WorldWideScience

Sample records for receptor short form

  1. Genetic deletion of melanin-concentrating hormone neurons impairs hippocampal short-term synaptic plasticity and hippocampal-dependent forms of short-term memory.

    Science.gov (United States)

    Le Barillier, Léa; Léger, Lucienne; Luppi, Pierre-Hervé; Fort, Patrice; Malleret, Gaël; Salin, Paul-Antoine

    2015-11-01

    The cognitive role of melanin-concentrating hormone (MCH) neurons, a neuronal population located in the mammalian postero-lateral hypothalamus sending projections to all cortical areas, remains poorly understood. Mainly activated during paradoxical sleep (PS), MCH neurons have been implicated in sleep regulation. The genetic deletion of the only known MCH receptor in rodent leads to an impairment of hippocampal dependent forms of memory and to an alteration of hippocampal long-term synaptic plasticity. By using MCH/ataxin3 mice, a genetic model characterized by a selective deletion of MCH neurons in the adult, we investigated the role of MCH neurons in hippocampal synaptic plasticity and hippocampal-dependent forms of memory. MCH/ataxin3 mice exhibited a deficit in the early part of both long-term potentiation and depression in the CA1 area of the hippocampus. Post-tetanic potentiation (PTP) was diminished while synaptic depression induced by repetitive stimulation was enhanced suggesting an alteration of pre-synaptic forms of short-term plasticity in these mice. Behaviorally, MCH/ataxin3 mice spent more time and showed a higher level of hesitation as compared to their controls in performing a short-term memory T-maze task, displayed retardation in acquiring a reference memory task in a Morris water maze, and showed a habituation deficit in an open field task. Deletion of MCH neurons could thus alter spatial short-term memory by impairing short-term plasticity in the hippocampus. Altogether, these findings could provide a cellular mechanism by which PS may facilitate memory encoding. Via MCH neuron activation, PS could prepare the day's learning by increasing and modulating short-term synaptic plasticity in the hippocampus. © 2015 Wiley Periodicals, Inc.

  2. 48 CFR 53.301-1438 - Settlement Proposal (Short Form).

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 2 2010-10-01 2010-10-01 false Settlement Proposal (Short Form). 53.301-1438 Section 53.301-1438 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION (CONTINUED) CLAUSES AND FORMS FORMS Illustrations of Forms 53.301-1438 Settlement Proposal (Short...

  3. 7 CFR 3015.156 - Application for Federal assistance (short form).

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 15 2010-01-01 2010-01-01 false Application for Federal assistance (short form). 3015... Application for Federal Assistance § 3015.156 Application for Federal assistance (short form). Governments shall use the Application for Federal Assistance (Short Form) form prescribed by Circular A-102 in...

  4. Multicultural personality questionnaire : Development of a short form

    NARCIS (Netherlands)

    Van Der Zee, Karen; Van Oudenhoven, Jan Pieter; Ponterotto, Joseph G.; Fietzer, Alexander W.

    2013-01-01

    This study reports on the development of the Multicultural Personality Questionnaire-Short Form among 511 participants. Using a split-sample scale validation design, Study 1 (N = 260) employed a principal component analysis and rigorous item selection criteria to extract a 40-item short form

  5. Validity of Two WPPSI Short Forms in Outpatient Clinic Settings.

    Science.gov (United States)

    Haynes, Jack P.; Atkinson, David

    1983-01-01

    Investigated the validity of subtest short forms for the Wechsler Preschool and Primary Scale of Intelligence in an outpatient population of 116 children. Data showed that the short forms underestimated actual level of intelligence and supported use of a short form only as a brief screening device. (LLL)

  6. 48 CFR 1852.223-72 - Safety and Health (Short Form).

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Safety and Health (Short... and Clauses 1852.223-72 Safety and Health (Short Form). As prescribed in 1823.7001(e), insert the following clause: Safety and Health (Short Form) (APR 2002) (a) Safety is the freedom from those conditions...

  7. Modular Short Form Videos for Library Instruction

    Directory of Open Access Journals (Sweden)

    Cindy Craig

    2017-10-01

    Full Text Available In Brief Expensive software isn’t necessary to create effective tutorials. Quick, unedited tutorials created on social media, such as on Instagram or Snapchat, may be more effective. These short form videos (SFVs combine the advantages of animated GIFs with the advantages of screencasts: modularity, repetition of steps, and animated visuals supported by pertinent audio. SFVs are cheap (or free and easy to make with materials libraries already possess, such as Internet access, computers, and smartphones. They are easily replaceable if the subject changes. The short form forces librarians to get right to the point. Finally, SFVs are easily disseminated on social media and have the potential to go viral.

  8. Human orexin/hypocretin receptors form constitutive homo- and heteromeric complexes with each other and with human CB1 cannabinoid receptors

    International Nuclear Information System (INIS)

    Jäntti, Maria H.; Mandrika, Ilona; Kukkonen, Jyrki P.

    2014-01-01

    Highlights: • OX 1 and OX 2 orexin and CB 1 cannabinoid receptor dimerization was investigated. • Bioluminescence resonance energy transfer method was used. • All receptors readily formed constitutive homo- and heteromeric complexes. - Abstract: Human OX 1 orexin receptors have been shown to homodimerize and they have also been suggested to heterodimerize with CB 1 cannabinoid receptors. The latter has been suggested to be important for orexin receptor responses and trafficking. In this study, we wanted to assess the ability of the other combinations of receptors to also form similar complexes. Vectors for expression of human OX 1 , OX 2 and CB 1 receptors, C-terminally fused with either Renilla luciferase or GFP 2 green fluorescent protein variant, were generated. The constructs were transiently expressed in Chinese hamster ovary cells, and constitutive dimerization between the receptors was assessed by bioluminescence energy transfer (BRET). Orexin receptor subtypes readily formed homo- and hetero(di)mers, as suggested by significant BRET signals. CB 1 receptors formed homodimers, and they also heterodimerized with both orexin receptors. Interestingly, BRET efficiency was higher for homodimers than for almost all heterodimers. This is likely to be due to the geometry of the interaction; the putatively symmetric dimers may place the C-termini in a more suitable orientation in homomers. Fusion of luciferase to an orexin receptor and GFP 2 to CB 1 produced more effective BRET than the opposite fusions, also suggesting differences in geometry. Similar was seen for the OX 1 –OX 2 interaction. In conclusion, orexin receptors have a significant propensity to make homo- and heterodi-/oligomeric complexes. However, it is unclear whether this affects their signaling. As orexin receptors efficiently signal via endocannabinoid production to CB 1 receptors, dimerization could be an effective way of forming signal complexes with optimal cannabinoid concentrations

  9. Development and Validation of a Short-Form Safety Net Medical Home Scale.

    Science.gov (United States)

    Nocon, Robert S; Gunter, Kathryn E; Gao, Yue; Lee, Sang Mee; Chin, Marshall H

    2017-12-01

    To develop a short-form Safety Net Medical Home Scale (SNMHS) for assessing patient-centered medical home (PCMH) capability in safety net clinics. National surveys of federally qualified health centers (FQHCs). Interviews with FQHC directors. We constructed three short-form SNMHS versions and examined correlations with full SNMHS and related primary care assessments. We tested usability with FQHC directors and reviewed scale development with an advisory group. Federally qualified health center surveys were administered in 2009 and 2013, by mail and online. Usability testing was conducted through telephone interviews with FQHC directors in 2013. Six-, 12-, and 18-question short-form SNMHS versions had Pearson correlations with full scale of 0.84, 0.92, and 0.96, respectively. All versions showed a level of convergent validity with other primary care assessment scales comparable to the full SNMHS. User testers found short forms to be low-burden, though missing some PCMH concepts. Advisory group members expressed caution over missing concepts and appropriate use of short-form self-assessments. Short-form versions of SNMHS showed strong correlations with full scale and may be useful for brief assessment of safety net PCMH capability. Each short-form SNMHS version may be appropriate for different research, quality improvement, and assessment purposes. © Health Research and Educational Trust.

  10. Short forms of the Social Interaction Anxiety Scale and the Social Phobia Scale.

    Science.gov (United States)

    Fergus, Thomas A; Valentiner, David P; McGrath, Patrick B; Gier-Lonsway, Stephanie L; Kim, Hyun-Soo

    2012-01-01

    Mattick and Clarke's (1998) Social Interaction Anxiety Scale (SIAS) and Social Phobia Scale (SPS) are commonly used self-report measures that assess 2 dimensions of social anxiety. Given the need for short, readable measures, this research proposes short forms of both scales. Item-level analyses of readability characteristics of the SIAS and SPS items led to the selection of 6 items from each scale for use in the short forms. The SIAS and SPS short forms had reading levels at approximately the 6th and 5th grade level, respectively. Results using nonclinical (Study 1: N = 469) and clinical (Study 2: N = 145) samples identified these short forms as being factorially sound, possessing adequate internal consistency, and having strong convergence with their full-length counterparts. Moreover, these short forms showed convergence with other measures of social anxiety, showed divergence from measures assessing related constructs, and predicted concurrent interpersonal functioning. Recommendations for the use of these short forms are discussed.

  11. Human orexin/hypocretin receptors form constitutive homo- and heteromeric complexes with each other and with human CB{sub 1} cannabinoid receptors

    Energy Technology Data Exchange (ETDEWEB)

    Jäntti, Maria H., E-mail: maria.jantti@helsinki.fi [Department of Veterinary Biosciences, POB 66, FIN-00014 University of Helsinki (Finland); Mandrika, Ilona, E-mail: ilona@biomed.lu.lv [Latvian Biomedical Research and Study Centre, Ratsupites Str. 1, Riga LV 1067 (Latvia); Kukkonen, Jyrki P., E-mail: jyrki.kukkonen@helsinki.fi [Department of Veterinary Biosciences, POB 66, FIN-00014 University of Helsinki (Finland)

    2014-03-07

    Highlights: • OX{sub 1} and OX{sub 2} orexin and CB{sub 1} cannabinoid receptor dimerization was investigated. • Bioluminescence resonance energy transfer method was used. • All receptors readily formed constitutive homo- and heteromeric complexes. - Abstract: Human OX{sub 1} orexin receptors have been shown to homodimerize and they have also been suggested to heterodimerize with CB{sub 1} cannabinoid receptors. The latter has been suggested to be important for orexin receptor responses and trafficking. In this study, we wanted to assess the ability of the other combinations of receptors to also form similar complexes. Vectors for expression of human OX{sub 1}, OX{sub 2} and CB{sub 1} receptors, C-terminally fused with either Renilla luciferase or GFP{sup 2} green fluorescent protein variant, were generated. The constructs were transiently expressed in Chinese hamster ovary cells, and constitutive dimerization between the receptors was assessed by bioluminescence energy transfer (BRET). Orexin receptor subtypes readily formed homo- and hetero(di)mers, as suggested by significant BRET signals. CB{sub 1} receptors formed homodimers, and they also heterodimerized with both orexin receptors. Interestingly, BRET efficiency was higher for homodimers than for almost all heterodimers. This is likely to be due to the geometry of the interaction; the putatively symmetric dimers may place the C-termini in a more suitable orientation in homomers. Fusion of luciferase to an orexin receptor and GFP{sup 2} to CB{sub 1} produced more effective BRET than the opposite fusions, also suggesting differences in geometry. Similar was seen for the OX{sub 1}–OX{sub 2} interaction. In conclusion, orexin receptors have a significant propensity to make homo- and heterodi-/oligomeric complexes. However, it is unclear whether this affects their signaling. As orexin receptors efficiently signal via endocannabinoid production to CB{sub 1} receptors, dimerization could be an effective way

  12. Automatic loudness control in short-form content for broadcasting.

    Science.gov (United States)

    Pires, Leandro da S; Vieira, Maurílio N; Yehia, Hani C

    2017-03-01

    During the early years of the International Telecommunication Union (ITU) loudness calculation standard for sound broadcasting [ITU-R (2006), Rec. BS Series, 1770], the need for additional loudness descriptors to evaluate short-form content, such as commercials and live inserts, was identified. This work proposes a loudness control scheme to prevent loudness jumps, which can bother audiences. It employs short-form content audio detection and dynamic range processing methods for the maximum loudness level criteria. Detection is achieved by combining principal component analysis for dimensionality reduction and support vector machines for binary classification. Subsequent processing is based on short-term loudness integrators and Hilbert transformers. The performance was assessed using quality classification metrics and demonstrated through a loudness control example.

  13. Opposing roles for GABAA and GABAC receptors in short-term memory formation in young chicks.

    Science.gov (United States)

    Gibbs, M E; Johnston, G A R

    2005-01-01

    The inhibitory neurotransmitter GABA has both inhibitory and enhancing effects on short-term memory for a bead discrimination task in the young chick. Low doses of GABA (1-3 pmol/hemisphere) injected into the multimodal association area of the chick forebrain, inhibit strongly reinforced memory, whereas higher doses (30-100 pmol/hemisphere) enhance weakly reinforced memory. The effect of both high and low doses of GABA is clearly on short-term memory in terms of both the time of injection and in the time that the memory loss occurs. We argue on the basis of relative sensitivities to GABA and to selective GABA receptor antagonists that low doses of GABA act at GABAC receptors (EC50 approximately 1 microM) and the higher doses of GABA act via GABAA receptors (EC50 approximately 10 microM). The selective GABAA receptor antagonist bicuculline inhibited strongly reinforced memory in a dose and time dependent manner, whereas the selective GABAC receptor antagonists TPMPA and P4MPA enhanced weakly reinforced in a dose and time dependent manner. Confirmation that different levels of GABA affect different receptor subtypes was demonstrated by the shift in the GABA dose-response curves to the selective antagonists. It is clear that GABA is involved in the control of short-term memory formation and its action, enhancing or inhibiting, depends on the level of GABA released at the time of learning.

  14. The patient safety climate in healthcare organizations (PSCHO) survey: Short-form development.

    Science.gov (United States)

    Benzer, Justin K; Meterko, Mark; Singer, Sara J

    2017-08-01

    Measures of safety climate are increasingly used to guide safety improvement initiatives. However, cost and respondent burden may limit the use of safety climate surveys. The purpose of this study was to develop a 15- to 20-item safety climate survey based on the Patient Safety Climate in Healthcare Organizations survey, a well-validated 38-item measure of safety climate. The Patient Safety Climate in Healthcare Organizations was administered to all senior managers, all physicians, and a 10% random sample of all other hospital personnel in 69 private sector hospitals and 30 Veterans Health Administration hospitals. Both samples were randomly divided into a derivation sample to identify a short-form subset and a confirmation sample to assess the psychometric properties of the proposed short form. The short form consists of 15 items represented 3 overarching domains in the long-form scale-organization, work unit, and interpersonal. The proposed short form efficiently captures 3 important sources of variance in safety climate: organizational, work-unit, and interpersonal. The short-form development process was a practical method that can be applied to other safety climate surveys. This safety climate short form may increase response rates in studies that involve busy clinicians or repeated measures. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

  15. Modulation of central glucocorticoid receptors in short- and long-term experimental hyperthyroidism.

    Science.gov (United States)

    Nikolopoulou, Elena; Mytilinaios, Dimitrios; Calogero, Aldo E; Kamilaris, Themis C; Troupis, Theodore; Chrousos, George P; Johnson, Elizabeth O

    2015-08-01

    Hyperthyroidism is associated with a significant increase in circulating glucocorticoid levels and hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis. The aim of this study was to examine whether the HPA axis hyperactivity observed in hyperthyroidism may be explained by a disturbed feedback inhibition of endogenous glucocorticoids through two specific intracellular receptors in the brain: the high affinity mineralocorticoid receptor (MR) and the lower affinity glucocorticoid receptor (GR). Cytosolic receptor binding and gene expression was assessed in rats with short (7 days) and long standing (60 days) eu- and hyperthyroidism. Glucocorticoid receptor number and binding affinity (Kd) in the hippocampus were measured using [(3)H2]-dexamethasone radioreceptor assay. In situ hybridization was employed to examine the effects of hyperthyroidism on the GR and MR mRNA levels in the hippocampus and the pituitary. Both short- and long-term hyperthyroid rats showed pronounced reduction in the concentration of cytosolic GR in the hippocampus, without changes in binding affinity or changes in GR expression. In contrast, GR mRNA in the pituitary increased after 7 days and decreased after 60 days of thyroxin treatment. MR mRNA was moderately affected. Hyperthyroidism is associated with significant decreases in hippocampal GR levels supporting the hypothesis that hyperactivity of the HPA axis observed in experimentally induced hyperthyroidism may be attributed, at least in part, to decreased negative feedback at the level of the hippocampus. These findings further support the notion that a central locus is principally responsible for the hyperactivity of the HPA axis observed in hyperthyroidism.

  16. The School Short-Form Coopersmith Self-Esteem Inventory: Revised and Improved

    Science.gov (United States)

    Hills, Peter R.; Francis, Leslie J.; Jennings, Penelope

    2011-01-01

    The school short form of the Coopersmith Self-Esteem Inventory is a widely used measure of children's global self-esteem. Unlike the full-length scale, however, it has been generally understood that the short form does not allow differentiation between the major individual sources of self-esteem. The present study has examined the internal…

  17. Enhanced Long-Term and Impaired Short-Term Spatial Memory in GluA1 AMPA Receptor Subunit Knockout Mice: Evidence for a Dual-Process Memory Model

    Science.gov (United States)

    Sanderson, David J.; Good, Mark A.; Skelton, Kathryn; Sprengel, Rolf; Seeburg, Peter H.; Rawlins, J. Nicholas P.; Bannerman, David M.

    2009-01-01

    The GluA1 AMPA receptor subunit is a key mediator of hippocampal synaptic plasticity and is especially important for a rapidly-induced, short-lasting form of potentiation. GluA1 gene deletion impairs hippocampus-dependent, spatial working memory, but spares hippocampus-dependent spatial reference memory. These findings may reflect the necessity of…

  18. FcγRll: Characterisation of novel Fc receptor interactions and a new receptor form.

    OpenAIRE

    JESSICA CLAIRE ANANIA

    2018-01-01

    Leukocyte Fc receptors (FcR) bind to immunogloulins (Ig) to link the innate and humoral immune system to help balance the immune system and clear infections. We have characterised a novel FcR for IgG (FcγR) form, designated FcγRIIa3, which contains a 19 amino acid insert. This insert interacts with cytoskeletal structures allowing the receptor to be retained for longer periods of time at the cells surface upon activation, higher cell signalling which causes greater cellular activation. Theref...

  19. Validation of the Short Form of the Academic Procrastination Scale.

    Science.gov (United States)

    Yockey, Ronald D

    2016-02-01

    The factor structure, internal consistency reliability, and convergent validity of the five-item Academic Procrastination Scale-Short Form was investigated on an ethnically diverse sample of college students. The results provided support for the Academic Procrastination Scale-Short Form as a unidimensional measure of academic procrastination, which possessed good internal consistency reliability in this sample of 282 students. The scale also demonstrated good convergent validity, with moderate to large correlations with both the Procrastination Assessment Scale-Students and the Tuckman Procrastination Scale. Implications of the results are discussed and recommendations for future work provided.

  20. A Comparison of the Interest Accuracy of Two Short Forms of the WAIS-R.

    Science.gov (United States)

    Cella, David F.; And Others

    1985-01-01

    Examined relative efficacy of two short forms of Wechsler Adult Intelligence Scale-Revised (WAIS-R) with respect to accurate subtest profile scatter (N=50). Subtest scores of both split-half Satz-Mogel short form and criterion referenced Modified WAIS-R (WAIS-RM) short form were found to differ significantly from full-length WAIS-R subtest scores.…

  1. Rapidly-administered short forms of the Wechsler Adult Intelligence Scale-3rd edition.

    Science.gov (United States)

    Donnell, Alison J; Pliskin, Neil; Holdnack, James; Axelrod, Bradley; Randolph, Christopher

    2007-11-01

    Although the Wechsler Full Scale IQ (FSIQ) is a common component of most neuropsychological evaluations, there are many clinical situations where the complete administration of this battery is precluded by various constraints, including limitations of time and patient compliance. These constraints are particularly true for dementia evaluations involving elderly patients. The present study reports data on two short forms particularly suited to dementia evaluations, each requiring less than 20min of administration time. One of the short forms was previously validated in dementia for the WAIS-R [Randolph, C., Mohr, E., & Chase, T. N. (1993). Assessment of intellectual function in dementing disorders: Validity of WAIS-R short forms for patients with Alzheimer's, Huntington's, and Parkinson's disease. Journal of Clinical and Experimental Neuropsychology, 15, 743-753]; the second was developed specifically for patients with motor disabilities. These short forms were validated using the WAIS-III normative standardization sample (N=2450), neurologic sample (N=63), and matched controls (N=49), and a separate mixed clinical sample (N=70). The results suggest that each short form provides an accurate and reliable estimate of WAIS-III FSIQ, validating their use in appropriate clinical contexts. The present data support the use of these short forms for dementia evaluations, and suggests that they may be applicable for the evaluation of other neurological and neuropsychiatric disorders that involve acquired neurocognitive impairment.

  2. 48 CFR 52.246-9 - Inspection of Research and Development (Short Form).

    Science.gov (United States)

    2010-10-01

    ... Clauses 52.246-9 Inspection of Research and Development (Short Form). As prescribed in 46.309, insert the following clause: Inspection of Research and Development (Short Form) (APR 1984) The Government has the... 48 Federal Acquisition Regulations System 2 2010-10-01 2010-10-01 false Inspection of Research and...

  3. Dyadic Short Forms of the Wechsler Adult Intelligence Scale-IV.

    Science.gov (United States)

    Denney, David A; Ringe, Wendy K; Lacritz, Laura H

    2015-08-01

    Full Wechsler Adult Intelligence Scale-Fourth Edition (WAIS-IV) administration can be time-consuming and may not be necessary when intelligence quotient estimates will suffice. Estimated Full Scale Intelligence Quotient (FSIQ) and General Ability Index (GAI) scores were derived from nine dyadic short forms using individual regression equations based on data from a clinical sample (n = 113) that was then cross validated in a separate clinical sample (n = 50). Derived scores accounted for 70%-83% of the variance in FSIQ and 77%-88% of the variance in GAI. Predicted FSIQs were strongly associated with actual FSIQ (rs = .73-.88), as were predicted and actual GAIs (rs = .80-.93). Each of the nine dyadic short forms of the WAIS-IV was a good predictor of FSIQ and GAI in the validation sample. These data support the validity of WAIS-IV short forms when time is limited or lengthier batteries cannot be tolerated by patients. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  4. Accuracy of Short Forms of the Dutch Wechsler Preschool and Primary Scale of Intelligence: Third Edition.

    Science.gov (United States)

    Hurks, Petra; Hendriksen, Jos; Dek, Joelle; Kooij, Andress

    2016-04-01

    This article investigated the accuracy of six short forms of the Dutch Wechsler Preschool and Primary Scale of Intelligence-Third edition (WPPSI-III-NL) in estimating intelligent quotient (IQ) scores in healthy children aged 4 to 7 years (N = 1,037). Overall, accuracy for each short form was studied, comparing IQ equivalences based on the short forms with the original WPPSI-III-NL Full Scale IQ (FSIQ) scores. Next, our sample was divided into three groups: children performing below average, average, or above average, based on the WPPSI-III-NL FSIQ estimates of the original long form, to study the accuracy of WPPSI-III-NL short forms at the tails of the FSIQ distribution. While studying the entire sample, all IQ estimates of the WPPSI-III-NL short forms correlated highly with the FSIQ estimates of the original long form (all rs ≥ .83). Correlations decreased significantly while studying only the tails of the IQ distribution (rs varied between .55 and .83). Furthermore, IQ estimates of the short forms deviated significantly from the FSIQ score of the original long form, when the IQ estimates were based on short forms containing only two subtests. In contrast, unlike the short forms that contained two to four subtests, the Wechsler Abbreviated Scale of Intelligence short form (containing the subtests Vocabulary, Similarities, Block Design, and Matrix Reasoning) and the General Ability Index short form (containing the subtests Vocabulary, Similarities, Comprehension, Block Design, Matrix Reasoning, and Picture Concepts) produced less variations when compared with the original FSIQ score. © The Author(s) 2015.

  5. Modulation of short-term social memory in rats by adenosine A1 and A(2A) receptors.

    Science.gov (United States)

    Prediger, Rui D S; Takahashi, Reinaldo N

    2005-03-16

    The recognition of an unfamiliar juvenile rat by an adult rat has been shown to imply short-term memory processes. The present study was designed to examine the role of adenosine receptors in the short-term social memory of rats using the social recognition paradigm. Adenosine (5.0-10.0 mg/kg), the selective adenosine A1 receptor agonist 2-chloro-N6-cyclopentyladenosine (CCPA, 0.025-0.05 mg/kg) and the selective adenosine A(2A) receptor agonist N6-[2-(3,5-dimethoxyphenyl)-2-(2-methylphenyl)ethyl]adenosine (DPMA, 1.0-5.0 mg/kg), given by i.p. route 30 min before the test, disrupted the juvenile recognition ability of adult rats. This negative effect of adenosine (5.0 mg/kg, i.p.) on social memory was prevented by pretreatment with the non-selective adenosine receptor antagonist caffeine (10.0 mg/kg, i.p.), the adenosine A1 antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 1.0 mg/kg, i.p.) and the adenosine A(2A) antagonist 4-(2-[7-amino-2-{2-furyl}{1,2,4}triazolo-{2,3-a}{1,3,5}triazin-5-yl-amino]ethyl)phenol (ZM241385, 1.0 mg/kg, i.p.). Furthermore, acute administration of caffeine (10.0-30.0 mg/kg, i.p.), DPCPX (1.0-3.0 mg/kg, i.p.) or ZM241385 (0.5-1.0 mg/kg, i.p.) improved the short-term social memory in a specific manner. These results indicate that adenosine modulates the short-term social memory in rats by acting on both A1 and A(2A) receptors, with adenosine receptor agonists and antagonists, respectively, disrupting and enhancing the social memory.

  6. How Do Earth-Sized, Short-Period Planets Form?

    Science.gov (United States)

    Kohler, Susanna

    2017-08-01

    Matching theory to observation often requires creative detective work. In a new study, scientists have used a clever test to reveal clues about the birth of speedy, Earth-sized planets.Former Hot Jupiters?Artists impression of a hot Jupiter with an evaporating atmosphere. [NASA/Ames/JPL-Caltech]Among the many different types of exoplanets weve observed, one unusual category is that of ultra-short-period planets. These roughly Earth-sized planets speed around their host stars at incredible rates, with periods of less than a day.How do planets in this odd category form? One popular theory is that they were previously hot Jupiters, especially massive gas giants orbiting very close to their host stars. The close orbit caused the planets atmospheres to be stripped away, leaving behind only their dense cores.In a new study, a team of astronomers led by Joshua Winn (Princeton University) has found a clever way to test this theory.Planetary radius vs. orbital period for the authors three statistical samples (colored markers) and the broader sample of stars in the California Kepler Survey. [Winn et al. 2017]Testing MetallicitiesStars hosting hot Jupiters have an interesting quirk: they typically have metallicities that are significantly higher than an average planet-hosting star. It is speculated that this is because planets are born from the same materials as their host stars, and hot Jupiters require the presence of more metals to be able to form.Regardless of the cause of this trend, if ultra-short-period planets are in fact the solid cores of former hot Jupiters, then the two categories of planets should have hosts with the same metallicity distributions. The ultra-short-period-planet hosts should therefore also be weighted to higher metallicities than average planet-hosting stars.To test this, the authors make spectroscopic measurements and gather data for a sample of stellar hosts split into three categories:64 ultra-short-period planets (orbital period shorter than a

  7. Expression of the short chain fatty acid receptor GPR41/FFAR3 in autonomic and somatic sensory ganglia

    DEFF Research Database (Denmark)

    Nøhr, Mark Klitgaard; Egerod, K L; Christiansen, S H

    2015-01-01

    G-protein-coupled receptor 41 (GPR41) also called free fatty acid receptor 3 (FFAR3) is a Gαi-coupled receptor activated by short-chain fatty acids (SCFAs) mainly produced from dietary complex carbohydrate fibers in the large intestine as products of fermentation by microbiota. FFAR3 is expressed...

  8. Development and Validation of A Short Form of the Attitude Toward Poverty Scale

    Directory of Open Access Journals (Sweden)

    Sung Hyun Yun

    2010-10-01

    Full Text Available This study outlines the development and validation of a short form of the 37-item Attitude toward Poverty (ATP scale. Employing a cross-sectional survey design, the authors sampled 319 undergraduate students at a mid-sized university located in central Canada. The short form evinced high levels of internal consistency ranging from .87 to .89. Evidence for the validity was established through correlational analyses and independent samples t-tests. The findings suggest the short form is a feasible alternative to the original ATP scale for researchers and academics seeking to assess the poverty-related attitudes of university students.

  9. Individual stress vulnerability is predicted by short-term memory and AMPA receptor subunit ratio in the hippocampus.

    Science.gov (United States)

    Schmidt, Mathias V; Trümbach, Dietrich; Weber, Peter; Wagner, Klaus; Scharf, Sebastian H; Liebl, Claudia; Datson, Nicole; Namendorf, Christian; Gerlach, Tamara; Kühne, Claudia; Uhr, Manfred; Deussing, Jan M; Wurst, Wolfgang; Binder, Elisabeth B; Holsboer, Florian; Müller, Marianne B

    2010-12-15

    Increased vulnerability to aversive experiences is one of the main risk factors for stress-related psychiatric disorders as major depression. However, the molecular bases of vulnerability, on the one hand, and stress resilience, on the other hand, are still not understood. Increasing clinical and preclinical evidence suggests a central involvement of the glutamatergic system in the pathogenesis of major depression. Using a mouse paradigm, modeling increased stress vulnerability and depression-like symptoms in a genetically diverse outbred strain, and we tested the hypothesis that differences in AMPA receptor function may be linked to individual variations in stress vulnerability. Vulnerable and resilient animals differed significantly in their dorsal hippocampal AMPA receptor expression and AMPA receptor binding. Treatment with an AMPA receptor potentiator during the stress exposure prevented the lasting effects of chronic social stress exposure on physiological, neuroendocrine, and behavioral parameters. In addition, spatial short-term memory, an AMPA receptor-dependent behavior, was found to be predictive of individual stress vulnerability and response to AMPA potentiator treatment. Finally, we provide evidence that genetic variations in the AMPA receptor subunit GluR1 are linked to the vulnerable phenotype. Therefore, we propose genetic variations in the AMPA receptor system to shape individual stress vulnerability. Those individual differences can be predicted by the assessment of short-term memory, thereby opening up the possibility for a specific treatment by enhancing AMPA receptor function.

  10. Psychometric testing of the properties of the spiritual health scale short form.

    Science.gov (United States)

    Hsiao, Ya-Chu; Chiang, Yi-Chien; Lee, Hsiang-Chun; Han, Chin-Yen

    2013-11-01

    To further examine the psychometric properties of the spiritual health scale short form, including its reliability and validity. Spirituality is one of the main factors associated with good health outcomes. A reliable and valid instrument to measure spirituality is essential to identify the spiritual needs of an individual and to evaluate the effect of spiritual care. A cross-sectional study design was used. The study was conducted in six nursing schools in northern, central and southern Taiwan. The inclusion criterion for participants was nursing students with clinical practice experience. Initially, 1141 participants were recruited for the study, but 67 were absent and 48 did not complete the questionnaires. A total of 1026 participants were finally recruited, indicating a response rate of 89·9%. The psychometric testing of the spiritual health scale short form included construct validity with confirmatory factor analysis, known-group validity and internal consistency reliability. The results of the confirmatory factor analysis supported the five-factor model as an acceptable model fit. In the known-group validity, the results indicated that people who are in the category of primary religious affiliation have better spiritual health than people in the category of secondary religious affiliation and atheism. The result also indicated that the 24-item spiritual health scale short form achieved an acceptable internal consistency coefficient. The findings suggest that the spiritual health scale short form is a valid and reliable instrument for the appraisal of individual spiritual health. The spiritual health scale short form could provide useful information to guide clinical practice in assessing and managing people's spiritual health in Taiwan. © 2013 John Wiley & Sons Ltd.

  11. Activation of adenosine low-affinity A3 receptors inhibits the enteric short interplexus neural circuit triggered by histamine.

    Science.gov (United States)

    Bozarov, Andrey; Wang, Yu-Zhong; Yu, Jun Ge; Wunderlich, Jacqueline; Hassanain, Hamdy H; Alhaj, Mazin; Cooke, Helen J; Grants, Iveta; Ren, Tianhua; Christofi, Fievos L

    2009-12-01

    We tested the novel hypothesis that endogenous adenosine (eADO) activates low-affinity A3 receptors in a model of neurogenic diarrhea in the guinea pig colon. Dimaprit activation of H2 receptors was used to trigger a cyclic coordinated response of contraction and Cl(-) secretion. Contraction-relaxation was monitored by sonomicrometry (via intracrystal distance) simultaneously with short-circuit current (I(sc), Cl(-) secretion). The short interplexus reflex coordinated response was attenuated or abolished by antagonists at H2 (cimetidine), 5-hydroxytryptamine 4 receptor (RS39604), neurokinin-1 receptor (GR82334), or nicotinic (mecamylamine) receptors. The A1 agonist 2-chloro-N(6)-cyclopentyladenosine (CCPA) abolished coordinated responses, and A1 antagonists could restore normal responses. A1-selective antagonists alone [8-cyclopentyltheophylline (CPT), 1,3-dipropyl-8-(2-amino-4-chlorophenyl)xanthine (PACPX), or 8-cyclopentyl-N(3)-[3-(4-(fluorosulfonyl)benzoyloxy)propyl]-xanthine (FSCPX)] caused a concentration-dependent augmentation of crypt cell secretion or contraction and acted at nanomolar concentrations. The A3 agonist N(6)-(3-iodobenzyl)-adenosine-5'-N-methyluronamide (IB-MECA) abolished coordinated responses and the A3 antagonist 3-ethyl-5-benzyl-2-methyl-4-phenylethynyl-6-phenyl-1,4-(+/-)-dihydropyridine-3,5-dicarboxylate (MRS1191) could restore and further augment responses. The IB-MECA effect was resistant to knockdown of adenosine A1 receptor with the irreversible antagonist FSCPX; the IC(50) for IB-MECA was 0.8 microM. MRS1191 alone could augment or unmask coordinated responses to dimaprit, and IB-MECA suppressed them. MRS1191 augmented distension-evoked reflex I(sc) responses. Adenosine deaminase mimicked actions of adenosine receptor antagonists. A3 receptor immunoreactivity was differentially expressed in enteric neurons of different parts of colon. After tetrodotoxin, IB-MECA caused circular muscle relaxation. The data support the novel concept that

  12. Comparison of WAIS-III Short Forms for Measuring Index and Full-Scale Scores

    Science.gov (United States)

    Girard, Todd A.; Axelrod, Bradley N.; Wilkins, Leanne K.

    2010-01-01

    This investigation assessed the ability of the Wechsler Adult Intelligence Scale-Third Edition (WAIS-III) short forms to estimate both index and IQ scores in a large, mixed clinical sample (N = 809). More specifically, a commonly used modification of Ward's seven-subtest short form (SF7-A), a recently proposed index-based SF7-C and eight-subtest…

  13. Do serotonin(1-7) receptors modulate short and long-term memory?

    Science.gov (United States)

    Meneses, A

    2007-05-01

    Evidence from invertebrates to human studies indicates that serotonin (5-hydroxytryptamine; 5-HT) system modulates short- (STM) and long-term memory (LTM). This work is primarily focused on analyzing the contribution of 5-HT, cholinergic and glutamatergic receptors as well as protein synthesis to STM and LTM of an autoshaping learning task. It was observed that the inhibition of hippocampal protein synthesis or new mRNA did not produce a significant effect on autoshaping STM performance but it did impair LTM. Both non-contingent protein inhibition and 5-HT depletion showed no effects. It was basically the non-selective 5-HT receptor antagonist cyproheptadine, which facilitated STM. However, the blockade of glutamatergic and cholinergic transmission impaired STM. In contrast, the selective 5-HT(1B) receptor antagonist SB-224289 facilitated both STM and LTM. Selective receptor antagonists for the 5-HT(1A) (WAY100635), 5-HT(1D) (GR127935), 5-HT(2A) (MDL100907), 5-HT(2C/2B) (SB-200646), 5-HT(3) (ondansetron) or 5-HT(4) (GR125487), 5-HT(6) (Ro 04-6790, SB-399885 and SB-35713) or 5-HT(7) (SB-269970) did not impact STM. Nevertheless, WAY100635, MDL100907, SB-200646, GR125487, Ro 04-6790, SB-399885 or SB-357134 facilitated LTM. Notably, some of these changes shown to be independent of food-intake. Concomitantly, these data indicate that '5-HT tone via 5-HT(1B) receptors' might function in a serial manner from STM to LTM, whereas working in parallel using 5-HT(1A), 5-HT(2A), 5-HT(2B/2C), 5-HT(4), or 5-HT(6) receptors.

  14. The Development of a Motor-Free Short-Form of the Wechsler Intelligence Scale for Children-Fifth Edition.

    Science.gov (United States)

    Piovesana, Adina M; Harrison, Jessica L; Ducat, Jacob J

    2017-12-01

    This study aimed to develop a motor-free short-form of the Wechsler Intelligence Scale for Children-Fifth Edition (WISC-V) that allows clinicians to estimate the Full Scale Intelligence Quotients of youths with motor impairments. Using the reliabilities and intercorrelations of six WISC-V motor-free subtests, psychometric methodologies were applied to develop look-up tables for four Motor-free Short-form indices: Verbal Comprehension Short-form, Perceptual Reasoning Short-form, Working Memory Short-form, and a Motor-free Intelligence Quotient. Index-level discrepancy tables were developed using the same methods to allow clinicians to statistically compare visual, verbal, and working memory abilities. The short-form indices had excellent reliabilities ( r = .92-.97) comparable to the original WISC-V. This motor-free short-form of the WISC-V is a reliable alternative for the assessment of intellectual functioning in youths with motor impairments. Clinicians are provided with user-friendly look-up tables, index level discrepancy tables, and base rates, displayed similar to those in the WISC-V manuals to enable interpretation of assessment results.

  15. Developing Item Response Theory-Based Short Forms to Measure the Social Impact of Burn Injuries.

    Science.gov (United States)

    Marino, Molly E; Dore, Emily C; Ni, Pengsheng; Ryan, Colleen M; Schneider, Jeffrey C; Acton, Amy; Jette, Alan M; Kazis, Lewis E

    2018-03-01

    To develop self-reported short forms for the Life Impact Burn Recovery Evaluation (LIBRE) Profile. Short forms based on the item parameters of discrimination and average difficulty. A support network for burn survivors, peer support networks, social media, and mailings. Burn survivors (N=601) older than 18 years. Not applicable. The LIBRE Profile. Ten-item short forms were developed to cover the 6 LIBRE Profile scales: Relationships with Family & Friends, Social Interactions, Social Activities, Work & Employment, Romantic Relationships, and Sexual Relationships. Ceiling effects were ≤15% for all scales; floor effects were item bank, computerized adaptive test, and short forms are all scored along the same metric, and therefore scores are comparable regardless of the mode of administration. Copyright © 2017 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  16. Closed Form Solution of Synchronous Machine Short Circuit Transients

    Directory of Open Access Journals (Sweden)

    Gibson H.M. Sianipar

    2010-05-01

    Full Text Available This paper presents the closed form solution of the synchronous machine transients undergoing short circuit. That analytic formulation has been derived based on linearity and balanced conditions of the fault. Even though restrictive, the proposed method will serve somehow or other as a new resource for EMTP productivity. Indisputably superior, the closed-form formulation has some features inimitable by discretization such as continuity, accuracy and absolute numerical stability. Moreover, it enables us to calculate states at one specific instant independent of previous states or a snapshot, which any discretization methods cannot do.

  17. Short-term ionic plasticity at GABAergic synapses

    Directory of Open Access Journals (Sweden)

    Joseph Valentino Raimondo

    2012-10-01

    Full Text Available Fast synaptic inhibition in the brain is mediated by the pre-synaptic release of the neurotransmitter γ-Aminobutyric acid (GABA and the post-synaptic activation of GABA-sensitive ionotropic receptors. As with excitatory synapses, it is being increasinly appreciated that a variety of plastic processes occur at inhibitory synapses, which operate over a range of timescales. Here we examine a form of activity-dependent plasticity that is somewhat unique to GABAergic transmission. This involves short-lasting changes to the ionic driving force for the postsynaptic receptors, a process referred to as short-term ionic plasticity. These changes are directly related to the history of activity at inhibitory synapses and are influenced by a variety of factors including the location of the synapse and the post-synaptic cell’s ion regulation mechanisms. We explore the processes underlying this form of plasticity, when and where it can occur, and how it is likely to impact network activity.

