control of downstream targets of OS-2. We show that osmotic stress in N. crassa induced the phosphorylation of a eukaryotic elongation factor-2 (eEF-2) kinase, radiation sensitivity complementing kinase-2 (RCK-2), and that RCK-2 is necessary for high-level phosphorylation of eEF-2, a key regulator of translation elongation. The levels of phosphorylated RCK-2 and phosphorylated eEF-2 cycle in abundance in wild-type cells but not in cells deleted for OS-2 or the core clock component FREQUENCY (FRQ). Translation extracts from cells grown in constant conditions show decreased translational activity in the late subjective morning, coincident with the peak in eEF-2 phosphorylation, and rhythmic translation of glutathione S-transferase (GST-3) from constitutive mRNA levels in vivo is dependent on circadian regulation of eEF-2 activity. In contrast, rhythms in phosphorylated eEF-2 levels are not necessary for rhythms in accumulation of the clock protein FRQ, indicating that clock control of eEF-2 activity promotes rhythmic translation of specific mRNAs. PMID:27506798

  7. The MazEF Toxin-Antitoxin System Alters the β-Lactam Susceptibility of Staphylococcus aureus.

    PubMed

    Schuster, Christopher F; Mechler, Lukas; Nolle, Nicoletta; Krismer, Bernhard; Zelder, Marc-Eric; Götz, Friedrich; Bertram, Ralph

    2015-01-01

    Toxin-antitoxin (TA) systems are genetic elements of prokaryotes which encode a stable toxin and an unstable antitoxin that can counteract toxicity. TA systems residing on plasmids are often involved in episomal maintenance whereas those on chromosomes can have multiple functions. The opportunistic pathogen Staphylococcus aureus possesses at least four different families of TA systems but their physiological roles are elusive. The chromosomal mazEF system encodes the RNase toxin MazF and the antitoxin MazE. In the light of ambiguity regarding the cleavage activity, we here verify that MazF specifically targets UACAU sequences in S. aureus in vivo. In a native strain background and under non-stress conditions, cleavage was observed in the absence or presence of mazE. Transcripts of spa (staphylococcal protein A) and rsbW (anti-σB factor) were cut, but translational reporter fusions indicated that protein levels of the encoded products were unaffected. Despite a comparable growth rate as the wild-type, an S. aureus mazEF deletion mutant was more susceptible to β-lactam antibiotics, which suggests that further genes, putatively involved in the antibiotic stress response or cell wall synthesis or turnover, are controlled by this TA system.

  8. The MazEF Toxin-Antitoxin System Alters the β-Lactam Susceptibility of Staphylococcus aureus

    PubMed Central

    Schuster, Christopher F.; Mechler, Lukas; Nolle, Nicoletta; Krismer, Bernhard; Zelder, Marc-Eric; Götz, Friedrich; Bertram, Ralph

    2015-01-01

    Toxin-antitoxin (TA) systems are genetic elements of prokaryotes which encode a stable toxin and an unstable antitoxin that can counteract toxicity. TA systems residing on plasmids are often involved in episomal maintenance whereas those on chromosomes can have multiple functions. The opportunistic pathogen Staphylococcus aureus possesses at least four different families of TA systems but their physiological roles are elusive. The chromosomal mazEF system encodes the RNase toxin MazF and the antitoxin MazE. In the light of ambiguity regarding the cleavage activity, we here verify that MazF specifically targets UACAU sequences in S. aureus in vivo. In a native strain background and under non-stress conditions, cleavage was observed in the absence or presence of mazE. Transcripts of spa (staphylococcal protein A) and rsbW (anti-σB factor) were cut, but translational reporter fusions indicated that protein levels of the encoded products were unaffected. Despite a comparable growth rate as the wild-type, an S. aureus mazEF deletion mutant was more susceptible to β-lactam antibiotics, which suggests that further genes, putatively involved in the antibiotic stress response or cell wall synthesis or turnover, are controlled by this TA system. PMID:25965381

  9. Restrictions on cosmogenic neutrinos and UHECR from Fermi 3 years data

    NASA Astrophysics Data System (ADS)

    Gelmini, Graciela B.; Kalashev, Oleg; Semikoz, Dmitri V.

    2012-07-01

    Ultra-high energy cosmic ray protons accelerated in astrophysical objects produce secondary electromagnetic cascades during propagation in the cosmic microwave and infrared backgrounds. Those cascades contribute to the GeV-TeV diffuse photon flux, measured by Fermi LAT experiment. Recent studies of 3 years of Fermi LAT data have shown that diffuse gamma-ray background at E > 10GeV is about factor of 2 smaller then original one year data. This affects both models of UHECR and secondary cosmogenic neutrino fluxes. We show the allowed range of cosmogenic neutrino fluxes scanning over unknown UHECR parameters such as injected proton maximum energy and power law index, evolution of sources, systematic shift of UHECR energy scale. We consider three evolution models in which the UHECR sources are assumed to have the same evolution of either the star formation rate (SFR), or the gamma-ray burst (GRB) rate, or the active galactic nuclei (AGN) rate in the Universe and found that the last two are disfavored (and in the dip model rejected) by the new VHE gamma-ray background. We show that the largest fluxes predicted in the dip model would be detectable by IceCube in about 10 years of observation and are within the reach of a few years of observation with the ARA project. In the incomplete UHECR model in which protons are assumed to dominate only above 1019 eV, the cosmogenic neutrino fluxes could be a factor of 2 or 3 larger.

  10. Deep Phenotyping of Systemic Arterial Hemodynamics in HFpEF (Part 1): Physiologic and Technical Considerations.

    PubMed

    Chirinos, Julio A

    2017-02-16

    A better understanding of the pathophysiology of heart failure with a preserved left ventricular ejection fraction (HFpEF) is important. Detailed phenotyping of pulsatile hemodynamics has provided important insights into the pathophysiology of left ventricular remodeling and fibrosis, diastolic dysfunction, microvascular disease, and impaired oxygen delivery to peripheral skeletal muscle, all of which contribute to exercise intolerance, the cardinal feature of HFpEF. Furthermore, arterial pulsatile hemodynamic mechanisms likely contribute to the frequent presence of comorbidities, such as renal failure and dementia, in this population. Our therapeutic approach to HFpEF can be enhanced by clinical phenotyping tools with the potential to "segment" this population into relevant pathophysiologic categories or to identify individuals exhibiting prominent specific abnormalities that can be targeted by pharmacologic interventions. This review describes relevant technical and physiologic aspects regarding the deep phenotyping of arterial hemodynamics in HFpEF. In an accompanying review, the potential of this approach to enhance our clinical and therapeutic approach to HFpEF is discussed.

  11. A coupled Bio-EF process for mineralization of the pharmaceuticals furosemide and ranitidine: Feasibility assessment.

    PubMed

    Olvera-Vargas, Hugo; Oturan, Nihal; Buisson, Didier; Oturan, Mehmet A

    2016-07-01

    A coupled Bio-EF treatment has been applied as a reliable process for the degradation of the pharmaceuticals furosemide (FRSM) and ranitidine (RNTD) in aqueous medium, in order to reduce the high energy consumption related to electrochemical technology. In the first stage of this study, electrochemical degradation of the drugs was assessed by the electro-Fenton process (EF) using a BDD/carbon-felt cell. Biodegradability of the drugs solutions was enhanced reaching BOD5/COD ratios close to the biodegradability threshold of 0.4, evidencing the formation of bio-compatible by-products (mainly short-chain carboxylic acids) which are suitable for biological post-treatment. Moreover, toxicity evaluation by the Microtox(®) method revealed that EF pre-treatment was able of detoxifying both, FRSM and RNTD solutions, constituting another indicator of biodegradability of EF treated solutions. In the second stage, electrolyzed solutions were treated by means of an aerobic biological process. A significant part of the short-chain carboxylic acids formed during the electrochemical phase was satisfactorily removed by the used selected microorganisms. The results obtained demonstrate the efficiency and feasibility of the integrated Bio-EF process.

  12. Cloning and expression of translation elongation factor 2 (EF-2) in zebrafish.

    PubMed

    Zhang, Shu-Hong; Yao, Ji-Hua; Song, Huai-Dong; Wang, Lu; Xue, Jing-Lun

    2008-02-01

    We have identified a developmentally regulated gene translation elongation factor 2 (EF-2) in zebrafish (GenBank Accession No. AAQ91234). Analysis of DNA sequence of zebrafish EF-2 shows that the 2826 bp cDNA spans an open reading frame from nucleotide 55 to 2631 and encodes a protein of 858 amino acids. It shares an identity of 92, 93, 93, 92, 79 and 80% in amino acid sequence to human, mouse, Chinese hamster, Gallus gullus, C. elegans and Drosophila EF-2, respectively. Zebrafish EF-2 protein has 16 conserved domains, GTP-binding domain is found in the NH2 terminus, and the ADP-ribosylation domain locates at the COOH terminus. Whole mount in situ hybridization on zebrafish embryos shows that the transcripts of EF-2 gene are detected during the early development of zebrafish embryo and constantly change from 5-somite stage to protruding-mouth stage. It expresses strongly throughout envelope at 5-somite stage. Then the stained cells concentrate strongly in the eyes, brain and muscle tissue. From prim-25 stage the stained cells only appear strongly in the lens and the anterior portion of the cerebellum.

  13. A conserved PUF/Ago/eEF1A complex attenuates translation elongation

    PubMed Central

    Friend, Kyle; Campbell, Zachary T.; Cooke, Amy; Kroll-Conner, Peggy; Wickens, Marvin P.; Kimble, Judith

    2011-01-01

    SUMMARY PUF (Pumilio/FBF) RNA-binding proteins and Argonaute (Ago) miRNA-binding proteins regulate mRNAs post-transcriptionally, each acting through similar yet distinct mechanisms. Here, we report that PUF and Ago proteins can also function together in a complex with a core translation elongation factor, eEF1A, to repress translation elongation. Both nematode and mammalian PUF/Ago/eEF1A complexes were identified, using co-immunoprecipitation and recombinant protein assays. Nematode CSR-1 (Ago) promotes repression of FBF (PUF) target mRNAs in in vivo assays, and the FBF-1/CSR-1 heterodimer inhibits EFT-3 (eEF1A) GTPase activity in vitro. Mammalian PUM2/Ago/eEF1A inhibits translation of nonadenylated and polyadenylated reporter mRNAs in vitro. This repression occurs after translation initiation and leads to ribosome accumulation within the open reading frame, roughly at the site where the nascent polypeptide emerges from the ribosomal exit tunnel. Together, these data suggest that a conserved PUF/Ago/eEF1A complex attenuates translation elongation. PMID:22231398

  14. EF24 inhibits tumor growth and metastasis via suppressing NF-kappaB dependent pathways in human cholangiocarcinoma

    PubMed Central

    Yin, Da-long; Liang, Ying-jian; Zheng, Tong-sen; Song, Rui-peng; Wang, Jia-bei; Sun, Bo-shi; Pan, Shang-ha; Qu, Lian-dong; Liu, Jia-ren; Jiang, Hong-chi; Liu, Lian-xin

    2016-01-01

    A synthetic monoketone analog of curcumin, termed 3, 5-bis (2-flurobenzylidene) piperidin-4-one (EF24), has been reported to inhibit the growth of a variety of cancer cells both in vitro and in vivo. However, whether EF24 has anticancer effects on cholangiocarcinoma (CCA) cells and the mechanisms remain to be investigated. The aim of our study was to evaluate the molecular mechanisms underlying the anticancer effects of EF24 on CCA tumor growth and metastasis. Cell proliferation, apoptosis, migration, invasion, tumorigenesis and metastasis were examined. EF24 exhibited time- and dose-dependent inhibitory effects on HuCCT-1, TFK-1 and HuH28 human CCA cell lines. EF24 inhibited CCA cell proliferation, migration, and induced G2/M phase arrest. EF24 induced cell apoptosis along with negative regulation of NF-κB- X-linked inhibitor of apoptosis protein (XIAP) signaling pathway. XIAP inhibition by lentivirus mediated RNA interference enhanced EF24-induced apoptosis, while XIAP overexpression reduced it in CCA cells. In vivo, EF24 significantly suppressed the growth of CCA tumor xenografts and tumor metastasis while displaying low toxicity levels. Our findings indicate that EF24 is a potent antitumor agent that inhibits tumor growth and metastasis by inhibiting NF-κB dependent signaling pathways. EF24 may represent a novel approach for CCA treatment. PMID:27571770

  15. Impact of EfOM size on competition in activated carbon adsorption of organic micro-pollutants from treated wastewater.

    PubMed

    Zietzschmann, Frederik; Worch, Eckhard; Altmann, Johannes; Ruhl, Aki Sebastian; Sperlich, Alexander; Meinel, Felix; Jekel, Martin

    2014-11-15

    The competitive impacts of different fractions of wastewater treatment plant effluent organic matter (EfOM) on organic micro-pollutant (OMP) adsorption were investigated. The fractionation was accomplished using separation by nanofiltration (NF). The waters resulting from NF were additionally treated to obtain the same dissolved organic carbon (DOC) concentrations as the initial water. Using size exclusion chromatography (LC-OCD) it could be shown that the NF treatment resulted in an EfOM separation by size. Adsorption tests showed different competitive effects of the EfOM fractions with the OMP. While large EfOM compounds that were retained in NF demonstrated a reduced competition as compared to the raw water, the NF-permeating EfOM compounds showed an increased competition with the majority of the measured OMP. The effects of small size EfOM are particularly negative for OMP which are weak/moderate adsorbates. Adsorption analysis was carried out for the differently fractionized waters. The small sized EfOM contain better adsorbable compounds than the raw water while the large EfOM are less adsorbable. This explains the observed differences in the EfOM competitiveness. The equivalent background compound (EBC) model was applied to model competitive adsorption between OMP and EfOM and showed that the negative impacts of EfOM on OMP adsorption increase with decreasing size of the EfOM fractions. The results suggest that direct competition for adsorption sites on the internal surface of the activated carbon is more substantial than indirect competition due to pore access restriction by blockage. Another explication for reduced competition by large EfOM compounds could be the inability to enter and block the pores due to size exclusion.

  16. Immediate implants and immediate loading in periodontally compromised patients-a 3-year prospective clinical study.

    PubMed

    Alves, Celia Coutinho; Correia, Andre Ricardo; Neves, Manuel

    2010-10-01

    To avoid the necessity of a removable provisional prosthesis, and therefore preserve the patient's functional outcome, esthetics, and quality of life, a clinical protocol was developed to approach periodontally compromised patients presenting a full-arch irreversibly lost dentition: full-arch extraction and immediate replacement with a provisional acrylic resin implant-supported fixed partial denture (FPD). A total of 23 periodontally compromised patients (11 women, 12 men; 4 smokers, 4 controlled diabetics) were included in this study. Pretreatment casts were taken and vertical dimension of occlusion was determined. In most patients, 6 Straumann implants were distributed along the arch according to the surgical guide or bone availability, with the most distal ones in the maxilla slightly tilted so they could emerge more distally. A total of 168 implants (146 Straumann, 10 Nobel Biocare, 8 Biomet 3i, and 4 Lifecore) were placed (83 in the maxilla, 85 in the mandible). Of those in the maxilla, 74 were loaded immediately (implant stability quotient mentor [ISQm] > 70) and 9 placed with delayed loading (ISQm =/< 70). Of the 85 implants placed in the mandible, all were loaded immediately (ISQm > 70). If an FPD had not been fabricated already, impressions were taken during surgery to do so. The prosthesis was then adapted (cemented or screwed) to the 6 implants within the first 48 hours postsurgery. After 2 months, definitive impressions were taken, and a definitive porcelain-fused-to-metal implant-supported 12-element FPD was fabricated and cemented or screwed to all 6 implants. Of the 168 implants, 108 were immediate implants and 159 immediately loaded. Only 2 implants (1 in the mandible, 1 in the maxilla) did not osseointegrate. This yields a 3-year cumulative survival rate of 98.74% (98.65% in the maxilla, 98.82% in the mandible). From a total of 26 immediately loaded prostheses (12 in the maxilla, 14 in the mandible), 6 were cemented and 20 screw-retained. The 3

  17. Electrostatics effects on Ca(2+) binding and conformational changes in EF-hand domains: Functional implications for EF-hand proteins.

    PubMed

    Ababou, Abdessamad; Zaleska, Mariola

    2015-12-01

    Mutations of Gln41 and Lys75 with nonpolar residues in the N-terminal domain of calmodulin (N-Cam) revealed the importance of solvation energetics in conformational change of Ca(2+) sensor EF-hand domains. While in general these domains have polar residues at these corresponding positions yet the extent of their conformational response to Ca(2+) binding and their Ca(2+) binding affinity can be different from N-Cam. Consequently, here we address the charge state of the polar residues at these positions. The results show that the charge state of these polar residues can affect substantially the conformational change and the Ca(2+) binding affinity of our N-Cam variants. Since all the variants kept their conformational activity in the presence of Ca(2+) suggests that the differences observed among them mainly originate from the difference in their molecular dynamics. Hence we propose that the molecular dynamics of Ca(2+) sensor EF-hand domains is a key factor in the multifunctional aspect of EF-hand proteins.

  18. Evolution of EF-hand calcium-modulated proteins. IV. Exon shuffling did not determine the domain compositions of EF-hand proteins

    NASA Technical Reports Server (NTRS)

    Kretsinger, R. H.; Nakayama, S.

    1993-01-01

    In the previous three reports in this series we demonstrated that the EF-hand family of proteins evolved by a complex pattern of gene duplication, transposition, and splicing. The dendrograms based on exon sequences are nearly identical to those based on protein sequences for troponin C, the essential light chain myosin, the regulatory light chain, and calpain. This validates both the computational methods and the dendrograms for these subfamilies. The proposal of congruence for calmodulin, troponin C, essential light chain, and regulatory light chain was confirmed. There are, however, significant differences in the calmodulin dendrograms computed from DNA and from protein sequences. In this study we find that introns are distributed throughout the EF-hand domain and the interdomain regions. Further, dendrograms based on intron type and distribution bear little resemblance to those based on protein or on DNA sequences. We conclude that introns are inserted, and probably deleted, with relatively high frequency. Further, in the EF-hand family exons do not correspond to structural domains and exon shuffling played little if any role in the evolution of this widely distributed homolog family. Calmodulin has had a turbulent evolution. Its dendrograms based on protein sequence, exon sequence, 3'-tail sequence, intron sequences, and intron positions all show significant differences.

  19. An evaluation of the F/FB/EF-111 crew/voice message system

    NASA Astrophysics Data System (ADS)

    Hassoun, John A.; Barnaba, J. M.; Matheson, E. M.

    1989-01-01

    In support of the F/FB/EF-111 Digital Flight Control System Program Office, subjective and performance data were collected in order to provide the government and contractor engineers with information needed in the design of a Voice Message Unit (VMU) interface for the F/FB/EF-111 aircraft. The VMU, one of the new safety of flight systems, is being included as part of the Digital Flight Control Computer. The VMU will be used as a means for alerting crew members to flight critical conditions. The evaluation was comprised of two phases. During the first phase, questionnaire data were collected from a sample of 119 operational F/FB/EF-111 crew members. The second phase of the evaluation involved the mechanization of the VMU interface in an FB-111 simulator, located at the Crew Station Design Facility, for pilots' on-hand experience with the content of the voice messages and the mechanization aspects of the interface.

  20. Interleukin-11 binds specific EF-hand proteins via their conserved structural motifs.

    PubMed

    Kazakov, Alexei S; Sokolov, Andrei S; Vologzhannikova, Alisa A; Permyakova, Maria E; Khorn, Polina A; Ismailov, Ramis G; Denessiouk, Konstantin A; Denesyuk, Alexander I; Rastrygina, Victoria A; Baksheeva, Viktoriia E; Zernii, Evgeni Yu; Zinchenko, Dmitry V; Glazatov, Vladimir V; Uversky, Vladimir N; Mirzabekov, Tajib A; Permyakov, Eugene A; Permyakov, Sergei E

    2017-01-01

    Interleukin-11 (IL-11) is a hematopoietic cytokine engaged in numerous biological processes and validated as a target for treatment of various cancers. IL-11 contains intrinsically disordered regions that might recognize multiple targets. Recently we found that aside from IL-11RA and gp130 receptors, IL-11 interacts with calcium sensor protein S100P. Strict calcium dependence of this interaction suggests a possibility of IL-11 interaction with other calcium sensor proteins. Here we probed specificity of IL-11 to calcium-binding proteins of various types: calcium sensors of the EF-hand family (calmodulin, S100B and neuronal calcium sensors: recoverin, NCS-1, GCAP-1, GCAP-2), calcium buffers of the EF-hand family (S100G, oncomodulin), and a non-EF-hand calcium buffer (α-lactalbumin). A specific subset of the calcium sensor proteins (calmodulin, S100B, NCS-1, GCAP-1/2) exhibits metal-dependent binding of IL-11 with dissociation constants of 1-19 μM. These proteins share several amino acid residues belonging to conservative structural motifs of the EF-hand proteins, 'black' and 'gray' clusters. Replacements of the respective S100P residues by alanine drastically decrease its affinity to IL-11, suggesting their involvement into the association process. Secondary structure and accessibility of the hinge region of the EF-hand proteins studied are predicted to control specificity and selectivity of their binding to IL-11. The IL-11 interaction with the EF-hand proteins is expected to occur under numerous pathological conditions, accompanied by disintegration of plasma membrane and efflux of cellular components into the extracellular milieu.

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

    PubMed

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

    2014-01-01

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

  2. EFL GTPase in cryptomonads and the distribution of EFL and EF-1alpha in chromalveolates.

    PubMed

    Gile, Gillian H; Patron, Nicola J; Keeling, Patrick J

    2006-10-01

    EFL (EF-like protein) is a member of the GTPase superfamily that includes several translation factors. Because it has only been found in a few eukaryotic lineages and its presence correlates with the absence of the related core translation factor EF-1alpha, its distribution is hypothesized to be the result of lateral gene transfer and replacement of EF-1alpha. In one supergroup of eukaryotes, the chromalveolates, two major lineages were found to contain EFL (dinoflagellates and haptophytes), while the others encode EF-1alpha (apicomplexans, ciliates, heterokonts and cryptomonads). For each of these groups, this distribution was deduced from whole genome sequence or expressed sequence tag (EST) data from several species, with the exception of cryptomonads from which only a single EF-1alpha PCR product from one species was known. By sequencing ESTs from two cryptomonads, Guillardia theta and Rhodomonas salina, and searching for all GTPase translation factors, we revealed that EFL is present in both species, but, contrary to expectations, we found EF-1alpha in neither. On balance, we suggest the previously reported EF-1alpha from Rhodomonas salina is likely an artefact of contamination. We also identified EFL in EST data from two members of the dinoflagellate lineage, Karlodinium micrum and Oxyrrhis marina, and from an ongoing genomic sequence project from a third, Perkinsus marinus. Karlodinium micrum is a symbiotic pairing of two lineages that would have both had EFL (a dinoflagellate and a haptophyte), but only the dinoflagellate gene remains. Oxyrrhis marina and Perkinsus marinus are early diverging sister-groups to dinoflagellates, and together show that EFL originated early in this lineage. Phylogenetic analysis confirmed that these genes are all EFL homologues, and showed that cryptomonad genes are not detectably related to EFL from other chromalveolates, which collectively form several distinct groups. The known distribution of EFL now includes a third group

  3. The Role of Protein Elongation Factor eEF1A2 in Breast Cancer

    DTIC Science & Technology

    2006-09-01

    31, 301-5. Page 11 Appendix A. Figures. Page 12 negative or weak moderate or strong years from diagnosis p= 0.005 cu m m u la ti ve s u rv iv al3...function of years following diagnosis . The difference is significant at p = 0.005. b 0 1 2 3 4 5 6 7 8 9 eEF1A2 negative eEF1A2 positive T u m o u r si ze...mouse model of aristolochic acid nephropathy , and human kidney-proximal tubule cells. Satisfyingly, one of these targets is Dishevelled 2 (DVL2

  4. Crystal structure of calcium-free human sorcin: a member of the penta-EF-hand protein family.

    PubMed

    Xie, X; Dwyer, M D; Swenson, L; Parker, M H; Botfield, M C

    2001-12-01

    Sorcin is a 22 kD calcium-binding protein that is found in a wide variety of cell types, such as heart, muscle, brain and adrenal medulla. It belongs to the penta-EF-hand (PEF) protein family, which contains five EF-hand motifs that associate with membranes in a calcium-dependent manner. Prototypic members of this family are the calcium-binding domains of calpain, such as calpain dVI. Full-length human sorcin has been crystallized in the absence of calcium and the structure determined at 2.2 A resolution. Apart from an extended N-terminal portion, the sorcin molecule has a globular shape. The C-terminal domain is predominantly alpha-helical, containing eight alpha-helices and connecting loops incorporating five EF hands. Sorcin forms dimers through the association of the unpaired EF5, confirming this as the mode of association in the dimerization of PEF proteins. Comparison with calpain dVI reveals that the general folds of the individual EF-hand motifs are conserved, especially that of EF1, the novel EF-hand motif characteristic of the family. Detailed structural comparisons of sorcin with other members of PEF indicate that the EF-hand pair EF1-EF2 is likely to correspond to the two physiologically relevant calcium-binding sites and that the calcium-induced conformational change may be modest and localized within this pair of EF-hands. Overall, the results derived from the structural observations support the view that, in sorcin, calcium signaling takes place through the first pair of EF-hands.

  5. The Development of Reading and Spelling Abilities in the First 3 Years of Learning Arabic

    ERIC Educational Resources Information Center

    Mohamed, Wessam; Elbert, Thomas; Landerl, Karin

    2011-01-01

    In a cross-sectional study, we investigated the development of fluent reading and spelling in the first 3 years of learning Arabic. The goals of our study were to: (1) validate suitable measures for fluent reading and spelling in the first 3 years of learning Arabic; (2) trace the developmental course of the relationship between fluent reading and…

  6. Changes in Strength Abilities of Adolescent Girls: The Effect of a 3-Year Physical Education Curriculum

    ERIC Educational Resources Information Center

    Czarniecka, Renata; Milde, Katarzyna; Tomaszewski, Pawel

    2012-01-01

    Study aim: To evaluate changes in strength abilities of adolescent girls that underwent a 3-year physical education curriculum. Material and methods: The research participants comprised 141 girls aged 13.3 plus or minus 0.35 years who participated in a 3-year physical education curriculum (PEC). Evaluation was based on the following EUROFIT…

  7. Enterococcus faecium HDRsEf1 Protects the Intestinal Epithelium and Attenuates ETEC-Induced IL-8 Secretion in Enterocytes

    PubMed Central

    Xiao, Yuncai; Wang, Xiliang; Bi, Dingren

    2016-01-01

    The probiotic Enterococcus faecium HDRsEf1 (Ef1) has been shown to have positive effects on piglet diarrhoea, but the mechanism has not yet been elucidated. In this study, using the IPEC-J2 cell line to mimic intestinal epithelial cells and enterotoxigenic Escherichia coli (ETEC) K88ac as a representative intestinal pathogen, the mechanism underlying Ef1 protection against an enteropathogen was investigated. The results demonstrated that Ef1 was effective in displacing K88ac from the IPEC-J2 cell layer. Moreover, Ef1 and its cell-free supernatant (S-Ef1) modulate IL-8 released by IPEC-J2 cells. Ef1 and its cell-free supernatant showed the potential to protect enterocytes from an acute inflammatory response. In addition, Ef1 and its cell-free supernatant increased the transepithelial electrical resistance (TEER) of the enterocyte monolayer, thus strengthening the intestinal barrier against ETEC. These results may contribute to the development of therapeutic interventions using Ef1 in intestinal disorders of piglets. PMID:27890970

  8. EF4 disengages the peptidyl-tRNA CCA end and facilitates back-translocation on the 70S ribosome.

    PubMed

    Zhang, Dejiu; Yan, Kaige; Liu, Guangqiao; Song, Guangtao; Luo, Jiejian; Shi, Yi; Cheng, Erchao; Wu, Shan; Jiang, Taijiao; Lou, Jizhong; Gao, Ning; Qin, Yan

    2016-02-01

    EF4 catalyzes tRNA back-translocation through an unknown mechanism. We report cryo-EM structures of Escherichia coli EF4 in post- and pretranslocational ribosomes (Post- and Pre-EF4) at 3.7- and 3.2-Å resolution, respectively. In Post-EF4, peptidyl-tRNA occupies the peptidyl (P) site, but the interaction between its CCA end and the P loop is disrupted. In Pre-EF4, the peptidyl-tRNA assumes a unique position near the aminoacyl (A) site, denoted the A site/EF4 bound (A/4) site, with a large displacement at its acceptor arm. Mutagenesis analyses suggest that a specific region in the EF4 C-terminal domain (CTD) interferes with base-pairing between the peptidyl-tRNA 3'-CCA and the P loop, whereas the EF4 CTD enhances peptidyl-tRNA interaction at the A/4 site. Therefore, EF4 induces back-translocation by disengaging the tRNA's CCA end from the peptidyl transferase center of the translating ribosome.

  9. Long-term effectiveness of four pulpotomy techniques: 3-year randomised controlled trial.

    PubMed

    Huth, Karin Christine; Hajek-Al-Khatar, Niran; Wolf, Petra; Ilie, Nicoleta; Hickel, Reinhard; Paschos, Ekaterini

    2012-08-01

    A pulpotomy is the therapy for management of pulp exposures due to caries in symptom-free primary molars. The aim was to longitudinally compare the relative effectiveness of the Er:YAG laser, calcium hydroxide and ferric sulphate techniques with dilute formocresol in retaining symptom-free molars. Two hundred primary molars in 107 healthy children were included and randomly allocated to one technique. The treated teeth were blindly reevaluated after 6, 12, 18, 24 and 36 months. Descriptive data analysis and logistic regression analysis accounting for multiple observations per patient by generalised estimating equation were used. Additionally, various influences including tooth type, upper and lower jaws, type of anaesthesia, operator and the final restoration on treatment success were evaluated (Wald chi-square test). After 36 months, the following total (considering clinical and clinically symptom-free radiographic failures) and clinical success rates were determined (in percent): Formocresol 72 (92), laser 73 (89), calcium hydroxide 46 (75), ferric sulphate 76 (97). No significant differences were detected between formocresol and any other technique after 36 months. However, the odds ratio of failure appeared to be three times higher for calcium hydroxide than for formocresol. No significant differences in total success rates were seen regarding the aforementioned influencing clinical parameters. The correct diagnosis of the pulpal status, bleeding control and the specific technique are highly important for long-term success of pulpotomies in primary molars. According to the presented long-term data, pulpotomies using ferric sulphate revealed the best treatment outcome among the used techniques, while calcium hydroxide resulted in the lowest success rates after 3 years. Therefore, we can recommend ferric sulphate for easy and successful treatment of primary molars with caries-exposed pulps.

  10. The cultural and linguistic diversity of 3-year-old children with hearing loss.

    PubMed

    Crowe, Kathryn; McLeod, Sharynne; Ching, Teresa Y C

    2012-01-01

    Understanding the cultural and linguistic diversity of young children with hearing loss informs the provision of assessment, habilitation, and education services to both children and their families. Data describing communication mode, oral language use, and demographic characteristics were collected for 406 children with hearing loss and their caregivers when children were 3 years old. The data were from the Longitudinal Outcomes of Children with Hearing Impairment (LOCHI) study, a prospective, population-based study of children with hearing loss in Australia. The majority of the 406 children used spoken English at home; however, 28 other languages also were spoken. Compared with their caregivers, the children in this study used fewer spoken languages and had higher rates of oral monolingualism. Few children used a spoken language other than English in their early education environment. One quarter of the children used sign to communicate at home and/or in their early education environment. No associations between caregiver hearing status and children's communication mode were identified. This exploratory investigation of the communication modes and languages used by young children with hearing loss and their caregivers provides an initial examination of the cultural and linguistic diversity and heritage language attrition of this population. The findings of this study have implications for the development of resources and the provision of early education services to the families of children with hearing loss, especially where the caregivers use a language that is not the lingua franca of their country of residence.

  11. Negative cognitive styles synergistically predict suicidal ideation in bipolar spectrum disorders: a 3-year prospective study.

    PubMed

    Stange, Jonathan P; Hamilton, Jessica L; Burke, Taylor A; Kleiman, Evan M; O'Garro-Moore, Jared K; Seligman, Nicole D; Abramson, Lyn Y; Alloy, Lauren B

    2015-03-30

    Rates of suicidal ideation and behavior are extremely high in bipolar spectrum disorders (BSDs). However, relatively little work has evaluated potentially synergistic relationships between cognitive and emotion-regulatory processes proposed by theoretical models of suicidality in BSDs. The present study evaluated whether negative cognitive style and subtypes of rumination would exacerbate the impact of self-criticism on suicidal ideation in a prospective study of individuals with BSDs. Seventy-two young adults with BSDs (bipolar II, bipolar NOS, or cyclothymia) completed diagnostic interviews and trait measures of self-criticism, negative cognitive style, and brooding and reflective rumination at a baseline assessment. The occurrence of suicidal ideation was assessed as part of diagnostic interviews completed every 4 months for an average of 3 years of follow-up. Negative cognitive style and reflective rumination strengthened the association between self-criticism and the prospective occurrence of suicidal ideation across follow-up. Individuals with high levels of self-criticism in conjunction with negative cognitive style or reflective rumination were most likely to experience the onset of suicidal ideation. Self-criticism may work synergistically with negative cognitive style and rumination to confer risk for suicidal ideation in bipolar spectrum disorders. These results support theoretical models of suicidality in BSDs and indicate that evaluating and understanding negative cognitive styles may help to identify individuals who are at risk of suicide.

  12. The Cultural and Linguistic Diversity of 3-Year-Old Children with Hearing Loss

    PubMed Central

    Crowe, Kathryn

    2012-01-01

    Understanding the cultural and linguistic diversity of young children with hearing loss informs the provision of assessment, habilitation, and education services to both children and their families. Data describing communication mode, oral language use, and demographic characteristics were collected for 406 children with hearing loss and their caregivers when children were 3 years old. The data were from the Longitudinal Outcomes of Children with Hearing Impairment (LOCHI) study, a prospective, population-based study of children with hearing loss in Australia. The majority of the 406 children used spoken English at home; however, 28 other languages also were spoken. Compared with their caregivers, the children in this study used fewer spoken languages and had higher rates of oral monolingualism. Few children used a spoken language other than English in their early education environment. One quarter of the children used sign to communicate at home and/or in their early education environment. No associations between caregiver hearing status and children’s communication mode were identified. This exploratory investigation of the communication modes and languages used by young children with hearing loss and their caregivers provides an initial examination of the cultural and linguistic diversity and heritage language attrition of this population. The findings of this study have implications for the development of resources and the provision of early education services to the families of children with hearing loss, especially where the caregivers use a language that is not the lingua franca of their country of residence. PMID:22942315

  13. A 3-year evolution of linguistic disorders in aphasia after stroke.

    PubMed

    El Hachioui, Hanane; van de Sandt-Koenderman, Mieke W M E; Dippel, Diederik W J; Koudstaal, Peter J; Visch-Brink, Evy G

    2011-09-01

    Aphasia recovery after stroke has been the subject of several studies, but in none the deficits on the various linguistic levels were examined, even though in the diagnosis and treatment of aphasia the emphasis lays more and more on these linguistic level disorders. In this observational prospective follow-up study, we explored whether it is meaningful to investigate the recovery of semantics, phonology, and syntax separately. Fifteen patients with aphasia poststroke were assessed at 3 and 10 days, 7 weeks, 4 and 7 months, and 3 years postonset with the ScreeLing, a linguistic level test, the Aphasia Severity Rating Scale (spontaneous speech) and the Token Test. Group results showed improvement for the overall ScreeLing (P<0.01) and its subparts semantics (P<0.01) and syntax (P<0.01) up to 7 weeks, just as the Token Test (P<0.01). Phonology improved up to 4 months (P<0.05) and spontaneous speech up to 7 months (P<0.05). The recovery pattern of the three linguistic levels did not follow a parallel course, with a great deal of variability in linguistic recovery curves between and within patients. These results suggest that it is meaningful to assess the recovery of the linguistic levels separately, starting from the acute stage poststroke.

  14. 9 CFR 205.204 - Filing “notice” of EFS.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Filing ânoticeâ of EFS. 205.204 Section 205.204 Animals and Animal Products GRAIN INSPECTION, PACKERS AND STOCKYARDS ADMINISTRATION (PACKERS AND STOCKYARDS PROGRAMS), DEPARTMENT OF AGRICULTURE CLEAR TITLE-PROTECTION FOR PURCHASERS OF...

  15. Two distinct EF-Tu epitopes induce immune responses in rice and Arabidopsis.

    PubMed

    Furukawa, Takehito; Inagaki, Hiroaki; Takai, Ryota; Hirai, Hiroyuki; Che, Fang-Sik

    2014-02-01

    Plants sense potential pathogens by recognizing conserved pathogen-associated molecular patterns (PAMPs) that cause PAMP-triggered immunity (PTI). We previously reported that rice recognizes flagellin from the rice-incompatible N1141 strain of Acidovorax avenae and subsequently induces immune responses. Cell extracts isolated from flagellin-deficient N1141 (Δfla1141) still induced PTI responses, suggesting that Δfla1141 possesses an additional PAMP distinct from flagellin. Here, we show that elongation factor Tu (EF-Tu), one of the most abundant bacterial proteins, acts as a PAMP in rice and causes several PTI responses. In Brassicaceae species, EF-Tu and an N-acetylated peptide comprising the first 18 amino acids of the N-terminus, termed elf18, are fully active as inducers of PTI responses. By contrast, elf18 did not cause any immune responses in rice, whereas an EF-Tu middle region comprising Lys176 to Gly225, termed EFa50, is fully active as a PAMP in rice. In the leaves of rice plants, EF-Tu induced H2O2 generation and callose deposition, and also triggered resistance to coinfection with pathogenic bacteria. Taken together, these data demonstrate that rice recognizes EFa50, which is distinct from elf18, and that this epitope induces PTI responses.

  16. Single-molecule structural dynamics of EF-G--ribosome interaction during translocation.

    PubMed

    Wang, Yuhong; Qin, Haiou; Kudaravalli, Rama D; Kirillov, Stanislas V; Dempsey, Graham T; Pan, Dongli; Cooperman, Barry S; Goldman, Yale E

    2007-09-25

    EF-G catalyzes translocation of mRNA and tRNAs within the ribosome during protein synthesis. Detection of structural states in the reaction sequence that are not highly populated can be facilitated by studying the process one molecule at a time. Here we present single-molecule studies of translocation showing that, for ribosomes engaged in poly(Phe) synthesis, fluorescence resonance energy transfer (FRET) between the G' domain of EF-G and the N-terminal domain of ribosomal protein L11 occurs within two rapidly interconverting states, having FRET efficiencies of 0.3 and 0.6. The antibiotic fusidic acid increases the population of the 0.6 state, indicating that it traps the ribosome.EF-G complex in a preexisting conformation formed during translation. Only the 0.3 state is observed when poly(Phe) synthesis is prevented by omission of EF-Tu, or in studies on vacant ribosomes. These results suggest that the 0.6 state results from the conformational lability of unlocked ribosomes formed during translocation. An idling state, possibly pertinent to regulation of protein synthesis, is detected in some ribosomes in the poly(Phe) system.

  17. Extra EF hand unit (DX) mediated stabilization and calcium independency of α-amylase.

    PubMed

    Sadeghi, Leila; Khajeh, Khosro; Mollania, Nasrin; Dabirmanesh, Bahareh; Ranjbar, Bijan

    2013-03-01

    It is the common feature of α-amylases that calcium ion is required for their structural integrity and thermal stability. All amylases have at least one Ca(2+) per molecule; therefore amino acids involved in calcium binding are specific and conserved. In this study, sequence analysis revealed the presence of EF-hand-like motif in calcium-binding loop of Bacillus megaterium WHO (BMW)-amylase that was previously isolated from BMW. The EF-hand motif and its variants (EF-hand-like motif) are the most common calcium-binding motifs found in a large number of protein families. To investigate the effect of calcium ion on the thermal stability and activity of BMW-amylase, we used site-directed mutagenesis to replace histidine 58 with Asp (D), Ile (I), Tyr (Y), Phe (F), and Arg (R) at the seventh position of EF-hand-like motif. Upon the addition of an extra DX unit to the calcium-binding loop in H58D variant, thermal stability, catalytic activity, and chelating power of the enzyme improved due to higher affinity toward calcium. H58D variant demonstrated calcium independency compared to the wild type and other created mutants. Conformational changes in the presence and absence of Ca(2+) were monitored using fluorescence technique.

  18. Spitzer IRS Spectroscopy of the 10 Myr-Old EF Cha Debris Disk: Evidence for Phyllosilicate-Rich Dust in the Terrestrial Zone

    NASA Technical Reports Server (NTRS)

    Currie, Thayne; Lisse, Carey M.; Sicillia-Aguilar, Aurora; Rieke, George H.; Su, Kate Y. L.

    2011-01-01

    We describe Spitzer IRS spectroscopic observations of the approx. 10 Myr-old star, EF Chao Compositional modeling of the spectra from 5 micron to 35 micron confirms that it is surrounded by a luminous debris disk with L(sub D)/L(sub *) approx. 10(exp -3), containing dust with temperatures between 225 K and 430 K characteristic of the terrestrial zone. The EF Cha spectrum shows evidence for many solid-state features, unlike most cold, low-luminosity debris disks but like some other 10-20 Myr-old luminous, warm debris disks (e.g. HD 113766A). The EF Cha debris disk is unusually rich in a species or combination of species whose emissivities resemble that of finely-powdered, laboratory-measured phyllosilicate species (talc, saponite, and smectite), which are likely produced by aqueous alteration of primordial anhydrous rocky materials. The dust and, by inference, the parent bodies of the debris also contain abundant amorphous silicates and metal sulfides, and possibly water ice. The dust's total olivine to pyroxene ratio of approx. 2 also provides evidence of aqueous alteration. The large mass volume of grains with sizes comparable to or below the radiation blow-out limit implies that planetesimals may be colliding at a rate high enough to yield the emitting dust but not so high as to devolatize the planetesimals via impact processing. Because phyllosilicates are produced by the interactions between anhydrous rock and warm, reactive water, EF Cha's disk is a likely signpost for water delivery to the terrestrial zone of a young planetary system.

  19. Spitzer Infrared Spectrograph Spectroscopy of the 10 Myr Old EF Cha Debris Disk: Evidence for Phyllosilicate-rich Dust in the Terrestrial Zone

    NASA Astrophysics Data System (ADS)

    Currie, Thayne; Lisse, Carey M.; Sicilia-Aguilar, Aurora; Rieke, George H.; Su, Kate Y. L.

    2011-06-01

    We describe Spitzer Infrared Spectrograph spectroscopic observations of the ~10 Myr old star, EF Cha. Compositional modeling of the spectra from 5 μm to 35 μm confirms that it is surrounded by a luminous debris disk with LD /L sstarf ~ 10-3, containing dust with temperatures between 225 K and 430 K, characteristic of the terrestrial zone. The EF Cha spectrum shows evidence for many solid-state features, unlike most cold, low-luminosity debris disks but like some other 10-20 Myr old luminous, warm debris disks (e.g., HD 113766A). The EF Cha debris disk is unusually rich in a species or combination of species whose emissivities resemble that of finely powdered, laboratory-measured phyllosilicate species (talc, saponite, and smectite), which are likely produced by aqueous alteration of primordial anhydrous rocky materials. The dust and, by inference, the parent bodies of the debris also contain abundant amorphous silicates and metal sulfides, and possibly water ice. The dust's total olivine to the pyroxene ratio of ~2 also provides evidence of aqueous alteration. The large mass volume of grains with sizes comparable to or below the radiation blow-out limit implies that planetesimals may be colliding at a rate high enough to yield the emitting dust but not so high as to devolatize the planetesimals via impact processing. Because phyllosilicates are produced by the interactions between anhydrous rock and warm, reactive water, EF Cha's disk is a likely signpost for water delivery to the terrestrial zone of a young planetary system.

  20. Crystal structure of calpain-3 penta-EF-hand (PEF) domain - a homodimerized PEF family member with calcium bound at the fifth EF-hand

    SciTech Connect

    Partha, Sarathy K.; Ravulapalli, Ravikiran; Allingham, John S.; Campbell, Robert L.; Davies, Peter L.

    2014-08-21

    Calpains are Ca2+dependent intracellular cysteine proteases that cleave a wide range of protein substrates to help implement Ca2+ signaling in the cell. The major isoforms of this enzyme family, calpain-1 and calpain-2, are heterodimers of a large and a small subunit, with the main dimer interface being formed through their C-terminal penta-EF hand (PEF) domains. Calpain-3, or p94, is a skeletal muscle-specific isoform that is genetically linked to limb-girdle muscular dystrophy. Biophysical and modeling studies with the PEF domain of calpain-3 support the suggestion that full-length calpain-3 exists as a homodimer. Here, we report the crystallization of calpain-3's PEF domain and its crystal structure in the presence of Ca2+, which provides evidence for the homodimer architecture of calpain-3 and supports the molecular model that places a protease core at either end of the elongated dimer. Unlike other calpain PEF domain structures, the calpain-3 PEF domain contains a Ca2+ bound at the EF5-hand used for homodimer association. Three of the four Ca2+-binding EF-hands of the PEF domains are concentrated near the protease core, and have the potential to radically change the local charge within the dimer during Ca2+ signaling. Examination of the homodimer interface shows that there would be steric clashes if the calpain-3 large subunit were to try to pair with a calpain small subunit.

  1. Paroxetine inhibited the relaxations induced by EFS in mice corpus cavernosum: is it a NOS inhibition?

    PubMed

    Kadioglu, Mine; Muci, Efnan; Ozyavuz, Rasin; Yaris, Ersin; Kesim, Murat; Kalyoncu, Nuri I

    2010-02-01

    Selective serotonin reuptake inhibitors are used in the treatment of psychiatric disorders but are associated with high incidence of sexual dysfunction such as ejaculation disorders by sertraline and fluoxetine, erection disorders by paroxetine. The aim of this study is to evaluate the effects of paroxetine, sertraline and fluoxetine on relaxation of smooth muscle of corpus cavernosum on the basis of nitric oxide (NO). Male mice were killed by cervical dislocation and their penile tissues were immediately removed. The tissues were incubated in organ baths containing Krebs solution at 37 degrees C and bubbled with 95% O(2) and 5% CO(2). The corpus cavernosum strips were contracted with 10(-5 )m phenylephrine (PHE) and relaxed with either paroxetine, sertraline, fluoxetine (10(-8)-10(-4 )m) or electrical field stimulation (EFS). The effects of paroxetine, sertraline and fluoxetine were examined on EFS-induced relaxations. While paroxetine did not show any effect on the corpus cavernosum strips precontracted with PHE, sertraline and fluoxetine caused a relaxation at concentrations of 3 x 10(-5)-10(-4 )m. The relaxations induced by sertraline and fluoxetine were completely abolished by L-NAME, but not D-NAME. The relaxations induced by EFS could be inhibited by L-NAME but not D-NAME. Paroxetine inhibited the relaxations at high concentrations. L-arginine potentiated the relaxations induced by EFS; however in the presence of paroxetine these relaxations were not observed. In contrast, sertraline (10(-8)-10(-5 )m) and fluoxetine (10(-8)-10(-5)m) increased the relaxations induced by EFS. Sertraline and fluoxetine seem to be releasing some relaxing factor(s) and this factor may be NO. Paroxetine probably has a NOS inhibitory activity either on nNOS or eNOS, in contrast to sertraline and fluoxetine.

  2. 1996 Wholesale Power and Transmission Rate Schedules.

    SciTech Connect

    United States. Bonneville Power Administration.

    1996-10-01

    Bonneville Power Administration`s (BPA) 1996 Wholesale Power Rate Schedules, 1996 Ancillary Products and Services Rate Schedule, 1996 Transmission Rate Schedules, and General Rate Schedule Provisions, contained herein, were approved on an interim basis effective October 1, 1996. These rate schedules and provisions were approved by the Federal Energy Regulatory Commission (FERC), United States Department of Energy, in September 1996 (Docket Nos EF96-2011-000 and EF96f-2021-000). These rate schedules and General Rate Schedule Provisions were approved on a final basis by the FERC July 30, 1997, in Dept. of Energy--Bonneville Power Administration, Docket Nos. EF96-2011-000 and EF96-2021-000. Except as noted elsewhere, these 1996 rate schedules and provisions supersede BPA`s Wholesale Power Rate Schedules and General Rate Schedule Provisions, and Transmission Rate Schedules and General Transmission Rate Schedule Provisions, effective October 1, 1995. These rate schedules and general rate schedule provisions include all errata.

  3. Energy Partitioning during Frictional Sliding at Coseismic Slip Rates

    NASA Astrophysics Data System (ADS)

    Hirose, T.; Mizoguchi, K.

    2008-12-01

    Determination of the energy partitioning during an earthquake is key to understanding the physics of earthquakes (e.g., Kanamori and Rivera, 2006). Observations made on natural faults that have experienced earthquakes suggest that part of the energy dissipates into a volume of rock surrounding the fault though grain crushing processes, forming fault gouge (e.g., Wilson et al., 2005). Thus we performed high-velocity wear experiments using a rotary-shear apparatus, in order to estimate the partitioning of the frictional work into heat and surface energy during frictional sliding at nearly coseismic slip rates. In particular, we attempted to test whether the ratio of the energy partitioning varies as a function of slip rate. The ratio of dissipated energy as heat to the total frictional work was estimated from the difference between measured temperature around the sliding surfaces and calculated temperature by 2D-FEM on the assumption that all frictional work converts into heat. The surface energy was estimated based on the particle size distribution of the wear materials, which was determined by FE-SEM image analysis. The particles size ranged between 0.03 and 10 μm in average diameter. In the experiments, hollow cylindrical specimens of gabbro were slid at slip rates of 0.004 to 0.3 m/s and normal stresses of 0.2 to 5.6 MPa under unconfined and dry conditions. Rock powder (gouge) was continuously produced by abrasive wear of initially bare fault surfaces during sliding. Because the sliding surfaces were not confined in the experiments, the gouge was extruded from the fault surfaces, resulting in shortening of axial length of specimen. In this study, we defined the dimensionless wear rate, given by that an axial shortening rate of the specimen was divided by slip rate. Then, we examined how the wear rate and temperature changed as a function of the rate of frictional work per a unit fault area, Ef, determined by shear stress multiplied by slip rate. Hereafter, Q and

  4. Parental Styles and Religious Values among Teenagers: A 3-Year Prospective Analysis

    ERIC Educational Resources Information Center

    Heaven, Patrick C. L.; Ciarrochi, Joseph; Leeson, Peter

    2010-01-01

    The authors examined the effect of Grade 7 parental styles on Grade 10 religious values. The authors surveyed 784 participants (382 boys, 394 girls; 8 unreported) in Grade 7. The mean age of the group at Time 1 was 12.3 years (SD = 0.5 years). Time 2 occurred 3 years later when students were in Grade 10 (372 boys, 375 girls). In addition to…

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

    PubMed

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

    2015-12-01

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

  6. The acquisition of allophones among bilingual Spanish-English and French-English 3-year-old children.

    PubMed

    MacLeod, Andrea A N; Fabiano-Smith, Leah

    2015-03-01

    Children are exposed to highly variable input from multiple sources within their speech community. This study examines the acquisition of allophones in Spanish and French by monolingual and bilingual children. We hypothesised that two factors would influence allophone acquisition: (1) the amount of exposure to phonological input, and (2) the degree of variability of the allophonic pattern. Thirty-four typically developing 3-year-old participated in the study. The analyses revealed that regardless of the language, the monolingual children produced similar error rates in the production of the target allophones. In contrast, the bilingual children produced different patterns of acquisition of the allophones: the Spanish-English bilinguals produced higher error rates than the monolinguals, whereas the French-English bilinguals produced lower error rates than the monolinguals. Possibilities for these differences are discussed within the context of structural complexity as well as in light of the effects of between-language interaction on bilingual phonological development.

  7. Food insufficiency and women's mental health: findings from a 3-year panel of welfare recipients.

    PubMed

    Heflin, Colleen M; Siefert, Kristine; Williams, David R

    2005-11-01

    Household food insufficiency is a significant problem in the United States, and has been associated with poor outcomes on mental health indicators among low-income women. However, it is difficult to disentangle the mental health consequences of household food insufficiency from poverty and other shared risk factors. Drawing on theories of the social production of health and disease, research evidence linking food insufficiency with poor mental health, and high rates of food insufficiency among welfare recipients, we examined whether a change in household food insufficiency is associated with a change in women's self-reported mental health in a sample of current and recent welfare recipients over a 3-year period of time, controlling for common risk factors. Data were obtained from a prospective survey of women who were welfare recipients in an urban Michigan county in February 1997 (n=753). We estimated fixed effect models for changes in mental health status that make use of information on household food insufficiency gathered in the fall of 1997, 1998, and 1999. The relationship between household food insufficiency and respondents' meeting the diagnostic screening criteria for major depression remained highly significant even when controlling for factors known to confer increased risk of depression and time invariant unobserved heterogeneity. These findings add to growing evidence that household food insufficiency has potentially serious consequences for low-income women's mental health. If confirmed by further research, they suggest that the public health burden of depression in welfare recipients and other low-income women could be reduced by policy-level interventions to reduce their exposure to household food insufficiency.