  18. Wechsler Intelligence Scale for Children-fourth edition (WISC-IV) short-form validity: a comparison study in pediatric epilepsy.

    Science.gov (United States)

    Hrabok, Marianne; Brooks, Brian L; Fay-McClymont, Taryn B; Sherman, Elisabeth M S

    2014-01-01

    The purpose of this article was to investigate the accuracy of the WISC-IV short forms in estimating Full Scale Intelligence Quotient (FSIQ) and General Ability Index (GAI) in pediatric epilepsy. One hundred and four children with epilepsy completed the WISC-IV as part of a neuropsychological assessment at a tertiary-level children's hospital. The clinical accuracy of eight short forms was assessed in two ways: (a) accuracy within +/- 5 index points of FSIQ and (b) the clinical classification rate according to Wechsler conventions. The sample was further subdivided into low FSIQ (≤ 80) and high FSIQ (> 80). All short forms were significantly correlated with FSIQ. Seven-subtest (Crawford et al. [2010] FSIQ) and 5-subtest (BdSiCdVcLn) short forms yielded the highest clinical accuracy rates (77%-89%). Overall, a 2-subtest (VcMr) short form yielded the lowest clinical classification rates for FSIQ (35%-63%). The short form yielding the most accurate estimate of GAI was VcSiMrBd (73%-84%). Short forms show promise as useful estimates. The 7-subtest (Crawford et al., 2010) and 5-subtest (BdSiVcLnCd) short forms yielded the most accurate estimates of FSIQ. VcSiMrBd yielded the most accurate estimate of GAI. Clinical recommendations are provided for use of short forms in pediatric epilepsy.

  19. Novel receptor-like protein kinases induced by Erwinia carotovora and short oligogalacturonides in potato.

    Science.gov (United States)

    Montesano, M; Kõiv, V; Mäe, A; Palva, E T

    2001-11-01

    summary Identification of potato genes responsive to cell wall-degrading enzymes of Erwinia carotovora resulted in the isolation of cDNA clones for four related receptor-like protein kinases. One of the putative serine-threonine protein kinases might have arisen through alternative splicing. These potato receptor-like kinases (PRK1-4) were highly equivalent (91-99%), most likely constituting a family of related receptors. All PRKs and four other plant RLKs share in their extracellular domain a conserved bi-modular pattern of cysteine repeats distinct from that in previously characterized plant RLKs, suggesting that they represent a new class of receptors. The corresponding genes were rapidly induced by E. carotovora culture filtrate (CF), both in the leaves and tubers of potato. Furthermore, the genes were transiently induced by short oligogalacturonides. The structural identity of PRKs and their induction pattern suggested that they constitute part of the early response of potato to E. carotovora infection.

  20. Bombyx neuropeptide G protein-coupled receptor A7 is the third cognate receptor for short neuropeptide F from silkworm.

    Science.gov (United States)

    Ma, Qiang; Cao, Zheng; Yu, Yena; Yan, Lili; Zhang, Wenjuan; Shi, Ying; Zhou, Naiming; Huang, Haishan

    2017-12-15

    The short neuropeptide F (sNPF) neuropeptides, closely related to vertebrate neuropeptide Y (NPY), have been suggested to exert pleiotropic effects on many physiological processes in insects. In the silkworm ( Bombyx mori ) two orphan G protein-coupled receptors, Bombyx neuropeptide G protein-coupled receptor (BNGR) A10 and A11, have been identified as cognate receptors for sNPFs, but other sNPF receptors and their signaling mechanisms in B. mori remain unknown. Here, we cloned the full-length cDNA of the orphan receptor BNGR-A7 from the brain of B. mori larvae and identified it as a receptor for Bombyx sNPFs. Further characterization of signaling and internalization indicated that BNGR-A7, -A10, and -A11 are activated by direct interaction with synthetic Bombyx sNPF-1 and -3 peptides. This activation inhibited forskolin or adipokinetic hormone-induced adenylyl cyclase activity and intracellular Ca 2+ mobilization via a G i/o -dependent pathway. Upon activation by sNPFs, BNGR-A7, -A10, and -A11 evoked ERK1/2 phosphorylation and underwent internalization. On the basis of these findings, we designated the receptors BNGR-A7, -A10, and -A11 as Bommo -sNPFR-1, -2, and -3, respectively. Moreover, the results obtained with quantitative RT-PCR analysis revealed that the three Bombyx sNPF receptor subtypes exhibit differential spatial and temporal expression patterns, suggesting possible roles of sNPF signaling in the regulation of a wide range of biological processes. Our findings provide the first in-depth information on sNPF signaling for further elucidation of the roles of the Bombyx sNPF/sNPFR system in the regulation of physiological activities. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  1. Development of a Short Form of the Boston Naming Test for Individuals with Aphasia

    Science.gov (United States)

    del Toro, Christina M.; Bislick, Lauren P.; Comer, Matthew; Velozo, Craig; Romero, Sergio; Rothi, Leslie J. Gonzalez; Kendall, Diane L.

    2011-01-01

    Purpose: The purpose of this study was to develop a short form of the Boston Naming Test (BNT; Kaplan, Goodglass, & Weintraub, 2001) for individuals with aphasia and compare it with 2 existing short forms originally analyzed with responses from people with dementia and neurologically healthy adults. Method: Development of the new BNT-Aphasia Short…

  2. Development and Validation of the Drinking Motive Questionnaire Revised Short Form (DMQ-R SF)

    Science.gov (United States)

    Kuntsche, Emmanuel; Kuntsche, Sandra

    2009-01-01

    A short form of the Drinking Motive Questionnaire Revised (DMQ-R; Cooper, 1994) was developed, using different item selection strategies based on a national representative sample of 5,617 12- to 18-year-old students in Switzerland. To confirm the concurrent validity of the short-form questionnaire, or DMQ-R SF, data from a second national sample…

  3. 48 CFR 46.309 - Research and development contracts (short form).

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Research and development... REGULATION CONTRACT MANAGEMENT QUALITY ASSURANCE Contract Clauses 46.309 Research and development contracts... Development (Short Form), in solicitations and contracts for research and development when the clause...

  4. VIP receptors from porcine liver: High yield solubilization in a GTP-insensitive form

    International Nuclear Information System (INIS)

    Voisin, T.; Couvineau, A.; Guijarro, L.; Laburthe, M.

    1990-01-01

    Vasoactive intestinal peptide (VIP) receptors were solubilized from porcine liver membranes using CHAPS. The binding of 125 I-VIP to solubilized receptors was reversible, saturable and specific. Scatchard analysis indicated the presence of one binding site with a Kd of 6.5 ± 0.3 nM and a Bmax of 1.20 ± 0.15 pmol/mg protein. Solubilized and membrane-bound receptors displayed the same pharmacological profile since VIP and VIP-related peptides inhibited 125 I-VIP binding to both receptor preparations with the same rank order of potency e.g. VIP>helodermin>rat GRF>rat PHI>secretin>human GRF. GTP inhibited 125 I-VIP binding to membrane-bound receptors but not to solubilized receptors supporting functional uncoupling of VIP receptor and G protein during solubilization. Affinity labeling of solubilized and membrane-bound VIP receptors with 125 I-VIP revealed the presence of a single molecular component with Mr 55,000 in both cases. It is concluded that VIP receptors from porcine liver can be solubilized with a good yield, in a GTP-insensitive, G protein-free form. This represents a major advance towards the purification of VIP receptors

  5. Developing brief fatigue short forms calibrated to a common mathematical metric: is content-balancing important?

    Directory of Open Access Journals (Sweden)

    Karon F Cook

    2010-08-01

    Full Text Available Karon F Cook1, Seung W Choi2, Kurt L Johnson1, Dagmar Amtmann11Department of Rehabilitation Medicine, University of Washington, Seattle, WA; 2Northwestern University Feinberg School of Medicine, Chicago, IL, USAAbstract: There are clinical and research settings in which concerns about respondent burden make the use of longer self-report measures impractical. Though computer adaptive testing provides an efficient strategy for measuring patient reported outcomes, the requirement of a computer interface makes it impractical for some settings. This study evaluated how well brief short forms, constructed from a longer measure of patient reported fatigue, reproduced scores on the full measure. When the items of an item bank are calibrated using an item response theory model, it is assumed that the items are fungible units. Theoretically, there should be no advantage to balancing the content coverage of the items. We compared short forms developed using a random item selection process to short forms developed with consideration of the items relation to subdomains of fatigue (ie, physical and cognitive fatigue. Scores on short forms developed using content balancing more successfully predicted full item bank scores than did scores on short forms developed by random selection of items.Keywords: psychometrics, outcomes, quality of life, measurement, fatigue

  6. Short Forms of Wechsler Scales Assessing the Intellectually Gifted Children Using Simulation Data

    Directory of Open Access Journals (Sweden)

    Alexandre Aubry

    2018-05-01

    Full Text Available Intellectual giftedness is usually defined in terms of having a very high Intellectual Quotient (IQ. The intellectual capacity is assessed by a standardized test such as the Wechsler Intelligence Scale for Children (WISC. However, the identification of intellectually gifted children (IGC often remains time-consuming. A short-form WISC can be used as a screening instrument. The practitioners and researchers in this field can then make a more in-depth evaluation of the IGC's cognitive and socioemotional characteristics if needed. The aim of our study is thus to determine the best short tests, in terms of their psychometric qualities, for the identification of IGC. The current study is composed of three-step analyses. Firstly, we created nine IQs short forms (IQSF with 2-subtests, and nine IQSF with 4-subtests from the WISC-IV (Wechsler, 2005. Secondly, we estimated psychometric parameters (i.e., reliability and validity from empirical and simulated dataset with WISC-IV. The difference in the estimation of psychometric qualities of each IQSF from the simulated data is very close to those derived from empirical data. We thus selected the three best IQSF based on these psychometrics parameters estimated from simulated datasets. For each selected short form of the WISC-IV, we estimated the screening quality in our sample of IGC. Thirdly, we created IQSF with 2- and 4-subtests from the WISC-V (Wechsler, 2016 with simulated dataset. We then highlighted the three best short forms of WISC-V based on the estimated psychometric parameters. The results are interpreted in terms of validity, reliability and screening quality of IGC. In spite of the important changes in the WISC-V, our findings show that the 2-subtest form, Similitaries + Matrix Reasoning, and 4-subtest form, Similitaries + Vocabulary + Matrix Reasoning + Block Design, are the most efficient to identify the IGC at the two recent versions of Wechsler scales. Finally, we discuss the advantages

  7. [Development of a Japanese version of a short form of the Profile of Emotional Competence].

    Science.gov (United States)

    Nozaki, Yuki; Koyasu, Masuo

    2015-06-01

    Emotional competence refers to individual differences in the ability to appropriately identity, understand, express, regulate, and utilize one's own emotions and those of others. This study developed a Japanese version of a short form of the Profile of Emotional Competence, a measure that allows the comprehensive assessment of intra- and interpersonal emotional competence with shorter items, and investigated its reliability and validity. In Study 1, we selected items for a short version and compared it with the full scale in terms of scores, internal consistency, and validity. In Study 2, we examined the short form's test-retest reliability. Results supported the original two-factor model and the measure had adequate reliability and validity. We discuss the construct validity and practical applicability of the short form of the Profile of Emotional Competence.

  8. Functional labeling of insulin receptor subunits in live cells. Alpha 2 beta 2 species is the major autophosphorylated form

    International Nuclear Information System (INIS)

    Le Marchand-Brustel, Y.; Ballotti, R.; Gremeaux, T.; Tanti, J.F.; Brandenburg, D.; Van Obberghen, E.

    1989-01-01

    Both receptor subunits were functionally labeled in order to provide methods allowing, in live cells and in broken cell systems, concomitant evaluation of the insulin receptor dual function, hormone binding, and kinase activity. In cell-free systems, insulin receptors were labeled on their alpha-subunit with 125I-photoreactive insulin, and on their beta-subunit by autophosphorylation. Thereafter, phosphorylated receptors were separated from the complete set of receptors by means of anti-phosphotyrosine antibodies. Using this approach, a subpopulation of receptors was found which had bound insulin, but which were not phosphorylated. Under nonreducing conditions, receptors appeared in three oligomeric species identified as alpha 2 beta 2, alpha 2 beta, and alpha 2. Mainly the alpha 2 beta 2 receptor species was found to be phosphorylated while insulin was bound to alpha 2 beta 2, alpha 2 beta, and alpha 2 forms. In live cells, biosynthetic labeling of insulin receptors was used. Receptors were first labeled with [35S]methionine. Subsequently, the addition of insulin led to receptor autophosphorylation by virtue of the endogenous ATP pool. The total amount of [35S]methionine-labeled receptors was precipitated with antireceptor antibodies, whereas with anti-phosphotyrosine antibodies, only the phosphorylated receptors were isolated. Using this approach we made the two following key findings: (1) Both receptor species, alpha 2 beta 2 and alpha 2 beta, are present in live cells and in comparable amounts. This indicates that the alpha 2 beta form is not a degradation product of the alpha 2 beta 2 form artificially generated during receptor preparation. (2) The alpha 2 beta 2 species is the prevalently autophosphorylated form

  9. 48 CFR 52.249-1 - Termination for Convenience of the Government (Fixed-Price) (Short Form).

    Science.gov (United States)

    2010-10-01

    ... Convenience of the Government (Fixed-Price) (Short Form). 52.249-1 Section 52.249-1 Federal Acquisition... CONTRACT CLAUSES Text of Provisions and Clauses 52.249-1 Termination for Convenience of the Government... Convenience of the Government (Fixed-Price) (Short Form) (APR 1984) The Contracting Officer, by written notice...

  10. Short forms of the Texas Social Behavior Inventory /TSBI/, an objective measure of self-esteem

    Science.gov (United States)

    Helmreich, R.; Stapp, J.

    1974-01-01

    Two short (16 item) forms of the Helmreich, Stapp, and Ervin (1974) Texas Social Behavior Inventory, a validated, objective measure of self-esteem or social competence are presented. Normative data and other statistics are described for males and females. Correlations between each short form and long (32-item) scale were .97. Factor analysis and part-whole correlations verified the similarity of the two forms. The utility of the scale in research is described.

  11. The Social Interaction Anxiety Scale (SIAS) and the Social Phobia Scale (SPS): a comparison of two short-form versions.

    Science.gov (United States)

    Fergus, Thomas A; Valentiner, David P; Kim, Hyun-Soo; McGrath, Patrick B

    2014-12-01

    The widespread use of Mattick and Clarke's (1998) Social Interaction Anxiety Scale (SIAS) and Social Phobia Scale (SPS) led 2 independent groups of researchers to develop short forms of these measures (Fergus, Valentiner, McGrath, Gier-Lonsway, & Kim, 2012; Peters, Sunderland, Andrews, Rapee, & Mattick, 2012). This 3-part study examined the psychometric properties of Fergus et al.'s and Peters et al.'s short forms of the SIAS and SPS using an American nonclinical adolescent sample in Study 1 (N = 98), American patient sample with an anxiety disorder in Study 2 (N = 117), and both a South Korean college student sample (N = 341) and an American college student sample (N = 550) in Study 3. Scores on both sets of short forms evidenced adequate internal consistency, interitem correlations, and measurement invariance. Scores on Fergus et al.'s short forms, particularly their SIAS short form, tended to capture more unique variance in scores of criterion measures than did scores on Peters et al.'s short forms. Implications for the use of these 2 sets of short forms are discussed. (c) 2014 APA, all rights reserved.

  12. Development of a Short Form of the Five-Factor Narcissism Inventory: the FFNI-SF.

    Science.gov (United States)

    Sherman, Emily D; Miller, Joshua D; Few, Lauren R; Campbell, W Keith; Widiger, Thomas A; Crego, Cristina; Lynam, Donald R

    2015-09-01

    The Five-Factor Narcissism Inventory (FFNI; Glover, Miller, Lynam, Crego, & Widiger, 2012) is a 148-item self-report inventory of 15 traits designed to assess the basic elements of narcissism from the perspective of a 5-factor model. The FFNI assesses both vulnerable (i.e., cynicism/distrust, need for admiration, reactive anger, and shame) and grandiose (i.e., acclaim seeking, arrogance, authoritativeness, entitlement, exhibitionism, exploitativeness, grandiose fantasies, indifference, lack of empathy, manipulativeness, and thrill seeking) variants of narcissism. The present study reports the development of a short-form version of the FFNI in 4 diverse samples (i.e., 2 undergraduate samples, a sample recruited from MTurk, and a clinical community sample) using item response theory. The validity of the resultant 60-item short form was compared against the validity of the full scale in the 4 samples at both the subscale level and the level of the grandiose and vulnerable composites. Results indicated that the 15 subscales remain relatively reliable, possess a factor structure identical to the structure of the long-form scales, and manifest correlational profiles highly similar to those of the long-form scales in relation to a variety of criterion measures, including basic personality dimensions, other measures of grandiose and vulnerable narcissism, and indicators of externalizing and internalizing psychopathology. Grandiose and vulnerable composites also behave almost identically across the short- and long-form versions. It is concluded that the FFNI-Short Form (FFNI-SF) offers a well-articulated assessment of the basic traits comprising grandiose and vulnerable narcissism, particularly when assessment time is limited. (c) 2015 APA, all rights reserved.

  13. A short form of the neonatal intensive care unit family needs inventory

    Directory of Open Access Journals (Sweden)

    Elisabete Alves

    2016-02-01

    Full Text Available ABSTRACT OBJECTIVE: The identification of parental needs in Neonatal Intensive Care Units is essential to design and implement family-centered care. This article aims to validate the Neonatal Intensive Care Units Family Needs Inventory for the Portuguese population, and to propose a Short Form. METHODS: A linguistic adaptation of the Neonatal Intensive Care Units Family Needs Inventory, a self-report scale with 56-items, was performed. The instrument was administered to 211 parents of infants hospitalized in all level III Neonatal Intensive Care Units in the North of Portugal, 15-22 days after admission (July of 2013-June of 2014. The number of items needed to achieve reliability close to 0.8 was calculated using by the Spearman-Brown formula. The global goodness of fit of the scale was evaluated using the comparative fit index. Construct validity was assessed through association of each dimension score with socio-demographic and obstetric characteristics. RESULTS: Exploratory factor analysis revealed two dimensions, one focused on parents' needs and another on the infant's needs. To compose the Short Form Inventory, items with ceiling effect were eliminated and 22 items were submitted to confirmatory analysis, which supported the existence of two dimensions (CFI = 0.925. The Short Form showed a high degree of reliability (alpha ≥ 0.76. Less educated and older parents more frequently attributed a significantly higher importance to parent-centered needs, while parents of multiples revealed a tendency to value infant-centered needs. CONCLUSIONS: The Short Form of the Neonatal Intensive Care Units Family Needs Inventory is a brief, simple, and valid instrument with a high degree of reliability. Further studies are needed to explore associations with practices of family-centered care.

  14. Emotional Intelligence and Nurse Recruitment: Rasch and confirmatory factor analysis of the trait emotional intelligence questionnaire short form.

    Science.gov (United States)

    Snowden, Austyn; Watson, Roger; Stenhouse, Rosie; Hale, Claire

    2015-12-01

    To examine the construct validity of the Trait Emotional Intelligence Questionnaire Short form. Emotional intelligence involves the identification and regulation of our own emotions and the emotions of others. It is therefore a potentially useful construct in the investigation of recruitment and retention in nursing and many questionnaires have been constructed to measure it. Secondary analysis of existing dataset of responses to Trait Emotional Intelligence Questionnaire Short form using concurrent application of Rasch analysis and confirmatory factor analysis. First year undergraduate nursing and computing students completed Trait Emotional Intelligence Questionnaire-Short Form in September 2013. Responses were analysed by synthesising results of Rasch analysis and confirmatory factor analysis. Participants (N = 938) completed Trait Emotional Intelligence Questionnaire Short form. Rasch analysis showed the majority of the Trait Emotional Intelligence Questionnaire-Short Form items made a unique contribution to the latent trait of emotional intelligence. Five items did not fit the model and differential item functioning (gender) accounted for this misfit. Confirmatory factor analysis revealed a four-factor structure consisting of: self-confidence, empathy, uncertainty and social connection. All five misfitting items from the Rasch analysis belonged to the 'social connection' factor. The concurrent use of Rasch and factor analysis allowed for novel interpretation of Trait Emotional Intelligence Questionnaire Short form. Much of the response variation in Trait Emotional Intelligence Questionnaire Short form can be accounted for by the social connection factor. Implications for practice are discussed. © 2015 John Wiley & Sons Ltd.

  15. Taming a Wandering Attention: Short-Form Mindfulness Training in Student Cohorts

    Directory of Open Access Journals (Sweden)

    Alexandra B. Morrison

    2014-01-01

    Full Text Available Mindfulness training (MT is a form of mental training in which individuals engage in exercises to cultivate an attentive, present centered, and non-reactive mental mode. The present study examines the putative benefits of MT in University students for whom mind wandering can interfere with learning and academic success. We tested the hypothesis that short-form MT (7 hours over 7 weeks contextualized for the challenges and concerns of University students may reduce mind wandering and improve working memory. Performance on the sustained attention response task (SART and two working memory tasks (operation span, delayed-recognition with distracters was indexed in participants assigned to a waitlist control group or the MT course. Results demonstrated MT-related benefits in SART performance. Relative to the control group, MT participants had higher task accuracy and self-reported being more on-task after the 7-week training period. MT did not significantly benefit the operation span task or accuracy on the delayed-recognition task. Together these results suggest that while short-form MT did not bolster working memory task performance, it may help curb mind wandering and should, therefore, be further investigated for its use in academic contexts.

  16. Cross-cultural adaptation of the US consumer form of the short Primary Care Assessment Tool (PCAT): the Korean consumer form of the short PCAT (KC PCAT) and the Korean standard form of the short PCAT (KS PCAT).

    Science.gov (United States)

    Jeon, Ki-Yeob

    2011-01-01

    It is well known that countries with well-structured primary care have better health outcomes, better health equity and reduced healthcare costs. This study aimed to culturally modify and validate the US consumer form of the short Primary Care Assessment Tool (PCAT) in primary care in the Republic of Korea (hereafter referred to as Korea). The Korean consumer form of the short PCAT (KC PCAT) was cross-culturally modified from the original version using a standardised transcultural adaptation method. A pre-test version of the KC PCAT was formulated by replacement of four items and modification of a further four items from the 37 items of the original consumer form of the short PCAT at face value evaluation meetings. Pilot testing was done with a convenience sample of 15 responders at two different sites. Test-retest showed high reliability. To validate the KC PCAT, 606 clients participated in a survey carried out in Korea between February and May 2006. Internal consistency reliability, test-retest reliability and factor analysis were conducted in order to test validity. Psychometric testing was carried out on 37 items of the KC PCAT to make the KS PCAT which has 30 items and has seven principal domains: first contact utilisation, first contact accessibility, ongoing accountable care (ongoing care and coordinated rapport care), integrated care (patient-centred care with integration between primary and specialty care or between different specialties), comprehensive care, community-oriented care and culturally-oriented care. Component factors of the verified KS PCAT explained 58.28% of the total variance in the total item scores of primary care. The verified KS PCAT has been characterised by the seven classic domains of primary care with minor modifications. This may provide clues concerning differences in expectations for primary care in the Korean population as compared with that of the US. The KS PCAT is a reliable and valid tool for the evaluation of the quality of

  17. A short form of the neonatal intensive care unit family needs inventory

    Directory of Open Access Journals (Sweden)

    Elisabete Alves

    2016-01-01

    Conclusions: The Short Form of the NICU Family Needs Inventory is a brief, simple, and valid instrument with a high degree of reliability. Further studies are needed to explore associations with practices of family‐centered care.

  18. Empirical versus Random Item Selection in the Design of Intelligence Test Short Forms--The WISC-R Example.

    Science.gov (United States)

    Goh, David S.

    1979-01-01

    The advantages of using psychometric thoery to design short forms of intelligence tests are demonstrated by comparing such usage to a systematic random procedure that has previously been used. The Wechsler Intelligence Scale for Children Revised (WISC-R) Short Form is presented as an example. (JKS)

  19. Translation and cross-cultural adaptation of the Brazilian Portuguese version of the Driving Anger Scale (DAS: long form and short form

    Directory of Open Access Journals (Sweden)

    Jessye Almeida Cantini

    2015-03-01

    Full Text Available Introduction: Driving anger has attracted the attention of researchers in recent years because it may induce individuals to drive aggressively or adopt risk behaviors. The Driving Anger Scale (DAS was designed to evaluate the propensity of drivers to become angry or aggressive while driving. This study describes the cross-cultural adaptation of a Brazilian version of the short form and the long form of the DAS.Methods: Translation and adaptation were made in four steps: two translations and two back-translations carried out by independent evaluators; the development of a brief version by four bilingual experts in mental health and driving behaviors; a subsequent experimental application; and, finally, an investigation of operational equivalence.Results: Final Brazilian versions of the short form and of the long form of the DAS were made and are presented. Conclusions: This important instrument, which assesses driving anger and aggressive behaviors, is now available to evaluate the driving behaviors of the Brazilian population, which facilitates research in this field.

  20. Internal consistency of a Spanish translation of the Francis Scale of Attitude Toward Christianity Short Form.

    Science.gov (United States)

    Campo-Arias, Adalberto; Oviedo, Heidi Celina; Díaz, Carmen Elena; Cogollo, Zuleima

    2006-12-01

    This study evaluated the internal consistency of a Spanish version of the short form of the Francis Scale of Attitude Toward Christianity based on responses of 405 Colombian adolescent students ages 13 to 17 years. This translated short-form version of the scale had an internal consistency of .80. This estimate indicates suitable internal consistency reliability for research use in this population.

  1. A comparison of computerized adaptive testing and fixed-length short forms for the Prosthetic Limb Users Survey of Mobility (PLUS-MTM).

    Science.gov (United States)

    Amtmann, Dagmar; Bamer, Alyssa M; Kim, Jiseon; Bocell, Fraser; Chung, Hyewon; Park, Ryoungsun; Salem, Rana; Hafner, Brian J

    2017-09-01

    New health status instruments can be administered by computerized adaptive test or short forms. The Prosthetic Limb Users Survey of Mobility (PLUS-M TM ) is a self-report measure of mobility for prosthesis users with lower limb loss. This study used the PLUS-M to examine advantages and disadvantages of computerized adaptive test and short forms. To compare scores obtained from computerized adaptive test to scores obtained from fixed-length short forms (7-item and 12-item) in order to provide guidance to researchers and clinicians on how to select the best form of administration for different uses. Cross-sectional, observational study. Individuals with lower limb loss completed the PLUS-M by computerized adaptive test and short forms. Administration time, correlations between the scores, and standard errors were compared. Scores and standard errors from the computerized adaptive test, 7-item short form, and 12-item short form were highly correlated and all forms of administration were efficient. Computerized adaptive test required less time to administer than either paper or electronic short forms; however, time savings were minimal compared to the 7-item short form. Results indicate that the PLUS-M computerized adaptive test is most efficient, and differences in scores between administration methods are minimal. The main advantage of the computerized adaptive test was more reliable scores at higher levels of mobility compared to short forms. Clinical relevance Health-related item banks, like the Prosthetic Limb Users Survey of Mobility (PLUS-M TM ), can be administered by computerized adaptive testing (CAT) or as fixed-length short forms (SFs). Results of this study will help clinicians and researchers decide whether they should invest in a CAT administration system or whether SFs are more appropriate.

  2. Chimeric antigen receptor T cells form nonclassical and potent immune synapses driving rapid cytotoxicity.

    Science.gov (United States)

    Davenport, A J; Cross, R S; Watson, K A; Liao, Y; Shi, W; Prince, H M; Beavis, P A; Trapani, J A; Kershaw, M H; Ritchie, D S; Darcy, P K; Neeson, P J; Jenkins, M R

    2018-02-27

    Chimeric antigen receptor T (CAR-T) cells are effective serial killers with a faster off-rate from dying tumor cells than CAR-T cells binding target cells through their T cell receptor (TCR). Here we explored the functional consequences of CAR-mediated signaling using a dual-specific CAR-T cell, where the same cell was triggered via TCR (tcrCTL) or CAR (carCTL). The carCTL immune synapse lacked distinct LFA-1 adhesion rings and was less reliant on LFA to form stable conjugates with target cells. carCTL receptors associated with the synapse were found to be disrupted and formed a convoluted multifocal pattern of Lck microclusters. Both proximal and distal receptor signaling pathways were induced more rapidly and subsequently decreased more rapidly in carCTL than in tcrCTL. The functional consequence of this rapid signaling in carCTL cells included faster lytic granule recruitment to the immune synapse, correlating with faster detachment of the CTL from the target cell. This study provides a mechanism for how CAR-T cells can debulk large tumor burden quickly and may contribute to further refinement of CAR design for enhancing the quality of signaling and programming of the T cell. Copyright © 2018 the Author(s). Published by PNAS.

  3. Deletion of the GluA1 AMPA Receptor Subunit Alters the Expression of Short-Term Memory

    Science.gov (United States)

    Sanderson, David J.; Sprengel, Rolf; Seeburg, Peter H.; Bannerman, David M.

    2011-01-01

    Deletion of the GluA1 AMPA receptor subunit selectively impairs short-term memory for spatial locations. We further investigated this deficit by examining memory for discrete nonspatial visual stimuli in an operant chamber. Unconditioned suppression of magazine responding to visual stimuli was measured in wild-type and GluA1 knockout mice.…

  4. Development and validation of an item response theory-based Social Responsiveness Scale short form.

    Science.gov (United States)

    Sturm, Alexandra; Kuhfeld, Megan; Kasari, Connie; McCracken, James T

    2017-09-01

    Research and practice in autism spectrum disorder (ASD) rely on quantitative measures, such as the Social Responsiveness Scale (SRS), for characterization and diagnosis. Like many ASD diagnostic measures, SRS scores are influenced by factors unrelated to ASD core features. This study further interrogates the psychometric properties of the SRS using item response theory (IRT), and demonstrates a strategy to create a psychometrically sound short form by applying IRT results. Social Responsiveness Scale analyses were conducted on a large sample (N = 21,426) of youth from four ASD databases. Items were subjected to item factor analyses and evaluation of item bias by gender, age, expressive language level, behavior problems, and nonverbal IQ. Item selection based on item psychometric properties, DIF analyses, and substantive validity produced a reduced item SRS short form that was unidimensional in structure, highly reliable (α = .96), and free of gender, age, expressive language, behavior problems, and nonverbal IQ influence. The short form also showed strong relationships with established measures of autism symptom severity (ADOS, ADI-R, Vineland). Degree of association between all measures varied as a function of expressive language. Results identified specific SRS items that are more vulnerable to non-ASD-related traits. The resultant 16-item SRS short form may possess superior psychometric properties compared to the original scale and emerge as a more precise measure of ASD core symptom severity, facilitating research and practice. Future research using IRT is needed to further refine existing measures of autism symptomatology. © 2017 Association for Child and Adolescent Mental Health.

  5. Validation of a Short Form of an Indecision Test: The Vocational Assessment Test

    Science.gov (United States)

    Picard, France; Frenette, Éric; Guay, Frédéric; Labrosse, Julie

    2015-01-01

    The purpose of this research was to validate the scores of a short form of a new instrument, "l'Épreuve de décision vocationnelle, forme scolaire" (EDV-9S; vocational assessment test), which measures six indecision-related problems (lack of self-knowledge, lack of readiness, lack of method in decision making, lack of information,…

  6. Enhanced long-term and impaired short-term spatial memory in GluA1 AMPA receptor subunit knockout mice: evidence for a dual-process memory model.

    Science.gov (United States)

    Sanderson, David J; Good, Mark A; Skelton, Kathryn; Sprengel, Rolf; Seeburg, Peter H; Rawlins, J Nicholas P; Bannerman, David M

    2009-06-01

    The GluA1 AMPA receptor subunit is a key mediator of hippocampal synaptic plasticity and is especially important for a rapidly-induced, short-lasting form of potentiation. GluA1 gene deletion impairs hippocampus-dependent, spatial working memory, but spares hippocampus-dependent spatial reference memory. These findings may reflect the necessity of GluA1-dependent synaptic plasticity for short-term memory of recently visited places, but not for the ability to form long-term associations between a particular spatial location and an outcome. This hypothesis is in concordance with the theory that short-term and long-term memory depend on dissociable psychological processes. In this study we tested GluA1-/- mice on both short-term and long-term spatial memory using a simple novelty preference task. Mice were given a series of repeated exposures to a particular spatial location (the arm of a Y-maze) before their preference for a novel spatial location (the unvisited arm of the maze) over the familiar spatial location was assessed. GluA1-/- mice were impaired if the interval between the trials was short (1 min), but showed enhanced spatial memory if the interval between the trials was long (24 h). This enhancement was caused by the interval between the exposure trials rather than the interval prior to the test, thus demonstrating enhanced learning and not simply enhanced performance or expression of memory. This seemingly paradoxical enhancement of hippocampus-dependent spatial learning may be caused by GluA1 gene deletion reducing the detrimental effects of short-term memory on subsequent long-term learning. Thus, these results support a dual-process model of memory in which short-term and long-term memory are separate and sometimes competitive processes.

  7. Prognostic and predictive value of intact and cleaved forms of the urokinase plasminogen activator receptor in metastatic prostate cancer

    DEFF Research Database (Denmark)

    Almasi, Charlotte E; Brasso, Klaus; Iversen, Peter

    2011-01-01

    The purpose of this study was to investigate the prognostic value of different forms of the urokinase receptor, uPAR, in serum from prostate cancer (PC) patients.......The purpose of this study was to investigate the prognostic value of different forms of the urokinase receptor, uPAR, in serum from prostate cancer (PC) patients....

  8. Multilevel Confirmatory Factor Analysis of the Teacher My Class Inventory-Short Form

    Science.gov (United States)

    Villares, Elizabeth; Mariani, Melissa; Sink, Christopher A.; Colvin, Kimberly

    2016-01-01

    Researchers analyzed data from elementary teachers (N = 233) to further establish the psychometric soundness of the Teacher My Class Inventory-Short Form. Supporting previous psychometric research, confirmatory factor analyses findings supported the factorial validity of the hypothesized five-factor solution. Internal reliability estimates were…

  9. Subthreshold pharmacological and genetic approaches to analyzing CaV2.1-mediated NMDA receptor signaling in short-term memory.

    Science.gov (United States)

    Takahashi, Eiki; Niimi, Kimie; Itakura, Chitoshi

    2010-10-25

    Ca(V)2.1 is highly expressed in the nervous system and plays an essential role in the presynaptic modulation of neurotransmitter release machinery. Recently, the antiepileptic drug levetiracetam was reported to inhibit presynaptic Ca(V)2.1 functions, reducing glutamate release in the hippocampus, although the precise physiological role of Ca(V)2.1-regulated synaptic functions in cognitive performance at the system level remains unknown. This study examined whether Ca(V)2.1 mediates hippocampus-dependent spatial short-term memory using the object location and Y-maze tests, and perirhinal cortex-dependent nonspatial short-term memory using the object recognition test, via a combined pharmacological and genetic approach. Heterozygous rolling Nagoya (rol/+) mice carrying the Ca(V)2.1alpha(1) mutation had normal spatial and nonspatial short-term memory. A 100mg/kg dose of levetiracetam, which is ineffective in wild-type controls, blocked spatial short-term memory in rol/+ mice. At 5mg/kg, the N-methyl-D-aspartate (NMDA) receptor blocker (+/-)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP), which is ineffective in wild-type controls, also blocked the spatial short-term memory in rol/+ mice. Furthermore, a combination of subthreshold doses of levetiracetam (25 mg/kg) and CPP (2.5mg/kg) triggered a spatial short-term memory deficit in rol/+ mice, but not in wild-type controls. Similar patterns of nonspatial short-term memory were observed in wild-type and rol/+ mice when injected with levetiracetam (0-300 mg/kg). These results indicate that Ca(V)2.1-mediated NMDA receptor signaling is critical in hippocampus-dependent spatial short-term memory and differs in various regions. The combination subthreshold pharmacological and genetic approach presented here is easily performed and can be used to study functional signaling pathways in neuronal circuits. Copyright © 2010 Elsevier B.V. All rights reserved.

  10. Clinical validation of three short forms of the Dutch Wechsler Memory Scale-Fourth Edition (WMS-IV-NL) in a mixed clinical sample.

    Science.gov (United States)

    Bouman, Zita; Hendriks, Marc P H; Van Der Veld, William M; Aldenkamp, Albert P; Kessels, Roy P C

    2016-06-01

    The reliability and validity of three short forms of the Dutch version of the Wechsler Memory Scale-Fourth Edition (WMS-IV-NL) were evaluated in a mixed clinical sample of 235 patients. The short forms were based on the WMS-IV Flexible Approach, that is, a 3-subtest combination (Older Adult Battery for Adults) and two 2-subtest combinations (Logical Memory and Visual Reproduction and Logical Memory and Designs), which can be used to estimate the Immediate, Delayed, Auditory and Visual Memory Indices. All short forms showed good reliability coefficients. As expected, for adults (16-69 years old) the 3-subtest short form was consistently more accurate (predictive accuracy ranged from 73% to 100%) than both 2-subtest short forms (range = 61%-80%). Furthermore, for older adults (65-90 years old), the predictive accuracy of the 2-subtest short form ranged from 75% to 100%. These results suggest that caution is warranted when using the WMS-IV-NL Flexible Approach short forms to estimate all four indices. © The Author(s) 2015.

  11. Ghrelin plasma levels in patients with idiopathic short stature.

    Science.gov (United States)

    Iñiguez, Germán; Román, Rossana; Youlton, Ronald; Cassorla, Fernando; Mericq, Verónica

    2011-02-01

    Novel molecular insights have suggested that ghrelin may be involved in the pathogenesis of some forms of short stature. Recently, growth hormone secretagogue receptor (GHSR) mutations that segregate with short stature have been reported. To study plasma ghrelin levels in prepubertal patients with idiopathic short stature (ISS). Fasting total plasma ghrelin levels (radioimmunoassay) in 41 prepubertal patients with ISS (18 females, age 7.9 ± 0.5 years) compared with 42 age- and sex-matched controls (27 females, age 8.0 ± 0.3 years) with normal height. In a subset of 28 patients, the ghrelin receptor was sequenced. ISS patients exhibited a higher level of ghrelin (1,458 ± 137 vs. 935 ± 55 pg/ml, p ghrelin levels greater than +2 SDS compared to controls. These patients did not differ in height, BMI or IGF-I SDS compared to ISS patients with ghrelin levels within the normal range. Molecular analysis of GHSR did not show any mutations, but showed some polymorphisms. These results suggest that in ISS patients, short stature does not appear to be frequently caused by abnormalities in ghrelin signaling. Copyright © 2010 S. Karger AG, Basel.

  12. Adiponectin receptors form homomers and heteromers exhibiting distinct ligand binding and intracellular signaling properties.

    Science.gov (United States)

    Almabouada, Farid; Diaz-Ruiz, Alberto; Rabanal-Ruiz, Yoana; Peinado, Juan R; Vazquez-Martinez, Rafael; Malagon, Maria M

    2013-02-01

    Adiponectin binds to two widely expressed receptors (AdipoR1 and AdipoR2) that contain seven transmembrane domains but, unlike G-protein coupled receptors, present an extracellular C terminus and a cytosolic N terminus. Recently, AdipoR1 was found to associate in high order complexes. However, it is still unknown whether AdipoR2 may also form homomers or heteromers with AdipoR1 or if such interactions may be functionally relevant. Herein, we have analyzed the oligomerization pattern of AdipoRs by FRET and immunoprecipitation and evaluated both the internalization of AdipoRs in response to various adiponectin isoforms and the effect of adiponectin binding to different AdipoR combinations on AMP-activated protein kinase phosphorylation and peroxisome proliferator-activated receptor α activation. Transfection of HEK293AD cells with AdipoR1 and AdipoR2 showed that both receptors colocalize at both the plasma membrane and the endoplasmic reticulum. Co-transfection with the different AdipoR pairs yielded high FRET efficiencies in non-stimulated cells, which indicates that AdipoR1 and AdipoR2 form homo- and heteromeric complexes under resting conditions. Live FRET imaging suggested that both homo- and heteromeric AdipoR complexes dissociate in response to adiponectin, but heteromers separate faster than homomers. Finally, phosphorylation of AMP-activated protein kinase in response to adiponectin was delayed in cells wherein heteromer formation was favored. In sum, our findings indicate that AdipoR1 and AdipoR2 form homo- and heteromers that present unique interaction behaviors and signaling properties. This raises the possibility that the pleiotropic, tissue-dependent functions of adiponectin depend on the expression levels of AdipoR1 and AdipoR2 and, therefore, on the steady-state proportion of homo- and heteromeric complexes.