  8. Serum pentosidine levels after 3 years of bisphosphonate treatment in post-menopausal osteoporotic women.

    PubMed

    Hashidate, Hiroyuki; Kamimura, Mikio; Ikegami, Shota; Mukaiyama, Keijiro; Uchiyama, Shigeharu; Nakamura, Yukio; Kato, Hiroyuki

    2015-01-01

    The present study measured changes in plasma pentosidine and bone turnover markers in elderly patients with osteoporosis treated using bisphosphonate. The relationship between pentosidine and bone turnover markers and bone mineral density (BMD) was investigated. This study consisted of post-menopausal osteoporotic women who could be treated using bisphosphonate for 3 years were included in the present analysis. The study population consisted of 58 cases, all women, ranging in age from 53 to 86 years (mean, 67.1 years). Bisphosphonate treatment significantly increased BMD of the lumbar spine to 0.914 ± 0.141 g/cm(2) and BMD of the femoral neck to 0.708 ± 0.086 g/cm(2) after 3 years (p < 0.001 versus baseline). The mean BAP level was 27.3 ± 8.3 U/L in patients at baseline. After bisphosphonate treatment, BAP significantly decreased to 18.1 ± 7.2 U/L at 3 years (p < 0.001). Urinary NTX also decreased after bisphosphonate treatment. After 3 years of treatment, urinary NTX significantly decreased from 50.0 ± 19.0 nmol BCE/mmol Cr to 24.6 ± 10.2 nmol BCE/mmol Cr at 3 years (p < 0.001). Serum pentosidine levels were 0.0413 ± 0.0094 μg/mL at baseline and 0.0413 ± 0.0122 μg/mL after 3 years. They were not significantly changed by bisphosphonate treatment. Serum pentosidine levels were not changed by treatment with bisphosphonates. Thus, serum pentosidine may not be suitable as a marker of bone quality after 3 years of bisphosphonate treatment.

  9. Liposome-encapsulated EF24-HPβCD inclusion complex: a preformulation study and biodistribution in a rat model

    PubMed Central

    Agashe, H.; Lagisetty, P.; Sahoo, K.; Bourne, D.; Grady, B.

    2011-01-01

    3,5-Bis(2-fluorobenzylidene)-4-piperidone (EF24) is an anti-proliferative diphenyldifluoroketone analog of curcumin with more potent activity. The authors describe a liposome preparation of EF24 using a “drug-in-CD-in liposome” approach. An aqueous solution of EF24 and hydroxypropyl-β-cyclodextrin (HPβCD) inclusion complex (IC) was used to prepare EF24 liposomes. The liposome size was reduced by a combination of multiple freeze–thaw cycles. Co-encapsulation of glutathione inside the liposomes conferred them with the capability of labeling with imageable radionuclide Tc-99m. Phase solubility analysis of EF24-HPβCD mixture provided k1:1 value of 9.9 M−1. The enhanced aqueous solubility of EF24 (from 1.64 to 13.8 mg/mL) due to the presence of HPβCD helped in the liposome preparation. About 19% of the EF24 IC was encapsulated inside the liposomes (320.5 ± 2.6 nm) by dehydration–rehydration technique. With extrusion technique, the size of 177 ± 6.5 nm was obtained without any effect on encapsulation efficiency. The EF24-liposomes were evaluated for anti-proliferative activity in lung adenocarcinoma H441 and prostate cancer PC-3 cells. The EF24-liposomes demonstrated anti-proliferative activity superior to that of plain EF24 at 10 μM dose. When injected in rats, the Tc-99m-labeled EF24-liposomes cleared from blood with an α-t1/2 of 21.4 min and β-t1/2 of 397 min. Tissue radioactivity counting upon necropsy showed that the majority of clearance was due to the uptake in liver and spleen. The results suggest that using “drug-in-CD-in liposome” approach is a feasible strategy to formulate an effective parenteral preparation of EF24. In vitro studies show that the liposomal EF24 remains anti-proliferative, while presenting an opportunity to image its biodistribution. PMID:21779150

  10. Cognitive, Parent and Teacher Rating Measures of Executive Functioning: Shared and Unique Influences on School Achievement

    PubMed Central

    Dekker, Marielle C.; Ziermans, Tim B.; Spruijt, Andrea M.; Swaab, Hanna

    2017-01-01

    Very little is known about the relative influence of cognitive performance-based executive functioning (EF) measures and behavioral EF ratings in explaining differences in children's school achievement. This study examined the shared and unique influence of these different EF measures on math and spelling outcome for a sample of 84 first and second graders. Parents and teachers completed the Behavior Rating Inventory of Executive Function (BRIEF), and children were tested with computer-based performance tests from the Amsterdam Neuropsychological Tasks (ANT). Mixed-model hierarchical regression analyses, including intelligence level and age, showed that cognitive performance and teacher's ratings of working memory and shifting concurrently explained differences in spelling. However, teacher's behavioral EF ratings did not explain any additional variance in math outcome above cognitive EF performance. Parent's behavioral EF ratings did not add any unique information for either outcome measure. This study provides support for the ecological validity of performance- and teacher rating-based EF measures, and shows that both measures could have a complementary role in identifying EF processes underlying spelling achievement problems. The early identification of strengths and weaknesses of a child's working memory and shifting capabilities, might help teachers to broaden their range of remedial intervention options to optimize school achievement. PMID:28194121

  11. Electrical properties of REF308, REF320, EF-AR20, and RSF200 foam encapsulants.

    SciTech Connect

    Russick, Edward Mark

    2006-01-01

    Foam encapsulants are used to encapsulate electromechanical assemblies for reasons such as shock mitigation, structural support, and voltage breakdown protection. Characterization of electrical properties of polymer encapsulants is important in situations where potting materials are in intimate contact with electrical components (e.g., printed wiring boards). REF308, REF320, RSF200, and EF-AR20 foams were developed for encapsulation in some potting applications at Sandia. Select electrical properties were measured for these Sandia encapsulants to characterize them for use in electromechanical potting applications. Dielectric constant with dissipation factors, volume resistivity, and dielectric strength were measured for REF308, REF320, RSF200, and EF-AR20 encapsulants. Fabrication of foam test specimens and the electrical test procedures will be discussed, and electrical testing results will be reported.

  12. Protein kinase Darkener of apricot and its substrate EF1γ regulate organelle transport along microtubules.

    PubMed

    Serpinskaya, Anna S; Tuphile, Karine; Rabinow, Leonard; Gelfand, Vladimir I

    2014-01-01

    Regulation of organelle transport along microtubules is important for proper distribution of membrane organelles and protein complexes in the cytoplasm. RNAi-mediated knockdown in cultured Drosophila S2 cells demonstrates that two microtubule-binding proteins, a unique isoform of Darkener of apricot (DOA) protein kinase, and its substrate, translational elongation factor EF1γ, negatively regulate transport of several classes of membrane organelles along microtubules. Inhibition of transport by EF1γ requires its phosphorylation by DOA on serine 294. Together, our results indicate a new role for two proteins that have not previously been implicated in regulation of the cytoskeleton. These results further suggest that the biological role of some of the proteins binding to the microtubule track is to regulate cargo transport along these tracks.

  13. F18 EF5 PET/CT Imaging in Patients with Brain Metastases from Breast Cancer

    DTIC Science & Technology

    2013-07-01

    with Brain Metastases from Breast Cancer PRINCIPAL INVESTIGATOR: Lilie Lin, MD CONTRACTING ORGANIZATION: University of Pennsylvania...Annual 3. DATES COVERED 01 July 2012 to 30 June 2013 4. TITLE AND SUBTITLE F18 EF5 PET/CT Imaging in Patients with Brain Metastases from Breast 5a...SUPPLEMENTARY NOTES 14. ABSTRACT The aim of this study is to estimate the degree of residual hypoxia after whole brain radiation therapy in patients

  14. Role of a ribosomal RNA phosphate oxygen during the EF-G-triggered GTP hydrolysis.

    PubMed

    Koch, Miriam; Flür, Sara; Kreutz, Christoph; Ennifar, Eric; Micura, Ronald; Polacek, Norbert

    2015-05-19

    Elongation factor-catalyzed GTP hydrolysis is a key reaction during the ribosomal elongation cycle. Recent crystal structures of G proteins, such as elongation factor G (EF-G) bound to the ribosome, as well as many biochemical studies, provide evidence that the direct interaction of translational GTPases (trGTPases) with the sarcin-ricin loop (SRL) of ribosomal RNA (rRNA) is pivotal for hydrolysis. However, the precise mechanism remains elusive and is intensively debated. Based on the close proximity of the phosphate oxygen of A2662 of the SRL to the supposedly catalytic histidine of EF-G (His87), we probed this interaction by an atomic mutagenesis approach. We individually replaced either of the two nonbridging phosphate oxygens at A2662 with a methyl group by the introduction of a methylphosphonate instead of the natural phosphate in fully functional, reconstituted bacterial ribosomes. Our major finding was that only one of the two resulting diastereomers, the SP methylphosphonate, was compatible with efficient GTPase activation on EF-G. The same trend was observed for a second trGTPase, namely EF4 (LepA). In addition, we provide evidence that the negative charge of the A2662 phosphate group must be retained for uncompromised activity in GTP hydrolysis. In summary, our data strongly corroborate that the nonbridging proSP phosphate oxygen at the A2662 of the SRL is critically involved in the activation of GTP hydrolysis. A mechanistic scenario is supported in which positioning of the catalytically active, protonated His87 through electrostatic interactions with the A2662 phosphate group and H-bond networks are key features of ribosome-triggered activation of trGTPases.

  15. Draft Genome Sequence of the Murine Bacterial Isolate Lactobacillus murinus EF-1

    PubMed Central

    Fritz, Eric

    2017-01-01

    ABSTRACT   Screening for lysogenic lactobacilli in rat fecal samples has identified Lactobacillus murinus EF-1. Whole-genome sequencing revealed a 2.30-Mb draft genome with 39.6% G+C content and 2,196 open reading frames. PHAST analysis identified three intact prophages of 26.1 kb, 25.4 kb, and 49.6 kb in size. PMID:28336601

  16. Parental Involvement in Cognitive Behavior Therapy for Children with Anxiety Disorders: 3-Year Follow-Up.

    PubMed

    Walczak, Monika; Esbjørn, Barbara H; Breinholst, Sonja; Reinholdt-Dunne, Marie Louise

    2016-07-12

    Parental factors have been linked to childhood anxiety, hence, parental involvement in cognitive behavioral therapy (CBT) for anxious children has been examined. However, findings do not consistently show added effects of parent-enhanced CBT, longitudinal investigations are scarce and long-term effects unclear. In the present study, 40 out of 54 families who, 3 years previously, completed one of two types of CBT treatment: with limited or active parental involvement, were assessed using semi-structured diagnostic interviews. Diagnostic status at 3-years follow-up was compared between groups. Changes in diagnostic status across assessment points: posttreatment, 6-month and 3-year follow-up were analyzed within groups. Diagnostic change from 6-month to 3-year follow-up was compared between groups. Intent-to-treat analyses revealed no significant difference in diagnostic status between groups at 3-year follow-up. Nonetheless, children whose parents actively participated in treatment showed significantly more remission from 6-month to 3-year follow-up than children with limited parental participation.

  17. Dietary energy density and body weight changes after 3 years in the PREDIMED study.

    PubMed

    Razquin, Cristina; Sanchez-Tainta, Ana; Salas-Salvadó, Jordi; Buil-Cosiales, Pilar; Corella, Dolores; Fito, Montserrat; Ros, Emilio; Estruch, Ramón; Arós, Fernando; Gómez-Gracia, Enrique; Fiol, Miquel; Lapetra, José; Serra-Majem, Luis; Pinto, Xavier; Schröder, Helmut; Tur, Josep; Sorlí, José V; Lamuela-Raventós, Rosa M; Bulló, Mónica; Bes-Rastrollo, Maira; Martinez-Gonzalez, Miguel A

    2017-03-06

    The association of dietary energy density (ED) and overweight is not clear in the literature. Our aim was to study in 4259 of the PREDIMED trial whether an increase in dietary ED based on a higher adherence to a Mediterranean dietary pattern was associated with 3-year weight gain. A validated 137-item food-frequency questionnaire was administered. Multivariable-adjusted models were used to analyze the association between 3-year ED change and the subsequent 3-year body weight change. The most important weight reduction after 3-year follow-up was observed in the two lowest quintiles and the highest quintile of ED change. The highest ED increase was characterized by an increased intake of extra virgin olive oil (EVOO) and nuts and a decreased intake of other oils, vegetable and fruit consumption (p < .001). In conclusion, increased 3-year ED in the PREDIMED study, associated with a higher EVOO and nuts consumption, was not associated with weight gain.

  18. Identification of a new EF-hand superfamily member from Trypanosoma brucei

    NASA Technical Reports Server (NTRS)

    Wong, S.; Kretsinger, R. H.; Campbell, D. A.

    1992-01-01

    We identified several open reading frames between the regions encoding calmodulin and ubiquitin-EP52/1 in the genome of Trypanosoma brucei. One of these, EFH5, encodes a protein 192 amino acids long. The EFH5 transcript is present in poly(A)+ mRNA and is present at similar levels in the mammalian bloodstream form and the insect procyclic form. EFH5 contains four EF-hand homolog domains, two of which are inferred to bind Ca2+ ions. We expressed EFH5 as a fusion protein in Escherichia coli and demonstrated calcium-binding activity of the fusion protein using the 45Ca-overlay technique. The function of EFH5 remains unknown; however, as the fourth EF-hand homolog identified in trypanosomes, it attests to the broad range of functions assumed by calcium functioning as a second messenger. EFH5, which is most closely related to LAV1-2 from Physarum, represents a distinct subfamily among the EF-hand-containing proteins.

  19. Implementation Of EF From SEBS In A LUE Model In A Rapeseed Cropland

    NASA Astrophysics Data System (ADS)

    Pardo, N.; Timmermans, J.; Perez, I. A.; Garcia, M. A.; Su, Z.; Sanchez, M. L.

    2013-12-01

    In assessment of global carbon cycle, evaluation of gross primary production, GPP, of an ecosystem is the main endeavour. The most adequate way to address this study is to apply a Light Use Efficiency, LUE, model in combination with an Eddy Covariance, EC, system. In this paper, evaporative fraction, EF, from two different databases (ground-based measurements and calculated by the Surface Energy Balance System, SEBS, algorithm developed at ITC) are applied to a LUE model in order to calculate a final ɛ0 value which is the maximum PAR conversion efficiency of the cropland. The LUE model was found to fit properly using both EF databases, with squared correlation coefficients of 0.89 and 0.81 for ground measurements and SEBS results, respectively. Final values for maximum efficiency were of 2.82±0.19 gC MJ-1 (measured EF) and 2.59±0.23 gC MJ-1 (SEBS). All these results were obtained with FPAR provided by MERIS.

  20. Complications with using ratios for environmental data: Comparing enantiomeric ratios (ERs) and enantiomer fractions (EFs)

    USGS Publications Warehouse

    Ulrich, E.M.; Helsel, D.R.; Foreman, W.T.

    2003-01-01

    Complications arise when ratios are used to present environmental data because ratios are an unbounded, multiplicative scale that can lead to asymmetrical (skewed) data distributions. Enantiomeric ratios (ERs), historically used in discussions of chiral signatures, often are published as mean ER??single-value standard deviation. Application of statistical summaries, such as the widely used sample mean and standard deviation, to skewed ratio data is misleading and often inappropriate. Comparison of statistically summarized ER and enantiomer fraction (EF) data (which are based on a bounded, additive scale) for a range of hypothetical values reveals substantial discrepancies when conversion between ER and EF formats is used. These discrepancies are largest when the ratio data are greater than one and have large variability, because the data are more skewed. In many cases, the use of fractions instead of ratios can help to minimize misrepresentation of environmental data, including chiral data. The use of nonparametric statistical summaries, e.g., median and percentiles, provides a more robust indicator of the typical value and spread for both ER and EF data. ?? 2003 Elsevier Ltd. All rights reserved.

  1. Energy-filtered Photoelectron Emission Microscopy (EF-PEEM) for imaging nanoelectronic materials

    SciTech Connect

    Renault, Olivier; Chabli, Amal

    2007-09-26

    Photoelectron-Emission Microscopy (PEEM) is the most promising approach to photoemission-based (XPS, UPS) imaging techniques with high lateral resolution, typically below 100 nm. It has now reached its maturity with a new generation of instruments with energy-filtering capabilities. Therefore UPS and XPS imaging with energy-filtered PEEM (EF-PEEM) can be applied to technologically-relevant samples. UPS images with contrast in local work function, obtained with laboratory UV sources, are obtained in ultra-high vacuum environment with lateral resolutions better than 50 nm and sensitivies of 20 meV. XPS images with elemental and bonding state contrast can show up lateral resolution better than 200 nm with synchrotron excitation. In this paper, we present the principles and capabilities of EF-PEEM and nanospectroscopy. Then, we focus on an example of application to non-destructive work-function imaging of polycrystalline copper for advanced interconnects, where it is shown that EF-PEEM is an alternative to Kelvin probes.

  2. Class V lesions restored with four different tooth-colored materials--3-year results.

    PubMed

    Folwaczny, M; Loher, C; Mehl, A; Kunzelmann, K H; Hickel, R

    2001-03-01

    The aim of this study was to compare the treatment results using four different types of tooth colored materials for restoring class V lesions. A total of 197 class V restorations (n = 197) were placed by one dentist in 37 patients on incisors, canines and premolars. The fillings were placed due to different indications: erosion/non-carious cervical defects (n = 69), primary carious lesions (n = 57), and for replacing defective existing fillings (n = 71). The teeth were assigned on a random basis to four groups for restoration with either a composite (group 1: n = 36; Tetric, Vivadent), or a polyacid-modified resin composite (group 2: n = 79; Dyract, Dentsply), or one of two different resin-modified glass ionomer cements (group 3: n = 51, Fuji II LC,GC; group 4: n = 31, Photac-Fil, Espe). The restorations were evaluated by a single-blind design, according to a modified USPHS system 36 months following placement. Statistical analysis was completed with the Pearson Chi-square test for comparing the results of the four groups (P < 0.05). Additionally, the survival rates were analyzed with the Kaplan-Meier estimator and the Log-rank test (P < 0.05). The Alpha ratings were as follows (Tetric/Dyract/Fuji II LC/Photac Fil): shade match (86%/77%/58%/40%), surface texture (81%/83%/16%/9%), marginal integrity (enamel) (73%/67%/61%/61%), marginal integrity (dentin) (86%/70%/55%/61%), marginal discoloration (enamel) (59%/44%/58%/52%), marginal discoloration (dentin) (82%/84%/71%/48%), anatomic contours (91%/83%/39%/35%). One Tetric restoration, five Dyract restorations, two Fuji II LC restorations and three Photac restorations were dislodged within the study period. The retention of the restorations showed no significant difference among the four materials. However, the clinical performance of the restorations retained over the 3-year period showed distinct differences for the four materials. The best clinical performance was observed for the resin composite, whereas the

  3. 3D Printing/Additive Manufacturing Single Titanium Dental Implants: A Prospective Multicenter Study with 3 Years of Follow-Up.

    PubMed

    Tunchel, Samy; Blay, Alberto; Kolerman, Roni; Mijiritsky, Eitan; Shibli, Jamil Awad

    2016-01-01

    This prospective 3-year follow-up clinical study evaluated the survival and success rates of 3DP/AM titanium dental implants to support single implant-supported restorations. After 3 years of loading, clinical, radiographic, and prosthetic parameters were assessed; the implant survival and the implant-crown success were evaluated. Eighty-two patients (44 males, 38 females; age range 26-67 years) were enrolled in the present study. A total of 110 3DP/AM titanium dental implants (65 maxilla, 45 mandible) were installed: 75 in healed alveolar ridges and 35 in postextraction sockets. The prosthetic restorations included 110 single crowns (SCs). After 3 years of loading, six implants failed, for an overall implant survival rate of 94.5%; among the 104 surviving implant-supported restorations, 6 showed complications and were therefore considered unsuccessful, for an implant-crown success of 94.3%. The mean distance between the implant shoulder and the first visible bone-implant contact was 0.75 mm (±0.32) and 0.89 (±0.45) after 1 and 3 years of loading, respectively. 3DP/AM titanium dental implants seem to represent a successful clinical option for the rehabilitation of single-tooth gaps in both jaws, at least until 3-year period. Further, long-term clinical studies are needed to confirm the present results.

  4. 3D Printing/Additive Manufacturing Single Titanium Dental Implants: A Prospective Multicenter Study with 3 Years of Follow-Up

    PubMed Central

    2016-01-01

    This prospective 3-year follow-up clinical study evaluated the survival and success rates of 3DP/AM titanium dental implants to support single implant-supported restorations. After 3 years of loading, clinical, radiographic, and prosthetic parameters were assessed; the implant survival and the implant-crown success were evaluated. Eighty-two patients (44 males, 38 females; age range 26–67 years) were enrolled in the present study. A total of 110 3DP/AM titanium dental implants (65 maxilla, 45 mandible) were installed: 75 in healed alveolar ridges and 35 in postextraction sockets. The prosthetic restorations included 110 single crowns (SCs). After 3 years of loading, six implants failed, for an overall implant survival rate of 94.5%; among the 104 surviving implant-supported restorations, 6 showed complications and were therefore considered unsuccessful, for an implant-crown success of 94.3%. The mean distance between the implant shoulder and the first visible bone-implant contact was 0.75 mm (±0.32) and 0.89 (±0.45) after 1 and 3 years of loading, respectively. 3DP/AM titanium dental implants seem to represent a successful clinical option for the rehabilitation of single-tooth gaps in both jaws, at least until 3-year period. Further, long-term clinical studies are needed to confirm the present results. PMID:27313616

  5. Interaction of turnip yellow mosaic virus Val-RNA with eukaryotic elongation factor EF-1 [alpha]. Search for a function.

    PubMed

    Joshi, R L; Ravel, J M; Haenni, A L

    1986-06-01

    The 3'-terminal tRNA-like structure in turnip yellow mosaic virus (TYMV) RNA can be adenylated by tRNA nucleotidyltransferase and subsequently aminoacylated by valyl-tRNA synthetase. Here we present evidence that TYMV Val-RNA can form a stable complex with eukaryotic wheat germ elongation factor EF-1alpha and GTP: the Val-RNA is protected by EF-1alpha.. GTP against digestion by RNase A. By affinity chromatography of TYMV Val-RNA fragments on immobilized EF-1alpha . GTP, it has been established that the valylated aminoacyl RNA domain, which in TYMV RNA is formed by the 3' half of the tRNA-like region, is sufficient for complex formation with EF-1alpha . GTP. The aminoacyl RNA domain is equivalent in tRNAs to the continuous helix formed by the acceptor stem and the T stem and loop. In line with these results, the aminoacyl RNA domain in TYMV Val-RNA complexed to EF-1 alpha . GTP is resistant to digestion by RNase A. It is also shown that the TYMV RNA replicase (RNA-dependent RNA polymerase) isolated from TYMV-infected Chinese cabbage leaves does not contain tRNA nucleotidyltransferase, valyl-tRNA synthetase or EF-1alpha. This suggests that interaction of TYMV RNA with EF-1alpha is not mandatory for replicase activity.

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

    PubMed

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

    2014-09-16

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

  7. EF24 Suppresses Invasion and Migration of Hepatocellular Carcinoma Cells In Vitro via Inhibiting the Phosphorylation of Src

    PubMed Central

    Tin, Lamtin; Wu, Yiqi; Jin, Yinji; Jin, Xiaoming; Zhang, Fengmin

    2016-01-01

    Diphenyl difluoroketone (EF24), a curcumin analog, is a promising anticancer compound that exerts its effects by inhibiting cell proliferation and inducing apoptosis. However, the efficacy of EF24 against cancer metastasis, particularly in hepatocellular carcinoma (HCC), remains elusive. In this study, the effect of EF24 on HCCLM-3 and HepG2 cell migration and invasion was detected by wound healing and transwell assay, respectively. The results revealed that EF24 suppressed the migration and invasion of both HCCLM-3 and HepG2 cells. Furthermore, EF24 treatment decreased the formation of filopodia on the cell surface and inhibited the phosphorylation of Src in both cell lines, which may help contribute towards understanding the mechanism underlying the suppressive effect of EF24 on HCC migration and invasion. Additionally, the expression of total- and phosphorylated-Src in primary HCC tissues and their paired lymph node metastatic tissues was detected, and phosphorylated-Src was found to be associated with HCC lymph node metastasis. The results of this study suggest that Src is a novel and promising therapeutic target in HCC and provide evidence to support the hypothesis that EF24 may be a useful therapeutic agent for the treatment of HCC. PMID:27999817

  8. Cloning, sequencing and overexpression of the gene for prokaryotic factor EF-P involved in peptide bond synthesis.

    PubMed Central

    Aoki, H; Adams, S L; Chung, D G; Yaguchi, M; Chuang, S E; Ganoza, M C

    1991-01-01

    A soluble protein EF-P (elongation factor P) from Escherichia coli has been purified and shown to stimulate efficient translation and peptide-bond synthesis on native or reconstituted 70S ribosomes in vitro. Based on the partial amino acid sequence of EF-P, 18- and 24-nucleotide DNA probes were synthesized and used to screen lambda phage clones from the Kohara Gene Bank. The entire EF-P gene was detected on lambda clone #650 which contains sequences from the 94 minute region of the E.coli genome. Two DNA fragments, 3.0 and 0.78 kilobases in length encompassing the gene, were isolated and cloned into pUC18 and pUC19. Partially purified extracts from cells transformed with these plasmids overrepresented a protein which co-migrates with EF-P upon SDS polyacrylamide gel electrophoresis, and also exhibited increased EF-P mediated peptide-bond synthetic activity. Based on DNA sequence analysis of this gene, the EF-P protein consists of 187 amino acids with a calculated molecular weight of 20,447. The sequence and chromosomal location of EF-P establishes it as a unique gene product. Images PMID:1956781

  9. Impaired associative taste learning and abnormal brain activation in kinase-defective eEF2K mice.

    PubMed

    Gildish, Iness; Manor, David; David, Orit; Sharma, Vijendra; Williams, David; Agarwala, Usha; Wang, Xuemin; Kenney, Justin W; Proud, Chris G; Rosenblum, Kobi

    2012-02-24

    Memory consolidation is defined temporally based on pharmacological interventions such as inhibitors of mRNA translation (molecular consolidation) or post-acquisition deactivation of specific brain regions (systems level consolidation). However, the relationship between molecular and systems consolidation are poorly understood. Molecular consolidation mechanisms involved in translation initiation and elongation have previously been studied in the cortex using taste-learning paradigms. For example, the levels of phosphorylation of eukaryotic elongation factor 2 (eEF2) were found to be correlated with taste learning in the gustatory cortex (GC), minutes following learning. In order to isolate the role of the eEF2 phosphorylation state at Thr-56 in both molecular and system consolidation, we analyzed cortical-dependent taste learning in eEF2K (the only known kinase for eEF2) ki mice, which exhibit reduced levels of eEF2 phosphorylation but normal levels of eEF2 and eEF2K. These mice exhibit clear attenuation of cortical-dependent associative, but not of incidental, taste learning. In order to gain a better understanding of the underlying mechanisms, we compared brain activity as measured by MEMRI (manganese-enhanced magnetic resonance imaging) between eEF2K ki mice and WT mice during conditioned taste aversion (CTA) learning and observed clear differences between the two but saw no differences under basal conditions. Our results demonstrate that adequate levels of phosphorylation of eEF2 are essential for cortical-dependent associative learning and suggest that malfunction of memory processing at the systems level underlies this associative memory impairment.

  10. Impaired associative taste learning and abnormal brain activation in kinase-defective eEF2K mice

    PubMed Central

    Gildish, Iness; Manor, David; David, Orit; Sharma, Vijendra; Williams, David; Agarwala, Usha; Wang, Xuemin; Kenney, Justin W.; Proud, Chris G.; Rosenblum, Kobi

    2012-01-01

    Memory consolidation is defined temporally based on pharmacological interventions such as inhibitors of mRNA translation (molecular consolidation) or post-acquisition deactivation of specific brain regions (systems level consolidation). However, the relationship between molecular and systems consolidation are poorly understood. Molecular consolidation mechanisms involved in translation initiation and elongation have previously been studied in the cortex using taste-learning paradigms. For example, the levels of phosphorylation of eukaryotic elongation factor 2 (eEF2) were found to be correlated with taste learning in the gustatory cortex (GC), minutes following learning. In order to isolate the role of the eEF2 phosphorylation state at Thr-56 in both molecular and system consolidation, we analyzed cortical-dependent taste learning in eEF2K (the only known kinase for eEF2) ki mice, which exhibit reduced levels of eEF2 phosphorylation but normal levels of eEF2 and eEF2K. These mice exhibit clear attenuation of cortical-dependent associative, but not of incidental, taste learning. In order to gain a better understanding of the underlying mechanisms, we compared brain activity as measured by MEMRI (manganese-enhanced magnetic resonance imaging) between eEF2K ki mice and WT mice during conditioned taste aversion (CTA) learning and observed clear differences between the two but saw no differences under basal conditions. Our results demonstrate that adequate levels of phosphorylation of eEF2 are essential for cortical-dependent associative learning and suggest that malfunction of memory processing at the systems level underlies this associative memory impairment. PMID:22366775

  11. Specific interaction between EF-G and RRF and its implication for GTP-dependent ribosome splitting into subunits

    PubMed Central

    Gao, Ning; Zavialov, Andrey V.; Ehrenberg, Måns; Frank, Joachim

    2008-01-01

    Summary After termination of protein synthesis, the bacterial ribosome is split into its 30S and 50S subunits by the action of ribosome recycling factor (RRF) and elongation factor G (EF-G) in a GTP-hydrolysis dependent manner. Based on a previous cryo-electron microscopy (cryo-EM) study of ribosomal complexes, we have proposed that the binding of EF-G to an RRF containing post-termination ribosome triggers an inter-domain rotation of RRF, which destabilizes two strong intersubunit bridges (B2a and B3) and, ultimately, separates the two subunits. Here, we present a 9 Å (FSC at 0.5 cutoff) cryo-EM map of a 50S EFG GDPNP RRF complex and a quasi-atomic model derived from it, showing the interaction between EF-G and RRF on the 50S subunit in the presence of the non-cleavable GTP analogue GDPNP. The detailed information in this model and a comparative analysis of EF-G structures in various nucleotide- and ribosome-bound states show how rotation of the RRF head domain may be triggered by various domains of EF-G. For validation of our structural model, all known mutations in EF-G and RRF that relate to ribosome recycling have been taken into account. More importantly, our results indicate a substantial conformational change in the Switch I region of EF-G, suggesting that a conformational signal transduction mechanism, similar to that employed in tRNA translocation on the ribosome by EF-G, translates a large-scale movement of EF-G’s domain IV, induced by GTP hydrolysis, into the domain rotation of RRF that eventually splits the ribosome into subunits. PMID:17996252

  12. Effect of Mutations in the Cytochrome b ef Loop on the Electron Transfer Reactions of the Rieske Iron-Sulfur Protein in the Cytochrome bc1 Complex

    PubMed Central

    Rajagukguk, Sany; Yang, Shaoqing; Yu, Chang-An; Yu, Linda; Durham, Bill; Millett, Francis

    2008-01-01

    Long range movement of the iron-sulfur protein (ISP) between the cytochrome b (cyt b) and cyt c1 redox centers plays a key role in electron transfer within the cyt bc1 complex. A series of 21 mutants in the cyt b ef loop of Rhodobacter sphaeroides cyt bc1 were prepared to examine the role of this loop in controlling the capture and release of the ISP from cyt b. Electron transfer in the cyt bc1 complex was studied using a ruthenium dimer to rapidly photooxidize cyt c1 within 1 μs and initiate the reaction. The rate constant for electron transfer from the iron-sulfur center [2Fe2S] center to cyt c1 was k1 = 60,000 s−1. Famoxadone binding to the Qo site decreases k1 to 5,400 s−1, indicating that a conformational change on the surface of cyt b decreases the rate of release of the ISP from cyt b. The mutation I292A on the surface of the ISP binding crater decreased k1 to 4,400 s−1, while addition of famoxadone further decreased it to 3,000 s−1. The mutation L286A at the tip of the ef loop decreased k1 to 33,000 s−1, but famoxadone binding caused no further decrease, suggesting that this mutation blocked the conformational change induced by famoxadone. Studies of all the mutants provide further evidence that the ef loop plays an important role in regulating the domain movement of the ISP to facilitate productive electron transfer and prevent short-circuit reactions. PMID:17253777

  13. Pilot Study of Intensive Chemotherapy with Peripheral Hematopoietic Cell Support for Children Less than 3 Years of Age with Malignant Brain Tumors, The CCG-99703 Phase I/II Study. A Report from the Children’s Oncology Group

    PubMed Central

    Cohen, Bruce H.; Geyer, J. Russell; Miller, Douglas C.; Curran, John G.; Zhou, Tianni; Holmes, Emi; Ingles, Sue Ann; Dunkel, Ira J.; Hilden, Joanne; Packer, Roger J.; Pollack, Ian F.; Gajjar, Amar; Finlay, Jonathan L.

    2016-01-01

    Background The primary goals of the CCG-99703 study were to assess the feasibility and tolerability of, as well as the response rate to, a novel dose-intensive chemotherapy regimen. Methods Between March 1998 and October 2004, 92 eligible patients were enrolled. Following biopsy/resection, patients received three identical cycles of Induction chemotherapy (vincristine, cyclophosphamide, etoposide and cisplatin) administered every 21–28 days. Patients without tumor progression then received three Consolidation cycles of marrow-ablative chemotherapy (thiotepa and carboplatin) followed by autologous hematopoietic cell rescue. Results The Maximum Tolerated Dose (MTD) of thiotepa was 10mg/kg/day x 2 days per cycle. The toxic mortality rate was zero during Induction and 2.6% during Consolidation. Centrally evaluated response rates to Induction and Consolidation in evaluable patients with residual tumor were 73.3% and 66.7% respectively. Disease progression rates on Induction and Consolidation were 4%. Five-year EFS and OS were 43.9±5.2% and 63.6±5% respectively. Gross total resection (GTR) versus EFS and OS of 54.4±7% versus 28.9±7% (p= .0065) and 75.9±8% versus 48.7±8% (p= .0034) respectively. The 5-year EFS for localized (M0) versus metastatic (M1+) medulloblastoma was 67.5+/−9.5% versus 30+/−14.5% (p= .007). The 5-year EFS and OS for desmoplastic medulloblastoma patients versus other medulloblastoma were 78.6+/−11% versus 50.5+/−12% (p= .038) and 85.7±9.4% versus 60.6±11.6% (p= .046) respectively. Conclusions This phase I dose-escalation study of marrow-ablative thiotepa regimen determined an MTD that had acceptable toxicity. Overall survival data justify this strategy for current COG studies. PMID:26092413

  14. Postoperative Mortality after Hip Fracture Surgery: A 3 Years Follow Up

    PubMed Central

    Un, Canan; Sacan, Ozlem; Gamli, Mehmet; Baskan, Semih; Baydar, Mustafa

    2016-01-01

    Background and Aims To determine mortality rates and predisposing factors in patients operated for a hip fracture in a 3-year follow-up period. Methods The study included patients who underwent primary surgery for a hip fracture.The inclusion criteria were traumatic, non-traumatic, osteoporotic and pathological hip fractures requiring surgery in all age groups and both genders. Patients with periprosthetic fractures or previous contralateral hip fracture surgery and patients who could not be contacted by telephone were excluded. At 36 months after surgery, evaluation was made using a structured telephone interview and a detailed examination of the hospital medical records, especially the documents written during anesthesia by the anesthesiologists and the documents written at the time of follow-up visits by the orthopaedic surgeons. A total of 124 cases were analyzed and 4 patients were excluded due to exclusion criteria. The collected data included demographics, type of fracture, co-morbidities, American Society of Anesthesiologists (ASA) scores, anesthesia techniques, operation type (intramedullary nailing or arthroplasty; cemented-noncemented), peroperative complications, refracture during the follow-up period, survival period and mortality causes. Results The total 120 patients evaluated comprised 74 females(61.7%) and 46 males(38.3%) with a mean age of 76.9±12.8 years (range 23–95 years). The ASA scores were ASA I (0.8%), ASA II (21.7%), ASA III (53.3%) and ASA IV (24.2%). Mortality was seen in 44 patients (36.7%) and 76 patients (63.3%) survived during the 36-month follow-up period. Of the surviving patients, 59.1% were female and 40.9% were male.The survival period ranged between 1–1190 days. The cumulative mortality rate in the first, second and third years were 29.17%, 33.33% and 36.67% respectively. The factors associated with mortality were determined as increasing age, high ASA score, coronary artery disease, congestive heart failure, Alzheimer

  15. Patterns of nonfatal heroin overdose over a 3-year period: findings from the Australian treatment outcome study.

    PubMed

    Darke, Shane; Williamson, Anna; Ross, Joanne; Mills, Katherine L; Havard, Alys; Teesson, Maree

    2007-03-01

    To determine annual patterns and correlates of nonfatal heroin overdose across 3 years, data were analyzed on 387 heroin users recruited for the Australian Treatment Outcome Study (ATOS), interviewed at 12, 24, and 36 months. A heroin overdose across follow-up was reported by 18.6%, and naloxone had been administered to 11.9%. Annual rates of overdose declined between baseline and 12 months and then remained stable. Previous overdose experience was strongly related to subsequent overdose. Those with a history of overdose before ATOS were significantly more likely to overdose during the study period. In particular, there was a strong association between overdose experience in any 1 year and increased overdose risk in the subsequent year. This is the first study to examine long-term annual trends in nonfatal heroin overdose. While overdose rates declined after extensive treatment, substantial proportions continued to overdose in each year, and this was strongly associated with overdose history.

  16. A 3-year follow-up study of various types of orthodontic canine-to-canine retainers.

    PubMed

    Artun, J; Spadafora, A T; Shapiro, P A

    1997-10-01

    The present study was performed to test the tendency for plaque and calculus build-up along the wire of different types of bonded orthodontic canine-to-canine retainers, whether the presence of such retainers causes any damage to the teeth involved, the failure rate of the retainers, and any changes in incisor alignment during a 3-year period of retention. The four test groups received either retainers made of thick plain wire bonded only to the canines (n = 11); thick spiral wire bonded only to the canines (n = 13); thin, flexible spiral wire bonded to each tooth (n = 11); or removable retainers (n = 14). Accumulation of plaque and calculus along the gingival margin, gingival inflammation and probing attachment level were scored in lingual areas from canine to canine at the time of fixed appliance removal and again 3 years after retainer insertion. Incisor irregularity was measured on plaster models made at the same time periods. Accumulation of plaque and calculus and development of caries along the wire were scored at follow-up. Retainer failures were recorded whenever they occurred. The results revealed no intergroup differences in changes between baseline and follow-up examinations or status along the retainer wire for any of the variables. Gingival inflammation and plaque accumulation were scored less frequently after 3 years in retention than at the time of debonding. No signs of caries were seen adjacent to the wire. Failures were observed of one, four and three of the fixed retainer types, respectively. These patients showed a greater increase in incisor irregularity than the other patients.

  17. 9 CFR 205.102 - Name of person subjecting a farm product to a security interest, on EFS and master list-format.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... product to a security interest, on EFS and master list-format. 205.102 Section 205.102 Animals and Animal... of person subjecting a farm product to a security interest, on EFS and master list—format. On an EFS, and on a master list, the name of the person subjecting a farm product to a security interest...

  18. Paternal Psychosocial Characteristics and Corporal Punishment of Their 3-Year-Old Children

    ERIC Educational Resources Information Center

    Lee, Shawna J.; Perron, Brian E.; Taylor, Catherine A.; Guterman, Neil B.

    2011-01-01

    This study uses data from 2,309 biological fathers who participated in the Fragile Families and Child Well-Being Study (FFCWS) to examine associations between psychosocial characteristics and levels of corporal punishment (CP) toward their 3-year-old children over the past month. Results indicate that 61% of the fathers reported no CP over the…

  19. Enhancing the Executive Functions of 3-Year-Olds in the Dimensional Change Card Sort Task

    ERIC Educational Resources Information Center

    Perone, Sammy; Molitor, Stephen J.; Buss, Aaron T.; Spencer, John P.; Samuelson, Larissa K.

    2015-01-01

    Executive functions enable flexible thinking, something young children are notoriously bad at. For instance, in the dimensional change card sort (DCCS) task, 3-year-olds can sort cards by one dimension (shape), but continue to sort by this dimension when asked to switch (to color). This study tests a prediction of a dynamic neural field model that…

  20. Abstract Sentence Representations in 3-Year-Olds: Evidence from Language Production and Comprehension

    ERIC Educational Resources Information Center

    Bencini, Giulia M. L.; Valiana, Virginia V.

    2008-01-01

    We use syntactic priming to test the abstractness of the sentence representations of young 3-year-olds (35-42 months). In describing pictures with inanimate participants, 18 children primed with passives produced more passives (11 with a strict scoring scheme, 16 with lax scoring) than did 18 children primed with actives (2 on either scheme) or 12…

  1. Directly Observed Physical Activity among 3-Year-Olds in Finnish Childcare

    ERIC Educational Resources Information Center

    Soini, Anne; Villberg, Jari; Sääkslahti, Arja; Gubbels, Jessica; Mehtälä, Anette; Kettunen, Tarja; Poskiparta, Marita

    2014-01-01

    The main purpose of the study was to determine 3-year-olds' physical activity levels and how these vary across season, gender, time of day, location, and the physical and social environment in childcare settings in Finland. A modified version of the Observational System for Recording Physical Activity in Children-Preschool (OSRAC-P) was used to…

  2. Learning To Learn: Children's Progress through the First 3 Years of School. Junior School Study.

    ERIC Educational Resources Information Center

    Wylie, Cathy; Smith, Lesley

    This study organized in 2 sections examined the progress of 32 New Zealand children during their first 3 years at school. Their achievement levels in reading, mathematics, and writing were examined based on interviews with the children, their teachers, and their parents; school records; notes; and video recordings. Section 1 deals with perceptions…

  3. Earth Science. Developing an Early Interest in Science: A Preschool Science Curriculum. (3-Year-Olds).

    ERIC Educational Resources Information Center

    Summer, Gail L.; Giovannini, Kathleen

    This teaching guide on earth sciences for 3-year-old children is based on a modification of the "Plan, Do, Review" approach to education devised by High Scope in Ypsilanti, Michigan. First implemented as an outreach early childhood program in North Carolina, the science activities described in this guide can be adapted to various early childhood…

  4. Turning Believers into Skeptics: 3-Year-Olds' Sensitivity to Cues to Speaker Credibility

    ERIC Educational Resources Information Center

    Jaswal, Vikram K.; Malone, Lauren S.

    2007-01-01

    Under most circumstances, children (and adults) can safely assume that the testimony they hear is true. In two studies, we investigated whether 3-year-olds (N = 100) would continue to hold this assumption even if the person who provided the testimony behaved in an uncertain, ignorant, and/or distracted manner. In Study 1, children were less likely…

  5. The Baltimore City Drug Treatment Court: 3-Year Self-Report Outcome Study

    ERIC Educational Resources Information Center

    Gottfredson, Denise C.; Kearley, Brook W.; Najaka, Stacy S.; Rocha, Carlos M.

    2005-01-01

    This study reports results from interviews with 157 research participants who were interviewed 3 years after randomization into treatment and control conditions in the evaluation of the Baltimore City Drug Treatment Court. The interviews asked about crime, substance use, welfare, employment, education, mental and physical health, and family and…

  6. Examining Communicative Behaviors in a 3-Year-Old Boy Who Is Blind.

    ERIC Educational Resources Information Center

    Perfect, Michelle M.

    2001-01-01

    The communication patterns of a 3-year-old boy who is blind were observed during 35 videotaped classroom sessions to determine if his echolalic responses varied according to school activity and message category. Analysis revealed that, although the child was expressive with adults, he had difficulty communicating with his peers and in producing…

  7. Words, Shape, Visual Search and Visual Working Memory in 3-Year-Old Children

    ERIC Educational Resources Information Center

    Vales, Catarina; Smith, Linda B.

    2015-01-01

    Do words cue children's visual attention, and if so, what are the relevant mechanisms? Across four experiments, 3-year-old children (N = 163) were tested in visual search tasks in which targets were cued with only a visual preview versus a visual preview and a spoken name. The experiments were designed to determine whether labels facilitated…

  8. Dimensions of Oppositional Defiant Disorder in 3-Year-Old Preschoolers

    ERIC Educational Resources Information Center

    Ezpeleta, Lourdes; Granero, Roser; de la Osa, Nuria; Penelo, Eva; Domenech, Josep M.

    2012-01-01

    Background: To test the factor structure of oppositional defiant disorder (ODD) symptoms and to study the relationships between the proposed dimensions and external variables in a community sample of preschool children. Method: A sample of 1,341 3-year-old preschoolers was randomly selected and screened for a double-phase design. In total, 622…

  9. Predictors of Reading Development in Deaf Children: A 3-Year Longitudinal Study

    ERIC Educational Resources Information Center

    Kyle, Fiona E.; Harris, Margaret

    2010-01-01

    The development of reading ability in a group of deaf children was followed over a 3-year period. A total of 29 deaf children (7-8 years of age at the first assessment) participated in the study, and every 12 months they were given a battery of literacy, cognitive, and language tasks. Earlier vocabulary and speechreading skills predicted…

  10. Basic Facts about Low-Income Children: Children under 3 Years, 2013. Fact Sheet

    ERIC Educational Resources Information Center

    Jiang, Yang; Ekono, Mercedes; Skinner, Curtis

    2015-01-01

    Children under 18 years represent 23 percent of the population, but they comprise 33 percent of all people in poverty. Among all children, 44 percent live in low-income families and approximately one in every five (22 percent) live in poor families. Our very youngest children--infants and toddlers under age 3 years--appear to be particularly…

  11. A Field Training Model for Creative Arts Therapies: Report from a 3-Year Program Evaluation

    ERIC Educational Resources Information Center

    Orkibi, Hod

    2012-01-01

    Clinical field training is an essential component of educating future therapists. This article discusses a creative arts therapies field training model in Israel as designed and modified from 3 years of program evaluation in a changing regulatory context. A clinical seminar structure puts beginning students in the role of participant-observer in…

  12. Emotional and Personality-Related Career Decision-Making Difficulties: A 3-Year Follow-Up

    ERIC Educational Resources Information Center

    Gati, Itamar; Asulin-Peretz, Lisa; Fisher, Ahinoam

    2012-01-01

    This study tests the temporal stability and the concurrent and predictive validity of the Emotional and Personality-related Career decision-making Difficulties (EPCD) model and questionnaire. Five hundred forty-three participants filled out the EPCD twice, 3 years apart. The Anxiety cluster was the most stable of the three, followed by the…

  13. Leadership Coaching in an Induction Program for Novice Principals: A 3-Year Study

    ERIC Educational Resources Information Center

    Lochmiller, Chad R.

    2014-01-01

    This article presents results from a study of leadership coaches who worked with novice principals in a university-based induction program for a 3-year period. The qualitative case study describes how the support the coaches provided to the novice principals changed over time. The study reveals that coaches adapted their leadership coaching…

  14. Behavioral and Emotional Problems among Turkish Children at Ages 2 to 3 Years.

    ERIC Educational Resources Information Center

    Erol, Nese; Simsek, Zeynep; Oner, Ozgur; Munir, Kerim

    2005-01-01

    Objective: Within the framework of the Mental Health Surveys of Turkey, the authors investigated the distribution and prevalence of parent-reported behavioral and emotional problems in a nationally representative sample of 2- to 3-year-old children. Method: A cross-sectional population-based survey from October 1996 through March 1997 using a…

  15. Does Attention Constrain Developmental Trajectories in Fragile X Syndrome? A 3-Year Prospective Longitudinal Study

    ERIC Educational Resources Information Center

    Cornish, Kim; Cole, Victoria; Longhi, Elena; Karmiloff-Smith, Annette; Scerif, Gaia

    2012-01-01

    Basic attentional processes and their impact on developmental trajectories in fragile X syndrome were assessed in a 3-year prospective study. Although fragile X syndrome is a monogenic X-linked disorder, there is striking variability in outcomes even in young boys with the condition. Attention is a key factor constraining interactions with the…

  16. Enhancing Students' Engagement: Report of a 3-Year Intervention with Middle School Teachers

    ERIC Educational Resources Information Center

    Turner, Julianne C.; Christensen, Andrea; Kackar-Cam, Hayal Z.; Trucano, Meg; Fulmer, Sara M.

    2014-01-01

    All teachers (N = 32) at one middle school participated in a university-led intervention to improve student engagement. Teachers discussed four principles of motivation and related instructional strategies. Teachers enacted instructional strategies in their classrooms. We observed six randomly selected teachers and their students over 3 years.…

  17. The Semiotic Landscape and 3-Year-Olds' Emerging Understanding of Multimodal Communication Practices

    ERIC Educational Resources Information Center

    Yamada-Rice, Dylan

    2014-01-01

    This article considers the impact of the increasing use of the visual mode in texts found in urban landscapes on two 3-year-olds' understanding of communication practices. The data discussed are taken from a study into a group of 3- to 6-year-olds' interaction with and emerging comprehension of the visual mode and its connection to writing in…

  18. How Selective Are 3-Year-Olds in Imitating Novel Linguistic Material?

    ERIC Educational Resources Information Center

    Bannard, Colin; Klinger, Jörn; Tomasello, Michael

    2013-01-01

    In 3 studies we explored when 3-year-olds would imitate novel words in utterances produced by adult speakers. Child and experimenter took turns in requesting objects from a game master. The experimenter always went first and always preceded the object's familiar name with a novel adjective (e.g., "the dilsige duck"). In the first 2…

  19. 3-Year-Old Children Make Relevance Inferences in Indirect Verbal Communication

    ERIC Educational Resources Information Center

    Schulze, Cornelia; Grassmann, Susanne; Tomasello, Michael

    2013-01-01

    Three studies investigated 3-year-old children's ability to determine a speaker's communicative intent when the speaker's overt utterance related to that intent only indirectly. Studies 1 and 2 examined children's comprehension of indirectly stated requests (e.g., "I find Xs good" can imply, in context, a request for…

  20. Prevalence of malocclusion traits and sucking habits among 3-year-old children.

    PubMed

    Dimberg, Lillemor; Bondemark, Lars; Söderfeldt, Björn; Lennartsson, Bertil

    2010-01-01

    The aim of the present study was to evaluate the prevalence of malocclusion traits and sucking habits among 3-year-old children. A sample of 457 3-year-old children (234 girls and 223 boys) was obtained from three Public Dental Health clinics in Orebro County Council, Sweden. Data from clinical examination and a questionnaire were used to determine malocclusion traits, sucking habits, snoring and breathing pattern including nocturnal breathing disturbances. The results showed that 70% had one or more malocclusion traits at 3 years of age. The most common malocclusion traits were anterior open bite (50%), Class II occlusion (26%), increased overjet (23%) and posterior crossbite (19%). The prevalence of sucking habit was 66% and dummy sucking was dominating and in connection with more malocclusion traits than finger/thumb sucking. A significant association was found between the sucking habits and the most prevalent malocclusions, anterior open bite, Class II occlusion, increased overjet and posterior crossbite. In conclusion, the prevalence of malocclusion traits in 3-year-old children was high. Sucking habits was highly prevalent and dummy sucking resulted in more malocclusion traits than finger/thumb sucking did.

  1. Risk of Mother-Reported Child Abuse in the First 3 Years of Life

    ERIC Educational Resources Information Center

    Windham, Amy M.; Rosenberg, Leon; Fuddy, Loretta; McFarlane, Elizabeth; Sia, Calvin; Duggan, Anne K

    2004-01-01

    Objective: The purpose of this research was to investigate, within an at-risk population, parent and child characteristics associated with a mother's self-reports of severe physical assault and assault on the self-esteem of the child in the first 3 years of life. Design: The study population consisted of a community-based sample of mothers of…

  2. Two-and 3-Year-Olds Know What Others Have and Have Not Heard

    ERIC Educational Resources Information Center

    Moll, Henrike; Carpenter, Malinda; Tomasello, Michael

    2014-01-01

    Recent studies have established that even infants can determine what others know based on previous visual experience. In the current study, we investigated whether 2-and 3-year-olds know what others know based on previous auditory experience. A child and an adult heard the sound of one object together, but only the child heard the sound of another…

  3. Prekindergarten Children's Executive Functioning Skills and Achievement Gains: The Utility of Direct Assessments and Teacher Ratings

    ERIC Educational Resources Information Center

    Fuhs, Mary Wagner; Farran, Dale Clark; Nesbitt, Kimberly Turner

    2015-01-01

    An accumulating body of evidence suggests that young children who exhibit greater executive functioning (EF) skills in early childhood also achieve more academically. The goal of the present study was to examine the unique contributions of direct assessments and teacher ratings of children's EF skills at the beginning of prekindergarten (pre-k) to…

  4. Translation Elongation Factor eEF1A2 is a Novel Anticancer Target for the Marine Natural Product Plitidepsin

    PubMed Central

    Losada, Alejandro; Muñoz-Alonso, María José; García, Carolina; Sánchez-Murcia, Pedro A.; Martínez-Leal, Juan Fernando; Domínguez, Juan Manuel; Lillo, M. Pilar; Gago, Federico; Galmarini, Carlos M.

    2016-01-01

    eEF1A2 is one of the isoforms of the alpha subunit of the eukaryotic Elongation Factor 1. It is overexpressed in human tumors and is endowed with oncogenic properties, favoring tumor cell proliferation while inhibiting apoptosis. We demonstrate that plitidepsin, an antitumor agent of marine origin that has successfully completed a phase-III clinical trial for multiple myeloma, exerts its antitumor activity by targeting eEF1A2. The drug interacts with eEF1A2 with a KD of 80 nM and a target residence time of circa 9 min. This protein was also identified as capable of binding [14C]-plitidepsin in a cell lysate from K-562 tumor cells. A molecular modelling approach was used to identify a favorable binding site for plitidepsin at the interface between domains 1 and 2 of eEF1A2 in the GTP conformation. Three tumor cell lines selected for at least 100-fold more resistance to plitidepsin than their respective parental cells showed reduced levels of eEF1A2 protein. Ectopic expression of eEF1A2 in resistant cells restored the sensitivity to plitidepsin. FLIM-phasor FRET experiments demonstrated that plitidepsin localizes in tumor cells sufficiently close to eEF1A2 as to suggest the formation of drug-protein complexes in living cells. Altogether, our results strongly suggest that eEF1A2 is the primary target of plitidepsin. PMID:27713531

  5. Toxoplasma gondii Elongation Factor 1-Alpha (TgEF-1α) Is a Novel Vaccine Candidate Antigen against Toxoplasmosis.

    PubMed

    Wang, Shuai; Zhang, Zhenchao; Wang, Yujian; Gadahi, Javaid A; Xu, Lixin; Yan, Ruofeng; Song, Xiaokai; Li, Xiangrui

    2017-01-01

    Toxoplasma gondii (T. gondii) is an obligate intracellular parasite which can infect almost all warm-blood animals, leading to toxoplasmosis. Screening and discovery of an effective vaccine candidate or new drug target is crucial for the control of this disease. In this study, the recombinant T. gondii elongation factor 1-alpha (rTgEF-1α) was successfully expressed in in Escherichia coli. Passive immunization of mice with anti-rTgEF-1α polyclonal antibody following challenge with a lethal dose of tachyzoites significantly increased the survival time compared with PBS control group. The survival time of mice challenged with tachyzoites pretreated with anti-rTgEF-1α PcAb also was significantly increased. Invasion of tachyzoites into mouse macrophages was significantly inhibited in the anti-rTgEF-1α PcAb pretreated group. Mice vaccinated with rTgEF-1α induced a high level of specific anti-T. gondii antibodies and production of IFN-gamma, interleukin-4. The expression levels of MHC-I and MHC-II molecules as well as the percentages of CD4(+) and CD8(+) T cells in mice vaccinated with rTgEF-1α was significantly increased, respectively (P < 0.05), compared with all the controls. Immunization with rTgEF-1α significantly (P < 0.05) prolonged survival time (14.53 ± 1.72 days) after challenge infection with the virulent T. gondii RH strain. These results indicate that T. gondii EF-1α plays an essential role in mediating host cell invasion by the parasite and, as such, could be a candidate vaccine antigen against toxoplasmosis.

  6. Remediation of hemorrhagic shock-induced intestinal barrier dysfunction by treatment with diphenyldihaloketones EF24 and CLEFMA.

    PubMed

    Yadav, Vivek R; Hussain, Alamdar; Sahoo, Kaustuv; Awasthi, Vibhudutta

    2014-11-01

    Gut is very sensitive to hypoperfusion and hypoxia, and deranged gastrointestinal barrier is implicated in systemic failure of various organs. We recently demonstrated that diphenyldihaloketone EF24 [3,5-bis(2-fluorobenzylidene)piperidin-4-one] improves survival in a rat model of hemorrhagic shock. In this study, we tested EF24 and its other analog CLEFMA (4-[3,5-bis(2-chlorobenzylidene)-4-oxo-piperidine-1-yl]-4-oxo-2-butenoic acid) for their effect on intestinal barrier dysfunction in hypovolemic shock. Hypovolemia was induced in rats by withdrawing 50% of blood. EF24 or CLEFMA (0.4 mg/kg i.p.) treatment was provided, without volume resuscitation, after 1 hour of hemorrhage. Ileum was collected 5 hours after the treatment to investigate the expression of tight junction proteins (zonula occludens, claudin, and occludin) and epithelial injury markers [myeloperoxidase, ileal lipid-binding protein (ILBP), CD163, and plasma citrulline]. The ileal permeability for dextran-fluoroisothiocyanate and Evan's blue dye was determined. EF24 and CLEFMA reduced the hypovolemia-induced plasma citrulline levels and the ileal expression of myeloperoxidase, ILBP, and CD163. The drugs also restored the basal expression levels of zonula occludens, claudin, and occludin, which were substantially deranged by hypovolemia. In ischemic ileum, the expression of phospho(tyrosine)-zonula occludens-1 was reduced, which was reinstated by EF24 and CLEFMA. In contrast, the drug treatments maintained the hypovolemia-induced expression of phospho(threonine)-occludin, but reduced that of phospho(tyrosine)-occludin. Both EF24 and CLEFMA treatments reduced the intestinal permeability enhanced by hypovolemia. EF24 and CLEFMA attenuate hypovolemic gut pathology and protect barrier function by restoring the status of tight junction proteins. These effects were observed in unresuscitated shock, implying the benefit of EF24 and CLEFMA in prehospital care of shock.

  7. Translation elongation factor EF-Tu modulates filament formation of actin-like MreB protein in vitro.

    PubMed

    Defeu Soufo, Hervé Joël; Reimold, Christian; Breddermann, Hannes; Mannherz, Hans G; Graumann, Peter L

    2015-04-24

    EF-Tu has been shown to interact with actin-like protein MreB and to affect its localization in Escherichia coli and in Bacillus subtilis cells. We have purified YFP-MreB in an active form, which forms filaments on glass slides in vitro and was active in dynamic light-scattering assays, polymerizing in milliseconds after addition of magnesium. Purified EF-Tu enhanced the amount of MreB filaments, as seen by sedimentation assays, the speed of filament formation and the length of MreB filaments in vitro. EF-Tu had the strongest impact on MreB filaments in a 1:1 ratio, and EF-Tu co-sedimented with MreB filaments, revealing a stoichiometric interaction between both proteins. This was supported by cross-linking assays where 1:1 species were well detectable. When expressed in E. coli cells, B. subtilis MreB formed filaments and induced the formation of co-localizing B. subtilis EF-Tu structures, indicating that MreB can direct the positioning of EF-Tu structures in a heterologous cell system. Fluorescence recovery after photobleaching analysis showed that MreB filaments have a higher turnover in B. subtilis cells than in E. coli cells, indicating different filament kinetics in homologous or heterologous cell systems. The data show that MreB can direct the localization of EF-Tu in vivo, which in turn positively affects the formation and dynamics of MreB filaments. Thus, EF-Tu is a modulator of the activity of a bacterial actin-like protein.

  8. Kidney-Sparing Methods for Extended-Field Intensity-Modulated Radiotherapy (EF-IMRT) in Cervical Carcinoma Treatment

    PubMed Central

    Kunogi, Hiroaki; Yamaguchi, Nanae; Terao, Yasuhisa; Sasai, Keisuke

    2016-01-01

    Coplanar extended-field intensity-modulated radiation therapy (EF-IMRT) targeting the whole-pelvic and para-aortic lymph nodes in patients with advanced cervical cancer results in impaired creatinine clearance. An improvement in renal function cannot be expected unless low-dose (approximately 10 Gy) kidney exposure is reduced. The dosimetric method should be considered during EF-IMRT planning to further reduce low-dose exposure to the kidneys. To assess the usefulness of non-coplanar EF-IMRT with kidney-avoiding beams to spare the kidneys during cervical carcinoma treatment in dosimetric analysis between non-coplanar and coplanar EF-IMRT, we compared the doses of the target organ and organs at risk, including the kidney, in 10 consecutive patients. To estimate the influence of EFRT on renal dysfunction, creatinine clearance values after treatment were also examined in 18 consecutive patients. Of these 18 patients, 10 patients who were included in the dosimetric analysis underwent extended field radiation therapy (EFRT) with concurrent chemotherapy, and eight patients underwent whole-pelvis radiation therapy with concurrent chemotherapy to treat cervical carcinoma between April 2012 and March 2015 at our institution. In the dosimetric analysis, non-coplanar EF-IMRT was effective at reducing low-dose (approximately 10 Gy) exposure to the kidneys, thus maintaining target coverage and sparing other organs at risk, such as the small bowel, rectum, and bladder, compared with coplanar EF-IMRT. Renal function in all 10 patients who underwent EFRT, including coplanar EF-IMRT (with kidney irradiation), was low after treatment, and differed significantly from that of the eight patients who underwent WPRT (no kidney irradiation) 6 months after the first day of treatment (P = 0.005). In conclusion, non-coplanar EF-IMRT should be considered in patients with advanced cervical cancer, particularly in patients with a long life expectancy or with pre-existing renal dysfunction. PMID

  9. Toxoplasma gondii Elongation Factor 1-Alpha (TgEF-1α) Is a Novel Vaccine Candidate Antigen against Toxoplasmosis

    PubMed Central

    Wang, Shuai; Zhang, Zhenchao; Wang, Yujian; Gadahi, Javaid A.; Xu, Lixin; Yan, Ruofeng; Song, Xiaokai; Li, Xiangrui

    2017-01-01

    Toxoplasma gondii (T. gondii) is an obligate intracellular parasite which can infect almost all warm-blood animals, leading to toxoplasmosis. Screening and discovery of an effective vaccine candidate or new drug target is crucial for the control of this disease. In this study, the recombinant T. gondii elongation factor 1-alpha (rTgEF-1α) was successfully expressed in in Escherichia coli. Passive immunization of mice with anti-rTgEF-1α polyclonal antibody following challenge with a lethal dose of tachyzoites significantly increased the survival time compared with PBS control group. The survival time of mice challenged with tachyzoites pretreated with anti-rTgEF-1α PcAb also was significantly increased. Invasion of tachyzoites into mouse macrophages was significantly inhibited in the anti-rTgEF-1α PcAb pretreated group. Mice vaccinated with rTgEF-1α induced a high level of specific anti-T. gondii antibodies and production of IFN-gamma, interleukin-4. The expression levels of MHC-I and MHC-II molecules as well as the percentages of CD4+ and CD8+ T cells in mice vaccinated with rTgEF-1α was significantly increased, respectively (P < 0.05), compared with all the controls. Immunization with rTgEF-1α significantly (P < 0.05) prolonged survival time (14.53 ± 1.72 days) after challenge infection with the virulent T. gondii RH strain. These results indicate that T. gondii EF-1α plays an essential role in mediating host cell invasion by the parasite and, as such, could be a candidate vaccine antigen against toxoplasmosis. PMID:28243226

  10. The impact of remedial intervention on 3-year recidivism among first-time DUI offenders in Mississippi.

    PubMed

    Robertson, Angela A; Gardner, Sheena; Xu, Xiaohe; Costello, Humphrey

    2009-09-01

    This study examines the impact of the Mississippi Alcohol Safety Education Program (MASEP), a court-mandated intervention program, on 3-year recidivism rates among first-time DUI offenders (i.e. those convicted of a first offense for driving under the influence of alcohol or another drug). It also examines whether a new version of the curriculum that incorporates activities to enhance motivation for change further ameliorates recidivism. Cox proportional hazard regression models are used to compare recidivism rates among DUI offenders who completed MASEP with those who did not complete or who failed to enroll in the program. Recidivism rates were also compared for MASEP participants across time periods during which curriculum revisions were introduced. The hazard of recidivism was lower for individuals who completed the program than for individuals who did not complete or did not enroll in the program. Recidivism rates were further reduced following the introduction of curriculum revisions. Attendance of court-mandated remedial intervention programs lower subsequent DUI arrests and program content is associated with lower rates.

  11. The non-canonical hydroxylase structure of YfcM reveals a metal ion-coordination motif required for EF-P hydroxylation.

    PubMed

    Kobayashi, Kan; Katz, Assaf; Rajkovic, Andrei; Ishii, Ryohei; Branson, Owen E; Freitas, Michael A; Ishitani, Ryuichiro; Ibba, Michael; Nureki, Osamu

    2014-10-29

    EF-P is a bacterial tRNA-mimic protein, which accelerates the ribosome-catalyzed polymerization of poly-prolines. In Escherichia coli, EF-P is post-translationally modified on a conserved lysine residue. The post-translational modification is performed in a two-step reaction involving the addition of a β-lysine moiety and the subsequent hydroxylation, catalyzed by PoxA and YfcM, respectively. The β-lysine moiety was previously shown to enhance the rate of poly-proline synthesis, but the role of the hydroxylation is poorly understood. We solved the crystal structure of YfcM and performed functional analyses to determine the hydroxylation mechanism. In addition, YfcM appears to be structurally distinct from any other hydroxylase structures reported so far. The structure of YfcM is similar to that of the ribonuclease YbeY, even though they do not share sequence homology. Furthermore, YfcM has a metal ion-coordinating motif, similar to YbeY. The metal ion-coordinating motif of YfcM resembles a 2-His-1-carboxylate motif, which coordinates an Fe(II) ion and forms the catalytic site of non-heme iron enzymes. Our findings showed that the metal ion-coordinating motif of YfcM plays an essential role in the hydroxylation of the β-lysylated lysine residue of EF-P. Taken together, our results suggested the potential catalytic mechanism of hydroxylation by YfcM.

  12. Simultaneous removal of phosphorus and EfOM using MIEX, coagulation, and low-pressure membrane filtration.

    PubMed

    Kim, Hyun-Chul; Timmes, Thomas C; Dempsey, Brian A

    2015-01-01

    The feasibility of using magnetic ion exchange (MIEX) treatment, in-line alum coagulation, and low-pressure membrane filtration was investigated for the simultaneous removal of total phosphorus (TP) and effluent organic matter (EfOM) from biologically treated wastewater. The focus was also placed on minimizing fouling of polyvinylidene fluoride and polyethersulfone membranes, which are the most commonly used low-pressure membranes in new and retrofit wastewater treatment plants. MIEX alone was effective for the removal of EfOM, and MIEX plus a small alum dose was very effective in removing both EfOM and TP. MIEX removed phosphorus, but organic acids in EfOM were preferentially removed, and the effects of competing anions on the removal of EfOM were insignificant. All the pretreatment strategies decreased the resistance to filtration. The greatest decrease in fouling was achieved by using MIEX (15 mL L⁻¹) plus a very low dose of alum (∼0.5 mg Al L⁻¹). Sweep floc coagulation using alum and without MIEX also significantly decreased fouling but did not effectively remove EfOM and produced high floc volume that could be problematic for inside-out hollow-fibre modules. The addition of these reagents into rapid mix followed by membrane filtration would provide operational simplicity and could be easily retrofitted at existing membrane filtration facilities.

  13. Detection of trace elements in DI water and comparison of several water solutions by using EF-FLRD chemical sensors

    NASA Astrophysics Data System (ADS)

    Kaya, M.; Wang, C.

    2017-02-01

    Detection of trace elements in DI water and comparison of several types of water respons such as DI water, tap water, and ocean water were studied by using EF-FLRD chemical sensors. Solutions of Mg, Fe, P, and Cd elements with a concentration of 1000 µg/ml (1 mg/ml) which corresponds to 1000 ppm by weight were tested. DI water, tap water, and real ocean water were utilized as medium to observe refractive index difference of solutions. The EF sensing technique which is based on the EF scattering effect was employed for the detection of trace chemicals and recording of solution responses. Due to the refractive index differences between solutions, optical loss of the sensor was different when the sensor head was immersed into solutions of approximately 10 ml each. The differences of the refractive indices are presented by recording ringdown times when the sensor head was immersed into the solutions. Fast response (˜1s), high sensitive, and reproducible EF-FLRD chemical sensors were fabricated and tested in laboratory conditions. High sensitivity of the sensors due to being capability of detecting smaller differences between measurands without any additional components or treatment makes the EF-FLRD sensors more attractive. Enhanced sensitivity of the EF-FLRD chemical sensors as a result of the multi-pass nature of the FLRD technique has potential application in detecting of trace elements in monitoring of water quality.

  14. Regulation of trunk neural crest delamination by δEF1 and Sip1 in the chicken embryo.

    PubMed

    Yasumi, Takahiro; Inoue, Masashi; Maruhashi, Mitsuji; Kamachi, Yusuke; Higashi, Yujiro; Kondoh, Hisato; Uchikawa, Masanori

    2016-02-01

    The vertebrate Zfhx1 transcription factor family comprises δEF1 and Sip1, which bind to CACCT-containing sequences and act as transcriptional repressors. It has been a longstanding question whether these transcription factors share the same regulatory functions in vivo. It has been shown that neural crest (NC) delamination depends on the Sip1 activity at the cranial level in mouse and chicken embryos, and it remained unclear how NC delamination is regulated at the trunk level. We observed that the expression of δEF1 and Sip1 overlaps in many tissues in chicken embryos, including NC cells at the trunk level. To clarify the above questions, we separately knocked down δEF1 and Sip1 or in combination in NC cells by electroporation of vectors expressing short hairpin RNAs (shRNAs) against respective mRNAs on the dorsal side of neural tubes that generate NC cells. In all cases, the migrating NC cell population was significantly reduced, paralleled by the decreased expression of δEF1 or Sip1 targeted by shRNAs. Expression of Sox10, the major transcription factor that regulates NC development, was also decreased by the shRNAs against δEF1 or Sip1. We conclude that the trunk NC delamination is regulated by both δEF1 and Sip1 in an analogous manner, and that these transcription factors can share equivalent regulatory functions in embryonic tissues.

  15. Cloning, expression, and characterization of a novel Opisthorchis viverrini calcium-binding EF-hand protein.

    PubMed

    Senawong, Gulsiri; Laha, Thewarach; Loukas, Alex; Brindley, Paul J; Sripa, Banchob

    2012-03-01

    A novel 22.8 kDa of Opisthorchis viverrini (Ov) calcium-binding EF-hand protein (Ov CaBP) was identified and isolated from an immunoscreening of the adult stage Ov cDNA library by using a human cholangiocarcinoma (CCA) serum. This protein was related to other calcium-binding proteins and conserved among the trematodes. Ov CaBP shared 98% amino acid identity to 22.8 kDa of Clonorchis sinensis CaBP and both were classified as a new group of CaBP EF-hand protein by multiple sequence alignment and phylogenetic tree analysis. The open reading frame of Ov CaBP was 585 bp which encoded for 194 amino acids. The N-terminal part is composed of two calcium-binding EF-hand motifs whereas the C-terminal part contains a dynein light chain motif (DLC). In addition, transcription analysis by RT-PCR revealed that it was constitutively transcribed in all stages, including metacercariae, juvenile, and adult. Furthermore, recombinant Ov CaBP protein (rOv CaBP) was expressed as a soluble protein and antibody generated against this rOv CaBP protein was capable of detecting Ov CaBP in the Ov somatic extracts but not in Ov ES products. This anti-rOv CaBP serum was also used to localize Ov CaBP in Ov infected hamster's liver sections which the distribution of Ov CaBP was located in gut epithelium, miracidia in eggs and slightly in parenchyma. Moreover, rOv CaBP protein showed a calcium-binding property in non-denaturing gel mobility shift assay.

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

    PubMed

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

    2017-01-01

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

  17. 2ND EF Conference in Turbulent Heat Transfer, Manchester, UK 1998. Volume 1

    DTIC Science & Technology

    1998-06-01

    1WB.7C 1W1UC •v*ataj «vnlMlai i-V 1 iBriMHI MWBlaj fprriatfa ■ HSV Of»U» Ia»fUC T-4UC : BBIW OIJIHIIM 1 *>IMC T»«MC (g) (h) Figure 7 Local...t’ k THE UNIVERSITY y MANCHESTER UMIST 2nd EF Conference in TURBULENT HEAT TRANSFER Manchester, UK 1 998 Approved /or public vil...QXTALTTY INSPECTED 1 CONTENTS VOLUME I Session 1 : Heat Transfer Under Simple Shearing (Chairmen: B. E. Launder and T. J. Hanratty) Y. Na, D. V

  18. HFNEF, HFpEF, HF-PEF, or DHF: what is in an acronym?

    PubMed

    Sanderson, John E

    2014-02-01

    It is well recognized that many patients presenting with heart failure have a normal left ventricular ejection fraction. There has been debate about the correct name for this condition including originally Diastolic Heart Failure (DHF), Heart Failure with a Normal Ejection Fraction (HFNEF), and more recently Heart Failure with a Preserved Ejection Fraction, usually abbreviated to HFpEF. In this viewpoint is it argued that 'Preserved' is the least appropriate word to use, as ejection fraction declines over time and furthermore it is never explained why the 'p' is small. The most honest acronym is HFNEF.

  19. Rare Perilunate Injury as a Result of Chronic Trauma in 3-Year-Old Girl

    PubMed Central

    Tomaszewski, Ryszard

    2015-01-01

    A 3-year-old girl was reported to have perilunate dislocation. The child had suffered, approximately 18 months before, a repetitive wrist injury by means of frequent pulling and bending of the hand by the father who may have physically abused the child for approximately 2 months. At the age of 3 years and 4 months, we performed the reduction of the perilunate dislocation and the plasty of the dorsal scapholunate ligament using the capsular flap prepared from the extensor retinaculum. The wrist was immobilized for 6 weeks. Two months after surgery, patient started the physiotherapy for 3 months. The patient could flex up the wrist to 40 degrees and extend up to 45 degrees (mobility of the healthy wrist was 60, 50 degrees) during the examination 24 months' post-op. Only the surgical treatment of the perilunate dislocation can lead to obtain the good surgical result. PMID:26788457

  20. A 3 Year-Old Male Child Ingested Approximately 750 Grams of Elemental Mercury

    PubMed Central

    Uysalol, Metin; Parlakgül, Güneş; Yılmaz, Yasin; Çıtak, Agop; Uzel, Nedret

    2016-01-01

    Background: The oral ingestion of elemental mercury is unlikely to cause systemic toxicity, as it is poorly absorbed through the gastrointestinal system. However, abnormal gastrointestinal function or anatomy may allow elemental mercury into the bloodstream and the peritoneal space. Systemic effects of massive oral intake of mercury have rarely been reported. Case Report: In this paper, we are presenting the highest single oral intake of elemental mercury by a child aged 3 years. A Libyan boy aged 3 years ingested approximately 750 grams of elemental mercury and was still asymptomatic. Conclusion: The patient had no existing disease or abnormal gastrointestinal function or anatomy. The physical examination was normal. His serum mercury level was 91 µg/L (normal: <5 µg/L), and he showed no clinical manifestations. Exposure to mercury in children through different circumstances remains a likely occurrence. PMID:27606146

  1. Rational action selection in 1½- to 3-year-olds following an extended training experience.

    PubMed

    Klossek, Ulrike M H; Dickinson, Anthony

    2012-02-01

    Previous studies failed to find evidence for rational action selection in children under 2 years of age. The current study investigated whether younger children required more training to encode the relevant causal relationships. Children between 1½ and 3 years of age were trained over two sessions to perform actions on a touch-sensitive screen to obtain video clips as outcomes. Subsequently, a visual habituation procedure was employed to devalue one of the training outcomes. As in previous studies, 2- and 3-year-olds chose actions associated with an expected valued outcome significantly more often during a subsequent choice test. Moreover, analysis of children's first responses in the post-devaluation test revealed evidence of rational action selection even in the youngest age group (18-23 months). Consistent with dual-process accounts of action control, the findings support the view that the ability to make rational action choices develops gradually.

  2. Probabilistic assessment of exposure to cosmetic products by French children aged 0-3 years.

    PubMed

    Ficheux, A S; Dornic, N; Bernard, A; Chevillotte, G; Roudot, A C

    2016-08-01

    Very few exposure data are available for children in Europe and worldwide. The aim of this study was to assess the exposure to cosmetic products used on children aged 0-3 years using recent consumption data generated for the French population. Exposure was assessed using a probabilistic method for 24 products including cleanser, skin care, fragrance, solar and bottom products. The exposure data obtained in this study for children aged 0-3 years were higher than the values fixed by the SCCS for all common products: liquid shampoo, face moisturizer cream, toothpaste, shower gel and body moisturizer cream. Exposure was assessed for the first time for many products such as sunscreens, Eau de toilette and massage products. These new French exposure values will be useful for safety assessors and for safety agencies.

  3. Concurrent and Predictive Validity of Parent Reports of Child Language at Ages 2 and 3 Years

    PubMed Central

    Campbell, Thomas F.; Kurs-Lasky, Marcia; Rockette, Howard E.; Dale, Philip S.; Colborn, D. Kathleen; Paradise, Jack L.

    2005-01-01

    The MacArthur–Bates Communicative Development Inventories (CDI; Dale, 1996; Fenson et al., 1994), parent reports about language skills, are being used increasingly in studies of theoretical and public health importance. This study (N = 113) correlated scores on the CDI at ages 2 and 3 years with scores at age 3 years on tests of cognition and receptive language and measures from parent–child conversation. Associations indicated reasonable concurrent and predictive validity. The findings suggest that satisfactory vocabulary scores at age 2 are likely to predict normal language skills at age 3, although some children with limited skills at age 3 will have had satisfactory scores at age 2. Many children with poor vocabulary scores at 2 will have normal skills at 3. PMID:16026501

  4. Pharyngoesophageal perforation 3 years after anterior cervical spine surgery: a rare case report and literature review.

    PubMed

    Yin, Dan-Hui; Yang, Xin-Ming; Huang, Qi; Yang, Mi; Tang, Qin-Lai; Wang, Shu-Hui; Wang, Shuang; Liu, Jia-Jia; Yang, Tao; Li, Shi-Sheng

    2015-08-01

    Pharyngoesophageal perforation after anterior cervical spine surgery is rare and the delayed cases were more rarely reported but potentially life-threatening. We report a case of pharyngoesophageal perforation 3 years after anterior cervical spine surgery. The patient presented with dysphagia, fever, left cervical mass and developing dyspnea 3 years after cervical spine surgery for trauma. After careful examinations, he underwent an emergency tracheostomy, neck exploration, hardware removal, abscess drainage and infected tissue debridement. 14 days after surgery, CT of the neck with oral contrast demonstrated no contrast extravasation from the esophagus. Upon review of literature, only 14 cases of pharyngoesophageal perforation more than 1 year after anterior cervical spine surgery were found. We discussed possible etiology, diagnosis and management and concluded that in cases of dysphagia, dyspnea, cervical pain, swelling and edema of the cervical area even long time after anterior cervical spine surgery, potential pharyngoesophageal damage should be considered.

  5. Truncation of the A,A(∗),A' helices segment impairs the actin bundling activity of mammalian eEF1A1.

    PubMed

    Vlasenko, Dmytro O; Novosylna, Oleksandra V; Negrutskii, Boris S; El'skaya, Anna V

    2015-05-08

    Translation elongation factor eEF1A is a G-protein which has a crucial role in the ribosomal polypeptide elongation and possesses a number of non-translational functions. Here, we show that the A,A(∗),A' helices segment of mammalian eEF1A is dispensable for the eEF1A*eEF1Bα complex formation. The A,A(∗),A' helices region did not interact with actin; however, its removal eliminates the actin bundling activity of eEF1A, probably due to the destruction of a dimeric structure of eEF1A. The translation function of monomers and the actin-bundling function of dimers of mammalian eEF1A is suggested.

  6. Suspected disseminated histiocytic sarcoma in a 3-year-old Perro de Presa Canario dog.

    PubMed

    Denstedt, Emily

    2014-02-01

    A 3-year-old intact male Perro de Presa Canario dog was presented with acutely inflamed and edematous right hind limb, scrotum, prepuce, and an enlarged left carpus. Two weeks later the dog returned with weight loss, draining tracts in the right hind limb, dermal nodules, a palpable abdominal mass, and uveitis in the left eye. The dog succumbed to his illness 2 days later and a widely disseminated round cell tumor compatible with histiocytic sarcoma was diagnosed following postmortem examination.

  7. Maternal intake of methyl-donor nutrients and child cognition at 3 years of age.

    PubMed

    Villamor, Eduardo; Rifas-Shiman, Sheryl L; Gillman, Matthew W; Oken, Emily

    2012-07-01

    Methyl-donor nutrients are substrates for methylation reactions involved in neurodevelopment processes. The role of maternal intake of these nutrients on cognitive performance of the offspring is poorly understood. We examined the associations of maternal intake of folate, vitamin B12, choline, betaine and methionine during the first and second trimesters of pregnancy, with tests of cognitive performance in the offspring at 3 years of age using data from 1210 participants in Project Viva, a prospective pre-birth cohort study in Massachusetts. We assessed nutrient intake with the use of food frequency questionnaires. Children's cognition at age 3 years was evaluated with the Peabody Picture Vocabulary Test III (PPVT-III) and visual-motor skills with the Wide Range Assessment of Visual Motor Abilities test. In multivariable models adjusting for potential sociobehavioural and nutritional confounders, for each 600 µg/day increment in total folate intake during the first trimester, PPVT-III score at age 3 years was 1.6 points [95% confidence interval (CI) 0.1, 3.1; P = 0.04] higher. There was a weak inverse association between vitamin B12 intake during the second trimester and PPVT-III scores [-0.4 points per 2.6 µg/day; 95% CI -0.8, -0.1; P = 0.01]. We did not find associations between choline, betaine or methionine and cognitive outcomes at this age. Results of this study suggest that higher intake of folate in early pregnancy is associated with higher scores on the PPVT-III, a test of receptive language that predicts overall intelligence, at age 3 years.

  8. Maternal experiences of racial discrimination and child weight status in the first 3 years of life.

    PubMed

    Dixon, B; Rifas-Shiman, S L; James-Todd, T; Ertel, K; Krieger, N; Kleinman, K P; Rich-Edwards, J W; Gillman, M W; Taveras, E M

    2012-12-01

    Among US racial/ethnic minority women, we examined associations between maternal experiences of racial discrimination and child growth in the first 3 years of life. We analyzed data from Project Viva, a pre-birth cohort study. We restricted analyses to 539 mother-infant pairs; 294 were Black, 127 Hispanic, 110 Asian and 8 from additional racial/ethnic groups. During pregnancy, mothers completed the Experiences of Discrimination survey that measured lifetime experiences of racial discrimination in diverse domains. We categorized responses as 0, 1-2 or ≥3 domains. Main outcomes were birth weight for gestational age z-score; weight for age (WFA) z-score at 6 months of age; and at 3 years of age, body mass index (BMI) z-score. In multivariable analyses, we adjusted for maternal race/ethnicity, nativity, education, age, pre-pregnancy BMI, household income and child sex and age. Among this cohort of mostly (58.2%) US-born and economically non-impoverished mothers, 33% reported 0 domains of discrimination, 33% reported discrimination in 1-2 domains and 35% reported discrimination in ≥3 domains. Compared with children whose mothers reported no discrimination, those whose mothers reported ≥3 domains had lower birth weight for gestational age z-score (β -0.25; 95% CI: -0.45, -0.04), lower 6 month WFA z-score (β -0.34; 95% CI: -0.65, -0.03) and lower 3-year BMI z-score (β -0.33; 95% CI: -0.66, 0.00). In conclusion, we found that among this cohort of US racial/ethnic minority women, mothers' report of experiencing lifetime discrimination in ⩾ 3 domains was associated with lower fetal growth, weight at 6 months and 3-year BMI among their offspring.

  9. Acute myeloid leukemia with basophilic differentiation in a 3-year-old Standardbred gelding

    PubMed Central

    Furness, Mary Catherine; Setlakwe, Emile; Sallaway, John; Wood, Darren; Fromstein, Jordan; Arroyo, Luis G.

    2016-01-01

    A 3-year-old Standardbred gelding with a history of pyrexia, persistent hemorrhage from the oral cavity, and a large, soft swelling at the junction of the caudal aspect of the mandibular rami and proximal neck was evaluated. The horse had neutropenia and anemia, with atypical granulated cells in a blood smear. Additional tests confirmed acute myeloid leukemia with basophilic differentiation, which has been reported in humans, cats, dogs, and cattle but not horses. PMID:27708445

  10. Housing and mothering: their effects upon the developmental levels of 3-year-old children.

    PubMed Central

    Pollak, M

    1979-01-01

    The development of 200 3-year-old children was measured, using Gesell parameters of development. The levels of development were matched against the adequacy, or inadequacy, of maternal care and housing, the scales for which were derived from a questionnaire completed by the children's mothers. Housing was not found to affect the children's developmental levels, while the adequacy of maternal care was highly significantly related to satisfactory child development. PMID:420522

  11. The Rapid Development of Explicit Gaze Judgment Ability at 3 years

    ERIC Educational Resources Information Center

    Doherty, Martin J.; Anderson, James R.; Howieson, Lynne

    2009-01-01

    Two studies examined development of the ability to judge what another person is looking at. In Study 1, 54 2- to 4-year-olds judged where someone was looking in real-life, photograph, and drawing formats. A minority of 2-year-olds, but a majority of older children, passed all tasks, suggesting that the ability arises at around 3 years of age.…

  12. The Neural Correlates of Processing Newborn and Adult Faces in 3-Year-Old Children

    ERIC Educational Resources Information Center

    Peykarjou, Stefanie; Westerlund, Alissa; Cassia, Viola Macchi; Kuefner, Dana; Nelson, Charles A.

    2013-01-01

    The current study examines the processing of upright and inverted faces in 3-year-old children (n = 35). Event-related potentials (ERPs) were recorded during a passive looking paradigm including adult and newborn face stimuli. We observed three face-sensitive components, the P1, the N170 and the P400. Inverted faces elicited shorter P1 latency and…

  13. Acute myeloid leukemia with basophilic differentiation in a 3-year-old Standardbred gelding.

    PubMed

    Furness, Mary Catherine; Setlakwe, Emile; Sallaway, John; Wood, Darren; Fromstein, Jordan; Arroyo, Luis G

    2016-10-01

    A 3-year-old Standardbred gelding with a history of pyrexia, persistent hemorrhage from the oral cavity, and a large, soft swelling at the junction of the caudal aspect of the mandibular rami and proximal neck was evaluated. The horse had neutropenia and anemia, with atypical granulated cells in a blood smear. Additional tests confirmed acute myeloid leukemia with basophilic differentiation, which has been reported in humans, cats, dogs, and cattle but not horses.

  14. Gestational age-dependency of height and body mass index trajectories during the first 3 years in Japanese small-for-gestational age children

    PubMed Central

    Maeyama, Kaori; Morioka, Ichiro; Iwatani, Sota; Fukushima, Sachiyo; Kurokawa, Daisuke; Yamana, Keiji; Nishida, Kosuke; Ohyama, Shohei; Fujioka, Kazumichi; Awano, Hiroyuki; Taniguchi-Ikeda, Mariko; Nozu, Kandai; Nagase, Hiroaki; Nishimura, Noriyuki; Shirai, Chika; Iijima, Kazumoto

    2016-01-01

    Gestational age (GA) is thought to affect height growth in small-for-gestational age (SGA) children. However, the GA-specific trajectories in body mass index (BMI) and early appearances of adiposity rebound (AR) have not been fully investigated in a cohort of Japanese SGA children. A longitudinal cohort study was conducted with 1063 SGA children born in Kobe, Japan, with sufficient records from birth to 3 years of age. Subjects were divided into subgroups based on GA: 39–41 weeks GA (n = 723), 37–38 weeks GA (n = 256), 34–36 weeks GA (n = 62), and <34 weeks GA (n = 22). Height and BMI were assessed at 4 months, 9 months, 1.5 years, and 3 years of age. The catch-up rate for height was GA-dependent. Most children with 39–41 weeks GA (91%) caught up by 4 months of age; however, lower GA was associated with a slower elevation in the catch-up rate. The BMI trajectory during the first 3 years was also GA-dependent, with a change in GA dependency at a boundary of 37 weeks GA. Approximately 7% of SGA children had already developed AR before 3 years of age. In conclusion, growth patterns during infancy and early childhood in SGA children differ depending on GA. PMID:27934914

  15. Utilization of matrix population models to assess a 3-year single treatment nonsurgical contraception program versus surgical sterilization in feral cat populations.

    PubMed

    Budke, Christine M; Slater, Margaret R

    2009-01-01

    This study constructed matrix population models to explore feral cat population growth for a hypothetical population (a) in the absence of intervention; (b) with a traditional surgical sterilization-based trap, neuter, and return program; and (c) with a single treatment 3-year nonsurgical contraception program. Model outcomes indicated that cessation of population growth would require surgical sterilization for greater than 51% of adult and 51% of juvenile (<1 year) intact female cats annually, assuming an approximate 3-year mean life span. After the population stabilizes, this would equate to sterilizing approximately 14% of the total female population per year or having approximately 71% of the total female and 81% of the adult female population sterilized at all times. In the absence of juvenile sterilization, 91% of adult intact females would need to be sterilized annually to halt population growth. In comparison, with a 3-year nonsurgical contraception program, an annual contraception rate of 60% of female juvenile and adult intact cats would be required to halt population growth, assuming that treated cats were retrapped at the same rate after 3 years.

  16. Battery Energy Storage System battery durability and reliability under electric utility grid operations: Analysis of 3 years of real usage

    NASA Astrophysics Data System (ADS)

    Dubarry, Matthieu; Devie, Arnaud; Stein, Karl; Tun, Moe; Matsuura, Marc; Rocheleau, Richard

    2017-01-01

    Battery Energy Storage Systems (BESSs) show promise to help renewable energy sources integration onto the grid. These systems are expected to last for a decade or more, but the actual battery degradation under different real world conditions is still largely unknown. In this paper we analyze 3 years of usage of a lithium titanate BESS installed and in operation on an island power system in Hawai'i. The BESS was found to be operational 90% of the time and stored a cumulative 1.5 GWh of energy, which represents more than 5000 equivalent full cycles on the cells. This paper presents a statistical analysis of the BESS usage, develops a representative duty cycle, and provides an initial estimate of BESS degradation. The battery duty cycle was characterized based on 5 parameters: pulses duration, pulses intensity (current), SOC swing range, SOC event ramp rate, and temperature.

  17. Management of symphysis fracture in a 3-year-old child with prefabricated acrylic splint and circum-mandibular wiring.

    PubMed

    Srinivasan, Ila; Kumar, M Naveen; Kumaran, P Satish; Bhandari, Arihant; Udhya, J

    2013-01-01

    Pediatric mandibular fractures are often the sequelae of facial skeletal injuries in patients with trauma and frequently require hospitalization. Due to the retrusive mid-face position relative to the calvarial prominence, facial fractures are rare in children younger than 5 years of age. Although rare, they most often occur as a result of motor vehicle accidents. The purpose of this report is to describe the management of a mandibular symphysis fracture in a 3-year-old boy with displacement between the primary mandibular left central and lateral incisors. The fracture was reduced and the fractured segment was stabilized under general anesthesia with a prefabricated acrylic splint with circum-mandibular wiring. Children have greater osteogenic potential and faster healing rates than adults; therefore, anatomic reduction in children is best accomplished earlier.

  18. Odontogenic myxoma involving the orbit in a 3-year-old boy: removal, reconstruction and review of the literature.

    PubMed

    Hansen, Teis Schjals; Danielsson, Lina Isabella; Fast, Søren; Thygesen, Torben H

    2016-02-17

    We present a rare case of a 3-year-old boy with an odontogenic myxoma (OM) involving the orbita. Including our case, only nine cases of OM have been reported to involve the eye in children.There is no gold standard for treatment of OM in children with orbital involvement. The recurrence rate of OM in children seems low, which advocates for less invasive surgery. A gentle resection of the OM was carried out. The floor and medial wall of the orbit was reconstructed immediately using a non-resorbable Medpor implant with passive adaptation. Reconstruction with a Medpor implant in children has rarely been reported in the literature. No clinical or radiological recurrence was observed 24 months after surgical removal, and the patient presented with symmetric appearance and normal vision.

  19. Racial and Ethnic Differentials in Overweight and Obesity Among 3-Year-Old Children

    PubMed Central

    Kimbro, Rachel Tolbert; Brooks-Gunn, Jeanne; McLanahan, Sara

    2007-01-01

    Objectives. We estimated racial/ethnic differences in overweight and obesity in a national sample of 3-year-olds from urban, low-income families and assessed possible determinants of differences. Methods. Survey, in-home observation, and interview data were collected at birth, 1 year, and 3 years. We used logistic regression analyses and adjusted for a range of covariates in examining overweight and obesity differentials according to race/ethnicity. Results. Thirty-five percent of the study children were overweight or obese. Hispanic children were twice as likely as either Black or White children to be overweight or obese. Although we controlled for a wide variety of characteristics, we were unable to explain either White–Hispanic or Black–Hispanic differences in overweight and obesity. However, birthweight, taking a bottle to bed, and mother’s weight status were important predictors of children’s overweight or obesity at age 3 years. Conclusions. Children’s problems with overweight and obesity begin as early as age 3, and Hispanic children and those with obese mothers are especially at risk. PMID:17194857

  20. Development of temporomandibular disorder symptoms: a 3-year cohort study of university students.

    PubMed

    Akhter, R; Morita, M; Esaki, M; Nakamura, K; Kanehira, T

    2011-06-01

    The aims of this study were to examine the incidence of temporomandibular disorders (TMDs) over a 3-year period and to evaluate the risk of self-reported TMDs among university students in Japan. The study population comprised 2374 university students examined at the start of their undergraduate course and 492 students re-examined after 3 years using questionnaires on symptoms of TMD and experiences of jaw injury, stress, orthodontic treatment and parafunctional habits. Cumulative incidence (%) and relative risks were calculated overall. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to determine the degree of risks of these variables for symptoms of TMDs using logistic regression. Results of logistic regression analysis showed that male subjects with experience of jaw injury had a 3·54 (CI=1·45-8·68, P<0·01)-fold higher risk of temporomandibular joint (TMJ) pain than that for those who did not. Female subjects who reported experiencing stress and bruxism had 10·56 (CI=1·28-87·54, P<0·05)- and 5·00 (CI=1·21-20·71, P<0·05)-fold higher risks of TMJ sound, respectively, than the risk for female subjects who had not experienced stress or bruxism. The results indicated that experiences of jaw injury, stress and bruxism were significantly associated with increased risks of development of TMJ disorders in a 3-year cohort.

  1. Radiological evaluation of the Cresco system in combination with Osseospeed implants: a preliminary 3-year report

    PubMed Central

    BALDINI, N.; DE SANCTIS, M.; CAGIDIACO, M.C.; BALLERI, P.; VIGNOLETTI, F.; GORACCI, C.; FERRARI, M.

    2014-01-01

    SUMMARY Aim. In this preliminary study, the 3-year radiological outcomes of Osseospeed implant-supported fixed complete or partial prostheses made with two different laboratory protocols were compared. Methods. A convenience sample of 34 patients, who were either partially or completely edentulous in either jaw, were randomly assigned to two groups, of 17 patients each, using either a traditional laboratory protocol (control group) or the Cresco one (test group). The study’s objective was an assessment of marginal bone loss around implants, measured on intraoral radiographs at 3-year follow-up. Results. None of the implants inserted was lost during the study and radiological measurements of marginal bone level changes revealed that the mean marginal bone loss was respectively 0,73±0,33mm for test group and 0,88±1,13mm for control group. The differences between test and control groups were not statistically significant. Conclusion. This preliminary study did not demonstrate statistically significant differences in marginal bone loss around implant-prostheses prepared with the two different laboratory protocols, over the 3-year observational period. PMID:25694796

  2. Stability analysis of an F/A-18 E/F cable mount m odel

    NASA Technical Reports Server (NTRS)

    Thompson, Nancy; Farmer, Moses

    1994-01-01

    A full-span F/A-18 E/F cable mounted wind tunnel model is part of a flutter clearance program at the NASA Langley Transonic Dynamics Tunnel. Parametric analysis of this model using GRUMCBL software was conducted to assess stability for wind tunnel tests. Two configurations of the F/A-18 E/F were examined. The parameters examined were pulley-cable friction, mach number, dynamic pressure, cable geometry, center of gravity location, cable tension, snubbing the model, drag, and test medium. For the nominal cable geometry (Cable Geometry 1), Configuration One was unstable for cases with higher pulley-cable friction coefficients. A new cable geometry (Cable Geometry 3) was determined in which Configuration One was stable for all cases evaluated. Configuration Two with the nominal center of gravity position was found to be unstable for cases with higher pulley-cable friction coefficients; however, the model was stable when the center of gravity moved forward 1/2. The model was tested using the cable mount system during the initial wind tunnel entry and was stable as predicted.

  3. Arabidopsis EF-Tu receptor enhances bacterial disease resistance in transgenic wheat.

    PubMed

    Schoonbeek, Henk-Jan; Wang, Hsi-Hua; Stefanato, Francesca L; Craze, Melanie; Bowden, Sarah; Wallington, Emma; Zipfel, Cyril; Ridout, Christopher J

    2015-04-01

    Perception of pathogen (or microbe)-associated molecular patterns (PAMPs/MAMPs) by pattern recognition receptors (PRRs) is a key component of plant innate immunity. The Arabidopsis PRR EF-Tu receptor (EFR) recognizes the bacterial PAMP elongation factor Tu (EF-Tu) and its derived peptide elf18. Previous work revealed that transgenic expression of AtEFR in Solanaceae confers elf18 responsiveness and broad-spectrum bacterial disease resistance. In this study, we developed a set of bioassays to study the activation of PAMP-triggered immunity (PTI) in wheat. We generated transgenic wheat (Triticum aestivum) plants expressing AtEFR driven by the constitutive rice actin promoter and tested their response to elf18. We show that transgenic expression of AtEFR in wheat confers recognition of elf18, as measured by the induction of immune marker genes and callose deposition. When challenged with the cereal bacterial pathogen Pseudomonas syringae pv. oryzae, transgenic EFR wheat lines had reduced lesion size and bacterial multiplication. These results demonstrate that AtEFR can be transferred successfully from dicot to monocot species, further revealing that immune signalling pathways are conserved across these distant phyla. As novel PRRs are identified, their transfer between plant families represents a useful strategy for enhancing resistance to pathogens in crops.

  4. Oncomodulin, an EF-Hand Ca2+ Buffer, Is Critical for Maintaining Cochlear Function in Mice

    PubMed Central

    Tong, Benton; Hornak, Aubrey J.; Maison, Stéphane F.; Ohlemiller, Kevin K.; Liberman, M. Charles

    2016-01-01

    Oncomodulin (Ocm), a member of the parvalbumin family of calcium binding proteins, is expressed predominantly by cochlear outer hair cells in subcellular regions associated with either mechanoelectric transduction or electromotility. Targeted deletion of Ocm caused progressive cochlear dysfunction. Although sound-evoked responses are normal at 1 month, by 4 months, mutants show only minimal distortion product otoacoustic emissions and 70–80 dB threshold shifts in auditory brainstem responses. Thus, Ocm is not critical for cochlear development but does play an essential role for cochlear function in the adult mouse. SIGNIFICANCE STATEMENT Numerous proteins act as buffers, sensors, or pumps to control calcium levels in cochlear hair cells. In the inner ear, EF-hand calcium buffers may play a significant role in hair cell function but have been very difficult to study. Unlike other reports of genetic disruption of EF-hand calcium buffers, deletion of oncomodulin (Ocm), which is predominately found in outer hair cells, leads to a progressive hearing loss after 1 month, suggesting that Ocm critically protects hearing in the mature ear. PMID:26843644

  5. Reprogramming EF-hands for design of catalytically amplified lanthanide sensors.

    PubMed

    Mack, Korrie L; Moroz, Olesia V; Moroz, Yurii S; Olsen, Alissa B; McLaughlin, Jaclyn M; Korendovych, Ivan V

    2013-04-01

    We recently reported that a computationally designed catalyst nicknamed AlleyCat facilitates C-H proton abstraction in Kemp elimination at neutral pH in a selective and calcium-dependent fashion by a factor of approximately 100,000 (Korendovych et al. in Proc. Natl. Acad. Sci. USA 108:6823, 2011). Kemp elimination produced a colored product that can be easily read out, thus making AlleyCat a catalytically amplified metal sensor for calcium. Here we report that metal-binding EF-hand motifs in AlleyCat could be redesigned to incorporate trivalent metal ions without significant loss of catalytic activity. Mutation of a single neutral residue at position 9 of each of the EF-hands to glutamate results in almost a two orders of magnitude improvement of selectivity for trivalent metal ions over calcium. Development of this new lanthanide-dependent switchable Kemp eliminase, named CuSeCat EE, provides the foundation for further selectivity improvement and broadening the scope of the repertoire of metals for sensing. A concerted effort in the design of switchable enzymes has many environmental, sensing, and metal ion tracking applications.

  6. Characterization of a mazEF Toxin-Antitoxin Homologue from Staphylococcus equorum

    PubMed Central

    Schuster, Christopher F.; Park, Jung-Ho; Prax, Marcel; Herbig, Alexander; Nieselt, Kay; Rosenstein, Ralf; Inouye, Masayori

    2013-01-01

    Toxin-antitoxin (TA) systems encoded in prokaryotic genomes fall into five types, typically composed of two distinct small molecules, an endotoxic protein and a cis-encoded antitoxin of ribonucleic or proteinaceous nature. In silico analysis revealed seven putative type I and three putative type II TA systems in the genome of the nonpathogenic species strain Staphylococcus equorum SE3. Among these, a MazEF system orthologue termed MazEFseq was further characterized. 5′ rapid amplification of cDNA ends (RACE) revealed the expression and the transcriptional start site of mazEseq, indicating an immediately upstream promoter. Heterologous expression of the putative toxin-encoding mazFseq gene imposed growth cessation but not cell death on Escherichia coli. In vivo and in vitro, MazFseq was shown to cleave at UACAU motifs, which are remarkably abundant in a number of putative metabolic and regulatory S. equorum gene transcripts. Specific interaction between MazFseq and the putative cognate antitoxin MazEseq was demonstrated by bacterial two-hybrid analyses. These data strongly suggest that MazEFseq represents the first characterized TA system in a nonpathogenic Staphylococcus species and indicate that MazEF modules in staphylococci may also control processes beyond pathogenicity. PMID:23104807

  7. Molecular Dynamics of the Neuronal EF-Hand Ca2+-Sensor Caldendrin

    PubMed Central

    Reddy, Pasham Parameshwar; Raghuram, Vijeta; Hradsky, Johannes; Spilker, Christina; Chakraborty, Asima; Sharma, Yogendra; Mikhaylova, Marina; Kreutz, Michael R.

    2014-01-01

    Caldendrin, L- and S-CaBP1 are CaM-like Ca2+-sensors with different N-termini that arise from alternative splicing of the Caldendrin/CaBP1 gene and that appear to play an important role in neuronal Ca2+-signaling. In this paper we show that Caldendrin is abundantly present in brain while the shorter splice isoforms L- and S-CaBP1 are not detectable at the protein level. Caldendrin binds both Ca2+ and Mg2+ with a global Kd in the low µM range. Interestingly, the Mg2+-binding affinity is clearly higher than in S-CaBP1, suggesting that the extended N-terminus might influence Mg2+-binding of the first EF-hand. Further evidence for intra- and intermolecular interactions of Caldendrin came from gel-filtration, surface plasmon resonance, dynamic light scattering and FRET assays. Surprisingly, Caldendrin exhibits very little change in surface hydrophobicity and secondary as well as tertiary structure upon Ca2+-binding to Mg2+-saturated protein. Complex inter- and intramolecular interactions that are regulated by Ca2+-binding, high Mg2+- and low Ca2+-binding affinity, a rigid first EF-hand domain and little conformational change upon titration with Ca2+ of Mg2+-liganted protein suggest different modes of binding to target interactions as compared to classical neuronal Ca2+-sensors. PMID:25058677

  8. Conversion from cyclosporine to everolimus at 4.5 months posttransplant: 3-year results from the randomized ZEUS study.

    PubMed

    Budde, K; Lehner, F; Sommerer, C; Arns, W; Reinke, P; Eisenberger, U; Wüthrich, R P; Scheidl, S; May, C; Paulus, E-M; Mühlfeld, A; Wolters, H H; Pressmar, K; Stahl, R; Witzke, O

    2012-06-01

    The long-term effect of conversion from calcineurin inhibitor (CNI) therapy to an mTOR inhibitor requires clarification. Following completion of the 12-month, open-label, multicenter ZEUS study, in which 300 kidney transplant recipients were randomized to continue cyclosporine (CsA) or convert to everolimus at 4.5 months posttransplant, outcomes were assessed at month 36 (n = 284; 94.7%). CNI therapy was reintroduced in 28.4% of everolimus patients by month 36. The primary efficacy endpoint, estimated glomerular filtration rate (Nankivell, ANCOVA) was significantly higher with everolimus versus the CsA group at month 24 (7.6 mL/min/1.73 m(2) , 95%CI 4.3, 11.0 mL/min/1.73 m(2) ; p < 0.001) and month 36 (7.5 mL/min/1.73 m(2) , 95%CI 3.6, 11.4 mL/min/1.73 m(2) ; p < 0.001). The incidence of biopsy-proven acute rejection from randomization to month 36 was 13.0% in the everolimus arm and 4.8% in the CsA arm (p = 0.015). Patient and graft survival, as well as incidences of malignancy, severe infections and hospitalization, were similar between groups. Kidney transplant patients who are converted from CsA to everolimus at month 4.5 and who remain on everolimus thereafter may achieve a significant improvement in renal function that is maintained to 3 years. There was a significantly higher rate of rejection in the everolimus arm but this did not exert a deleterious effect by 3 years posttransplant.

  9. Off-treatment efficacy of 3-year nucleos(t)ide analogues in chronic hepatitis B patients.

    PubMed

    Lin, Ching-Chung; Bair, Ming-Jong; Chen, Chih-Jen; Lee, Keng-Han; Chen, Ming-Jen; Liu, Chia-Yuan; Chang, Chen-Wang; Hu, Kuang-Chun; Liou, Tai-Cherng; Lin, Shee-Chan; Wang, Horng-Yuan; Chu, Cheng-Hsin; Shih, Shou-Chuan; Wang, Tsang-En

    2016-01-01

    Lamivudine, telbivudine, and entecavir are the first-line drugs covered by the Taiwan National Health Insurance as 3-year treatments for patients with chronic hepatitis B virus (HBV), but the optimal treatment duration of each remains unclear. We aimed to detect HBV treatment-cessation durability, and compare the predictors in patients with and without clinical relapse. In this retrospective cohort study, 210 patients with chronic HBV who tested hepatitis B e-antigen positive or hepatitis B e-antigen negative were treated for 3 years with a nucleos(t)ide analogue. Of these, 102 patients continued therapy after 3 years, while 88 patients stopped treatment and were followed for 1 year due to financial difficulties. Efficacy was assessed in terms of alanine aminotransferase (ALT) level normalization, HBV DNA clearance, virus breakthrough, clinical relapse, and liver decompensation. The durability predictors were evaluated by host factors, HBV DNA, and drug differences. Eighty patients (14 on lamivudine, 19 on telbivudine, and 47 on entecavir) were recruited. There was no difference in clinical-relapse rate among lamivudine, telbivudine, and entecavir (35.7% vs. 36.8% vs. 31.9%, respectively; p = 0.916), and liver decompensated hepatitis was absent. In baseline clinical characteristics, there were no differences between the clinical-relapse and nonrelapse groups in age, sex, cirrhosis, prior treatment, HBV DNA, pretreatment ALT, or hepatitis B e-antigen (HBeAg). The mean 3(rd) year serum ALT level differed significantly between clinical-relapse and nonrelapse patients (37.5 U/L vs. 27.7 U/L, respectively; p = 0.044). The 3-year nucleos(t)ide analogue off-treatment in patients with chronic HBV delivered according to the Taiwan National Health Insurance guidelines had an overall 33.8% 1-year clinical-relapse rate without any decompensated hepatitis flare-ups.