  13. Psychometric evaluation and short form development of The Balanced Inventory of Desirable Responding (BIDR-6

    Directory of Open Access Journals (Sweden)

    Subotić Siniša

    2016-01-01

    Full Text Available The goals of this research were to evaluate the Bosnian-Croatian-Serbian (BCS translation of the BIDR-6 scale, develop its short form, and to present its initial convergent/discriminative validation. The sample included 827 participants. MIRT CFA analysis revealed that fourfactor model (containing 32/40 items fits the data best, with Self-Deceptive Enhancement (SDE and Impression Management (IM both splitting into the denial (SD-D and IM-D and enhancement (SD-E and IM-E factors. Fit and item properties were generally mediocre. SD-D and IM-E subscales were the strongest sources of misfit, thus SD-E and IM-D subscales were retained in the short form, which had good fit and replicated almost all main patterns of associations with other variables of interest (e.g., HEXACO personality traits typically reported for the full SDE and IM scales in other research. Thus, 17-item BIDR-6 short form, containing only SD-E and IM-D subscales, is recommended for use in the BCS speaking area.

  14. The short story as a form of self-legitimation and self-reflexion (on the example of a Bosnian and Hercegovinian short story

    Directory of Open Access Journals (Sweden)

    Larisa Softić-Gasal

    2015-09-01

    Full Text Available The short story, as a new literary genre of Bosnian and Herzegovinian literature of the transitional period, has found its way to enter the market of recipients. The role of the reader as a member of a specific cultural group is very important when trying to define the short story. The reader is one of the participants of a contextual network that makes all literary works “open”, thus offering enormous possibilities of detailed reading, rereading and reflection. Previous attempts to define the short story depict it as a modern, contemporary and intensive prose form and a response to the internal raptures of modern recipients. Engaging readers in the process of creating has been achieved by the well-known Brechtian waking up to reality which breaks, to some extent, both the narrative and theatrical illusions. By comparing the so called open forms of stories/dramas,a particular pattern of linguistic behaviour of characters is observed that reflects their difficulties to articulate their feelings, to express them and to reveal them to themselves and to others. Most of the compared short stories/dramas of open forms are characterized by impaired communication between characters. Their statements barely follow one another or, in turn, come with hesitation and have the characteristics of intellectual disability. Zlatko Topčić’s stories Garib and Hasanaginica present the social problem of accepting the allegorical morality/mentality of male society, while promoting the characters as carriers of both the burden of otherness and their own immanent perspective of resistance. Games of signifiers (God, ownership, state represent the power of the ideology of modern class society. Many short stories from the period of transition of Bosnian and Herzegovinian society are a valuable challenge to the reader’s sensibility to grasp the relativity of the perspective of all socially assumed standards of evaluation.

  15. Motor competence assessment in children: convergent and discriminant validity between the BOT-2 Short Form and KTK testing batteries.

    Science.gov (United States)

    Fransen, Job; D'Hondt, Eva; Bourgois, Jan; Vaeyens, Roel; Philippaerts, Renaat M; Lenoir, Matthieu

    2014-06-01

    This study investigated convergent and discriminant validity between two motor competence assessment instruments in 2485 Flemish children: the Bruininks-Oseretsky Test of Motor Proficiency 2 Short Form (BOT-2 Short Form) and the KörperKoördinationsTest für Kinder (KTK). A Pearson correlation assessed the relationship between BOT-2 Short Form total, gross and fine motor composite scores and KTK Motor Quotient in three age cohorts (6-7, 8-9, 10-11 years). Crosstabs were used to measure agreement in classification in children scoring below percentile 5 and 15 and above percentile 85 and 95. Moderately strong positive (r=0.44-0.64) associations between BOT-2 total and gross motor composite scores and KTK Motor Quotient and weak positive correlations between BOT-2 Short Form fine motor composite and KTK Motor Quotient scores (r=0.25-0.37) were found. Levels of agreement were fair to moderate. Therefore, some proof of convergent and discriminant validity between BOT-2 Short Form and KTK was established in this study, underlining the notion that the evaluation of motor competence should not be based upon a single assessment instrument. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. A new Drosophila octopamine receptor responds to serotonin.

    Science.gov (United States)

    Qi, Yi-Xiang; Xu, Gang; Gu, Gui-Xiang; Mao, Fen; Ye, Gong-Yin; Liu, Weiwei; Huang, Jia

    2017-11-01

    As the counterparts of the vertebrate adrenergic transmitters, octopamine and tyramine are important physiological regulators in invertebrates. They control and modulate many physiological and behavioral functions in insects. In this study, we reported the pharmacological properties of a new α2-adrenergic-like octopamine receptor (CG18208) from Drosophila melanogaster, named DmOctα2R. This new receptor gene encodes two transcripts by alternative splicing. The long isoform DmOctα2R-L differs from the short isoform DmOctα2R-S by the presence of an additional 29 amino acids within the third intracellular loop. When heterologously expressed in mammalian cell lines, both receptors were activated by octopamine, tyramine, epinephrine and norepinephrine, resulting in the inhibition of cAMP production in a dose-dependent manner. The long form is more sensitive to the above ligands than the short form. The adrenergic agonists naphazoline, tolazoline and clonidine can stimulate DmOctα2R as full agonists. Surprisingly, serotonin and serotoninergic agonists can also activate DmOctα2R. Several tested adrenergic antagonists and serotonin antagonists blocked the action of octopamine or serotonin on DmOctα2R. The data presented here reported an adrenergic-like G protein-coupled receptor activated by serotonin, suggesting that the neurotransmission and neuromodulation in the nervous system could be more complex than previously thought. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Short-term desensitization of the histamine H1 receptor in human HeLa cells : involvement of protein kinase C dependent and independent pathways

    NARCIS (Netherlands)

    Smit, M J; Bloemers, S M; Leurs, R; Tertoolen, L G; Bast, A; de Laat, S W; Timmerman, H

    1992-01-01

    1. In this study we have investigated the effects of short-term exposure of cells to histamine on the subsequent H1 receptor responsiveness in HeLa cells, using Ca2+ fluorescence microscopy and video digital imaging. 2. In HeLa cells, histamine (100 microM) induces an immediate H1 receptor-mediated

  18. Temporal stability of the Francis Scale of Attitude toward Christianity short-form: test-retest data over one week.

    Science.gov (United States)

    Lewis, Christopher Alan; Cruise, Sharon Mary; McGuckin, Conor

    2005-04-01

    This study evaluated the test-retest reliability of the Francis Scale of Attitude toward Christianity short-form. 39 Northern Irish undergraduate students completed the measure on two occasions separated by one week. Stability across the two administrations was high, r = .92, and there was no significant change between Time 1(M = 25.2, SD = 5.4) and Time 2 (M = 25.7, SD = 6.2). These data support the short-term test-retest reliability of the Francis Scale of Attitude toward Christianity short-form.

  19. Modulation of short-term plasticity in the corticothalamic circuit by group III metabotropic glutamate receptors.

    Science.gov (United States)

    Kyuyoung, Christine L; Huguenard, John R

    2014-01-08

    Recurrent connections in the corticothalamic circuit underlie oscillatory behavior in this network and range from normal sleep rhythms to the abnormal spike-wave discharges seen in absence epilepsy. The propensity of thalamic neurons to fire postinhibitory rebound bursts mediated by low-threshold calcium spikes renders the circuit vulnerable to both increased excitation and increased inhibition, such as excessive excitatory cortical drive to thalamic reticular (RT) neurons or heightened inhibition of thalamocortical relay (TC) neurons by RT. In this context, a protective role may be played by group III metabotropic receptors (mGluRs), which are uniquely located in the presynaptic active zone and typically act as autoreceptors or heteroceptors to depress synaptic release. Here, we report that these receptors regulate short-term plasticity at two loci in the corticothalamic circuit in rats: glutamatergic cortical synapses onto RT neurons and GABAergic synapses onto TC neurons in somatosensory ventrobasal thalamus. The net effect of group III mGluR activation at these synapses is to suppress thalamic oscillations as assayed in vitro. These findings suggest a functional role of these receptors to modulate corticothalamic transmission and protect against prolonged activity in the network.

  20. Depressive symptoms in breast cancer: Beck Depression Inventory - Short Form

    OpenAIRE

    Cangussu, Renata de Oliveira; Soares, Thiago Barbabela de Castro; Barra, Alexandre de Almeida; Nicolato, Rodrigo

    2010-01-01

    Objetivos: Verificar a prevalência de sintomas depressivos em mulheres com câncer de mama e identificar os fatores de risco associados à sua ocorrência. Métodos: Foi realizado um estudo transversal, em que foram entrevistadas 71 mulheres com câncer de mama. Foram empregados dois instrumentos: um questionário para verificar os dados sociodemográficos e clínicos e o Inventário de Depressão de Beck – Short Form (BDI-SF), para avaliação dos sintomas depressivos. Para análise dos da...

  1. Short-chain free fatty acid receptors FFA2/GPR43 and FFA3/GPR41 as new potential therapeutic targets

    DEFF Research Database (Denmark)

    Ulven, Trond

    2012-01-01

    The deorphanization of the free fatty acid (FFA) receptors FFA1 (GPR40), FFA2 (GPR43), FFA3 (GPR41), GPR84, and GPR120 has made clear that the body is capable of recognizing and responding directly to nonesterified fatty acid of virtually any chain length. Colonic fermentation of dietary fiber...... produces high concentrations of the short-chain fatty acids (SCFAs) acetate, propionate and butyrate, a process which is important to health. The phylogenetically related 7-transmembrane (7TM) receptors free fatty acid receptor 2 (FFA2) and FFA3 are activated by these SCFAs, and several lines of evidence...... in general have properties that make them less than ideal as such tools, but published patent applications indicate that better tool compounds might soon become available which should enable studies critical to validate the receptors as new drug targets....

  2. [Validation of the French version of the Maternal Self-report Inventory (short form)].

    Science.gov (United States)

    Denis, A; Séjourné, N; Callahan, S

    2013-06-01

    Self-esteem is defined as the opinion of one's self that one establishes and maintains during the lifetime. Self-esteem is considered to be based on general as well as specific elements that define the individual's identity. Whereas overall self-esteem evolves over the lifespan, specific elements change regularly and thus have an impact on these specific types of self-esteem. Maternity is a central defining element of a woman's life, and it is believed that a woman can develop a specific self-esteem based on her experience of motherhood. Many studies have shown how overall self-esteem is affected during the perinatal period, and the relationship between self-esteem and other variables, notably post-partum depression. The objective of this study was to translate, evaluate, and validate the short version of the Maternal Self-Esteem Inventory (MSI, Shea & Tronick in 1988) for use in French populations. The MSI short form is a 26-item questionnaire using a Likert response format in five points. The sample was composed of 251 French female participants (mean age 30; SD=4.52) who had given birth two days earlier. Participants completed the MSI and the Edinburgh Post-natal Depression Scale (EDPS). The results of a factorial analysis showed five factors which partially correspond to the original English version of the MSI short form. These five factors were negatively correlated to the EPDS. The five factors showed good to excellent internal consistency. The current study provides a translated and validated version of the MSI short form in French. It provides a specific indicator of self-esteem with regards to motherhood and the experience of maternity. The MSI can provide useful data that can help identify women at risk for negative feelings about themselves, which can lead later to manifestations of perinatal psychopathology (e.g, post-partum depression). Copyright © 2012 L’Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.

  3. Development and Evaluation of the Boston University Osteoarthritis Functional Pain Short Form (BU-OA-FPS).

    Science.gov (United States)

    Goode, Adam P; Ni, Pengshend; Jette, Alan; Fitzgerald, G Kelley

    2018-04-19

    Pragmatic studies have gained popularity, thus emphasizing the need for patient-reported outcomes (PRO) to be integrated into electronic health records. This study describes the development of a customized short form from the Boston University Osteoarthritis Functional Assessment PRO (BU-OA-PRO) for a specific pragmatic clinical trial. A Functional Pain Short Form was created from an existing item bank of deidentified data in the BU-OA-PRO. Item response theory (IRT) methods were used to select items. Reliability was measured with the Cronbach alpha, then with IRT simulation methods. To examine validity, ceiling and floor effects, correlations between the short-form scores and scores from the BU-OA-PRO and the Western Ontario McMasters University Osteoarthritis Index (WOMAC) Pain and Difficulty subscales, and the area under the curve (AUC) were calculated. A minimum detectable change at 90% confidence (MDC90) was calculated based on a calibration sample. The BU-OA PRO was reduced from 126 items to 10 items to create the BU-OA Functional Pain Short Form (BU-OA-FPS). The Cronbach alpha indicated high internal consistency (0.91), and reliability distribution estimates were 0.96 (uniform) and 0.92 (normal). Low ceiling effects (4.57%), and floor effects (0%) were found. Moderate-to-high correlations between the BU-OA PRO and BU-OA-FPS were found with WOMAC Pain (BU-OA-FPS = 0.67; BU-OA-PRO = 0.64) and Difficulty (BU-OA-FPS = 0.73; BU-OA-PRO = 0.69) subscales. The correlation between the BU-OA-PRO and BU-OA-FPS was 0.94. The AUC ranged from 0.80 to 0.88. The MDC90 was approximately 6 standardized points. The BU-OA-FPS provides reliable and valid measurement of functional pain. Pragmatic studies may consider the BU-OA-FPS for use in electronic health records to capture outcomes.

  4. Evaluating Short-Form Versions of the CES-D for Measuring Depressive Symptoms among Immigrants from Mexico

    Science.gov (United States)

    Grzywacz, Joseph G.; Hovey, Joseph D.; Seligman, Laura D.; Arcury, Thomas A.; Quandt, Sara A.

    2006-01-01

    This article examines the feasibility of using a short-form version of the Center for Epidemiologic Studies-Depression Scale (CES-D) in community mental health research with Mexican immigrants. Several features of three published short versions of the CES-D were examined using data combined from seven diverse Mexican immigrant samples from across…

  5. Psychometric properties of Positive and Negative Affect Schedule (PANAS) original and short forms in an African American community sample.

    Science.gov (United States)

    Merz, Erin L; Malcarne, Vanessa L; Roesch, Scott C; Ko, Celine M; Emerson, Marc; Roma, Vincenzo G; Sadler, Georgia Robins

    2013-12-01

    The Positive and Negative Affect Schedule (PANAS) has been widely used as a self-report measure of affect in community and clinical contexts. However, evaluations of the psychometric properties of PANAS scores have been limited in diverse ethnic groups. Several short forms of the PANAS have also been proposed, but very little is known about the psychometric properties of these versions. The present study investigated the psychometric properties, including the factor structure of the original PANAS and two short forms in an African American community sample (N=239). Descriptive, internal consistency reliability, factorial validity, and measurement invariance analyses were conducted. All PANAS subscales from the original and short forms had adequate internal consistency. For the original PANAS, the model specifying three correlated factors (Positive Affect, Afraid, Upset) with correlated uniquenesses from redundant items provided the best fit to the data. However, the two-factor model (Positive Affect, Negative Affect) with correlated uniquenesses was also supported. For both short forms, the two-factor model with correlated uniquenesses fit the data best. Factors from all forms were generally invariant across age and gender, although there was some minor invariance at the item level. Participants were from a limited geographic area and one ethnic group. Indicators of anxiety, depression, and cultural characteristics were not measured. The factor structure was replicated, suggesting no immediate concerns regarding the valid interpretation of PANAS scores. The results support the reliability and validity of the PANAS and its short forms for use among African Americans. © 2013 Elsevier B.V. All rights reserved.

  6. The roles of Eph receptors in contextual fear conditioning memory formation.

    Science.gov (United States)

    Dines, Monica; Grinberg, Svetlana; Vassiliev, Maria; Ram, Alon; Tamir, Tal; Lamprecht, Raphael

    2015-10-01

    Eph receptors regulate glutamate receptors functions, neuronal morphology and synaptic plasticity, cellular events believed to be involved in memory formation. In this study we aim to explore the roles of Eph receptors in learning and memory. Toward that end, we examined the roles of EphB2 and EphA4 receptors, key regulators of synaptic functions, in fear conditioning memory formation. We show that mice lacking EphB2 (EphB2(-/-)) are impaired in short- and long-term contextual fear conditioning memory. Mice that express a carboxy-terminally truncated form of EphB2 that lacks forward signaling, instead of the full EphB2, are impaired in long-term, but not short-term, contextual fear conditioning memory. Long-term contextual fear conditioning memory is attenuated in CaMKII-cre;EphA4(lx/-) mice where EphA4 is removed from all pyramidal neurons of the forebrain. Mutant mice with targeted kinase-dead EphA4 (EphA4(KD)) exhibit intact long-term contextual fear conditioning memory showing that EphA4 kinase-mediated forward signaling is not needed for contextual fear memory formation. The ability to form long-term conditioned taste aversion (CTA) memory is not impaired in the EphB2(-/-) and CaMKII-cre;EphA4(lx/-) mice. We conclude that EphB2 forward signaling is required for long-term contextual fear conditioning memory formation. In contrast, EphB2 mediates short-term contextual fear conditioning memory formation in a forward signaling-independent manner. EphA4 mediates long-term contextual fear conditioning memory formation in a kinase-independent manner. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Differential involvement of cortical muscarinic and NMDA receptors in short- and long-term taste aversion memory.

    Science.gov (United States)

    Ferreira, G; Gutiérrez, R; De La Cruz, V; Bermúdez-Rattoni, F

    2002-09-01

    In conditioned taste aversion, an animal avoids a taste previously associated with toxic effects, and this aversive memory formation requires an intact insular cortex. In this paper, we investigated the possible differential involvement of cholinergic and glutamatergic receptors in the insular cortex in short-term memory (STM) and long-term memory (LTM) of taste aversion in rats. Taste aversion was induced by intraperitoneal administration of lithium chloride (a malaise-inducing drug) 15 min after experience with an unfamiliar taste. In order to test STM and LTM of taste aversion, taste stimulus was again presented 4 h and 72 h after lithium injection, respectively. During the acquisition, microinjection of the muscarinic antagonist, scopolamine, in the insular cortex before, but not after, the presentation of the new taste, abolished STM as well as LTM. Blockade of the NMDA receptor, in the insular cortex, by AP5 before, but not after, the presentation of the taste stimulus, impaired LTM but left STM intact. Moreover, when injected 1 h after malaise induction (i.e., during taste-illness association), AP5 disrupted both STM and LTM. These results suggest that activation of muscarinic receptors in the insular cortex is involved in the acquisition of taste memory, whereas NMDA receptors participate in taste memory consolidation. These data demonstrate that different neurochemical mechanisms subserve different memory phases. NMDA receptors are also probably involved in processing the visceral input, thus allowing subsequent taste-illness association. This indicates that in the same cortical area the same neurotransmitter system can be involved in distinct processes: taste memory consolidation vs. taste-illness association.

  8. Accuracy of WISC-III and WAIS-IV short forms in patients with neurological disorders

    NARCIS (Netherlands)

    van Ool, Jans S.; Hurks, Petra P.M.; Snoeijen-Schouwenaars, Francesca M.; Tan, In Y.; Schelhaas, Helenius J.; Klinkenberg, Sylvia; Aldenkamp, Albert P.; Hendriksen, Jos G.M.

    2018-01-01

    The assessment of intellectual abilities is intensive, time-consuming, and might be considered burdensome for patients. We examined psychometric qualities of short forms (SFs) of the Wechsler Intelligence Scales for Children (WISC-third edition) and for adults (WAIS-fourth edition), in children (n =

  9. A Factor Analytic Study of the Coopersmith Self-Esteem Inventory Adult Short Form.

    Science.gov (United States)

    Haines, Janet; Wilson, George V.

    1988-01-01

    A factor analysis was conducted on the Coopersmith Self-Esteem Inventory-Adult Short Form using 237 college students and 43 female office workers in Australia. Factors were found corresponding with three of the four subscales: general self, social self-peers, and home-parents (family). No factor related to the school-academic (work) subscale. (SLD)

  10. Short form of Demodex species mite in the dog: occurrence and measurements.

    Science.gov (United States)

    Chesney, C J

    1999-02-01

    A form of Demodex species mite shorter in length than Demodex canis was found in six consecutive cases of canine demodicosis. The mean length of the parasite was 122.6 microns (SD 12.0 microns, 39 mites counted), significantly shorter than either male or female forms of D canis (P < 0.0001). The proportion of short to long mites in each case varied from 0.5 to 22 per 100. In young dogs, skin signs associated with the presence of mites were first noted after about seven months, while in the oldest subject the disease became apparent at 10 years of age. This form of mite has now been found in four countries over three continents, the findings suggesting that it is not uncommon and is acquired in puppyhood, although it may be carried unnoticed for many years.

  11. Effects of ethanolic extract and naphthoquinones obtained from the bulbs of Cipura paludosa on short-term and long-term memory: involvement of adenosine A₁ and A₂A receptors.

    Science.gov (United States)

    Lucena, Greice M R S; Matheus, Filipe C; Ferreira, Vania M; Tessele, Priscila B; Azevedo, Mariangela S; Cechinel-Filho, Valdir; Prediger, Rui D

    2013-04-01

    Previous studies from our group have indicated important biological properties of the ethanolic extract and isolated compounds from the bulbs of Cipura paludosa (Iridaceae), a native plant widely distributed in northern Brazil, including antioxidant, neuroprotective and anti-nociceptive activities. In the present study, the effects of the ethanolic extract and its two naphthoquinones (eleutherine and isoeleutherine) on the short- and long-term memory of adult rodents were assessed in social recognition and inhibitory avoidance tasks. Acute pre-training oral administration of the ethanolic extract improved the short-term social memory in rats as well as facilitated the step-down inhibitory avoidance short- and long-term memory in mice. Moreover, the co-administration of 'non-effective' doses of the extract of Cipura paludosa and the adenosine receptor antagonists caffeine (non-selective), DPCPX (adenosine A1 receptor antagonist) and ZM241385 (adenosine A2A receptor antagonist) improved the social recognition memory of rats. In the inhibitory avoidance task, the co-administration of sub-effective doses of the extract with caffeine or ZM241385, but not with DPCPX, improved the short- and long-term memory of mice. Finally, the acute oral administration of eleutherine and isoeleutherine facilitated the inhibitory avoidance short- and long-term memory in mice. These results demonstrate for the first time the cognitive-enhancing properties of the extract and isolated compounds from the bulbs of Cipura paludosa in rodents and suggest a possible involvement of adenosine A1 and A2A receptors in these effects. © 2012 The Authors Basic & Clinical Pharmacology & Toxicology © 2012 Nordic Pharmacological Society.

  12. Neurotrophins play differential roles in short and long-term recognition memory.

    Science.gov (United States)

    Callaghan, Charlotte K; Kelly, Aine M

    2013-09-01

    The neurotrophin family of proteins are believed to mediate various forms of synaptic plasticity in the adult brain. Here we have assessed the roles of these proteins in object recognition memory in the rat, using icv infusions of function-blocking antibodies or the tyrosine kinase antagonist, tyrphostin AG879, to block Trk receptors. We report that tyrphostin AG879 impairs both short-term and long-term recognition memory, indicating a requirement for Trk receptor activation in both processes. The effect of inhibition of each of the neurotrophins with activity-blocking neutralising antibodies was also tested. Treatment with anti-BDNF, anti-NGF or anti-NT4 had no effect on short-term memory, but blocked long-term recognition memory. Treatment with anti-NT3 had no effect on either process. We also assessed changes in expression of neurotrophins and their respective receptors in the hippocampus, dentate gyrus and perirhinal cortex over a 24 h period following training in the object recognition task. We observed time-dependent changes in expression of the Trk receptors and their ligands in the dentate gyrus and perirhinal cortex. The data are consistent with a pivotal role for neurotrophic factors in the expression of recognition memory. Copyright © 2013 Elsevier Inc. All rights reserved.

  13. German Translation and Validation of the Cognitive Style Questionnaire Short Form (CSQ-SF-D.

    Directory of Open Access Journals (Sweden)

    Quentin J M Huys

    Full Text Available The Cognitive Style Questionnaire is a valuable tool for the assessment of hopeless cognitive styles in depression research, with predictive power in longitudinal studies. However, it is very burdensome to administer. Even the short form is still long, and neither this nor the original version exist in validated German translations.The questionnaire was translated from English to German, back-translated and commented on by clinicians. The reliability, factor structure and external validity of an online form of the questionnaire were examined on 214 participants. External validity was measured on a subset of 90 subjects.The resulting CSQ-SF-D had good to excellent reliability, both across items and subscales, and similar external validity to the original English version. The internality subscale appeared less robust than other subscales. A detailed analysis of individual item performance suggests that stable results could be achieved with a very short form (CSQ-VSF-D including only 27 of the 72 items.The CSQ-SF-D is a validated and freely distributed translation of the CSQ-SF into German. This should make efficient assessment of cognitive style in German samples more accessible to researchers.

  14. Validity and Reliability of International Physical Activity Questionnaire-Short Form in Chinese Youth

    Science.gov (United States)

    Wang, Chao; Chen, Peijie; Zhuang, Jie

    2013-01-01

    Purpose: The psychometric profiles of the widely used International Physical Activity Questionnaire-Short Form (IPAQ-SF) in Chinese youth have not been reported. The purpose of this study was to examine the validity and reliability of the IPAQ-SF using a sample of Chinese youth. Method: One thousand and twenty-one youth (M[subscript age] = 14.26 ±…

  15. Soluble urokinase-type plasminogen activator receptor forms in plasma as markers of atherosclerotic plaque vulnerability

    DEFF Research Database (Denmark)

    Olson, Fredrik J; Thurison, Tine; Ryndel, Mikael

    2009-01-01

    OBJECTIVES:: To test if circulating forms of the soluble urokinase-type plasminogen activator receptor (suPAR) are potential biomarkers of plaque vulnerability. DESIGN AND METHODS:: Plasma concentrations of suPAR(I-III), suPAR(II-III) and uPAR(I) were measured by time-resolved fluorescence immuno...

  16. Methodical Challenges and a Possible Resolution in the Assessment of Receptor Reserve for Adenosine, an Agonist with Short Half-Life

    Directory of Open Access Journals (Sweden)

    Judit Zsuga

    2017-05-01

    Full Text Available The term receptor reserve, first introduced and used in the traditional receptor theory, is an integrative measure of response-inducing ability of the interaction between an agonist and a receptor system (consisting of a receptor and its downstream signaling. The underlying phenomenon, i.e., stimulation of a submaximal fraction of receptors can apparently elicit the maximal effect (in certain cases, provides an opportunity to assess the receptor reserve. However, determining receptor reserve is challenging for agonists with short half-lives, such as adenosine. Although adenosine metabolism can be inhibited several ways (in order to prevent the rapid elimination of adenosine administered to construct concentration–effect (E/c curves for the determination, the consequent accumulation of endogenous adenosine biases the results. To address this problem, we previously proposed a method, by means of which this bias can be mathematically corrected (utilizing a traditional receptor theory-independent approach. In the present investigation, we have offered in silico validation of this method by simulating E/c curves with the use of the operational model of agonism and then by evaluating them using our method. We have found that our method is suitable to reliably assess the receptor reserve for adenosine in our recently published experimental setting, suggesting that it may be capable for a qualitative determination of receptor reserve for rapidly eliminating agonists in general. In addition, we have disclosed a possible interference between FSCPX (8-cyclopentyl-N3-[3-(4-(fluorosulfonylbenzoyloxypropyl]-N1-propylxanthine, an irreversible A1 adenosine receptor antagonist, and NBTI (S-(2-hydroxy-5-nitrobenzyl-6-thioinosine, a nucleoside transport inhibitor, i.e., FSCPX may blunt the effect of NBTI.

  17. 48 CFR 52.249-4 - Termination for Convenience of the Government (Services) (Short Form).

    Science.gov (United States)

    2010-10-01

    ... Convenience of the Government (Services) (Short Form). 52.249-4 Section 52.249-4 Federal Acquisition... CONTRACT CLAUSES Text of Provisions and Clauses 52.249-4 Termination for Convenience of the Government... convenience of the Government, limit termination settlement charges to services rendered before the date of...

  18. Immunologic differentiation of two high-affinity neurotensin receptor isoforms in the developing rat brain.

    Science.gov (United States)

    Boudin, H; Lazaroff, B; Bachelet, C M; Pélaprat, D; Rostène, W; Beaudet, A

    2000-09-11

    Earlier studies have demonstrated overexpression of NT1 neurotensin receptors in rat brain during the first 2 weeks of life. To gain insight into this phenomenon, we investigated the identity and distribution of NT1 receptor proteins in the brain of 10-day-old rats by using two different NT1 antibodies: one (Abi3) directed against the third intracellular loop and the other (Abi4) against the C-terminus of the receptor. Immunoblot experiments that used Abi3 revealed the presence of two differentially glycosylated forms of the NT1 receptor in developing rat brain: one migrating at 54 and the other at 52 kDa. Whereas the 54-kDa form was expressed from birth to adulthood, the 52-kDa form was detected only at 10 and 15 days postnatal. Only the 52-kDa isoform was recognized by Abi4. By immunohistochemistry, both forms of the receptor were found to be predominantly expressed in cerebral cortex and dorsal hippocampus, in keeping with earlier radioligand binding and in situ hybridization data. However, whereas Abi4 immunoreactivity was mainly concentrated within nerve cell bodies and extensively colocalized with the Golgi marker alpha-mannosidase II, Abi3 immunoreactivity was predominantly located along neuronal processes. These results suggest that the transitorily expressed 52-kDa protein corresponds to an immature, incompletely glycosylated and largely intracellular form of the NT1 receptor and that the 54-kDa protein corresponds to a mature, fully glycosylated, and largely membrane-associated form. They also indicate that antibodies directed against different sequences of G-protein-coupled receptors may yield isoform-specific immunohistochemical labeling patterns in mammalian brain. Finally, the selective expression of the short form of the NT1 receptor early in development suggests that it may play a specific role in the establishment of neuronal circuitry. Copyright 2000 Wiley-Liss, Inc.

  19. Specific immunoassays for detection of intact and cleaved forms of the urokinase receptor

    DEFF Research Database (Denmark)

    Piironen, Timo; Laursen, Birgitte; Pass, Jesper

    2004-01-01

    BACKGROUND: The cell surface receptor (uPAR) for urokinase plasminogen activator (uPA) is a strong prognostic marker in several types of cancer. uPA cleaves the three-domain protein uPAR(I-III) into two fragments: uPAR(I), which contains domain I; and uPAR(II-III), which contains domains II and III...... of the diagnostic and prognostic value of individual uPAR forms in cancer patients....

  20. Real-Time G-Protein-Coupled Receptor Imaging to Understand and Quantify Receptor Dynamics

    Directory of Open Access Journals (Sweden)

    María S. Aymerich

    2011-01-01

    Full Text Available Understanding the trafficking of G-protein-coupled receptors (GPCRs and their regulation by agonists and antagonists is fundamental to develop more effective drugs. Optical methods using fluorescent-tagged receptors and spinning disk confocal microscopy are useful tools to investigate membrane receptor dynamics in living cells. The aim of this study was to develop a method to characterize receptor dynamics using this system which offers the advantage of very fast image acquisition with minimal cell perturbation. However, in short-term assays photobleaching was still a problem. Thus, we developed a procedure to perform a photobleaching-corrected image analysis. A study of short-term dynamics of the long isoform of the dopamine type 2 receptor revealed an agonist-induced increase in the mobile fraction of receptors with a rate of movement of 0.08 μm/s For long-term assays, the ratio between the relative fluorescence intensity at the cell surface versus that in the intracellular compartment indicated that receptor internalization only occurred in cells co-expressing G protein-coupled receptor kinase 2. These results indicate that the lateral movement of receptors and receptor internalization are not directly coupled. Thus, we believe that live imaging of GPCRs using spinning disk confocal image analysis constitutes a powerful tool to study of receptor dynamics.

  1. Comparing short forms of the Social Interaction Anxiety Scale and the Social Phobia Scale.

    Science.gov (United States)

    Carleton, R Nicholas; Thibodeau, Michel A; Weeks, Justin W; Teale Sapach, Michelle J N; McEvoy, Peter M; Horswill, Samantha C; Heimberg, Richard G

    2014-12-01

    The Social Interaction Anxiety Scale (SIAS) and the Social Phobia Scale (SPS; Mattick & Clarke, 1998) are companion scales developed to measure anxiety in social interaction and performance situations, respectively. The measures have strong discriminant and convergent validity; however, their factor structures remain debated, and furthermore, the combined administration length (i.e., 39 items) can be prohibitive for some settings. There have been 4 attempts to assess the factor structures of the scales and reduce the item content: the 14-item Social Interaction Phobia Scale (SIPS; Carleton et al., 2009), the 12-item SIAS-6/SPS-6 (Peters, Sunderland, Andrews, Rapee, & Mattick, 2012), the 21-item abbreviated SIAS/SPS (ASIAS/ASPS; Kupper & Denollet, 2012), and the 12-item Readability SIAS and SPS (RSIAS/RSPS; Fergus, Valentiner, McGrath, Gier-Lonsway, & Kim, 2012). The current study compared the short forms on (a) factor structure, (b) ability to distinguish between clinical and non-clinical populations, (c) sensitivity to change following therapy, and (d) convergent validity with related measures. Participants included 3,607 undergraduate students (55% women) and 283 patients with social anxiety disorder (43% women). Results of confirmatory factor analyses, sensitivity analyses, and correlation analyses support the robust utility of items in the SIPS and the SPS-6 and SIAS-6 relative to the other short forms; furthermore, the SIPS and the SPS-6 and SIAS-6 were also supported by convergent validity analyses within the undergraduate sample. The RSIAS/RSPS and the ASIAS/ASPS were least supported, based on the current results and the principle of parsimony. Accordingly, researchers and clinicians should consider carefully which of the short forms will best suit their needs. (c) 2014 APA, all rights reserved.

  2. The role of the form factor and short-range correlation in the relativistic Hartree-Fock model for nuclear matter

    Science.gov (United States)

    Hu, J.; Toki, H.; Wen, W.; Shen, H.

    2010-03-01

    The role of the form factor and short-range correlation in nuclear matter is studied within the relativistic Hartree-Fock approximation. We take, first, the mean-field approximation for meson fields and obtain the fluctuation terms of mesons to be used for the Fock energies. We introduce form factors in the meson-nucleon coupling vertices to take into account the finite-size effect of the nucleon. We use further the unitary correlation operator method for the treatment of the short-range correlation. The form factors of the size ( Λ ˜ 1.0 -2.0GeV) of the nucleon-nucleon interaction cut down largely the contribution of the ρ -meson in the Fock term. The short-range correlation effect is not large but has a significant effect on the pion and ρ -meson energies in the relativistic Hartree-Fock approximation for nuclear matter.

  3. The Balanced Inventory of Desirable Responding Short Form (BIDR-16

    Directory of Open Access Journals (Sweden)

    Claire M. Hart

    2015-12-01

    Full Text Available Self-report studies often call for assessment of socially desirable responding. Many researchers use the Marlowe–Crowne Scale for its brief versions; however, this scale is outdated, and contemporary models of social desirability emphasize its multi-dimensional nature. The 40-item Balanced Inventory of Desirable Responding (BIDR incorporates Self-Deceptive Enhancement (honest but overly positive responding and Impression Management (bias toward pleasing others. However, its length limits its practicality. This article introduces the BIDR-16. In four studies, we shorten the BIDR from 40 items to 16 items, while retaining its two-factor structure, reliability, and validity. This short form will be invaluable to researchers wanting to assess social desirability when time is limited.

  4. Internal consistency, reliability, and temporal stability of the Oxford Happiness Questionnaire short-form: Test-retest data over two weeks

    OpenAIRE

    MCGUCKIN, CONOR

    2006-01-01

    PUBLISHED The Oxford Happiness Questionnaire short-form is a recently developed eight-item measure of happiness. This study evaluated the internal consistency reliability and test-retest reliability of the Oxford Happiness Questionnaire short-form among 55 Northern Irish undergraduate university students who completed the measure on two occasions separated by two weeks. Internal consistency of the measure on both occasions was satisfactory at both Time 1 (alpha = .62) and Time 2 (alpha = ....

  5. Influence of Estradiol-17beta on Progesterone and Estrogen Receptor mRNA Expression in Porcine Follicular Granulosa Cells during Short-Term, In Vitro Real-Time Cell Proliferation

    Directory of Open Access Journals (Sweden)

    Sylwia Ciesiółka

    2016-01-01

    Full Text Available Progesterone (P4 and estradiol (E2 play a significant role in mammalian reproduction. Our study demonstrated that separated porcine cumulus cells (CCs and/or granulosa cells (GCs might proliferate in vitro during short-term, real-time primary culture. The GCs were analyzed according to gene expression of the progesterone receptor (nuclear form (pgr, progesterone receptor membrane component 1 (pgrmc1, and estrogen-related receptor beta 3 (esrrb3 in relation to two housekeeping genes: actb and pbgd. GCs were cultivated in medium with the E2. Both pgr/actb and pgr/pbgd revealed higher expression between 24 and 168 h of IVC of prolonged E2 treatment and at 48 h of IVC after acute E2 administration. The pgrmc1/actb and pgrmc1/pbgd displayed increased expression after prolonged E2 treatment between 24 and 120 h of IVC. The highest level of esrrb3/actb at 120 and 144 h, as well as esrrb3/pbgd at 120 h, in untreated controls as compared to the hormone-stimulated group, was observed. We suggest that E2 significantly influences the upregulation of pgr, pgrmc1, and esrrb3 expression in porcine GCs during real-time cell proliferation. Since esrrb3 expression is stimulated by E2 in both an acute and prolonged manner, estradiol may be recognized as a potential estrogen receptor agonist in GCs.

  6. [Anti-Ma2, anti-NMDA-receptor and anti-GluRε2 limbic encephalitis with testicular seminoma: short-term memory disturbance].

    Science.gov (United States)

    Kubota, Akihiro; Tajima, Takashi; Narukawa, Shinya; Yamazato, Masamizu; Fukaura, Hikoaki; Takahashi, Yukitoshi; Tanaka, Keiko; Shimizu, Jun; Nomura, Kyoichi

    2012-01-01

    A 36-year-old man presented with cognitive impairment and disturbance of short-term memory functions with character change. Cerebrospinal fluid analysis revealed no abnormalities; however, brain MRI revealed high-signal intensity from bilateral hippocampus lesions on fluid attenuated inversion recovery (FLAIR) images and T(2) weighted images. The 18F-fluorodeoxyglucose PET demonstrated high glucose uptake in the bilateral hippocampus lesions. He was diagnosed as limbic encephalitis, and was administered high-dose intravenous methylprednisolone and immune adsorption plasma therapy followed by intravenous immunoglobulin therapy. MRI abnormalities improved after treatment but recent memory disturbance remained. Ma2 antibody, NMDA-receptor antibody, and GluRε2 antibody were positive. Eleven months atter the onset of disease, the tumor was identified in left testicle by ultrasound and removed the tumor. The pathological findings were seminoma. We experienced a case of paraneoplastic limbic encephalitis associated with seminoma with short-term memory disturbance. The occurrence of paraneoplastic limbic encephalitis with antibodies against cell membrane (NMDA-receptor antibody and GluRε2 antibody) and intracellular (Ma2 antibody) is rare even in the literature.

  7. Development and validation of a short form of the self-efficacy measurement tool for Iranian patients with myocardial infarction

    Directory of Open Access Journals (Sweden)

    Soleiman Zand

    2017-09-01

    Full Text Available To assess efficacy in patients with heart failure need to have a scientific tool based on psychometric features is evident. The researchers developed a scientific tool based on psychometric principles for assessing self-efficacy beliefs in patients with Myocardial Infarction (MI as the only tool of its kind; however, Due to the large number of questions in the questionnaire, respondents may not desire to complete it accuracy. The present study was conducted to develop and validate a short form of this tool. This study was conducted on a sample of 311 patients diagnosed with MI by a cardiologist and selected through convenience sampling. The 80-20 rule was used for evaluating the 60 items of the short-form MI Self-Efficacy Measurement Tool (SF-SEMT and for eliminating items without an adequate sensitivity and accuracy. The factor analysis revealed 5 factors that explained a total of 87.92% the variance; the kaiser-meyer-olkin index was calculated as 0.915 with a probable significance level of 0.001. A total of 22 items and 5 factors were extracted for this short-form tool. The reliability of the tool was confirmed with Cronbach’s alpha coefficients of 0.96 to 0.97 for the factors and 0.97 for the entire tool. The short-form MI self-efficacy measurement tool has better psychometric features than the original long form, as the former was found to have a better factor structure compared to the latter

  8. Wechsler Adult Intelligence Scale-Third Edition short form for index and IQ scores in a psychiatric population.

    Science.gov (United States)

    Christensen, Bruce K; Girard, Todd A; Bagby, R Michael

    2007-06-01

    An eight-subtest short form (SF8) of the Wechsler Adult Intelligence Scale, Third Edition (WAIS-III), maintaining equal representation of each index factor, was developed for use with psychiatric populations. Data were collected from a mixed inpatient/outpatient sample (99 men and 101 women) referred for neuropsychological assessment. Psychometric analyses revealed an optimal SF8 comprising Vocabulary, Similarities, Arithmetic, Digit Span, Picture Completion, Matrix Reasoning, Digit Symbol Coding, and Symbol Search, scored by linear scaling. Expanding on previous short forms, the current SF8 maximizes the breadth of information and reduces administration time while maintaining the original WAIS-III factor structure. (c) 2007 APA, all rights reserved

  9. Readdressing gender bias in the Coopersmith Self-Esteem Inventory-short form.

    Science.gov (United States)

    Chapman, Paula L; Mullis, Ann K

    2002-12-01

    The short form of the Coopersmith Self-Esteem Inventory (SEI) was evaluated for gender bias. The authors replicated a study by L. Francis and D. James (1998) and administered the SEI to 361 middle and high school students (146 boys, 2l5 girls). They found that gender bias existed in 6 of the 25 items on the SEI, with 5 of those items favoring boys. Because recent literature indicates that male and female adolescents experience problems in different areas of their lives, the authors suggest that researchers consider such differences when selecting items for a standardized measure.

  10. The importance of short-term off-target effects in estimating the long-term renal and cardiovascular protection of angiotensin receptor blockers

    DEFF Research Database (Denmark)

    Smink, P A; Miao, Y; Eijkemans, M J C

    2014-01-01

    Angiotensin receptor blockers (ARBs) have multiple effects that may contribute to their efficacy on renal/cardiovascular outcomes. We developed and validated a risk score that incorporated short-term changes in multiple risk markers to predict the ARB effect on renal/cardiovascular outcomes.......98), in addition to being markedly more accurate than predicted RRRs based on changes in single markers. The score was validated in an independent ARB trial. Predictions of long-term renal/cardiovascular ARB effects are more accurate when considering short-term changes in multiple risk markers, challenging the use...

  11. A soluble form of the transcobalamin receptor CD320 can be detected in human serum

    DEFF Research Database (Denmark)

    Arendt, Johan Frederik Berg; Quadros, Edward V.; Christensen, Anna Lisa

    2010-01-01

    Background: Recently, the cell-surface receptor involved in the internalisation of the cobalamin(vitamin B12, Cbl) transporting protein, transcobalamin(TC), was described, and was found to be CD320(1). So far, it remains unsolved whether CD320 is present in a soluble form (sCD320) in serum. Our aim...

  12. Validity, Reliability, and Potential Bias of Short Forms of Students' Evaluation of Teaching: The Case of UAE University

    Science.gov (United States)

    Dodeen, Hamzeh

    2013-01-01

    Students' opinions continue to be a significant factor in the evaluation of teaching in higher education institutions. The purpose of this study was to psychometrically assess short students evaluation of teaching (SET) forms using the UAE University form as a model. The study evaluated the form validity, reliability, the overall question, and…

  13. The role of the form factor and short-range correlation in the relativistic Hartree-Fock model for nuclear matter

    International Nuclear Information System (INIS)

    Hu, J.; Toki, H.; Wen, W.; Shen, H.

    2010-01-01

    The role of the form factor and short-range correlation in nuclear matter is studied within the relativistic Hartree-Fock approximation. We take, first, the mean-field approximation for meson fields and obtain the fluctuation terms of mesons to be used for the Fock energies. We introduce form factors in the meson-nucleon coupling vertices to take into account the finite-size effect of the nucleon. We use further the unitary correlation operator method for the treatment of the short-range correlation. The form factors of the size (Λ∝1.0 -2.0 GeV) of the nucleon-nucleon interaction cut down largely the contribution of the ρ-meson in the Fock term. The short-range correlation effect is not large but has a significant effect on the pion and ρ-meson energies in the relativistic Hartree-Fock approximation for nuclear matter. (orig.)

  14. Validation of the Spanish versions of the long (26 items) and short (12 items) forms of the Self-Compassion Scale (SCS).

    Science.gov (United States)

    Garcia-Campayo, Javier; Navarro-Gil, Mayte; Andrés, Eva; Montero-Marin, Jesús; López-Artal, Lorena; Demarzo, Marcelo Marcos Piva

    2014-01-10

    Self-compassion is a key psychological construct for assessing clinical outcomes in mindfulness-based interventions. The aim of this study was to validate the Spanish versions of the long (26 item) and short (12 item) forms of the Self-Compassion Scale (SCS). The translated Spanish versions of both subscales were administered to two independent samples: Sample 1 was comprised of university students (n = 268) who were recruited to validate the long form, and Sample 2 was comprised of Aragon Health Service workers (n = 271) who were recruited to validate the short form. In addition to SCS, the Mindful Attention Awareness Scale (MAAS), the State-Trait Anxiety Inventory-Trait (STAI-T), the Beck Depression Inventory (BDI) and the Perceived Stress Questionnaire (PSQ) were administered. Construct validity, internal consistency, test-retest reliability and convergent validity were tested. The Confirmatory Factor Analysis (CFA) of the long and short forms of the SCS confirmed the original six-factor model in both scales, showing goodness of fit. Cronbach's α for the 26 item SCS was 0.87 (95% CI = 0.85-0.90) and ranged between 0.72 and 0.79 for the 6 subscales. Cronbach's α for the 12-item SCS was 0.85 (95% CI = 0.81-0.88) and ranged between 0.71 and 0.77 for the 6 subscales. The long (26-item) form of the SCS showed a test-retest coefficient of 0.92 (95% CI = 0.89-0.94). The Intraclass Correlation (ICC) for the 6 subscales ranged from 0.84 to 0.93. The short (12-item) form of the SCS showed a test-retest coefficient of 0.89 (95% CI: 0.87-0.93). The ICC for the 6 subscales ranged from 0.79 to 0.91. The long and short forms of the SCS exhibited a significant negative correlation with the BDI, the STAI and the PSQ, and a significant positive correlation with the MAAS. The correlation between the total score of the long and short SCS form was r = 0.92. The Spanish versions of the long (26-item) and short (12-item) forms of the SCS are valid and

  15. Reliability and Validity Study of the Attitude towards Mathematics Instruments Short Form

    Directory of Open Access Journals (Sweden)

    Güney HACIÖMEROĞLU

    2017-05-01

    Full Text Available Purpose of this study was to investigate the reliability and validity of the Turkish form of the Attitude Towards Mathematics Instrument Short Form developed by Lim and Chapman (2013. In this study, data gathered from 310 elementary students were utilized for Exploratory and Confirmatory Factor Analysis to determine the structure of factor loading. The factor loading among the sub-scales were different from original. Confirmatory Factor analysis revealed that the model was acceptable. There were three sub-scales, value, self-confidence, enjoyment and motivation. Cronbach’s alpha coefficient for the overall instrument was calculated as .84, respectively. The adapted instrument includes three sub-scales: value (α=.91, self-confidence (α=.86, enjoyment and motivation (α=.82. Turkish adaptation of the questionnaire is valid and reliable and appropriate to use in Turkish culture.

  16. Measurement invariance of the Mental Health Continuum-Short Form (MHC-SF) across three cultural groups

    NARCIS (Netherlands)

    Joshanloo, Mohsen; Wissing, Marie P.; Khumalo, Itumeleng P.; Lamers, S.M.A.

    2013-01-01

    This study investigated the factorial structure and invariance of the Mental Health Continuum-Short Form (MHC-SF) across cultural groups from three nations, namely, the Netherlands, South Africa, and Iran (N = 1120). The three-dimensional structure of mental well-being was supported in all the

  17. Development of Short-Form Versions of the Screener and Opioid Assessment for Patients with Pain-Revised (SOAPP-R): A Proof-of-Principle Study.

    Science.gov (United States)

    Finkelman, Matthew D; Smits, Niels; Kulich, Ronald J; Zacharoff, Kevin L; Magnuson, Britta E; Chang, Hong; Dong, Jinghui; Butler, Stephen F

    2017-07-01

    The Screener and Opioid Assessment for Patients with Pain-Revised (SOAPP-R) is a 24-item questionnaire designed to assess risk of aberrant medication-related behaviors in chronic pain patients. The introduction of short forms of the SOAPP-R may save time and increase utilization by practitioners. To develop and evaluate candidate SOAPP-R short forms. Retrospective study. Pain centers. Four hundred and twenty-eight patients with chronic noncancer pain. Subjects had previously been administered the full-length version of the SOAPP-R and been categorized as positive or negative for aberrant medication-related behaviors via the Aberrant Drug Behavior Index (ADBI). Short forms of the SOAPP-R were developed using lasso logistic regression. Sensitivity, specificity, and area under the curve (AUC) of all forms were calculated with respect to the ADBI using the complete data set, training-test analysis, and 10-fold cross-validation. The coefficient alpha of each form was also calculated. An external set of 12 pain practitioners reviewed the forms for content. In the complete data set analysis, a form of 12 items exhibited sensitivity, specificity, and AUC greater than or equal to those of the full-length SOAPP-R (which were 0.74, 0.67, and 0.76, respectively). The short form had a coefficient alpha of 0.76. In the training-test analysis and 10-fold cross-validation, it exhibited an AUC value within 0.01 of that of the full-length SOAPP-R. The majority of external practitioners reported a preference for this short form. The 12-item version of the SOAPP-R has potential as a short risk screener and should be tested prospectively. © 2016 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

  18. Short-term exposure to oleandrin enhances responses to IL-8 by increasing cell surface IL-8 receptors

    Science.gov (United States)

    Raviprakash, Nune; Manna, Sunil Kumar

    2014-01-01

    BACKGROUND AND PURPOSE One of the first steps in host defence is the migration of leukocytes. IL-8 and its receptors are a chemokine system essential to such migration. Up-regulation of these receptors would be a viable strategy to treat dysfunctional host defence. Here, we studied the effects of the plant glycoside oleandrin on responses to IL-8 in a human monocytic cell line. EXPERIMENTAL APPROACH U937 cells were incubated with oleandrin (1-200 ng mL−1) for either 1 h (pulse) or for 24 h (non-pulse). Apoptosis; activation of NF-κB, AP-1 and NFAT; calcineurin activity and IL-8 receptors (CXCR1 and CXCR2) were measured using Western blotting, RT-PCR and reporter gene assays. KEY RESULTS Pulse exposure to oleandrin did not induce apoptosis or cytoxicity as observed after non-pulse exposure. Pulse exposure enhanced activation of NF-κB induced by IL-8 but not that induced by TNF-α, IL-1, EGF or LPS. Exposure to other apoptosis-inducing compounds (azadirachtin, resveratrol, thiadiazolidine, or benzofuran) did not enhance activation of NF-κB. Pulse exposure to oleandrin increased expression of IL-8 receptors and chemotaxis, release of enzymes and activation of NF-κB, NFAT and AP-1 along with increased IL-8-mediated calcineurin activation, and wound healing. Pulse exposure increased numbers of cell surface IL-8 receptors. CONCLUSIONS AND IMPLICATIONS Short-term (1 h; pulse) exposure to a toxic glycoside oleandrin, enhanced biological responses to IL-8 in monocytic cells, without cytoxicity. Pulse exposure to oleandrin could provide a viable therapy for those conditions where leukocyte migration is defective. PMID:24172227

  19. The Aggression Observation Short Form Identified Episodes Not Reported on the Staff Observation Aggression Scale-Revised

    DEFF Research Database (Denmark)

    Hvidhjelm, Jacob; Sestoft, Dorte; Bjørner, Jakob Bue

    2014-01-01

    The purpose of this study is to evaluate the underreporting of violence and aggression on the Staff Observation Aggression Scale-Revised (SOAS-R) when compared to a simpler assessment: the Aggression Observation Short Form (AOS). During a period of one year, two open and two closed wards gathered...... for open wards and for patients with short admission lengths. Standard instruments such as the SOAS-R underreport aggressive episodes by 45% or more. Underreporting can be reduced by introducing shorter instruments, but it cannot be completely eliminated....

  20. The subscales and short forms of the dizziness handicap inventory: are they useful for comparison of the patient groups?

    Science.gov (United States)

    Ardıç, Fazıl Necdet; Tümkaya, Funda; Akdağ, Beyza; Şenol, Hande

    2017-10-01

    Dizziness Handicap Inventory (DHI) is one of the most frequently used surveys for vertigo. The aim of the study was re-analyze the consistency of subscales and correlation between original and different short forms. The data of 2111 patients were analyzed. Original three subscales, screening form of DHI and short form of DHI were evaluated. The suitability of the data set for factor analysis and factor structure was analyzed with Kaiser-Meyer-Olkin (KMO) coefficient, Bartlett's Sphericity Test, and Varimax method. Pearson correlation analysis was performed. Factor analysis showed that two factor solutions are more prominent in our data. The factors proposed in different studies are not in harmony with each other. There is high correlation between the original and screening and short forms of DHI. This study indicated that the factor structure of the scale was not consistent. It is not advised to use subscale scores for comparison especially in international level. Therefore, total score should be used rather than the scores of the subscales. Using DHI screening form instead of original 25 questions is more convenient, because it is highly correlated with the original one and has fewer questions. Implications for rehabilitation Factor structure of the DHI is not consistent enough for comparison of the international studies. Total score of DHI is reliable. Using the screening version of DHI is better, because it is highly correlated with the original form and has fewer questions (10 questions).

  1. Psychometric Evaluation of the Hypogonadism Impact of Symptoms Questionnaire Short Form (HIS-Q-SF).

    Science.gov (United States)

    Gelhorn, Heather L; Roberts, Laurie J; Khandelwal, Nikhil; Revicki, Dennis A; DeRogatis, Leonard R; Dobs, Adrian; Hepp, Zsolt; Miller, Michael G

    2017-08-01

    The Hypogonadism Impact of Symptoms Questionnaire Short Form (HIS-Q-SF) is a patient-reported outcome measurement designed to evaluate the symptoms of hypogonadism. The HIS-Q-SF is an abbreviated version including17 items from the original 28-item HIS-Q. To conduct item analyses and reduction, evaluate the psychometric properties of the HIS-Q-SF, and provide guidance on score interpretation. A 12-week observational longitudinal study of hypogonadal men was conducted as part of the original HIS-Q psychometric evaluation. Participants completed the original HIS-Q every 2 weeks. Blood samples were collected to evaluate testosterone levels. Participants completed the Aging Male's Symptoms Scale, the International Index of Erectile Function, the Short Form-12, and the PROMIS Sexual Activity, Satisfaction with Sex Life, Sleep Disturbance, and Applied Cognition Scales (baseline and weeks 6 and 12). Clinicians completed the Clinical Global Impression of Severity and Change scales and a clinical form. Item performance was evaluated using descriptive statistics and Rasch analyses. Reliability (internal consistency and test-retest), validity (concurrent and know groups), and responsiveness were assessed. One hundred seventy-seven men participated (mean age = 54.1 years, range = 23-83). Similar to the full HIS-Q, the final abbreviated HIS-Q-SF instrument includes five domains (sexual, energy, sleep, cognition, and mood) with two sexual subdomains (libido and sexual function). For key domains, test-retest reliability was very good, and construct validity was good for all domains. Known-groups validity was demonstrated for all domain scores, subdomain scores, and total score based on the Clinical Global Impression-Severity. All domains and subdomains were responsive to change based on patient-rated anchor questions. The HIS-Q-SF could be a useful tool in clinical practice, epidemiologic studies, and other academic research settings. Careful consideration was given to the

  2. Adapting the short form of the Coping Inventory for Stressful Situations into Chinese

    Directory of Open Access Journals (Sweden)

    Li C

    2017-06-01

    Full Text Available Chun Li,1 Qing Liu,2 Ti Hu,3 Xiaoyan Jin1 1International School of Chinese Studies, Northeast Normal University, Changchun, 2Department of Nuclear Medicine and Medical PET Center, The Second Hospital of Zhejiang University School of Medicine, Zhejiang University, Hangzhou, 3School of Physical Education and Sports, Beijing Normal University, Beijing, People’s Republic of China Objectives: The Coping Inventory for Stressful Situations (CISS is a measurement tool for evaluating stress that has good psychometric properties. We investigated the applicability of a short-form version of the CISS in a large sample of Chinese university students. Methods: Nine hundred and seventy-two Chinese university students aged 18–30 years (mean =20.15, standard deviation =3.26 were chosen as subjects, of whom 101 were randomly selected to be retested after a 2-week interval. Results: The results of a confirmatory factor analysis revealed that the root mean square error of approximation of a four-factor model was 0.06, while the comparative fit index was 0.91, the incremental fit index was 0.93, the non-normed fit index was 0.91, and the root mean residual was 0.07. The Cronbach’s α coefficients for the task-oriented, emotion-oriented, distraction, and social diversion coping subscales were 0.81, 0.74, 0.7, and 0.66, respectively. The 2-week test–retest reliability was 0.78, 0.74, 0.7, and 0.65 for the task-oriented, emotion-oriented, distraction, and social diversion coping subscales, respectively. In the Chinese version of the CISS short form, task-oriented coping was positively correlated with positive affect and extraversion and negatively correlated with neuroticism; emotion-oriented coping was negatively correlated with extraversion and positively correlated with negative affect, anxiety, and neuroticism; distraction coping was positively correlated with neuroticism, extroversion, anxiety, positive affect, and negative affect and negatively

  3. Psychometric assessment of the patient activation measure short form (PAM-13) in rural settings.

    Science.gov (United States)

    Hung, Man; Carter, Marjorie; Hayden, Candace; Dzierzon, Rhonda; Morales, Jose; Snow, Laverne; Butler, Jorie; Bateman, Kim; Samore, Matthew

    2013-04-01

    The patient activation measure short form (PAM-13) assesses patients' self-reported health management skills, knowledge, confidence, and motivation. We used item response theory to evaluate the psychometric properties of the PAM-13 utilized in rural settings. A Rasch partial credit model analysis was conducted on the PAM-13 instrument using a sample of 812 rural patients recruited by providers and our research staff. Specially, we examined dimensionality, item fit, and quality of measures, category response curves, and item differential functioning. Convergent and divergent validities were also examined. The PAM-13 instrument has excellent convergent and divergent validities. It is fairly unidimensional, and all items fit the Rasch model well. It has relatively high person and item reliability indices. Majority of the items were free of item differential functioning. There were, however, some issues with ceiling effects. Additionally, there was a lack of responses for category one across all items. Patient activation measure short form (PAM-13) performs well in some areas, but not all. In general, more items need to be added to cover the upper end of the trait. The four response categories of PAM-13 should be collapsed into three.

  4. Trailers in between short video forms from digital games to movies and back

    OpenAIRE

    Gandolfi, Enrico; Semprebene, Roberto

    2017-01-01

    Promotional trailers represent a significant trend in most entertainment sectors. However, little efforts have been done in enlightening this expressive form when related to video games. This article aims to address such a lack by analyzing game/movie (inspired by digital games) trailers as a crossroad between digital entertainment and films. The main intent is to exploit a comparative lens to uncover leading traits of short videos according to the medium that that they are portraying. Theref...

  5. Adaptation and Validation of the Foot Function Index-Revised Short Form into Polish

    OpenAIRE

    Rutkowski, Radosław; Gałczyńska-Rusin, Małgorzata; Gizińska, Małgorzata; Straburzyński-Lupa, Marcin; Zdanowska, Agata; Romanowski, Mateusz Wojciech; Romanowski, Wojciech; Budiman-Mak, Elly; Straburzyńska-Lupa, Anna

    2017-01-01

    Purpose The aim of the present study was to adapt the Foot Function Index-Revised Short Form (FFI-RS) questionnaire into Polish and verify its reliability and validity in a group of patients with rheumatoid arthritis (RA). Methods The study included 211 patients suffering from RA. The FFI-RS questionnaire underwent standard linguistic adaptation and its psychometric parameters were investigated. The enrolled participants had been recruited for seven months as a convenient sample from the rheu...

  6. Evaluation of the Psychometric Properties of the Asian Adolescent Depression Scale and Construction of a Short Form: An Item Response Theory Analysis.

    Science.gov (United States)

    Lo, Barbara Chuen Yee; Zhao, Yue; Kwok, Alice Wai Yee; Chan, Wai; Chan, Calais Kin Yuen

    2017-07-01

    The present study applied item response theory to examine the psychometric properties of the Asian Adolescent Depression Scale and to construct a short form among 1,084 teenagers recruited from secondary schools in Hong Kong. Findings suggested that some items of the full form reflected higher levels of severity and were more discriminating than others, and the Asian Adolescent Depression Scale was useful in measuring a broad range of depressive severity in community youths. Differential item functioning emerged in several items where females reported higher depressive severity than males. In the short form construction, preliminary validation suggested that, relative to the 20-item full form, our derived short form offered significantly greater diagnostic performance and stronger discriminatory ability in differentiating depressed and nondepressed groups, and simultaneously maintained adequate measurement precision with a reduced response burden in assessing depression in the Asian adolescents. Cultural variance in depressive symptomatology and clinical implications are discussed.

  7. Development and Examination of the Five-Factor Obsessive-Compulsive Inventory-Short Form.

    Science.gov (United States)

    Griffin, Sarah A; Suzuki, Takakuni; Lynam, Donald R; Crego, Cristina; Widiger, Thomas A; Miller, Joshua D; Samuel, Douglas B

    2018-01-01

    The Five-Factor Obsessive-Compulsive Inventory (FFOCI) is an assessment of obsessive-compulsive personality disorder (OCPD) that is based on the conceptual framework of the five-factor model (FFM) of personality. The FFOCI has 12 subscales that assess those five-factor model facets relevant to the description of OCPD. Research has suggested that the FFOCI scores relate robustly to existing measures of OCPD and relevant scales from general personality inventories. Nonetheless, the FFOCI's length-120 items-may limit its clinical utility. This study derived a 48-item FFOCI-Short Form (FFOCI-SF) from the original measure using item response theory methods. The FFOCI-SF scales successfully recreated the nomological network of the original measure and improved discriminant validity relative to the long form. These results support the use of the FFOCI-SF as a briefer measure of the lower-order traits associated with OCPD.

  8. Obstacles to condom use: the combination of other forms of birth control and short-term monogamy.

    Science.gov (United States)

    Critelli, J W; Suire, D M

    1998-03-01

    Two hundred thirty-seven college students involved in heterosexual relationships were surveyed to determine the effects of relationship type and use of forms of contraception other than condoms on condom use. Findings indicated that in the context of a short-term, monogamous relationship, the use of another form of birth control was associated with decreased condom use. In addition, 20% of the participants reported that they had wanted to use a condom for disease prevention on at least one occasion but had decided not to do so because they were using another form of contraception. Implications for preventive health are discussed.

  9. The pro-Forms of Insulin-Like Growth Factor I (IGF-I) Are Predominant in Skeletal Muscle and Alter IGF-I Receptor Activation

    Science.gov (United States)

    Durzyńska, Julia; Philippou, Anastassios; Brisson, Becky K.; Nguyen-McCarty, Michelle

    2013-01-01

    IGF-I is a key regulator of muscle development and growth. The pre-pro-peptide produced by the Igf1gene undergoes several posttranslational processing steps to result in a secreted mature protein, which is thought to be the obligate ligand for the IGF-I receptor (IGF-IR). The goals of this study were to determine what forms of IGF-I exist in skeletal muscle, and whether the mature IGF-I protein was the only form able to activate the IGF-IR. We measured the proportion of IGF-I species in murine skeletal muscle and found that the predominant forms were nonglycosylated pro-IGF-I and glycosylated pro-IGF-I, which retained the C-terminal E peptide extension, instead of mature IGF-I. These forms were validated using samples subjected to viral expression of IGF-I combined with furin and glycosidase digestion. To determine whether the larger molecular weight IGF-I forms were also ligands for the IGF-IR, we generated each specific form through transient transfection of 3T3 cells and used the enriched media to perform kinase receptor activation assays. Compared with mature IGF-I, nonglycosylated pro-IGF-I had similar ability to activate the IGF-IR, whereas glycosylation of pro-IGF-I significantly reduced receptor activation. Thus, it is important to understand not only the quantity, but also the proportion of IGF-I forms produced, to evaluate the true biological activity of this growth factor. PMID:23407451

  10. Crystal structure of the urokinase receptor in a ligand-free form

    DEFF Research Database (Denmark)

    Xu, Xiang; Gårdsvoll, Henrik; Yuan, Cai

    2012-01-01

    The urokinase receptor urokinase-type plasminogen activator receptor (uPAR) is a surface receptor capable of not only focalizing urokinase-type plasminogen activator (uPA)-mediated fibrinolysis to the pericellular micro-environment but also promoting cell migration and chemotaxis. Consistent...

  11. The Short Form of the Five-Factor Narcissism Inventory: Psychometric Equivalence of the Turkish Version

    Science.gov (United States)

    Eksi, Füsun

    2016-01-01

    This study intends to examine the psychometric properties of the Turkish version of the short form of the Five-Factor Narcissism Inventory (FFNI-SF). The study group consists of a total of 526 university students (54% were female) whose ages range from 18 to 32. In the translational equivalence study made over a two-week interval, the FFNI-SF…

  12. Short forms of the Utrecht-Management of Identity Commitments Scale (U-MICS) with the domains of job, romantic relationship, and region.

    Science.gov (United States)

    Schubach, Elisabeth; Zimmermann, Julia; Noack, Peter; Neyer, Franz J

    2017-01-01

    The U-MICS is a self-report questionnaire designed to assess the identity dimensions from a domain-specific perspective. The present study reports on the development of a short-form version for the domains of job and romantic relationship in young adults from Germany and extends this scale to include the domain of region (n Sample1  = 95, 84% female, mean age 22.45 years; n Sample2  = 1,795, 71% female, mean age 24.53 years). We found the short form to possess adequate psychometric properties and to demonstrate a factor structure congruent to the long-form version. Regarding validity, the small correlations across domains within dimensions support a domain-specific approach to identity. The associations between the different identity domains with personality traits are similar, indicating a consistent pattern of convergent validity for all domains. We conclude that "region" provides a valuable complement to the established domains that can all be reliably assessed with the U-MICS-Short Form. Copyright © 2016 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.

  13. Validation of a short form of the Western Ontario and McMaster Universities Osteoarthritis Index function subscale in hip and knee osteoarthritis.

    Science.gov (United States)

    Baron, Gabriel; Tubach, Florence; Ravaud, Philippe; Logeart, Isabelle; Dougados, Maxime

    2007-05-15

    A short version of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) function scale has recently been developed to enhance the applicability of the scale in routine practice and clinical research for patients with hip and knee osteoarthritis. The goal of the present study was to validate this short form. We conducted a prospective 4-week cohort study of 1,036 outpatients. Performance on the WOMAC function long form (LF) and short form (SF) was compared. Agreement between responses on the 2 forms was examined according to a Bland-Altman plot. Responsiveness to change (by standardized response mean [SRM]), reproducibility (intraclass correlation coefficient [ICC]), and internal consistency (Cronbach's alpha) were computed for both forms. Construct validity was assessed based on functional impairment as measured on a numerical rating scale. At baseline, 24% of patients who completed the WOMAC LF had missing data for at least 1 item as compared with only 6% of patients who completed the WOMAC SF. The mean WOMAC SF score was greater than the mean WOMAC LF score (mean +/- SD difference -4.3 +/- 4.8 on a 0-100 scale). SRMs were 0.61 and 0.73, ICCs were 0.76 and 0.68, and Cronbach's alphas were 0.93 and 0.85 for the WOMAC LF and SF, respectively. The 2 forms had comparable correlation with functional impairment. The WOMAC function short form has a low rate of missing data and is a responsive, reproducible, and valid measure. The mean SF score was 4 points higher than the mean LF score.

  14. Short-term treatment with VEGF receptor inhibitors induces retinopathy of prematurity-like abnormal vascular growth in neonatal rats.

    Science.gov (United States)

    Nakano, Ayuki; Nakahara, Tsutomu; Mori, Asami; Ushikubo, Hiroko; Sakamoto, Kenji; Ishii, Kunio

    2016-02-01

    Retinal arterial tortuosity and venous dilation are hallmarks of plus disease, which is a severe form of retinopathy of prematurity (ROP). In this study, we examined whether short-term interruption of vascular endothelial growth factor (VEGF) signals leads to the formation of severe ROP-like abnormal retinal blood vessels. Neonatal rats were treated subcutaneously with the VEGF receptor (VEGFR) tyrosine kinase inhibitors, KRN633 (1, 5, or 10 mg/kg) or axitinib (10 mg/kg), on postnatal day (P) 7 and P8. The retinal vasculatures were examined on P9, P14, or P21 in retinal whole-mounts stained with an endothelial cell marker. Prevention of vascular growth and regression of some preformed capillaries were observed on P9 in retinas of rats treated with KRN633. However, on P14 and P21, density of capillaries, tortuosity index of arterioles, and diameter of veins significantly increased in KRN633-treated rats, compared to vehicle (0.5% methylcellulose)-treated animals. Similar observations were made with axitinib-treated rats. Expressions of VEGF and VEGFR-2 were enhanced on P14 in KRN633-treated rat retinas. The second round of KRN633 treatment on P11 and P12 completely blocked abnormal retinal vascular growth on P14, but thereafter induced ROP-like abnormal retinal blood vessels by P21. These results suggest that an interruption of normal retinal vascular development in neonatal rats as a result of short-term VEGFR inhibition causes severe ROP-like abnormal retinal vascular growth in a VEGF-dependent manner. Rats treated postnatally with VEGFR inhibitors could serve as an animal model for studying the mechanisms underlying the development of plus disease. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Factor Structure and Psychometric Properties of the Young Schema Questionnaire (Short Form) in Chinese Undergraduate Students

    Science.gov (United States)

    Cui, Lixia; Lin, Wenwen; Oei, Tian P. S.

    2011-01-01

    This study investigated cross-cultural differences in the factor structure and psychometric properties of the Young Schema Questionnaire (short form; YSQ-SF). The participants were 712 Chinese undergraduate students. The total sample was randomly divided into two sub-samples. Exploratory Factor Analysis (EFA) was conducted on questionnaire results…

  16. Heteroreceptor Complexes Formed by Dopamine D1, Histamine H3, and N-Methyl-D-Aspartate Glutamate Receptors as Targets to Prevent Neuronal Death in Alzheimer's Disease.

    Science.gov (United States)

    Rodríguez-Ruiz, Mar; Moreno, Estefanía; Moreno-Delgado, David; Navarro, Gemma; Mallol, Josefa; Cortés, Antonio; Lluís, Carme; Canela, Enric I; Casadó, Vicent; McCormick, Peter J; Franco, Rafael

    2017-08-01

    Alzheimer's disease (AD) is a neurodegenerative disorder causing progressive memory loss and cognitive dysfunction. Anti-AD strategies targeting cell receptors consider them as isolated units. However, many cell surface receptors cooperate and physically contact each other forming complexes having different biochemical properties than individual receptors. We here report the discovery of dopamine D 1 , histamine H 3 , and N-methyl-D-aspartate (NMDA) glutamate receptor heteromers in heterologous systems and in rodent brain cortex. Heteromers were detected by co-immunoprecipitation and in situ proximity ligation assays (PLA) in the rat cortex where H 3 receptor agonists, via negative cross-talk, and H 3 receptor antagonists, via cross-antagonism, decreased D 1 receptor agonist signaling determined by ERK1/2 or Akt phosphorylation, and counteracted D 1 receptor-mediated excitotoxic cell death. Both D 1 and H 3 receptor antagonists also counteracted NMDA toxicity suggesting a complex interaction between NMDA receptors and D 1 -H 3 receptor heteromer function. Likely due to heteromerization, H 3 receptors act as allosteric regulator for D 1 and NMDA receptors. By bioluminescence resonance energy transfer (BRET), we demonstrated that D 1 or H 3 receptors form heteromers with NR1A/NR2B NMDA receptor subunits. D 1 -H 3 -NMDA receptor complexes were confirmed by BRET combined with fluorescence complementation. The endogenous expression of complexes in mouse cortex was determined by PLA and similar expression was observed in wild-type and APP/PS1 mice. Consistent with allosteric receptor-receptor interactions within the complex, H 3 receptor antagonists reduced NMDA or D 1 receptor-mediated excitotoxic cell death in cortical organotypic cultures. Moreover, H 3 receptor antagonists reverted the toxicity induced by ß 1-42 -amyloid peptide. Thus, histamine H 3 receptors in D 1 -H 3 -NMDA heteroreceptor complexes arise as promising targets to prevent neurodegeneration.

  17. Short-chain free fatty acid receptors FFA2/GPR43 and FFA3/GPR41 as new potential therapeutic targets.

    Science.gov (United States)

    Ulven, Trond

    2012-01-01

    The deorphanization of the free fatty acid (FFA) receptors FFA1 (GPR40), FFA2 (GPR43), FFA3 (GPR41), GPR84, and GPR120 has made clear that the body is capable of recognizing and responding directly to nonesterified fatty acid of virtually any chain length. Colonic fermentation of dietary fiber produces high concentrations of the short-chain fatty acids (SCFAs) acetate, propionate and butyrate, a process which is important to health. The phylogenetically related 7-transmembrane (7TM) receptors free fatty acid receptor 2 (FFA2) and FFA3 are activated by these SCFAs, and several lines of evidence indicate that FFA2 and FFA3 mediate beneficial effects associated with a fiber-rich diet, and that they may be of interest as targets for treatment of inflammatory and metabolic diseases. FFA2 is highly expressed on immune cells, in particular neutrophils, and several studies suggest that the receptor plays a role in diseases involving a dysfunctional neutrophil response, such as inflammatory bowel disease (IBD). Both FFA2 and FFA3 have been implicated in metabolic diseases such as type 2 diabetes and in regulation of appetite. More research is however required to clarify the potential of the receptors as drug targets and establish if activation or inhibition would be the preferred mode of action. The availability of potent and selective receptor modulators is a prerequisite for these studies. The few modulators of FFA2 or FFA3 that have been published hitherto in the peer-reviewed literature in general have properties that make them less than ideal as such tools, but published patent applications indicate that better tool compounds might soon become available which should enable studies critical to validate the receptors as new drug targets.

  18. Short-chain free fatty acid receptors FFA2/GPR43 and FFA3/GPR41 as new potential therapeutic targets

    Directory of Open Access Journals (Sweden)

    Trond eUlven

    2012-10-01

    Full Text Available The deorphanization of the free fatty acid (FFA receptors FFA1 (GPR40, FFA2 (GPR43, FFA3 (GPR41, GPR84 and GPR120 made clear that the body is capable of recognizing and responding directly to nonesterified fatty acid of virtually any chain length. Colonic fermentation of dietary fiber produces high concentrations of the short-chain fatty acids (SCFAs acetate, propionate and butyrate, a process which is important to health. The phylogenetically related 7-transmembrane receptors free fatty acid receptor 2 (FFA2 and FFA3 are activated by these SCFAs, and several lines of evidence indicate that FFA2 and FFA3 mediate beneficial effects associated with a fiber-rich diet, and that they may be of interest as targets for treatment of inflammatory and metabolic diseases. FFA2 is highly expressed on immune cells, in particular neutrophils, and several studies suggest that the receptor plays a role in diseases involving a dysfunctional neutrophil response, such as inflammatory bowel disease (IBD. Both FFA2 and FFA3 have been implicated in metabolic diseases such as type 2 diabetes and regulation of appetite. More research is however required to clarify potential of the receptors as drug targets and establish if activation or inhibition would be the preferred mode of action. The availability of potent and selective receptor modulators is a prerequisite for these studies. The few modulators of FFA2 or FFA3 that have been published hitherto in the peer-reviewed literature in general have properties that make them less than ideal as such tools, but published patent applications indicate that the situation may soon improve, and that proper tool compounds will enable studies critical to validate the receptors as new drug targets.

  19. Comparison Review of Short-Acting and Long-Acting Glucagon-like Peptide-1 Receptor Agonists.

    Science.gov (United States)

    Uccellatore, Annachiara; Genovese, Stefano; Dicembrini, Ilaria; Mannucci, Edoardo; Ceriello, Antonio

    2015-09-01

    Glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1 RAs) are useful tools for treating type 2 diabetes mellitus. In their recent position statement, the American Diabetes Association and European Association for the Study of Diabetes recommend GLP1-RAs as add-on to metformin when therapeutic goals are not achieved with monotherapy, particularly for patients who wish to avoid weight gain or hypoglycemia. GLP1-RAs differ substantially in their duration of action, frequency of administration and clinical profile. Members of this class approved for clinical use include exenatide twice-daily, exenatide once-weekly, liraglutide and lixisenatide once-daily. Recently, two new once-weekly GLP1-RAs have been approved: dulaglutide and albiglutide. This article summarizes properties of short- and long-acting GLP-1 analogs, and provides useful information to help choose the most appropriate compound for individual patients.

  20. Development of short-form measures to assess four types of elder mistreatment: Findings from an evidence-based study of APS elder abuse substantiation decisions.

    Science.gov (United States)

    Beach, Scott R; Liu, Pi-Ju; DeLiema, Marguerite; Iris, Madelyn; Howe, Melissa J K; Conrad, Kendon J

    2017-01-01

    Improving the standardization and efficiency of adult protective services (APS) investigations is a top priority in APS practice. Using data from the Elder Abuse Decision Support System (EADSS), we developed short-form measures of four types of elder abuse: financial, emotional/psychological, physical, and neglect. The EADSS data set contains 948 elder abuse cases (age 60+) with yes/no abuse substantiation decisions for each abuse type following a 30-day investigation. Item sensitivity/specificity analyses were conducted on long-form items with the substantiation decision for each abuse type as the criterion. Validity was further tested using receiver-operator characteristic (ROC) curve analysis, correlation with long forms and internal consistency. The four resulting short-form measures, containing 36 of the 82 original items, have validity similar to the original long forms. These short forms can be used to standardize and increase efficiency of APS investigations, and may also offer researchers new options for brief elder abuse assessments.

  1. Validation of the Short Form of the Career Development Inventory with an Iranian High School Sample

    Science.gov (United States)

    Sadeghi, Ahmad; Baghban, Iran; Bahrami, Fatemeh; Ahmadi, Ahmad; Creed, Peter

    2011-01-01

    A short 33-item form of the Career Development Inventory was validated on a sample of 310 Iranian high school students. Factor analysis indicated that attitude and cognitive subscale items loaded on their respective factors, and that internal reliability coefficients at all levels were satisfactory to good. Support for validity was demonstrated by…

  2. Effects of ibuprofen on cognition and NMDA receptor subunit expression across aging.

    Science.gov (United States)

    Márquez Loza, Alejandra; Elias, Valerie; Wong, Carmen P; Ho, Emily; Bermudez, Michelle; Magnusson, Kathy R

    2017-03-06

    Age-related declines in long- and short-term memory show relationships to decreases in N-methyl-d-aspartate (NMDA) receptor expression, which may involve inflammation. This study was designed to determine effects of an anti-inflammatory drug, ibuprofen, on cognitive function and NMDA receptor expression across aging. Male C57BL/6 mice (ages 5, 14, 20, and 26months) were fed ibuprofen (375ppm) in NIH31 diet or diet alone for 6weeks prior to testing. Behavioral testing using the Morris water maze showed that older mice performed significantly worse than younger in spatial long-term memory, reversal, and short-term memory tasks. Ibuprofen enhanced overall performance in the short-term memory task, but this appeared to be more related to improved executive function than memory. Ibuprofen induced significant decreases over all ages in the mRNA densities for GluN2B subunit, all GluN1 splice variants, and GluN1-1 splice forms in the frontal cortex and in protein expression of GluN2A, GluN2B and GluN1 C2' cassettes in the hippocampus. GluN1-3 splice form mRNA and C2' cassette protein were significantly increased across ages in frontal lobes of ibuprofen-treated mice. Ibuprofen did not alter expression of pro-inflammatory cytokines IL-1β and TNFα, but did reduce the area of reactive astrocyte immunostaining in frontal cortex of aged mice. Enhancement in executive function showed a relationship to increased GluN1-3 mRNA and decreased gliosis. These findings suggest that inflammation may play a role in executive function declines in aged animals, but other effects of ibuprofen on NMDA receptors appeared to be unrelated to aging or inflammation. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  3. Role of 5-HT1-7 receptors in short- and long-term memory for an autoshaping task: intrahippocampal manipulations.