  10. The Measurement of Executive Function at Age 3 Years: Psychometric Properties and Criterion Validity of a New Battery of Tasks

    ERIC Educational Resources Information Center

    Willoughby, Michael T.; Blair, Clancy B.; Wirth, R. J.; Greenberg, Mark

    2010-01-01

    In this study, the authors examined the psychometric properties and criterion validity of a newly developed battery of tasks that were designed to assess executive function (EF) abilities in early childhood. The battery was included in the 36-month assessment of the Family Life Project (FLP), a prospective longitudinal study of 1,292 children…

  11. The measurement of executive function at age 3 years: psychometric properties and criterion validity of a new battery of tasks.

    PubMed

    Willoughby, Michael T; Blair, Clancy B; Wirth, R J; Greenberg, Mark

    2010-06-01

    In this study, the authors examined the psychometric properties and criterion validity of a newly developed battery of tasks that were designed to assess executive function (EF) abilities in early childhood. The battery was included in the 36-month assessment of the Family Life Project (FLP), a prospective longitudinal study of 1,292 children oversampled from low-income and African American families. Ninety-one percent of children were able to complete 1 or more of the tasks. Psychometric analyses were used to test the dimensionality of each task, evaluate the item and task properties, test the dimensionality of the task battery, and evaluate the criterion validity of the battery with multi-informant measures of attention-deficit/hyperactivity disorder (ADHD) symptomatology and child performance on two subtests of the Wechsler Preschool and Primary Scale of Intelligence. Results indicated that the tasks were successful in measuring interindividual differences in child EF ability, that task scores were most informative about ability level for children in the low to moderate range of ability, that children's performance across the entire battery was adequately summarized by a single factor, and that individual differences on the EF battery were related to ADHD symptomatology and intelligence in expected ways. Results are discussed with respect to the importance of developing psychometrically sound, scalable instruments that facilitate the measurement of interindividual differences in intraindividual change of EF across the early childhood period.

  12. Maternal HIV infection, drug use, and growth of uninfected children in their first 3 years.

    PubMed Central

    Ross, A; Raab, G M; Mok, J; Gilkison, S; Hamilton, B; Johnstone, F D

    1995-01-01

    OBJECTIVE--To determine the separate effects of maternal HIV infection and drug use during pregnancy on growth of uninfected children in their first 3 years. DESIGN--Retrospective analysis of measurements from health visitor records made during routine child health surveillance at 6 weeks, 10 months, and 3 years of age. Multilevel analysis allowed for between-infant variation in fitted growth lines, and adjustment for other factors. Growth was described in terms of an intercept (z score at term) and growth slopes (change in z score per year) up to, and from, 4 months. SUBJECTS--290 case babies delivered in Edinburgh hospitals to women who reported injection drug use by either themselves or their HIV infected partner, and 186 community controls. A total of 131 (45%) of the case babies were born to women who used drugs, predominantly opiates, during pregnancy and 93 (32%) to HIV infected women. The eight infected children were excluded from analysis. MAIN OUTCOME MEASURES--Age and sex standardised z scores for height, weight, and body mass index. RESULTS--459 (96%) of the 476 records for cases and controls were traced, yielding 1432 weight and 939 height measurements. Maternal HIV infection was not found to affect growth; at 3 years the estimated effect on weight z score was 0.16 with 95% confidence interval (-0.25 to 0.57) and for height 0.18 (-0.19 to 0.55). Drug use during pregnancy was associated with lighter babies at 40 weeks followed by depressed growth in the first four months, these infants remaining just slightly smaller at 3 years with an estimated effect on z scores of -0.5 for weight with 95% confidence interval (-0.89 to -0.11) and -0.37 (-0.72 to -0.02) for height. CONCLUSIONS--Maternal HIV infection does not adversely affect growth in uninfected infants, and the effect of drug use during pregnancy is limited to small decrease in size at 3 years. PMID:8546501

  13. Klucel™ EF and ELF polymers for immediate-release oral dosage forms prepared by melt extrusion technology.

    PubMed

    Mohammed, Noorullah Naqvi; Majumdar, Soumyajit; Singh, Abhilasha; Deng, Weibin; Murthy, Narasimha S; Pinto, Elanor; Tewari, Divya; Durig, Thomas; Repka, Michael A

    2012-12-01

    The objective of this research work was to evaluate Klucel™ hydroxypropylcellulose (HPC) EF and ELF polymers, for solubility enhancement as well as to address some of the disadvantages associated with solid dispersions. Ketoprofen (KPR), a Biopharmaceutics Classification System class II drug with poor solubility, was utilized as a model compound. Preliminary thermal studies were performed to confirm formation of a solid solution/dispersion of KPR in HPC matrix and also to establish processing conditions for hot-melt extrusion. Extrudates pelletized and filled into capsules exhibited a carrier-dependent release with ELF polymer exhibiting a faster release. Tablets compressed from milled extrudates exhibited rapid release owing to the increased surface area of the milled extrudate. Addition of mannitol (MNT) further enhanced the release by forming micro-pores and increasing the porosity of the extrudates. An optimized tablet formulation constituting KPR, MNT, and ELF in a 1:1:1 ratio exhibited 90% release in 15 min similar to a commercial capsule formulation. HPC polymers are non-ionic hydrophilic polymers that undergo polymer-chain-length-dependent solubilization and can be used to enhance solubility or dissolution rate of poorly soluble drugs. Dissolution/release rate could be tailored for rapid-release applications by selecting a suitable HPC polymer and altering the final dosage form. The release obtained from pellets was carrier-dependent and not drug-dependent, and hence, such a system can be effectively utilized to address solubility or precipitation issues with poorly soluble drugs in the gastrointestinal environment.

  14. The communication factor EDF and the toxin-antitoxin module mazEF determine the mode of action of antibiotics.

    PubMed

    Kolodkin-Gal, Ilana; Sat, Boaz; Keshet, Alex; Engelberg-Kulka, Hanna

    2008-12-16

    It was recently reported that the production of Reactive Oxygen Species (ROS) is a common mechanism of cell death induced by bactericidal antibiotics. Here we show that triggering the Escherichia coli chromosomal toxin-antitoxin system mazEF is an additional determinant in the mode of action of some antibiotics. We treated E. coli cultures by antibiotics belonging to one of two groups: (i) Inhibitors of transcription and/or translation, and (ii) DNA damaging. We found that antibiotics of both groups caused: (i) mazEF-mediated cell death, and (ii) the production of ROS through MazF action. However, only antibiotics of the first group caused mazEF-mediated cell death that is ROS-dependent, whereas those of the second group caused mazEF-mediated cell death by an ROS-independent pathway. Furthermore, our results showed that the mode of action of antibiotics was determined by the ability of E. coli cells to communicate through the signaling molecule Extracellular Death Factor (EDF) participating in mazEF induction.

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

    NASA Astrophysics Data System (ADS)

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

    2015-06-01

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

  16. Formation of the First Peptide Bond: The Structure of EF-P Bound to the 70S Ribosome

    SciTech Connect

    Blaha, Gregor; Stanley, Robin E.; Steitz, Thomas A.; Yale

    2009-10-21

    Elongation factor P (EF-P) is an essential protein that stimulates the formation of the first peptide bond in protein synthesis. Here we report the crystal structure of EF-P bound to the Thermus thermophilus 70S ribosome along with the initiator transfer RNA N-formyl-methionyl-tRNAi (fMet-tRNA{sub i}{sup fMet}) and a short piece of messenger RNA (mRNA) at a resolution of 3.5 angstroms. EF-P binds to a site located between the binding site for the peptidyl tRNA (P site) and the exiting tRNA (E site). It spans both ribosomal subunits with its amino-terminal domain positioned adjacent to the aminoacyl acceptor stem and its carboxyl-terminal domain positioned next to the anticodon stem-loop of the P site-bound initiator tRNA. Domain II of EF-P interacts with the ribosomal protein L1, which results in the largest movement of the L1 stalk that has been observed in the absence of ratcheting of the ribosomal subunits. EF-P facilitates the proper positioning of the fMet-tRNA{sub i}{sup fMet} for the formation of the first peptide bond during translation initiation.

  17. Formation of the First Peptid Bond: the Structure of EF-P Bound to the 70S Ribosome

    SciTech Connect

    Blaha, G.; Stanley, R; Steitz, T

    2009-01-01

    Elongation factor P (EF-P) is an essential protein that stimulates the formation of the first peptide bond in protein synthesis. Here we report the crystal structure of EF-P bound to the Thermus thermophilus 70S ribosome along with the initiator transfer RNA N-formyl-methionyl-tRNAi (fMet-tRNAifMet) and a short piece of messenger RNA (mRNA) at a resolution of 3.5 angstroms. EF-P binds to a site located between the binding site for the peptidyl tRNA (P site) and the exiting tRNA (E site). It spans both ribosomal subunits with its amino-terminal domain positioned adjacent to the aminoacyl acceptor stem and its carboxyl-terminal domain positioned next to the anticodon stem-loop of the P site-bound initiator tRNA. Domain II of EF-P interacts with the ribosomal protein L1, which results in the largest movement of the L1 stalk that has been observed in the absence of ratcheting of the ribosomal subunits. EF-P facilitates the proper positioning of the fMet-tRNAifMet for the formation of the first peptide bond during translation initiation.

  18. Elongation Factor-Tu (EF-Tu) proteins structural stability and bioinformatics in ancestral gene reconstruction

    NASA Astrophysics Data System (ADS)

    Dehipawala, Sunil; Nguyen, A.; Tremberger, G.; Cheung, E.; Schneider, P.; Lieberman, D.; Holden, T.; Cheung, T.

    2013-09-01

    A paleo-experimental evolution report on elongation factor EF-Tu structural stability results has provided an opportunity to rewind the tape of life using the ancestral protein sequence reconstruction modeling approach; consistent with the book of life dogma in current biology and being an important component in the astrobiology community. Fractal dimension via the Higuchi fractal method and Shannon entropy of the DNA sequence classification could be used in a diagram that serves as a simple summary. Results from biomedical gene research provide examples on the diagram methodology. Comparisons between biomedical genes such as EEF2 (elongation factor 2 human, mouse, etc), WDR85 in epigenetics, HAR1 in human specificity, DLG1 in cognitive skill, and HLA-C in mosquito bite immunology with EF Tu DNA sequences have accounted for the reported circular dichroism thermo-stability data systematically; the results also infer a relatively less volatility geologic time period from 2 to 3 Gyr from adaptation viewpoint. Comparison to Thermotoga maritima MSB8 and Psychrobacter shows that Thermus thermophilus HB8 EF-Tu calibration sequence could be an outlier, consistent with free energy calculation by NUPACK. Diagram methodology allows computer simulation studies and HAR1 shows about 0.5% probability from chimp to human in terms of diagram location, and SNP simulation results such as amoebic meningoencephalitis NAF1 suggest correlation. Extensions to the studies of the translation and transcription elongation factor sequences in Megavirus Chiliensis, Megavirus Lba and Pandoravirus show that the studied Pandoravirus sequence could be an outlier with the highest fractal dimension and lowest entropy, as compared to chicken as a deviant in the DNMT3A DNA methylation gene sequences from zebrafish to human and to the less than one percent probability in computer simulation using the HAR1 0.5% probability as reference. The diagram methodology would be useful in ancestral gene

  19. The complex of tmRNA-SmpB and EF-G on translocating ribosomes.

    PubMed

    Ramrath, David J F; Yamamoto, Hiroshi; Rother, Kristian; Wittek, Daniela; Pech, Markus; Mielke, Thorsten; Loerke, Justus; Scheerer, Patrick; Ivanov, Pavel; Teraoka, Yoshika; Shpanchenko, Olga; Nierhaus, Knud H; Spahn, Christian M T

    2012-05-06

    Bacterial ribosomes stalled at the 3' end of malfunctioning messenger RNAs can be rescued by transfer-messenger RNA (tmRNA)-mediated trans-translation. The SmpB protein forms a complex with the tmRNA, and the transfer-RNA-like domain (TLD) of the tmRNA then enters the A site of the ribosome. Subsequently, the TLD-SmpB module is translocated to the P site, a process that is facilitated by the elongation factor EF-G, and translation is switched to the mRNA-like domain (MLD) of the tmRNA. Accurate loading of the MLD into the mRNA path is an unusual initiation mechanism. Despite various snapshots of different ribosome-tmRNA complexes at low to intermediate resolution, it is unclear how the large, highly structured tmRNA is translocated and how the MLD is loaded. Here we present a cryo-electron microscopy reconstruction of a fusidic-acid-stalled ribosomal 70S-tmRNA-SmpB-EF-G complex (carrying both of the large ligands, that is, EF-G and tmRNA) at 8.3 Å resolution. This post-translocational intermediate (TI(POST)) presents the TLD-SmpB module in an intrasubunit ap/P hybrid site and a tRNA(fMet) in an intrasubunit pe/E hybrid site. Conformational changes in the ribosome and tmRNA occur in the intersubunit space and on the solvent side. The key underlying event is a unique extra-large swivel movement of the 30S head, which is crucial for both tmRNA-SmpB translocation and MLD loading, thereby coupling translocation to MLD loading. This mechanism exemplifies the versatile, dynamic nature of the ribosome, and it shows that the conformational modes of the ribosome that normally drive canonical translation can also be used in a modified form to facilitate more complex tasks in specialized non-canonical pathways.

  20. Coincident 1.3-year Periodicities in the ap Geomagnetic Index and the Solar Wind

    NASA Technical Reports Server (NTRS)

    Paularena, K. I.; Szabo, A.; Richardson, J. D.

    1995-01-01

    Recent observations show an approximately 1.3-year period in the speed of the solar wind detected by the IMP 8 and Voyager 2 spacecraft. A similar period is also seen in the north-south (GSE) component of the magnetic field observed by IMP 8. Since both parameters are commonly used as input to models of geomagnetic activity, the 'ap' index (a measure of geomagnetic disturbance) is examined to look for this periodicity. The Lomb-Scargle periodogram method is used on the ap, plasma, and magnetic field data during the 1973-1994 time range. A dynamic FFT periodogram method is also used to analyze the ap data during this time, as well as to look for periods present between 1932 and 1972. A clear 1.3-year periodicity is present in the post-1986 data when the same period is observed in the plasma and field data. The V(2)B(zsm) and V(2)B(s) proxies for geomagnetic activity also show this periodicity. However, the southward (GSM) component of the magnetic field does not have a 1.3-year period, and neither do solar wind or ap data from 1973-1985. This demonstrates that the ap geomagnetic index can act as a proxy for solar wind periodicities at this time scale. Historic ap data are examined, and show that a similar periodicity in ap exists around 1942. Since auroral data show a 1.4-year periodicity, all these similar periods may result from a common underlying solar mechanism.

  1. In vivo degradation of resin-dentin bonds in humans over 1 to 3 years.

    PubMed

    Hashimoto, M; Ohno, H; Kaga, M; Endo, K; Sano, H; Oguchi, H

    2000-06-01

    The longevity of resin restorations is currently an area of great interest in adhesive dentistry. However, no work has been conducted to investigate the durability of resin-dentin bond structures using human substrate in vivo. The purpose of this study was to investigate the degradation of the resin-dentin bond structures aged in an oral environment for 1, 2, or 3 years. Cavities were prepared in primary molars, and an adhesive resin system (Scotchbond Multi-Purpose) was applied to the cavity. After 1 to 3 years, following the eruption of the succedaneous permanent teeth, the resin-restored teeth were extracted. Immediately after extraction, those teeth were sectioned perpendicular to the adhesive interface and trimmed to produce an hourglass-shaped specimen. Then, a micro-tensile test was performed at a crosshead speed of 1.0 mm/min. The mean bond strengths were statistically compared with one-way ANOVA and Fisher's PLSD test (p < 0.05). Further, all fractured surfaces were observed by SEM, and the area fraction of failure mode was calculated by means of a digital analyzer on SEM photomicrographs. There were significant differences in tensile-bond strength among all 3 groups (p < 0.05), with mean values ranging from 28.3 +/- 11.3 MPa (control), to 15.2 +/- 4.4 MPa (1 to 2 years), to 9.1 +/- 5.1 MPa (2 to 3 years). Moreover, under fractographic analysis, the proportion of demineralized dentin at the fractured surface in specimens aged in an oral environment was greater than that in control specimens. Furthermore, degradation of resin composite and the depletion of collagen fibrils was observed among the specimens aged in an oral environment. Analysis of the results of this study indicated that the degradation of resin-dentin bond structures occurs after aging in the oral cavity.

  2. Oxidation of a Cysteine Residue in Elongation Factor EF-Tu Reversibly Inhibits Translation in the Cyanobacterium Synechocystis sp. PCC 6803.

    PubMed

    Yutthanasirikul, Rayakorn; Nagano, Takanori; Jimbo, Haruhiko; Hihara, Yukako; Kanamori, Takashi; Ueda, Takuya; Haruyama, Takamitsu; Konno, Hiroki; Yoshida, Keisuke; Hisabori, Toru; Nishiyama, Yoshitaka

    2016-03-11

    Translational elongation is susceptible to inactivation by reactive oxygen species (ROS) in the cyanobacterium Synechocystis sp. PCC 6803, and elongation factor G has been identified as a target of oxidation by ROS. In the present study we examined the sensitivity to oxidation by ROS of another elongation factor, EF-Tu. The structure of EF-Tu changes dramatically depending on the bound nucleotide. Therefore, we investigated the sensitivity to oxidation in vitro of GTP- and GDP-bound EF-Tu as well as that of nucleotide-free EF-Tu. Assays of translational activity with a reconstituted translation system from Escherichia coli revealed that GTP-bound and nucleotide-free EF-Tu were sensitive to oxidation by H2O2, whereas GDP-bound EF-Tu was resistant to H2O2. The inactivation of EF-Tu was the result of oxidation of Cys-82, a single cysteine residue, and subsequent formation of both an intermolecular disulfide bond and sulfenic acid. Replacement of Cys-82 with serine rendered EF-Tu resistant to inactivation by H2O2, confirming that Cys-82 was a target of oxidation. Furthermore, oxidized EF-Tu was reduced and reactivated by thioredoxin. Gel-filtration chromatography revealed that some of the oxidized nucleotide-free EF-Tu formed large complexes of >30 molecules. Atomic force microscopy revealed that such large complexes dissociated into several smaller aggregates upon the addition of dithiothreitol. Immunological analysis of the redox state of EF-Tu in vivo showed that levels of oxidized EF-Tu increased under strong light. Thus, resembling elongation factor G, EF-Tu appears to be sensitive to ROS via oxidation of a cysteine residue, and its inactivation might be reversed in a redox-dependent manner.

  3. The translation elongation factor eEF2 is a novel tumor-associated antigen overexpressed in various types of cancers

    PubMed Central

    OJI, YUSUKE; TATSUMI, NAOYA; FUKUDA, MARI; NAKATSUKA, SHIN-ICHI; AOYAGI, SAYAKA; HIRATA, ERIKA; NANCHI, ISAMU; FUJIKI, FUMIHIRO; NAKAJIMA, HIROKO; YAMAMOTO, YUMIKO; SHIBATA, SYOHEI; NAKAMURA, MICHIYO; HASEGAWA, KANA; TAKAGI, SAYAKA; FUKUDA, IKUYO; HOSHIKAWA, TOMOKO; MURAKAMI, YUI; MORI, MASAHIDE; INOUE, MASAYOSHI; NAKA, TETSUJI; TOMONAGA, TAKESHI; SHIMIZU, YOSHIFUMI; NAKAGAWA, MASASHI; HASEGAWA, JUNICHI; NEZU, RIICHIRO; INOHARA, HIDENORI; IZUMOTO, SHUICHI; NONOMURA, NORIO; YOSHIMINE, TOSHIKI; OKUMURA, MEINOSHIN; MORII, EIICHI; MAEDA, HAJIME; NISHIDA, SUMIYUKI; HOSEN, NAOKI; TSUBOI, AKIHIRO; OKA, YOSHIHIRO; SUGIYAMA, HARUO

    2014-01-01

    Recent studies have shown that cancer immunotherapy could be a promising therapeutic approach for the treatment of cancer. In the present study, to identify novel tumor-associated antigens (TAAs), the proteins expressed in a panel of cancer cells were serologically screened by immunoblot analysis and the eukaryotic elongation factor 2 (eEF2) was identified as an antigen that was recognized by IgG autoantibody in sera from a group of patients with head and neck squamous cell carcinoma (HNSCC) or colon cancer. Enzyme-linked immunosorbent assay showed that serum eEF2 IgG Ab levels were significantly higher in colorectal and gastric cancer patients compared to healthy individuals. Immunohistochemistry experiments showed that the eEF2 protein was overexpressed in the majority of lung, esophageal, pancreatic, breast and prostate cancers, HNSCC, glioblastoma multiforme and non-Hodgkin’s lymphoma (NHL). Knockdown of eEF2 by short hairpin RNA (shRNA) significantly inhibited the growth in four eEF2-expressing cell lines, PC14 lung cancer, PCI6 pancreatic cancer, HT1080 fibrosarcoma and A172 glioblastoma cells, but not in eEF2-undetectable MCF7 cells. Furthermore, eEF2-derived 9-mer peptides, EF786 (eEF2 786–794 aa) and EF292 (eEF2 292–300 aa), elicited cytotoxic T lymphocyte (CTL) responses in peripheral blood mononuclear cells (PBMCs) from an HLA-A*24:02- and an HLA-A*02:01-positive healthy donor, respectively, in an HLA-A-restricted manner. These results indicated that the eEF2 gene is overexpressed in the majority of several types of cancers and plays an oncogenic role in cancer cell growth. Moreover, the eEF2 gene product is immunogenic and a promising target molecule of cancer immunotherapy for several types of cancers. PMID:24589652

  4. The EF-hand Ca2+ Binding Domain Is Not Required for Cytosolic Ca2+ Activation of the Cardiac Ryanodine Receptor.

    PubMed

    Guo, Wenting; Sun, Bo; Xiao, Zhichao; Liu, Yingjie; Wang, Yundi; Zhang, Lin; Wang, Ruiwu; Chen, S R Wayne

    2016-01-29

    Activation of the cardiac ryanodine receptor (RyR2) by elevating cytosolic Ca(2+) is a central step in the process of Ca(2+)-induced Ca(2+) release, but the molecular basis of RyR2 activation by cytosolic Ca(2+) is poorly defined. It has been proposed recently that the putative Ca(2+) binding domain encompassing a pair of EF-hand motifs (EF1 and EF2) in the skeletal muscle ryanodine receptor (RyR1) functions as a Ca(2+) sensor that regulates the gating of RyR1. Although the role of the EF-hand domain in RyR1 function has been studied extensively, little is known about the functional significance of the corresponding EF-hand domain in RyR2. Here we investigate the effect of mutations in the EF-hand motifs on the Ca(2+) activation of RyR2. We found that mutations in the EF-hand motifs or deletion of the entire EF-hand domain did not affect the Ca(2+)-dependent activation of [(3)H]ryanodine binding or the cytosolic Ca(2+) activation of RyR2. On the other hand, deletion of the EF-hand domain markedly suppressed the luminal Ca(2+) activation of RyR2 and spontaneous Ca(2+) release in HEK293 cells during store Ca(2+) overload or store overload-induced Ca(2+) release (SOICR). Furthermore, mutations in the EF2 motif, but not EF1 motif, of RyR2 raised the threshold for SOICR termination, whereas deletion of the EF-hand domain of RyR2 increased both the activation and termination thresholds for SOICR. These results indicate that, although the EF-hand domain is not required for RyR2 activation by cytosolic Ca(2+), it plays an important role in luminal Ca(2+) activation and SOICR.

  5. Conjunctival Splendore-Hoeppli phenomenon in a 3-year-old child.

    PubMed

    Orhan, Diclehan; Kiratli, Hayyam; Kocabeyoğlu, Sibel

    2006-01-01

    A case of benign granulomas of the conjunctiva in a 3-year-old girl is reported. Histologic features of the excised conjunctival lesions were consistent with Splendore-Hoeppli phenomenon. This phenomenon is thought to be a granulomatous reaction to an antigen-antibody precipitate related to parasites or fungi. No causative agent is identified in our patient. Immunohistochemical analysis showed no immunoreactivity for immunoglobulin G (IgG), IgM, IgA, or the C3 component of the complement. We propose that the presence of small amelanotic nodular conjunctival tumors should arouse suspicion related to the Splendore-Hoeppli phenomenon even in early childhood.

  6. Suspected disseminated histiocytic sarcoma in a 3-year-old Perro de Presa Canario dog

    PubMed Central

    Denstedt, Emily

    2014-01-01

    A 3-year-old intact male Perro de Presa Canario dog was presented with acutely inflamed and edematous right hind limb, scrotum, prepuce, and an enlarged left carpus. Two weeks later the dog returned with weight loss, draining tracts in the right hind limb, dermal nodules, a palpable abdominal mass, and uveitis in the left eye. The dog succumbed to his illness 2 days later and a widely disseminated round cell tumor compatible with histiocytic sarcoma was diagnosed following postmortem examination. PMID:24489399

  7. [Atypical presentation of hepatosplenic cat scratch disease in a 3-year-old child].

    PubMed

    Boiron, E; Soto, B; Zimmermann, B; Jullien, M

    2012-06-01

    Cat scratch disease is caused by a facultative intracellular Gram-negative bacteria, Bartonella henselae. This disease is transmitted by cat scratches or bites. The typical form is a large and rough adenopathy, with no general signs. In a few cases, the symptoms are aspecific and various, which makes the diagnosis difficult. A 3-year-old child presented a prolonged fever with an aspecific skin eruption and hepatosplenic lesions seen 1 month after the beginning of the disease, which led to the diagnosis of hepatosplenic cat scratch disease. An adapted antibiotic therapy completely cured the disease.

  8. Chronic paroxysmal hemicrania in a 3-year, 10-month-old female.

    PubMed

    Talvik, Inga; Koch, Kadri; Kolk, Anneli; Talvik, Tiina

    2006-03-01

    This is the report of a 3-year, 10-month-old female with classical symptoms of chronic paroxysmal hemicrania and favorable response to indomethacin therapy. The patient was admitted because of frequent episodes of severe unilateral headaches during the day and nighttime as well as agitation. During the episodes, she complained of severe pains on the left orbital and supraorbital region. Subsequent lacrimation from the left eye was also documented. Initially, focal epileptic attack was diagnosed and during the following 10 months several antiepileptic drugs were used without effect. After 10 months, chronic paroxysmal hemicrania was diagnosed because of the typical symptoms along with a favorable response to indomethacin therapy.

  9. Axial Length/Corneal Radius of Curvature Ratio and Myopia in 3-Year-Old Children

    PubMed Central

    Foo, Valencia Hui Xian; Verkicharla, Pavan Kumar; Ikram, Mohammad Kamran; Chua, Sharon Yu Lin; Cai, Shirong; Tan, Chuen Seng; Chong, Yap-Seng; Kwek, Kenneth; Gluckman, Peter; Wong, Tien-Yin; Ngo, Cheryl; Saw, Seang-Mei; on behalf of the GUSTO study group

    2016-01-01

    Purpose This study investigated the association of axial length (AL) to corneal radius of curvature (CRC) ratio with spherical equivalent (SE) in a 3-year old Asian cohort. Methods Three-hundred forty-nine 3-year old Asian children from The Growing Up in Singapore towards Healthy Outcomes (GUSTO) birth cohort study underwent AL and CRC measurements with a noncontact ocular biometer and cycloplegic refraction using an autorefractor. The ratio of AL to CRC (AL/CRC) was calculated for all the participants, and subsequently AL, CRC, and AL/CRC were analyzed in relationship to SE. Results The SE showed better correlation with AL/CRC (Spearman's correlation coefficient, ρ = −0.53; 95% confidence interval [CI]: −0.66; −0.49; P < 0.001) compared to either AL or CRC alone ([ρ = −0.36; 95% CI: −0.51 to 0.51; P = 0.01] and [ρ = 0.05; 95% CI: −0.04 to 0.17; P = 0.34], respectively). Mean AL/CRC was 2.91 ± 0.06 among myopes and decreased to 2.79 ± 0.06 among hyperopes. Axial length to corneal radius of curvature was strongly correlated with SE in myopes (ρ = −0.78; 95% CI: −3.76; −0.79; P = < 0.001), but not in emmetropes and hyperopes ([ρ = −0.39; 95% CI: −10.73; −0.57; P = 0.01] and [ρ = −0.18; 95% CI: −17.28; 12.42; P = 0.38], respectively). Linear regression adjusted for gender and ethnicity showed a 0.74-diopter shift in SE towards myopia with every 0.1 increase in AL/CRC ratio (P < 0.001, r2 = 0.33). Conclusion The correlation between SE and AL/CRC is stronger than that between AL or CRC alone. This suggests that in a research setting, when cycloplegic refraction is difficult to perform on 3-year-old children, AL/CRC may be the next best reference for refractive error. Translational Relevance In the research setting, AL/CRC may be the next best reference for refractive error over AL alone when cycloplegic refraction is unavailable in 3-year old children. PMID:26929885

  10. Bilateral cochlear nerve absence in a 3 year old child with VACTERL association.

    PubMed

    Rudić, Milan; Wong, Winson; Viner, Stuart; Strachan, David; Raine, Christopher

    2017-02-01

    We report a case of a 3 year old boy with bilateral profound sensorineural hearing loss diagnosed from New Born Hearing Screening, with severe form of VACTERL association. He was referred to our Cochlear Implant Unit for assessment with regard to the possibility of cochlear implantation. MRI findings have showed bilateral vestibulocochlear cystic abnormalities. Only single nerve noted within the IAM on the right and likely single nerve within the IAM on the left. Hence, decision was made not to offer cochlear implantation. This is the first report of severe bilateral cochleovestibular nerve abnormalities to be associated with VACTERL.

  11. Mycoplasma pneumoniae associated stroke in a 3-year-old girl

    PubMed Central

    Kim, Gun-Ha; Seo, Won Hee; Je, Bo-Kyung

    2013-01-01

    Infectious diseases precede a significant proportion of acute ischemic strokes in children. Here, we report a case of acute ischemic stroke in a 3-year-old girl with a Mycoplasma pneumonia-associated respiratory tract infection. She developed an acquired prothrombotic state of protein S deficiency and had increased fibrinogen and fibrinogen degradation product levels and increased titer of antinuclear antibodies. However, these conditions were completely alleviated at the 1-month follow-up examination. Infection with M. pneumoniae may cause a transient prothrombotic state that can potentially cause a thrombus. PMID:24223604

  12. Fever and rash in a 3-year-old girl: Rocky Mountain spotted fever.

    PubMed

    Kaufmann, Julie M; Zaenglein, Andrea L; Kaul, Aditya; Chang, Mary Wu

    2002-09-01

    Initial symptoms of Rocky Mountain spotted fever (RMSF), a tick-borne illness caused by Rickettsia rickettsii, are nonspecific and include headache, gastrointestinal disturbances, malaise, and myalgias, followed by fever and rash. The classic triad of fever, rash, and history of tick exposure is uncommon at presentation. Clinical manifestations of RMSF range from virtually asymptomatic to severe. Because of the potentially fatal outcome of RMSF, presumptive clinical diagnosis and empiric antimicrobial therapy can be critical. We present the case of a 3-year-old girl from New York State who presented with fever and rash.

  13. A special case of lower back pain in a 3-year-old girl

    PubMed Central

    Tassinari, Davide; Forti, Sara; Torella, Michele; Tani, Giovanni

    2013-01-01

    We describe the case of a 3-year-old girl with a 15-day clinical history of lower back pain. We diagnosed a spondylodiscitis of vertebral bodies L5–S1 caused by Salmonella species group B that totally recovered with appropriate antibiotic therapy. Spondylodiscitis in children is a rare condition and Salmonella infection is one of the rarest aetiology. A high index of suspicion is needed for prompt diagnosis to ensure better long-term outcome. Microbiological diagnosis is essential for the appropriate choice of antibiotic treatment. PMID:23475989

  14. Baldrige-based quality awards: Veterans Health Administration's 3-year experience.

    PubMed

    Shirks, Allan; Weeks, William B; Stein, Annie

    2002-01-01

    This article describes the Veterans Health Administration's (VHA's) 3-year experience with an internal, Baldrige-based quality award. The authors examined scores for Veterans Integrated Service Networks (VISNs), which received site visits, variation in year-to-year survey outcomes for repeat applicants, and variation in survey team reports for a VISN with multiple surveys. Individual VISNs that applied in multiple years had mixed results. Variation in feedback reports was not significant. Although some VISNs increased their scores over time, there was not measurable, systemwide improvement. Three years may be too short a time to significantly affect Baldrige scores in an organization as large as VHA.

  15. Primary prevention in health care employees: a prospective intervention study with a 3-year training period.

    PubMed

    Löffler, Harald; Bruckner, Thomas; Diepgen, Thomas; Effendy, Isaak

    2006-04-01

    Irritant contact dermatitis is a mayor problem in health care employees. Because educational programs have shown convincing success in certain occupations (e.g. in hairdressers), this study investigates the effect of a special training program in health care trainees. 521 trainees from 14 nursing schools in Central Germany were randomly divided in 2 groups, (i) an intervention group with a regular teaching protocol regarding all aspects of primary prevention and (ii) a control group without any further teaching. Morphological changes of the hands, use of hand care creams and knowledge regarding skin care were evaluated regularly during their 3 years lasting training period (1999-2002). In the intervention group, we found at the end of the 3-year training period a significant better skin condition of the hands than in the control group: a 3-year prevalence of morphological skin changes of 66.7% versus 89.3%. The unteached trainees (control group) had an odds ratio (OR) of 4.8 [95% confidential interval (CI): 2.9-7.8] for developing any skin changes on the hands after 3 years. Besides the effect of the teaching, the history of hand dermatitis before the study start was an independent risk factor for development of further hand dermatitis [OR 1.9, 95% CI: 1.0-3.6). Age and sex showed no influence on the skin condition. Atopic constitution had an influence on the development of skin changes only at the evaluation after 18 month. The observed effect in the intervention group may best be explained by different behaviour of the trainees, e.g. the amount of hand washing was reduced, while procedure of hand disinfection remained unchanged compared with the control group. However, the amount of used skin care cream did not differ between the both groups. This study shows that primary prevention of skin disease by regularly teaching during the training period of medical employees can effectively reduce the risk of development of irritant skin changes of the hands. Therefore

  16. IQ trajectory, cognitive reserve, and clinical outcome following a first episode of psychosis: a 3-year longitudinal study.

    PubMed

    Leeson, Verity C; Sharma, Pranev; Harrison, Masuma; Ron, Maria A; Barnes, Thomas R E; Joyce, Eileen M

    2011-07-01

    Comparison of current and estimated premorbid IQ in schizophrenia suggests that there are subgroups with low IQ, deteriorated IQ (DIQ), or preserved IQ and that this is established by psychosis onset. There are no controlled studies examining the trajectory of these IQ subgroups longitudinally or their relationship with clinical and social outcomes. Of 129 individuals with first-episode schizophrenia or schizoaffective disorder, 25% showed stable low IQ, 31% showed stable IQ in the average/high range, and 44% demonstrated intellectual deterioration by 10 points or more. Patients in the low and deteriorated groups were equally impaired on tests of memory and executive function compared with the preserved average/high-IQ group and controls and showed more negative and disorganization symptoms than the preserved average/high-IQ group. Sixty patients and 27 controls were assessed again 1 and 3 years later. There was no evidence that those with IQ deterioration at baseline continued on a declining cognitive trajectory or that those with preserved average/high IQ experienced subsequent IQ decline. The low IQ group showed no change in IQ, whereas both the DIQ and the preserved IQ groups improved. However, the rate of improvement of these 2 subgroups was no greater than that of the healthy controls, suggesting that this reflected practice effects. Both the low and the deteriorated groups had longer index admissions, more core negative symptoms, and worse occupational outcomes at 3 years. These data suggest that following psychosis onset, IQ is stable and that it is IQ at psychosis onset rather than premorbid IQ predicts a more severe illness.

  17. Screening for inborn errors of metabolism in high-risk children: a 3-year pilot study in Zhejiang Province, China

    PubMed Central

    2012-01-01

    Background Tandem mass spectrometry (MS/MS) has been available in China for 8 years. This technique makes it possible to screen for a wide range of previously unscreened inborn errors of metabolism (IEM) using a single test. This 3-year pilot study investigated the screening, diagnosis, treatment and outcomes of IEM in symptomatic infants and children. Methods All children encountered in the Newborn Screening Center of Zhejiang Province during a 3-year period with symptoms suspicious for IEM were screened for metabolic diseases. Dried blood spots were collected and analyzed by tandem mass spectrometry. The diagnoses were further confirmed by clinical symptoms and biochemical analysis. Neonatal intrahepatic cholestasis caused by citrin deficiency, ornithine transcarbamylase deficiency and primary carnitine deficiency were confirmed by DNA analysis. Results A total of 11,060 symptomatic patients (6,720 boys, 4,340 girls) with a median age of 28.8 months (range: 0.04-168.2 months) were screened. Among these, 62 were diagnosed with IEM, with a detection rate of 0.56%. Thirty-five were males and 27 females and the median age was 3.55 months (range 0.07-143.9 months). Of the 62 patients, 27 (43.5%) had aminoacidemias, 26 (41.9%) had organic acidemias and nine (14.5%) had fatty acid oxidation disorders. Conclusions Because most symptomatic patients are diagnosed at an older age, mental retardation and motor delay are difficult to reverse. Additionally, poor medication compliance reduces the efficacy of treatment. More extensive newborn screening is thus imperative for ensuring early diagnosis and enhancing the treatment efficacy of IEM. PMID:22364411

  18. A large prospective European cohort study of patients treated with strontium ranelate and followed up over 3 years.

    PubMed

    Audran, M; Jakob, F J; Palacios, S; Brandi, M-L; Bröll, H; Hamdy, N A T; McCloskey, E V

    2013-09-01

    Strontium ranelate has been available as an osteoporosis treatment in Europe since 2004. This article describes a large European observational survey of the use of strontium ranelate in clinical daily practice. A retrospective observational registry included 32,446 women consulting for postmenopausal osteoporosis in seven countries. Within the registry, 12,046 women were receiving strontium ranelate and were followed up over 3 years. The baseline characteristics of the follow-up cohort were similar to those of the whole registry cohort (age, 68.9 ± 10.3 years; body mass index, 25.6 ± 4.3 kg/m(2); lumbar spine T-score, -2.57 ± 0.85 SD; femoral neck T-score, -2.11 ± 0.86 SD). At baseline, 77 % of patients had at least one risk factor for osteoporosis, and 46 % had a previous history of osteoporotic fracture. Mean duration of follow-up was 32.0 ± 9.7 months, and treatment duration was 25.2 ± 13.7 months (24,956 patient-years of treatment). Persistence with strontium ranelate was 80 % at 1 year, 68 % at 2 years, and 64 % at 32 months; most patients (about 80 %) reported rarely omitting a dose. At least one emergent adverse event was reported in 2,674 (22 %) patients, most frequently gastrointestinal side effects. The crude incidence of venous thromboembolic events was 2.1/1,000 patient-years. No cases of hypersensitivity reactions, such as drug rash with eosinophilia and systemic symptoms (DRESS), Steven-Johnson syndrome, or toxic epidermal necrolysis, were reported. During follow-up, a fracture occurred in 890 patients (7 %); 429 of the fractures were nonvertebral fractures. Our observational survey over 32 months indicated good rates of adherence with strontium ranelate and confirmed its good safety profile in the management of postmenopausal osteoporosis.

  19. F/A-18 E/F flutter clearance model in the Langley TDT

    NASA Technical Reports Server (NTRS)

    1994-01-01

    An 18 percent aeroelastically-scaled, full span F/A-18 E/F model was tested during multiple wind-tunnel entries in the Langley Transonic Dynamics Tunnel. The primary purpose of these entries was to assist in clearing the flight vehicle design of flutter within its operating envelope. The wind-tunnel model was tested on a string and on a cable-mount system (as shown). All lifting surfaces were flutter cleared up to M=1.2 with the model string mounted. The model was then flutter cleared on the cable-mount system to assess the influence of rigid-body dynamics and fuselage flexibility on flutter. Several configuration parametric studies were also completed, including many external store configurations.

  20. Crystal Structures of EF-G-Ribosome Complexes Trapped in Intermediate States of Translocation

    SciTech Connect

    Zhou, Jie; Lancaster, Laura; Donohue, John Paul; Noller, Harry F.

    2013-11-12

    Translocation of messenger and transfer RNA (mRNA and tRNA) through the ribosome is a crucial step in protein synthesis, whose mechanism is not yet understood. The crystal structures of three Thermus ribosome-tRNA-mRNA–EF-G complexes trapped with β,γ-imidoguanosine 5'-triphosphate (GDPNP) or fusidic acid reveal conformational changes occurring during intermediate states of translocation, including large-scale rotation of the 30S subunit head and body. In all complexes, the tRNA acceptor ends occupy the 50S subunit E site, while their anticodon stem loops move with the head of the 30S subunit to positions between the P and E sites, forming chimeric intermediate states. Two universally conserved bases of 16S ribosomal RNA that intercalate between bases of the mRNA may act as “pawls” of a translocational ratchet. These findings provide new insights into the molecular mechanism of ribosomal translocation.

  1. Sequence analysis of the EF-1 alpha gene family of Mucor racemosus.

    PubMed Central

    Sundstrom, P; Lira, L M; Choi, D; Linz, J E; Sypherd, P S

    1987-01-01

    Our previous studies have shown that Mucor racemosus possesses three genes (TEF-1, -2 and -3) for EF-1 alpha, and that all three genes are transcribed. However, the level of transcription varies markedly between the three genes, with TEF-1 mRNA levels being approximately two fold higher than TEF-3 and 6 fold higher than TEF-2. We have now completed the DNA sequence of both strands of all three genes and have found that these genes are highly homologous. TEF-2 and TEF-3 are more similar to each other than they are to TEF-1. The TEF-2 and the TEF-3 coding regions differ from TEF-1 at 30 and 37 positions respectively out of 1374 nucleotides. Twenty-six of these nucleotide substitutions were common to both TEF-2 and TEF-3, and the majority of the substitutions were clustered in the 5' region of the coding sequences. While the majority of these changes were silent, TEF-2 and TEF-3 differed from TEF-1 by having a lysine instead of a glutamate at amino acid position 41. In addition, TEF-2 and -3, but not TEF-1, each have an intron located near the 5' end of the coding region, although its size and sequence is not conserved between the two genes. All three genes have a conserved intron near the 3' end of the coding region. The sequence data have been analyzed with respect to the structure and function of EF-1 alpha in protein biosynthesis. PMID:3697088

  2. AGE AND GENDER-DEPENDENT ALTERNATIVE SPLICING OF P/Q-TYPE CALCIUM CHANNEL EF-HAND

    PubMed Central

    Chang, Siao Yun; Yong, Tan Fong; Yu, Chye Yun; Liang, Mui Cheng; Pletnikova, Olga; Troncoso, Juan C.; Burgunder, Jean-Marc; Soong, Tuck Wah

    2007-01-01

    Cav2.1 Ca2+ channels (P/Q-type), which participate in various key roles in the central nervous systems by mediating calcium influx, are extensively spliced. One of its alternatively-spliced exon is 37, which forms part of the EF hand. The expression of exon 37a (EFa form), but not exon 37b (EFb form), confers the channel an activity-dependent enhancement of channel opening known as Ca2+-dependent facilitation (CDF). In this study, we analyzed the trend of EF hand splice variant distributions in mouse, rat and human brain tissues. We observed a developmental switch in rodents, as well as an age and gender bias in human brain tissues, suggestive of a possible role of these EF hand splice variants in neurophysiological specialization. A parallel study performed on rodent brains showed that the data drawn from human and rodent tissues may not necessarily correlate in the process of aging. PMID:17291689

  3. [Sodium cromoglycate in the treatment of food hypersensitivity in children under 3 years of age].

    PubMed

    Zur, E; Kaczmarski, M

    2001-09-01

    Dietary elimination is a treatment of first choice in food hypersensitivity. Such therapy is not always enough to stop the disease and introduction of pharmacological treatment is necessary. In prevention and long term treatment antiallergic drugs are recommended. The aim of the study was to assess efficacy and safety of oral sodium cromoglycate in treatment of food hypersensitivity in the youngest children. In our study we examined: the group of 25 children aged 6 months-3 years treated with oral cromolyn sodium during the period 4-20 weeks and 29 children aged 6 months-3 years treated with ketotifen. Symptoms from skin, digestive and respiratory tract, behaviour status were evaluated for drugs efficacy. Cromolyn and ketotifen effected a significant decrease in total symptoms score. The treatment was well tolerated. No serious side effects were noted. The incidents of skin rash, disquiet during the night, diarrhoea and urticaria were only 8 percent. Sodium cromoglycate is safe and effective drug in treatment of food allergy in children; specially in symptoms from gastrointestinal tract and multi-organs allergy.

  4. Growth, behavior, development and intelligence in rural children between 1-3 years of life.

    PubMed

    Agarwal, D K; Awasthy, A; Upadhyay, S K; Singh, P; Kumar, J; Agarwal, K N

    1992-04-01

    In a rural cohort of 625 children registered from 1981 to 1983 in 10 villages of K.V. Block, Varanasi, 196 children were assessed for physical growth, development, intelligence and concept development between 1 and 3 years of age. Home environment was also assessed using Caldwell Home inventory. These rural children remained below 3rd centile of NCHS standard for weight, height, skull and mid-arm circumferences throughout the study. Malnourished children scored poorly in all the areas of development, i.e., motor, adaptive, language and personal social, 9% in Grade I and 16.6% children in Grade II + III had IQ less than 79 (inferior). Concept for color shape and size was poorly developed in malnourished children. Maternal involvement and stimulation was strongly associated with better behavior development and intelligence. Multiple regression analysis showed that the effect of home environment on development and intelligence was of a higher magnitude as compared to status and family variables and nutritional status during 1-3 years of age.

  5. 3-Year-olds' comprehension, production, and generalization of Sesotho passives.

    PubMed

    Demuth, Katherine; Moloi, Francina; Machobane, Malillo

    2010-05-01

    Researchers have long been puzzled by the challenge English passive constructions present for language learners, with adult-like comprehension and production emerging only around the age of 5. It has therefore been of significant interest that researchers of other languages, including the Bantu language Sesotho, have reported acquisition of the passive by the age of 3 (Demuth, 1989). Such reports have typically been based on spontaneous production data, calling for further investigation. This study carried out a series of experiments with Sesotho-speaking 3-year-olds, testing their ability to comprehend the passive, produce the passive, and generalize novel verbs to passive frames. The results showed that passive comprehension was good, with no effect of actional/non-actional verb type. Elicited production of the passive was also good, with no difference between adversive and non-adversive verbs. Finally, all participants made both active and passive generalizations to novel verbs. These findings provide strong evidence that Sesotho-speaking 3-year-olds have robust, abstract knowledge of passive syntax. The paper concludes with a discussion of the factors that contribute to the early learning of the Sesotho passive, why acquisition of the passive may be delayed in English, and the implications for understanding grammatical development more generally.

  6. Joint action modulates motor system involvement during action observation in 3-year-olds.

    PubMed

    Meyer, Marlene; Hunnius, Sabine; van Elk, Michiel; van Ede, Freek; Bekkering, Harold

    2011-06-01

    When we are engaged in a joint action, we need to integrate our partner's actions with our own actions. Previous research has shown that in adults the involvement of one's own motor system is enhanced during observation of an action partner as compared to during observation of an individual actor. The aim of this study was to investigate whether similar motor system involvement is present at early stages of joint action development and whether it is related to joint action performance. In an EEG experiment with 3-year-old children, we assessed the children's brain activity and performance during a joint game with an adult experimenter. We used a simple button-pressing game in which the two players acted in turns. Power in the mu- and beta-frequency bands was compared when children were not actively moving but observing the experimenter's actions when (1) they were engaged in the joint action game and (2) when they were not engaged. Enhanced motor involvement during action observation as indicated by attenuated sensorimotor mu- and beta-power was found when the 3-year-olds were engaged in the joint action. This enhanced motor activation during action observation was associated with better joint action performance. The findings suggest that already in early childhood the motor system is differentially activated during action observation depending on the involvement in a joint action. This motor system involvement might play an important role for children's joint action performance.

  7. The relation between student motivation and student grades in physical education: A 3-year investigation.

    PubMed

    Barkoukis, V; Taylor, I; Chanal, J; Ntoumanis, N

    2014-10-01

    Enhancing students' academic engagement is the key element of the educational process; hence, research in this area has focused on understanding the mechanisms that can lead to increased academic engagement. The present study investigated the relation between motivation and grades in physical education (PE) employing a 3-year longitudinal design. Three hundred fifty-four Greek high school students participated in the study. Students completed measures of motivation to participate in PE on six occasions; namely, at the start and the end of the school year in the first, second, and third year of junior high school. Students' PE grades were also recorded at these time points. The results of the multilevel growth models indicated that students' PE grades increased over the 3 years and students had better PE grades at the end of each year than at the beginning of the subsequent year. In general, students and classes with higher levels of controlling motivation achieved lower PE grades, whereas higher levels of autonomous motivation were associated with higher PE grades. These findings provide new insight on the associations between class- and individual-level motivation with objectively assessed achievement in PE.

  8. Spatial but not verbal cognitive deficits at age 3 years in persistently antisocial individuals.

    PubMed

    Raine, Adrian; Yaralian, Pauline S; Reynolds, Chandra; Venables, Peter H; Mednick, Sarnoff A

    2002-01-01

    Previous studies have repeatedly shown verbal intelligence deficits in adolescent antisocial individuals, but it is not known whether these deficits are in place prior to kindergarten or, alternatively, whether they are acquired throughout childhood. This study assesses whether cognitive deficits occur as early as age 3 years and whether they are specific to persistently antisocial individuals. Verbal and spatial abilities were assessed at ages 3 and 11 years in 330 male and female children, while antisocial behavior was assessed at ages 8 and 17 years. Persistently antisocial individuals (N = 47) had spatial deficits in the absence of verbal deficits at age 3 years compared to comparisons (N = 133), and also spatial and verbal deficits at age 11 years. Age 3 spatial deficits were independent of social adversity, early hyperactivity, poor test motivation, poor test comprehension, and social discomfort during testing, and they were found in females as well as males. Findings suggest that early spatial deficits contribute to persistent antisocial behavior whereas verbal deficits are developmentally acquired. An early-starter model is proposed whereby early spatial impairments interfere with early bonding and attachment, reflect disrupted right hemisphere affect regulation and expression, and predispose to later persistent antisocial behavior.

  9. Psychotherapy with a 3-Year-Old Child: The Role of Play in the Unfolding Process

    PubMed Central

    Salcuni, Silvia; Di Riso, Daniela; Mabilia, Diana; Lis, Adriana

    2017-01-01

    Few studies have investigated the outcomes and process of psychodynamic psychotherapies with children. Among the limited number of studies, some only paid attention to play and verbal production, as they are fundamental aspects in assessing the psychotherapy process. This paper focuses on an empirical investigation of a 3-year, once-a-week psychodynamic psychotherapy carried out with a 3-year-old girl. A process-outcome design was implemented to evaluate play and verbal discourse in in the initial, middle, and final parts of 30 psychotherapy sessions. Repeated measurements of standardized play categories (the Play Category System and the Affect in Play Scale—Preschool version) and verbal discourse (Verbal Production) were analyzed. To increase the clinical validity of the study, data from the assessment phase and vignettes from the sessions were reported to deepen the patient’s picture during the unfolding therapy process. Parent reports before and after the therapy were also included. Empirically measured changes in play and verbal production were fundamental in evaluating the young patient’s psychotherapy process. Verbal production and discourse ability progressively increased and took the place of play, which instead became more symbolic. Developmental issues as well as psychotherapy’s influence on the patient’s change, were discussed in relation to the role of play in enhancing the development of verbal dialog and the expression of the child’s emotions, needs, and desires. PMID:28101070

  10. Mental Health Diagnoses 3 Years After Receiving or Being Denied an Abortion in the United States

    PubMed Central

    Neuhaus, John M.; Foster, Diana G.