    Science.gov (United States)

    Liy-Salmeron, Gustavo; Meneses, Alfredo

    2007-05-25

    It was previously reported that brain areas containing serotonin (5-hydroxytryptamine, 5-HT) receptors mediate memory consolidation as well as short (STM)- and long-term memory (LTM). Here the effects of systemic and intrahippocampal administration of 5-HT agonists and antagonists on an autoshaping learning task were explored, which requires hippocampal translation and transduction as well as 5-HT receptors expression. As previously reported ketamine (glutamatergic antagonist) and two well-known amnesic drugs, scopolamine (cholinergic antagonist) and dizocilpine (NMDA antagonist) impaired STM but not LTM; dizocilpine even improved the latter. Since ketamine produces hallucinations and impairs memory in humans, we address the question if well-known antipsychotic haloperidol and clozapine might affect STM deficit. Indeed, systemic administration of clozapinereceptors, systemic and intrahippocampal administration of 5-HT drugs were further explored. The ketamine STM-induced deficit was blocked by 8-OHDPAT (5-HT(1A/7) agonist) and SB-399885 (a 5-HT(6) antagonist) but not by 5-HT(1B), 5-HT(2) and 5-HT(7) antagonists, thus implicating 5-HT(1A/7) and 5-HT(6) receptors. These data also suggest that ketamine (at 10 mg/kg) represents a reliable pharmacological tool to explore memory deficits related to hippocampus and schizophrenia.

  4. Equivalent molecular mass of cytosolic and nuclear forms of Ah receptor from Hepa-1 cells determined by photoaffinity labeling with 2,3,7,8-[3H]tetrachlorodibenzo-p-dioxin

    International Nuclear Information System (INIS)

    Prokipcak, R.D.; Okey, A.B.

    1990-01-01

    The structure of the Ah receptor previously has been extensively characterized by reversible binding of the high affinity ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin. We report the use of [ 3 H]2,3,7,8-tetrachlorodibenzo-p-dioxin as a photoaffinity ligand for Ah receptor from the mouse hepatoma cell line Hepa-1c1c9. Both cytosolic and nuclear forms of Ah receptor could be specifically photoaffinity-labeled, which allowed determination of molecular mass for the two forms under denaturing conditions. After analysis by fluorography of polyacrylamide gels run in the presence of sodium dodecyl sulfate, molecular mass for the cytosolic form of Ah receptor was estimated at 92,000 +/- 4,300 and that for the nuclear form was estimated at 93,500 +/- 3,400. Receptor in mixture of cytosol and nuclear extract (each labeled separately with [ 3 H]2,3,7,8-tetrachlorodibenzo-p-dioxin) migrated as a single band. These results are consistent with the presence of a common ligand-binding subunit of identical molecular mass in both cytosolic and nuclear complexes

  5. Structure-function relationships for the interleukin 2 receptor system

    Directory of Open Access Journals (Sweden)

    Richard J. Robb

    1987-01-01

    Full Text Available Receptors for interleukin 2 (IL-2 esit in at least three forms which differ in their subunit compositio, their affinity for ligand and their ability to mediate a cellular reponse. Type I receptors occur following cellular acitivation and consist of the 55,000 m. w. glycoprotein Tac. These receptors bind IL-2 with a low affinity, do not internalize ligand and have not been definitively associated with any response. Type II receptors, on the other hand, conssit of one or more glycoproteins of 70,000 m. w. which have been termed "beta ([beta] chains." They bind IL-2 with an intermediate affinity and rapidly internalize the ligand. [Beta] proteins mediate many cellular IL-2-dependent reponses, including the short-term activation of natural killer cells and the induction of Tac protein expression. Type III receptors consist of a ternary complex of the Tac protein, the [beta] chain(s and IL-2. They are characterized by a paricularly high affinity for ligand association. Type III receptors also internalize ligand and mediate IL-2-dependent responses at low factor concentrations. The identification of two independent IL-2-binding molecules, Tac and [beta], thus provides the elusive molecular explanation for the differences in IL-2 receptor affinity and suggests the potential for selective therapeutic manipulation of IL-2 reponses.

  6. Comparative Responsiveness of the PROMIS Pain Interference Short Forms, Brief Pain Inventory, PEG, and SF-36 Bodily Pain Subscale.

    Science.gov (United States)

    Kean, Jacob; Monahan, Patrick O; Kroenke, Kurt; Wu, Jingwei; Yu, Zhangsheng; Stump, Tim E; Krebs, Erin E

    2016-04-01

    To compare the sensitivity to change and the responsiveness to intervention of the PROMIS Pain Interference short forms, Brief Pain Inventory (BPI), 3-item PEG scale, and SF-36 Bodily Pain subscale in a sample of patients with persistent musculoskeletal pain of moderate severity. Standardized response means, standardized effect sizes, and receiver operating curve analyses were used to assess change between baseline and 3-month assessments in 250 participants who participated in a randomized clinical effectiveness trial of collaborative telecare management for moderate to severe and persistent musculoskeletal pain. The BPI, PEG, and SF-36 Bodily Pain measures were more sensitive to patient-reported global change than the PROMIS Pain Interference short forms, especially for the clinically improved group, for which the change detected by the PROMIS short forms was not statistically significant. The BPI was more responsive to the clinical intervention than the SF-36 Bodily Pain and PROMIS Pain Interference measures. Post hoc analyses exploring these findings did not suggest that differences in content or rating scale structure (number of response options or anchoring language) adequately explained the observed differences in the detection of change. In this clinical trial, the BPI and PEG measures were better able to detect change than the SF-36 Bodily Pain and PROMIS Pain Interference measures.

  7. Linguistic Features of Persuasive Communication: The Case of DRTV Short Form Spots

    Directory of Open Access Journals (Sweden)

    Smiljana Komar

    2015-12-01

    Full Text Available Direct response television commercials (DRTV exhibit a very specific style of speech and delivery whose main function is to boost the product’s value and sales. This paper presents the findings of the structural and the linguistic analyses of three English DRTV short form spots as seen on Highstreet TV. The emphasis is on the verbal strategies used by advertisers to get the consumers’ attention, develop their interest and desire to own the product and to convince them to purchase it. These strategies include different lexical, syntactic and prosodic features. The structural analysis focuses mainly on non-verbal strategies of broadcasting advertisements whose purpose is to inspire interest and credibility in potential consumers.

  8. Identification of high- and low-affinity NGF receptors during development of the chicken central nervous system

    International Nuclear Information System (INIS)

    Escandon, E.; Chao, M.V.

    1990-01-01

    In order to study regulation of the nerve growth factor (NGF) receptor during embryogenesis in chick brain, we have used affinity crosslinking of tissues with 125 I-NGF. NGF interacts with high- and low-affinity receptors; high-affinity receptors are required for the majority of NGF's actions. Most measurements of receptor levels do not distinguish between high- and low-affinity forms of the receptor. We have used the lipophilic crosslinking agent HSAB to identify the high-affinity, functional receptor during development of the chicken central nervous system. A peak of expression during Embryonic Days 5-10 was detected in all regions of the chicken central nervous system, but, shortly after birth, only the cerebellar region displays significant levels of NGF receptor protein. The time course of expression confirms the dramatic regulation of the NGF receptor gene during defined embryonic periods. The detection of high-affinity NGF receptors in brain and neural retina provides strong evidence that NGF is involved in essential ontogenetic events in the development of the chicken central nervous system

  9. Nicotine response and nicotinic receptors in long-sleep and short-sleep mice.

    Science.gov (United States)

    De Fiebre, C M; Medhurst, L J; Collins, A C

    1987-01-01

    Nicotine response and nicotinic receptor binding were characterized in long-sleep (LS) and short-sleep (SS) mice which have been selectively bred for differential "sleep-time" following ethanol administration. LS mice are more sensitive than SS mice to nicotine as measured by a battery of behavioral and physiological tests and as measured by sensitivity to nicotine-induced seizures. The greater sensitivity of the LS mice is not due to differences in binding of [3H]nicotine. Unlike inbred mouse strains which differ in sensitivity to nicotine-induced seizures, these selected mouse lines do not differ in levels of binding of [125I]alpha-bungarotoxin (BTX) in the hippocampus. Significant differences in BTX binding were found in the cerebellum and striatum. Although these two mouse lines do not differ in blood levels of nicotine following nicotine administration, they differ slightly in brain levels of nicotine indicating differential distribution of the drug. Since this distribution difference is much smaller than the observed behavioral differences, these mice probably differ in CNS sensitivity to nicotine; however, follow-up studies are necessary to test whether the differential response of these mice is due to subtle differences in distribution of nicotine to the brain.

  10. Further characterization of benzodiazepine receptor differences in long-sleep and short-sleep mice

    International Nuclear Information System (INIS)

    Marley, R.J.; Stinchcomb, A.; Wehner, J.M.

    1988-01-01

    Molecular and conformational characteristics of benzodiazepine (BZ) receptors in cortex and cerebellum from long-sleep and mice were investigated using heat inactivation and beta-carboline competition techniques. To investigate differences in the allosteric coupling between GABA and BZ receptors, the protection of BZ receptors from heat inactivation, by GABA, was also evaluated. The two genotypes do not differ in the affinity or number of BZ receptors in the cortex or cerebellum. They do, however, appear to differ in the molecular structure and/or regulation of the conformational state of the receptor in the cortex, as indicated by a greater sensitivity of LS mice to both heat inactivation and beta-carboline competition of 3 H-flunitrazepam (FNZ) binding in this region. Evidence for differences in the nature of coupling between GABA and BZ receptors is provided by the finding in that in both regions, GABA protected BZ receptors from inactivation to a greater degree in LS mice. The relationship between these differences and the multiplicity of expression of BZ receptors is discussed

  11. Development and Cross-Validation of the Short Form of the Cultural Competence Scale for Nurses

    Directory of Open Access Journals (Sweden)

    Duckhee Chae, PhD, RN

    2018-03-01

    Full Text Available Purpose: To develop and validate the short form of the Korean adaptation of the Cultural Competence Scale for Nurses. Methods: To shorten the 33-item Cultural Competence Scale for Nurses, an expert panel (N = 6 evaluated its content validity. The revised items were pilot tested using a sample of nine nurses, and clarity was assessed through cognitive interviews with respondents. The original instrument was shortened and validated through item analysis, exploratory factor analysis, convergent validity, and reliability using data from 277 hospital nurses. The 14-item final version was cross-validated through confirmatory factor analysis, convergent validity, discriminant validity, known-group comparisons, and reliability using data from 365 nurses belonging to 19 hospitals. Results: A 4-factor, 14-item model demonstrated satisfactory fit with significant factor loadings. The convergent validity between the developed tool and transcultural self-efficacy was significant (r = .55, p < .001. The convergent validity evaluated using the Average Variance Extracted and discriminant validity were acceptable. Known-group comparisons revealed significant differences in the mean scores of the groups who spent more than one month abroad (p = .002 were able to communicate in a foreign language (p < .001 and had education to care for foreign patients (p = .039. Cronbach's α was .89, and the reliability of the subscales ranged from .74 to .91. Conclusion: The Cultural Competence Scale for Nurses-Short Form demonstrated good reliability and validity. It is a short and appropriate instrument for use in clinical and research settings to assess nurses' cultural competence. Keywords: cultural competence, psychometric properties, nurse

  12. The dependence of the nuclear charge form factor on short range correlations and surface fluctuation effects

    International Nuclear Information System (INIS)

    Massen, S. E.; Garistov, V. P.; Grypeos, M. E.

    1996-01-01

    The effects of nuclear surface fluctuations on harmonic oscillator elastic charge form factor of light nuclei are investigated, simultaneously approximating the short-range correlations through a Jastrow correlation factor. Inclusion of the surface fluctuation effects within this description, by truncating the cluster expansion at the two-body part, is found to improve somewhat the fit to the elastic charge form-factor of 16 O and 40 Ca. However, the convergence of the cluster expansion is expected to deteriorate. An additional finding is that surface-fluctuation correlations produce a drastic change in the asymptotic behaviour of the point-proton form-factor, which now falls off quite slowly (i.e. as const.q -4 ) at large values of the momentum transfer q

  13. Cognitive impairment as assessed by a short form of MMSE was predictive of mortality

    DEFF Research Database (Denmark)

    Schultz-Larsen, Kirsten; Rahmanfard, Naghmeh; Kreiner, Svend

    2008-01-01

    OBJECTIVE: This study explores the association between cognitive impairment and mortality in late senescence. A specific purpose was to validate the ability of a short form of the Mini-Mental State Examination (MMSE) in predicting mortality. STUDY DESIGN AND SETTING: The cognition-mortality link,...... chronic diseases and mortality. A short, valid MMSE subscale, which was a powerful predictor of mortality especially among men, is attractive for research and clinical practice......., as assessed by the original MMSE and D-MMSE (a subscale associated to dementia) was estimated on a community sample of 1,111 older people using Cox proportional hazards models. RESULTS: Impaired cognitive function as assessed by both the original MMSE and D-MMSE predicted mortality in older men and women over...... long intervals. The association persisted after controlling for sociodemographic variables, Body Mass Index, mobility, and comorbidity and was unaffected by self-reported specific chronic diseases in both men and women. In addition, disease related risk of mortality was substantially reduced...

  14. Development and validation of a short form of the Fugl-Meyer motor scale in patients with stroke.

    NARCIS (Netherlands)

    Hsieh, Y.W.; Hsueh, I.P.; Chou, Y.T.; Sheu, C.F.; Hsieh, C.L.; Kwakkel, G.

    2007-01-01

    BACKGROUND AND PURPOSE: The 50-item Fugl-Meyer motor scale (FM) is commonly used in outcome studies. However, the lengthy administration time of the FM keeps it from being widely accepted for routine clinical use. We aimed to develop a short form of the FM (the S-FM) with sound psychometric

  15. Composite Reliability and Standard Errors of Measurement for a Seven-Subtest Short Form of the Wechsler Adult Intelligence Scale-Revised.

    Science.gov (United States)

    Schretlen, David; And Others

    1994-01-01

    Composite reliability and standard errors of measurement were computed for prorated Verbal, Performance, and Full-Scale intelligence quotient (IQ) scores from a seven-subtest short form of the Wechsler Adult Intelligence Scale-Revised. Results with 1,880 adults (standardization sample) indicate that this form is as reliable as the complete test.…

  16. Development and Psychometric Validation of the EDE-QS, a 12 Item Short Form of the Eating Disorder Examination Questionnaire (EDE-Q)

    Science.gov (United States)

    Gideon, Nicole; Hawkes, Nick; Mond, Jonathan; Saunders, Rob; Tchanturia, Kate; Serpell, Lucy

    2016-01-01

    Objective The aim of this study was to develop and validate a short form of the Eating Disorder Examination Questionnaire (EDE-Q) for routine, including session by session, outcome assessment. Method The current, 28-item version (6.0) of the EDE-Q was completed by 489 individuals aged 18–72 with various eating disorders recruited from three UK specialist eating disorder services. Rasch analysis was carried out on factors identified by means of principal component analysis, which in combination with expert ratings informed the development of an EDE-Q short form. The shortened questionnaire’s reliability, validity and sensitivity was assessed based on online data collected from students of a UK university and volunteers with a history of eating disorders recruited from a national eating disorders charity aged 18–74 (N = 559). Results A 12-item short form, the Eating Disorder Examination Questionnaire Short (EDE-QS) was derived. The new measure showed high internal consistency (Cronbach’s α = .913) and temporal stability (ICC = .93; p eating disorder and comorbid psychopathology. It was sufficiently sensitive to distinguish between people with and without eating disorders. Discussion The EDE-QS is a brief, reliable and valid measure of eating disorder symptom severity that performs similarly to the EDE-Q and that lends itself for the use of sessional outcome monitoring in treatment and research. PMID:27138364

  17. NMDA receptor activation upstream of methyl farnesoate signaling for short day-induced male offspring production in the water flea, Daphnia pulex.

    Science.gov (United States)

    Toyota, Kenji; Miyakawa, Hitoshi; Yamaguchi, Katsushi; Shigenobu, Shuji; Ogino, Yukiko; Tatarazako, Norihisa; Miyagawa, Shinichi; Iguchi, Taisen

    2015-03-14

    The cladoceran crustacean Daphnia pulex produces female offspring by parthenogenesis under favorable conditions, but in response to various unfavorable external stimuli, it produces male offspring (environmental sex determination: ESD). We recently established an innovative system for ESD studies using D. pulex WTN6 strain, in which the sex of the offspring can be controlled simply by changes in the photoperiod: the long-day and short-day conditions can induce female and male offspring, respectively. Taking advantage of this system, we demonstrated that de novo methyl farnesoate (MF) synthesis is necessary for male offspring production. These results indicate the key role of innate MF signaling as a conductor between external environmental stimuli and the endogenous male developmental pathway. Despite these findings, the molecular mechanisms underlying up- and downstream signaling of MF have not yet been well elucidated in D. pulex. To elucidate up- and downstream events of MF signaling during sex determination processes, we compared the transcriptomes of daphnids reared under the long-day (female) condition with short-day (male) and MF-treated (male) conditions. We found that genes involved in ionotropic glutamate receptors, known to mediate the vast majority of excitatory neurotransmitting processes in various organisms, were significantly activated in daphnids by the short-day condition but not by MF treatment. Administration of specific agonists and antagonists, especially for the N-methyl-D-aspartic acid (NMDA) receptor, strongly increased or decreased, respectively, the proportion of male-producing mothers. Moreover, we also identified genes responsible for male production (e.g., protein kinase C pathway-related genes). Such genes were generally shared between the short-day reared and MF-treated daphnids. We identified several candidate genes regulating ESD which strongly suggests that these genes may be essential factors for male offspring production as an

  18. The macrophage scavenger receptor CD163

    DEFF Research Database (Denmark)

    Nielsen, Marianne Jensby; Madsen, Mette; Møller, Holger J

    2006-01-01

    CD163 is the monocyte/macrophage-specific receptor for haptoglobin-hemoglobin (Hp-Hb) complexes. The cytoplasmic tail of human CD163 exists as a short tail variant and two long tail variants. Reverse transcriptase-polymerase chain reaction analysis indicated that all three CD163 variants are subs......CD163 is the monocyte/macrophage-specific receptor for haptoglobin-hemoglobin (Hp-Hb) complexes. The cytoplasmic tail of human CD163 exists as a short tail variant and two long tail variants. Reverse transcriptase-polymerase chain reaction analysis indicated that all three CD163 variants...

  19. Region-specific expression and hormonal regulation of the first exon variants of rat prolactin receptor mRNA in rat brain and anterior pituitary gland.

    Science.gov (United States)

    Nogami, H; Hoshino, R; Ogasawara, K; Miyamoto, S; Hisano, S

    2007-08-01

    Recent studies have revealed the occurrence of five first exon variants of the rat prolactin receptor mRNA, suggesting that multiple promoters direct prolactin receptor transcription in response to different regulatory factors. In the present study, regional expression of these first exon variants, as well as two prolactin receptor subtypes generated by alternative splicing, was examined in the brains and anterior pituitary glands of female rats. Expression of the long-form was detected in the choroid plexus, hypothalamus, hippocampus, cerebral cortex and anterior pituitary gland, whereas the short form was detected only in the choroid plexus. E1-3 mRNA, a first exon variant, was detected in the choroid plexus, hypothalamus, and anterior pituitary gland, whereas E1-4 was detected only in the choroid plexus. Other variants were not detectable by the polymerase chain reaction protocol employed in this study. Ovariectomy increased the short form in the choroid plexus and the E1-3 expression in the choroid plexus and pituitary gland, but changes in the long-form and E1-4 expression were minimal. Replacement of oestrogens and prolactin suggest that oestrogens down-regulate E1-3 expression in the choroid plexus and pituitary gland, and that the negative effect of oestrogen is mediated by prolactin in the pituitary gland. The present results revealed the region-specific promoter usage in prolactin receptor mRNA transcription, as well as the involvement of oestrogens in the regulation of E1-3 mRNA expression in the brain and pituitary gland.

  20. Evaluation of the psychometric properties of two short forms of the social interaction anxiety scale and the social phobia scale.

    Science.gov (United States)

    Le Blanc, Allura L; Bruce, Laura C; Heimberg, Richard G; Hope, Debra A; Blanco, Carlos; Schneier, Franklin R; Liebowitz, Michael R

    2014-06-01

    The Social Interaction Anxiety Scale and Social Phobia Scale are widely used measures of social anxiety. Using data from individuals with social anxiety disorder (n = 435) and nonanxious controls (n = 86), we assessed the psychometric properties of two independently developed short forms of these scales. Indices of convergent and discriminant validity, diagnostic specificity, sensitivity to treatment, and readability were examined. Comparisons of the two sets of short forms to each other and the original long forms were conducted. Both sets of scales demonstrated adequate internal consistency in the patient sample, showed expected patterns of correlation with measures of related and unrelated constructs, adequately discriminated individuals with social anxiety disorder from those without, and showed decreases in scores over the course of cognitive-behavioral therapy and/or pharmacotherapy. However, some significant differences in scale performance were noted. Implications for the clinical assessment of social anxiety are discussed. © The Author(s) 2014.

  1. Relationship between variant forms of estrogen receptor RNA and an apoptosis-related RNA, TRPM-2, with survival in patients with breast cancer.

    Science.gov (United States)

    Rennie, P S; Mawji, N R; Coldman, A J; Godolphin, W; Jones, E C; Vielkind, J R; Bruchovsky, N

    1993-12-15

    Although smaller variant forms of estrogen receptor (ER) messenger RNA (mRNA) have been detected in breast tumors, neither their prevalence nor their prognostic significance have been evaluated. Similarly, TRPM-2 mRNA, the product of a gene induced principally during the onset of apoptosis, is present in mouse and human breast cancer cell lines, but whether it also occurs in primary breast tumors and is related to disease outcome is unknown. The relative expression and transcript size of ER mRNA and TRPM-2 mRNA in 126 primary breast tumors were measured by Northern analysis and compared with tumor grade, hormone receptor status, extent of tumor necrosis, and survival. In ER-positive tumors, 64% of the tumors had only the normal 6.5 kb ER mRNA, an additional 9% had the normal plus smaller ER mRNA, and 2% had variant forms. Only 8% of ER-negative tumors had ER mRNA transcripts. There were significant relationships between the occurrence of ER mRNA and low tumor grade, ER-positive receptor status, and better survival. In contrast, TRPM-2 mRNA was found in only 17% of breast tumors, none of which could be grouped with respect to grade, hormone receptor status, or survival. The presence of smaller variant forms of ER mRNA either alone or in association with the normal ER transcript is not indicative of an unfavorable prognosis, whereas TRPM-2 mRNA occurs in many primary breast tumors, but has no apparent relationship to survival.

  2. A comparison study on algorithms of detecting long forms for short forms in biomedical text

    Directory of Open Access Journals (Sweden)

    Wu Cathy H

    2007-11-01

    Full Text Available Abstract Motivation With more and more research dedicated to literature mining in the biomedical domain, more and more systems are available for people to choose from when building literature mining applications. In this study, we focus on one specific kind of literature mining task, i.e., detecting definitions of acronyms, abbreviations, and symbols in biomedical text. We denote acronyms, abbreviations, and symbols as short forms (SFs and their corresponding definitions as long forms (LFs. The study was designed to answer the following questions; i how well a system performs in detecting LFs from novel text, ii what the coverage is for various terminological knowledge bases in including SFs as synonyms of their LFs, and iii how to combine results from various SF knowledge bases. Method We evaluated the following three publicly available detection systems in detecting LFs for SFs: i a handcrafted pattern/rule based system by Ao and Takagi, ALICE, ii a machine learning system by Chang et al., and iii a simple alignment-based program by Schwartz and Hearst. In addition, we investigated the conceptual coverage of two terminological knowledge bases: i the UMLS (the Unified Medical Language System, and ii the BioThesaurus (a thesaurus of names for all UniProt protein records. We also implemented a web interface that provides a virtual integration of various SF knowledge bases. Results We found that detection systems agree with each other on most cases, and the existing terminological knowledge bases have a good coverage of synonymous relationship for frequently defined LFs. The web interface allows people to detect SF definitions from text and to search several SF knowledge bases. Availability The web site is http://gauss.dbb.georgetown.edu/liblab/SFThesaurus.

  3. Immunolocalization of the short neuropeptide F receptor in queen brains and ovaries of the red imported fire ant (Solenopsis invicta Buren

    Directory of Open Access Journals (Sweden)

    Pietrantonio Patricia V

    2011-06-01

    Full Text Available Abstract Background Insect neuropeptides are involved in diverse physiological functions and can be released as neurotransmitters or neuromodulators acting within the central nervous system, and as circulating neurohormones in insect hemolymph. The insect short neuropeptide F (sNPF peptides, related to the vertebrate neuropeptide Y (NPY peptides, have been implicated in the regulation of food intake and body size, and play a gonadotropic role in the ovaries of some insect species. Recently the sNPF peptides were localized in the brain of larval and adult Drosophila. However, the location of the sNPF receptor, a G protein-coupled receptor (GPCR, has not yet been investigated in brains of any adult insect. To elucidate the sites of action of the sNPF peptide(s, the sNPF receptor tissue expression and cellular localization were analyzed in queens of the red imported fire ant, Solenopsis invicta Buren (Hymenoptera, an invasive social insect. Results In the queen brains and subesophageal ganglion about 164 cells distributed in distinctive cell clusters (C1-C9 and C12 or as individual cells (C10, C11 were immuno-positive for the sNPF receptor. Most of these neurons are located in or near important sensory neuropils including the mushroom bodies, the antennal lobes, the central complex, and in different parts of the protocerebrum, as well as in the subesophageal ganglion. The localization of the sNPF receptor broadly links the receptor signaling pathway with circuits regulating learning and feeding behaviors. In ovaries from mated queens, the detection of sNPF receptor signal at the posterior end of oocytes in mid-oogenesis stage suggests that the sNPF signaling pathway may regulate processes at the oocyte pole. Conclusions The analysis of sNPF receptor immunolocalization shows that the sNPF signaling cascade may be involved in diverse functions, and the sNPF peptide(s may act in the brain as neurotransmitter(s or neuromodulator(s, and in the ovaries

  4. Monkeys have a limited form of short-term memory in audition.

    Science.gov (United States)

    Scott, Brian H; Mishkin, Mortimer; Yin, Pingbo

    2012-07-24

    A stimulus trace may be temporarily retained either actively [i.e., in working memory (WM)] or by the weaker mnemonic process we will call passive short-term memory, in which a given stimulus trace is highly susceptible to "overwriting" by a subsequent stimulus. It has been suggested that WM is the more robust process because it exploits long-term memory (i.e., a current stimulus activates a stored representation of that stimulus, which can then be actively maintained). Recent studies have suggested that monkeys may be unable to store acoustic signals in long-term memory, raising the possibility that they may therefore also lack auditory WM. To explore this possibility, we tested rhesus monkeys on a serial delayed match-to-sample (DMS) task using a small set of sounds presented with ~1-s interstimulus delays. Performance was accurate whenever a match or a nonmatch stimulus followed the sample directly, but it fell precipitously if a single nonmatch stimulus intervened between sample and match. The steep drop in accuracy was found to be due not to passive decay of the sample's trace, but to retroactive interference from the intervening nonmatch stimulus. This "overwriting" effect was far greater than that observed previously in serial DMS with visual stimuli. The results, which accord with the notion that WM relies on long-term memory, indicate that monkeys perform serial DMS in audition remarkably poorly and that whatever success they had on this task depended largely, if not entirely, on the retention of stimulus traces in the passive form of short-term memory.

  5. A Comparison of the Psychometric Properties of the Psychopathic Personality Inventory Full-Length and Short-Form Versions

    Science.gov (United States)

    Kastner, Rebecca M.; Sellbom, Martin; Lilienfeld, Scott O.

    2012-01-01

    The Psychopathic Personality Inventory (PPI) has shown promising construct validity as a measure of psychopathy. Because of its relative efficiency, a short-form version of the PPI (PPI-SF) was developed and has proven useful in many psychopathy studies. The validity of the PPI-SF, however, has not been thoroughly examined, and no studies have…

  6. Proteolytic receptor cleavage in the pathogenesis of blood rheology and co-morbidities in metabolic syndrome. Early forms of autodigestion.

    Science.gov (United States)

    Mazor, Rafi; Schmid-Schönbein, Geert W

    2015-01-01

    Abnormal blood rheological properties seldom occur in isolation and instead are accompanied by other complications, often designated as co-morbidities. In the metabolic syndrome with complications like hypertension, diabetes and lack of normal microvascular blood flow, the underlying molecular mechanisms that simultaneously lead to elevated blood pressure and diabetes as well as abnormal microvascular rheology and other cell dysfunctions have remained largely unknown. In this review, we propose a new hypothesis for the origin of abnormal cell functions as well as multiple co-morbidities. Utilizing experimental models for the metabolic disease with diverse co-morbidities we summarize evidence for the presence of an uncontrolled extracellular proteolytic activity that causes ectodomain receptor cleavage and loss of their associated cell function. We summarize evidence for unchecked degrading proteinase activity, e.g. due to matrix metalloproteases, in patients with hypertension, Type II diabetes and obesity, in addition to evidence for receptor cleavage in the form of receptor fragments and decreased extracellular membrane expression levels. The evidence suggest that a shift in blood rheological properties and other co-morbidities may in fact be derived from a common mechanism that is due to uncontrolled proteolytic activity, i.e. an early form of autodigestion. Identification of the particular proteases involved and the mechanisms of their activation may open the door to treatment that simultaneously targets multiple co-morbidities in the metabolic syndrome.

  7. A Study Investigating the Feasibility of Creating a Short Form of the WISC-R for Disabled Readers.

    Science.gov (United States)

    Brown, David M.; Otts, David A.

    The purpose of this study was to investigate the feasibility of creating a short form of the Wechsler Intelligence Scale for Children-Revised (WISC-R) for use in a clinical setting with disabled readers. The subjects were 100 clients ages six to sixteen of the Belser-Parton Reading Center at the University of Alabama whose files contained scores…

  8. Crystallization and preliminary X-ray diffraction of human interleukin-7 bound to unglycosylated and glycosylated forms of its α-receptor

    Energy Technology Data Exchange (ETDEWEB)

    Wickham, Joseph Jr; Walsh, Scott T. R., E-mail: walsh.220@osu.edu [Department of Molecular and Cellular Biochemistry, Comprehensive Cancer Center, Ohio State University, 467 Hamilton Hall, 1645 Neil Avenue, Columbus, OH 43210 (United States)

    2007-10-01

    Bacterial and insect cell expression systems have been developed to produce unglycosylated and glycosylated forms of human interleukin-7 (IL-7) and the extracellular domain of its α receptor, IL-7Rα. We report the crystallization and X-ray diffraction of IL-7 complexes to both unglycosylated and glycosylated forms of the IL-7Rα to 2.7 and 3.0 Å, respectively. The interleukin-7 (IL-7) signaling pathway plays an essential role in the development, proliferation and homeostasis of T and B cells in cell-mediated immunity. Understimulation and overstimulation of the IL-7 signaling pathway leads to severe combined immunodeficiency, autoimmune reactions, heart disease and cancers. Stimulation of the IL-7 pathway begins with IL-7 binding to its α-receptor, IL-7Rα. Protein crystals of unglycosylated and glycosylated complexes of human IL-7–IL-7Rα extracellular domain (ECD) obtained using a surface entropy-reduction approach diffract to 2.7 and 3.0 Å, respectively. Anomalous dispersion methods will be used to solve the unglycosylated IL-7–IL-7Rα ECD complex structure and this unglycosylated structure will then serve as a model in molecular-replacement attempts to solve the structure of the glycosylated IL-7–α-receptor complex.

  9. Crystallization and preliminary X-ray diffraction of human interleukin-7 bound to unglycosylated and glycosylated forms of its α-receptor

    International Nuclear Information System (INIS)

    Wickham, Joseph Jr; Walsh, Scott T. R.

    2007-01-01

    Bacterial and insect cell expression systems have been developed to produce unglycosylated and glycosylated forms of human interleukin-7 (IL-7) and the extracellular domain of its α receptor, IL-7Rα. We report the crystallization and X-ray diffraction of IL-7 complexes to both unglycosylated and glycosylated forms of the IL-7Rα to 2.7 and 3.0 Å, respectively. The interleukin-7 (IL-7) signaling pathway plays an essential role in the development, proliferation and homeostasis of T and B cells in cell-mediated immunity. Understimulation and overstimulation of the IL-7 signaling pathway leads to severe combined immunodeficiency, autoimmune reactions, heart disease and cancers. Stimulation of the IL-7 pathway begins with IL-7 binding to its α-receptor, IL-7Rα. Protein crystals of unglycosylated and glycosylated complexes of human IL-7–IL-7Rα extracellular domain (ECD) obtained using a surface entropy-reduction approach diffract to 2.7 and 3.0 Å, respectively. Anomalous dispersion methods will be used to solve the unglycosylated IL-7–IL-7Rα ECD complex structure and this unglycosylated structure will then serve as a model in molecular-replacement attempts to solve the structure of the glycosylated IL-7–α-receptor complex

  10. Blocking muscarinic receptors in the olfactory bulb impairs performance on an olfactory short term memory task

    Directory of Open Access Journals (Sweden)

    Sasha eDevore

    2012-09-01

    Full Text Available Cholinergic inputs to cortical processing networks have long been associated with attentional and top-down processing. Experimental and theoretical studies suggest that cholinergic inputs to the main olfactory bulb (OB can modulate both neural and behavioral odor discrimination. Previous experiments from our laboratory and others demonstrate that blockade of nicotinic receptors directly impairs olfactory discrimination, whereas blockade of muscarinic receptors only measurably impairs olfactory perception when task demands are made more challenging, such as when very low-concentration odors are used or rats are required to maintain sensory memory over long durations. To further investigate the role of muscarinic signaling in the OB, we developed an olfactory delayed match-to-sample task using a digging-based behavioral paradigm. We find that rats are able to maintain robust short-term odor memory for tens to hundreds of seconds. To investigate the role of muscarinic signaling in task performance, we bilaterally infused scopolamine into the OB. We find that high dosages of scopolamine (38 mM impair performance on the task across all delays tested, including the baseline condition with no delay, whereas lower dosages (7.6 mM and 22.8 mM had no measureable effects. These results indicate that general execution of the match-to-sample task, even with no delay, is at least partially dependent on muscarinic signaling in the OB.

  11. Blocking muscarinic receptors in the olfactory bulb impairs performance on an olfactory short-term memory task.

    Science.gov (United States)

    Devore, Sasha; Manella, Laura C; Linster, Christiane

    2012-01-01

    Cholinergic inputs to cortical processing networks have long been associated with attentional and top-down processing. Experimental and theoretical studies suggest that cholinergic inputs to the main olfactory bulb (OB) can modulate both neural and behavioral odor discrimination. Previous experiments from our laboratory and others demonstrate that blockade of nicotinic receptors directly impairs olfactory discrimination, whereas blockade of muscarinic receptors only measurably impairs olfactory perception when task demands are made more challenging, such as when very low-concentration odors are used or rats are required to maintain sensory memory over long durations. To further investigate the role of muscarinic signaling in the OB, we developed an olfactory delayed match-to-sample task using a digging-based behavioral paradigm. We find that rats are able to maintain robust short-term odor memory for 10-100 s. To investigate the role of muscarinic signaling in task performance, we bilaterally infused scopolamine into the OB. We find that high dosages of scopolamine (38 mM) impair performance on the task across all delays tested, including the baseline condition with no delay, whereas lower dosages (7.6 mM and 22.8 mM) had no measureable effects. These results indicate that general execution of the match-to-sample task, even with no delay, is at least partially dependent on muscarinic signaling in the OB.

  12. Exploration of N-arylpiperazine Binding Sites of D2 Dopaminergic Receptor.

    Science.gov (United States)

    Soskic, Vukic; Sukalovic, Vladimir; Kostic-Rajacic, Sladjana

    2015-01-01

    The crystal structures of the D3 dopamine receptor and several other G-protein coupled receptors (GPCRs) were published in recent times. Those 3D structures are used by us and other scientists as a template for the homology modeling and ligand docking analysis of related GPCRs. Our main scientific interest lies in the field of pharmacologically active N-arylpiperazines that exhibit antipsychotic and/or antidepressant properties, and as such are dopaminergic and serotonergic receptor ligands. In this short review article we are presenting synthesis and biological data on the new N-arylpipereazine as well our results on molecular modeling of the interactions of those N-arylpiperazines with the model of D2 dopamine receptors. To obtain that model the crystal structure of the D3 dopamine receptor was used. Our results show that the N-arylpiperazines binding site consists of two pockets: one is the orthosteric binding site where the N-arylpiperazine part of the ligand is docked and the second is a non-canonical accessory binding site for N-arylpipereazine that is formed by a second extracellular loop (ecl2) of the receptor. Until now, the structure of this receptor region was unresolved in crystal structure analyses of the D3 dopamine receptor. To get a more complete picture of the ligand - receptor interaction, DFT quantum mechanical calculations on N-arylpiperazine were performed and the obtained models were used to examine those interactions.

  13. Development and Psychometric Validation of the EDE-QS, a 12 Item Short Form of the Eating Disorder Examination Questionnaire (EDE-Q.

    Directory of Open Access Journals (Sweden)

    Nicole Gideon

    Full Text Available The aim of this study was to develop and validate a short form of the Eating Disorder Examination Questionnaire (EDE-Q for routine, including session by session, outcome assessment.The current, 28-item version (6.0 of the EDE-Q was completed by 489 individuals aged 18-72 with various eating disorders recruited from three UK specialist eating disorder services. Rasch analysis was carried out on factors identified by means of principal component analysis, which in combination with expert ratings informed the development of an EDE-Q short form. The shortened questionnaire's reliability, validity and sensitivity was assessed based on online data collected from students of a UK university and volunteers with a history of eating disorders recruited from a national eating disorders charity aged 18-74 (N = 559.A 12-item short form, the Eating Disorder Examination Questionnaire Short (EDE-QS was derived. The new measure showed high internal consistency (Cronbach's α = .913 and temporal stability (ICC = .93; p < .001. It was highly correlated with the original EDE-Q (r = .91 for people without ED; r = .82 for people with ED and other measures of eating disorder and comorbid psychopathology. It was sufficiently sensitive to distinguish between people with and without eating disorders.The EDE-QS is a brief, reliable and valid measure of eating disorder symptom severity that performs similarly to the EDE-Q and that lends itself for the use of sessional outcome monitoring in treatment and research.

  14. Multivalent Fcγ-receptor engagement by a hexameric Fc-fusion protein triggers Fcγ-receptor internalisation and modulation of Fcγ-receptor functions.

    Science.gov (United States)

    Qureshi, O S; Rowley, T F; Junker, F; Peters, S J; Crilly, S; Compson, J; Eddleston, A; Björkelund, H; Greenslade, K; Parkinson, M; Davies, N L; Griffin, R; Pither, T L; Cain, K; Christodoulou, L; Staelens, L; Ward, E; Tibbitts, J; Kiessling, A; Smith, B; Brennan, F R; Malmqvist, M; Fallah-Arani, F; Humphreys, D P

    2017-12-06

    Engagement of Fcγ-receptors triggers a range of downstream signalling events resulting in a diverse array of immune functions. As a result, blockade of Fc-mediated function is an important strategy for the control of several autoimmune and inflammatory conditions. We have generated a hexameric-Fc fusion protein (hexameric-Fc) and tested the consequences of multi-valent Fcγ-receptor engagement in in vitro and in vivo systems. In vitro engagement of hexameric-Fc with FcγRs showed complex binding interactions that altered with receptor density and triggered the internalisation and degradation of Fcγ-receptors. This caused a disruption of Fc-binding and phagocytosis. In vivo, in a mouse ITP model we observed a short half-life of hexameric-Fc but were nevertheless able to observe inhibition of platelet phagocytosis several days after hexameric-Fc dosing. In cynomolgus monkeys, we again observed a short half-life, but were able to demonstrate effective FcγR blockade. These findings demonstrate the ability of multi-valent Fc-based therapeutics to interfere with FcγR function and a potential mechanism through which they could have a sustained effect; the internalisation and degradation of FcγRs.