    2015-01-01

    Objectives. We set out to assess the occurrence of new depression and anxiety diagnoses in women 3 years after they sought an abortion. Methods. We conducted semiannual telephone interviews of 956 women who sought abortions from 30 US facilities. Adjusted multivariable discrete-time logistic survival models examined whether the study group (women who obtained abortions just under a facility’s gestational age limit, who were denied abortions and carried to term, who were denied abortions and did not carry to term, and who received first-trimester abortions) predicted depression or anxiety onset during seven 6-month time intervals. Results. The 3-year cumulative probability of professionally diagnosed depression was 9% to 14%; for anxiety it was 10% to 15%, with no study group differences. Women in the first-trimester group and women denied abortions who did not give birth had greater odds of new self-diagnosed anxiety than did women who obtained abortions just under facility gestational limits. Conclusions. Among women seeking abortions near facility gestational limits, those who obtained abortions were at no greater mental health risk than were women who carried an unwanted pregnancy to term. PMID:26469674

  11. HDAC inhibitors, MS-275 and salermide, potentiates the anticancer effect of EF24 in human pancreatic cancer cells

    PubMed Central

    Yar Saglam, Atiye Seda; Yilmaz, Akin; Onen, Hacer Ilke; Alp, Ebru; Kayhan, Handan; Ekmekci, Abdullah

    2016-01-01

    Histone deacetylases (HDACs) play a major role in the regulation of chromatin structure and gene expression by changing acetylation status of histone and non-histone proteins. MS-275 (entinostat, MS) is a well-known benzamide-based HDACI and Salermide (SAL), a reverse amide compound HDACI, have antiproliferative effects on several human cancer cells. In this study, we aimed to investigate the effects of HDACIs (MS and SAL) alone and/or combined use with EF24 (EF), a novel synthetic curcumin analog, on human pancreatic cancer cell line (BxPC-3). In vitro, BxPC-3 cells were exposed to varying concentrations of MS, SAL with or without EF, and their effects on cell viability, acetylated Histone H3 and H4 levels, cytotoxicity, and cleaved caspase 3 levels, and cell cycle distribution were measured. The viability of BxPC-3 cells decreased significantly after treatment with EF, MS and SAL treatments. MS and SAL treatment increased the acetylation of histone H3 and H4 in a dose dependent manner. MS and SAL alone or combined with EF were increased the number of cells in G1 phase. In addition, treatment with agents significantly decreased the ratio of cell in G2/M phase. There were significant dose-dependent increases at cleaved Caspase 3 levels after MS treatment but not after SAL treatment. Our results showed that HDAC inhibitors (MS and SAL), when combined with EF, may effectively reduce pancreatic cancer cell (BxPC-3) progression and stop the cell cycle at G1 phase. Further molecular analyses are needed to understand the fundamental molecular consequences of HDAC inhibition in pancreas cancer cells. PMID:27330528

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

    PubMed Central

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

    2017-01-01

    A major factor in the resilience of Listeria monocytogenes is the alternative sigma factor B (σB). Type II Toxin/Antitoxin (TA) systems are also known to have a role in the bacterial stress response upon activation via the ClpP or Lon proteases. Directly upstream of the σB operon in L. monocytogenes is the TA system mazEF, which can cleave mRNA at UACMU sites. In this study, we showed that the mazEF TA locus does not affect the level of persister formation during treatment with antibiotics in lethal doses, but exerts different effects according to the sub-inhibitory stress added. Growth of a ΔmazEF mutant was enhanced relative to the wildtype in the presence of sub-inhibitory norfloxacin and at 42 °C, but was decreased when challenged with ampicillin and gentamicin. In contrast to studies in Staphylococcus aureus, we found that the mazEF locus did not affect transcription of genes within the σB operon, but MazEF effected the expression of the σB-dependent genes opuCA and lmo0880, with a 0.22 and 0.05 fold change, respectively, compared to the wildtype under sub-inhibitory norfloxacin conditions. How exactly this system operates remains an open question, however, our data indicates it is not analogous to the system of S. aureus, suggesting a novel mode of action for MazEF in L. monocytogenes. PMID:28098783

  13. The radiation response of cells from 9L gliosarcoma tumours is correlated with [F18]-EF5 uptake

    PubMed Central

    KOCH, CAMERON J.; SHUMAN, ANNE L.; JENKINS, WALTER T.; KACHUR, ALEXANDER V.; KARP, JOEL S.; FREIFELDER, RICHARD; DOLBIER, WILLIAM R.; EVANS, SYDNEY M.

    2014-01-01

    Purpose Tumour hypoxia affects cancer biology and therapy-resistance in both animals and humans. The purpose of this study was to determine whether EF5 ([2-(2-nitro-1-H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl)-acetamide]) binding and/or radioactive drug uptake correlated with single-dose radiation response in 9L gliosarcoma tumours. Materials and methods Twenty-two 9L tumours were grown in male Fischer rats. Rats were administered low specific activity 18F-EF5 and their tumours irradiated and assessed for cell survival and hypoxia. Hypoxia assays included EF5 binding measured by antibodies against bound-drug adducts and gamma counts of 18F-EF5 tumour uptake compared with uptake by normal muscle and blood. These assays were compared with cellular radiation response (in vivo to in vitro assay). In six cases, uptake of tumour versus muscle was also assayed using images from a PET (positron emission tomography) camera (PENN G-PET). Results The intertumoural variation in radiation response of 9L tumour-cells was significantly correlated with uptake of 18F-labelled EF5 (i.e., including both bound and non-bound drug) using either tumour to muscle or tumour to blood gamma count ratios. In the tumours where imaging was performed, there was a significant correlation between the image analysis and gamma count analysis. Intertumoural variation in cellular radiation response of the same 22 tumours was also correlated with mean flow cytometry signal due to EF5 binding. Conclusion To our knowledge, this is the first animal model/drug combination demonstrating a correlation of radioresponse for tumour-cells from individual tumours with drug metabolism using either immunohistochemical or non-invasive techniques. PMID:19995239

  14. Presence of translation elongation factor-1A (eEF1A) in the excitatory postsynaptic density of rat cerebral cortex.

    PubMed

    Cho, Sun-Jung; Jung, Jae-Seob; Ko, Bok Hyun; Jin, IngNyol; Moon, Il Soo

    2004-08-05

    The postsynaptic density (PSD) is a proteinaceous cellular structure that is specialized for postsynaptic signal transduction. Here, we show that eukaryotic translation factor-1A (eEF1A; formerly known as eEF-1alpha) is associated with the excitatory PSD in rat forebrain. Immunoblot analysis showed that eEF1A in the PSD fraction is enriched over homogenate. Salt (1.0M NaCl), but not non-ionic detergents such as Triton X-100 (1.0%) and n-octyl glucoside (1.0%), could dissociate eEF1A from the PSD core. In cultured cortical neurons, eEF1A was colocalized with postsynaptic markers (PSD95 and SynGAPalpha), but not with a presynaptic marker (synaptophysin). These results indicate that eEF1A is present in the PSD of the excitatory synapses.

  15. Critical determinants of Ca(2+)-dependent inactivation within an EF-hand motif of L-type Ca(2+) channels.

    PubMed Central

    Peterson, B Z; Lee, J S; Mulle, J G; Wang, Y; de Leon, M; Yue, D T

    2000-01-01

    L-type (alpha(1C)) calcium channels inactivate rapidly in response to localized elevation of intracellular Ca(2+), providing negative Ca(2+) feedback in a diverse array of biological contexts. The dominant Ca(2+) sensor for such Ca(2+)-dependent inactivation has recently been identified as calmodulin, which appears to be constitutively tethered to the channel complex. This Ca(2+) sensor induces channel inactivation by Ca(2+)-dependent CaM binding to an IQ-like motif situated on the carboxyl tail of alpha(1C). Apart from the IQ region, another crucial site for Ca(2+) inactivation appears to be a consensus Ca(2+)-binding, EF-hand motif, located approximately 100 amino acids upstream on the carboxyl terminus. However, the importance of this EF-hand motif for channel inactivation has become controversial since the original report from our lab implicating a critical role for this domain. Here, we demonstrate not only that the consensus EF hand is essential for Ca(2+) inactivation, but that a four-amino acid cluster (VVTL) within the F helix of the EF-hand motif is itself essential for Ca(2+) inactivation. Mutating these amino acids to their counterparts in non-inactivating alpha(1E) calcium channels (MYEM) almost completely ablates Ca(2+) inactivation. In fact, only a single amino acid change of the second valine within this cluster to tyrosine (V1548Y) supports much of the functional knockout. However, mutations of presumed Ca(2+)-coordinating residues in the consensus EF hand reduce Ca(2+) inactivation by only approximately 2-fold, fitting poorly with the EF hand serving as a contributory inactivation Ca(2+) sensor, in which Ca(2+) binds according to a classic mechanism. We therefore suggest that while CaM serves as Ca(2+) sensor for inactivation, the EF-hand motif of alpha(1C) may support the transduction of Ca(2+)-CaM binding into channel inactivation. The proposed transduction role for the consensus EF hand is compatible with the detailed Ca(2+)-inactivation

  16. A Review of the R.O.K. Decision to Coassemble F-5E/F Aircraft.

    DTIC Science & Technology

    1980-03-01

    DECISION TO COASSEM3LE F-5E/F AIRCRAFT.. ’( A\\~ THESIS ’ ./AFIT/GSfl/SM/80M-j/ou, Kun Woo -.- trc ROKAF IJ 3 1930) 80 5 066 ~. AFIT/GSM/SM/80M-16 A...REVIEW OF THE R.O.K. DECISION TO COASSEMBLE r-5E/F AIRCRAFT THESIS Presented to the Faculty of the School of Engineering of the Air Force Institute of...potential problem areas and makes recommendations for solutions. CHAVIFP I I NIROUtICT I ON Background Security assistance (S.A.) has been a major

  17. Effect of hydroxypropyl cellulose (HPC) on dissolution rate of hydrochlorothiazide tablets.

    PubMed

    Desai, D; Rinaldi, F; Kothari, S; Paruchuri, S; Li, D; Lai, M; Fung, S; Both, D

    2006-02-03

    Hydrochlorothiazide (HCTZ) 60 mg strength tablets containing commonly used excipients and hydroxypropyl cellulose, marketed as either Klucel-EF (HPC, NF from Hercules, USA) or HPC-L (HPC, NF from Nippon Soda, Japan), as a binder were manufactured using identical aqueous wet granulation process. The tablets containing Klucel-EF as a binder exhibited higher dissolution rates than those manufactured using HPC-L. The granulations containing Klucel-EF or HPC-L showed no significant differences in compressibility and compactibility based on analysis performed using the Instron-Stress-Strain Analyzer. Both HPC grades met NF specifications and there were no differences for the NF test results in the certificates of analysis by their respective vendors. Further evaluation of both HPC grades indicated that the cloud point values for Klucel-EF and HPC-L in water were 39(+/- 1) and 48 degrees C, respectively. The differences in cloud points of Klucel-EF and HPC-L were correlated to the differences in the percent hydroxypropoxy content and the degree of molecular substitution, which were higher for Klucel-EF than for HPC-L. These structural features make Klucel-EF less hydrophilic. Since the cloud point of Klucel-EF was similar to the dissolution medium temperature of 37(+/- 2) degrees C, it may present a less viscous layer surrounding the HCTZ granules enabling faster dissolution of the drug.

  18. Heterozygous mutation of eEF1A1b resulted in spermatogenesis arrest and infertility in male tilapia, Oreochromis niloticus

    PubMed Central

    Chen, Jinlin; Jiang, Dongneng; Tan, Dejie; Fan, Zheng; Wei, Yingying; Li, Minghui; Wang, Deshou

    2017-01-01

    Eukaryotic elongation factor 1 alpha (eEF1A) is an essential component of the translational apparatus. In the present study, eEF1A1b was isolated from the Nile tilapia. Real-time PCR and Western blot revealed that eEF1A1b was expressed highly in the testis from 90 dah (days after hatching) onwards. In situ hybridization and immunohistochemistry analyses showed that eEF1A1b was highly expressed in the spermatogonia of the testis. CRISPR/Cas9 mediated mutation of eEF1A1b resulted in spermatogenesis arrest and infertility in the F0 XY fish. Consistently, heterozygous mutation of eEF1A1b (eEF1A1b+/−) resulted in an absence of spermatocytes at 90 dah, very few spermatocytes, spermatids and spermatozoa at 180 dah, and decreased Cyp11b2 and serum 11-ketotestosterone level at both stages. Further examination of the fertilization capacity of the sperm indicated that the eEF1A1b+/− XY fish were infertile due to abnormal spermiogenesis. Transcriptomic analyses of the eEF1A1b+/− testis from 180 dah XY fish revealed that key elements involved in spermatogenesis, steroidogenesis and sperm motility were significantly down-regulated compared with the control XY. Transgenic overexpression of eEF1A1b rescued the spermatogenesis arrest phenotype of the eEF1A1b+/− testis. Taken together, our data suggested that eEF1A1b is crucial for spermatogenesis and male fertility in the Nile tilapia. PMID:28266557

  19. COMPLETE STEROID AVOIDANCE IS EFFECTIVE AND SAFE IN CHILDREN WITH RENAL TRANSPLANTS: A MULTICENTER RANDOMIZED TRIAL WITH 3 YEAR FOLLOW UP

    PubMed Central

    Sarwal, Minnie M.; Ettenger, Robert; Dharnidharka, Vikas; Benfield, Mark; Mathias, Robert; Portale, Anthony; McDonald, Ruth; Harmon, William; Kershaw, David; Vehaskari, V. Matti; Kamil, Elaine; Baluarte, H. Jorge; Warady, Bradley; Tang, Lily; Liu, Jun; Li, Li; Naesens, Maarten; Sigdel, Tara; Waskerwitz, Janie; Salvatierra, Oscar

    2012-01-01

    To determine whether steroid avoidance in pediatric kidney transplantation is safe and efficacious, a randomized, multicenter trial was performed in 12 pediatric kidney transplant centers. One hundred thirty children receiving primary kidney transplants were randomized to steroid-free (SF) or steroid-based (SB) immunosuppression, with concomitant tacrolimus, mycophenolate, and standard dose daclizumab (SB group) or extended dose daclizumab (SF group). Follow-up was 3 years post-transplant. Standardized height Z score change after 3 years follow-up was −0.99±2.20 in SF vs. −0.93±1.11 in SB; p=0.825. In subgroup analysis, recipients under 5 years of age showed improved linear growth with SF compared to SB treatment (change in standardized height Z score at 3 years −0.43±1.15 vs. −1.07±1.14; p=0.019). There were no differences in the rates of biopsy-proven acute rejection at 3 years after transplantation (16.7% in SF vs. 17.1% in SB; p=0.94). Patient survival was 100% in both arms; graft survival was 95% in the SF and 90% in the SB arms (p=0.30) at 3 years follow-up. Over the three year follow-up period, the SF group showed lower systolic BP (p=0.017) and lower cholesterol levels (p=0.034). In conclusion, complete steroid avoidance is safe and effective in unsensitized children receiving primary kidney transplants. PMID:22694755

  20. Laparoscopic Sleeve Gastrectomy Versus Roux-Y-Gastric Bypass for Morbid Obesity—3-Year Outcomes of the Prospective Randomized Swiss Multicenter Bypass Or Sleeve Study (SM-BOSS)

    PubMed Central

    Peterli, Ralph; Wölnerhanssen, Bettina Karin; Vetter, Diana; Nett, Philipp; Gass, Markus; Borbély, Yves; Peters, Thomas; Schiesser, Marc; Schultes, Bernd; Beglinger, Christoph; Drewe, Juergen; Bueter, Marco

    2017-01-01

    Objective: Laparoscopic sleeve gastrectomy (LSG) is performed almost as often in Europe as laparoscopic Roux-Y-Gastric Bypass (LRYGB). We present the 3-year interim results of the 5-year prospective, randomized trial comparing the 2 procedures (Swiss Multicentre Bypass Or Sleeve Study; SM-BOSS). Methods: Initially, 217 patients (LSG, n = 107; LRYGB, n = 110) were randomized to receive either LSG or LRYGB at 4 bariatric centers in Switzerland. Mean body mass index of all patients was 44 ± 11 kg/m2, mean age was 43 ± 5.3 years, and 72% of patients were female. Minimal follow-up was 3 years with a rate of 97%. Both groups were compared for weight loss, comorbidities, quality of life, and complications. Results: Excessive body mass index loss was similar between LSG and LRYGB at each time point (1 year: 72.3 ± 21.9% vs. 76.6 ± 20.9%, P = 0.139; 2 years: 74.7 ± 29.8% vs. 77.7 ± 30%, P = 0.513; 3 years: 70.9 ± 23.8% vs. 73.8 ± 23.3%, P = 0.316). At this interim 3-year time point, comorbidities were significantly reduced and comparable after both procedures except for gastro-esophageal reflux disease and dyslipidemia, which were more successfully treated by LRYGB. Quality of life increased significantly in both groups after 1, 2, and 3 years postsurgery. There was no statistically significant difference in number of complications treated by reoperation (LSG, n = 9; LRYGB, n = 16, P = 0.15) or number of complications treated conservatively. Conclusions: In this trial, LSG and LRYGB are equally efficient regarding weight loss, quality of life, and complications up to 3 years postsurgery. Improvement of comorbidities is similar except for gastro-esophageal reflux disease and dyslipidemia that appear to be more successfully treated by LRYGB. PMID:28170356

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

    PubMed

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

    2017-03-07

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

  2. Epidermoid Cyst in the Floor of the Mouth of a 3-Year-Old

    PubMed Central

    Pascual Dabán, Rossana; García Díez, Eloy; González Navarro, Beatriz; López-López, José

    2015-01-01

    Epidermoid cysts are a rare entity in the oral cavity and are even less frequent in the floor of the mouth, representing less than 0.01% of all the cases. We present the case of a 3-year-old girl with a growth in the floor of the mouth with 2 months of evolution and without changes since it was discovered by her parents. The lesion was asymptomatic; it did not cause dysphagia, dyspnea, or any other alteration. A CT scan with contrast was done which revealed the location and exact size of the lesion, allowing an intraoral approach for its excision. The histological examination confirmed the clinical speculation of an epidermoid cyst. PMID:25694831

  3. Workplace safety in Bangladesh ready-made garment sector: 3 years after the Rana Plaza collapse.

    PubMed

    Barua, Uttama; Ansary, Mehedi Ahmed

    2016-11-18

    Workplace safety is one of the most important issues in industries worldwide, and is endangered by industrial accidents. Different industrial disasters have resulted in several initiatives worldwide to protect human life and reduce material damage, both nationally and internationally. In Bangladesh, the ready-made garment (RMG) industry is one of the most important export-oriented business sectors, which is facing challenges to ensure workplace safety. The Rana Plaza collapse in Bangladesh is the consequence of such non-compliance. The accident resulted in different local and global initiatives to address the challenges. This article reviews progress and achievement of the initiatives to reduce vulnerability in the Bangladesh RMG industry within 3 years after the deadly accident. In the long run, the challenge is to maintain momentum already created for achieving sustainability in the RMG sector in Bangladesh and maintaining compliance even after the end of support from external partners.

  4. Hemiconvulsion-hemiplegia-epilepsy syndrome. Magnetic resonance findings in a 3-year-old boy.

    PubMed

    Salafia, Stefania; Praticò, Andrea D; Pizzo, Enza; Greco, Filippo; Di Bella, Domenico

    2013-01-01

    The term 'hemiconvulsion-hemiplegia-epilepsy syndrome' (HHE) was first used by Gastaut et al. to describe the se-quential combination of unilateral or predominantly unilateral clonic seizures (hemiconvulsion), occurring during the first 2 years of life, immediately followed by an ipsilateral flaccid hemiplegia lasting 7 or more days. In the following phase partial epileptic seizures occur. We report a case of HHE syndrome in a 3-year-old boy with partial seizures (hemiconvulsion lasting 15-30 minutes) followed by left hemiplegia and hyporeflexia. Magnetic resonance imaging showed diffuse and high signal hyperintensity of the whole right cerebral hemisphere. Diffusion-weighted images showed a reduction of the apparent diffusion coefficient in the subcortical region. Magnetic resonance arterio-graphy showed a narrow flow signal in the distal territory of the right middle cerebral artery. The authors emphasize the importance of neuroradiological findings in early diagnosis and in the follow-up of HHE syndrome.

  5. Use of Feldspathic Porcelain Veneers to Improve Smile Harmony: A 3-Year Follow-up Report.

    PubMed

    Federizzi, Leonardo; Gomes, Érica Alves; Báratro, Samantha Schaffer Pugilato; Baratto-Filho, Flares; Bacchi, Ataís; Spazzin, Aloísio Oro

    2016-01-01

    This case report describes an esthetic treatment to improve the shape and alignment of the anterior teeth, reestablishing smile harmony, using feldspathic porcelain veneers. Results of clinical follow up after 36 months are also presented. The advantages, disadvantages and limitations of the technique are detailed with reference to the relevant literature. This suggests that the success of treatment depends on adequate conditions of bonding between the veneers and the tooth complex, which involves parameters such as the strength and durability of the bond interface. Therefore, the clinical success of feldspathic porcelain veneers depends on the accurate selection of cases and correct execution of clinical and laboratory procedures. The rehabilitation involved from first right premolar to the left with feldspathic porcelain veneers made on refractory dies. After the 3-year follow up, excellent clinical results and patient satisfaction were achieved.

  6. The neural correlates of processing newborn and adult faces in 3-year-old children

    PubMed Central

    Peykarjou, Stefanie; Westerlund, Alissa; Macchi Cassia, Viola; Kuefner, Dana; Nelson, Charles A.

    2013-01-01

    The current study examines the processing of upright and inverted faces in 3-year-old children (n = 35). Event-related potentials (ERPs) were recorded during a passive-looking paradigm including adult and newborn face stimuli. We observed three face-sensitive components, the P1, the N170 and the P400. Inverted faces elicited shorter P1 latency and larger P400 amplitude. P1 and N170 amplitudes were larger for adult faces. To examine the role of experience in the development of face processing, the processing of adult and newborn faces was compared for children with a younger sibling (n = 23) and children without a younger sibling (n = 12). Age of sibling at test correlated negatively with P1 amplitude for adult and newborn faces. This may indicate more efficient processing of different face ages in children with a younger sibling and potentially reflects a more flexible face representation. PMID:24118716

  7. Does attention constrain developmental trajectories in fragile x syndrome? A 3-year prospective longitudinal study.

    PubMed

    Cornish, Kim; Cole, Victoria; Longhi, Elena; Karmiloff-Smith, Annette; Scerif, Gaia

    2012-03-01

    Basic attentional processes and their impact on developmental trajectories in fragile X syndrome were assessed in a 3-year prospective study. Although fragile X syndrome is a monogenic X-linked disorder, there is striking variability in outcomes even in young boys with the condition. Attention is a key factor constraining interactions with the environment, so it is a perfect candidate to predict trajectories in cognitive and behavioral outcomes. In this study, 48 boys with fragile X syndrome were assessed 3 times over 24 months. Although nonverbal IQ declined, there were significant improvements in nonverbal growth scores and in cognitive attention. In contrast, behavioral difficulties (i.e., autistic symptomatology, hyperactivity-inattention) remained stable over this time frame. Attentional markers in the visual and auditory modalities predicted intellectual abilities and classroom behavior, whereas auditory markers alone predicted autistic symptomatology.

  8. Oral Hemorrhage in a 3-year-old Boy Caused by Self-Mutilating Behavior

    PubMed Central

    Uy, Jenny Lyn Y.; Lapeña, José Florencio F.

    2016-01-01

    A 3-year-old boy referred for persistent tongue bleeding was diagnosed with a rare self-mutilating disease that had also affected his lip and fingers. He underwent multiple odontectomy and partial glossectomy and continues to undergo behavior therapy and on-demand splints and restraints. He has stopped self-biting and has gained appetite and weight. Lesch-Nyhan Syndrome can cause significant morbidity including self-inflicted oral hemorrhage and emergent measures are not easily decided. The long-term management of its neurobehavioral symptoms is problematic and multidisciplinary, and health providers remain challenged to find the best treatment, prolong lifespan and improve quality of life within their respective contexts. PMID:28083069

  9. Development, Validation and Parametric study of a 3-Year-Old Child Head Finite Element Model

    NASA Astrophysics Data System (ADS)

    Cui, Shihai; Chen, Yue; Li, Haiyan; Ruan, ShiJie

    2015-12-01

    Traumatic brain injury caused by drop and traffic accidents is an important reason for children's death and disability. Recently, the computer finite element (FE) head model has been developed to investigate brain injury mechanism and biomechanical responses. Based on CT data of a healthy 3-year-old child head, the FE head model with detailed anatomical structure was developed. The deep brain structures such as white matter, gray matter, cerebral ventricle, hippocampus, were firstly created in this FE model. The FE model was validated by comparing the simulation results with that of cadaver experiments based on reconstructing the child and adult cadaver experiments. In addition, the effects of skull stiffness on the child head dynamic responses were further investigated. All the simulation results confirmed the good biofidelity of the FE model.

  10. Paternal psychosocial characteristics and corporal punishment of their 3-year-old children.

    PubMed

    Lee, Shawna J; Perron, Brian E; Taylor, Catherine A; Guterman, Neil B

    2011-01-01

    This study uses data from 2,309 biological fathers who participated in the Fragile Families and Child Well-Being Study (FFCWS) to examine associations between psychosocial characteristics and levels of corporal punishment (CP) toward their 3-year-old children over the past month. Results indicate that 61% of the fathers reported no CP over the past month, 23% reported using CP once or twice, and 16% reported using CP a few times in the past month or more. In multivariate models controlling for important sociodemographic factors as well as characteristics of the child, fathers' parenting stress, major depression, heavy alcohol use, and drug use were significantly associated with greater use of CP, whereas involvement with the child and generalized anxiety disorder were not. Girls were less likely to be the recipient of CP than were boys, and child externalizing behavior problems but not internalizing behavior problems were associated with more CP.

  11. Drug-induced systemic lupus erythematosus in a child after 3 years of treatment with carbamazepine.

    PubMed

    Molina-Ruiz, Ana María; Lasanta, Begoña; Barcia, Ana; Pérez-Vega, Elisa; Requena, Luis

    2017-02-01

    Drug-induced lupus erythematosus (DILE) is a less severe variant of systemic lupus erythematosus (SLE) that generally resolves within weeks or months after the withdrawal of the implicated drug. DILE is unusual during childhood, with the most frequent age of presentation being at 50-70 years of age. Among different drugs, most commonly procainamide and hydralazine have been implicated as a cause of DILE. However carbamazepine (CBZ) is considered a low-risk drug and very few cases have been reported in children. We describe the case of CBZ-induced SLE in a 9-year-old girl following 3 years of CBZ therapy. This case report shows that drug-induced SLE is an important side-effect to be considered, even after long-term treatment with CBZ, and also during childhood.

  12. 3-year study of donepezil therapy in Alzheimer's disease: effects of early and continuous therapy.

    PubMed

    Winblad, B; Wimo, A; Engedal, K; Soininen, H; Verhey, F; Waldemar, G; Wetterholm, A-L; Haglund, A; Zhang, R; Schindler, R

    2006-01-01

    Delays in the diagnosis of Alzheimer's disease, and, therefore, delays in treatment, may have a detrimental effect on a patient's long-term well-being. This study assessed the effects of postponing donepezil treatment for 1 year by comparing patients treated continuously for 3 years with those who received placebo for 1 year followed by open-label donepezil for 2 years. Patients (n = 286) with possible or probable Alzheimer's disease (according to DSM-IV, NINCDS-ADRDA, and Mini-Mental State Examination criteria; see text) were randomized to receive donepezil (5 mg/day for 4 weeks, 10 mg/day thereafter) or placebo (delayed-start group) for 1 year. Of the 192 completers, 157 began a 2-year, open-label phase of donepezil treatment. Outcome measures were the Gottfries-Bråne-Steen scale, the Mini-Mental State Examination, the Global Deterioration Scale, the Progressive Deterioration Scale, the Neuropsychiatric Inventory, and safety (adverse events). Mixed regression analysis was used to compare changes between the groups over 3 years on the efficacy measures. There was a trend for patients receiving continuous therapy to have less global deterioration (Gottfries-Bråne-Steen scale) than those who had delayed treatment (p = 0.056). Small but statistically significant differences between the groups were observed for the secondary measures of cognitive function (Mini-Mental State Examination; p = 0.004) and cognitive and functional abilities (Global Deterioration Scale; p = 0.0231) in favor of continuous donepezil therapy. Over 90% of the patients in both cohorts experienced one treatment-emergent adverse event; most were considered mild or moderate. In conclusion, patients in whom the start of treatment is delayed may demonstrate slightly reduced benefits as compared with those seen in patients starting donepezil therapy early in the course of Alzheimer's disease. These data support the long-term efficacy and safety of donepezil.

  13. Impact of Cigarette Smoking: a 3-Year Clinical Outcome of Vasospastic Angina Patients

    PubMed Central

    Choi, Byoung Geol; Park, Taeshik; Choi, Se Yeon; Byun, Jae Kyeong; Shim, Min Suk; Xu, Shaopeng; Li, Hu; Park, Sang-Ho; Park, Ji Young; Choi, Woong Gil; Cho, Yun-Hyeong; Lee, Sunki; Na, Jin Oh; Choi, Cheol Ung; Lim, Hong Euy; Kim, Jin Won; Kim, Eung Ju; Park, Chang Gyu; Seo, Hong Seog; Oh, Dong Joo

    2016-01-01

    Background and Objectives Cigarette smoking is a risk significant factor in coronary artery disease (CAD) and vasospastic angina (VSA). However, it is largely unknown whether smoking adds to any long-term clinical risk in VSA patients. Subjects and Methods A total of 2797 patients without significant CAD underwent acetylcholine (Ach) provocation test between November 2004 and October 2010. Patients were divided into three groups, based on the presence of coronary artery spasm (CAS) and smoking habits (non-CAS group: n=1188, non-smoking CAS group: n=1214, smoking CAS group: n=395). All CAS patients were prescribed with anti-anginal medications for at least 6 months. The incidence of major clinical outcomes and recurrent angina of these groups were compared up to 3 years. Results There were considerable differences in the baseline clinical and angiographic characteristics among the three groups, but there was no difference in the endpoints among the three groups (including individual and composite hard endpoints) such as death, myocardial infarction, de novo percutaneous coronary intervention, cerebrovascular accident, and major adverse cardiac events. However, there was a higher incidence of recurrent angina in both the non-smoking CAS group and smoking CAS group, as compared to the non-CAS group. In multivariable adjusted Cox-proportional hazards regression analysis, smoking CAS group exhibited a higher incidence of recurrent angina compared with the non-CAS group (hazard ratio [HR]; 2.46, 95% confidence interval [CI]; 1.46-4.14, p=0.001) and non-smoking CAS group (HR; 1.76, 95% CI; 1.08-2.87, p=0.021). Conclusion Cigarette smoking CAS group exhibited higher incidence of recurrent angina during the 3-year clinical follow-up compared with both the non-CAS group and non-smoking CAS group. Quitting of smoking, paired with intensive medical therapy and close clinical follow-up, can help to prevent recurrent angina. PMID:27721853

  14. Periodontal status and subgingival microbiota of insulin-dependent juvenile diabetics: a 3-year longitudinal study.

    PubMed

    Sbordone, L; Ramaglia, L; Barone, A; Ciaglia, R N; Iacono, V J

    1998-02-01

    This study examined for 3 years the changes in periodontal status and the possible correlations with selected subgingival microbiota and diabetic conditions in a group of 16 insulin-dependent diabetes mellitus (IDDM, JD) patients as compared with their 16 healthy cohabiting siblings (HS). JD patients were monitored every 3 months for levels of glycosylated hemoglobin (HbA1C). Clinical and microbiological parameters were measured 6 weeks before drawing blood to determine levels of HbA1C. Periodontal parameters were measured at baseline (TO), year 2 (T2), year 3 (T3) and included: probing depth (PD), attachment level (AL), sulcus bleeding index (SBI), and plaque index (PI). Two sites in each patient were selected for microbial samples: a mesio-facial aspect of the maxillary right first molar (defined as constant site, CS) and a site with the greatest probing depth (defined as deepest site, DS). Microbial samples were analyzed by culture techniques. No significant differences in clinical parameters were found between diabetics and healthy siblings at any examination. The SBI in the non-diabetic group at T2 and at T3 was significantly lower than at baseline. PD and AL of constant sites in the diabetic group at T3 were significantly higher than baseline. There was a significant increase in Prevotella intermedia at T3 as compared with baseline for deepest sites in the diabetic group. Cluster analysis revealed, in a former study, two clusters (IV and V) at baseline which were significantly different from the overall mean regarding composition of Porphyromonas gingivalis and Capnocytophaga spp. They were not significantly different for periodontal parameters from TO to T3. These data would suggest no significant differences in clinical parameters between the diabetics and non-diabetic siblings throughout this 3-year longitudinal study.

  15. Home parenteral nutrition--a 3-year analysis of clinical and laboratory monitoring.

    PubMed

    Burnes, J U; O'Keefe, S J; Fleming, C R; Devine, R M; Berkner, S; Herrick, L

    1992-01-01

    We report a 3-year analysis (1986 to 1989) of the management of 63 home parenteral nutrition patients, 40 with short-bowel syndrome and 23 with chronic intestinal obstruction with or without intestinal resection. Intravenous fluid requirements varied from 0.9 to 6 L/day, and the content of glucose varied between 46 and 531 g/day, protein varied from .0 to 85 g/day, fat from .0 to 100 g/day, sodium from 37 to 695 mEq/day, potassium from 30 to 220 mEq/day, chloride from 60 to 760 mEq/day, and acetate from 0 to 200 mEq/day. Body weight was normalized and well maintained in the majority of patients, but using the strict definition of deficiency as the presence of one abnormal value during 3 years, more than half had abnormal plasma chloride, glucose, alkaline phosphatase, serum glutamic oxaloacetic transaminase, total protein, albumin, selenium, and iron concentrations, and more than a third had low calcium, magnesium, vitamin D, and vitamin C levels. Normochromic anemia was seen in 73% and high blood creatinine associated with low urine volumes in 42%. Most (78%) returned to relatively normal lifestyles, but employability was occasionally impaired by loss of third-party insurance coverage resulting from a therapy that may cost $100,000 per year. Overall mortality was low (5% per year), but 73% needed readmission to hospital, mainly for suspected catheter sepsis. The results indicate that home parenteral nutrition has allowed many patients to survive gut failure and return to work but problems with chronic fluid, electrolyte and micronutrient deficiencies, catheter sepsis, and insurance coverage often restrict optimal rehabilitation.

  16. Environmental controls on fungal community composition and abundance over 3 years in native and degraded shrublands.

    PubMed

    Glinka, Clare; Hawkes, Christine V

    2014-11-01

    Soil fungal communities have high local diversity and turnover, but the relative contribution of environmental and regional drivers to those patterns remains poorly understood. Local factors that contribute to fungal diversity include soil properties and the plant community, but there is also evidence for regional dispersal limitation in some fungal communities. We used different plant communities with different soil conditions and experimental manipulations of both vegetation and dispersal to distinguish among these factors. Specifically, we compared native shrublands with former native shrublands that had been disturbed or converted to pasture, resulting in soils progressively more enriched in carbon and nutrients. We tested the role of vegetation via active removal, and we manipulated dispersal by adding living soil inoculum from undisturbed native sites. Soil fungi were tracked for 3 years, with samples taken at ten time points from June 2006 to June 2009. We found that soil fungal abundance, richness, and community composition responded primarily to soil properties, which in this case were a legacy of plant community degradation. In contrast, dispersal had no effect on soil fungi. Temporal variation in soil fungi was partly related to drought status, yet it was much broader in native sites compared to pastures, suggesting some buffering due to the increased soil resources in the pasture sites. The persistence of soil fungal communities over 3 years in this study suggests that soil properties can act as a strong local environmental filter. Largely persistent soil fungal communities also indicate the potential for strong biotic resistance and soil legacies, which presents a challenge for both the prediction of how fungi respond to environmental change and our ability to manipulate fungi in efforts such as ecosystem restoration.

  17. Living with diabetes—Development of learning patterns over a 3-year period

    PubMed Central

    Kneck, Åsa; Fagerberg, Ingegerd; Eriksson, Lars E.; Lundman, Berit

    2014-01-01

    Background Learning involves acquiring new knowledge and skills, and changing our ways of thinking, acting, and feeling. Learning in relation to living with diabetes is a lifelong process where there is limited knowledge of how it is experienced and established over time. It was considered important to explore how learning was developed over time for persons living with diabetes. Aim The aim of the study was to identify patterns in learning when living with diabetes, from recently being diagnosed, and over a 3-year period. Materials and methods A longitudinal qualitative descriptive design was used. Thirteen participants, with both type I and type II diabetes, were interviewed at three different occasions during a 3-year period. Qualitative content analysis was used in different steps in order to distinguish patterns. Findings Five main patterns of learning were identified. Two of the patterns (I and II) were characterized by gradually becoming comfortable living with diabetes, whereas for one pattern (IV) living with diabetes became gradually more difficult. For pattern V living with diabetes was making only a limited impact on life, whereas for Pattern III there was a constant management of obstacles related to illness. The different patterns in the present study showed common and different ways of learning and using different learning strategies at different timespans. Conclusion The present study showed that duration of illness is not of importance for how far a person has come in his own learning process. A person-centered care is needed to meet the different and changing needs of persons living with diabetes in relation to learning to live with a lifelong illness. PMID:25030359

  18. Utility of the nuclear protein-coding gene, elongation factor-1 gamma (EF-1gamma), for spider systematics, emphasizing family level relationships of tarantulas and their kin (Araneae: Mygalomorphae).

    PubMed

    Ayoub, Nadia A; Garb, Jessica E; Hedin, Marshal; Hayashi, Cheryl Y

    2007-02-01

    Spider systematics has overwhelmingly relied on morphological characters to resolve higher-level phylogenetic questions. Molecular phylogenetic studies of spiders above the genus level have been rare, partly because of a paucity of characterized genes available for amplification and sequencing. Here we show the phylogenetic utility of a new molecular marker, elongation factor-1 gamma (EF-1gamma) for discerning family level relationships in the spider infraorder, Mygalomorphae. We included genomic sequences from 26 mygalomorph genera in 14 families as well as cDNA sequences from 10 families in the infraorder Araneomorphae. We found strong support for the traditional split of mygalomorphs into atypoids (Antrodiaetidae, Atypidae, and Mecicobothriidae) and non-atypoids (all other families). Some families with multiple generic representatives were found to be polyphyletic or paraphyletic, such as the Nemesiidae, Ctenizidae, and Hexathelidae. A small portion of genomic EF-1gamma that could be amplified from araneomorphs contained a short intron, suggesting that longer genomic sequences could not be amplified due to the presence of introns. This intron may be useful for intra-familial araneomorph relationships. A tentative timeline for spider evolution is proposed using the evolutionary rate of EF-1gamma, estimated to be approximately 0.22% pairwise divergence per million years based on a non-parametric smoothing method (NPRS) and fossil constraints.

  19. Mechanism of fusidic acid inhibition of RRF- and EF-G-dependent splitting of the bacterial post-termination ribosome

    PubMed Central

    Borg, Anneli; Pavlov, Michael; Ehrenberg, Måns

    2016-01-01

    The antibiotic drug fusidic acid (FA) is commonly used in the clinic against gram-positive bacterial infections. FA targets ribosome-bound elongation factor G (EF-G), a translational GTPase that accelerates both messenger RNA (mRNA) translocation and ribosome recycling. How FA inhibits translocation was recently clarified, but FA inhibition of ribosome recycling by EF-G and ribosome recycling factor (RRF) has remained obscure. Here we use fast kinetics techniques to estimate mean times of ribosome splitting and the stoichiometry of GTP hydrolysis by EF-G at varying concentrations of FA, EF-G and RRF. These mean times together with previous data on uninhibited ribosome recycling were used to clarify the mechanism of FA inhibition of ribosome splitting. The biochemical data on FA inhibition of translocation and recycling were used to model the growth inhibitory effect of FA on bacterial populations. We conclude that FA inhibition of translocation provides the dominant cause of bacterial growth reduction, but that FA inhibition of ribosome recycling may contribute significantly to FA-induced expression of short regulatory open reading frames, like those involved in FA resistance. PMID:27001509

  20. Mechanism of fusidic acid inhibition of RRF- and EF-G-dependent splitting of the bacterial post-termination ribosome.

    PubMed

    Borg, Anneli; Pavlov, Michael; Ehrenberg, Måns

    2016-04-20

    The antibiotic drug fusidic acid (FA) is commonly used in the clinic against gram-positive bacterial infections. FA targets ribosome-bound elongation factor G (EF-G), a translational GTPase that accelerates both messenger RNA (mRNA) translocation and ribosome recycling. How FA inhibits translocation was recently clarified, but FA inhibition of ribosome recycling by EF-G and ribosome recycling factor (RRF) has remained obscure. Here we use fast kinetics techniques to estimate mean times of ribosome splitting and the stoichiometry of GTP hydrolysis by EF-G at varying concentrations of FA, EF-G and RRF. These mean times together with previous data on uninhibited ribosome recycling were used to clarify the mechanism of FA inhibition of ribosome splitting. The biochemical data on FA inhibition of translocation and recycling were used to model the growth inhibitory effect of FA on bacterial populations. We conclude that FA inhibition of translocation provides the dominant cause of bacterial growth reduction, but that FA inhibition of ribosome recycling may contribute significantly to FA-induced expression of short regulatory open reading frames, like those involved in FA resistance.

  1. A comparison study of the EF-18 agar/Hydrophobic Grid Membrane Filter (HGMF) method and the enzyme linked antibody (ELA)/HGMF method to the HPB standard method in the isolation of Salmonella.

    PubMed

    Warburton, D W; Arling, V; Worobec, S; Mackenzie, J; Todd, E C; Lacasse, P; Lamontagne, G; Plante, R; Shaw, S; Bowen, B

    1994-09-01

    As part of a comparative and collaborative study of rapid methods for the detection of Salmonella and the standard Health Protection Branch (HPB) method, six Federal and Provincial Laboratories compared the EF-18 agar/Hydrophobic Grid Membrane Filters (HGMF) method to the standard HPB method. Two Federal Laboratories also compared the enzyme linked antibody (ELA)/HGMF method (which is a further development of the EF-18 agar/HGMF method) to the standard method. During this study the false-negative rates ranged from 0% to 15% for the standard HPB method, from 5.88% to 43.5% for the EF-18 agar/HGMF method, and from 0% to 10.5% for the ELA/HGMF method. The EF-18 agar/HGMF method did not compare well with the standard HPB method due to the number of false-negatives. Problems with this method resulted from the inability to isolate colonies of Salmonella on the HGMF due to the small colony size, abnormal colony coloration, and overgrowth by competitors. The ELA/HGMF method, however, was shown to be comparable to the standard HPB method. The main advantages of this method are that the antibody-staining step is independent of colony coloration and carbohydrate utilization on the plating media; the ability to detect some unusual strains of Salmonella irrespective of their atypical reactions on the media; and the ELA staining can indicate the presence of Salmonella even when the HGMF is overgrown by competitors. Also, cultural confirmation can proceed simultaneously yet independently of the ELA staining procedure. The data presented here indicate that this method is worth further study.

  2. Integrative bioinformatics and proteomics-based discovery of an eEF2K inhibitor (cefatrizine) with ER stress modulation in breast cancer cells.

    PubMed

    Yao, Zhiqiang; Li, Juntang; Liu, Zhongyu; Zheng, Lu; Fan, Naijun; Zhang, Ying; Jia, Nan; Lv, Jingjing; Liu, Ningning; Zhu, Xiaoshan; Du, Jiangbo; Lv, Ci; Xie, Feng; Liu, Yigang; Wang, Xingke; Fei, Zhou; Gao, Chunfang

    2016-03-01

    Eukaryotic elongation factor-2 kinase (eEF2K), a unique calcium/calmodulin-dependent protein kinase, is well known to regulate apoptosis, autophagy and ER stress in many types of human cancers. Therefore, eEF2K would be regarded as a promising therapeutic target; however, the eEF2K-regulated mechanism and its targeted inhibitor still remain to be discovered in cancer. Herein, we constructed a protein-protein interaction (PPI) network of eEF2K and achieved an eEF2K-regulated ER stress subnetwork by bioinformatics prediction. Then, we found that the differential protein expressions involved in ER stress in the context of si-eEF2K-treated MCF-7 and MDA-MB-436 cells by iTRAQ-based analyses, respectively. Integrated into these aforementioned results, we constructed a core eEF2K-regulated ER stress subnetwork in breast cancer cells. Subsequently, we screened a series of candidate compounds targeting eEF2K and discovered a novel eEF2K inhibitor (cefatrizine) with an anti-proliferative activity toward breast cancer cells. Moreover, we found that cefatrizine induced ER stress in both MCF-7 and MDA-MB-436 cells. Interestingly, we demonstrated that the mechanism of cefatrizine-induced ER stress was in good agreement with our bioinformatics and proteomics-based results. In conclusion, these results demonstrate that a novel eEF2K inhibitor (cefatrizine) induces ER stress in breast cancer cells by integrating bioinformatics prediction, proteomics analyses and experimental validation, which would provide a clue for exploring more mechanisms of eEF2K and its targeted inhibitors in cancer therapy.

  3. Structure of human peptidyl-prolyl cis–trans isomerase FKBP22 containing two EF-hand motifs

    PubMed Central

    Boudko, Sergei P; Ishikawa, Yoshihiro; Nix, Jay; Chapman, Michael S; Bächinger, Hans Peter

    2014-01-01

    The FK506-binding protein (FKBP) family consists of proteins with a variety of protein–protein interaction domains and versatile cellular functions. It is assumed that all members are peptidyl-prolyl cis–trans isomerases with the enzymatic function attributed to the FKBP domain. Six members of this family localize to the mammalian endoplasmic reticulum (ER). Four of them, FKBP22 (encoded by the FKBP14 gene), FKBP23 (FKBP7), FKBP60 (FKBP9), and FKBP65 (FKBP10), are unique among all FKBPs as they contain the EF-hand motifs. Little is known about the biological roles of these proteins, but emerging genetics studies are attracting great interest to the ER resident FKBPs, as mutations in genes encoding FKBP10 and FKBP14 were shown to cause a variety of matrix disorders. Although the structural organization of the FKBP-type domain as well as of the EF-hand motif has been known for a while, it is difficult to conclude how these structures are combined and how it affects the protein functionality. We have determined a unique 1.9 Å resolution crystal structure for human FKBP22, which can serve as a prototype for other EF hand-containing FKBPs. The EF-hand motifs of two FKBP22 molecules form a dimeric complex with an elongated and predominantly hydrophobic cavity that can potentially be occupied by an aliphatic ligand. The FKBP-type domains are separated by a cleft and their putative active sites can catalyze isomerazation of two bonds within a polypeptide chain in extended conformation. These structural results are of prime interest for understanding biological functions of ER resident FKBPs containing EF-hand motifs. PMID:24272907

  4. Dynamics and energetics: a consensus analysis of the impact of calcium on EF-CaM protein complex.

    PubMed

    Laine, Elodie; Blondel, Arnaud; Malliavin, Thérèse E

    2009-02-18

    We have studied the relationship between dynamical correlations and energetic contributions in an attempt to model the transmission of information inside protein-protein complexes. The complex formed between the edema factor (EF) of Bacillus anthracis and calmodulin (CaM) was taken as an example, as the formation and stability of the complex depend on the calcium complexation level. The effect of calcium through EF-CaM residue network has been investigated with various approaches: 1), the elastic network model; 2), the local feature analysis; 3), the generalized correlations; and 4), the energetic dependency maps (EDMs), on 15-ns molecular dynamics simulations of the complex loaded with 0, 2, or 4 Ca2+ ions. The elastic network model correctly describes the basic architecture of the complex but is poorly sensitive to the level of calcium compared to the other methods. The local feature analysis allows us to characterize the local dynamics of the complex and the propagation of the calcium signal through CaM. The analyses of global dynamics and energetics--through generalized correlations and EDMs--provide a comprehensive picture of EF-CaM architecture and can be unified by using the concept of residue network connectedness. A medium connectedness, defined as the ability of each residue to communicate with all remaining parts of the complex, is observed for the 2Ca2+ level, which was experimentally identified as the most stable form of EF-CaM. The hierarchy of relative stabilities given by the EDMs sheds a new light on the EF-CaM interaction mechanism described experimentally and supports an organization of the complex architecture centered around nucleation points.

  5. Automated peritoneal dialysis as the modality of choice: a single-center, 3-year experience with 458 children in Mexico.

    PubMed

    Fabian Velasco, Rosaura; Lagunas Muñoz, Jesus; Sanchez Saavedra, Veronica; Mena Brito Trejo, Jorge E; Qureshi, Abdul Rashid; García-López, Elvia; Divino Filho, Jose C

    2008-03-01

    Automated peritoneal dialysis (APD) has been considered as the ideal dialysis modality for pediatric patients. This study reports the 3-year APD experience with 458 end-stage renal disease (ESRD) children who started APD in a single pediatric center in Mexico City between June 2003 and June 2006. By June 2003, there were 310 patients being treated with continuous ambulatory peritoneal dialysis (CAPD). At that time, these patients were gradually switched to APD, with priority being given to those prescribed more than four exchanges per day, younger than 6 years of age, or presenting complications [hernias or decreased ultrafiltration (UF)]. An improvement of daily UF was observed when the patients were switched from CAPD (590 +/- 340 ml/day) to APD (846 +/- 335 ml/day). The presence of edema decreased (from 67% to 8%) as well as the percentage of patients requiring antihypertensive drugs (from 83% to 38%), the peritonitis rate improved from one episode every 35 patient/month to one episode every 47 patient/month, the total number of hospitalizations decreased (from 384 to 51), and 85% of children attended school. While waiting for renal transplant, APD is the dialysis modality of choice for ESRD children at the La Raza Medical Center in Mexico City.

  6. Experience and outcome of 3 years of a European EQA scheme for genetic testing of the spinocerebellar ataxias.

    PubMed

    Seneca, Sara; Morris, Michael A; Patton, Simon; Elles, Rob; Sequeiros, Jorge

    2008-08-01

    The European Molecular Genetics Quality Network (EMQN) has been organizing an external quality assessment (EQA) scheme for molecular genetic testing of trinucleotide repeat mutations in the spinocerebellar ataxias (SCAs) since 2004. DNA samples were validated by at least two independent labs and two different methods. Together with mock clinical case descriptions and requests for specific SCA gene analyses, these were sent to registered participants each year. Laboratories were asked to use their routine procedures and protocols. A panel of assessors reviewed the final returns, including genotype results and reports, to assess the quality of (1) genotyping and (2) interpretation and reporting. A description of methods and raw data were also requested and were very useful for the final analysis. Altogether, during 3 years, 239 reports were received from the laboratories. Overall genotype error rate ranged 1.1-5.2%, a significant cause of concern. Scores for interpretation and reporting also showed that there is still much room for progress, although performance has improved over this period of assessment. The consequences of suboptimal laboratory practices, genotyping errors and misdiagnosis and of incorrect or incomplete interpretation and reporting have wide implications for patient lives, as well as for health management and counselling of relatives. EQA schemes are an important part of quality assurance in molecular genetic laboratories, and their use should become a routine part of laboratory diagnostic practice. Current evidence shows also that it is important that laboratories participate on a yearly basis and that this becomes mandatory for reference laboratories.

  7. Therapeutic hypothermia for neonatal encephalopathy: a report from the first 3 years of the Baby Cooling Registry of Japan

    PubMed Central

    Tsuda, Kennosuke; Mukai, Takeo; Iwata, Sachiko; Shibasaki, Jun; Tokuhisa, Takuya; Ioroi, Tomoaki; Sano, Hiroyuki; Yutaka, Nanae; Takahashi, Akihito; Takeuchi, Akihito; Takenouchi, Toshiki; Araki, Yuko; Sobajima, Hisanori; Tamura, Masanori; Hosono, Shigeharu; Nabetani, Makoto; Iwata, Osuke; Adachi, Hiroyuki; Aiba, Satoru; Akiyoshi, Shinnosuke; Amizuka, Takasuke; Aoki, Mikihiro; Arai, Hirokazu; Arai, Junichi; Asanuma, Hideomi; Baba, Atsushi; Bonno, Motoki; Daimon, Yusuke; Egashira, Tomoko; Fukuhara, Rie; Fukushima, Naoki; Futamura, Masahide; Harada, Sayaka; Hattori, Tsukasa; Henmi, Nobuhide; Hiroma, Takehiko; Hisano, Tadashi; Ieda, Kuniko; Iida, Koichi; Iijima, Shigeo; Imai, Ken; Imamura, Takashi; Inoue, Shinkai; Ishiguro, Akio; Suzuki, Keiji; Ishii, Tsutomu; Ito, Takashi; Iwai, Masanori; Iwataki, Shinnichiro; Jinnai, Wataru; Kai, Akihiko; Kanbe, Taro; Kinoshita, Masahiro; Kanda, Hiroshi; Kaneko, Masatoshi; Kawase, Akihiko; Kawato, Hitoshi; Kida, Yoshikazu; Kihara, Minako; Kitano, Hiroyuki; Kishigami, Makoto; Shibata, Naoaki; Kito, Osamu; Kobayashi, Akira; Kohno, Yoshinori; Kokubo, Minoru; Kondo, Masatoshi; Konishi, Eri; Kugo, Masaki; Kouwaki, Masanori; Kumagai, Takeshi; Kusaka, Takashi; Kusuda, Takeshi; Maeda, Tomoki; Maede, Yoshinobu; Maji, Tomoaki; Makiya, Tomoko; Maruyama, Kennichi; Masunaga, Ken; Matsumoto, Atsushi; Matsumoto, Hiroshi; Matsumoto, Naoko; Mima, Aya; Minagawa, Kyoko; Minosaki, Yoshihiro; Minowa, Hideki; Miura, Mazumi; Miyata, Masafumi; Miyazono, Yayoi; Mizumoto, Hiroshi; Mori, Kazuhiro; Morioka, Ichiro; Morisawa, Takeshi; Nagaya, Ken; Nagayama, Yoshihisa; Naito, Atsushi; Nakamura, Kenji; Nakamura, Makoto; Nakao, Atsushi; Nakao, Hideto; Nakazawa, Yusuke; Nishimura, Yutaka; Nishizaki, Naoto; Nosaka, Kazuhiko; Nozaki, Masatoshi; Ochiai, Masayuki; Ohashi, Atsushi; Ohki, Shigeru; Omori, Isaku; Osone, Yoshiteru; Saito, Junko; Sato, Yoshiaki; Sato, Yoshitake; Seki, Kazuo; Shirakawa, Yoshitsugu; Shiro, Hiroyuki; Suzumura, Hiroshi; Takahashi, Ritsuko; Takahata, Yasushi; Taki, Atsuko; Tanaka, Taihei; Tateishi, Itaru; Tsunei, Mikio; Usuda, Touhei; Yada, Yukari; Yamamoto, Junko; Yamamoto, Masahito; Yoda, Hitoshi; Yokoi, Akiko; Yoshida, Shinobu; Yoshida, Taketoshi; Yoshida, Tomohide; Yoshikawa, Kayo

    2017-01-01

    Therapeutic hypothermia is recommended for moderate and severe neonatal encephalopathy, but is being applied to a wider range of neonates than originally envisaged. To examine the clinical use of therapeutic hypothermia, data collected during the first 3 years (2012–2014) of the Baby Cooling Registry of Japan were analysed. Of 485 cooled neonates, 96.5% were ≥36 weeks gestation and 99.4% weighed ≥1,800 g. Severe acidosis (pH < 7 or base deficit ≥16 mmol/L) was present in 68.9%, and 96.7% required resuscitation for >10 min. Stage II/III encephalopathy was evident in 88.3%; hypotonia, seizures and abnormal amplitude-integrated electroencephalogram were observed in the majority of the remainder. In-hospital mortality was 2.7%; 90.7% were discharged home. Apgar scores and severity of acidosis/encephalopathy did not change over time. The time to reach the target temperature was shorter in 2014 than in 2012. The proportion undergoing whole-body cooling rose from 45.4% to 81.6%, while selective head cooling fell over time. Mortality, duration of mechanical ventilation and requirement for tube feeding at discharge remained unchanged. Adherence to standard cooling protocols was high throughout, with a consistent trend towards cooling being achieved more promptly. The mortality rate of cooled neonates was considerably lower than that reported in previous studies. PMID:28051172

  8. Maxillary overdentures supported by four splinted direct metal laser sintering implants: a 3-year prospective clinical study.

    PubMed

    Mangano, Francesco; Luongo, Fabrizia; Shibli, Jamil Awad; Anil, Sukumaran; Mangano, Carlo

    2014-01-01

    Purpose. Nowadays, the advancements in direct metal laser sintering (DMLS) technology allow the fabrication of titanium dental implants. The aim of this study was to evaluate implant survival, complications, and peri-implant marginal bone loss of DMLS implants used to support bar-retained maxillary overdentures. Materials and Methods. Over a 2-year period, 120 implants were placed in the maxilla of 30 patients (18 males, 12 females) to support bar-retained maxillary overdentures (ODs). Each OD was supported by 4 implants splinted by a rigid cobalt-chrome bar. At each annual follow-up session, clinical and radiographic parameters were assessed. The outcome measures were implant failure, biological and prosthetic complications, and peri-implant marginal bone loss (distance between the implant shoulder and the first visible bone-to-implant contact, DIB). Results. The 3-year implant survival rate was 97.4% (implant-based) and 92.9% (patient-based). Three implants failed. The incidence of biological complication was 3.5% (implant-based) and 7.1% (patient-based). The incidence of prosthetic complication was 17.8% (patient-based). No detrimental effects on marginal bone level were evidenced. Conclusions. The use of 4 DMLS titanium implants to support bar-retained maxillary ODs seems to represent a safe and successful procedure. Long-term clinical studies on a larger sample of patients are needed to confirm these results.

  9. Maxillary Overdentures Supported by Four Splinted Direct Metal Laser Sintering Implants: A 3-Year Prospective Clinical Study

    PubMed Central

    Mangano, Francesco; Shibli, Jamil Awad; Anil, Sukumaran

    2014-01-01

    Purpose. Nowadays, the advancements in direct metal laser sintering (DMLS) technology allow the fabrication of titanium dental implants. The aim of this study was to evaluate implant survival, complications, and peri-implant marginal bone loss of DMLS implants used to support bar-retained maxillary overdentures. Materials and Methods. Over a 2-year period, 120 implants were placed in the maxilla of 30 patients (18 males, 12 females) to support bar-retained maxillary overdentures (ODs). Each OD was supported by 4 implants splinted by a rigid cobalt-chrome bar. At each annual follow-up session, clinical and radiographic parameters were assessed. The outcome measures were implant failure, biological and prosthetic complications, and peri-implant marginal bone loss (distance between the implant shoulder and the first visible bone-to-implant contact, DIB). Results. The 3-year implant survival rate was 97.4% (implant-based) and 92.9% (patient-based). Three implants failed. The incidence of biological complication was 3.5% (implant-based) and 7.1% (patient-based). The incidence of prosthetic complication was 17.8% (patient-based). No detrimental effects on marginal bone level were evidenced. Conclusions. The use of 4 DMLS titanium implants to support bar-retained maxillary ODs seems to represent a safe and successful procedure. Long-term clinical studies on a larger sample of patients are needed to confirm these results. PMID:25580124

  10. Impact of a 3-year pet management program on pet population and owner's perception.

    PubMed

    Dias Costa, Esther; Martins, Camila Marinelli; Cunha, Graziela Ribeiro; Catapan, Dariane Cristina; Ferreira, Fernando; Oliveira, Simone Tostes; Garcia, Rita de Cassia Maria; Biondo, Alexander Welker

    2017-04-01

    Although pet population management programs have been established worldwide, few reports on program evaluation have been carried out to date. Accordingly, a 3-year longitudinal study has been carried out in a 4000 household neighborhood located within the metropolitan area of Curitiba, the eighth most populated city of Brazil. Visits were conducted and questionnaires completed to estimate and characterize the local pet population (animal sex, reproductive and vaccination status, street access). Care provided by owners, community perception on stray dog management and the possible changes were compared in these variables over time (2010 and 2013) were evaluated, after the establishment of a city pet population management program. In addition, associations between having children, owning dogs and cats, responsible pet ownership education and owner's perception on stray dogs were statistically tested. A total of 354/4000 (8.9%) household families were interviewed in 2010 and 70/354 (19.8%) of the same families again in 2013. No significant changes were found in overall number of dogs and cats and average pet age, animal care and owner's perception on stray dogs following the 3-year population management program. In 2010, an average of 1.6 dogs and 0.3 cats were found per family, with slightly more females (51.3% dogs and 51.1% cats), adults (4.0±3.5years for dogs and 2.1±2.4 for cats), intact (not neutered; 94.2% dogs and 84.0% cats) and lacking regular visit to veterinarian (71.6%). Although more families (53.1%) had children under 12 years old, no association was found between having children and having dogs and cats. Questionnaires revealed that owners perceived neutering/spaying to be the best pet population control method (42.4%), with "society" (50%) and "government" (49.4%) as responsible for pet population management. A significant positive association has been found between education level and the best way to control stray dogs (p=0.03), between having dogs

  11. ANALYZING THE LOW STATE OF EF ERIDANI WITH HUBBLE SPACE TELESCOPE ULTRAVIOLET SPECTRA

    SciTech Connect

    Szkody, Paula; Mukadam, Anjum; Gaensicke, Boris T.; Campbell, Ryan K.; Harrison, Thomas E.; Holtzman, Jon; Boberg, Owen; Howell, Steve B.; Walter, Frederick M.; Henden, Arne; Dillon, William; Dealaman, Shannon; Perone, Christian S. E-mail: anjum@astro.washington.ed

    2010-06-20

    Time-resolved spectra throughout the orbit of EF Eri during its low accretion state were obtained with the solar blind channel on the Advanced Camera for Surveys on board the Hubble Space Telescope. The overall spectral distribution exhibits peaks at 1500 and 1700 A, while the UV light curves display a quasi-sinusoidal modulation over the binary orbit. Models of white dwarfs (WDs) with a hot spot and cyclotron emission were attempted to fit the spectral variations throughout the orbit. A non-magnetic WD with a temperature of {approx}10,000 K and a hot spot with a central temperature of 15,000 K generally match the broad absorptions at 1400 and 1600 A with those expected for the quasi-molecular H features H{sub 2} and H{sup +}{sub 2}. However, the flux in the core of the Ly{alpha} absorption does not go to zero, implying an additional component, and the flux variations throughout the orbit are not well matched at long wavelengths. Alternatively, a 9500 K WD with a 100 MG cyclotron component can fit the lowest (phase 0.0) fluxes, but the highest fluxes (phase 0.5) require an additional source of magnetic field or temperature. The 100 MG field required for the UV fit is much higher than that which fits the optical/IR wavelengths, which would support previous suggestions of a complex field structure in polars.

  12. Stochastic Lagrangian dynamics for charged flows in the E-F regions of ionosphere

    SciTech Connect

    Tang Wenbo; Mahalov, Alex

    2013-03-15

    We develop a three-dimensional numerical model for the E-F region ionosphere and study the Lagrangian dynamics for plasma flows in this region. Our interest rests on the charge-neutral interactions and the statistics associated with stochastic Lagrangian motion. In particular, we examine the organizing mixing patterns for plasma flows due to polarized gravity wave excitations in the neutral field, using Lagrangian coherent structures (LCS). LCS objectively depict the flow topology-the extracted attractors indicate generation of ionospheric density gradients, due to accumulation of plasma. Using Lagrangian measures such as the finite-time Lyapunov exponents, we locate the Lagrangian skeletons for mixing in plasma, hence where charged fronts are expected to appear. With polarized neutral wind, we find that the corresponding plasma velocity is also polarized. Moreover, the polarized velocity alone, coupled with stochastic Lagrangian motion, may give rise to polarized density fronts in plasma. Statistics of these trajectories indicate high level of non-Gaussianity. This includes clear signatures of variance, skewness, and kurtosis of displacements taking polarized structures aligned with the gravity waves, and being anisotropic.

  13. Hypoxia-inducible genes encoding small EF-hand proteins in rice and tomato.

    PubMed

    Otsuka, Chie; Minami, Ikuko; Oda, Kenji

    2010-01-01

    Rice has evolved metabolic and morphological adaptations to low-oxygen stress to grow in submerged paddy fields. To characterize the molecular components that mediate the response to hypoxia in rice, we identified low-oxygen stress early response genes by microarray analysis. Among the highly responsive genes, five genes, OsHREF1 to OsHREF5, shared strong homology. They encoded small proteins harboring two EF-hands, typical Ca(2+)-binding motifs. Homologous genes were found in many land plants, including SlHREF in tomato, which is also strongly induced by hypoxia. SlHREF induction was detected in both roots and shoots of tomato plants under hypoxia. With the exception of OsHREF5, OsHREF expression was unaffected by drought, salinity, cold, or osmotic stress. Fluorescent signals of green fluorescent protein-fused OsHREFs were detected in the cytosol and nucleus. Ruthenium red, an inhibitor of intracellular Ca(2+) release, repressed induction of OsHREF1-4 under hypoxia. The HREFs may be related to the Ca(2+) response to hypoxia.

  14. Characterising the Profile of Everyday Executive Functioning and Relation to IQ in Adults with Williams Syndrome: Is the BRIEF Adult Version a Valid Rating Scale?

    PubMed

    Hocking, Darren R; Reeve, Jessica; Porter, Melanie A

    2015-01-01

    Although there is evidence of a distinct profile of executive dysfunction in Williams syndrome (WS), a rare genetically based neurodevelopmental disorder, the utility of informant reports of everyday executive function (EF) impairments and their relation to intelligence is not yet clear. Here we aimed to evaluate the functional impact of executive dysfunction in adults with WS and to establish the validity of child and adult versions of the most commonly used rating scale for EF assessment, the Behaviour Rating Inventory of Executive Function (BRIEF). We were also interested in whether distinct components of everyday EF relate to intelligence in WS. Parent report child (BRIEF-C) and adult (BRIEF-A) ratings were collected on 20 adults with WS (aged 18.5 to 53 years), with a mean IQ of 60.95 (SD = 17.67). Neuropsychological measures of EF included: The Shape School Test (Espy, 2007); select subdomains of EF from the Woodcock-Johnson III Tests of Cognitive Abilities, Australian Adaptation (WJ III COG); and select subdomains from the Vineland Adaptive Behaviour Scales, Second Edition-Parent Survey (Vineland-II). Results showed that the BRIEF-A, but not the BRIEF-C, was the most highly correlated with neuropsychological measures of EF, suggesting that it was a valid measure of the profile of EF impairments in adults with WS. The profile of everyday EF dysfunction revealed relative impairments in monitoring, working memory, planning and organisation in WS. In addition, both neuropsychological and rating scale measures showed an association between the shifting component of EF and intelligence. These findings indicate that the BRIEF-A is a valid measure of the multidimensional nature of real-world impairments in EF, and highlight its utility as a less labor intensive and low-cost screening tool for measuring specific EF impairments that could become the focus of targeted intervention in adults with WS.

  15. Gender Abuse, Depressive Symptoms, and Substance Use Among Transgender Women: A 3-Year Prospective Study

    PubMed Central

    Bockting, Walter; Rosenblum, Andrew; Hwahng, Sel; Mason, Mona; Macri, Monica; Becker, Jeffrey

    2014-01-01

    Objectives. We examined the effects of gender abuse (enacted stigma), depressive symptoms, and demographic, economic, and lifestyle factors on substance use among transgender women. Methods. We conducted a 3-year prospective study (December 2004 to September 2007) of 230 transgender women aged 19 to 59 years from the New York Metropolitan Area. Statistical techniques included generalized estimating equations with logistic and linear regression links. Results. Six-month prevalence of any substance use at baseline was 76.2%. Across assessment points, gender abuse was associated with alcohol, cannabis, cocaine, or any substance use during the previous 6 months, the number of days these substances were used during the previous month, and the number of substances used. Additional modeling associated changes in gender abuse with changes in substance use across time. Associations of gender abuse and substance use were mediated 55% by depressive symptoms. Positive associations of employment income, sex work, transgender identity, and hormone therapy with substance use were mediated 19% to 42% by gender abuse. Conclusions. Gender abuse, in conjunction with depressive symptoms, is a pervasive and moderately strong risk factor for substance use among transgender women. Improved substance abuse treatment is sorely needed for this population. PMID:25211716

  16. Urinary 1-Hydroxypyrene as a Biomarker of PAH Exposure in 3-Year-Old Ukrainian Children

    PubMed Central

    Mucha, Amy Pelka; Hryhorczuk, Daniel; Serdyuk, Andrij; Nakonechny, Joseph; Zvinchuk, Alexander; Erdal, Serap; Caudill, Motria; Scheff, Peter; Lukyanova, Elena; Shkiryak-Nyzhnyk, Zoreslava; Chislovska, Natalia

    2006-01-01

    Urinary 1-hydroxypyrene (1-OHP) is a biomarker of polycyclic aromatic hydrocarbon (PAH) exposure. We measured urinary 1-OHP in 48 children 3 years of age in Mariupol, Ukraine, who lived near a steel mill and coking facility and compared these with 1-OHP concentrations measured in 42 children of the same age living in the capital city of Kiev, Ukraine. Children living in Mariupol had significantly higher urinary 1-OHP and creatinine-adjusted urinary 1-OHP than did children living in Kiev (adjusted: 0.69 vs. 0.34 μmol/mol creatinine, p < 0.001; unadjusted: 0.42 vs. 0.30 ng/mL, p = 0.002). Combined, children in both cities exposed to environmental tobacco smoke in their homes had higher 1-OHP than did children not exposed (0.61 vs. 0.42 μmol/mol creatinine; p = 0.04; p = 0.07 after adjusting for city). In addition, no significant differences were seen with sex of the children. Our sample of children in Mariupol has the highest reported mean urinary 1-OHP concentrations in children studied to date, most likely due to their proximity to a large industrial point source of PAHs. PMID:16581553

  17. Periosteal desmoplastic fibroma of the tibia in a 3-year-old child.

    PubMed

    Sferopoulos, N K

    2015-12-01

    Desmoplastic fibroma is a rare benign fibrogenic, locally aggressive, primary bone tumor. It is the intraosseous counterpart of soft tissue aggressive fibromatosis. The lesion may very rarely appear as a superficial bone lesion arising from the periosteum; in such cases, a soft tissue mass with changes in the adjacent bone is evident. Periosteal lesions are very rare in the literature; diagnosis is usually based on the radiographic findings, and histological proof of the tumor origin is missing. A periosteal desmoplastic fibroma of the distal tibial metaphysis in a 3-year-old boy is presented. Radiographic investigation included plain radiographs and computed tomography imaging. Both demonstrated a soft tissue lesion involving the superficial bone tissues with non-aggressive looking borders and a pressure effect with a sclerotic rim in the bone. The lesion was excised, and the surgical as well as the histological findings indicated the diagnosis of a desmoplastic fibroma of bone arising from the periosteum. No recurrence was detected 5 years after surgery.

  18. Idiopathic midaortic syndrome with malignant hypertension in 3-year-old boy

    PubMed Central

    Ahn, Kyung Jin; Yoon, Ja Kyoung; Kwon, Bo Sang; Bae, Eun Jung; Noh, Chung Il

    2016-01-01

    Midaortic syndrome (MAS) is a rare vascular disease that commonly causes renovascular hypertension. The lumen of the abdominal aorta narrows and the ostia of the branches show stenosis. MAS is associated with diminished pulses in the lower extremities compared with the upper extremities, severe hypertension with higher blood pressure in the upper rather than lower extremities, and an abdominal bruit. The clinical symptoms are variable, and recognition in children with hypertension can aid early diagnosis and optimal treatment. Hypertension with MAS is malignant and often refractory to several antihypertensive drugs. Recently, radiologic modalities have been developed and have led to numerous interventional procedures. We describe the case of a 3-year-old boy presenting with left ventricular hypertrophy whose severely elevated blood pressure led to the diagnosis of idiopathic MAS. This case highlights the importance of measuring blood pressure and conducting a detailed physical examination to diagnose MAS. This is the first reported case of idiopathic MAS diagnosed in childhood in Korea. PMID:28018454

  19. The impact of early literacy guidance on language skills of 3-year-olds.

    PubMed

    Theriot, Judy A; Franco, Sofia M; Sisson, Barbara A; Metcalf, Sharon C; Kennedy, Mary A; Bada, Henrietta S

    2003-03-01

    The objective of this prospective study was to determine the impact of early literacy anticipatory guidance (AG) with provision of books on language development in 3-year-olds in an early literacy program at a University-affiliated inner-city pediatric clinic. The Peabody Picture Vocabulary Test (PPVT-III) and the Expressive One Word Picture Vocabulary Test (EOWPVT-R) were administered to 33-39-month-old children exposed to an early literacy program, which included AG and provision of an age-appropriate book at each well-child visit starting at 2 months old. Children with developmental delays were excluded. Parental surveys on literacy and demographic data were obtained. Univariate and multivariate analyses were performed. Sixty-four children were evaluated; 88% African American, 89% Medicaid recipients. Fifty-eight percent of families reported family-centered literacy orientation. The PPVT-III scores directly correlated with the number of AG visits with book given x number of books purchased (r2 = 0.025, p = 0.0006). Higher scores in EOWPVT-R were predicted by race and the number of visits with books given x number of books purchased (r2 = 0.182, p = 0.0009). All families reported reading together, half reporting positive family-centered literacy. Given the same number of books purchased for each child, the outcome scores were higher the greater the number of clinic visits wherein AG included early literacy and provision of books.

  20. Growth of children with Down's syndrome: birth to age 3 years.

    PubMed

    Cronk, C E

    1978-04-01

    A sample of 90 children with Down's syndrome were measured for recumbent length and weight from birth to age 36 months at the Children's Hospital Medical Center in Boston. At birth, means for both length and weight were reduced by about 0.5 SDs from the control group means. By 36 months, mean recumbent length was greater than 2 SDs below that for the control group, while the mean for weight was reduced by about 1.5 SDs from the control group mean. Growth velocity for both length and weight was most deficient within the first two years of life. About 30% of the sample demonstrated excess weight for length relations by 36 months. Children with moderate or severe heart disease were significantly smaller than those without or with mild cardiac problems at all times after birth. Measurements of a subsample of children at 4, 5, and 6 years of age suggested that growth velocity after 3 years of age may be within the range of normal. Assessment of growth of the child with Down's syndrome may be carried out with reference to charts plotting tenth to 90th percentiles based on these data.

  1. The Megha-Tropiques Mission: Review and Status after 3 Years in Orbit

    NASA Astrophysics Data System (ADS)

    Roca, R.

    2014-12-01

    The Megha-Tropiques satellite is the indo-french contribution to the Global Precipitation Mission constellation.The operation of the MT mission has recently been formally extended for 2015 and 2016 after reaching in october this year its original 3 years duration. While the MADRAS instrument stopped data acquisition in January 2013, the SAPHIR multichannel 183 GHz sounder is up and running nominally. Real time distribution of SAPHIR is performed by EUMETSAT via the EUMETcast system since mid-2014.In this presentation, I will review the performances of the microwave radiometers on-board MT and illustrate thescientific outcome of the mission as well as the results of the extensive validation exercices which have been finalized. I will put the emphasis on the impact of the low inclinaison orbit on assimilation, convective systems monitoring and estimation of precipitation. In particular, I will show how the SAPHIR radiometer data are used in our GPM multiple platforms merged 1°-1day accumulated rainfall product to mitigate the loss of MADRAS.

  2. Iron Status and Febrile Seizure- A Case Control Study in Children Less Than 3 Years

    PubMed Central

    SADEGHZADEH, Mansour; KHOSHNEVIS ASL, Parisa; MAHBOUBI, Esrafil

    2012-01-01

    Objective Febrile seizure is one of the most common neurological conditions of childhood. Several theories, such as iron deficiency anemia have been proposed as the pathogenesis of this condition. The aim of this study was to find the association between iron deficiency anemia and febrile seizures in children aged 6 months to 3 years admitted in Valie Asr hospital in Zanjan. Materials &Methods Hemoglobin (Hb), mean corpuscular volume (MCV), serum iron (SI), total iron binding capacity (TIBC) and SI/TIBC ratio were assessed in one hundred children with febrile seizures and compared to the values of one hundred healthy children presenting in a heath care center in the same period as the control group. Results A total of 6% of cases had iron deficiency anemia which was similar to the control group. In the case group SI/TIBC ratio below 12% was seen in 58% of children which was significantly higher than that of the control group (29%). Conclusion The results of this study suggest that although anemia was not common among febrile seizure patients, iron deficiency was more frequent in these patients. PMID:24665277

  3. Urinary interleukin-6 as a predictor of radiographic progression in rheumatoid arthritis: A 3-year evaluation

    PubMed Central

    Park, Yune-Jung; Yoo, Seung-Ah; Kim, Ga-Ram; Cho, Chul-Soo; Kim, Wan-Uk

    2016-01-01

    Previously, we demonstrated that the urine proteome signature of patients with rheumatoid arthritis (RA) reflects inflammation-related cellular processes. Here, we measured interleukin (IL)-6, IL-8, and chemokine ligand 2 (CCL2) concentrations in the urine of RA patients and prospectively investigated their role in predicting RA activity and prognosis. One hundred seventy-three RA patients and 62 non-RA controls were recruited. Urinary IL-6, CCL2, and IL-8 levels were elevated in RA patients and correlated well with disease activity. Urinary IL-6 level at presentation was an independent risk factor of radiographic progression at 1 and 3 years. High urinary IL-6 level increased the risk ratio of radiographic progression by 2.9-fold, which was comparable to high serum CRP. Moreover, combination of urinary IL-6 and serum CRP measures synergistically increased the predictability of radiographic progression. In a subgroup with normal ESR, patients with the highest tertile of urinary IL-6 were at 6.4-fold greater risk of radiographic progression. Conclusively, high urinary IL-6 level at presentation is an independent risk factor for radiographic progression of RA, reflecting disease activity. Urinary IL-6 in combination with serum CRP may be a useful parameter for estimating RA prognosis. PMID:27731382

  4. Sustained Effectiveness of the Maternal Pertussis Immunization Program in England 3 Years Following Introduction

    PubMed Central

    Amirthalingam, Gayatri; Campbell, Helen; Ribeiro, Sonia; Fry, Norman K.; Ramsay, Mary; Miller, Elizabeth; Andrews, Nick

    2016-01-01

    The effectiveness of maternal immunization in preventing infant pertussis was first demonstrated in England, 1 year after the program using diphtheria–tetanus–5-component acellular pertussis–inactivated polio vaccine (dT5aP-IPV) was introduced in 2012. Vaccine effectiveness against laboratory-confirmed pertussis has been sustained >90% in the 3 years following its introduction, despite changing to another acellular vaccine with different antigen composition. Consistent with this, disease incidence in infants <3 months of age has remained low despite high activity persisting in those aged 1 year and older. Vaccine effectiveness against infant deaths was estimated at 95% (95% confidence interval, 79%–100%). Additional protection from maternal immunization is retained in infants who received their first dose of the primary series. There is no longer evidence of additional protection from maternal vaccination after the third infant dose. Although numbers are small and ongoing assessment is required, there is no evidence of increased risk of disease after primary immunization in infants whose mothers received maternal vaccination. PMID:27838678

  5. Words, shape, visual search and visual working memory in 3-year-old children

    PubMed Central

    Vales, Catarina; Smith, Linda B.

    2014-01-01

    Do words cue children’s visual attention, and if so, what are the relevant mechanisms? Across four experiments, 3-year-old children (N = 163) were tested in visual search tasks in which targets were cued with only a visual preview versus a visual preview and a spoken name. The experiments were designed to determine whether labels facilitated search times and to examine one route through which labels could have their effect: By influencing the visual working memory representation of the target. The targets and distractors were pictures of instances of basic-level known categories and the labels were the common name for the target category. We predicted that the label would enhance the visual working memory representation of the target object, guiding attention to objects that better matched the target representation. Experiments 1 and 2 used conjunctive search tasks, and Experiment 3 varied shape discriminability between targets and distractors. Experiment 4 compared the effects of labels to repeated presentations of the visual target, which should also influence the working memory representation of the target. The overall pattern fits contemporary theories of how the contents of visual working memory interact with visual search and attention, and shows that even in very young children heard words affect the processing of visual information. PMID:24720802

  6. A statistical skull geometry model for children 0-3 years old.

    PubMed

    Li, Zhigang; Park, Byoung-Keon; Liu, Weiguo; Zhang, Jinhuan; Reed, Matthew P; Rupp, Jonathan D; Hoff, Carrie N; Hu, Jingwen

    2015-01-01

    Head injury is the leading cause of fatality and long-term disability for children. Pediatric heads change rapidly in both size and shape during growth, especially for children under 3 years old (YO). To accurately assess the head injury risks for children, it is necessary to understand the geometry of the pediatric head and how morphologic features influence injury causation within the 0-3 YO population. In this study, head CT scans from fifty-six 0-3 YO children were used to develop a statistical model of pediatric skull geometry. Geometric features important for injury prediction, including skull size and shape, skull thickness and suture width, along with their variations among the sample population, were quantified through a series of image and statistical analyses. The size and shape of the pediatric skull change significantly with age and head circumference. The skull thickness and suture width vary with age, head circumference and location, which will have important effects on skull stiffness and injury prediction. The statistical geometry model developed in this study can provide a geometrical basis for future development of child anthropomorphic test devices and pediatric head finite element models.

  7. Acquired unilateral pulmonary vein atresia in a 3-year-old boy.

    PubMed

    Firdouse, Mohammed; Agarwal, Arnav; Grosse-Wortmann, Lars; Mondal, Tapas K

    2015-03-01

    While unilateral pulmonary venous atresia (UPVA) most commonly presents as an extremely rare late embryological defect resulting in complete occlusion or absence of the PV pathway, it may also be an acquired pathology. We present a 3-year-old boy who presented with mild respiratory distress. Neonatal echocardiographic investigations revealed normal mediastinal anatomy and pulmonary vasculature with a bicuspid aortic valve. However, follow-up Doppler investigation revealed a pulmonary artery size difference with minimal forward flow and reverse flow during diastole. Absence of the left pulmonary veins and the presence of collaterals draining to the innominate vein confirmed the diagnosis of acquired UPVA. Our case represents the first case of acquired UPVA in conjunction with a normally functioning bicuspid aortic valve. The Doppler flow patterns discussed might be of significant interest to pediatricians, cardiologists and imaging specialists. These findings suggest that acquired UPVA should be considered in the differential diagnosis of such patients when radiographic and echocardiographic findings may rule out other more common diagnoses. While the management of such a condition remains unclear and conservative management was agreed upon for our patient, the vulnerability of such cases warrants timely diagnosis and routine monitoring.

  8. Successful Medical Treatment of Adult Nesidioblastosis With Pasireotide over 3 Years

    PubMed Central

    Schwetz, Verena; Horvath, Karl; Kump, Patrizia; Lackner, Carolin; Perren, Aurel; Forrer, Flavio; Pieber, Thomas R.; Treiber, Gerlies; Sourij, Harald; Mader, Julia K.

    2016-01-01

    Abstract Nesidioblastosis is a rare cause of endogenous hyperinsulinemic hypoglycemia in adults. Diagnosis is often challenging and therapeutic options are scarce. In 2009, a 46-year-old female patient presented with recurrent severe hypoglycemia and immediate recovery after glucose ingestion. Although 72-h-fasting test was positive, various imaging technologies (sonography, computed tomography, somatostatin receptor scintigraphy, dopamine receptor positron emission tomography [DOPA-PET]) were negative. Endoscopic ultrasound revealed a lesion in the pancreatic corpus, whereas selective arterial calcium stimulation test, portal venous sampling and GLP-1-receptor scintigraphy were indicative of a lesion in the pancreatic tail, which was surgically removed. The histopathologic examination revealed beta cell hyperplasia and microadenomas expressing glucagon. After surgery, the patient was free of symptoms for 6 months, after which hypoglycemic episodes recurred. After unsuccessful treatment with corticosteroids and somatostatin analogs, treatment with pasireotide, a novel somatostatin analog with high affinity to somatostatin receptor 5 and a possible side effect of hyperglycemia, was initiated (0.6 mg BID). To date, our patient has been free of severe hypoglycemic episodes ever since. Yearly repeated imaging procedures have shown no abnormities over the last 3 years. We report for the first time that pasireotide was successfully used in the treatment of adult nesidioblastosis. PMID:27057885

  9. Intestinal Obstruction in a 3-Year-Old Girl by Ascaris lumbricoides Infestation

    PubMed Central

    Andrade, Angel Medina; Perez, Yeudiel; Lopez, Cecilia; Collazos, Stephanie Serrano; Andrade, Alejandro Medina; Ramirez, Grecia Ortiz; Andrade, Laura Medina

    2015-01-01

    Abstract Ascaris lumbricoides infection affects approximately 1.5 billion people globally. Children with environmental and socio-economic risk factors are more susceptible to infestation, with serious complications such as intestinal obstruction (IO), volvulus, intussusception, and intestinal necrosis. We present the case of a 3-year-old girl who arrived at emergency department with abdominal pain and diarrhea for the last 3 days. The previous day she took an unspecified anthelmintic. Symptoms worsened with vomiting and diarrhea, with expulsion of roundworms through mouth and anus. Physical examination revealed bloating, absence of bowel sounds, abdominal tenderness, and a palpable mass in right hemi-abdomen. Abdominal radiographs showed air-fluid levels with mild bowel distention and shadows of roundworms. The diagnosis of IO by A lumbricoides. infestation was established and surgical approach scheduled. During exploratory laparotomy an intraluminal bolus of roundworms from jejunum to ascendant colon was evident. An ileum enterotomy was performed and worms were removed. Fluid therapy and antibiotics for 72 hours were administered, with posterior albendazol treatment for 3 days. Patient was uneventfully discharged on the tenth day. Reduction in parasitic load by means of improvements in sanitation, health education, and anthelmintic treatment must be implemented in endemic zones to prevent serious life-threatening complications by A lumbricoides. infestation, because some of them require urgent surgical treatment. PMID:25906092

  10. Words, shape, visual search and visual working memory in 3-year-old children.

    PubMed

    Vales, Catarina; Smith, Linda B

    2015-01-01

    Do words cue children's visual attention, and if so, what are the relevant mechanisms? Across four experiments, 3-year-old children (N = 163) were tested in visual search tasks in which targets were cued with only a visual preview versus a visual preview and a spoken name. The experiments were designed to determine whether labels facilitated search times and to examine one route through which labels could have their effect: By influencing the visual working memory representation of the target. The targets and distractors were pictures of instances of basic-level known categories and the labels were the common name for the target category. We predicted that the label would enhance the visual working memory representation of the target object, guiding attention to objects that better matched the target representation. Experiments 1 and 2 used conjunctive search tasks, and Experiment 3 varied shape discriminability between targets and distractors. Experiment 4 compared the effects of labels to repeated presentations of the visual target, which should also influence the working memory representation of the target. The overall pattern fits contemporary theories of how the contents of visual working memory interact with visual search and attention, and shows that even in very young children heard words affect the processing of visual information.

  11. Diffuse Spinal Leptomeningeal Spread of a Pilocytic Astrocytoma in a 3-year-old Child.

    PubMed

    Alyeldien, Ameer; Teuber-Hanselmann, Sarah; Cheko, Azad; Höll, Tanja; Scholz, Martin; Petridis, Athanasios K

    2016-03-25

    Pilocytic astrocytomas correspond to low-grade gliomas and therefore metastasize exceedingly rare. However, pilocytic astrocytomas are able to and leptomeningeal dissemination may be seen. What are the treatment options of these cases? We present a case report of a 3-year-old child with a pilocytic astrocytoma of the optic chiasm with leptomeningeal dissemination of the spinal meninges. Partial resection of the cerebral tumor has been performed. Since the leptomeningeal dissemination was seen all over the spinal meninges, the child did not undergo further surgical treatment. A wait and watch strategy were followed. Chemotherapy was initiated, if a 25% tumor growth was seen. Leptomeningeal dissemination of a pilocytic astrocytoma is seen so infrequently that no standard therapy is established. Since these metastases may occur even up to 2 decades after primary tumor resection, long-term follow-up is indicated. In case of spinal metastases, surgical treatment should be performed if feasible. Otherwise observation should be possessed and/or chemotherapy should be initiated.

  12. Diffuse Spinal Leptomeningeal Spread of a Pilocytic Astrocytoma in a 3-year-old Child

    PubMed Central

    Alyeldien, Ameer; Teuber-Hanselmann, Sarah; Cheko, Azad; Höll, Tanja; Scholz, Martin; Petridis, Athanasios K.

    2016-01-01

    Pilocytic astrocytomas correspond to low-grade gliomas and therefore metastasize exceedingly rare. However, pilocytic astrocytomas are able to and leptomeningeal dissemination may be seen. What are the treatment options of these cases? We present a case report of a 3-year-old child with a pilocytic astrocytoma of the optic chiasm with leptomeningeal dissemination of the spinal meninges. Partial resection of the cerebral tumor has been performed. Since the leptomeningeal dissemination was seen all over the spinal meninges, the child did not undergo further surgical treatment. A wait and watch strategy were followed. Chemotherapy was initiated, if a 25% tumor growth was seen. Leptomeningeal dissemination of a pilocytic astrocytoma is seen so infrequently that no standard therapy is established. Since these metastases may occur even up to 2 decades after primary tumor resection, long-term follow-up is indicated. In case of spinal metastases, surgical treatment should be performed if feasible. Otherwise observation should be possessed and/or chemotherapy should be initiated. PMID:27162602

  13. Impact of Exhaled Breath Acetone in the Prognosis of Patients with Heart Failure with Reduced Ejection Fraction (HFrEF). One Year of Clinical Follow-up

    PubMed Central

    Saldiva, Paulo H. N.; Mangini, Sandrigo; Issa, Victor S.; Ayub-Ferreira, Silvia M.; Bocchi, Edimar A.

    2016-01-01

    Background The identification of new biomarkers of heart failure (HF) could help in its treatment. Previously, our group studied 89 patients with HF and showed that exhaled breath acetone (EBA) is a new noninvasive biomarker of HF diagnosis. However, there is no data about the relevance of EBA as a biomarker of prognosis. Objectives To evaluate whether EBA could give prognostic information in patients with heart failure with reduced ejection fraction (HFrEF). Methods After breath collection and analysis by gas chromatography-mass spectrometry and by spectrophotometry, the 89 patients referred before were followed by one year. Study physicians, blind to the results of cardiac biomarker testing, ascertained vital status of each study participant at 12 months. Results The composite endpoint death and heart transplantation (HT) were observed in 35 patients (39.3%): 29 patients (32.6%) died and 6 (6.7%) were submitted to HT within 12 months after study enrollment. High levels of EBA (≥3.7μg/L, 50th percentile) were associated with a progressively worse prognosis in 12-month follow-up (log-rank = 11.06, p = 0.001). Concentrations of EBA above 3.7μg/L increased the risk of death or HT in 3.26 times (HR = 3.26, 95%CI = 1.56–6.80, p = 0.002) within 12 months. In a multivariable cox regression model, the independent predictors of all-cause mortality were systolic blood pressure, respiratory rate and EBA levels. Conclusions High EBA levels could be associated to poor prognosis in HFrEF patients. PMID:28030609

  14. Comparison of ozone and HO· induced conversion of effluent organic matter (EfOM) using ozonation and UV/H2O2 treatment.

    PubMed

    Audenaert, W T M; Vandierendonck, D; Van Hulle, S W H; Nopens, I

    2013-05-01

    This study experimentally examined the impact of oxidation on the properties of effluent organic matter (EfOM) using two different oxidation techniques: ozonation and UV/H2O2 treatment. Multiple surrogates for EfOM related to its spectral properties, molecular size, concentration, polarity and biodegradability were used to study the oxidant induced conversions. Spectral calculations as differential absorbance spectra (DAS) and absorbance slope index (ASI) were applied for the first time to describe EfOM oxidation and proved to be useful to unravel differences in working mechanism between ozone and hydroxyl radical (HO) induced transformation of EfOM. Effluent ozonation inherently led to significant HO production as a result of electron transfers between ozone and electron rich moieties of EfOM. HO production increased as function of ozone dose and was strongly correlated to UV absorption at 254 nm (UV254). During the UV moderated process, pseudo steady-state behaviour of the HO concentration was observed. Ozone decomposition was extremely sensitive to EfOM reactivity. Most likely, the degree of dissociation of EfOM controlled its reactivity towards ozone. The pH effect was quantified by calculating the pseudo-first order decay constant for ozone as function of reaction time and pH. Treatment with both processes led to more oxygen rich, less hydrophobic and more biodegradable EfOM.

  15. Relationship between the brain natriuretic peptide (BNP) level and remission of diabetic nephropathy with microalbuminuria: a 3-year follow-up study.

    PubMed

    Seki, N; Matsumoto, T; Fukazawa, M

    2015-02-01

    The aim of the study was to examine the relationship between the brain natriuretic peptide (BNP) level and progression or remission of diabetic nephropathy with microalbuminuria for 3 years. The subjects were 100 Japanese type 2 diabetes mellitus outpatients with microalbuminuria. Associations between metabolic parameters at baseline [HbA1c, systolic blood pressure (SBP), urine albumin-creatinine ratio (ACR), estimated glomerular filtration rate (eGFR), and BNP] and the progression or remission of diabetic nephropathy were examined for 3 years. A total of 83 patients were examined at the end of the 3-year period, including 17 with remission to normoalbuminuria, 47 with continuing microalbuminuria, and 19 with progression to macroalbuminuria. HbA1c, ACR, and BNP differed significantly among the 3 groups (p=0.024, p<0.001, p=0.002, respectively). Among baseline factors, HbA1c and BNP were significant predictors of the percentage increase in ACR for 3 years in multiple linear regression analysis (β=0.259, p=0.02; β=0.299, p=0.007, respectively). In multivariate logistic regression analysis, HbA1c and ACR were independently associated with progression of diabetic nephropathy (p=0.008, p=0.023, respectively), and ACR and BNP were independently associated with remission of diabetic nephropathy (p=0.029, p=0.012, respectively). ROC curve analysis gave a cutoff value for BNP of 14.9 pg/ml for prediction of remission of diabetic nephropathy (p=0.016). The BNP level has a relationship with diabetic nephropathy and a low BNP level predicts remission of diabetic nephropathy. Therefore, monitoring of BNP can play an important role in management of diabetic nephropathy.

  16. Acute undifferentiated febrile illness in rural Cambodia: a 3-year prospective observational study.

    PubMed

    Mueller, Tara C; Siv, Sovannaroth; Khim, Nimol; Kim, Saorin; Fleischmann, Erna; Ariey, Frédéric; Buchy, Philippe; Guillard, Bertrand; González, Iveth J; Christophel, Eva-Maria; Abdur, Rashid; von Sonnenburg, Frank; Bell, David; Menard, Didier

    2014-01-01

    In the past decade, malaria control has been successfully implemented in Cambodia, leading to a substantial decrease in reported cases. Wide-spread use of malaria rapid diagnostic tests (RDTs) has revealed a large burden of malaria-negative fever cases, for which no clinical management guidelines exist at peripheral level health facilities. As a first step towards developing such guidelines, a 3-year cross-sectional prospective observational study was designed to investigate the causes of acute malaria-negative febrile illness in Cambodia. From January 2008 to December 2010, 1193 febrile patients and 282 non-febrile individuals were recruited from three health centers in eastern and western Cambodia. Malaria RDTs and routine clinical examination were performed on site by health center staff. Venous samples and nasopharyngeal throat swabs were collected and analysed by molecular diagnostic tests. Blood cultures and blood smears were also taken from all febrile individuals. Molecular testing was applied for malaria parasites, Leptospira, Rickettsia, O. tsutsugamushi, Dengue- and Influenza virus. At least one pathogen was identified in 73.3% (874/1193) of febrile patient samples. Most frequent pathogens detected were P. vivax (33.4%), P. falciparum (26.5%), pathogenic Leptospira (9.4%), Influenza viruses (8.9%), Dengue viruses (6.3%), O. tsutsugamushi (3.9%), Rickettsia (0.2%), and P. knowlesi (0.1%). In the control group, a potential pathogen was identified in 40.4%, most commonly malaria parasites and Leptospira. Clinic-based diagnosis of malaria RDT-negative cases was poorly predictive for pathogen and appropriate treatment. Additional investigations are needed to understand their impact on clinical disease and epidemiology, and the possible role of therapies such as doxycycline, since many of these pathogens were seen in non-febrile subjects.

  17. Acute Undifferentiated Febrile Illness in Rural Cambodia: A 3-Year Prospective Observational Study

    PubMed Central

    Mueller, Tara C.; Siv, Sovannaroth; Khim, Nimol; Kim, Saorin; Fleischmann, Erna; Ariey, Frédéric; Buchy, Philippe; Guillard, Bertrand; González, Iveth J.; Christophel, Eva-Maria; Abdur, Rashid; von Sonnenburg, Frank; Bell, David; Menard, Didier

    2014-01-01

    In the past decade, malaria control has been successfully implemented in Cambodia, leading to a substantial decrease in reported cases. Wide-spread use of malaria rapid diagnostic tests (RDTs) has revealed a large burden of malaria-negative fever cases, for which no clinical management guidelines exist at peripheral level health facilities. As a first step towards developing such guidelines, a 3-year cross-sectional prospective observational study was designed to investigate the causes of acute malaria-negative febrile illness in Cambodia. From January 2008 to December 2010, 1193 febrile patients and 282 non-febrile individuals were recruited from three health centers in eastern and western Cambodia. Malaria RDTs and routine clinical examination were performed on site by health center staff. Venous samples and nasopharyngeal throat swabs were collected and analysed by molecular diagnostic tests. Blood cultures and blood smears were also taken from all febrile individuals. Molecular testing was applied for malaria parasites, Leptospira, Rickettsia, O. tsutsugamushi, Dengue- and Influenza virus. At least one pathogen was identified in 73.3% (874/1193) of febrile patient samples. Most frequent pathogens detected were P. vivax (33.4%), P. falciparum (26.5%), pathogenic Leptospira (9.4%), Influenza viruses (8.9%), Dengue viruses (6.3%), O. tsutsugamushi (3.9%), Rickettsia (0.2%), and P. knowlesi (0.1%). In the control group, a potential pathogen was identified in 40.4%, most commonly malaria parasites and Leptospira. Clinic-based diagnosis of malaria RDT-negative cases was poorly predictive for pathogen and appropriate treatment. Additional investigations are needed to understand their impact on clinical disease and epidemiology, and the possible role of therapies such as doxycycline, since many of these pathogens were seen in non-febrile subjects. PMID:24755844

  18. Schistosoma mansoni in infants (aged < 3 years) along the Ugandan shoreline of Lake Victoria.

    PubMed

    Odogwu, S E; Ramamurthy, N K; Kabatereine, N B; Kazibwe, F; Tukahebwa, E; Webster, J P; Fenwick, A; Stothard, J R

    2006-06-01

    In two complementary epidemiological surveys of villages on the Ugandan shoreline of Lake Victoria, the putative occurrence of intestinal schistosomiasis in the local infants (children aged < 3 years) was investigated. When, during the first survey, 136 mother-and-infant pairs from a total of 12 villages were studied, only 7% of the infants but 45% of the mothers were found to be egg-patent for Schistosoma mansoni infection. The use of dipstick tests for urine-circulating cathodic antigen indicated, however, a much higher prevalence, of approximately 40%, among the infants. In the second survey, urine samples and multiple, not single, stool samples were collected from another 19 mother-and-infant pairs in two of the 12 study villages (Bugoto and Bwondha), and a standardized questionnaire was implemented. The prevalence of egg-patent infection was then found to be markedly higher in the study infants from Bugoto (86%) than in those from Bwondha (25%). A greater level of mother-and-infant water contact, a higher abundance of (infected) Biomphalaria choanomphala, and an unusual lakeshore topology may explain why S. mansoni infection was so much more common in the Bugoto subjects than in the Bwondha. All but one of the infants studied in the second survey were found to be anaemic (with <110 g haemoglobin/litre). Taken together, these children were less likely to be found infected with hookworm (16%), Hymenolepis nana (11%) or Trichuris trichiura (5%) than with S. mansoni (47%). Infection with the parasites causing intestinal schistosomiasis can be common among the infants living in these lakeshore villages. Although the immediate and later-life clinical impacts of such infection have yet to be elucidated, such infants would probably benefit from regular de-worming. Mothers should be strongly encouraged to visit the nearest health-services clinic, with their infants, for any necessary anthelmintic treatment.

  19. Gender-specific factors associated with shorter sleep duration at age 3 years.

    PubMed

    Plancoulaine, Sabine; Lioret, Sandrine; Regnault, Nolwenn; Heude, Barbara; Charles, Marie-Aline

    2015-12-01

    Total sleep duration has been decreasing among children in the last decades. Short sleep duration (SSD) has been associated with deleterious health consequences, such as excess weight/obesity. Risk factors for SSD have already been studied among school-aged children and adolescents, but inconsistent results have been reported regarding possible gender differences. Studies reporting such relationships are scarce in preschoolers, despite the importance of this period for adopting healthy behaviour. We aimed to investigate factors associated with SSD in 3-year-old boys (n = 546) and girls (n = 482) in a French Mother-Child Cohort (EDEN Study). Children were born between 2003 and 2006 in two French university hospitals. Clinical examinations and parent self-reported questionnaires allowed us to collect sociodemographic (e.g. income, education, family situation, child-minding system), maternal [e.g. body mass index (BMI), parity, depression, breastfeeding duration] and child's characteristics (e.g. gender, birth weight, term, physical activity and TV viewing duration, food consumption, usual sleep time). Sleep duration/24-h period was calculated and SSD was defined as <12 h. Analyses were performed using logistic regression. The mean sleep duration was 12 h 35 ± 56 min, with 91% of the children napping. Patterns of risk factors associated with SSD differed according to gender. In addition to parental presence when falling asleep, short sleep duration was associated strongly positively with high BMI Z-score and TV viewing duration among boys and with familial home child-minding and lower scores on the 'fruits and vegetables' dietary pattern among girls. These results suggest either a patterning of parental behaviours that differs according to gender, or a gender-specific sleep physiology, or both.

  20. NASA IKONOS Multispectral Radiometric Calibration and 3-Year Temporal Stability Assessment

    NASA Technical Reports Server (NTRS)

    Pagnutti, Mary; Carver, David; Holekamp, Kara; Ryan, Robert; Zanoni, Vicki; Thome, Kurtis; Schiller, Stephen; Aaran, David

    2003-01-01

    Radiometric calibration of commercial imaging satellite products is required to ensure that science and application communities can place confidence in the imagery they use and can fully understand its properties. Inaccurate radiometric calibrations can lead to erroneous decisions and invalid conclusions and can limit intercomparisons with other system. In addition, the user community has little or no insight into the design and operation of commercial sensors or into the methods involved in generating commercial products. To address this calibration need, the NASA Stennis Space Center (SSC) Earth Science Applications (ESA) Directorate established a commercial satellite imaging radiometric calibration team consisting of three independent groups: NASA, SSC,ESA, the University of Arizona Remote Sensing Group, and South Dacota State University. Each group determined the absolute radiometric calibration coefficients of the Space Imaging IKONOS 4-band, 4 m multispectral product covering the visible through near-infrared spectral region. For a three year period beginning in 2000, each team employed some variant of a reflectance-based vicarious calibration approach, requiring ground-based measurements coincident with IKONOS image acquisitions and radiative transfer calculations. Several study sites throughout the United States were employed that covered nearly the entire dynamic range of the IKONOS sensor. IKONOS at-sensor radiance values were compared to those estimated by each independent group to determine the IKONOS sensor's radiometric accuracy and stability. Over 10 individual vicariously determined at-sensor radiance estimates were used each year. When combined, these estimates provided a high-precision radiometric gain calibration coefficient. No significant calibration offset was observed. The results of this evaluation provide the scientific community with an independent assessment of the IKONOS sensor's absolute calibration and temporal stability over the 3

  1. Predictors of child-to-parent aggression: A 3-year longitudinal study.

    PubMed

    Calvete, Esther; Orue, Izaskun; Gamez-Guadix, Manuel; Bushman, Brad J

    2015-05-01

    Although we rarely hear about it, children sometimes aggress against their parents. This is a difficult topic to study because abused parents and abusive children are both reluctant to admit the occurrence of child-to-parent aggression. There are very few research studies on this topic, and even fewer theoretical explanations of why it occurs. We predicted that exposure to violence in the home (e.g., parents aggressing against each other) and ineffective parenting (i.e., parenting that is overly permissive or lacks warmth) influences cognitive schemas of how children perceive themselves and the world around them (i.e., whether aggression is normal, whether they develop grandiose self-views, and whether they feel disconnected and rejected), which, in turn, predicts child-to-parent aggression. In a 3-year longitudinal study of 591 adolescents and their parents, we found that exposure to violence in Year 1 predicted child-to-parent aggression in Year 3. In addition, parenting characterized by lack of warmth in Year 1 was related to narcissistic and entitled self-views and disconnection and rejection schemas in Year 2, which, in turn, predicted child-to-mother and child-to-father aggression in Year 3. Gender comparisons indicated that narcissism predicted child-to-parent aggression only in boys and that exposure to violence was a stronger predictor of child-to-father violence in boys. This longitudinal study increases our understanding of the understudied but important topic of child-to-parent aggression, and will hopefully stimulate future research.

  2. Molecular Diagnosis of Toxoplasmosis in Immunocompromised Patients: a 3-Year Multicenter Retrospective Study

    PubMed Central

    Sterkers, Yvon; Yera, Hélène; Accoceberry, Isabelle; Menotti, Jean; Cassaing, Sophie; Brenier-Pinchart, Marie-Pierre; Hennequin, Christophe; Delhaes, Laurence; Bonhomme, Julie; Villena, Isabelle; Scherer, Emeline; Dalle, Frédéric; Touafek, Feriel; Filisetti, Denis; Varlet-Marie, Emmanuelle; Pelloux, Hervé; Bastien, Patrick

    2015-01-01

    Toxoplasmosis is a life-threatening infection in immunocompromised patients (ICPs). The definitive diagnosis relies on parasite DNA detection, but little is known about the incidence and burden of disease in HIV-negative patients. A 3-year retrospective study was conducted in 15 reference laboratories from the network of the French National Reference Center for Toxoplasmosis, in order to record the frequency of Toxoplasma gondii DNA detection in ICPs and to review the molecular methods used for diagnosis and the prevention measures implemented in transplant patients. During the study period, of 31,640 PCRs performed on samples from ICPs, 610 were positive (323 patients). Blood (n = 337 samples), cerebrospinal fluid (n = 101 samples), and aqueous humor (n = 100 samples) were more frequently positive. Chemoprophylaxis schemes in transplant patients differed between centers. PCR follow-up of allogeneic hematopoietic stem cell transplant (allo-HSCT) patients was implemented in 8/15 centers. Data from 180 patients (13 centers) were further analyzed regarding clinical setting and outcome. Only 68/180 (38%) patients were HIV+; the remaining 62% consisted of 72 HSCT, 14 solid organ transplant, and 26 miscellaneous immunodeficiency patients. Cerebral toxoplasmosis and disseminated toxoplasmosis were most frequently observed in HIV and transplant patients, respectively. Of 72 allo-HSCT patients with a positive PCR result, 23 were asymptomatic; all were diagnosed in centers performing systematic blood PCR follow-up, and they received specific treatment. Overall survival of allo-HSCT patients at 2 months was better in centers with PCR follow-up than in other centers (P < 0.01). This study provides updated data on the frequency of toxoplasmosis in HIV-negative ICPs and suggests that regular PCR follow-up of allo-HSCT patients could guide preemptive treatment and improve outcome. PMID:25762774

  3. Modified Pfannenstiel approach for radical retropubic prostatectomy: a 3-year experience.

    PubMed

    Manoharan, M; Ayyathurai, R; Nieder, A M; Soloway, M S

    2008-01-01

    A modified Pfannenstiel approach for radical retropubic prostatectomy (RRP) has been described previously. We present our experience with this approach for performing a RRP over the past 3 years. Between January 2003 and July 2006, 544 consecutive RRPs by modified Pfannenstiel approach between January 2003 and July 2006 were performed. We analyzed blood loss, transfusions, use of drain, pain score, analgesia and hospital stay. Patients were followed up at 6 weeks, three monthly for a year and six monthly thereafter. All clinical and operative variables were entered into a database and analyzed. A total of 544 men underwent RRP with median follow-up of 11 (s.d.+/-10.5) months. The mean age was 60 (s.d.+/-7) years. About 83, 91 and 95% of patients had nerve sparing, bladder neck preservation and a lymph node dissection, respectively. Fifty-three patients had a concurrent inguinal hernia repair through the same incision. Mean estimated blood loss was 431 (s.d.+/-267) ml. The pathological staging distribution was T2, 82%; T3a, 9%; and T3b, 9%. The mean pain score at days 1 and 7 were 3.7 (s.d.+/-2.5) and 3.3 (s.d.+/-3), respectively. The median hospital stay was 36 h (s.d.+/-24). About 5.5% have had biochemical recurrence. At 12 months 97% were continent and 46% potent. RRP using a modified Pfannenstiel approach offers safety and efficacy. It facilitates repair of associated inguinal hernia through the same incision.