  15. Dopamine-induced apoptosis of lactotropes is mediated by the short isoform of D2 receptor.

    Science.gov (United States)

    Radl, Daniela Betiana; Ferraris, Jimena; Boti, Valeria; Seilicovich, Adriana; Sarkar, Dipak Kumar; Pisera, Daniel

    2011-03-25

    Dopamine, through D2 receptor (D2R), is the major regulator of lactotrope function in the anterior pituitary gland. Both D2R isoforms, long (D2L) and short (D2S), are expressed in lactotropes. Although both isoforms can transduce dopamine signal, they differ in the mechanism that leads to cell response. The administration of D2R agonists, such as cabergoline, is the main pharmacological treatment for prolactinomas, but resistance to these drugs exists, which has been associated with alterations in D2R expression. We previously reported that dopamine and cabergoline induce apoptosis of lactotropes in primary culture in an estrogen-dependent manner. In this study we used an in vivo model to confirm the permissive action of estradiol in the apoptosis of anterior pituitary cells induced by D2R agonists. Administration of cabergoline to female rats induced apoptosis, measured by Annexin-V staining, in anterior pituitary gland from estradiol-treated rats but not from ovariectomized rats. To evaluate the participation of D2R isoforms in the apoptosis induced by dopamine we used lactotrope-derived PR1 cells stably transfected with expression vectors encoding D2L or D2S receptors. In the presence of estradiol, dopamine induced apoptosis, determined by ELISA and TUNEL assay, only in PR1-D2S cells. To study the role of p38 MAPK in apoptosis induced by D2R activation, anterior pituitary cells from primary culture or PR1-D2S were incubated with an inhibitor of the p38 MAPK pathway (SB203850). SB203580 blocked the apoptotic effect of D2R activation in lactotropes from primary cultures and PR1-D2S cells. Dopamine also induced p38 MAPK phosphorylation, determined by western blot, in PR1-D2S cells and estradiol enhanced this effect. These data suggest that, in the presence of estradiol, D2R agonists induce apoptosis of lactotropes by their interaction with D2S receptors and that p38 MAPK is involved in this process.

  16. Assessing the Psychometric Properties of the Attitudes toward Seeking Professional Psychological Help Scale-Short Form in Mainland China

    Science.gov (United States)

    Fang, Ke; Pieterse, Alex L.; Friedlander, Myrna; Cao, Junhong

    2011-01-01

    This investigation tested the psychometric properties of the Attitudes Toward Seeking Professional Psychological Help Scale-Short Form (ATSPPH-SF; Fisher and Farina ["Journal of College Student Development, 36", 368-373, 1995]) in a sample of 338 Mainland Chinese college students. Using back-translation, the ATSPPH-SF was translated into…

  17. The Cannabinoid Receptor CB1 Modulates the Signaling Properties of the Lysophosphatidylinositol Receptor GPR55*

    Science.gov (United States)

    Kargl, Julia; Balenga, Nariman; Parzmair, Gerald P.; Brown, Andrew J.; Heinemann, Akos; Waldhoer, Maria

    2012-01-01

    The G protein-coupled receptor (GPCR) 55 (GPR55) and the cannabinoid receptor 1 (CB1R) are co-expressed in many tissues, predominantly in the central nervous system. Seven transmembrane spanning (7TM) receptors/GPCRs can form homo- and heteromers and initiate distinct signaling pathways. Recently, several synthetic CB1 receptor inverse agonists/antagonists, such as SR141716A, AM251, and AM281, were reported to activate GPR55. Of these, SR141716A was marketed as a promising anti-obesity drug, but was withdrawn from the market because of severe side effects. Here, we tested whether GPR55 and CB1 receptors are capable of (i) forming heteromers and (ii) whether such heteromers could exhibit novel signaling patterns. We show that GPR55 and CB1 receptors alter each others signaling properties in human embryonic kidney (HEK293) cells. We demonstrate that the co-expression of FLAG-CB1 receptors in cells stably expressing HA-GPR55 specifically inhibits GPR55-mediated transcription factor activation, such as nuclear factor of activated T-cells and serum response element, as well as extracellular signal-regulated kinases (ERK1/2) activation. GPR55 and CB1 receptors can form heteromers, but the internalization of both receptors is not affected. In addition, we observe that the presence of GPR55 enhances CB1R-mediated ERK1/2 and nuclear factor of activated T-cell activation. Our data provide the first evidence that GPR55 can form heteromers with another 7TM/GPCR and that this interaction with the CB1 receptor has functional consequences in vitro. The GPR55-CB1R heteromer may play an important physiological and/or pathophysiological role in tissues endogenously co-expressing both receptors. PMID:23161546

  18. Clinical assessment of early language development: a simplified short form of the Mandarin communicative development inventory.

    Science.gov (United States)

    Soli, Sigfrid D; Zheng, Yun; Meng, Zhaoli; Li, Gang

    2012-09-01

    The purpose of this study was to develop a practical mean for clinical evaluation of early pediatric language development by establishing developmental trajectories for receptive and expressive vocabulary growth in children between 6 and 32 months of age using a simple, time-efficient assessment tool. Simplified short form versions of the Words and Gestures and Words and Sentences vocabulary inventories in the Mandarin Communicative Development Inventory [1] were developed and used to assess early language development in developmentally normal children from 6 to 32 months of age during routine health checks. Developmental trajectories characterizing the rate of receptive and expressive vocabulary growth between 6 and 32 months of age are reported. These trajectories allow the equivalent age corresponding to a score to be determined after a brief structured interview with the child's parents that can be conducted in a busy clinical setting. The simplified short forms of the Mandarin Communicative Development Inventories can serve as a clinically useful tool to assess early child language development, providing a practical mean of objectively assessing early language development following early interventions to treat young children with hearing impairment as well as speech and language delays. Objective evidence of language development is essential for achievement of effective (re)habilitation outcomes. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  19. Investigating self-esteem in individuals with schizophrenia: relevance of the Self-Esteem Rating Scale-Short Form.

    Science.gov (United States)

    Lecomte, Tania; Corbière, Marc; Laisné, François

    2006-06-30

    Studies investigating self-esteem in individuals with severe mental illness, either as a treatment goal, outcome or correlate to other variables, have increased over the past few years. One of the main difficulties in assessing self-esteem is the assessment itself, often measuring global and stable self-esteem as in the Rosenberg Self-Esteem Scale, or requiring extensive training and long interviews. The present article aims at demonstrating the relevance of the French and English versions of the Self-Esteem Rating Scale-Short Form with individuals with severe mental illness. The instrument's reliability and validity were investigated in a sample of 250 French Canadian college students, 247 British college students and three samples of English- or French-speaking individuals with severe mental illness (N=254, N=150 and N=171). Confirmatory factor analysis revealed that a shorter version of the instrument (20 items), with a positive and a negative self-esteem factor, had a great validity for all the samples studied. The Self-Esteem Rating Scale-Short Form, with its positive and negative self-esteem subscales, appears to be a valid and reliable self-esteem measure for individuals with mental health problems. Limitations of this study and future directions are discussed.

  20. Structural basis for corepressor assembly by the orphan nuclear receptor TLX.

    Science.gov (United States)

    Zhi, Xiaoyong; Zhou, X Edward; He, Yuanzheng; Searose-Xu, Kelvin; Zhang, Chun-Li; Tsai, Chih-Cheng; Melcher, Karsten; Xu, H Eric

    2015-02-15

    The orphan nuclear receptor TLX regulates neural stem cell self-renewal in the adult brain and functions primarily as a transcription repressor through recruitment of Atrophin corepressors, which bind to TLX via a conserved peptide motif termed the Atro box. Here we report crystal structures of the human and insect TLX ligand-binding domain in complex with Atro box peptides. In these structures, TLX adopts an autorepressed conformation in which its helix H12 occupies the coactivator-binding groove. Unexpectedly, H12 in this autorepressed conformation forms a novel binding pocket with residues from helix H3 that accommodates a short helix formed by the conserved ALXXLXXY motif of the Atro box. Mutations that weaken the TLX-Atrophin interaction compromise the repressive activity of TLX, demonstrating that this interaction is required for Atrophin to confer repressor activity to TLX. Moreover, the autorepressed conformation is conserved in the repressor class of orphan nuclear receptors, and mutations of corresponding residues in other members of this class of receptors diminish their repressor activities. Together, our results establish the functional conservation of the autorepressed conformation and define a key sequence motif in the Atro box that is essential for TLX-mediated repression. © 2015 Zhi et al.; Published by Cold Spring Harbor Laboratory Press.

  1. Validity and reliability of short forms of parental-caregiver perception and family impact scale in a Telugu speaking population of India.

    Science.gov (United States)

    Kumar, Santhosh; Kroon, Jeroen; Lalloo, Ratilal; Johnson, Newell W

    2016-03-01

    Parental-Caregiver Perception Questionnaire (P-CPQ) and Family Impact Scale (FIS) are commonly used measures to evaluate the parent's perception of the impact of children's oral health on quality of life and family respectively. Recently, shorter forms of P-CPQ and FIS have been developed. No study has sought to validate these short forms in other languages and cultures. This study aimed to evaluate the validity and reliability of FIS, 8 and 16-item P-CPQ in a Telugu speaking population of India. For this cross-sectional study, a multi-stage random sampling technique was used to recruit 11-13 year-old schoolchildren of Medak district, Telangana, India and their parents (n = 1342). Parents were approached with questionnaires through their children who underwent clinical examinations for dental caries, fluorosis and malocclusion. The translated versions underwent pilot testing (n = 40), test-retest reliability was also assessed (n = 161). The overall summary scale and subscales of the short forms of P-CPQ and FIS failed to discriminate between the categories of dental caries severity. Also, malocclusion status was not related to the domain or overall scores of both the short forms of P-CPQ. There were significant differences in subscale and overall scores of 16 and 8-item P-CPQ and FIS between the fluorosis categories. Both 16 and 8-item P-CPQ summary scales were significantly related to parent's global rating of oral health (16-item, r = 0.30, p internal consistency and reliability on repeated administrations.

  2. Developing a short form of the simple Rathus assertiveness schedule using a sample of adults with sickle cell disease.

    Science.gov (United States)

    Jenerette, Coretta; Dixon, Jane

    2010-10-01

    Ethnic and cultural norms influence an individual's assertiveness. In health care, assertiveness may play an important role in health outcomes, especially for predominantly minority populations, such as adults with sickle cell disease. Therefore, it is important to develop measures to accurately assess assertiveness. It is also important to reduce response burden of lengthy instruments while retaining instrument reliability and validity. The purpose of this article is to describe development of a shorter version of the Simple Rathus Assertiveness Schedule (SRAS). Data from a cross-sectional descriptive study of adults with sickle cell disease were used to construct a short form of the SRAS, guided by stepwise regression analysis. The 19-item Simple Rathus Assertiveness Scale-Short Form (SRAS-SF) had acceptable reliability (α = .81) and construct validity and was highly correlated with the SRAS (r = .98, p = .01). The SRAS-SF reduces response burden, while maintaining reliability and validity.

  3. Incremental Validity of the Trait Emotional Intelligence Questionnaire-Short Form (TEIQue-SF).

    Science.gov (United States)

    Siegling, A B; Vesely, Ashley K; Petrides, K V; Saklofske, Donald H

    2015-01-01

    This study examined the incremental validity of the adult short form of the Trait Emotional Intelligence Questionnaire (TEIQue-SF) in predicting 7 construct-relevant criteria beyond the variance explained by the Five-factor model and coping strategies. Additionally, the relative contributions of the questionnaire's 4 subscales were assessed. Two samples of Canadian university students completed the TEIQue-SF, along with measures of the Big Five, coping strategies (Sample 1 only), and emotion-laden criteria. The TEIQue-SF showed consistent incremental effects beyond the Big Five or the Big Five and coping strategies, predicting all 7 criteria examined across the 2 samples. Furthermore, 2 of the 4 TEIQue-SF subscales accounted for the measure's incremental validity. Although the findings provide good support for the validity and utility of the TEIQue-SF, directions for further research are emphasized.

  4. Enhanced discrimination of benign from malignant prostatic disease by selective measurements of cleaved forms of urokinase receptor in serum

    DEFF Research Database (Denmark)

    Piironen, Timo; Haese, Alexander; Huland, Hartwig

    2006-01-01

    BACKGROUND: Early detection of prostate cancer (PCa) centers on measurements of prostate-specific antigen (PSA), but current testing practices suffer from lack of specificity and generate many unnecessary prostate biopsies. Soluble urokinase plasminogen activator receptor (uPAR) is present in blood...... in both intact and cleaved forms. Increased uPAR in blood is correlated with poor prognosis in various cancers, but uPAR has not been shown to be useful in PCa diagnostics. We assessed the ability of immunoassays for specific uPAR forms to discriminate PCa from benign conditions. METHODS: We measured...

  5. Measuring patient activation in the Netherlands: translation and validation of the American short form Patient Activation Measure (PAM13).

    NARCIS (Netherlands)

    Rademakers, J.; Nijman, J.; Hoek, L. van der; Heijmans, M.; Rijken, M.

    2012-01-01

    Background: The American short form Patient Activation Measure (PAM) is a 13-item instrument which assesses patient (or consumer) self-reported knowledge, skills and confidence for self-management of one's health or chronic condition. In this study the PAM was translated into a Dutch version;

  6. Habituation of the C-start response in larval zebrafish exhibits several distinct phases and sensitivity to NMDA receptor blockade.

    Directory of Open Access Journals (Sweden)

    Adam C Roberts

    Full Text Available The zebrafish larva has been a valuable model system for genetic and molecular studies of development. More recently, biologists have begun to exploit the surprisingly rich behavioral repertoire of zebrafish larvae to investigate behavior. One prominent behavior exhibited by zebrafish early in development is a rapid escape reflex (the C-start. This reflex is mediated by a relatively simple neural circuit, and is therefore an attractive model behavior for neurobiological investigations of simple forms of learning and memory. Here, we describe two forms of short-lived habituation of the C-start in response to brief pulses of auditory stimuli. A rapid form, persisting for ≥1 min but <15 min, was induced by 120 pulses delivered at 0.5-2.0 Hz. A more extended form (termed "short-term habituation" here, which persisted for ≥25 min but <1 h, was induced by spaced training. The spaced training consisted of 10 blocks of auditory pulses delivered at 1 Hz (5 min interblock interval, 900 pulses per block. We found that these two temporally distinguishable forms of habituation are mediated by different cellular mechanisms. The short-term form depends on activation of N-methyl-d-aspartate receptors (NMDARs, whereas the rapid form does not.

  7. Psychometric qualities of a tetrad WAIS-III short form for use in individuals with mild to borderline intellectual disability

    NARCIS (Netherlands)

    Duijvenbode, N. van; Didden, H.C.M.; Hazel, T. van den; Engels, R.C.M.E.

    2016-01-01

    Objective: To investigate the reliability and validity of a Wechsler Abbreviated Scale of Intelligence-based Wechsler Adult Intelligence Scale - third edition (WAIS-III) short form (SF) in a sample of individuals with mild to borderline intellectual disability (MBID) (N=117; M-IQ=71.34; SDIQ=8.00,

  8. Assessing the Validity of the Quality of Life Enjoyment and Satisfaction Questionnaire--Short Form in Adults with ADHD

    Science.gov (United States)

    Mick, Eric; Faraone, Stephen V.; Spencer, Thomas; Zhang, Huabin F.; Biederman, Joseph

    2008-01-01

    Objective: The authors assessed the psychometric properties of the Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-QSF) in adults with ADHD. Method: One hundred fifty ADHD and 134 non-ADHD adults from a case-control study and 173 adults randomized to placebo or methylphenidate were assessed with the Q-LES-QSF and the…

  9. Receptor tyrosine kinase-like orphan receptor 2 (ROR2) and Indian hedgehog regulate digit outgrowth mediated by the phalanx-forming region.

    Science.gov (United States)

    Witte, Florian; Chan, Danny; Economides, Aris N; Mundlos, Stefan; Stricker, Sigmar

    2010-08-10

    Elongation of the digit rays resulting in the formation of a defined number of phalanges is a process poorly understood in mammals, whereas in the chicken distal mesenchymal bone morphogenetic protein (BMP) signaling in the so-called phalanx-forming region (PFR) or digit crescent (DC) seems to be involved. The human brachydactylies (BDs) are inheritable conditions characterized by variable degrees of digit shortening, thus providing an ideal model to analyze the development and elongation of phalanges. We used a mouse model for BDB1 (Ror2(W749X/W749X)) lacking middle phalanges and show that a signaling center corresponding to the chick PFR exists in the mouse, which is diminished in BDB1 mice. This resulted in a strongly impaired elongation of the digit condensations due to reduced chondrogenic commitment of undifferentiated distal mesenchymal cells. We further show that a similar BMP-based mechanism accounts for digit shortening in a mouse model for the closely related condition BDA1 (Ihh(E95K/E95K)), altogether indicating the functional significance of the PFR in mammals. Genetic interaction experiments as well as pathway analysis in BDB1 mice suggest that Indian hedgehog and WNT/beta-catenin signaling, which we show is inhibited by receptor tyrosine kinase-like orphan receptor 2 (ROR2) in distal limb mesenchyme, are acting upstream of BMP signaling in the PFR.

  10. A short form of the Diabetes Quality of Life for Youth questionnaire

    DEFF Research Database (Denmark)

    Skinner, T. C.; Hoey, H.; McGee, H. M.

    2006-01-01

    Aims/hypothesis: The aim of this study was to test the construct validity of the Diabetes Quality of Life for Youth (DQOLY) questionnaire in a large representative sample of young people with type 1 diabetes mellitus. Methods: The 52-item DQOLY questionnaire was completed by 2,077 adolescent...... of a revised questionnaire, two with four factors and one with six factors, with all models indicating the presence of one satisfaction scale, but with many of the impact and worry scale items either double loading or not loading on any factors. Subsequent confirmatory analysis indicated that compared...... with the original DQOLY scales, the six-factor solution was the best-fitting model. Conclusions/interpretation: The DQOLY factor structure does not show construct validity in a large, diverse representative sample of young people with type 1 diabetes. However, a revised (short-form) version of the DQOLY is proposed...

  11. A juvenile form of postsynaptic hippocampal long-term potentiation in mice deficient for the AMPA receptor subunit GluR-A

    NARCIS (Netherlands)

    Jensen, V.; Kaiser, K.M.M.; Borchardt, T.; Adelmann, G.; Rozov, A.; Burnashev, N.; Brix, C.; Frotscher, M.; Anderson, P.; Hvalby, O.; Sakmann, B.; Seeburg, P.H.; Sprengel, R.

    2003-01-01

    In adult mice, long-term potentiation (LTP) of synaptic transmission at CA3-to-CA1 synapses induced by tetanic stimulation requires L-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors containing GluR-A subunits. Here, we report a GluR-A-independent form of LTP, which is comparable in

  12. [Myocardial perfusion scintigraphy - short form of the German guideline].

    Science.gov (United States)

    Lindner, O; Burchert, W; Hacker, M; Schaefer, W; Schmidt, M; Schober, O; Schwaiger, M; vom Dahl, J; Zimmermann, R; Schäfers, M

    2013-01-01

    This guideline is a short summary of the guideline for myocardial perfusion scintigraphy published by the Association of the Scientific Medical Societies in Ger-many (AWMF). The purpose of this guideline is to provide practical assistance for indication and examination procedures as well as image analysis and to present the state-of-the-art of myocardial-perfusion-scintigraphy. After a short introduction on the fundamentals of imaging, precise and detailed information is given on the indications, patient preparation, stress testing, radiopharmaceuticals, examination protocols and techniques, radiation exposure, data reconstruction as well as information on visual and quantitative image analysis and interpretation. In addition possible pitfalls, artefacts and key elements of reporting are described.

  13. Dopamine-induced apoptosis of lactotropes is mediated by the short isoform of D2 receptor.

    Directory of Open Access Journals (Sweden)

    Daniela Betiana Radl

    Full Text Available Dopamine, through D2 receptor (D2R, is the major regulator of lactotrope function in the anterior pituitary gland. Both D2R isoforms, long (D2L and short (D2S, are expressed in lactotropes. Although both isoforms can transduce dopamine signal, they differ in the mechanism that leads to cell response. The administration of D2R agonists, such as cabergoline, is the main pharmacological treatment for prolactinomas, but resistance to these drugs exists, which has been associated with alterations in D2R expression. We previously reported that dopamine and cabergoline induce apoptosis of lactotropes in primary culture in an estrogen-dependent manner. In this study we used an in vivo model to confirm the permissive action of estradiol in the apoptosis of anterior pituitary cells induced by D2R agonists. Administration of cabergoline to female rats induced apoptosis, measured by Annexin-V staining, in anterior pituitary gland from estradiol-treated rats but not from ovariectomized rats. To evaluate the participation of D2R isoforms in the apoptosis induced by dopamine we used lactotrope-derived PR1 cells stably transfected with expression vectors encoding D2L or D2S receptors. In the presence of estradiol, dopamine induced apoptosis, determined by ELISA and TUNEL assay, only in PR1-D2S cells. To study the role of p38 MAPK in apoptosis induced by D2R activation, anterior pituitary cells from primary culture or PR1-D2S were incubated with an inhibitor of the p38 MAPK pathway (SB203850. SB203580 blocked the apoptotic effect of D2R activation in lactotropes from primary cultures and PR1-D2S cells. Dopamine also induced p38 MAPK phosphorylation, determined by western blot, in PR1-D2S cells and estradiol enhanced this effect. These data suggest that, in the presence of estradiol, D2R agonists induce apoptosis of lactotropes by their interaction with D2S receptors and that p38 MAPK is involved in this process.

  14. Identification of G Protein-Coupled Receptors (GPCRs in Primary Cilia and Their Possible Involvement in Body Weight Control.

    Directory of Open Access Journals (Sweden)

    Yoshihiro Omori

    Full Text Available Primary cilia are sensory organelles that harbor various receptors such as G protein-coupled receptors (GPCRs. We analyzed subcellular localization of 138 non-odorant GPCRs. We transfected GPCR expression vectors into NIH3T3 cells, induced ciliogenesis by serum starvation, and observed subcellular localization of GPCRs by immunofluorescent staining. We found that several GPCRs whose ligands are involved in feeding behavior, including prolactin-releasing hormone receptor (PRLHR, neuropeptide FF receptor 1 (NPFFR1, and neuromedin U receptor 1 (NMUR1, localized to the primary cilia. In addition, we found that a short form of dopamine receptor D2 (DRD2S is efficiently transported to the primary cilia, while a long form of dopamine receptor D2 (DRD2L is rarely transported to the primary cilia. Using an anti-Prlhr antibody, we found that Prlhr localized to the cilia on the surface of the third ventricle in the vicinity of the hypothalamic periventricular nucleus. We generated the Npy2r-Cre transgenic mouse line in which Cre-recombinase is expressed under the control of the promoter of Npy2r encoding a ciliary GPCR. By mating Npy2r-Cre mice with Ift80 flox mice, we generated Ift80 conditional knockout (CKO mice in which Npy2r-positive cilia were diminished in number. We found that Ift80 CKO mice exhibited a body weight increase. Our results suggest that Npy2r-positive cilia are important for body weight control.

  15. Identification of G Protein-Coupled Receptors (GPCRs) in Primary Cilia and Their Possible Involvement in Body Weight Control.

    Science.gov (United States)

    Omori, Yoshihiro; Chaya, Taro; Yoshida, Satoyo; Irie, Shoichi; Tsujii, Toshinori; Furukawa, Takahisa

    2015-01-01

    Primary cilia are sensory organelles that harbor various receptors such as G protein-coupled receptors (GPCRs). We analyzed subcellular localization of 138 non-odorant GPCRs. We transfected GPCR expression vectors into NIH3T3 cells, induced ciliogenesis by serum starvation, and observed subcellular localization of GPCRs by immunofluorescent staining. We found that several GPCRs whose ligands are involved in feeding behavior, including prolactin-releasing hormone receptor (PRLHR), neuropeptide FF receptor 1 (NPFFR1), and neuromedin U receptor 1 (NMUR1), localized to the primary cilia. In addition, we found that a short form of dopamine receptor D2 (DRD2S) is efficiently transported to the primary cilia, while a long form of dopamine receptor D2 (DRD2L) is rarely transported to the primary cilia. Using an anti-Prlhr antibody, we found that Prlhr localized to the cilia on the surface of the third ventricle in the vicinity of the hypothalamic periventricular nucleus. We generated the Npy2r-Cre transgenic mouse line in which Cre-recombinase is expressed under the control of the promoter of Npy2r encoding a ciliary GPCR. By mating Npy2r-Cre mice with Ift80 flox mice, we generated Ift80 conditional knockout (CKO) mice in which Npy2r-positive cilia were diminished in number. We found that Ift80 CKO mice exhibited a body weight increase. Our results suggest that Npy2r-positive cilia are important for body weight control.

  16. Factors Influencing Short-term Synaptic Plasticity in the Avian Cochlear Nucleus Magnocellularis

    Directory of Open Access Journals (Sweden)

    Jason Tait Sanchez Quinones

    2015-01-01

    Full Text Available Defined as reduced neural responses during high rates of activity, synaptic depression is a form of short-term plasticity important for the temporal filtering of sound. In the avian cochlear nucleus magnocellularis (NM, an auditory brainstem structure, mechanisms regulating short-term synaptic depression include pre-, post-, and extrasynaptic factors. Using varied paired-pulse stimulus intervals, we found that the time course of synaptic depression lasts up to four seconds at late-developing NM synapses. Synaptic depression was largely reliant on exogenous Ca 2+ -dependent probability of presynaptic neurotransmitter release, and to a lesser extent, on the desensitization of postsynaptic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-type glutamate receptor (AMPA-R. Interestingly, although extrasynaptic glutamate clearance did not play a significant role in regulating synaptic depression, blocking glutamate clearance at early-developing synapses altered synaptic dynamics, changing responses from depression to facilitation. These results suggest a developmental shift in the relative reliance on pre-, post-, and extrasynaptic factors in regulating short-term synaptic plasticity in NM.

  17. Patient experience and satisfaction with inpatient service: development of short form survey instrument measuring the core aspect of inpatient experience.

    Directory of Open Access Journals (Sweden)

    Eliza L Y Wong

    Full Text Available Patient experience reflects quality of care from the patients' perspective; therefore, patients' experiences are important data in the evaluation of the quality of health services. The development of an abbreviated, reliable and valid instrument for measuring inpatients' experience would reflect the key aspect of inpatient care from patients' perspective as well as facilitate quality improvement by cultivating patient engagement and allow the trends in patient satisfaction and experience to be measured regularly. The study developed a short-form inpatient instrument and tested its ability to capture a core set of inpatients' experiences. The Hong Kong Inpatient Experience Questionnaire (HKIEQ was established in 2010; it is an adaptation of the General Inpatient Questionnaire of the Care Quality Commission created by the Picker Institute in United Kingdom. This study used a consensus conference and a cross-sectional validation survey to create and validate a short-form of the Hong Kong Inpatient Experience Questionnaire (SF-HKIEQ. The short-form, the SF-HKIEQ, consisted of 18 items derived from the HKIEQ. The 18 items mainly covered relational aspects of care under four dimensions of the patient's journey: hospital staff, patient care and treatment, information on leaving the hospital, and overall impression. The SF-HKIEQ had a high degree of face validity, construct validity and internal reliability. The validated SF-HKIEQ reflects the relevant core aspects of inpatients' experience in a hospital setting. It provides a quick reference tool for quality improvement purposes and a platform that allows both healthcare staff and patients to monitor the quality of hospital care over time.

  18. JAK1 kinase forms complexes with interleukin-4 receptor and 4PS/insulin receptor substrate-1-like protein and is activated by interleukin-4 and interleukin-9 in T lymphocytes.

    Science.gov (United States)

    Yin, T; Tsang, M L; Yang, Y C

    1994-10-28

    Interleukin (IL)-4 and IL-9 regulate the proliferation of T lymphocytes through interactions with their receptors. Previous studies have shown that unknown tyrosine kinases are involved in the proliferative signaling triggered by IL-4 and IL-9. Here we show that IL-4 and IL-9 induce overlapping (170, 130, and 125 kilodalton (kDa)) and distinct (45 and 88/90 kDa, respectively) protein tyrosine phosphorylation in T lymphocytes. We further identify the 170-kDa tyrosine-phosphorylated protein as 4PS/insulin receptor substrate-1-like (IRS-1L) protein and 130-kDa protein as JAK1 kinase. Furthermore, we demonstrate for the first time that JAK1 forms complexes with the IL-4 receptor and 4PS/IRS-1L protein following ligand-receptor interaction. In addition, we demonstrate that IL-9, but not IL-4, induced tyrosine phosphorylation of Stat 91 transcriptional factor. The overlapping and distinct protein tyrosine phosphorylation and activation of the same JAK1 kinase in T lymphocytes strongly suggests that IL-4 and IL-9 share the common signal transduction pathways and that the specificity for each cytokine could be achieved through the unique tyrosine-phosphorylated proteins triggered by individual cytokines.

  19. Stereocontrolled dopamine receptor binding and subtype selectivity of clebopride analogues synthesized from aspartic acid.

    Science.gov (United States)

    Einsiedel, Jürgen; Weber, Klaus; Thomas, Christoph; Lehmann, Thomas; Hübner, Harald; Gmeiner, Peter

    2003-10-06

    Employing the achiral 4-aminopiperidine derivative clebopride as a lead compound, chiral analogues were developed displaying dopamine receptor binding profiles that proved to be strongly dependent on the stereochemistry. Compared to the D1 receptor, the test compounds showed high selectivity for the D2-like subtypes including D2(long), D2(short), D3 and D4. The highest D4 and D3 affinities were observed for the cis-3-amino-4-methylpyrrolidines 3e and the enantiomer ent3e resulting in K(i) values of 0.23 and 1.8 nM, respectively. The benzamides of type 3 and 5 were synthesized in enantiopure form starting from (S)-aspartic acid and its unnatural optical antipode.

  20. Longitudinal evaluation of the mental health continuum-short form (MHC-SF): Measurement invariance across demographics, physical illness, and mental illness

    NARCIS (Netherlands)

    Lamers, S.M.A.; Glas, Cornelis A.W.; Westerhof, Gerben Johan; Bohlmeijer, Ernst Thomas

    2012-01-01

    This study evaluated the measurement invariance of the Mental Health Continuum-Short Form (MHC-SF), a 14-item self-report questionnaire for measuring emotional, social, and psychological well-being. The study draws on data of a representative panel (Longitudinal Internet Studies for the Social

  1. Melatonin modulation of presynaptic nicotinic acetylcholine receptors located on short noradrenergic neurons of the rat vas deferens: a pharmacological characterization

    Directory of Open Access Journals (Sweden)

    Zago W.M.

    1999-01-01

    Full Text Available Melatonin, the pineal hormone produced during the dark phase of the light-dark cycle, modulates neuronal acetylcholine receptors located presynaptically on nerve terminals of the rat vas deferens. Recently we showed the presence of high affinity nicotine-binding sites during the light phase, and low and high affinity binding sites during the dark phase. The appearance of the low affinity binding sites was due to the nocturnal melatonin surge and could be mimicked by exposure to melatonin in vitro. The aim of the present research was to identify the receptor subtypes responsible for the functional response during the light and the dark phase. The rank order of potency of agonists was dimethylphenylpiperazinium (DMPP = cytisine > nicotine > carbachol and DMPP = nicotine = cytisine > carbachol, during the light and dark phase, respectively, due to an increase in apparent affinity for nicotine. Mecamylamine similarly blocked the DMPP response during the light and the dark phase, while the response to nicotine was more efficiently blocked during the light phase. In contrast, methyllycaconitine inhibited the nicotine-induced response only at 21:00 h. Since a7 nicotinic acetylcholine receptors (nAChRs have low affinity for nicotine in binding assays, we suggest that a mixed population composed of a3ß4 - plus a7-bearing nAChR subtypes is present at night. This plasticity in receptor subtypes is probably driven by melatonin since nicotine-induced contraction in organs from animals sacrificed at 15:00 h and incubated with melatonin (100 pg/ml, 4 h is not totally blocked by mecamylamine. Thus melatonin, by acting directly on the short adrenergic neurons that innervate the rat vas deferens, induces the appearance of the low affinity binding site, probably an a7 nAChR subtype.

  2. GABA receptor imaging

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jong Doo [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2007-04-15

    GABA is primary an inhibitory neurotransmitter that is localized in inhibitory interneurons. GABA is released from presynaptic terminals and functions by binding to GABA receptors. There are two types of GABA receptors, GABA{sub A}-receptor that allows chloride to pass through a ligand gated ion channel and GABA{sub B}-receptor that uses G-proteins for signaling. The GABA{sub A}-receptor has a GABA binding site as well as a benzodiazepine binding sites, which modulate GABA{sub A}-receptor function. Benzodiazepine GABAA receptor imaging can be accomplished by radiolabeling derivates that activates benzodiazepine binding sites. There has been much research on flumazenil (FMZ) labeled with {sup 11}C-FMZ, a benzodiazepine derivate that is a selective, reversible antagonist to GABAA receptors. Recently, {sup 18}F-fluoroflumazenil (FFMZ) has been developed to overcome {sup 11}C's short half-life. {sup 18}F-FFMZ shows high selective affinity and good pharmacodynamics, and is a promising PET agent with better central benzodiazepine receptor imaging capabilities. In an epileptic focus, because the GABA/benzodiazepine receptor amount is decreased, using '1{sup 1}C-FMZ PET instead of {sup 18}F-FDG, PET, restrict the foci better and may also help find lesions better than high resolution MR. GABA{sub A} receptors are widely distributed in the cerebral cortex, and can be used as an viable neuronal marker. Therefore it can be used as a neuronal cell viability marker in cerebral ischemia. Also, GABA-receptors decrease in areas where neuronal plasticity develops, therefore, GABA imaging can be used to evaluate plasticity. Besides these usages, GABA receptors are related with psychological diseases, especially depression and schizophrenia as well as cerebral palsy, a motor-related disorder, so further in-depth studies are needed for these areas.

  3. GABA receptor imaging

    International Nuclear Information System (INIS)

    Lee, Jong Doo

    2007-01-01

    GABA is primary an inhibitory neurotransmitter that is localized in inhibitory interneurons. GABA is released from presynaptic terminals and functions by binding to GABA receptors. There are two types of GABA receptors, GABA A -receptor that allows chloride to pass through a ligand gated ion channel and GABA B -receptor that uses G-proteins for signaling. The GABA A -receptor has a GABA binding site as well as a benzodiazepine binding sites, which modulate GABA A -receptor function. Benzodiazepine GABAA receptor imaging can be accomplished by radiolabeling derivates that activates benzodiazepine binding sites. There has been much research on flumazenil (FMZ) labeled with 11 C-FMZ, a benzodiazepine derivate that is a selective, reversible antagonist to GABAA receptors. Recently, 18 F-fluoroflumazenil (FFMZ) has been developed to overcome 11 C's short half-life. 18 F-FFMZ shows high selective affinity and good pharmacodynamics, and is a promising PET agent with better central benzodiazepine receptor imaging capabilities. In an epileptic focus, because the GABA/benzodiazepine receptor amount is decreased, using '1 1 C-FMZ PET instead of 18 F-FDG, PET, restrict the foci better and may also help find lesions better than high resolution MR. GABA A receptors are widely distributed in the cerebral cortex, and can be used as an viable neuronal marker. Therefore it can be used as a neuronal cell viability marker in cerebral ischemia. Also, GABA-receptors decrease in areas where neuronal plasticity develops, therefore, GABA imaging can be used to evaluate plasticity. Besides these usages, GABA receptors are related with psychological diseases, especially depression and schizophrenia as well as cerebral palsy, a motor-related disorder, so further in-depth studies are needed for these areas

  4. The liberated domain I of urokinase plasminogen activator receptor--a new tumour marker in small cell lung cancer

    DEFF Research Database (Denmark)

    Almasi, Charlotte E; Drivsholm, Lars; Pappot, Helle

    2013-01-01

    The prognosis of small cell lung cancer (SCLC) remains poor with a 5-year survival rate of 4-6%. In non-small cell lung cancer (NSCLC), high levels of intact and cleaved forms of the receptor for urokinase plasminogen activator (uPAR) are significantly associated with short overall survival. Our...... measured using time-resolved fluorescence immunoassays (TR-FIA 1-3). Assessment of association of the uPAR forms to overall survival (OS) was done using Cox regression analysis adjusted for clinical covariates [age, gender, stage, lactate dehydrogenase (LDH), WHO performance status (PS)]. Multivariate...

  5. The red imported fire ant (Solenopsis invicta Buren kept Y not F: predicted sNPY endogenous ligands deorphanize the short NPF (sNPF receptor.

    Directory of Open Access Journals (Sweden)

    Prati Bajracharya

    Full Text Available Neuropeptides and their receptors play vital roles in controlling the physiology and behavior of animals. Short neuropeptide F (sNPF signaling regulates several physiological processes in insects such as feeding, locomotion, circadian rhythm and reproduction, among others. Previously, the red imported fire ant (Solenopsis invicta sNPF receptor (S. invicta sNPFR, a G protein-coupled receptor, was immunolocalized in queen and worker brain and queen ovaries. Differential distribution patterns of S. invicta sNPFR protein in fire ant worker brain were associated both with worker subcastes and with presence or absence of brood in the colony. However, the cognate ligand for this sNPFR has not been characterized and attempts to deorphanize the receptor with sNPF peptides from other insect species which ended in the canonical sequence LRLRFamide, failed. Receptor deorphanization is an important step to understand the neuropeptide receptor downstream signaling cascade. We cloned the full length cDNA of the putative S. invicta sNPF prepropeptide and identified the putative "sNPF" ligand within its sequence. The peptide ends with an amidated Tyr residue whereas in other insect species sNPFs have an amidated Phe or Trp residue at the C-terminus. We stably expressed the HA-tagged S. invicta sNPFR in CHO-K1 cells. Two S. invicta sNPFs differing at their N-terminus were synthesized that equally activated the sNPFR, SLRSALAAGHLRYa (EC50 = 3.2 nM and SALAAGHLRYa (EC50 = 8.6 nM. Both peptides decreased the intracellular cAMP concentration, indicating signaling through the Gαi-subunit. The receptor was not activated by sNPF peptides from other insect species, honey bee long NPF (NPY or mammalian PYY. Further, a synthesized peptide otherwise identical to the fire ant sequence but in which the C-terminal amidated amino acid residue 'Y' was switched to 'F', failed to activate the sNPFR. This discovery will now allow us to investigate the function of sNPY and

  6. Psychometric evaluation of the Chinese version of short-form Test of Functional Health Literacy in Adolescents.

    Science.gov (United States)

    Chang, Li-Chun; Hsieh, Pei-Lin; Liu, Chieh-Hsing

    2012-09-01

    The purpose of this study is to develop and evaluate the psychometric properties of the Chinese version of short-form Test of Functional Health Literacy in Adolescents. Assessing health literacy is vital to design health education programme; however, there are no measurement tools exist for use specifically in Chinese adolescents. A non-experimental design was used to test the psychometric properties of the Test of Functional Health Literacy in Adolescents. The short-form Test of Functional Health Literacy in Adolescents was translated and back translated into a Chinese language version. Thirty high school students were recruited to validate the scenario of Test of Functional Health Literacy in Adolescents. Based on the multiple-stage stratified random sampling method, 300 high school students from four counties in Taiwan were invited to participate in this study to evaluate the psychometric properties of Test of Functional Health Literacy in Adolescents. The Functional Health Literacy in Adolescents had good internal consistency reliability and excellent test-retest reliability. Confirmatory factor analysis resulted in a one-factor solution. Contrary to the original version of the Test of Functional Health Literacy in Adolescents, the findings revealed that the 36-item, one-factor model for the Test of Functional Health Literacy in Adolescents is the best-fit model. This is a suitable instrument to assess health literacy levels in Chinese adolescents before health education programmes can be appropriately planned, implemented and evaluated. © 2012 Blackwell Publishing Ltd.