  4. Blood Lead Concentrations in 1–3 Year Old Lebanese Children: A Cross-sectional study

    PubMed Central

    Nuwayhid, Iman; Nabulsi, Mona; Muwakkit, Samar; Kouzi, Sarah; Salem, George; Mikati, Mohamed; Ariss, Majd

    2003-01-01

    Background Childhood lead poisoning has not made the list of national public health priorities in Lebanon. This study aims at identifying the prevalence and risk factors for elevated blood lead concentrations (B-Pb ≥ 100 μg/L) among 1–3 year old children. It also examines the need for universal blood lead screening. Methods This is a cross-sectional study of 281 well children, presenting to the pediatric ambulatory services at the American University of Beirut Medical Center in 1997–98. Blood was drawn on participating children for lead analysis and a structured questionnaire was introduced to mothers asking about social, demographic, and residence characteristics, as well as potential risk factors for lead exposure. Children with B-Pb ≥ 100 μg/L were compared to those with B-Pb < 100 μg/L. Results Mean B-Pb was 66.0 μg/L (median 60.0; range 10–160; standard deviation 26.3) with 39 (14%) children with B-Pb ≥ 100 μg/L. Logistic regression analysis showed that elevated B-Pb was associated with paternal manual jobs (odds ratio [OR]: 4.74), residence being located in high traffic areas (OR: 4.59), summer season (OR: 4.39), using hot tap water for cooking (OR: 3.96), exposure to kohl (OR: 2.40), and living in older buildings (OR: 2.01). Conclusion Lead screening should be offered to high-risk children. With the recent ban of leaded gasoline in Lebanon, emphasis should shift to other sources of exposure in children. PMID:12780938

  5. A 3 year update on the influence of noise on performance and behavior.

    PubMed

    Clark, Charlotte; Sörqvist, Patrik

    2012-01-01

    The effect of noise exposure on human performance and behavior continues to be a focus for research activities. This paper reviews developments in the field over the past 3 years, highlighting current areas of research, recent findings, and ongoing research in two main research areas: Field studies of noise effects on children's cognition and experimental studies of auditory distraction. Overall, the evidence for the effects of external environmental noise on children's cognition has strengthened in recent years, with the use of larger community samples and better noise characterization. Studies have begun to establish exposure-effect thresholds for noise effects on cognition. However, the evidence remains predominantly cross-sectional and future research needs to examine whether sound insulation might lessen the effects of external noise on children's learning. Research has also begun to explore the link between internal classroom acoustics and children's learning, aiming to further inform the design of the internal acoustic environment. Experimental studies of the effects of noise on cognitive performance are also reviewed, including functional differences in varieties of auditory distraction, semantic auditory distraction, individual differences in susceptibility to auditory distraction, and the role of cognitive control on the effects of noise on understanding and memory of target speech materials. In general, the results indicate that there are at least two functionally different types of auditory distraction: One due to the interruption of processes (as a result of attention being captured by the sound), another due to interference between processes. The magnitude of the former type is related to individual differences in cognitive control capacities (e.g., working memory capacity); the magnitude of the latter is not. Few studies address noise effects on behavioral outcomes, emphasizing the need for researchers to explore noise effects on behavior in more

  6. Pyridoxine-dependent convulsions among children with refractory seizures: A 3-year follow-up study

    PubMed Central

    Chandra, Sadanandavalli Retnaswami; Issac, Thomas Gregor; Deepak, Sai; Teja, Ravi; Kuruthukulangara, Seby

    2016-01-01

    Introduction: Epilepsy accounts for 1% of the global disease burden and about 8–10 million epilepsy patients live in India. About 30–40% of these patients become drug-resistant and land up with palliative or disease-modifying surgeries. This is a situation causing great concern in view of the psychosocial and economic burden on the patient and the family apart from severe cognitive and motor consequences, especially in children. Therefore, it is mandatory to have an insight into the wide spectrum of causes with reference to refractoriness to antiepileptic medications in children with epilepsy. Patients and Methods: Children admitted under our team with refractory epilepsy as per the International League Against Epilepsy (ILAE) criteria in the last 3 years were included in the study. Results: Refractory epilepsy constituted 13.3% of inpatients in the pediatric group. Males dominated with 68.9% of these patients. Nearly 34.4% of these patients were found to suffer from various neurometabolic diseases. Almost 3.5% were due to pyridoxine-dependent convulsions. This group of patients showed an excellent response to dietary manipulation, disease-modifying treatment for the metabolic disorder, and supportive small-dose anticonvulsants. During follow-up, they showed very good response with reference to global development and seizure control. Conclusion: Pyridoxine-dependent convulsions are relatively rare forming about 3.5% of refractory epilepsies in this series. With initiation of appropriate therapy, results with reference to seizure control as well as neurodevelopment became evident within 2 weeks, and at 1-year follow-up, complete independence for majority of the needed activities is achieved with minimum cost, almost zero side effects, and absolute elimination of the need for palliative surgery. PMID:27857784

  7. Summary of Medipix Technology's 3-Years in Space and Plans for Future Developments

    NASA Astrophysics Data System (ADS)

    Pinsky, Lawrence

    2016-07-01

    NASA has evaluated 7 Timepix-based radiation imaging detectors from the CERN-based Medipix2 collaboration on the International Space Station (ISS), collecting more than 3-years of data, as well on the December, 2014 EFT-1 mission testing the new Orion Multi-Purpose Crew Vehicle. These data along with data collected at ground-based accelerator facilities including the NASA Space Radiation Lab (NSRL) at Brookhaven in the US, as well as at the HIMAC facility at the National Institute for Radiological Sciences in Japan, have allowed the development of software analysis techniques sufficient to provide a stand-alone accurate assessment of the space radiation environment for dosimetric purposes. Recent comparisons of the performance of the Timepix with both n-on-p and p-on-n Si sensors will be presented. The further evolution of the Timepix technology by the Medipix3 collaboration in the form of the Timepix3 chip, which employs a continuous data-driven readout scheme, is being evaluated for possible use in future space research applications. Initial performance evaluations at accelerators will be reported. The Medipix2 Collaboration is also in the process of designing an updated version of the Timepix chip, called the Timepix2, which will continue the frame-based readout scheme of the current Timepix chip, but add simultaneous charge encoding using the Time-Over-Threshold (TOT) and first-hit Time-of-Arrival (TOA) encoding. Current plans are to replace the Timepix by the Timepix2 with minimal reconfiguration of the supporting electronics. Longer-term plans include participation in the currently forming Medipix4 collaboration. A summary of these prospects will also be included.

  8. Molecular diagnosis of toxoplasmosis in immunocompromised patients: a 3-year multicenter retrospective study.

    PubMed

    Robert-Gangneux, Florence; Sterkers, Yvon; Yera, Hélène; Accoceberry, Isabelle; Menotti, Jean; Cassaing, Sophie; Brenier-Pinchart, Marie-Pierre; Hennequin, Christophe; Delhaes, Laurence; Bonhomme, Julie; Villena, Isabelle; Scherer, Emeline; Dalle, Frédéric; Touafek, Feriel; Filisetti, Denis; Varlet-Marie, Emmanuelle; Pelloux, Hervé; Bastien, Patrick

    2015-05-01

    Toxoplasmosis is a life-threatening infection in immunocompromised patients (ICPs). The definitive diagnosis relies on parasite DNA detection, but little is known about the incidence and burden of disease in HIV-negative patients. A 3-year retrospective study was conducted in 15 reference laboratories from the network of the French National Reference Center for Toxoplasmosis, in order to record the frequency of Toxoplasma gondii DNA detection in ICPs and to review the molecular methods used for diagnosis and the prevention measures implemented in transplant patients. During the study period, of 31,640 PCRs performed on samples from ICPs, 610 were positive (323 patients). Blood (n = 337 samples), cerebrospinal fluid (n = 101 samples), and aqueous humor (n = 100 samples) were more frequently positive. Chemoprophylaxis schemes in transplant patients differed between centers. PCR follow-up of allogeneic hematopoietic stem cell transplant (allo-HSCT) patients was implemented in 8/15 centers. Data from 180 patients (13 centers) were further analyzed regarding clinical setting and outcome. Only 68/180 (38%) patients were HIV(+); the remaining 62% consisted of 72 HSCT, 14 solid organ transplant, and 26 miscellaneous immunodeficiency patients. Cerebral toxoplasmosis and disseminated toxoplasmosis were most frequently observed in HIV and transplant patients, respectively. Of 72 allo-HSCT patients with a positive PCR result, 23 were asymptomatic; all were diagnosed in centers performing systematic blood PCR follow-up, and they received specific treatment. Overall survival of allo-HSCT patients at 2 months was better in centers with PCR follow-up than in other centers (P < 0.01). This study provides updated data on the frequency of toxoplasmosis in HIV-negative ICPs and suggests that regular PCR follow-up of allo-HSCT patients could guide preemptive treatment and improve outcome.

  9. Perfectionism, neuroticism, and daily stress reactivity and coping effectiveness 6 months and 3 years later.

    PubMed

    Dunkley, David M; Mandel, Tobey; Ma, Denise

    2014-10-01

    The present study addressed a fundamental gap between research and clinical work by advancing longitudinal explanatory conceptualizations of stress and coping processes that trigger daily affect in the short- and long-term for individuals with higher levels of personality vulnerability. Community adults completed measures of 2 higher order dimensions of perfectionism (personal standards [PS], self-criticism [SC]), neuroticism, and conscientiousness. Then, 6 months later and again 3 years later, participants completed daily questionnaires of stress, coping, and affect for 14 consecutive days. PS was associated with aggregated daily problem-focused coping and positive reinterpretation, whereas SC was uniquely associated with daily negative social interactions, avoidant coping, negative affect, and sadness at Month 6 and Year 3. Multilevel modeling results demonstrated that both individuals with higher PS and those with higher SC were emotionally reactive to event stress, negative social interactions, and avoidant coping at Month 6 and Year 3 and to less perceived control at Year 3. Positive reinterpretation was especially effective for individuals with higher SC at Month 6 and Year 3. The effects of PS on daily stress reactivity and coping (in)effectiveness were clearly distinguished from the effects of neuroticism and conscientiousness, whereas the SC effects were due to shared overlap with PS and neuroticism. The present findings demonstrate the promise of using repeated daily diary methodologies to help therapists and clients reliably predict future client reactions to daily stressors, which, in turn, could help guide interventions to break apart dysfunctional patterns connected to distress and build resilience for vulnerable individuals.

  10. Use of Corporal Punishment for 3-year Old Children and Associated Intimate Partner Aggression or Violence

    PubMed Central

    Taylor, Catherine A.; Lee, Shawna J.; Guterman, Neil B.; Rice, Janet C.

    2016-01-01

    Objective To examine associations between maternal and paternal use of corporal punishment (CP) for 3-year old children and intimate partner aggression or violence (IPAV) in a population-based sample. Methods The study sample (n = 1997) was derived from wave 3 of the Fragile Families and Child Well-being Study. Mother and father reports regarding their use of CP and their IPAV victimization were analyzed. IPAV included coercion, non-physical and physical aggression. Results About 65% of the children were spanked at least once in the prior month by one or both parents. Of those couples that reported any family aggression (87%), 54% reported that both CP and IPAV occurred. The most prevalent patterns of co-occurrence involved both parents as aggressors either toward each other (i.e., bilateral IPAV) or toward the child. The presence of bilateral IPAV essentially doubled the odds that one or both parents would use CP, even after controlling for potential confounders such as parenting stress, depression, and alcohol or other drug use. Of the five patterns of co-occurring family aggression assessed, the “single aggressor” model, in which only one parent aggressed in the family, received the least amount of empirical support. Conclusions Despite American Academy of Pediatrics’ recommendations against the use of CP, CP use remains common in the U.S. CP prevention and intervention efforts should carefully consider assumptions made about patterns of co-occurring aggression in families, given that adult victims of IPAV, including even minor, non-physical aggression between parents, have increased odds of using CP with their children. PMID:20732943

  11. Early childhood severe scalds in a developing country: A 3-year retrospective study.

    PubMed

    Agbenorku, Pius

    2013-01-01

    The burns intensive care unit (BICU) staff observed an increasing number of pediatric scald burn admissions as a result of increase injuries associated with the scald burns. A retrospective study was conducted to identify scalds demographics, etiologies, and mortality risk factors. This descriptive study comprised a total of 166 patients aged 0-5 years, who were admitted to the BICU of the Reconstructive Plastic Surgery and Burns Unit (RPSBU) through the Accident and Emergency (A and E) Centre of the Komfo Anokye Teaching Hospital (KATH)from May 1(st) 2009 to April 30(th) 2012. Source of information was the BICU Computerized Database System. Data extracted included demographics as well as treatment methods and outcomes. The study population was 166; 92 (55.4%) males and 74 (44.6%) females. Scalds admissions were 141 (84.9%); 13 (9.2%) of them died, 83 (58.9%) discharged, and 45 (31.9%) transferred-out to another burn ward and pediatric surgery ward in the hospital. Scald patients' demographics included 78 males (55.3%) and 63 females (44.7%); mean age was 2.18 years. Mortality risk factors identified were age <3 years (P = 0.044); scalds from hot water (P = 0.033), total burns surface area >30% (P = 0.017), and multiple body parts affected (P = 0.049). The current study showed age, hot water, and Total Burns Surface Area (TBSA) as risk factors of early childhood scalds. Education on scalds prevention targeting mothers/caregivers is needed to create awareness of the frequency, severity, and danger associated with pediatric scalds.

  12. Breastfeeding and dietary variety among preterm children aged 1-3 years.

    PubMed

    Husk, Jesse S; Keim, Sarah A

    2016-04-01

    Among infants born at term, breastfeeding is associated with increased dietary variety in childhood. Preterm birth can limit early feeding options while simultaneously increasing risk for negative health outcomes that could benefit from dietary-based preventative measures. We assessed whether breastfeeding is associated with increased dietary variety at 1-3 years amongst children born preterm. We analyzed baseline data from two clinical trials investigating cognitive development after fatty-acid supplementation for 10-39 month-old children born before 35 weeks gestation (n = 189). At baseline, mothers reported breastfeeding history and completed a 161-item food-frequency questionnaire for their child. Dietary variety was assessed via 3 measures: (1) proportion items consumed at least once per month, (2) servings of a given item consumed relative to total monthly food servings, (3) daily probability of consuming a given item. Overall, 88% of children were ever breastfed (median duration = 89 days, range = 0-539), and 48% of children were ever exclusively breastfed (median duration = 59 days, range = 3-240). Exclusive breastfeeding duration was associated with dietary variety increases of 0.9% (95% CI = 0.1-1.7) for vegetables, 1.6% (95% CI = 0.2-3.0) for meat/fish, and 1.3% (95% CI = 0.2-2.4) for grain/starch, for each additional month of exclusive breastfeeding after adjustment for key confounders. Correspondingly, the variety of sweets consumed decreased by 1.2% (CI: -2.1, -0.3) per month of any breastfeeding after adjustment. These results are consistent with those in children born at term, and if causal, could provide additional support for exclusive breastfeeding to improve diet and health in children born preterm.

  13. Clinical outcome following DIAM implantation for symptomatic lumbar internal disk disruption: a 3-year retrospective analysis

    PubMed Central

    Lu, Kang; Liliang, Po-Chou; Wang, Hao-Kuang; Chen, Jui-Sheng; Chen, Te-Yuan; Huang, Ruyi; Chen, Han-Jung

    2016-01-01

    Background/objective Internal disk disruption (IDD), an early event of lumbar disk degeneration, is the most common cause of low back pain. Since increased intradiskal pressure (IDP) is associated with symptoms and progression of disk degeneration, unloading a painful disk with an interspinous process device (IPD) is a rational treatment option. The goal of this study was to evaluate the effectiveness of dynamic stabilization with an IPD in the treatment of symptomatic IDD of the lumbar spine. Patients and methods Patients with symptomatic IDD were treated with implantation of an IPD, the device for intervertebral assisted motion (DIAM). Diagnosis of IDD was based on typical MRI finding of posterior annular high-intensity zone and positive provocative test on discography. IDP was analyzed intraoperatively. Axial back and leg pain was evaluated with visual analog scale, functional status with Oswestry Disability Index, and final clinical outcomes with Odom criteria. Data from 34 patients followed up for at least 3 years were collected. Results DIAM implantation significantly reduced IDP (n=11, P<0.0001). All 34 patients reported symptom relief. Thirty-one patients (91%) remained symptom free until the last followups. Three patients (9%) experienced recurrence of pain, of which the causes were unrelated to the IDD or surgery. Disk status at the DIAM-implanted segments remained stable. Segmental flexion/extension mobility was preserved in 27 of 30 patients with preoperative mobility. No proximal or distal adjacent segment degeneration was observed. The final clinical outcomes were excellent/good in 31 and fair/poor in three patients. Conclusion For patients with symptomatic IDD, dynamic stabilization with DIAM provides pain relief and functional improvement. The implantation maintains disk status and prevents progression of disk degeneration, without compromising segmental flexion/extension mobility or causing adjacent segment degeneration. PMID:27826214

  14. Pragmatic inference, not semantic competence, guides 3-year-olds' interpretation of unknown number words.

    PubMed

    Brooks, Neon; Audet, Jennifer; Barner, David

    2013-06-01

    Before children learn the specific meanings of numerals like six, do they know that they represent precise quantities? Previous studies have reported conflicting evidence and have found that children expect numerals to label precise quantities in some tasks but not in others (Condry & Spelke, 2008; Sarnecka & Gelman, 2004). In this article, we present evidence that some of children's apparent successes are best explained not by domain-specific semantic understanding of number but instead by language-general pragmatic abilities. In Experiment 1, we replicated the findings of the previous studies in a within-subject design. When 3-year-olds saw a set labeled with a number (e.g., five) and an item was added, they preferred a new label (six) over the old one, as though they believed that number words have precise meanings. However, when 1 of 2 sets was labeled (e.g., as five) and children were asked to find the same quantity (five) or a new quantity (six), they performed identically whether the original set was changed in quantity or merely rearranged. Thus, when 2 numerals were offered as alternative labels for 1 set, children behaved as though they had precise meanings, whereas when they were asked to determine which of 2 sets a single numeral referred to, they did not. In Experiment 2, children were tested using similar methods but with novel nouns and objects that were transformed, instead of sets. Children showed the identical pattern of results despite lacking meanings for these words, suggesting that their judgments for numerals may not have relied on semantic knowledge that numerals have precise meanings. We propose that children's behavior can be explained by the use of domain-general pragmatic inference and does not require positing domain-specific numerical knowledge.

  15. Disability multilevel modelling in first episodes of psychosis at 3-year follow-up.

    PubMed

    Mellor-Marsá, Blanca; Caballero, Francisco Félix; Cabello, María; Ayuso-Mateos, José Luis; Setién-Suero, Esther; Vázquez-Bourgon, Javier; Crespo-Facorro, Benedicto; Ayesa-Arriola, Rosa

    2017-01-03

    The description of longitudinal bio-psycho-social profiles in FEP samples may be useful for the prediction of disability trajectories. This study aimed to describe the differences between disability status of FEP patients at baseline and their change over time, analysing how variables associated to the psychological status, and the environment of the patient can affect his or her disability trajectory, once the influence of health condition and socio-demographic variables has been controlled for. Using data from a 3-year follow-up study on early psychosis (PAFIP), a multilevel structure in which the longitudinal measurements (within level) were nested within the individuals (between level), was modeled. The contribution of the different time-varying and time-invariant variables to the patients' disability outcomes was tested through eight nested models. Consecutive models, that successively added health related, socio-demographic, psychological and environmental variables to the unconditional model were estimated, by means of deviance and fit statistics. The present work revealed the importance of psychological and environmental factors in the explanation of disability changes in the context of FEP. We may conclude that longitudinal assessments of time-varying predictors - living situation (b=-0.10, p<0.05), economic support (b=0.11, p<0.01) and insight (b=-0.08, p<0.05) - explain a relevant amount of disability variation over time, independently from symptoms' severity, duration of untreated psychosis, age, gender and years of education. Additionally, the level of premorbid adjustment (b=0.05, p<0.001) was associated to differences in disability outcomes among FEP patients.

  16. Categorization and abstraction abilities in 3-year-old children: a comparison with monkey data.

    PubMed

    Bovet, Dalila; Vauclair, Jacques; Blaye, Agnès

    2005-01-01

    Three-year-old children were tested on three categorization tasks of increasing levels of abstraction (used with adult baboons in an earlier study): the first was a conceptual categorization task (food vs toys), the second a perceptual matching task (same vs different objects), and the third a relational matching task in which the children had to sort pairs according to whether or not the two items belonged to the same or different categories. The children were tested using two different procedures, the first a replication of the procedure used with the baboons (pulling one rope for a category or a relationship between two objects, and another rope for the other category or relationship), the second a task based upon children's prior experiences with sorting objects (putting in the same box objects belonging to the same category or a pair of objects exemplifying the same relation). The children were able to solve the first task (conceptual categorization) when tested with the sorting into boxes procedure, and the second task (perceptual matching) when tested with both procedures. The children were able to master the third task (relational matching) only when the rules were clearly explained to them, but not when they could only watch sorting examples. In fact, the relational matching task without explanation requires analogy abilities that do not seem to be fully developed at 3 years of age. The discrepancies in performances between children tested with the two procedures, with the task explained or not, and the discrepancies observed between children and baboons are discussed in relation to differences between species and/or problem-solving strategies.

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

    SciTech Connect

    Sun, Yu; Wong, Nicholas; Guan, Yinghui; Salamanca, Clara M.; Cheng, Jung Chien; Lee, Jonathan M.; Gray, Joe W.; Auersperg, Nelly

    2008-04-25

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

  18. Solution NMR structure of the C-terminal EF-hand domain of human cardiac sodium channel NaV1.5.

    PubMed

    Chagot, Benjamin; Potet, Franck; Balser, Jeffrey R; Chazin, Walter J

    2009-03-06

    The voltage-gated sodium channel NaV1.5 is responsible for the initial upstroke of the action potential in cardiac tissue. Levels of intracellular calcium modulate inactivation gating of NaV1.5, in part through a C-terminal EF-hand calcium binding domain. The significance of this structure is underscored by the fact that mutations within this domain are associated with specific cardiac arrhythmia syndromes. In an effort to elucidate the molecular basis for calcium regulation of channel function, we have determined the solution structure of the C-terminal EF-hand domain using multidimensional heteronuclear NMR. The structure confirms the existence of the four-helix bundle common to EF-hand domain proteins. However, the location of this domain is shifted with respect to that predicted on the basis of a consensus 12-residue EF-hand calcium binding loop in the sequence. This finding is consistent with the weak calcium affinity reported for the isolated EF-hand domain; high affinity binding is observed only in a construct with an additional 60 residues C-terminal to the EF-hand domain, including the IQ motif that is central to the calcium regulatory apparatus. The binding of an IQ motif peptide to the EF-hand domain was characterized by isothermal titration calorimetry and nuclear magnetic resonance spectroscopy. The peptide binds between helices I and IV in the EF-hand domain, similar to the binding of target peptides to other EF-hand calcium-binding proteins. These results suggest a molecular basis for the coupling of the intrinsic (EF-hand domain) and extrinsic (calmodulin) components of the calcium-sensing apparatus of NaV1.5.

  19. Binding of calcium ions and SNAP-25 to the hexa EF-hand protein secretagogin

    PubMed Central

    Rogstam, Annika; Linse, Sara; Lindqvist, Anders; James, Peter; Wagner, Ludwig; Berggård, Tord

    2006-01-01

    Secretagogin is a hexa EF-hand protein, which has been identified as a novel potential tumour marker. In the present study, we show that secretagogin binds four Ca2+ ions (log K1=7.1±0.4, log K2=4.7±0.6, log K3=3.6±0.7 and log K4=4.6±0.6 in physiological salt buffers) with a [Ca2+]0.5 of approx. 25 μM. The tertiary structure of secretagogin changes significantly upon Ca2+ binding, but not upon Mg2+ binding, and the amount of exposed hydrophobic surface in secretagogin increases upon Ca2+ binding, but not upon Mg2+ binding. These properties suggest that secretagogin belongs to the ‘sensor’ family of Ca2+-binding proteins. However, in contrast with the prototypical Ca2+ sensor calmodulin, which interacts with a very large number of proteins, secretagogin is significantly less promiscuous. Only one secretagogin-interacting protein was reproducibly identified from insulinoma cell lysates and from bovine and mouse brain homogenates. This protein was identified as SNAP-25 (25 kDa synaptosome-associated protein), a protein involved in Ca2+-induced exocytosis in neurons and in neuroendocrine cells. Kd was determined to be 1.2×10−7 M in the presence of Ca2+ and 1.5×10−6 M in the absence of Ca2+. The comparatively low Ca2+ affinity for secretagogin and the fact that it undergoes Ca2+-induced conformational changes and interacts with SNAP-25 raise the possibility that secretagogin may link Ca2+ signalling to exocytotic processes. PMID:16939418

  20. Penta-EF-Hand Protein Peflin Is a Negative Regulator of ER-To-Golgi Transport

    PubMed Central

    Held, Aaron; Sargeant, John; Thorsen, Kevin; Hay, Jesse C.

    2016-01-01

    Luminal calcium regulates vesicle transport early in the secretory pathway. In ER-to-Golgi transport, depletion of luminal calcium leads to significantly reduced transport and a buildup of budding and newly budded COPII vesicles and vesicle proteins. Effects of luminal calcium on transport may be mediated by cytoplasmic calcium sensors near ER exits sites (ERES). The penta-EF-hand (PEF) protein apoptosis-linked gene 2 (ALG-2) stabilizes sec31A at ER exit sites (ERES) and promotes the assembly of inner and outer shell COPII components. However, in vitro and intact cell approaches have not determined whether ALG-2 is a negative or positive regulator, or a regulator at all, under basal physiological conditions. ALG-2 interacts with another PEF protein, peflin, to form cytosolic heterodimers that dissociate in response to calcium. However, a biological function for peflin has not been demonstrated and whether peflin and the ALG-2/peflin interaction modulates transport has not been investigated. Using an intact, single cell, morphological assay for ER-to-Golgi transport in normal rat kidney (NRK) cells, we found that depletion of peflin using siRNA resulted in significantly faster transport of the membrane cargo VSV-G. Double depletion of peflin and ALG-2 blocked the increased transport resulting from peflin depletion, demonstrating a role for ALG-2 in the increased transport. Furthermore, peflin depletion caused increased targeting of ALG-2 to ERES and increased ALG-2/sec31A interactions, suggesting that peflin may normally inhibit transport by preventing ALG-2/sec31A interactions. This work identifies for the first time a clear steady state role for a PEF protein in ER-to-Golgi transport—peflin is a negative regulator of transport. PMID:27276012

  1. Analyzing the Low State of EF Eridani with Hubble Space Telescope Ultraviolet Spectra

    NASA Astrophysics Data System (ADS)

    Szkody, Paula; Mukadam, Anjum; Gänsicke, Boris T.; Campbell, Ryan K.; Harrison, Thomas E.; Howell, Steve B.; Holtzman, Jon; Walter, Frederick M.; Henden, Arne; Dillon, William; Boberg, Owen; Dealaman, Shannon; Perone, Christian S.

    2010-06-01

    Time-resolved spectra throughout the orbit of EF Eri during its low accretion state were obtained with the solar blind channel on the Advanced Camera for Surveys on board the Hubble Space Telescope. The overall spectral distribution exhibits peaks at 1500 and 1700 Å, while the UV light curves display a quasi-sinusoidal modulation over the binary orbit. Models of white dwarfs (WDs) with a hot spot and cyclotron emission were attempted to fit the spectral variations throughout the orbit. A non-magnetic WD with a temperature of ~10,000 K and a hot spot with a central temperature of 15,000 K generally match the broad absorptions at 1400 and 1600 Å with those expected for the quasi-molecular H features H2 and H+ 2. However, the flux in the core of the Lyα absorption does not go to zero, implying an additional component, and the flux variations throughout the orbit are not well matched at long wavelengths. Alternatively, a 9500 K WD with a 100 MG cyclotron component can fit the lowest (phase 0.0) fluxes, but the highest fluxes (phase 0.5) require an additional source of magnetic field or temperature. The 100 MG field required for the UV fit is much higher than that which fits the optical/IR wavelengths, which would support previous suggestions of a complex field structure in polars. Based on observations made with the NASA/ESA Hubble Space Telescope, obtained at the Space Telescope Science Institute, which is operated by the Association of Universities for Research in Astronomy, Inc., under NASA contract NAS 5-26555, and with the Apache Point Observatory 3.5 m telescope which is owned and operated by the Astrophysical Research Consortium.

  2. A high brightness proton injector for the Tandetron accelerator at Jožef Stefan Institute

    NASA Astrophysics Data System (ADS)

    Pelicon, Primož; Podaru, Nicolae C.; Vavpetič, Primož; Jeromel, Luka; Ogrinc Potocnik, Nina; Ondračka, Simon; Gottdang, Andreas; Mous, Dirk J. M.

    2014-08-01

    Jožef Stefan Institute recently commissioned a high brightness H- ion beam injection system for its existing tandem accelerator facility. Custom developed by High Voltage Engineering Europa, the multicusp ion source has been tuned to deliver at the entrance of the Tandetron™ accelerator H- ion beams with a measured brightness of 17.1 A m-2 rad-2 eV-1 at 170 μA, equivalent to an energy normalized beam emittance of 0.767 π mm mrad MeV1/2. Upgrading the accelerator facility with the new injection system provides two main advantages. First, the high brightness of the new ion source enables the reduction of object slit aperture and the reduction of acceptance angle at the nuclear microprobe, resulting in a reduced beam size at selected beam intensity, which significantly improves the probe resolution for micro-PIXE applications. Secondly, the upgrade strongly enhances the accelerator up-time since H and He beams are produced by independent ion sources, introducing a constant availability of 3He beam for fusion-related research with NRA. The ion beam particle losses and ion beam emittance growth imply that the aforementioned beam brightness is reduced by transport through the ion optical system. To obtain quantitative information on the available brightness at the high-energy side of the accelerator, the proton beam brightness is determined in the nuclear microprobe beamline. Based on the experience obtained during the first months of operation for micro-PIXE applications, further necessary steps are indicated to obtain optimal coupling of the new ion source with the accelerator to increase the normalized high-energy proton beam brightness at the JSI microprobe, currently at 14 A m-2 rad-2 eV-1, with the output current at 18% of its available maximum.

  3. Executive function moderates the relationship between depressive symptoms and resting heart rate variability in heart failure.

    PubMed

    Gathright, Emily C; Walter, Fawn A; Hawkins, Misty A W; Spitznagel, Mary Beth; Hughes, Joel W; Gunstad, John

    2016-04-01

    Heart failure (HF) is associated with high rates of depression. In turn, depression is associated with reduced heart rate variability (HRV), a marker of parasympathetic dysfunction and poorer cardiac outcomes. Cognitive impairment--especially executive dysfunction--is also highly prevalent in HF, but it is unknown whether executive function (EF) impacts the depression-HRV relationship. The primary objective of this paper is to examine whether EF moderates the relationship between depression and HRV in HF. Participants were 109 HF patients. Depressive symptoms were measured using the Beck Depression Inventory-II. EF was assessed using a composite of age-adjusted T scores on the Frontal Assessment Battery, Trail Making Test B, and Stroop Color Word subtest. Parasympathetic function was assessed using resting high frequency HRV (HF-HRV). Multiple hierarchical regression was used to conduct BDI × EF moderation analyses. BDI scores were associated with reduced resting HF-HRV (p < .05). No main effects were detected between EF and resting HF-HRV (p > .05). However, EF moderated the relationship between BDI scores and resting HF-HRV (β = 0.59, p < .01). Simple slope analyses revealed that among participants with poorer EF, higher BDI scores were associated with lower resting HF-HRV (p < .001). Structural brain changes common in HF may contribute to lower EF, increased depression, and poorer autonomic functioning. Alternatively, the results may indicate that individuals with intact EF engage in self-care strategies that negate the detrimental impact of depression on autonomic function. Additional work is needed to clarify these possibilities and the potential benefits of treating depression in HF patients with different cognitive abilities.

  4. Specific Interaction between eEF1A and HIV RT Is Critical for HIV-1 Reverse Transcription and a Potential Anti-HIV Target

    PubMed Central

    Rawle, Daniel J.; Qin, Fangyun; Wang, Rui; Soares, Dinesh C.; Jin, Hongping; Sivakumaran, Haran; Lin, Min-Hsuan; Spann, Kirsten; Abbott, Catherine M.; Harrich, David

    2015-01-01

    Reverse transcription is the central defining feature of HIV-1 replication. We previously reported that the cellular eukaryotic elongation factor 1 (eEF1) complex associates with the HIV-1 reverse transcription complex (RTC) and the association is important for late steps of reverse transcription. Here we show that association between the eEF1 and RTC complexes occurs by a strong and direct interaction between the subunit eEF1A and reverse transcriptase (RT). Using biolayer interferometry and co-immunoprecipitation (co-IP) assays, we show that association between the eEF1 and RTC complexes occurs by a strong (KD ~3–4 nM) and direct interaction between eEF1A and reverse transcriptase (RT). Biolayer interferometry analysis of cell lysates with titrated levels of eEF1A indicates it is a predominant cellular RT binding protein. Both the RT thumb and connection domains are required for interaction with eEF1A. A single amino acid mutation, W252A, within the thumb domain impaired co-IP between eEF1A and RT, and also significantly reduced the efficiency of late reverse transcription and virus replication when incorporated into infectious HIV-1. Molecular modeling analysis indicated that interaction between W252 and L303 are important for RT structure, and their mutation to alanine did not impair heterodimerisation, but negatively impacted interaction with eEF1A. Didemnin B, which specifically binds eEF1A, potently inhibited HIV-1 reverse transcription by greater than 2 logs at subnanomolar concentrations, especially affecting reverse transcription late DNA synthesis. Analysis showed reduced levels of RTCs from HIV-1-infected HEK293T treated with didemnin B compared to untreated cells. Interestingly, HIV-1 with a W252A RT mutation was resistant to didemnin B negative effects showing that didemnin B affects HIV-1 by targeting the RT-eEF1A interaction. The combined evidence indicates a direct interaction between eEF1A and RT is crucial for HIV reverse transcription and

  5. A Practical Guide for the Treatment of Symptomatic Heart Failure with Reduced Ejection Fraction (HFrEF)

    PubMed Central

    Reed, Brent N; Sueta, Carla A

    2015-01-01

    This review will outline the management of patients with symptomatic systolic heart failure or heart failure with reduced ejec-tion fraction (HFrEF), i.e., those with structural heart disease and previous or current symptoms. Determination of volume status and appropriate diuretic administration is important in heart failure management. Inhibition of the renin-angiotensin-aldosterone and sympathetic nervous systems improves survival and decreases hospitalizations in patients with systolic or reduced ejection fraction HF (HFrEF). Beta blockers and aldosterone antagonists improve ejection fraction. Indications for additional agents including nitrates plus hydralazine, digoxin, statins, omega 3 polyunsaturated fatty acids, anticoagulants, and antiarrhythmics will be discussed. Choice of agents, dose-related effects, strategies to minimize adverse effects, and medications to avoid will be presented. PMID:24251455

  6. Conductor and joint test results of JT-60SA CS and EF coils using the NIFS test facility

    NASA Astrophysics Data System (ADS)

    Obana, Tetsuhiro; Takahata, Kazuya; Hamaguchi, Shinji; Kizu, Kaname; Murakami, Haruyuki; Chikaraishi, Hirotaka; Noguchi, Hiroki; Kobuchi, Takashi; Moriuchi, Sadatomo; Imagawa, Shinsaku; Mito, Toshiyuki; Tsuchiya, Katsuhiko; Natsume, Kyohei; Yoshida, Kiyoshi; Nomoto, Kazuhiro; Kim, Tae-hyun

    2016-01-01

    In 2007, JAEA and NIFS launched the test project to evaluate the performance of cable-in-conduit (CIC) conductors and conductor joints for the JT-60SA CS and EF coils. In this project, conductor tests for four types of coil conductor and joint tests for seven types of conductor joint have been conducted for the past eight years using the NIFS test facility. As a result, the test project indicated that the CIC conductors and conductor joints fulfill the design requirement for the CS and EF coils. In addition, the NIFS test facility is expected to be utilized as the test facility for the development of a conductor and conductor joint for the purpose of the DEMO nuclear fusion power plant, provided that the required magnetic field strength is within 9 T.

  7. Probing Ca2+-binding capability of viral proteins with the EF-hand motif by grafting approach.

    PubMed

    Zhou, Yubin; Xue, Shenghui; Chen, Yanyi; Yang, Jenny J

    2013-01-01

    Ca(2+) is implicated in almost every step of the life cycle of viruses, including virus entry into host cells, virus replication, virion assembly, maturation, and release. However, due to the lack of prediction algorithms and rigorous validation methods, only limited cases of viral Ca(2+)-binding sites are reported. Here, we introduce a method to predict continuous EF-hand or EF-hand-like motifs in the viral genomes based on their primary sequences. We then introduce a grafting approach, and the use of luminescence resonance energy transfer and Ca(2+) competition assay for experimental verification of predicted Ca(2+)-binding sites. This protocol will be valuable for the prediction and identification of unknown Ca(2+)-binding sites in virus.

  8. Experimental and bioinformatic characterization of CaBP2933 an EF-Hand protein of Giardia intestinalis.

    PubMed

    Alvarado, Magda E; Rubiano, Claudia; Calvo, Eliana; Gómez, Vanessa; Wasserman, Moisés

    2017-03-31

    Giardia intestinalis is a parasite that inhabits the small intestine of humans. This parasite is a divergent eukaryote with a compact genome. The calcium ion is an essential messenger in cell signaling. Calcium's role as a messenger is mediated through calcium-binding proteins (CaBPs) that decode the message. The most important family of CaBPs is the EF-Hand protein family. In this study we have explored the role of EF-Hand protein CaBP2933. We analyzed its location, confirmed its ability to bind calcium and identified some of its interacting proteins. Take together our results suggest that CaBP2933 is involved in vesicular trafficking during encystation, via an interaction with kinesin-3 motor protein.

  9. Delayed Complications in Patients Surviving at Least 3 Years After Stereotactic Radiosurgery for Brain Metastases

    SciTech Connect

    Yamamoto, Masaaki; Kawabe, Takuya; Higuchi, Yoshinori; Sato, Yasunori; Nariai, Tadashi; Barfod, Bierta E.; Kasuya, Hidetoshi; Urakawa, Yoichi

    2013-01-01

    Purpose: Little is known about delayed complications after stereotactic radiosurgery in long-surviving patients with brain metastases. We studied the actual incidence and predictors of delayed complications. Patients and Methods: This was an institutional review board-approved, retrospective cohort study that used our database. Among our consecutive series of 2000 patients with brain metastases who underwent Gamma Knife radiosurgery (GKRS) from 1991-2008, 167 patients (8.4%, 89 women, 78 men, mean age 62 years [range, 19-88 years]) who survived at least 3 years after GKRS were studied. Results: Among the 167 patients, 17 (10.2%, 18 lesions) experienced delayed complications (mass lesions with or without cyst in 8, cyst alone in 8, edema in 2) occurring 24.0-121.0 months (median, 57.5 months) after GKRS. The actuarial incidences of delayed complications estimated by competing risk analysis were 4.2% and 21.2% at the 60th month and 120th month, respectively, after GKRS. Among various pre-GKRS clinical factors, univariate analysis demonstrated tumor volume-related factors: largest tumor volume (hazard ratio [HR], 1.091; 95% confidence interval [CI], 1.018-1.154; P=.0174) and tumor volume {<=}10 cc vs >10 cc (HR, 4.343; 95% CI, 1.444-12.14; P=.0108) to be the only significant predictors of delayed complications. Univariate analysis revealed no correlations between delayed complications and radiosurgical parameters (ie, radiosurgical doses, conformity and gradient indexes, and brain volumes receiving >5 Gy and >12 Gy). After GKRS, an area of prolonged enhancement at the irradiated lesion was shown to be a possible risk factor for the development of delayed complications (HR, 8.751; 95% CI, 1.785-157.9; P=.0037). Neurosurgical interventions were performed in 13 patients (14 lesions) and mass removal for 6 lesions and Ommaya reservoir placement for the other 8. The results were favorable. Conclusions: Long-term follow-up is crucial for patients with brain metastases

  10. Development and implementation of the Clinical Tooth Shade Differentiation Course – an evaluation over 3 years

    PubMed Central

    Olms, Constanze; Haak, Rainer; Jakstat, Holger A.

    2016-01-01

    Objective: Tooth shade differentiation concerns the identification and classification of tooth shades. The objective of this project was to implement the Clinical Tooth Shade Differentiation Course in the preclinical stage of studies and to evaluate the students' perspective over a period of 3 years. Methodology: The course is planned for a duration of 10 weeks with two 45-minute sessions per semester week. The entire attendance time was 10:15 h. 2 lectures of 90 minutes each, 2 seminars of 60 min each and 2 teaching units with the phantom head and role playing took place. In addition to the various parameters of tooth shade, changes in tooth shade and the basics of dental esthetics, clinical procedures for manual and digital tooth shade determination were explained and practiced. 96% (69 of 72) of the students participated in the first evaluation in 2012/2013 (T1), and 68% of these were women. In the following year, 2013/2014 (T2), 92% (45 of 48 students) took part; 62% of these were women and 38% men. The 2014/2015 evaluation (T3) comprised 94% (45 of 48 students). Of these, 67% were women. Results: In the evaluation, the students gave the course a positive grade. The questions in "General/Organization" were given a mean (M) of 1.5 (SD=0.7) in T1 and T2 , and 1.2 (SD=0.3) in T3. The "Overall Assessment" yielded MT1=1.6 (SD=0.6), MT2=1.5 (SD=0.5) and MT3=1.1 (SD=0.3). In T1 and T2, the item "The instructor actively involved the students in the course" was given a mean of 2.1 (SD=0.9), and in T3 a mean of 1.2 (SD=0.5). Conclusions: The course presented here conceptually shows how practical dental skills can be taught in a theoretical and clinical context. Educational objectives from the role of a dental expert were taken from the national competence-based catalog of educational objectives for dentistry and can also be supplemented. The objectives can be transferred to other dental faculties. PMID:26958650

  11. Does a risk questionnaire add anything to a colorectal screening project? Report of a 3-year screening experience.

    PubMed

    Niv, Y

    1992-07-01

    A questionnaire to detect persons at high risk for colorectal cancer was used in conjunction with fecal occult blood tests in a 3-year screening program in Northern Israel. Screening was offered to 2,590 persons over 40 years of age and accepted by 1,797 (compliance of 69.4%). In the subsequent 2 years, occult blood testing (Hemoccult II) was offered to those who had had negative tests (compliance rate of 99.6% and 100%). Six hundred and thirty persons (35.1%) had risk factors according to the questionnaire, and 195 of them underwent colonoscopy, with a predictive value of 15.9% for a neoplastic lesion. The Hemoccult II test was positive in 71 participants (4.0%) of whom 67 were investigated with a similar predictive value for neoplastic lesion (16.4%). In the second and third annual screening, the fecal occult blood test was positive in 29 (2.6%) and 27 (2.5%), and had a two and three times higher predictive value for neoplastic lesions, respectively. This was accompanied by a decrease in the cost of discovery. In all three stages, an adenomatous polyp was found in 48, and cancer in 10 participants (2.6% and 0.5% of the 1,797 original participants). Although a questionnaire may be fruitful in colorectal cancer screening, the higher number of participants subjected to further examinations makes this approach very expensive. The annual stool examination for occult blood has a higher predictive value for colonic neoplasm and a lower cost than a one stage, broader population based, study.

  12. Training in the fasted state facilitates re-activation of eEF2 activity during recovery from endurance exercise.

    PubMed

    Van Proeyen, K; De Bock, K; Hespel, P

    2011-07-01

    Nutrition is an important co-factor in exercise-induced training adaptations in muscle. We compared the effect of 6 weeks endurance training (3 days/week, 1-2 h at 75% VO(2peak)) in either the fasted state (F; n = 10) or in the high carbohydrate state (CHO, n = 10), on Ca(2+)-dependent intramyocellular signalling in young male volunteers. Subjects in CHO received a carbohydrate-rich breakfast before each training session, as well as ingested carbohydrates during exercise. Before (pretest) and after (posttest) the training period, subjects performed a 2 h constant-load exercise bout (~70% of pretest VO(2peak)) while ingesting carbohydrates (1 g/kg h(-1)). A muscle biopsy was taken from m. vastus lateralis immediately before and after the test, and after 4 h of recovery. Compared with pretest, in the posttest basal eukaryotic elongation factor 2 (eEF2) phosphorylation was elevated in CHO (P < 0.05), but not in F. In the pretest, exercise increased the degree of eEF2 phosphorylation about twofold (P < 0.05), and values returned to baseline within the 4 h recovery period in each group. However, in the posttest dephosphorylation of eEF2 was negated after recovery in CHO, but not in F. Independent of the dietary condition training enhanced the basal phosphorylation status of Phospholamban at Thr(17), 5'-AMP-activated protein kinase α (AMPKα), and Acetyl CoA carboxylase β (ACCβ), and abolished the exercise-induced increase of AMPKα and ACCβ (P < 0.05). In conclusion, training in the fasted state, compared with identical training with ample carbohydrate intake, facilitates post-exercise dephosphorylation of eEF2. This may contribute to rapid re-activation of muscle protein translation following endurance exercise.

  13. Electrical field stimulation (EFS)-induced relaxations turn into contractions upon removal of extracellular calcium in rat mesenteric artery.

    PubMed

    Ozkan, Melike Hacer; Ozturk, Elif Inci; Uma, Serdar

    2013-04-01

    In the present study, we aimed to examine the effect of blockade of L-type Ca(2+) channels (LTCC) and in addition the removal of extracellular Ca(2+), on EFS-induced relaxations in rings of rat mesenteric artery. EFS applied to the tissues precontracted with phenylephrine caused relaxations which were markedly inhibited by nifedipine (10(-7)M) and tetraethylammonium (TEA) (1mM). Addition of LTCC opener BAY K 8644 (10(-7)M) failed to enhance the relaxations. Upon removal of Ca(2+), EFS with the same stimulation parameters produced frequency-dependent transient contractions. Tetrodotoxin (10(-6)M), capsaicin (10(-5)M) and removal of endothelium did not alter these contractions suggesting that they were not neural in origin and endothelium-derived contracting factors were unlikely to be involved. However, they were increased by nearly 40% in response to BAY K 8644 (10(-7)M) and were inhibited by nifedipine (10(-7)M), indicating that activation of the LTCCs was essential. Inositol triphosphate (InsP3) receptor antagonist 2-APB (10(-4)M) significantly reduced, and high concentration of caffeine (20mM) almost totally suppressed the contractions. These results suggest that in the absence of extracellular Ca(2+) EFS through membrane depolarization, evokes the opening of the LTCCs which subsequently leads to the release of Ca(2+) from internal stores via InsP3 receptors, a phenomenon known as Ca(2+) channel-induced Ca(2+) release (CCICR), to trigger vasoconstriction. That activation of LTCCs causes arterial relaxation or contraction depending on the Ca(2+) status apparently exemplifies how the same messenger fulfils opposing physiological functions in a given cell.

  14. The more basic isoform of eEF1A relates to tumour cell phenotype and is modulated by hyper-proliferative/differentiating stimuli in normal lymphocytes and CCRF-CEM T-lymphoblasts.

    PubMed

    Scaggiante, Bruna; Dapas, Barbara; Pozzato, Gabriele; Grassi, Gabriele

    2013-06-01

    The elongation factor 1A proteins (eEF1A1/A2) are known to play a role in tumours. We previously found that a more basic isoform of eEF1A (MBI-eEF1A) is present in the cytoskeletal/nuclear-enriched extracts of CCRF-CEM T-lymphoblasts but not in those of normal lymphocytes. To obtain deeper knowledge about MBI-eEF1A biology, we investigate from which of the eEF1A proteins, eEF1A1 or eEF1A2, MBI-eEF1A originates and the possibility that its appearance can be modulated by the differentiated or proliferative cell status. CCRF-CEM T-lymphoblasts and normal lymphocytes were cultured with or without differentiation/pro-proliferative stimuli (Phorbol 12-Myristate 13-Acetate (PMA) alone or the combination of phytohaemagglutinin (PHA) with PMA, respectively), and the presence of MBI-eEF1A evaluated together with that of the eEF1A1/A2 mRNAs. Our data indicate that the MBI-eEF1A may derive from eEF1A1 as eEF1A2 is not expressed in CCRF-CEM and normal lymphocytes. Moreover, MBI-eEF1A is inducible in normal lymphocytes upon hyper-proliferative stimuli application; in CCRF-CEM, its presence can be abrogated by PMA-induced differentiation. Finally, MBI-eEF1A may have a functional role in hyper-proliferating/tumour cells as its disappearance reduces the growth of CCRF-CEM and that of PHA/PMA-stimulated lymphocytes. The presented data suggest that MBI-eEF1A may be related to oncogenic cell phenotype, rising the possibility to use MBI-eEF1A as target for novel therapeutic strategies.

  15. Parent Ratings of Executive Functioning in Children Adopted from Psychosocially Depriving Institutions

    PubMed Central

    Merz, Emily C.; McCall, Robert B.

    2010-01-01

    Background Previous studies have found that post-institutionalized (PI) children are particularly susceptible to attention problems and perform poorly on executive functioning (EF) lab tasks. Methods Parent ratings of EF were examined in 288 school-age and 130 preschool-age children adopted from psychosocially depriving Russian institutions that provided adequate physical resources but not one-on-one interactions with a consistent set of responsive caregivers. Results Results revealed a step-like association between age at adoption and EF deficits; school-age children adopted after 18 months of age had greater EF difficulties than younger-adopted children and the never-institutionalized normative sample. The onset of adolescence was associated with a greater increase in EF deficits for children adopted after 18 months than for younger-adopted children. Preschool-age children were not found to have greater EF difficulties than the normative sample. Conclusions These findings suggest that prolonged early psychosocial deprivation may increase children's risk of EF deficits and that the developmental stresses of adolescence may be particularly challenging for older-adopted PI children. PMID:20955189

  16. A conserved P-loop anchor limits the structural dynamics that mediate nucleotide dissociation in EF-Tu

    NASA Astrophysics Data System (ADS)

    Mercier, Evan; Girodat, Dylan; Wieden, Hans-Joachim

    2015-01-01

    The phosphate-binding loop (P-loop) is a conserved sequence motif found in mononucleotide-binding proteins. Little is known about the structural dynamics of this region and its contribution to the observed nucleotide binding properties. Understanding the underlying design principles is of great interest for biomolecular engineering applications. We have used rapid-kinetics measurements in vitro and molecular dynamics (MD) simulations in silico to investigate the relationship between GTP-binding properties and P-loop structural dynamics in the universally conserved Elongation Factor (EF) Tu. Analysis of wild type EF-Tu and variants with substitutions at positions in or adjacent to the P-loop revealed a correlation between P-loop flexibility and the entropy of activation for GTP dissociation. The same variants demonstrate more backbone flexibility in two N-terminal amino acids of the P-loop during force-induced EF-Tu.GTP dissociation in Steered Molecular Dynamics simulations. Amino acids Gly18 and His19 are involved in stabilizing the P-loop backbone via interactions with the adjacent helix C. We propose that these P-loop/helix C interactions function as a conserved P-loop anchoring module and identify the presence of P-loop anchors within several GTPases and ATPases suggesting their evolutionary conservation.

  17. Design, synthesis, and evaluation of asymmetric EF24 analogues as potential anti-cancer agents for lung cancer.

    PubMed

    Wu, Jianzhang; Wu, Shoubiao; Shi, Lingyi; Zhang, Shanshan; Ren, Jiye; Yao, Song; Yun, Di; Huang, Lili; Wang, Jiabing; Li, Wulan; Wu, Xiaoping; Qiu, Peihong; Liang, Guang

    2017-01-05

    The nuclear factor-kappa B (NF-κB) signaling pathway has been targeted for the therapy of various cancers, including lung cancer. EF24 was considered as a potent inhibitor of NF-κB signaling pathway. In this study, a series of asymmetric EF24 analogues were synthesized and evaluated for their anti-cancer activity against three lung cancer cell lines (A549, LLC, H1650). Most of the compounds exhibited good anti-tumor activity. Among them, compound 81 showed greater cytotoxicity than EF24. Compound 81 also possessed a potent anti-migration and anti-proliferative ability against A549 cells in a concentration-dependent manner. Moreover, compound 81 induced lung cancer cells death by inhibiting NF-κB signaling pathway, and activated the JNK-mitochondrial apoptotic pathway by increasing reactive oxygen species (ROS) generation resulting in apoptosis. In summary, compound 81 is a valuable candidate for anti-lung cancer therapy.