  7. Short-acting glucagon-like peptide-1 receptor agonists as add-on to insulin therapy in type 1 diabetes

    DEFF Research Database (Denmark)

    Albèr, Anders; Brønden, Andreas; Knop, Filip K

    2017-01-01

    emptying in patients with type 1 diabetes, which could translate into effective lowering of postprandial glucose excursions; however, these observations regarding short-acting GLP-1RAs are all derived from small open-label trials and should thus be interpreted with caution. In the present paper we review......A large proportion of patients with type 1 diabetes do not reach their glycaemic target of glycated hemoglobin (HbA1c) type 1 diabetes are overweight and obese. Treatment of type 1 diabetes is based on insulin therapy......, which is associated with well-described and unfortunate adverse effects such as hypoglycaemia and increased body weight. Glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) are the focus of increasing interest as a possible adjunctive treatment to insulin in type 1 diabetes because...

  8. The breastfeeding self-efficacy scale: psychometric assessment of the short form.

    Science.gov (United States)

    Dennis, Cindy-Lee

    2003-01-01

    The purpose of this study was to reduce the number of items on the original Breastfeeding Self-Efficacy Scale (BSES) and psychometrically assess the revised BSES-Short Form (BSES-SF). As part of a longitudinal study, participants completed mailed questionnaires at 1, 4, and 8 weeks postpartum. Health region in British Columbia. A population-based sample of 491 breastfeeding mothers. BSES, Edinburgh Postnatal Depression Scale, Rosenberg Self-Esteem Scale, and Perceived Stress Scale. Internal consistency statistics with the original BSES suggested item redundancy. As such, 18 items were deleted, using explicit reduction criteria. Based on the encouraging reliability analysis of the new 14-item BSES-SF, construct validity was assessed using principal components factor analysis, comparison of contrasted groups, and correlations with measures of similar constructs. Support for predictive validity was demonstrated through significant mean differences between breastfeeding and bottle feeding mothers at 4 (p self-efficacy and considered ready for clinical use to (a) identify breastfeeding mothers at high risk, (b) assess breastfeeding behaviors and cognitions to individualize confidence-building strategies, and (c) evaluate the effectiveness of various interventions and guide program development.

  9. Labeled receptor ligands for spect

    International Nuclear Information System (INIS)

    Kung, H.F.

    1989-01-01

    Receptor specific imaging agents for single photon emission computed tomography (SPECT) can potentially be useful in the understanding of basic biochemistry and pharmacology of receptors. SPECT images may also provide tools for evaluation of density and binding kinetics of a specific receptor, information important for diagnosis and patient management. Basic requirements for receptor imaging agents are: (a) they are labeled with short-lived isotopes, (b) they show high selectivity and specific uptake, (c) they exhibit high target/background ratio, and (d) they can be modeled to obtain quantitative information. Several good examples of CNS receptor specific ligands labeled with I-123 have been developed, including iodoQNB, iodoestrogen iodobenzadiazepine, iodobenazepine, iodobenzamides for muscarinic, estrogen benzadiazepine, D-1 and D-2 dopamine receptors. With the advent of newer and faster SPECT imaging devices, it may be feasible to quantitate the receptor density by in vivo imaging techniques. These new brain imaging agents can provide unique diagnostic information, which may not be available through other imaging modalities, such as CT and MRI

  10. Adenosine receptor desensitization and trafficking.

    Science.gov (United States)

    Mundell, Stuart; Kelly, Eamonn

    2011-05-01

    As with the majority of G-protein-coupled receptors, all four of the adenosine receptor subtypes are known to undergo agonist-induced regulation in the form of desensitization and trafficking. These processes can limit the ability of adenosine receptors to couple to intracellular signalling pathways and thus reduce the ability of adenosine receptor agonists as well as endogenous adenosine to produce cellular responses. In addition, since adenosine receptors couple to multiple signalling pathways, these pathways may desensitize differentially, while the desensitization of one pathway could even trigger signalling via another. Thus, the overall picture of adenosine receptor regulation can be complex. For all adenosine receptor subtypes, there is evidence to implicate arrestins in agonist-induced desensitization and trafficking, but there is also evidence for other possible forms of regulation, including second messenger-dependent kinase regulation, heterologous effects involving G proteins, and the involvement of non-clathrin trafficking pathways such as caveolae. In this review, the evidence implicating these mechanisms is summarized for each adenosine receptor subtype, and we also discuss those issues of adenosine receptor regulation that remain to be resolved as well as likely directions for future research in this field. Copyright © 2010 Elsevier B.V. All rights reserved.

  11. An Examination of the Structure of the Career Decision Self-Efficacy Scale (Short Form) among Italian High School Students

    Science.gov (United States)

    Presti, Alessandro Lo; Pace, Francesco; Mondo, Marina; Nota, Laura; Casarubia, Provvidenza; Ferrari, Lea; Betz, Nancy E.

    2013-01-01

    This study aims to evaluate the factor structure of Career Decision Self-Efficacy scale-short form in a sample of Italian high school adolescents. confirmatory factor analysis (CFA) was used to test the degree to which a one-factor structure and a five-factor structure provided the best fit. In view of available research the five-factor structure…

  12. When less is more: Psychometric properties of Norwegian short-forms of the Ambivalent Sexism Scales (ASI and AMI) and the Illinois Rape Myth Acceptance (IRMA) Scale.

    Science.gov (United States)

    Bendixen, Mons; Kennair, Leif Edward Ottesen

    2017-12-01

    This paper reports on the development and the psychometric properties of short forms of Ambivalent Sexism Scales toward women (ASI; Glick & Fiske, 1996) and men (AMI; Glick & Fiske, 1999), and a scale measuring rape stereotypes (IRMA; McMahon & Farmer, 2011). The short form AMI/ASI were applied for examining gender and educational differences in university students (N = 512) and in high school students (N = 1381), and for predicting individual differences in rape stereotypes in the latter. The short forms demonstrated good to excellent psychometric properties across samples of emerging adults. Relative to female students, male students reported markedly more hostility toward women and more stereotypical beliefs about rape. Despite sampling from a highly gender egalitarian and secular culture, these gender differences are on a par with those reported internationally. Rape stereotypes were predicted by sexism in high school students. Additional predictors were educational program, relationship status, and acceptance of derogatory sexual slurs. The paper questions the validity of separate constructs for benevolent sexism toward women versus men. The short form versions of the scales may substitute the original versions in future research, and help prevent attrition while measuring the same constructs. © 2017 Scandinavian Psychological Associations and John Wiley & Sons Ltd.

  13. Steroid hormone receptors: long- and short-term integrators of the internal milieu and the external environment.

    Science.gov (United States)

    Blaustein, J D

    2012-07-01

    Many of the influences of estrogens and progestins on the brain and behavior are mediated by estrogen receptors and progestin receptors, acting as transcriptional regulators. The homologous and heterologous regulation of the concentrations of these receptors by cognate hormones is well established. However, although they were discovered and characterized based on their binding to cognate hormone and their role in transcriptional regulation, steroid hormone receptors have a more complex role and serve many more functions than originally suspected. First, besides being regulated by steroid hormones, the intracellular concentrations of brain steroid hormone receptors are regulated by neurotransmitters, a pathway by which stimuli from the environment, including from conspecific animals, can modulate the concentration of particular steroid hormone receptors in subsets of cells. Further, besides being activated by cognate steroid hormones, the receptors can be activated by a variety of neurotransmitters and phosphorylation pathways, providing a route through which environmental stimulation can activate steroid-receptor-dependent functions in specific cells. In addition, the transcription factor, estrogen receptor-α, produced from the estrogen receptor-α gene, can be modified to be targeted to membranes, where it can signal via kinase pathways. Finally, developmental experiences, such as particular stressors during the pubertal period, can permanently remodel the brain's response to ovarian hormones, most likely by long-term changes in regulation of the receptors mediating those responses. In addition to their function in responding to cognate ligand, it is now more appropriate to think of steroid hormone receptors as integrators of a wide variety of signaling pathways. © Georg Thieme Verlag KG Stuttgart · New York.

  14. Molecular characterization of a novel human hybrid-type receptor that binds the alpha2-macroglobulin receptor-associated protein

    DEFF Research Database (Denmark)

    Jacobsen, Linda; Madsen, P; Moestrup, S K

    1996-01-01

    the corresponding cDNA. The gene, designated SORL1, maps to chromosome 11q 23/24 and encodes a 2214-residue type 1 receptor containing a furin cleavage site immediately preceding the N terminus determined in the purified protein. The receptor, designated sorLA-1, has a short cytoplasmic tail containing a tyrosine...... density lipoprotein receptor gene family receptors, and 3) six tandemly arranged fibronectin type III repeats also found in certain neural adhesion proteins. sorLA-1 may therefore be classified as a hybrid receptor. Northern blotting revealed specific mRNA transcripts in brain, spinal cord, and testis......The 39-40-kDa receptor-associated protein (RAP) binds to the members of the low density lipoprotein receptor gene family and functions as a specialized endoplasmic reticulum/Golgi chaperone. Using RAP affinity chromatography, we have purified a novel approximately 250-kDa brain protein and isolated...

  15. Molecular modeling of ligand-receptor interactions in the OR5 olfactory receptor.

    Science.gov (United States)

    Singer, M S; Shepherd, G M

    1994-06-02

    Olfactory receptors belong to the superfamily of seven transmembrane domain, G protein-coupled receptors. In order to begin analysis of mechanisms of receptor activation, a computer model of the OR5 olfactory receptor has been constructed and compared with other members of this superfamily. We have tested docking of the odor molecule lyral, which is known to activate the OR5 receptor. The results point to specific ligand-binding residues on helices III through VII that form a binding pocket in the receptor. Some of these residues occupy sequence positions identical to ligand-binding residues conserved among other superfamily members. The results provide new insights into possible molecular mechanisms of odor recognition and suggest hypotheses to guide future experimental studies using site-directed mutagenesis.

  16. Neuronal low-density lipoprotein receptor-related protein 1 binds and endocytoses prion fibrils via receptor cluster 4

    DEFF Research Database (Denmark)

    Jen, Angela; Parkyn, Celia J; Mootoosamy, Roy C

    2010-01-01

    For infectious prion protein (designated PrP(Sc)) to act as a template to convert normal cellular protein (PrP(C)) to its distinctive pathogenic conformation, the two forms of prion protein (PrP) must interact closely. The neuronal receptor that rapidly endocytoses PrP(C) is the low......-density lipoprotein receptor-related protein 1 (LRP1). We show here that on sensory neurons LRP1 is also the receptor that binds and rapidly endocytoses smaller oligomeric forms of infectious prion fibrils, and recombinant PrP fibrils. Although LRP1 binds two molecules of most ligands independently to its receptor...... both prion and LRP1 biology....

  17. Clonidine treatment delays postnatal motor development and blocks short-term memory in young mice.

    Directory of Open Access Journals (Sweden)

    Cristina Calvino-Núñez

    Full Text Available During the development of the nervous system, the perinatal period is particularly sensitive as neuronal connections are still forming in the brain of the neonate. Alpha2-adrenergic receptors are overexpressed temporarily in proliferative zones in the developing brain, reaching a peak during the first postnatal week of life. Both stimulation and blocking of these receptors during this period alter the development of neural circuits, affecting synaptic connectivity and neuronal responses. They even affect motor and cognitive skills later on in the adult. It's especially important to look for the early neurological consequences resulting from such modifications, because they may go unnoticed. The main objective of the present study has been to reaffirm the importance of the maturation of alpha-adrenergic system in mice, by carrying out a comprehensive examination of motor, behavioral and cognitive effects in neonates, during early postnatal development, following chronic administration of the drug Clonidine, an alpha2 adrenergic system agonist. Our study shows that mice treated postnatally with clonidine present a temporal delay in the appearance of developmental markers, a slow execution of vestibular reflexes during first postnatal week of life and a blockade of the short term memory in the novel object recognition task. Shortly after the treatment the startle response is hyperreactive.

  18. Validation of the Tamil version of short form Geriatric Depression Scale-15.

    Science.gov (United States)

    Sarkar, Sonali; Kattimani, Shivananand; Roy, Gautam; Premarajan, K C; Sarkar, Siddharth

    2015-01-01

    Local language screening instruments can be helpful in early assessment of depression in the elderly in the community and primary care population. This study describes the validation of a Tamil version of Geriatric Depression Scale (short form 15 [GDS-15] item) in a rural population. A Tamil version of GDS-15 was developed using standardized procedures. The questionnaire was applied in a sample of elderly (aged 60 years and above) from a village in South India. All the participants were also assessed for depression by a clinical interview by a psychiatrist. A total of 242 participants were enrolled, 64.9% of them being females. The mean score on GDS-15 was 7.4 (±3.4), while the point prevalence of depression was 6.2% by clinical interview. The area under the receiver-operator curve was 0.659. The optimal cut-off for the GDS in this sample was found at 7/8 with sensitivity and specificity being 80% and 47.6%, respectively. The Tamil version of GDS-15 can be a useful screening instrument for assessment of depression in the elderly population.

  19. Examination of Measurement Invariance across Culture and Gender on the RCMAS-2 Short Form among Singapore and U.S. Adolescents

    Science.gov (United States)

    Lowe, Patricia A.; Ang, Rebecca P.

    2016-01-01

    Tests of measurement invariance were conducted across culture and gender on the Revised Children's Manifest Anxiety Scale-Second Edition (RCMAS-2) Short Form in a sample of 1,003 Singapore and U.S. adolescents. The results of multi-group confirmatory factor analyses across culture and gender supported at least partial measurement invariance. ANOVA…

  20. p55-hGRF, a short natural form of the Ras-GDP exchange factor high yield production and characterization.

    Science.gov (United States)

    Meyer, P; Janin, J; Baudet-Nessler, S

    1999-08-01

    p55-hGRF, a natural short form of the guanine-nucleotide-releasing factor for p21-Ras from human brain, was expressed at high level in Escherichia coli as well as an engineered truncated form, p39-hGRF. A T7 polymerase expression system was used, resulting in the formation of insoluble cytoplasmic protein aggregates. The recombinant products were resolubilized, renatured and purified to homogeneity. The exchange activity of the refolded hGRF samples on H-Ras was comparable with that published for the soluble catalytic domain of the mouse counterpart, CDC25 Mm. Both p55-hGRF and p39-hGRF form dimers. We established a procedure to prepare and purify the complex with Ras. The results of the characterization study are consistent with a stoichiometry of 1:1 and an equilibrium between dimeric and monomeric forms of the complex.

  1. The GABA[subscript A] Receptor Agonist Muscimol Induces an Age- and Region-Dependent Form of Long-Term Depression in the Mouse Striatum

    Science.gov (United States)

    Zhang, Xiaoqun; Yao, Ning; Chergui, Karima

    2016-01-01

    Several forms of long-term depression (LTD) of glutamatergic synaptic transmission have been identified in the dorsal striatum and in the nucleus accumbens (NAc). Such experience-dependent synaptic plasticity might play important roles in reward-related learning. The GABA[subscript A] receptor agonist muscimol was recently found to trigger a…

  2. Development of short-form and screening cutoff point of the Smartphone Addiction Inventory (SPAI-SF).

    Science.gov (United States)

    Lin, Yu-Hsuan; Pan, Yuan-Chien; Lin, Sheng-Hsuan; Chen, Sue-Huei

    2017-06-01

    Smartphone addiction is considered a form of technological addiction that has attracted increasing attention. The present study developed and validated the short-form Smartphone Addiction Inventory (SPAI-SF) and established cutoff point for screening smartphone addiction based on diagnostic criteria established by psychiatric interview. A total of 268 participants completed an online survey that collected demographic data, smartphone use behaviours, and responses to the 26-item SPAI. Each participant also completed a psychiatric interview. Confirmatory factor analysis (CFA) revealed that the 10-item SPAI-SF replicated the structure of original 26-item SPAI accurately, yielding a four-factor model consisting of compulsive behaviour, functional impairment, withdrawal, and tolerance. For maximal diagnostic accuracy, a cutoff point of 24/25 best discriminated cases of smartphone addiction from diagnostic negatives. The present findings suggest that both the 26-item SPAI and SPAI-SF manifest the four constructs of behavioural addiction and the characteristics of smartphone addiction. The cutoff point determined by psychiatrists' diagnostic interview will be useful for clinical screening and epidemiologic research. Copyright © 2016 John Wiley & Sons, Ltd.

  3. Adrenomedullin increased the short-circuit current in the pig oviduct through chloride channels via the CGRP receptor: mediation by cAMP and calcium ions but not by nitric oxide.

    Science.gov (United States)

    Liao, S B; Cheung, K H; Cheung, M P L; To, Y T; O, W S; Tang, F

    2013-10-01

    The oviduct serves as a site for the fertilization of the ovum and the transport of the conceptus down to the uterus for implantation. In this study, we investigated the presence of adrenomedullin (ADM) and its receptor component proteins in the pig oviduct. The effect of ADM on oviductal secretion, the specific receptor, and the mechanisms involved were also investigated. The presence of ADM and its receptor component proteins in the pig oviduct were confirmed using immunostaining. Short-circuit current (I(sc)) technique was employed to study chloride ion secretion in the oviductal epithelium. ADM increased I(sc) through cAMP- and calcium-activated chloride channels, and this effect could be inhibited by the CGRP receptor antagonist, hCGRP8-37. In contrast, the nitric oxide synthase inhibitor, L-NG-nitroarginine methyl ester (L-NAME), could not block the effect of ADM on I(sc). In summary, ADM may increase oviductal fluid secretion via chloride secretion independent of the nitric oxide pathway for the transport of sperm and the conceptus.

  4. Prolactin modulates luteal activity in the short-nosed fruit bat, Cynopterus sphinx during delayed embryonic development.

    Science.gov (United States)

    Anuradha; Krishna, Amitabh

    2017-07-01

    The aim of this study was to evaluate the role of prolactin as a modulator of luteal steroidogenesis during the period of delayed embryonic development in Cynopterus sphinx. A marked decline in circulating prolactin levels was noted during the months of November through December coinciding with the period of decreased serum progesterone and delayed embryonic development. The seasonal changes in serum prolactin levels correlated positively with circulating progesterone (P) level, but inversely with circulating melatonin level during first pregnancy showing delayed development in Cynopterus sphinx. The results also showed decreased expression of prolactin receptor-short form (PRL-RS) both in the corpus luteum and in the utero-embryonic unit during the period of delayed embryonic development. Bats treated in vivo with prolactin during the period of delayed development showed significant increase in serum progesterone and estradiol levels together with significant increase in the expression of PRL-RS, luteinizing hormone receptor (LH-R), steroidogenic acute receptor protein (STAR) and 3β-hydroxysteroid dehydrogenase (3β-HSD) in the ovary. Prolactin stimulated ovarian angiogenesis (vascular endothelial growth factor) and cell survival (B-cell lymphoma 2) in vivo. Significant increases in ovarian progesterone production and the expression of prolactin-receptor, LH-R, STAR and 3β-HSD proteins were noted following the exposure of LH or prolactin in vitro during the delayed period. In conclusion, short-day associated increased melatonin level may be responsible for decreased prolactin release during November-December. The decline in prolactin level might play a role in suppressing P and estradiol-17β (E2) estradiol levels thereby causing delayed embryonic development in C. sphinx. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Reliability testing of the Danish version of the Kidney Disease Quality of Life Short Form

    DEFF Research Database (Denmark)

    Molsted, Stig; Heaf, James; Prescott, Lotte

    2005-01-01

    . MATERIAL AND METHODS: Translation into Danish and back-translation into English were performed. Pilot, field and internal consistency reliability tests were performed. RESULTS: Cronbach's alpha coefficients for the internal reliability test ranged from 0.77 to 0.93 for the eight generic scales. In a test......OBJECTIVE: The questionnaire Kidney Disease Quality of Life Short Form version 1.3 (KDQOL-SF) is valuable for assessing the health-related quality of life in patients treated with chronic dialysis. The aim of this study was to translate and test the reliability of the KDQOL-SF for use in Denmark...... involving all patients, two of the disease-specific scales had Cronbach's alpha coefficients of test of the scores...

  6. Clinical validity of the Japanese version of WAIS-III short forms: Adaptation for patients with mild neurocognitive disorder and dementia.

    Science.gov (United States)

    Takeda, Mihoko; Nakaya, Makoto; Kikuchi, Yoko; Inoue, Sayaka; Kamata, Tomoyuki

    2018-01-01

    We investigated the Japanese WAIS-III short form utility in mild neurocognitive disorder and dementia. Our sample consisted of 108 old patients (ages: 65-89; mean age = 78.3). Fifteen short forms (SFs) and full-scale (FS) IQs were compared. The SFs included Dyads (SF1, SF2), Triads (SF3), Tetrads (SF4, SF5, SF6, SF7), Pentad (SF8), Six-subtest (SF9), Seven-subtests (SF10(a)(b), SF11(a)(b), SF12), and Nine-subtest (SF13). Correlations between SFIQs and FSIQ were all significant. Significant differences also were found in paired t-test between FSIQ and 5 SFIQs (SF2: t = -4.16, SF5: t = -7.06, SF7; t = 2.59, SF10(a): t = 2.56, SF12: t = -4.82; p Arithmetic, Digit Span, Information, Picture Completion, Digit Symbol-Coding, and Matrix Reasoning (Ryan & Ward, 1999), and the formula (Axelrod et al., 2001) should be adopted to convert scaled scores into estimated IQ scores. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. The interaction of hepatitis A virus (HAV with soluble forms of its cellular receptor 1 (HAVCR1 share the physiological requirements of infectivity in cell culture

    Directory of Open Access Journals (Sweden)

    Kaplan Gerardo G

    2009-10-01

    Full Text Available Abstract Background Hepatitis A virus (HAV, an atypical Picornaviridae that causes acute hepatitis in humans, usurps the HAV cellular receptor 1 (HAVCR1 to infect cells. HAVCR1 is a class 1 integral membrane glycoprotein that contains two extracellular domains: a virus-binding immunoglobulin-like (IgV domain and a mucin-like domain that extends the IgV from the cell membrane. Soluble forms of HAVCR1 bind, alter, and neutralize cell culture-adapted HAV, which is attenuated for humans. However, the requirements of the HAV-HAVCR1 interaction have not been fully characterized, and it has not been determined whether HAVCR1 also serves as a receptor for wild-type (wt HAV. Here, we used HAV soluble receptor neutralization and alteration assays to study the requirements of the HAV-HAVCR1 interaction and to determine whether HAVCR1 is also a receptor for wt HAV. Results Treatment of HAV with a soluble form of HAVCR1 that contained the IgV and two-thirds of the mucin domain fused to the Fc fragment of human IgG1 (D1 muc-Fc, altered particles at 37°C but left a residual level of unaltered particles at 4°C. The kinetics of neutralization of HAV by D1 muc-Fc was faster at 37°C than at 4°C. Alteration of HAV particles by D1 muc-Fc required Ca, which could not be replaced by Li, Na, Mg, Mn, or Zn. Neutralization of HAV by D1 muc-Fc occurred at pH 5 to 8 but was more efficient at pH 6 to 7. D1 muc-Fc neutralized wt HAV as determined by a cell culture system that allows the growth of wt HAV. Conclusion The interaction of HAV with soluble forms of HAVCR1 shares the temperature, Ca, and pH requirements for infectivity in cell culture and therefore mimics the cell entry process of HAV. Since soluble forms of HAVCR1 also neutralized wt HAV, this receptor may play a significant role in pathogenesis of HAV.

  8. Sintomas depressivos no câncer de mama: Inventário de Depressão de Beck - Short Form Depressive symptoms in breast cancer: Beck Depression Inventory - Short Form

    Directory of Open Access Journals (Sweden)

    Renata de Oliveira Cangussu

    2010-01-01

    Full Text Available OBJETIVOS: Verificar a prevalência de sintomas depressivos em mulheres com câncer de mama e identificar os fatores de risco associados à sua ocorrência. MÉTODOS: Foi realizado um estudo transversal, em que foram entrevistadas 71 mulheres com câncer de mama. Foram empregados dois instrumentos: um questionário para verificar os dados sociodemográficos e clínicos e o Inventário de Depressão de Beck - Short Form (BDI-SF, para avaliação dos sintomas depressivos. Para análise dos dados, utilizaram-se medidas descritivas e o teste de qui-quadrado, que avaliou a associação entre variáveis sociodemográficas e clínicas e os sintomas depressivos. O nível de significância considerado foi de 5%. RESULTADOS: A prevalência de sintomas depressivos foi de 29,6%. Os fatores associados à presença desses sintomas foram o tratamento quimioterápico (p = 0,021, presença de dor (p = 0,018 e limitação do movimento do membro superior (p = 0,010 e pior percepção da saúde (p = 0,018. CONCLUSÃO: Sintomas depressivos são frequentes no câncer de mama, assim a saúde mental das mulheres com esse tipo de câncer deve ser investigada e tratada quando necessário, reduzindo o impacto desses sintomas na vida da mulher.OBJECTIVES: To verify the prevalence of depressive symptoms in women with breast cancer and identify risk factors associated to its occurrence. METHODS: It was a transversal study where 71 women with breast cancer were interviewed. Two instruments were applied, being one questionnaire used to verify sociodemographic and clinical data, and the Beck Depression Inventory - Short Form to evaluate depressive symptoms. Descriptive methods and chi-square test were utilized to analyze data, evaluating association between depressive symptoms, sociodemographic and clinical data. Significance level was considered of 5%. RESULTS: Depressive symptoms prevalence was 29,6%. Factors associated to the presence of this kind of symptoms were

  9. Constitutive dimerization of the G-protein coupled receptor, neurotensin receptor 1, reconstituted into phospholipid bilayers.

    Science.gov (United States)

    Harding, Peter J; Attrill, Helen; Boehringer, Jonas; Ross, Simon; Wadhams, George H; Smith, Eleanor; Armitage, Judith P; Watts, Anthony

    2009-02-01

    Neurotensin receptor 1 (NTS1), a Family A G-protein coupled receptor (GPCR), was expressed in Escherichia coli as a fusion with the fluorescent proteins eCFP or eYFP. A fluorophore-tagged receptor was used to study the multimerization of NTS1 in detergent solution and in brain polar lipid bilayers, using fluorescence resonance energy transfer (FRET). A detergent-solubilized receptor was unable to form FRET-competent complexes at concentrations of up to 200 nM, suggesting that the receptor is monomeric in this environment. When reconstituted into a model membrane system at low receptor density, the observed FRET was independent of agonist binding, suggesting constitutive multimer formation. In competition studies, decreased FRET in the presence of untagged NTS1 excludes the possibility of fluorescent protein-induced interactions. A simulation of the experimental data indicates that NTS1 exists predominantly as a homodimer, rather than as higher-order multimers. These observations suggest that, in common with several other Family A GPCRs, NTS1 forms a constitutive dimer in lipid bilayers, stabilized through receptor-receptor interactions in the absence of other cellular signaling components. Therefore, this work demonstrates that well-characterized model membrane systems are useful tools for the study of GPCR multimerization, allowing fine control over system composition and complexity, provided that rigorous control experiments are performed.

  10. Reliability of short form-36 in an Internet- and a pen-and-paper version

    DEFF Research Database (Denmark)

    Basnov, Maja; Kongsved, Sissel Marie; Bech, Per

    2009-01-01

    Use of Internet versions of questionnaires may have several advantages in clinical and epidemiological research, but we know little about if Internet versions differ with respect to validity and reliability. We aimed to compare Internet- and pen-and-paper versions of short form-36 (SF-36......) with respect to test-retest reliability and internal consistency. Women referred to mammography (n = 782) were randomised to receive either a paper version with a prepaid return envelope or a guideline on how to fill in the Internet version. A subgroup was asked to answer the questionnaire once again...... in the alternative version. Test-retest reliability was assessed by the intra-class correlation coefficient. Internal consistency was calculated as Cronbach's alpha. The between-version test-retest reliability for the eight subscales were between 0.63 and 0.92. Cronbach's alpha for the two versions were all between...

  11. Leveraging social and digital media for participant recruitment: A review of methods from the Bayley Short Form Formative Study

    OpenAIRE

    Burke-Garcia, Amelia; Mathew, Sunitha

    2017-01-01

    Introduction Social media is increasingly being used in research, including recruitment. Methods For the Bayley Short Form Formative Study, which was conducted under the the National Children’s Study, traditional methods of recruitment proved to be ineffective. Therefore, digital media were identified as potential channels for recruitment. Results Results included successful recruitment of over 1800 infant and toddler participants to the Study. Conclusions This paper outlines the methods, res...

  12. Leveraging social and digital media for participant recruitment: A review of methods from the Bayley Short Form Formative Study.

    Science.gov (United States)

    Burke-Garcia, Amelia; Mathew, Sunitha

    2017-06-01

    Social media is increasingly being used in research, including recruitment. For the Bayley Short Form Formative Study, which was conducted under the the National Children's Study, traditional methods of recruitment proved to be ineffective. Therefore, digital media were identified as potential channels for recruitment. Results included successful recruitment of over 1800 infant and toddler participants to the Study. This paper outlines the methods, results, and future research opportunities.

  13. Measuring volitional competences: psychometric properties of a short form of the Volitional Components Questionnaire (VCQ) in a clinical sample

    OpenAIRE

    Forstmeier, Simon; Rüddel, H

    2008-01-01

    Volitional competences (skills of will), including self-regulation skills such as self-motivation and emotion regulation and self-control skills such as impulse control, are particularly necessary for patients with psychiatric and psychosomatic disorders. The Volitional Components Questionnaire (VCQ) is an instrument designed to measure volitional competences. However, its length of 190 items prevents its routine application in clinical settings. This study evaluates a new 36-item short form ...

  14. Multiplex bead-based immunoassay for the free soluble forms of the HLA-G receptors, ILT2 and ILT4

    DEFF Research Database (Denmark)

    Wu, Ching-Lien; Svendsen, Signe Goul; Riviere, Adrien

    2016-01-01

    in the plasma of healthy controls, but that elevated levels of plasmatic sILT2 were present in non-muscle-infiltrating bladder cancer patients. This demonstrated that the titration test is indeed working, and that soluble ILT2 molecules do exist in pathological contexts, which relevance may now be sought......Human leukocyte antigen (HLA)-G is an immune-inhibitory molecule that exerts its function via interaction with two main inhibitory receptors: ILT2 and ILT4. This interaction is considered to be an immune checkpoint. HLA-G can be found as a soluble molecule, but it is not known if its receptors can...... reveals that it specifically detects the free soluble forms of sILT2 and sILT4, and not those complexed to HLA Class I molecules such as their ligand of highest affinity HLA-G. A study on two small cohorts of cancer patients demonstrated that soluble ILT2 and ILT4 molecules were of low abundance...

  15. The Personality Inventory for DSM-5 Short Form (PID-5-SF): psychometric properties and association with big five traits and pathological beliefs in a Norwegian population.

    Science.gov (United States)

    Thimm, Jens C; Jordan, Stian; Bach, Bo

    2016-12-07

    With the publication of the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), an alternative model for personality disorders based on personality dysfunction and pathological personality traits was introduced. The Personality Inventory for DSM-5 (PID-5) is a 220-item self-report inventory designed to assess the personality traits of this model. Recently, a short 100-item version of the PID-5 (PID-5-SF) has been developed. The aim of this study was to investigate the score reliability and structure of the Norwegian PID-5-SF. Further, criterion validity with the five factor model of personality (FFM) and pathological personality beliefs was examined. A derivation sample of university students (N = 503) completed the PID-5, the Big Five Inventory (BFI), and the Personality Beliefs Questionnaire - Short Form (PBQ-SF), whereas a replication sample of 127 students completed the PID-5-SF along with the aforementioned measures. The short PID-5 showed overall good score reliability and structural validity. The associations with FFM traits and pathological personality beliefs were conceptually coherent and similar for the two forms of the PID-5. The results suggest that the Norwegian PID-5 short form is a reliable and efficient measure of the trait criterion of the alternative model for personality disorders in DSM-5.

  16. Chinese version of the Optimism and Pessimism Scale: Psychometric properties in mainland China and development of a short form.

    Science.gov (United States)

    Xia, Jie; Wu, Daxing; Zhang, Jibiao; Xu, Yuanchao; Xu, Yunxuan

    2016-06-01

    This study aimed to validate the Chinese version of the Optimism and Pessimism Scale in a sample of 730 adult Chinese individuals. Confirmatory factor analyses confirmed the bidimensionality of the scale with two factors, optimism and pessimism. The total scale and optimism and pessimism factors demonstrated satisfactory reliability and validity. Population-based normative data and mean values for gender, age, and education were determined. Furthermore, we developed a 20-item short form of the Chinese version of the Optimism and Pessimism Scale with structural validity comparable to the full form. In summary, the Chinese version of the Optimism and Pessimism Scale is an appropriate and practical tool for epidemiological research in mainland China. © The Author(s) 2014.

  17. Receptor-receptor interactions within receptor mosaics. Impact on neuropsychopharmacology.

    Science.gov (United States)

    Fuxe, K; Marcellino, D; Rivera, A; Diaz-Cabiale, Z; Filip, M; Gago, B; Roberts, D C S; Langel, U; Genedani, S; Ferraro, L; de la Calle, A; Narvaez, J; Tanganelli, S; Woods, A; Agnati, L F

    2008-08-01

    representing a compensatory up-regulation to counteract the cocaine-induced increases in dopamine D(2) and D(3) signaling. Therefore, A(2A) agonists, through antagonizing D(2) and D(3) signaling within A(2A)/D(2) and A(2A)/D(3) RM heteromers in the nucleus accumbens, may be found useful as a treatment for cocaine dependence. Furthermore, antagonistic cannabinoid CB(1)/D(2) interactions requiring A(2A) receptors have also been discovered and possibly operate in CB(1)/D(2)/A(2A) RM located principally on striatal glutamate terminals but also on some ventral striato-pallidal GABA neurons, thereby opening up a new mechanism for the integration of endocannabinoid, DA and adenosine mediated signals. Thus, A(2A), mGluR5 and/or CB(1) receptors can form integrative units with D(2) receptors within RM displaying different compositions, topography and localization. Also galaninR/5-HT(1A) RM probably participates in the transmission of the ascending 5-hydroxytryptamine neurons, where galanin receptors antagonize 5-HT(1A) recognition and signaling. Subtype specific galanin receptor antagonists may therefore represent novel antidepressant drugs. These results suggest the importance of a complete understanding of the function of these RM with regard to disease. Ultimately receptor-receptor interactions within RM that modify dopaminergic and serotonergic signaling may give new strategies for treatment of a wide range of diseases associated with altered dopaminergic and serotonergic signaling.

  18. Hyperfunction of muscarinic receptor maintains long-term memory in 5-HT4 receptor knock-out mice.

    Directory of Open Access Journals (Sweden)

    Luis Segu

    Full Text Available Patients suffering from dementia of Alzheimer's type express less serotonin 4 receptors (5-HTR(4, but whether an absence of these receptors modifies learning and memory is unexplored. In the spatial version of the Morris water maze, we show that 5-HTR(4 knock-out (KO and wild-type (WT mice performed similarly for spatial learning, short- and long-term retention. Since 5-HTR(4 control mnesic abilities, we tested whether cholinergic system had circumvented the absence of 5-HTR(4. Inactivating muscarinic receptor with scopolamine, at an ineffective dose (0.8 mg/kg to alter memory in WT mice, decreased long-term but not short-term memory of 5-HTR(4 KO mice. Other changes included decreases in the activity of choline acetyltransferase (ChAT, the required enzyme for acetylcholine synthesis, in the septum and the dorsal hippocampus in 5-HTR(4 KO under baseline conditions. Training- and scopolamine-induced increase and decrease, respectively in ChAT activity in the septum in WT mice were not detected in the 5-HTR(4 KO animals. Findings suggest that adaptive changes in cholinergic systems may circumvent the absence of 5-HTR(4 to maintain long-term memory under baseline conditions. In contrast, despite adaptive mechanisms, the absence of 5-HTR(4 aggravates scopolamine-induced memory impairments. The mechanisms whereby 5-HTR(4 mediate a tonic influence on ChAT activity and muscarinic receptors remain to be determined.

  19. Cinematic diamonds : narrative storytelling strategies in short fiction film

    OpenAIRE

    Cantell, Saara (kirjoittaja); Jeremiah, Fleur (kääntäjä)

    2012-01-01

    Saara Cantell proposes and discusses alternative ways of approaching short film. This book emphasizes short film as an independent and challenging cinematic art form of its own right. The "mystery" of short film is approached by examining the aesthetics of other short forms, The structural parallels between e.g. jokes and short films, as well as narrative strategies found in poetry, offer meaningful references. The research consists of both the analysis of selected short films and the five sh...

  20. IMMUNOASSAYS FOR THE DETECTION OF UROKINASE RECEPTOR FORMS

    DEFF Research Database (Denmark)

    2004-01-01

    amounts of uPAR forms in a sample with data indicative of the presence of the cancer disease. The method can be used for staging, prognosis or diagnosis of prostate cancer. Two novel monoclonal antibodies and a kit and immunoassays for detecting at least one uPAR form(s) are also described in the present...

  1. An assessment of factorial structure and health-related quality of life in problem drug users using the Short Form 36 Health Survey

    NARCIS (Netherlands)

    Buchholz, Angela; Krol, Anneke; Rist, Fred; Nieuwkerk, Pythia T.; Schippers, Gerard M.

    2008-01-01

    AIMS: To confirm the factorial structure of the Short Form 36 Health Survey (SF-36) in problem drug users and to compare their health-related quality of life (HRQOL) with general Dutch population norms. METHOD: Data of 394 participants from the Amsterdam Cohort Study among drug users, who had

  2. The Psychometric Properties and Factor Structure of a Welsh Translation of the School Short Form of the Coopersmith Self-Esteem Inventory

    Science.gov (United States)

    Hills, Peter R.; Francis, Leslie J.; Thomas, Enlli

    2007-01-01

    The psychometric properties and factor structure of a Welsh translation of the school short form of the Coopersmith Self-esteem Inventory (SEI-SSF), which is widely used as a measure of children's global self-esteem, was investigated among a sample of 681 pupils attending Welsh-medium primary schools in Wales. It has generally been assumed that…

  3. Prostaglandin Receptor Signaling in Disease

    Directory of Open Access Journals (Sweden)

    Toshiyuki Matsuoka

    2007-01-01

    Full Text Available Prostanoids, consisting of the prostaglandins (PGs and the thromboxanes (TXs, are a group of lipid mediators formed in response to various stimuli. They include PGD2, PGE2, PGF2α, PGI2, and TXA2. They are released outside of the cells immediately after synthesis, and exert their actions by binding to a G-protein coupled rhodopsin-type receptor on the surface of target cells. There are eight types of the prostanoid receptors conserved in mammals from mouse to human. They are the PGD receptor (DP, four subtypes of the PGE receptor (EP1, EP2, EP3, and EP4, the PGF receptor (FP, PGI receptor (IP, and TXA receptor (TP. Recently, mice deficient in each of these prostanoid receptors were generated and subjected to various experimental models of disease. These studies have revealed the roles of PG receptor signaling in various pathological conditions, and suggest that selective manipulation of the prostanoid receptors may be beneficial in treatment of the pathological conditions. Here we review these recent findings of roles of prostanoid receptor signaling and their therapeutic implications.

  4. Development and Validation of the Marijuana Motives Measure Short Form.

    Science.gov (United States)

    Mezquita, Laura; Ruiz-Valero, Lucía; Martínez-Gómez, Naiara; Ibáñez, Manuel I; Ortet, Generós

    2018-01-15

    Marijuana motives are a proximal variable to marijuana use. This research aimed to adapt and validate the short form of the Marijuana Motives Measure (MMM; Simons, Correia, Carey, y Borsari, 1998), the MMM SF, in Spanish.  The sample comprised 232 participants (mean age = 25.11 (7.58), 50.43% males) who had tried marijuana at least once in their lifetime. Item and Rasch analyses were performed to choose the final pool of 15 items. Confirmatory Factor Analysis (CFA) showed an adequate 5-factor structure (S-BX2(80) = 121.30, p = .002; NNFI = .944; CFI = .958; IFI = .959; MFI = .915; RMSEA = .047(0.029, 0.063); AIC = -38.70), and the multi-group CFA between males and females showed acceptable fit indices (S-BX2(160) = 230.01, p = .000; NNFI = .900; CFI = .924; IFI = .927; MFI = .860; RMSEA = .062(.043, .078); AIC = -89.99). The questionnaire indicated metric (S-BX2diff (15) = 13.61, p = .556)), scalar (S-BX2diff (15) = 23.15, p = .081)) and error measurement invariance (S-BX2diff (15) = 8.65, p = .895)) between gender groups. The internal consistencies and ordinal omega of the scales were between .79 and .90. In the regression analysis, enhancement, coping and low conformity motives predicted frequency and quantity of marijuana smoked. The best predictor of frequency and quantity consumed during the heaviest smoking period was enhancement, while coping and, to a lesser extent, low conformity, were the only predictors of cannabis-related problems when marijuana frequency and quantity were controlled for.  The MMM SF shows adequate psychometric properties and is a suitable instrument to assess marijuana motives, especially during time-limited sessions.