  18. Diphthamide modification of eEF2 requires a J-domain protein and is essential for normal development.

    PubMed

    Webb, Tom R; Cross, Sally H; McKie, Lisa; Edgar, Ruth; Vizor, Lucie; Harrison, Jackie; Peters, Jo; Jackson, Ian J

    2008-10-01

    The intracellular target of diphtheria toxin is a modified histidine residue, diphthamide, in the translation elongation factor, eEF2 (also known as EFT1). This enigmatic modification occurs in all eukaryotes and is produced in yeast by the action of five gene products, DPH1 to DPH5. Sequence homologues of these genes are present in all sequenced eukaryotic genomes and, in higher eukaryotes, there is functional evidence for DPH1, DPH2, DPH3 and DPH5 acting in diphthamide biosynthesis. We identified a mouse that was mutant for the remaining gene, Dph4. Cells derived from homozygous mutant embryos lacked the diphthamide modification of eEF2 and were resistant to killing by diphtheria toxin. Reporter-tagged DPH4 protein localized to the cytoskeleton, in contrast to the localization of DPH1 and consistent with evidence that DPH4 is not part of a proposed complex containing DPH1, DPH2 and DPH3. Mice that were homozygous for the mutation were retarded in growth and development, and almost always die before birth. Those that survive long enough had preaxial polydactyly, a duplication of digit 1 of the hind foot. This same defect has been seen in embryos that were homozygous for mutation of DPH1, suggesting that lack of diphthamide on eEF2 could result in translational failure of specific proteins, rather than a generalized translation downregulation.

  19. The 51-63 base pair of tRNA confers specificity for binding by EF-Tu.

    PubMed

    Sanderson, Lee E; Uhlenbeck, Olke C

    2007-06-01

    Elongation factor Tu (EF-Tu) exhibits significant specificity for the different elongator tRNA bodies in order to offset its variable affinity to the esterified amino acid. Three X-ray cocrystal structures reveal that while most of the contacts with the protein involve the phosphodiester backbone of tRNA, a single hydrogen bond is observed between the Glu390 and the amino group of a guanine in the 51-63 base pair in the T-stem of tRNA. Here we show that the Glu390Ala mutation of Thermus thermophilus EF-Tu selectively destabilizes binding of those tRNAs containing a guanine at either position 51 or 63 and that mutagenesis of the 51-63 base pair in several tRNAs modulates their binding affinities to EF-Tu. A comparison of Escherichia coli tRNA sequences suggests that this specificity mechanism is conserved across the bacterial domain. While this contact is an important specificity determinant, it is clear that others remain to be identified.

  20. How EF-Tu can contribute to efficient proofreading of aa-tRNA by the ribosome

    PubMed Central

    Noel, Jeffrey K.; Whitford, Paul C.

    2016-01-01

    It has long been recognized that the thermodynamics of mRNA–tRNA base pairing is insufficient to explain the high fidelity and efficiency of aminoacyl-tRNA (aa-tRNA) selection by the ribosome. To rationalize this apparent inconsistency, Hopfield proposed that the ribosome may improve accuracy by utilizing a multi-step kinetic proofreading mechanism. While biochemical, structural and single-molecule studies have provided a detailed characterization of aa-tRNA selection, there is a limited understanding of how the physical–chemical properties of the ribosome enable proofreading. To this end, we probe the role of EF-Tu during aa-tRNA accommodation (the proofreading step) through the use of energy landscape principles, molecular dynamics simulations and kinetic models. We find that the steric composition of EF-Tu can reduce the free-energy barrier associated with the first step of accommodation: elbow accommodation. We interpret this effect within an extended kinetic model of accommodation and show how EF-Tu can contribute to efficient and accurate proofreading. PMID:27796304

  1. How EF-Tu can contribute to efficient proofreading of aa-tRNA by the ribosome

    NASA Astrophysics Data System (ADS)

    Noel, Jeffrey K.; Whitford, Paul C.

    2016-10-01

    It has long been recognized that the thermodynamics of mRNA-tRNA base pairing is insufficient to explain the high fidelity and efficiency of aminoacyl-tRNA (aa-tRNA) selection by the ribosome. To rationalize this apparent inconsistency, Hopfield proposed that the ribosome may improve accuracy by utilizing a multi-step kinetic proofreading mechanism. While biochemical, structural and single-molecule studies have provided a detailed characterization of aa-tRNA selection, there is a limited understanding of how the physical-chemical properties of the ribosome enable proofreading. To this end, we probe the role of EF-Tu during aa-tRNA accommodation (the proofreading step) through the use of energy landscape principles, molecular dynamics simulations and kinetic models. We find that the steric composition of EF-Tu can reduce the free-energy barrier associated with the first step of accommodation: elbow accommodation. We interpret this effect within an extended kinetic model of accommodation and show how EF-Tu can contribute to efficient and accurate proofreading.

  2. A conserved P-loop anchor limits the structural dynamics that mediate nucleotide dissociation in EF-Tu.

    PubMed

    Mercier, Evan; Girodat, Dylan; Wieden, Hans-Joachim

    2015-01-08

    The phosphate-binding loop (P-loop) is a conserved sequence motif found in mononucleotide-binding proteins. Little is known about the structural dynamics of this region and its contribution to the observed nucleotide binding properties. Understanding the underlying design principles is of great interest for biomolecular engineering applications. We have used rapid-kinetics measurements in vitro and molecular dynamics (MD) simulations in silico to investigate the relationship between GTP-binding properties and P-loop structural dynamics in the universally conserved Elongation Factor (EF) Tu. Analysis of wild type EF-Tu and variants with substitutions at positions in or adjacent to the P-loop revealed a correlation between P-loop flexibility and the entropy of activation for GTP dissociation. The same variants demonstrate more backbone flexibility in two N-terminal amino acids of the P-loop during force-induced EF-Tu · GTP dissociation in Steered Molecular Dynamics simulations. Amino acids Gly18 and His19 are involved in stabilizing the P-loop backbone via interactions with the adjacent helix C. We propose that these P-loop/helix C interactions function as a conserved P-loop anchoring module and identify the presence of P-loop anchors within several GTPases and ATPases suggesting their evolutionary conservation.

  3. MexEF-OprN efflux pump exports the Pseudomonas quinolone signal (PQS) precursor HHQ (4-hydroxy-2-heptylquinoline).

    PubMed

    Lamarche, Martin G; Déziel, Eric

    2011-01-01

    Bacterial cells have evolved the capacity to communicate between each other via small diffusible chemical signals termed autoinducers. Pseudomonas aeruginosa is an opportunistic pathogen involved, among others, in cystic fibrosis complications. Virulence of P. aeruginosa relies on its ability to produce a number of autoinducers, including 4-hydroxy-2-alkylquinolines (HAQ). In a cell density-dependent manner, accumulated signals induce the expression of multiple targets, especially virulence factors. This phenomenon, called quorum sensing, promotes bacterial capacity to cause disease. Furthermore, P. aeruginosa possesses many multidrug efflux pumps conferring adaptive resistance to antibiotics. Activity of some of these efflux pumps also influences quorum sensing. The present study demonstrates that the MexEF-OprN efflux pump modulates quorum sensing through secretion of a signalling molecule belonging to the HAQ family. Moreover, activation of MexEF-OprN reduces virulence factor expression and swarming motility. Since MexEF-OprN can be activated in infected hosts even in the absence of antibiotic selective pressure, it could promote establishment of chronic infections in the lungs of people suffering from cystic fibrosis, thus diminishing the immune response to virulence factors. Therapeutic drugs that affect multidrug efflux pumps and HAQ-mediated quorum sensing would be valuable tools to shut down bacterial virulence.

  4. BE, DO, and Modal Auxiliaries of 3-Year-Old African American English Speakers

    ERIC Educational Resources Information Center

    Newkirk-Turner, Brandi L.; Oetting, Janna B.; Stockman, Ida J.

    2014-01-01

    Purpose: This study examined African American English--speaking children's use of BE, DO, and modal auxiliaries. Method: The data were based on language samples obtained from 48 three-year-olds. Analyses examined rates of marking by auxiliary type, auxiliary surface form, succeeding element, and syntactic construction and by a number of child…

  5. Sustaining Research-Based Practices in Reading: A 3-Year Follow-Up.

    ERIC Educational Resources Information Center

    Klingner, Janette K.; Vaughn, Sharon; Hughes, Marie Tejero; Arguelles, Maria Elena

    1999-01-01

    Three years after seven teachers had participated in an intensive year-long professional development experience in three multilevel reading practices (partner reading, collaborative strategic reading, and making words), all but one teacher sustained one or more of the practices at a high rate, as determined by classroom observation and interviews.…

  6. Identification of DeltaEF1 as a novel target that is negatively regulated by LMO2 in T-cell leukemia.

    PubMed

    Sun, Wei; Yang, Shuang; Shen, Wenwen; Li, Huihui; Gao, Yang; Zhu, Tian-Hui

    2010-12-01

    The lmo2 gene is a specific oncogene in T-cell leukemia, for its ectopic expression causes both increased pro-T-cell proliferation and differentiation arrest, leading to the onset of leukemia. Notably, DeltaEF1 (also known as ZEB1), a member of zinc finger-homeodomain family transcription factor, also exhibits crucial function in promoting T-cell differentiation. In this study, we found that DeltaEF1 was positively regulated by T-lineage-specific transcriptional regulator GATA3, while ectopically expressed LMO2 targeted to DeltaEF1 promoter by interaction with GATA3 and inhibited DeltaEF1 expression in transcriptional level. Moreover, LMO2 interacted with the N-terminal zinc finger domain of DeltaEF1 protein and inhibited its positive transcriptional regulatory function by this interaction. Taken together, our findings revealed that ectopically expressed LMO2 impaired the function of DeltaEF1 in both transcriptional and protein levels and identified DeltaEF1 as a novel pathogenic target of LMO2 in T-cell leukemia.

  7. Characterization of the 1st and 2nd EF-hands of NADPH oxidase 5 by fluorescence, isothermal titration calorimetry, and circular dichroism

    PubMed Central

    2012-01-01

    Background Superoxide generated by non-phagocytic NADPH oxidases (NOXs) is of growing importance for physiology and pathobiology. The calcium binding domain (CaBD) of NOX5 contains four EF-hands, each binding one calcium ion. To better understand the metal binding properties of the 1st and 2nd EF-hands, we characterized the N-terminal half of CaBD (NCaBD) and its calcium-binding knockout mutants. Results The isothermal titration calorimetry measurement for NCaBD reveals that the calcium binding of two EF-hands are loosely associated with each other and can be treated as independent binding events. However, the Ca2+ binding studies on NCaBD(E31Q) and NCaBD(E63Q) showed their binding constants to be 6.5 × 105 and 5.0 × 102 M-1 with ΔHs of -14 and -4 kJ/mol, respectively, suggesting that intrinsic calcium binding for the 1st non-canonical EF-hand is largely enhanced by the binding of Ca2+ to the 2nd canonical EF-hand. The fluorescence quenching and CD spectra support a conformational change upon Ca2+ binding, which changes Trp residues toward a more non-polar and exposed environment and also increases its α-helix secondary structure content. All measurements exclude Mg2+-binding in NCaBD. Conclusions We demonstrated that the 1st non-canonical EF-hand of NOX5 has very weak Ca2+ binding affinity compared with the 2nd canonical EF-hand. Both EF-hands interact with each other in a cooperative manner to enhance their Ca2+ binding affinity. Our characterization reveals that the two EF-hands in the N-terminal NOX5 are Ca2+ specific. Graphical abstract PMID:22490336

  8. The effects of prenatal methamphetamine exposure on childhood growth patterns from birth to 3 years of age.

    PubMed

    Zabaneh, Rachel; Smith, Lynne M; LaGasse, Linda L; Derauf, Chris; Newman, Elana; Shah, Rizwan; Arria, Amelia; Huestis, Marilyn; Haning, William; Strauss, Arthur; Della Grotta, Sheri; Dansereau, Lynne M; Lin, Hai; Neal, Charles; Lester, Barry M

    2012-03-01

    We examined the effects of prenatal methamphetamine (MA) exposure on growth parameters from birth to age 3 years. The 412 subjects included (n = 204 exposed) were enrolled at birth in the Infant Development, Environment and Lifestyle study, a longitudinal study assessing the effects of prenatal MA exposure on childhood outcomes. Individual models were used to examine the effects of prenatal MA exposure on weight, head circumference, height, and weight-for-length growth trajectories. After adjusting for covariates, height trajectory was lower in the exposed versus the comparison children (p = 0.021) over the first 3 years of life. Both groups increased height on average by 2.27 cm per month by age 3 years. In term subjects, MA exposure was also associated with a lower height trajectory (p = 0.034), with both the exposed and comparison groups gaining 2.25 cm per month by age 3 years. There was no difference in weight, head circumference, or weight-for-length growth trajectories between the comparison and the exposed groups. Children exposed prenatally to MA have a modest decrease in height growth trajectory during the first 3 years of life with no observed difference in weight, head circumference, or weight-for-length trajectories.

  9. Structure–Function Analysis of the Two-Peptide Bacteriocin Plantaricin EF

    PubMed Central

    2016-01-01

    Plantaricin EF is a two-peptide bacteriocin that depends on the complementary action of two different peptides (PlnE and PlnF) to function. The structures of the individual peptides have previously been analyzed by nuclear magnetic resonance spectroscopy (Fimland, N. et al. (2008), Biochim. Biophys. Acta1784, 1711−171918555030), but the bacteriocin structure and how the two peptides interact have not been determined. All two-peptide bacteriocins identified so far contain GxxxG motifs. These motifs, together with GxxxG-like motifs, are known to mediate helix–helix interactions in membrane proteins. We have mutated all GxxxG and GxxxG-like motifs in PlnE and PlnF in order to determine if any of these motifs are important for antimicrobial activity and thus possibly for interactions between PlnE and PlnF. Moreover, the aromatic amino acids Tyr and Trp in PlnE and PlnF were substituted, and four fusion polypeptides were constructed in order to investigate the relative orientation of PlnE and PlnF in target cell membranes. The results obtained with the fusion polypeptides indicate that PlnE and PlnF interact in an antiparallel manner and that the C-terminus of PlnE and N-terminus of PlnF are on the outer part of target cell membranes and the N-terminus of PlnE and C-terminus of PlnF are on the inner part. The preference for an aromatic residue at position 6 in PlnE suggests a positioning of this residue in or near the membrane interface on the cells inside. Mutations in the GxxxG motifs indicate that the G5xxxG9 motif in PlnE and the S26xxxG30 motif in PlnF are involved in helix–helix interactions. Atomistic molecular dynamics simulation of a structural model consistent with the results confirmed the stability of the structure and its orientation in membranes. The simulation approved the anticipated interactions and revealed additional interactions that further increase the stability of the proposed structure. PMID:27538436

  10. Modulating Uranium Binding Affinity in Engineered Calmodulin EF-Hand Peptides: Effect of Phosphorylation

    PubMed Central

    Pardoux, Romain; Sauge-Merle, Sandrine; Lemaire, David; Delangle, Pascale; Guilloreau, Luc; Adriano, Jean-Marc; Berthomieu, Catherine

    2012-01-01

    To improve our understanding of uranium toxicity, the determinants of uranyl affinity in proteins must be better characterized. In this work, we analyzed the contribution of a phosphoryl group on uranium binding affinity in a protein binding site, using the site 1 EF-hand motif of calmodulin. The recombinant domain 1 of calmodulin from A. thaliana was engineered to impair metal binding at site 2 and was used as a structured template. Threonine at position 9 of the loop was phosphorylated in vitro, using the recombinant catalytic subunit of protein kinase CK2. Hence, the T9TKE12 sequence was substituted by the CK2 recognition sequence TAAE. A tyrosine was introduced at position 7, so that uranyl and calcium binding affinities could be determined by following tyrosine fluorescence. Phosphorylation was characterized by ESI-MS spectrometry, and the phosphorylated peptide was purified to homogeneity using ion-exchange chromatography. The binding constants for uranyl were determined by competition experiments with iminodiacetate. At pH 6, phosphorylation increased the affinity for uranyl by a factor of ∼5, from Kd = 25±6 nM to Kd = 5±1 nM. The phosphorylated peptide exhibited a much larger affinity at pH 7, with a dissociation constant in the subnanomolar range (Kd = 0.25±0.06 nM). FTIR analyses showed that the phosphothreonine side chain is partly protonated at pH 6, while it is fully deprotonated at pH 7. Moreover, formation of the uranyl-peptide complex at pH 7 resulted in significant frequency shifts of the νas(P-O) and νs(P-O) IR modes of phosphothreonine, supporting its direct interaction with uranyl. Accordingly, a bathochromic shift in νas(UO2)2+ vibration (from 923 cm−1 to 908 cm−1) was observed upon uranyl coordination to the phosphorylated peptide. Together, our data demonstrate that the phosphoryl group plays a determining role in uranyl binding affinity to proteins at physiological pH. PMID:22870263

  11. Iron overload accelerates bone loss in healthy postmenopausal women and middle-aged men: a 3-year retrospective longitudinal study.

    PubMed

    Kim, Beom-Jun; Ahn, Seong Hee; Bae, Sung Jin; Kim, Eun Hee; Lee, Seung-Hun; Kim, Hong-Kyu; Choe, Jae Won; Koh, Jung-Min; Kim, Ghi Su

    2012-11-01

    Despite extensive experimental and animal evidence about the detrimental effects of iron and its overload on bone metabolism, there have been no clinical studies relating iron stores to bone loss, especially in nonpathologic conditions. In the present study, we performed a large longitudinal study to evaluate serum ferritin concentrations in relation to annualized changes in bone mineral density (BMD) in healthy Koreans. A total of 1729 subjects (940 postmenopausal women and 789 middle-aged men) aged 40 years or older who had undergone comprehensive routine health examinations with an average 3 years of follow-up were enrolled. BMD in proximal femur sites (ie, the total femur, femur neck, and trochanter) was measured with dual-energy X-ray absorptiometry using the same equipment at baseline and follow-up. The mean age of women and men in this study was 55.8 ± 6.0 years and 55.5 ± 7.8 years, respectively, and serum ferritin levels were significantly higher in men than in women (p < 0.001). The overall mean annualized rates of bone loss in the total femur, femur neck, and trochanter were -1.14%/year, -1.17%/year, and -1.51%/year, respectively, in women, and -0.27%/year, -0.34%/year, and -0.41%/year, respectively, in men. After adjustment for potential confounders, the rates of bone loss in all proximal femur sites in both genders were significantly accelerated in a dose-response fashion across increasing ferritin quartile categories (p for trend = 0.043 to <0.001). Consistently, compared with subjects in the lowest ferritin quartile category, those in the third and/or highest ferritin quartile category showed significantly faster bone loss in the total femur and femur neck in both genders (p = 0.023 to <0.001). In conclusion, these data provide the first clinical evidence that increased total body iron stores could be an independent risk factor for accelerated bone loss, even in healthy populations.

  12. A 3-year randomized clinical trial evaluating two different bonded posterior restorations: Amalgam versus resin composite

    PubMed Central

    Kemaloglu, Hande; Pamir, Tijen; Tezel, Huseyin

    2016-01-01

    Objective: To compare the performance and postoperative sensitivity of a posterior resin composite with that of bonded amalgam in 40 (n = 20) large sized cavities and to evaluate whether resin composite could be an alternative for bonded amalgam. Materials and Methods: This was a randomized clinical trial. Twenty patients in need of at least two posterior restorations were recruited. Authors randomly assigned one half of the restorations to receive bonded amalgam and the other half to composite restorations. Forty bonded amalgams (n = 20) and composites (n = 20) were evaluated for their performance on modified-US Public Health Service criteria and postoperative sensitivity using visual analogue scale (VAS) for 36-months. Results: Success rate of this study was 100%. First clinical alterations were rated as Bravo after 1 year in marginal discoloration, marginal adaptation, anatomical form, and surface roughness for both amalgam and composite. At the 3rd year, overall “Bravo” rated restorations were 12 for bonded amalgam and 13 for resin composites. There were no significant differences among the VAS scores of composites and bonded amalgams for all periods (P > 0.05) except for the comparisons at the 3rd year evaluation (P < 0.05). Conclusions: Within the limitation of this study, both resin composite and bonded amalgam were clinically acceptable. Postoperative sensitivity results tend to decrease more in composite restorations rather than amalgams. Therefore, it was concluded that posterior resin composite can be used even in large sized cavities. PMID:27011734

  13. Evaluation of bacteremias in a Turkish university hospital: 3-year outcomes.

    PubMed

    Demirdal, Tuna; Demirturk, Nese; Cetinkaya, Zafer; Tufan, Gulnihal

    2007-01-01

    In this retrospective study, the investigators examined blood cultures from patients that had been diagnosed with bacteremias over a 3-y period. The study was conduced at Kocatepe University Hospital (Middle Anatolia, Turkey). Blood samples that arrived at the university's microbiology laboratory between 2002 and 2005 were evaluated retrospectively. These samples were classified as contamination, false positivity, community-acquired bacteremia (CAB), or hospital-acquired bacteremia (HAB). Patient age and sex, foci of bacteremia, present comorbidities, predisposing factors, pathogens, and mortality rates were evaluated. A total of 1783 blood cultures that had been drawn from 1441 patients during this 3-y period were examined retrospectively. Of 354 positive isolates, 61 (17.2%) were CABs and 293 (82.8%) were HABs. In HABs, the most commonly isolated microorganisms were Staphylococcus aureus (37.5%), coagulase-negative staphylococci (29.7%), and Escherichia coli (10.2%); in CABs, the most commonly isolated microorganisms were S aureus (29.5%), Brucella spp (26.2%), and E coli (24.6%). Crude mortality rates were determined to be 15.2% for HABs and 12.7% for CABs. This study yielded data on the most common foci of bacteremia, microbiologic factors, and the epidemiology associated with HABs and CABs. It is hoped that these data will enhance empirical antibiotic therapeutic approaches, thereby preventing delays in treatment and decreasing mortality rates associated with bacteremias.

  14. Sticking out and fitting in: culture-specific predictors of 3-year-olds' autobiographical memories during joint reminiscing.

    PubMed

    Schröder, Lisa; Kärtner, Joscha; Keller, Heidi; Chaudhary, Nandita

    2012-12-01

    The present study investigates the relationship between mother-child interaction styles with 19 months and children's autobiographical memory with 3 years of age in two cultural contexts: New Delhi, India (n = 25) and Berlin, Germany (n = 33). Results demonstrate similarities as well as culture specificities. In both contexts, maternal elaborations during reminiscing were related to children's memory contributions. Over time, maternal support for toddlers' self-expression during free play at 19 months predicted their children's memory elaborations at 3 years in the Berlin context. In the Delhi context, toddlers' willingness to carry out their mothers' requests at 19 months predicted their memory elaborations at 3 years. These results suggest different motivational bases underlying children's autobiographical memory contributions during mother-child reminiscing related to different cultural orientations.

  15. Posttraumatic stress disorder after motor vehicle accidents: 3-year follow-up of a prospective longitudinal study.

    PubMed

    Mayou, R A; Ehlers, A; Bryant, B

    2002-06-01

    The paper presents a 3-year follow-up of a prospective longitudinal study of posttraumatic stress disorder (PTSD) after motor vehicle accidents (J. Abnormal Psychol., 107 (1998) 508). Participants were 546 patients who had been assessed when attending an emergency clinic shortly after a motor vehicle accident, and at 3 months and 1 year afterwards. The prevalence of posttraumatic stress disorder PTSD at 3 years was 11%. Maintaining psychological factors, i.e. negative interpretation of intrusions, rumination, thought suppression and anger cognitions, were important in predicting the persistence of PTSD at 3 years, as were persistent health and financial problems after the accident. Other predictors were female sex, hospital admission for injuries, perceived threat and dissociation during the accident, and litigation.

  16. Cognitive and Psychiatric Predictors to Psychosis in Velocardiofacial Syndrome: A 3-year follow-up study

    PubMed Central

    Antshel, Kevin M.; Shprintzen, Robert; Fremont, Wanda; Higgins, Anne Marie; Faraone, Stephen V.; Kates, Wendy R.

    2010-01-01

    Objective To predict prodromal psychosis in adolescents with velocardiofacial syndrome (VCFS). Method 70 youth with VCFS, 27 siblings of youth with VCFS and 25 community controls were followed from childhood (Mean age = 11.8 years) into mid-adolescence (mean age 15.0 years). Psychological tests measuring intelligence, academic achievement, learning/memory, attention and executive functioning as well as measures of parent and clinician ratings of child psychiatric functioning were completed at both time points. Results Major depressive disorder, oppositional defiant disorder and generalized anxiety disorder diagnoses increased in the VCFS sample. With very low false positives, the best predictor of adolescent prodromal psychotic symptoms was parent ratings of childhood odd/eccentric symptoms and child performance on a measure of executive functioning, the Wisconsin Card Sorting Test. Conclusions Similar to the non-VCFS prodromal psychosis literature, a combination of cognitive and psychiatric variables appears to predict psychosis in adolescence. A child with VCFS who screens positive is noteworthy and demands clinical attention. PMID:20410726

  17. 3-Year follow-up after Lasik: assessing the risk factors for retreatment.

    PubMed

    Valdez-García, Jorge E; Hernandez-Camarena, Julio C; Martínez-Muñoz, Rosa

    2016-02-01

    The purpose of this study was to evaluate the correlation of important risk factors for LASIK retreatment and the retreatment rate. A retrospective cohort study was conducted. Records of patients who underwent LASIK between January 2011 and January 2012 at the Zambrano-Hellion Medical Center, Tec de Monterrey (México), and posteriorly underwent LASIK retreatment were identified and risk factors to receive retreatment were assessed using relative risk. Main outcomes were retreatment rate, risk factors for retreatment, and uncorrected distance visual acuity (UDVA). 482 eyes from 241 patients were available for a 36-month follow-up analysis. 68.5 % had primary myopic LASIK; 37 % were ≤ 2 diopters (D), 52 % were > 2 and < 6 D, and 11 % were ≥ 6 D of myopia. 31.5 % of the eyes had hyperopic LASIK. Retreatment was performed in 6.85 % eyes. Myopia > 6 D (RR 4.13), hyperopic refraction (RR 3.18), and age > 40 (RR 3.07) were the most important risk factors for retreatment (P = 0.004, P = 0.007, P = 0.006, respectively). UDVA was ≥ 20/40 in 92.1 % and ≥ 20/20 in 81.6 % of the retreated eyes and 82 % of the eyes within ± 0.50 D of target refraction. Increasing degrees of myopia, followed by hyperopic refraction, and age were the most important associated factors to retreatment. LASIK retreatment was safe and effective.

  18. Evolution of EF-hand calcium-modulated proteins. III. Exon sequences confirm most dendrograms based on protein sequences: calmodulin dendrograms show significant lack of parallelism

    NASA Technical Reports Server (NTRS)

    Nakayama, S.; Kretsinger, R. H.

    1993-01-01

    In the first report in this series we presented dendrograms based on 152 individual proteins of the EF-hand family. In the second we used sequences from 228 proteins, containing 835 domains, and showed that eight of the 29 subfamilies are congruent and that the EF-hand domains of the remaining 21 subfamilies have diverse evolutionary histories. In this study we have computed dendrograms within and among the EF-hand subfamilies using the encoding DNA sequences. In most instances the dendrograms based on protein and on DNA sequences are very similar. Significant differences between protein and DNA trees for calmodulin remain unexplained. In our fourth report we evaluate the sequences and the distribution of introns within the EF-hand family and conclude that exon shuffling did not play a significant role in its evolution.

  19. Domain motions of EF-G bound to the 70S ribosome: insights from a hand-shaking between multi-resolution structures.

    PubMed Central

    Wriggers, W; Agrawal, R K; Drew, D L; McCammon, A; Frank, J

    2000-01-01

    Molecular modeling and information processing techniques were combined to refine the structure of translocase (EF-G) in the ribosome-bound form against data from cryoelectron microscopy (cryo-EM). We devised a novel multi-scale refinement method based on vector quantization and force-field methods that gives excellent agreement between the flexibly docked structure of GDP. EF-G and the cryo-EM density map at 17 A resolution. The refinement reveals a dramatic "induced fit" conformational change on the 70S ribosome, mainly involving EF-G's domains III, IV, and V. The rearrangement of EF-G's structurally preserved regions, mediated and guided by flexible linkers, defines the site of interaction with the GTPase-associated center of the ribosome. PMID:10969026

  20. eEF1A mediates the nuclear export of SNAG-containing proteins via the Exportin5-aminoacyl-tRNA complex.

    PubMed

    Mingot, José Manuel; Vega, Sonia; Cano, Amparo; Portillo, Francisco; Nieto, M Angela

    2013-11-14

    Exportin5 mediates the nuclear export of double-stranded RNAs, including pre-microRNAs, adenoviral RNAs, and tRNAs. When tRNAs are aminoacylated, the Exportin5-aminoacyl (aa)-tRNA complex recruits and coexports the translation elongation factor eEF1A. Here, we show that eEF1A binds to Snail transcription factors when bound to their main target, the E-cadherin promoter, facilitating their export to the cytoplasm in association with the aa-tRNA-Exportin5 complex. Snail binds to eEF1A through the SNAG domain, a protein nuclear export signal present in several transcription factor families, and this binding is regulated by phosphorylation. Thus, we describe a nuclear role for eEF1A and provide a mechanism for protein nuclear export that attenuates the activity of SNAG-containing transcription factors.

  1. The impact of spina bifida on development across the first 3 years.

    PubMed

    Lomax-Bream, Laura E; Barnes, Marcia; Copeland, Kim; Taylor, Heather B; Landry, Susan H

    2007-01-01

    Early cognitive, motor, and language skills were evaluated in 165 children, 91 with Spina Bifida (SB) and 74 developing typically. Assessments were given at 5 time points (6, 12, 18, 24, and 36 months of age). Three latent growth curve models were conducted to evaluate the development of these early skills, with social economic status and etiology as predictors of growth. Lesion level and shunting effects were included for group comparison. Children with SB exhibited lower levels of functioning in all areas, with slower rates of growth in cognition and language, but more acceleration in growth of motor skills. The impact of lesion level and shunting significantly related to growth in cognition and motor skills but not in language.

  2. Skipping breakfast and less exercise are risk factors for bone loss in young Japanese adults: a 3-year follow-up study.

    PubMed

    Nagata, Keiji; Yoshida, Munehito; Ishimoto, Yuyu; Hashizume, Hiroshi; Yamada, Hiroshi; Yoshimura, Noriko

    2014-07-01

    Although bone loss contributes to osteoporosis (OP) in the elderly, little is known about changes in bone mineral density (BMD) in young adults that lead to bone loss. Here, we evaluated the rate of bone change and risk factors for bone loss in young men and women using data from a 3-year prospective study of Japanese medical students. The study included a self-administrated questionnaire survey, anthropometric measurements, and BMD measurements of the spine (L2-L4) and femoral neck (FN). After 3 years, the BMD of the participants was again measured at the same sites. In all, 458 students (95.4 %; 298 men and 160 women; age range, 18-29 years; mean age, 20.2 years) completed both the baseline and follow-up surveys. The mean L2-L4 BMD value at baseline increased significantly within 3 years. This tendency was also observed for the FN in men but not in women. The annual changes at L2-L4 were 1.78 % in men and 0.97 % in women per year; those for FN were 1.08 % in men and 0.08 % in women per year. However, 20.3 % and 38.5 % of the total freshmen lost BMD in the lumbar spine and FN, respectively. After adjustment for age and body mass index, logistic regression analysis revealed that bone loss in men at L2-L4 at the baseline was affected by skipping breakfast. In contrast, exercise (>2 h/week) increased lumbar spine BMD in both genders. These findings indicate that breakfast and exercise are important for maintaining BMD in young men and women.

  3. Qualitative Feasibility of Using Three Accelerometers With 2-3-Year-Old Children and Both Parents

    ERIC Educational Resources Information Center

    Costa, Silvia; Barber, Sally E.; Griffiths, Paula L.; Cameron, Noël; Clemes, Stacy A.

    2013-01-01

    Purpose: This study assessed mothers' opinions about the feasibility and acceptability of using the ActiGraph GT3X+, Actiheart, and activPAL3 with their 2- to 3-year-old children, as well as with themselves and their husbands/partners, for an 8-day period. Method: Six focus groups were run with Pakistani and White British mothers ("n" =…

  4. The Internal Validity and Acceptability of the Danish SI-3: A Language-Screening Instrument for 3-Year-Olds

    ERIC Educational Resources Information Center

    Bleses, Dorthe; Vach, Werner; Jorgensen, Rune N.; Worm, Torben

    2010-01-01

    Purpose: To document the development of a new parent- and day care-administered screening instrument (the Screening Instrument for 3-Year-Olds [SI-3]) to be used in a newly implemented, educationally motivated population language screening in Denmark. The authors investigated whether the basic principles of the SI-3 were working satisfactorily and…

  5. Professional Learning Communities in Partnership: A 3-Year Journey of Action and Advocacy to Bridge the Achievement Gap

    ERIC Educational Resources Information Center

    Hoffman, Patricia; Dahlman, Anne; Zierdt, Ginger

    2009-01-01

    This article details a strategic planning model and concurrent 3-year research study focusing on the benefits of preK-16 professional development school learning communities for the participating preK-16 educational leaders in a midwestern school-university partnership network. Results of the study, along with the strategic plan's success at…

  6. Emotion Situation Knowledge and Autobiographical Memory in Chinese, Immigrant Chinese, and European American 3-Year-Olds

    ERIC Educational Resources Information Center

    Wang, Qi; Hutt, Rachel; Kulkofsky, Sarah; McDermott, Melissa; Wei, Ruohong

    2006-01-01

    This study examined the influence of children's emotion situation knowledge (EK) on their autobiographical memory ability at both group and individual levels. Native Chinese, Chinese immigrant, and European American 3-year-old children participated (N = 189). During a home visit, children recounted 2 personal memories of recent, 1-time events with…

  7. Intergenerational Transmission of Warm-Sensitive-Stimulating Parenting: A Prospective Study of Mothers and Fathers of 3-Year-Olds

    ERIC Educational Resources Information Center

    Belsky, Jay; Jaffee, Sara R.; Sligo, Judith; Woodward, Lianne; Silva, Phil A.

    2005-01-01

    More than 200 New Zealand men and women studied repeatedly since age 3 were videotaped interacting with their own 3-year-old children to determine (a) whether childrearing and family climate experienced in 3 distinct developmental periods while growing up (i.e., early childhood, middle childhood, early adolescence) predicted parenting and (b)…

  8. Eudaimonic Growth: Narrative Growth Goals Predict Increases in Ego Development and Subjective Well-Being 3 Years Later

    ERIC Educational Resources Information Center

    Bauer, Jack J.; McAdams, Dan P.

    2010-01-01

    We examine (a) the normative course of eudaimonic well-being in emerging adulthood and (b) whether people's narratives of major life goals might prospectively predict eudaimonic growth 3 years later. We define eudaimonic growth as longitudinal increases in eudaimonic well-being, which we define as the combination of psychosocial maturity and…

  9. Combined Individual Cognitive Behavior Therapy and Parent Training for Childhood Depression: 2- to 3-Year Follow-up

    ERIC Educational Resources Information Center

    Eckshtain, Dikla; Gaynor, Scott T.

    2013-01-01

    Fourteen children with significant depressive symptoms from an open clinical trial of Primary and Secondary Control Enhancement Training augmented with Caregiver-Child Relationship Enhancement Training, participated in a 2- to 3-year follow-up assessment. The results suggested that the significant decreases in depressive symptoms observed at…

  10. 1 to 3-Year-Old Children in Day Care Centres in Finland: An Overview of Eight Doctoral Dissertations

    ERIC Educational Resources Information Center

    Hannikainen, Maritta

    2010-01-01

    This article gives a general picture of the policy and main structural features of early childhood education services for the younger children in Finland. It also provides an overview of the research on 1 to 3-year-old children in day care centres carried out in Finland during the last 15 years, the focus being on a review of all the eight…

  11. Aligning Teaching to Learning: A 3-Year Study Examining the Embedding of Language and Argumentation into Elementary Science Classrooms

    ERIC Educational Resources Information Center

    Hand, Brian; Norton-Meier, Lori A.; Gunel, Murat; Akkus, Recai

    2016-01-01

    How can classrooms become communities of inquiry that connect intellectually challenging science content with language-based activities (opportunities to talk, listen, read, and write) especially in settings with diverse populations? This question guided a 3-year mixed-methods research study using the Science Writing Heuristic (SWH) approach in…

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

    PubMed Central

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

    2016-01-01

    The elongation factor 2 kinase (eEF2K), likewise known as CaMKIII, has been demonstrated to be involved in antidepressant responses of NMDA receptor antagonists. Even so, it remains open whether direct inhibition of eEF2K without altering up-stream or other signaling pathways affects hippocampal synaptic transmission and neuronal network synchrony. Inhibition of eEF2K by the selective and potent eEF2K inhibitor A-484954 induced a fast pre-synaptically mediated enhancement of synaptic transmission and synchronization of neural network activity. The eEF2K-inhibition mediated potentiation of synaptic transmission of hippocampal CA1 neurons is most notably independent of protein synthesis and does not rely on protein kinase C, protein kinase A or mitogen-activated protein kinase (MAPK)/extracellular signal-regulated protein kinase 1/2. Moreover, the strengthening of synaptic transmission in the response to the inhibition of eEF2K was strongly attenuated by the inhibition of p38 MAPK. In addition, we show the involvement of barium-sensitive and more specific the TWIK-related potassium-1 (TREK-1) channels in the eEF2K-inhibition mediated potentiation of synaptic transmission. These findings reveal a novel pathway of eEF2K mediated regulation of hippocampal synaptic transmission. Further research is required to study whether such compounds could be beneficial for the development of mood disorder treatments with a fast-acting antidepressant response. PMID:27826228

  13. The First Year Inventory: A Longitudinal Follow-Up of 12-Month-Old to 3-Year-Old Children

    ERIC Educational Resources Information Center

    Turner-Brown, Lauren M.; Baranek, Grace T.; Reznick, J Steven; Watson, Linda R.; Crais, Elizabeth R.

    2013-01-01

    The First Year Inventory is a parent-report measure designed to identify 12-month-old infants at risk for autism spectrum disorder. First Year Inventory taps behaviors that indicate risk in the developmental domains of sensory--regulatory and social--communication functioning. This longitudinal study is a follow-up of 699 children at 3 years of…

  14. An infant oral health programme in Goiânia-GO, Brazil: results after 3 years of establishment.

    PubMed

    Pereira, Marina Batista Borges; do Carmo Matias Freire, Maria

    2004-01-01

    The objective of this study was to describe the outcomes of an infant oral health programme 3 years after implementation, a programme focused on health education for parents and caries prevention methods for children in a baby clinic. A retrospective cohort study was carried out. The setting was the Infant Oral Health Programme developed at the baby clinic of the State Department of Health, Goiânia-GO, Brazil. The sample comprised 100 children who entered the programme from birth to 12 months and were followed for 2 to 3 years. Variables investigated were caries experience, caries risk, and children's behaviour in the dental clinic. The number of children with caries experience was 1 at the initial visit and 8 after the follow-up. There was a dramatic decrease in the number of children in the high risk group, from 51% at the initial visit to only 1% after 2 to 3 years. Children's behaviour in the dental clinic was according to their psychological development. It was concluded that the Infant Oral Health Programme in Goiânia showed positive outcomes after 3 years of establishment. Further investigations should evaluate the cost-benefit, as well as the effectiveness of the procedures used in the programme.

  15. Determinants of Imitation of Hand-to-Body Gestures in 2- and 3-Year-Old Children

    ERIC Educational Resources Information Center

    Erjavec, Mihela; Horne, Pauline J.

    2008-01-01

    Twenty children, ten 2-year-olds and ten 3-year-olds, participated in an AB procedure. In the baseline phase, each child was trained the same four matching relations to criterion under intermittent reinforcement. During the subsequent imitation test, the experimenter modeled a total of 20 target gestures (six trials each) interspersed with…

  16. Results of a 3-Year, Nutrition and Physical Activity Intervention for Children in Rural, Low-Socioeconomic Status Elementary Schools

    ERIC Educational Resources Information Center

    King, Kristi McClary; Ling, Jiying

    2015-01-01

    Improving children's nutrition and physical activity have become priorities in the United States. This quasi-experimental study evaluated the longitudinal effects of a 3-year, school-based, health promotion intervention (i.e. nutrition and physical education, classroom physical activity, professional development and health promotion for teachers…

  17. Effects of treatment with bimatoprost 0.03% for 3 years in patients with normal-tension glaucoma

    PubMed Central

    Inoue, Kenji; Shiokawa, Minako; Fujimoto, Takayuki; Tomita, Goji

    2014-01-01

    Purpose To evaluate the effects of bimatoprost 0.03% single treatment for 3 years on intraocular pressure (IOP) and visual field performance. Methods We monitored the IOP of 62 patients with normal-tension glaucoma every 1–3 months. The Humphrey visual field test was performed every 6 months after treatment and the results obtained were compared to those before treatment. In addition, visual field performance was evaluated using trend and event analysis. Results The mean ± standard deviation (SD) of IOP after treatment with bimatoprost for 3 years (13.6±3.1 mmHg) was significantly lower than that before treatment (16.8±2.4 mmHg, P<0.0001). No change was observed in the mean deviation and pattern SD values of the Humphrey visual field before and 3 years after treatment. Worsening of visual field performance was observed in one patient (3.0%) by using trend analysis and in four patients (12.1%) by using event analysis. Treatment was discontinued in 17 patients (27.4%) because of adverse reactions. Conclusion Bimatoprost 0.03% single treatment was effective in reducing the IOP at least during the 3 years of treatment, but visual field performance worsened by 3.0%–12.1% in patients with normal-tension glaucoma. PMID:24970996

  18. Mouse pharmacokinetics and metabolism of the curcumin analog, 4-Piperidione,3,5-bis[(2-fluorophenyl)methylene]-acetate(3E,5E) (EF-24; NSC 716993)

    PubMed Central

    Reid, Joel M.; Buhrow, Sarah A.; Gilbert, Judith A.; Jia, Lee; Shoji, Mamoru; Snyder, James P.; Ames, Matthew M.

    2015-01-01

    Purpose Curcumin, a keto-enol constituent of turmeric, has in vitro and in vivo antitumor activity. However, in vivo potency is low due to poor oral absorption. The mono-carbonyl analog, 3,5-bis[(2-fluorophenyl)methylene]-4-piperidinone acetate (EF-24, NSC 716993), exhibited broad spectrum activity in the NCI anti-cancer cell line screen and potent anti-angiogenesis activity in a HUVEC cell migration assay. The purpose of this study was to characterize the preclinical pharmacology of EF-24 in mice. Methods EF-24 plasma stability, protein binding, pharmacokinetics and metabolism were characterized utilizing an LC/MS/MS assay. Results An LC/MS/MS assay that incorporated protein precipitation with methanol, reverse-phase HPLC separation under gradient elution using an aqueous methanol mobile phase containing 0.1% formic acid and positive electrospray ionization detection of the m/z 312 > 149 transition for EF-24. The assay was linear over the range 7.8-1000 nM. Plasma protein binding was > 98% with preferential binding to albumin. EF-24 plasma disposition in mice after i.v. administration of a 10 mg/kg dose was best fit to a 3-compartment open model. The terminal elimination half-life and plasma clearance values were 73.6 min and 0.482 L/min/kg, respectively. EF-24 bioavailability was 60% and 35% after oral and i.p. administration, respectively. NADPH-dependent metabolism of EF-24 loss in liver microsomal preparations yielded several metabolites consistent with EF-24 hydroxylation and reduction. PMID:24760417

  19. "No Shoes; They Walked Away?": Effects of Enhancements on Learning and Using Blissymbols by Normal 3-Year-Old Children.

    ERIC Educational Resources Information Center

    Raghavendra, Parimala; Fristoe, Macalyne

    1995-01-01

    Forty 3-year-olds learned either 12 standard Blissymbols (SBS) or their enhanced forms (EBS). Results demonstrated that the subjects learned EBS faster than SBS, remembered more EBS than SBS, did not differ in the communicative use of SBS and EBS, and were affected more negatively when presented with the untrained SBS than EBS. (Author/JDD)

  20. Malignant peripheral nerve sheath tumor of the third eyelid in a 3-year-old Rhodesian Ridgeback

    PubMed Central

    vom Hagen, Franziska; Romkes, Gwendolyna; Kershaw, Olivia; Eule, J Corinna

    2015-01-01

    Key Clinical Message A 3-year-old Rhodesian Ridgeback was presented with conjunctivitis, enlargement of the third eyelid and a dorsotemporal deviation of the right eye. A mass within the third eyelid was detected and excised. The histopathologic examination showed a malignant peripheral nerve sheath tumor, which most likely is a neurofibrosarcoma based on immunohistochemistry. PMID:25678975

  1. [Primary pulmonary artery sarcoma in 36-year-old women: 3-years follow-up after partial resection and radiotherapy].

    PubMed

    Drożdż, Jarosław; Warchoł, Ewa; Fijuth, Jacek; Filipiak, Krzysztof; Spych, Michał; Maciejewski, Marek; Piestrzeniewicz, Katarzyna; Ludomir, Stafańczyk; Janaszek-Sitkowska, Hanna; Januszewicz, Andrzej; Zembala, Marian

    2013-01-01

    Intimal sarcoma of the heart and pulmonary artery is a very rare, malignant, primary tumour. The prognosis in patients with primary sarcoma of the pulmonary artery, including intimal sarcoma, is poor. We present the case and 3-years follow-up of 36-year-old woman who was successfully treated with surgical, partial resection of the tumour followed by radiotherapy.

  2. The Magic Shrinking Machine Revisited: The Presence of Props at Recall Facilitates Memory in 3-Year-Olds

    ERIC Educational Resources Information Center

    Dahl, Jonna J.; Kingo, Osman S.; Krøjgaard, Peter

    2015-01-01

    In a seminal study Simcock and Hayne (2002) showed that 3-year-olds were unable to use newly acquired words to describe a "magic" event experienced 6 or 12 months earlier. In the reference study the children's verbal recall was tested without props being present. Inspired by recent evidence, the original design was replicated, testing…

  3. Effectiveness of Video Self-Modeling to Promote Social Initiations by 3-Year-Olds with Autism Spectrum Disorders

    ERIC Educational Resources Information Center

    Buggey, Tom

    2012-01-01

    Video Self-Modeling (VSM) provides individuals the opportunity to view themselves performing a task beyond their present functioning level through the careful editing of videos. In this study, a single-case multiple-baseline design was used to determine whether VSM would facilitate social initiations across three young children (M = 3 years 10…

  4. "A Spinach with a V on It": What 3-Year-Olds See in Standard and Enhanced Blissymbols.

    ERIC Educational Resources Information Center

    Raghavendra, Parimala; Fristoe, Macalyne

    1990-01-01

    Standard or enhanced Blissymbols, designed to represent familiar actions, attributes, and objects, were shown to 20 3 year olds, who guessed their meaning. The number of their guesses that referred to the enhancements was twice as great as the number that referred to the standard Blissymbol base. (Author/JDD)

  5. Sustaining "Truth": Changes in Youth Tobacco Attitudes and Smoking Intentions after 3 Years of a National Antismoking Campaign

    ERIC Educational Resources Information Center

    Farrelly, Matthew C.; Davis, Kevin C.; Duke, Jennifer; Messeri, Peter

    2009-01-01

    This study examines how the American Legacy Foundation's "truth[R]" campaign and Philip Morris's "Think. Don't Smoke" (TDS) campaign have influenced youth's tobacco-related attitudes, beliefs and intentions during the first 3 years of the truth campaign. We use data from eight nationally representative cross-sectional telephone surveys of 35,074…

  6. Rational Action Selection in 1 1/2- to 3-Year-Olds Following an Extended Training Experience

    ERIC Educational Resources Information Center

    Klossek, Ulrike M. H.; Dickinson, Anthony

    2012-01-01

    Previous studies failed to find evidence for rational action selection in children under 2 years of age. The current study investigated whether younger children required more training to encode the relevant causal relationships. Children between 1 1/2 and 3 years of age were trained over two sessions to perform actions on a touch-sensitive screen…

  7. Association between pneumonia in acute stroke stage and 3-year mortality in patients with acute first-ever ischemic stroke.

    PubMed

    Yu, Yi-Jing; Weng, Wei-Chieh; Su, Feng-Chieh; Peng, Tsung-I; Chien, Yu-Yi; Wu, Chia-Lun; Lee, Kuang-Yung; Wei, Yi-Chia; Lin, Shun-Wen; Zhu, Jun-Xiao; Huang, Wen-Yi

    2016-11-01

    The influence of pneumonia in acute stroke stage on the clinical presentation and long-term outcomes of patients with acute ischemic stroke is still controversial. We investigate the influence of pneumonia in acute stroke stage on the 3-year outcomes of patients with acute first-ever ischemic stroke. Nine-hundred and thirty-four patients with acute first-ever ischemic stroke were enrolled and had been followed for 3years. Patients were divided into two groups according to whether pneumonia occurred during acute stroke stage or not. Clinical presentations, risk factors for stroke, laboratory data, co-morbidities, and outcomes were recorded. The result showed that a total of 100 patients (10.7%) had pneumonia in acute stroke stage. The prevalence of older age, atrial fibrillation was significantly higher in patients with pneumonia in acute stroke stage. Total anterior circulation syndrome and posterior circulation syndrome occurred more frequently among patients with pneumonia in acute stroke stage (P<0.001 and P=0.009, respectively). Multivariate Cox regression revealed that pneumonia in acute stroke stage is a significant predictor of 3-year mortality (hazard ratio=6.39, 95% confidence interval=4.03-10.11, P<0.001). In conclusion, pneumonia during the acute stroke stage is associated with increased risk of 3-year mortality. Interventions to prevent pneumonia in acute stroke stage might improve ischemic stroke outcome.

  8. Poorly differentiated cutaneous carcinoma of non-sebaceous origin in a 3-year-old Mongolian gerbil (Meriones unguiculatus)

    PubMed Central

    Fenton, Heather; Forzán, María J.; Desmarchelier, Marion; Woodland, Meghan; Sayi, Soraya; Gilroy, Cornelia V.

    2016-01-01

    A 3-year-old female gerbil developed a non-healing skin wound due to a malignant neoplasm. Histology, immunohistochemistry (cytokeratin 19 positive; vimentin, estrogen, and progesterone receptor negative), and electron microscopy (no desmosomes or melanosomes) revealed an undifferentiated carcinoma with pulmonary metastasis. Unlike in previous reports, it did not arise from the abdominal pad’s sebaceous gland. PMID:26740704

  9. Eudaimonic growth: Narrative growth goals predict increases in ego development and subjective well-being 3 years later.

    PubMed

    Bauer, Jack J; McAdams, Dan P

    2010-07-01

    We examine (a) the normative course of eudaimonic well-being in emerging adulthood and (b) whether people's narratives of major life goals might prospectively predict eudaimonic growth 3 years later. We define eudaimonic growth as longitudinal increases in eudaimonic well-being, which we define as the combination of psychosocial maturity and subjective well-being (SWB). College freshmen and seniors took measures of ego development (ED; to assess maturity; Loevinger, 1976) and SWB at Time 1 (T1) and again 3 years later (Time 2). ED levels increased longitudinally across that time for men and T1 freshmen, but SWB levels did not change. Participants also wrote narratives of 2 major life goals at T1 that were coded for an explicit emphasis on specific kinds of personal growth. Participants' intellectual-growth goals (especially agentic ones) predicted increases in ED 3 years later, whereas participants' socioemotional-growth goals (especially communal ones) predicted increases in SWB 3 years later. These findings were independent of the effects of Big Five personality traits-notably conscientiousness, which on its own predicted increases in SWB. We discuss (a) emerging adulthood as the last stop for normative eudaimonic growth in modern society and (b) empirical and theoretical issues surrounding the relations among narrative identity, life planning, dispositional traits, eudaimonia, and 2 paths of personal growth.

  10. Why 3-Year-Old Children Get Spanked: Parent and Child Determinants as Reported by College-Educated Mothers.

    ERIC Educational Resources Information Center

    Holden, George W.; And Others

    1995-01-01

    Telephone interviews were conducted with 39 college-educated mothers of 3-year-old children to examine the conditions surrounding the occurrence of physical punishment. Responses suggest that certain types of misbehavior, notably aggression, were more likely to elicit spanking than other misbehavior. In addition, parents' positive attitudes toward…

  11. Elongation factor-1 alpha occurs as two copies in bees: implications for phylogenetic analysis of EF-1 alpha sequences in insects.

    PubMed

    Danforth, B N; Ji, S

    1998-03-01

    We report the complete sequence of a paralogous copy of elongation factor-1 alpha (EF-1 alpha) in the honeybee, Apis mellifera (Hymenoptera: Apidae). This copy differs from a previously described copy in the positions of five introns and in 25% of the nucleotide sites in the coding regions. The existence of two paralogous copies of EF-1 alpha in Drosophila and Apis suggests that two copies of EF-1 alpha may be widespread in the holometabolous insect orders. To distinguish between a single, ancient gene duplication and parallel, independent fly and bee gene duplications, we performed a phylogenetic analysis of hexapod EF-1 alpha sequences. Unweighted parsimony analysis of nucleotide sequences suggests an ancient gene duplication event, whereas weighted parsimony analysis of nucleotides and unweighted parsimony analysis of amino acids suggests the contrary: that EF-1 alpha underwent parallel gene duplications in the Diptera and the Hymenoptera. The hypothesis of parallel gene duplication is supported both by congruence among nucleotide and amino acid data sets and by topology-dependent permutation tail probability (T-PTP) tests. The resulting tree topologies are also congruent with current views on the relationships among the holometabolous orders included in this study (Diptera, Hymenoptera, and Lepidoptera). More sequences, from diverse orders of holometabolous insects, will be needed to more accurately assess the historical patterns of gene duplication in EF-1 alpha.

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

    PubMed

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

    2014-07-18

    The multidrug resistant bacterium Acinetobacter baumannii is a significant cause of nosocomial infection. Biofilm formation, that requires both disulfide bond forming and chaperone-usher pathways, is a major virulence trait in this bacterium. Our biochemical characterizations show that the periplasmic A. baumannii DsbA (AbDsbA) enzyme has an oxidizing redox potential and dithiol oxidase activity. We found an unexpected non-covalent interaction between AbDsbA and the highly conserved prokaryotic elongation factor, EF-Tu. EF-Tu is a cytoplasmic protein but has been localized extracellularly in many bacterial pathogens. The crystal structure of this complex revealed that the