  5. Characterization of serotonergic receptors in rabbit, porcine and human conjunctivae.

    Science.gov (United States)

    Turner, Helen C; Alvarez, Lawrence J; Candia, Oscar A; Bernstein, Audrey M

    2003-10-01

    To characterize the serotonin (5-HT) receptors linked to the modulation of adenylyl cyclase activity in rabbit, porcine and human conjunctivae. Serotonin receptor-subtype expression was examined using reverse transcription-polymerase chain reaction (RT-PCR) and receptor subtype-specific polyclonal antibodies for the immunofluorescent labeling of conjunctival cryosections. In addition, measurements of the effects of serotonergics on the short-circuit current (I(sc)) across rabbit and porcine conjunctivae were contrasted. RT-PCR assays indicated the expression of 5-HT(1B ) and 5-HT(1D) receptors, subtypes negatively coupled to adenylyl cyclase, in the rabbit conjunctiva. This approach also suggested the co-expression of 5-HT(1B), 5-HT(1D), 5-HT(1F), 5-HT(4) and 5-HT(7) mRNA's in the porcine conjunctiva, and 5-HT( 1D), 5-HT(1F) and 5-HT(7) in the human conjunctiva. Since the 5-HT(4) and 5-HT(7) receptors are positively linked to adenylyl cyclase, these results implied that the porcine and human tissues exhibited subtypes both positively and negatively linked to the enzyme. However, immunohistochemical observations, using currently available antibodies solely localized the 5-HT(7) moiety in the porcine and human epithelia, suggested that the 1B/1D forms may be minor elements. Consistent with this prospect, 5-HT was a stimulant of the transepithelial I(sc) across the porcine conjunctiva, an opposite response from earlier findings that demonstrated inhibitory effects by 5-HT on the rabbit I(sc), which are now explained by the localization of the 1B/1D receptors in the rabbit stratified epithelium. The 5-HT receptors expressed by mammalian conjunctivae are not identical. In terms of 5-HT receptor expression, the porcine tissue may be a more appropriate model for human, than is the rabbit, in that 5-HT may serve as a secretagogue in the human epithelium.

  6. GABA/benzodiazepine receptor complex in long-sleep and short-sleep mice

    International Nuclear Information System (INIS)

    Marley, R.J.

    1987-01-01

    LS mice are more sensitive to benzodiazepine-induced anesthesia; however, the two lines do not differ in their hypothermic response to flurazepam. SS mice are more resistant to 3-mercaptopropionic acid-induced seizures and more sensitive to the anticonvulsant effects of benzodiazepines. The various correlates of GABA and benzodiazepine actions probably are the results of different mechanisms of action and/or differential regional control. Bicuculline competition for 3 H-GABA binding sites is greater in SS cerebellar tissue and 3 H-flunitrazepam binding is greater in the mid-brain region of LS mice. GABA enhancement of 3 H-flunitrazepma binding is greater in SS mice. Ethanol also enhances 3 H-flunitrazepam binding and increases the levels of 3 H-flunitrazepam binding above those observed for GABA. Using correlational techniques on data from LS and SS mice and several inbred mouse strains, it was demonstrated that a positive relationship exists between the degree of receptor coupling within the GABA receptor complex and the degree of resistance to seizures

  7. Serotonin receptor activity is necessary for olfactory learning and memory in Drosophila melanogaster.

    Science.gov (United States)

    Johnson, O; Becnel, J; Nichols, C D

    2011-09-29

    Learning and memory in the fruit fly, Drosophila melanogaster, is a complex behavior with many parallels to mammalian learning and memory. Although many neurotransmitters including acetylcholine, dopamine, glutamate, and GABA have previously been demonstrated to be involved in aversive olfactory learning and memory, the role of serotonin has not been well defined. Here, we present the first evidence of the involvement of individual serotonin receptors in olfactory learning and memory in the fly. We initially followed a pharmacological approach, utilizing serotonin receptor agonists and antagonists to demonstrate that all serotonin receptor families present in the fly are necessary for short-term learning and memory. Isobolographic analysis utilizing combinations of drugs revealed functional interactions are occurring between 5-HT(1A)-like and 5-HT(2), and 5-HT(2) and 5-HT(7) receptor circuits in mediating short-term learning and memory. Examination of long-term memory suggests that 5-HT(1A)-like receptors are necessary for consolidation and important for recall, 5-HT(2) receptors are important for consolidation and recall, and 5-HT(7) receptors are involved in all three phases. Importantly, we have validated our pharmacological results with genetic experiments and showed that hypomorph strains for 5-HT(2)Dro and 5-HT(1B)Dro receptors, as well as knockdown of 5-HT(7)Dro mRNA, significantly impair performance in short-term memory. Our data highlight the importance of the serotonin system and individual serotonin receptors to influence olfactory learning and memory in the fly, and position the fly as a model system to study the role of serotonin in cognitive processes relevant to mammalian CNS function. Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

  8. Interaction of human laminin receptor with Sup35, the [PSI⁺] prion-forming protein from S. cerevisiae: a yeast model for studies of LamR interactions with amyloidogenic proteins.

    Directory of Open Access Journals (Sweden)

    Christine Pampeno

    Full Text Available The laminin receptor (LamR is a cell surface receptor for extracellular matrix laminin, whereas the same protein within the cell interacts with ribosomes, nuclear proteins and cytoskeletal fibers. LamR has been shown to be a receptor for several bacteria and viruses. Furthermore, LamR interacts with both cellular and infectious forms of the prion protein, PrP(C and PrP(Sc. Indeed, LamR is a receptor for PrP(C. Whether LamR interacts with PrP(Sc exclusively in a capacity of the PrP receptor, or LamR specifically recognizes prion determinants of PrP(Sc, is unclear. In order to explore whether LamR has a propensity to interact with prions and amyloids, we examined LamR interaction with the yeast prion-forming protein, Sup35. Sup35 is a translation termination factor with no homology or functional relationship to PrP. Plasmids expressing LamR or LamR fused with the green fluorescent protein (GFP were transformed into yeast strain variants differing by the presence or absence of the prion conformation of Sup35, respectively [PSI⁺] and [psi⁻]. Analyses by immunoprecipitation, centrifugal fractionation and fluorescent microscopy reveal interaction between LamR and Sup35 in [PSI⁺] strains. The presence of [PSI⁺] promotes LamR co-precipitation with Sup35 as well as LamR aggregation. In [PSI⁺] cells, LamR tagged with GFP or mCherry forms bright fluorescent aggregates that co-localize with visible [PSI⁺] foci. The yeast prion model will facilitate studying the interaction of LamR with amyloidogenic prions in a safe and easily manipulated system that may lead to a better understanding and treatment of amyloid diseases.

  9. 5-HT4-receptors modulate induction of long-term depression but not potentiation at hippocampal output synapses in acute rat brain slices.

    Directory of Open Access Journals (Sweden)

    Matthias Wawra

    Full Text Available The subiculum is the principal target of CA1 pyramidal cells and mediates hippocampal output to various cortical and subcortical regions of the brain. The majority of subicular pyramidal cells are burst-spiking neurons. Previous studies indicated that high frequency stimulation in subicular burst-spiking cells causes presynaptic NMDA-receptor dependent long-term potentiation (LTP whereas low frequency stimulation induces postsynaptic NMDA-receptor-dependent long-term depression (LTD. In the present study, we investigate the effect of 5-hydroxytryptamine type 4 (5-HT4 receptor activation and blockade on both forms of synaptic plasticity in burst-spiking cells. We demonstrate that neither activation nor block of 5-HT4 receptors modulate the induction or expression of LTP. In contrast, activation of 5-HT4 receptors facilitates expression of LTD, and block of the 5-HT4 receptor prevents induction of short-term depression and LTD. As 5-HT4 receptors are positively coupled to adenylate cyclase 1 (AC1, 5-HT4 receptors might modulate PKA activity through AC1. Since LTD is blocked in the presence of 5-HT4 receptor antagonists, our data are consistent with 5-HT4 receptor activation by ambient serotonin or intrinsically active 5-HT4 receptors. Our findings provide new insight into aminergic modulation of hippocampal output.

  10. Development and psychometric characteristics of the SCI-QOL Ability to Participate and Satisfaction with Social Roles and Activities item banks and short forms.

    Science.gov (United States)

    Heinemann, Allen W; Kisala, Pamela A; Hahn, Elizabeth A; Tulsky, David S

    2015-05-01

    To develop a spinal cord injury (SCI)-focused version of PROMIS and Neuro-QOL social domain item banks; evaluate the psychometric properties of items developed for adults with SCI; and report information to facilitate clinical and research use. We used a mixed-methods design to develop and evaluate Ability to Participate in Social Roles and Activities and Satisfaction with Social Roles and Activities items. Focus groups helped define the constructs; cognitive interviews helped revise items; and confirmatory factor analysis and item response theory methods helped calibrate item banks and evaluate differential item functioning related to demographic and injury characteristics. Five SCI Model System sites and one Veterans Administration medical center. The calibration sample consisted of 641 individuals; a reliability sample consisted of 245 individuals residing in the community. A subset of 27 Ability to Participate and 35 Satisfaction items demonstrated good measurement properties and negligible differential item functioning related to demographic and injury characteristics. The SCI-specific measures correlate strongly with the PROMIS and Neuro-QOL versions. Ten item short forms correlate >0.96 with the full banks. Variable-length CATs with a minimum of 4 items, variable-length CATs with a minimum of 8 items, fixed-length CATs of 10 items, and the 10-item short forms demonstrate construct coverage and measurement error that is comparable to the full item bank. The Ability to Participate and Satisfaction with Social Roles and Activities CATs and short forms demonstrate excellent psychometric properties and are suitable for clinical and research applications.

  11. Cloning, characterisation, and comparative quantitative expression analyses of receptor for advanced glycation end products (RAGE) transcript forms.

    Science.gov (United States)

    Sterenczak, Katharina A; Willenbrock, Saskia; Barann, Matthias; Klemke, Markus; Soller, Jan T; Eberle, Nina; Nolte, Ingo; Bullerdiek, Jörn; Murua Escobar, Hugo

    2009-04-01

    RAGE is a member of the immunoglobulin superfamily of cell surface molecules playing key roles in pathophysiological processes, e.g. immune/inflammatory disorders, Alzheimer's disease, diabetic arteriosclerosis and tumourigenesis. In humans 19 naturally occurring RAGE splicing variants resulting in either N-terminally or C-terminally truncated proteins were identified and are lately discussed as mechanisms for receptor regulation. Accordingly, deregulation of sRAGE levels has been associated with several diseases e.g. Alzheimer's disease, Type 1 diabetes, and rheumatoid arthritis. Administration of recombinant sRAGE to animal models of cancer blocked tumour growth successfully. In spite of its obvious relationship to cancer and metastasis data focusing sRAGE deregulation and tumours is rare. In this study we screened a set of tumours, healthy tissues and various cancer cell lines for RAGE splicing variants and analysed their structure. Additionally, we analysed the ratio of the mainly found transcript variants using quantitative Real-Time PCR. In total we characterised 24 previously not described canine and 4 human RAGE splicing variants, analysed their structure, classified their characteristics, and derived their respective protein forms. Interestingly, the healthy and the neoplastic tissue samples showed in majority RAGE transcripts coding for the complete receptor and transcripts showing insertions of intron 1.

  12. Orphan receptor GPR179 forms macromolecular complexes with components of metabotropic signaling cascade in retina ON-bipolar neurons.

    Science.gov (United States)

    Orlandi, Cesare; Cao, Yan; Martemyanov, Kirill A

    2013-10-29

    In the mammalian retina, synaptic transmission between light-excited rod photoreceptors and downstream ON-bipolar neurons is indispensable for dim vision, and disruption of this process leads to congenital stationary night blindness in human patients. The ON-bipolar neurons use the metabotropic signaling cascade, initiated by the mGluR6 receptor, to generate depolarizing responses to light-induced changes in neurotransmitter glutamate release from the photoreceptor axonal terminals. Evidence for the identity of the components involved in transducing these signals is growing rapidly. Recently, the orphan receptor, GPR179, a member of the G protein-coupled receptor (GPCR) superfamily, has been shown to be indispensable for the synaptic responses of ON-bipolar cells. In our study, we investigated the interaction of GPR179 with principle components of the signal transduction cascade. We used immunoprecipitation and proximity ligation assays in transfected cells and native retinas to characterize the protein-protein interactions involving GPR179. The influence of cascade components on GPR179 localization was examined through immunohistochemical staining of the retinas from genetic mouse models. We demonstrated that, in mouse retinas, GPR179 forms physical complexes with the main components of the metabotropic cascade, recruiting mGluR6, TRPM1, and the RGS proteins. Elimination of mGluR6 or RGS proteins, but not TRPM1, detrimentally affects postsynaptic targeting or GPR179 expression. These observations suggest that the mGluR6 signaling cascade is scaffolded as a macromolecular complex in which the interactions between the components ensure the optimal spatiotemporal characteristics of signal transduction.

  13. Exon 3-deleted/full-length growth hormone receptor polymorphism genotype frequencies in Spanish short small-for-gestational-age (SGA) children and adolescents (n = 247) and in an adult control population (n = 289) show increased fl/fl in short SGA.

    Science.gov (United States)

    Audí, Laura; Esteban, Cristina; Carrascosa, Antonio; Espadero, Rosa; Pérez-Arroyo, Annalisa; Arjona, Rosa; Clemente, María; Wollmann, Hartmut; Fryklund, Linda; Parodi, Luis A

    2006-12-01

    A polymorphism in the human GH receptor gene (d3/fl-GHR) resulting in genomic deletion of exon 3 has been associated with the degree of height increase in response to GH therapy. The objective of the study was to evaluate the frequencies of d3/fl-GHR polymorphism genotypes in control and short small-for-gestational-age (SGA) populations. An adult control population with heights normally distributed (ACPNH) between -2 and +2 sd score (SDS) and a short non-GH-deficient SGA child population were selected. Thirty Spanish hospitals participated in the selection of the short non-GH-deficient SGA children in the setting of a controlled, randomized trial, and one of these hospitals selected the ACPNH. CONTROLS AND PATIENTS: Two hundred eighty-nine adult subjects of both sexes constituted the ACPNH and 247 children and adolescents of both sexes the short SGA patients. Heights and weights were recorded in the ACPNH, and auxologic and biochemical data were recorded at each hospital for the SGA patients; d3/fl-GHR genotypes were determined and data analyzed in a single hospital. In short SGA patients, d3/fl-GHR genotype frequencies were significantly different from those in ACPNH, with a higher frequency of fl/fl genotype (P or=-2 SDS, n = 60). Our data showed significant differences in the frequency distribution of the d3/fl-GHR genotypes between a normally distributed adult height population and short SGA children, with the biologically less active fl/fl genotype being almost twice as frequent in SGA patients. These data suggest that the d3/fl-GHR polymorphism might be considered among the factors that contribute to the phenotypic expression of growth.

  14. "Short Courses Shouldn't Be Short-Lived!" Enhancing Longer-Term Impact of Short English as a Foreign Language INSET Initiatives in China

    Science.gov (United States)

    Yan, Chunmei; He, Chuanjun

    2015-01-01

    Short in-service teacher development (INSET) programmes have been globally used as a form of teacher development, but their impact has been under question. This study sought to examine teacher participants' perceptions of short INSET programmes to come up with better solutions to enhancing their effect on teachers' professional learning. A…

  15. Molecular alteration of a muscarinic acetylcholine receptor system during synaptogenesis

    International Nuclear Information System (INIS)

    Large, T.H.; Cho, N.J.; De Mello, F.G.; Klein, W.L.

    1985-01-01

    Biochemical properties of the muscarinic acetylcholine receptor system of the avian retina were found to change during the period when synapses form in ovo. Comparison of ligand binding to membranes obtained before and after synaptogenesis showed a significant increase in the affinity, but not proportion, of the high affinity agonist-binding state. There was no change in receptor sensitivity to antagonists during this period. Pirenzepine binding, which can discriminate muscarinic receptor subtypes, showed the presence of a single population of low affinity sites (M2) before and after synaptogenesis. The change in agonist binding was not due to the late development of receptor function. However, detergent-solubilization of membranes eliminated differences in agonist binding between receptors from embryos and hatched chicks, suggesting a developmental change in interactions of the receptor with functionally related membrane components. A possible basis for altered interactions was obtained from isoelectric point data showing that the muscarinic receptor population underwent a transition from a predominantly low pI form (4.25) in 13 day embryos to a predominantly high pI form (4.50) in newly hatched chicks. The possibility that biochemical changes in the muscarinic receptor play a role in differentiation of the system by controlling receptor position on the surface of nerve cells is discussed

  16. Assessment of Psychopathological Problems in the School Context: The Psychometric Properties of a Portuguese Version of the Adolescent Psychopathology Scale--Short Form

    Science.gov (United States)

    Lemos, Ida Timoteo; Faisca, Luis Madeira; Valadas, Sandra Teodosio

    2011-01-01

    The psychometric properties of a Portuguese version of the Adolescent Psychopathology Scale-Short Form (APS-SF) were studied in a sample of 656 Portuguese adolescents, aged 12 to 19 years, assessed in school context. Also, the aim of the study was to gather data concerning age- and gender-related differences in the expression of psychopathological…

  17. Personality Inventory for DSM-5-Short Form (PID-5-SF): Reliability, Factorial Structure, and Relationship With Functional Impairment in Dual Diagnosis Patients.

    Science.gov (United States)

    Díaz-Batanero, Carmen; Ramírez-López, Juan; Domínguez-Salas, Sara; Fernández-Calderón, Fermín; Lozano, Óscar M

    2017-11-01

    Section III of the Diagnostic and Statistical Manual of Mental Disorders-Fifth edition ( DSM-5) has generated a personality paradigm consisting of 25 personality facets identified in five domains. The developed assessment instrument Personality Inventory for DSM-5 (PID-5) has showed good psychometric properties, but the potential for certain improvements still remain. In this article, a sample of 282 dual diagnosis patients is used to provide evidence of the psychometric properties of the PID-5-Short Form. The mean value of Cronbach's alpha coefficients reached .73 on the facets and .84 for domains and test-retest values ranged between .57 to .83 for facets and .70 to .87 for the domains. Confirmatory factor analyses conducted showed good fit on both models tested: the five correlated factor structure and hierarchical structure of personality traits. The WHODAS 2.0 domains of understanding and communicating, and participating in society, appear to show the strongest relationship with personality facets. In general, the PID-5-Short Form shows adequate psychometric properties for use in dual diagnosis patients.

  18. Measuring psychological trauma after spinal cord injury: Development and psychometric characteristics of the SCI-QOL Psychological Trauma item bank and short form.

    Science.gov (United States)

    Kisala, Pamela A; Victorson, David; Pace, Natalie; Heinemann, Allen W; Choi, Seung W; Tulsky, David S

    2015-05-01

    To describe the development and psychometric properties of the SCI-QOL Psychological Trauma item bank and short form. Using a mixed-methods design, we developed and tested a Psychological Trauma item bank with patient and provider focus groups, cognitive interviews, and item response theory based analytic approaches, including tests of model fit, differential item functioning (DIF) and precision. We tested a 31-item pool at several medical institutions across the United States, including the University of Michigan, Kessler Foundation, Rehabilitation Institute of Chicago, the University of Washington, Craig Hospital and the James J. Peters/Bronx Veterans Administration hospital. A total of 716 individuals with SCI completed the trauma items The 31 items fit a unidimensional model (CFI=0.952; RMSEA=0.061) and demonstrated good precision (theta range between 0.6 and 2.5). Nine items demonstrated negligible DIF with little impact on score estimates. The final calibrated item bank contains 19 items The SCI-QOL Psychological Trauma item bank is a psychometrically robust measurement tool from which a short form and a computer adaptive test (CAT) version are available.

  19. Born dry in the photoevaporation desert: Kepler's ultra-short-period planets formed water-poor

    Science.gov (United States)

    Lopez, Eric D.

    2017-11-01

    Recent surveys have uncovered an exciting new population of ultra-short-period (USP) planets with orbital periods less than a day. These planets typically have radii ≲1.5 R⊕, indicating that they likely have rocky compositions. This stands in contrast to the overall distribution of planets out to ∼100 d, which is dominated by low-density sub-Neptunes above 2 R⊕, which must have gaseous envelopes to explain their size. However, on the USP orbits, planets are bombarded by intense levels of photoionizing radiation and consequently gaseous sub-Neptunes are extremely vulnerable to losing their envelopes to atmospheric photoevaporation. Using models of planet evolution, I show that the rocky USP planets can easily be produced as the evaporated remnants of sub-Neptunes with H/He envelopes and that we can therefore understand the observed dearth of USP sub-Neptunes as a natural consequence of photoevaporation. Critically however, planets on USP orbits could often retain their envelopes if they are formed with very high-metallicity water-dominated envelopes. Such water-rich planets would commonly be ≳2 R⊕ today, which is inconsistent with the observed evaporation desert, indicating that most USP planets likely formed from water-poor material within the snow-line. Finally, I examine the special case of 55 Cancri e and its possible composition in the light of recent observations, and discuss the prospects for further characterizing this population with future observations.

  20. Chemical bridges for enhancing hydrogen storage by spillover and methods for forming the same

    Science.gov (United States)

    Yang, Ralph T.; Li, Yingwei; Qi, Gongshin; Lachawiec, Jr., Anthony J.

    2012-12-25

    A composition for hydrogen storage includes a source of hydrogen atoms, a receptor, and a chemical bridge formed between the source and the receptor. The chemical bridge is formed from a precursor material. The receptor is adapted to receive hydrogen spillover from the source.

  1. Validation of a 16-Item Short Form of the Czech Version of the Experiences in Close Relationships Revised Questionnaire in a Representative Sample

    Czech Academy of Sciences Publication Activity Database

    Kaščáková, N.; Husárová, D.; Hašto, J.; Kolarčik, P.; Poláčková Šolcová, Iva; Madarasová Gecková, A.; Tavel, P.

    2016-01-01

    Roč. 119, č. 3 (2016), s. 804-825 ISSN 0033-2941 Institutional support: RVO:68081740 Keywords : Short form of the ECR-R * Experiences in Close Relationships Revised Questionnaire * validation * attachment anxiety * attachment avoidance * attachment styles * representative sample Subject RIV: AN - Psychology Impact factor: 0.629, year: 2016

  2. Asp330 and Tyr331 in the C-terminal cysteine-rich region of the luteinizing hormone receptor are key residues in hormone-induced receptor activation

    NARCIS (Netherlands)

    M.W.P. Bruysters (Martijn); M. Verhoef-Post (Miriam); A.P.N. Themmen (Axel)

    2008-01-01

    textabstractThe luteinizing hormone (LH) receptor plays an essential role in male and female gonadal function. Together with the follicle-stimulating hormone (FSH) and thyroid stimulating hormone (TSH) receptors, the LH receptor forms the family of glycoprotein hormone receptors. All glycoprotein

  3. Short- and long-term memory: differential involvement of neurotransmitter systems and signal transduction cascades

    Directory of Open Access Journals (Sweden)

    MÔNICA R.M. VIANNA

    2000-09-01

    Full Text Available Since William James (1890 first distinguished primary from secondary memory, equivalent to short- and long-term memory, respectively, it has been assumed that short-term memory processes are in charge of cognition while long-term memory is being consolidated. From those days a major question has been whether short-term memory is merely a initial phase of long-term memory, or a separate phenomena. Recent experiments have shown that many treatments with specific molecular actions given into the hippocampus and related brain areas after one-trial avoidance learning can effectively cancel short-term memory without affecting long-term memory formation. This shows that short-term memory and long-term memory involve separate mechanisms and are independently processed. Other treatments, however, influence both memory types similarly, suggesting links between both at the receptor and at the post-receptor level, which should not be surprising as they both deal with nearly the same sensorimotor representations. This review examines recent advances in short- and long-term memory mechanisms based on the effect of intra-hippocampal infusion of drugs acting upon neurotransmitter and signal transduction systems on both memory types.

  4. Rapid effects of estrogens on short-term memory: Possible mechanisms.

    Science.gov (United States)

    Paletta, Pietro; Sheppard, Paul A S; Matta, Richard; Ervin, Kelsy S J; Choleris, Elena

    2018-06-01

    Estrogens affect learning and memory through rapid and delayed mechanisms. Here we review studies on rapid effects on short-term memory. Estradiol rapidly improves social and object recognition memory, spatial memory, and social learning when administered systemically. The dorsal hippocampus mediates estrogen rapid facilitation of object, social and spatial short-term memory. The medial amygdala mediates rapid facilitation of social recognition. The three estrogen receptors, α (ERα), β (ERβ) and the G-protein coupled estrogen receptor (GPER) appear to play different roles depending on the task and brain region. Both ERα and GPER agonists rapidly facilitate short-term social and object recognition and spatial memory when administered systemically or into the dorsal hippocampus and facilitate social recognition in the medial amygdala. Conversely, only GPER can facilitate social learning after systemic treatment and an ERβ agonist only rapidly improved short-term spatial memory when given systemically or into the hippocampus, but also facilitates social recognition in the medial amygdala. Investigations into the mechanisms behind estrogens' rapid effects on short term memory showed an involvement of the extracellular signal-regulated kinase (ERK) and the phosphoinositide 3-kinase (PI3K) kinase pathways. Recent evidence also showed that estrogens interact with the neuropeptide oxytocin in rapidly facilitating social recognition. Estrogens can increase the production and/or release of oxytocin and other neurotransmitters, such as dopamine and acetylcholine. Therefore, it is possible that estrogens' rapid effects on short-term memory may occur through the regulation of various neurotransmitters, although more research is need on these interactions as well as the mechanisms of estrogens' actions on short-term memory. Copyright © 2018 Elsevier Inc. All rights reserved.

  5. An unusual protein kinase phosphorylates the chemotactic receptor of Dictystelium discoideum

    International Nuclear Information System (INIS)

    Meier, K.; Klein, C.

    1988-01-01

    The authors report the cAMP-dependent phosphorylation of the chemotactic receptor of Dictyostelium discoideum in partially purified plasma membranes. The protein kinase responsible for receptor phosphorylation is associated with this fraction and preferentially phosphorylates the ligand-occupied form of the receptor. 8-Azido[ 32 P]cAMP labeling of the cell surface has shown that the cAMP receptor exists in two forms. A 45-kDa protein is predominant on unstimulated cells. cAMP stimulation results in an increased receptor phosphorylation such that the receptor migrates on NaDodSO 4 /PAGE as a 47-kDa protein. Phosphorylation of the chemotactic receptor is not detected in membrane preparations unless cAMP is added to the incubation mixture. Only under those conditions is the phosphorylated 47-kDa form observed. The requirement for cAMP reflects the fact that the kinase involved preferentially uses the ligand-occupied receptor as a substrate. In vitro phosphorylation of the receptor does not involve tyrosine residues. The enzyme does not appear to be a cAMP- or cGMP-dependent protein kinase nor is it sensitive to guanine nucleotides, Ca 2+ /calmodulin, Ca 2+ /phospholipid, or EGTA. Similarities with the β-adrenergic receptor protein kinase are discussed

  6. Antiproliferation effects of an androgen receptor triple-helix forming oligonucleotide on prostate cancer cells

    International Nuclear Information System (INIS)

    Zhang Yong; Chen Weizhen; Xie Yao; Gao Jinhui

    2005-01-01

    Objective: To provide experimental basis for antigene radiation therapy through exploring the effects of antigene strategy on androgen receptor (AR) expression and proliferation of prostate cancer cells. Methods: The triple-helix forming oligonucleotide (TFO) targeting 2447-2461nt of AR cDNA was designed and transfected LNCaP prostate cancer cells with liposome. 24-72 h after transfection, the cellular proliferation was detected by 3 H-thymidine (TdR) incorporation test, the expression of AR gene was examined by reverse transcription-polymerase chain reaction (RT-PCR) and expression of AR protein was performed by radioligand binding assay. The results of TFO were compared with antisense oligonucleotide (ASON). Results: At all time points, the AR expression levels in TFO group were markedly lower than that of ASON group (P<0.05). The inhibitory rate of TFO for cellular proliferation was significantly higher than that of ASON (P<0.05). Conclusion: The TFO was a potent inhibitor for AR expression and cell proliferation of LNCaP cells , and could be used in antigene radiotherapy. (authors)

  7. Test-Retest Reliability of the Short-Form Survivor Unmet Needs Survey.

    Science.gov (United States)

    Taylor, Karen; Bulsara, Max; Monterosso, Leanne

    2018-01-01

    Reliable and valid needs assessment measures are important assessment tools in cancer survivorship care. A new 30-item short-form version of the Survivor Unmet Needs Survey (SF-SUNS) was developed and validated with cancer survivors, including hematology cancer survivors; however, test-retest reliability has not been established. The objective of this study was to assess the test-retest reliability of the SF-SUNS with a cohort of lymphoma survivors ( n = 40). Test-retest reliability of the SF-SUNS was conducted at two time points: baseline (time 1) and 5 days later (time 2). Test-retest data were collected from lymphoma cancer survivors ( n = 40) in a large tertiary cancer center in Western Australia. Intraclass correlation analyses compared data at time 1 (baseline) and time 2 (5 days later). Cronbach's alpha analyses were performed to assess the internal consistency at both time points. The majority (23/30, 77%) of items achieved test-retest reliability scores 0.45-0.74 (fair to good). A high degree of overall internal consistency was demonstrated (time 1 = 0.92, time 2 = 0.95), with scores 0.65-0.94 across subscales for both time points. Mixed test-retest reliability of the SF-SUNS was established. Our results indicate the SF-SUNS is responsive to the changing needs of lymphoma cancer survivors. Routine use of cancer survivorship specific needs-based assessments is required in oncology care today. Nurses are well placed to administer these assessments and provide tailored information and resources. Further assessment of test-retest reliability in hematology and other cancer cohorts is warranted.

  8. Low level postnatal methylmercury exposure in vivo alters developmental forms of short-term synaptic plasticity in the visual cortex of rat

    International Nuclear Information System (INIS)

    Dasari, Sameera; Yuan, Yukun

    2009-01-01

    Methylmercury (MeHg) has been previously shown to affect neurotransmitter release. Short-term synaptic plasticity (STP) is primarily related to changes in the probability of neurotransmitter release. To determine if MeHg affects STP development, we examined STP forms in the visual cortex of rat following in vivo MeHg exposure. Neonatal rats received 0 (0.9% NaCl), 0.75 or 1.5 mg/kg/day MeHg subcutaneously for 15 or 30 days beginning on postnatal day 5, after which visual cortical slices were prepared for field potential recordings. In slices prepared from rats treated with vehicle, field excitatory postsynaptic potentials (fEPSPs) evoked by paired-pulse stimulation at 20-200 ms inter-stimulus intervals showed a depression (PPD) of the second fEPSP (fEPSP2). PPD was also seen in slices prepared from rats after 15 day treatment with 0.75 or 1.5 mg/kg/day MeHg. However, longer duration treatment (30 days) with either dose of MeHg resulted in paired-pulse facilitation (PPF) of fEPSP2 in the majority of slices examined. PPF remained observable in slices prepared from animals in which MeHg exposure had been terminated for 30 days after completion of the initial 30 day MeHg treatment, whereas slices from control animals still showed PPD. MeHg did not cause any frequency- or region-preferential effect on STP. Manipulations of [Ca 2+ ] e or application of the GABA A receptor antagonist bicuculline could alter the strength and polarity of MeHg-induced changes in STP. Thus, these data suggest that low level postnatal MeHg exposure interferes with the developmental transformation of STP in the visual cortex, which is a long-lasting effect.

  9. Quality of life in South East Asian patients who consult for dyspepsia: Validation of the short form Nepean Dyspepsia Index

    OpenAIRE

    Mahadeva, Sanjiv; Wee, Hwee-Lin; Goh, Khean-Lee; Thumboo, Julian

    2009-01-01

    Abstract Background Treatment objectives for dyspepsia include improvements in both symptoms and health-related quality of life (HRQoL). There is a lack of disease-specific instruments measuring HRQoL in South East Asian dyspeptics. Objectives To validate English and locally translated version of the Short-Form Nepean Dyspepsia Index (SF-NDI) in Malaysian patients who consult for dyspepsia. Methods The English version of the SF-NDI was culturally adapted locally and a Malay translation was de...

  10. The export receptor Crm1 forms a dimer to promote nuclear export of HIV RNA.

    Science.gov (United States)

    Booth, David S; Cheng, Yifan; Frankel, Alan D

    2014-12-08

    The HIV Rev protein routes viral RNAs containing the Rev Response Element (RRE) through the Crm1 nuclear export pathway to the cytoplasm where viral proteins are expressed and genomic RNA is delivered to assembling virions. The RRE assembles a Rev oligomer that displays nuclear export sequences (NESs) for recognition by the Crm1-Ran(GTP) nuclear receptor complex. Here we provide the first view of an assembled HIV-host nuclear export complex using single-particle electron microscopy. Unexpectedly, Crm1 forms a dimer with an extensive interface that enhances association with Rev-RRE and poises NES binding sites to interact with a Rev oligomer. The interface between Crm1 monomers explains differences between Crm1 orthologs that alter nuclear export and determine cellular tropism for viral replication. The arrangement of the export complex identifies a novel binding surface to possibly target an HIV inhibitor and may point to a broader role for Crm1 dimerization in regulating host gene expression.

  11. Lipoprotein receptors in cultured bovine endothelial cells

    International Nuclear Information System (INIS)

    Struempfer, A.E.M.

    1983-07-01

    In this study, receptors that may be involved in the uptake of low density lipoproteins (LDL) and low density lipoproteins which have been modified by acetylation (AcLDL), were characterized. Aortic epithelial cells were used and a cell culture system which closely resembled the in vivo monolayer was established. Endothelial cell and lipoprotein interactions were examined by incubating the cells with 125 l-labelled lipoproteins under various conditions. The receptor affinity of bovine aortic endothelial cells was higher for AcLDL than that for LDL. Competition studies demonstrated that there were two distinct receptors for LDL and AcLDL on the endothelial cells. AcLDL did not compete with LDL for the LDL receptor, and conversely LDL did not compete with AcLDL for the AcLDL receptor. The receptor activities for LDL and AcLDL were examined as a function of culture age. Whereas the LDL receptor could be regulated, the AcLDL receptor was not as susceptible to regulation. Upon exposing endothelial cells for 72 h to either LDL or AcLDL, it was found that the total amount of cellular cholesterol increased by about 50%. However, the increase of total cholesterol was largely in the form of free cholesterol. This is in contrast to macrophages, where the increase in total cholesterol upon exposure to AcLDL is largely in the form cholesteryl esters

  12. Validation of the Long- and Short-Form of the Ethical Values Assessment (EVA): A Questionnaire Measuring the Three Ethics Approach to Moral Psychology

    Science.gov (United States)

    Padilla-Walker, Laura Maria; Jensen, Lene Arnett

    2016-01-01

    Moral psychology has been moving toward consideration of multiple kinds of moral concepts and values, such as the Ethics of Autonomy, Community, and Divinity. While these three ethics have commonly been measured qualitatively, the current study sought to validate the long and short forms of the Ethical Values Assessment (EVA), which is a…

  13. Interaction of GABAA receptors with purinergic P2X2 receptors

    International Nuclear Information System (INIS)

    Shrivastava, A.

    2010-01-01

    GABA A Rs in the spinal cord are evolving as an important target for drug development against pain. Purinergic P2X 2 Rs are also expressed in spinal cord neurons and are known to cross-talk with GABA A Rs. Here we investigated a possible 'dynamic' interaction between GABA A Rs and P2X 2 Rs using co-immunoprecipitation and FRET studies in HEK cells along with co-localization and single particle tracking studies in spinal cord neurons. Our results suggest that a significant proportion of P2X 2 Rs forms a transient complex with GABA A Rs inside the cell, thus stabilizing these receptors and using them for co-trafficking to the cell surface. P2X 2 Rs and GABA A Rs are then co-inserted into the cell membrane and are primarily located extra-synaptically. Furthermore, agonist induced activation of P2X 2 Rs results in disassembly of the receptor complex and destabilization of GABA A Rs whereas P2X 2 Rs are stabilized and form larger clusters. Antagonist-induced blocking of P2XRs results in co-stabilization of this receptor complex at the cell surface. These results suggest a novel mechanism where association of P2XRs with other receptors could be used for specific targeting to the neuronal membrane, thus providing an extrasynaptic receptor reserve that could regulate the excitability of neurons. We further conclude that blocking the excitatory activity of excessively released ATP under diseased state by P2XR antagonists could simultaneously enhance synaptic inhibition mediated by GABA A Rs.(author) (author) [de

  14. German Language Adaptation of the Headache Management Self-Efficacy Scale (HMSE-G) and Development of a New Short Form (HMSE-G-SF).

    Science.gov (United States)

    Graef, Julia E; Rief, Winfried; French, Douglas J; Nilges, Paul; Nestoriuc, Yvonne

    2015-01-01

    This study aims to develop and validate a German version of French and colleagues' Headache Management Self-efficacy Scale and to construct an abbreviated form for use in behavioral headache research. Furthermore, the contribution of headache-specific self-efficacy to pain-related disability in German chronic headache sufferers was examined. Headache-specific self-efficacy refers to an individuals' confidence that they can engage in behaviors to either prevent headache episodes or to manage headache-related pain and disability. Self-efficacy beliefs have been shown repeatedly to be positively associated with psychological well-being, effective coping, and enhanced treatment outcomes. A cross-sectional sample of 304 individuals diagnosed with either migraine, chronic tension-type headache, or a combination of 2 or more headache disorders completed the German Headache Management Self-efficacy Scale and questionnaires assessing headache activity, pain-related coping, general self-efficacy, depression, and anxiety. Responsiveness of the scale was analyzed in a longitudinal subsample of 32 inpatients undergoing headache treatment. Finally, a short form was constructed and evaluated regarding psychometric properties. The German Headache Management Self-efficacy Scale showed good reliability (Cronbach's α = 0.87) as did the 6-item short form (Cronbach's α = 0.72). In the longitudinal sample, both versions showed a good ability to change over time (SRM= 0.52-1.16). Chronic headache patients with higher levels of self-efficacy reported lower levels of disability (r = -0.26 to -0.31). Multiple regression analyses revealed headache intensity and headache-specific self-efficacy as strongest predictors of headache-related disability (βself-efficacy  = -0.21, βintensity  = 0.26). Both the 25-item version and the 6-item version appear to be valid, reliable measures of self-efficacy beliefs. These scales will allow clinicians to identify headache sufferers

  15. NMDA or 5-HT receptor antagonists impair memory reconsolidation and induce various types of amnesia.

    Science.gov (United States)

    Nikitin, V P; Solntseva, S V; Kozyrev, S A; Nikitin, P V; Shevelkin, A V

    2018-06-01

    Elucidation of amnesia mechanisms is one of the central problems in neuroscience with immense practical application. Previously, we found that conditioned food presentation combined with injection of a neurotransmitter receptor antagonist or protein synthesis inhibitor led to amnesia induction. In the present study, we investigated the time course and features of two amnesias: induced by impairment of memory reconsolidation using an NMDA glutamate receptor antagonist (MK-801) and a serotonin receptor antagonist (methiothepin, MET) on snails trained with food aversion conditioning. During the early period of amnesia (types of amnesia. Retraining an on 1st or 3rd day of amnesia induction facilitated memory formation, i.e. the number of CS + US pairings was lower than at initial training. On the 10th or 30th day after the MET/reminder, the number of CS + US pairings did not change between initial training and retraining. Retraining on the 10th or 30th day following the MK-801/reminder in the same or a new context of learning resulted in short, but not long-term, memory, and the number of CS + US pairings was higher than at the initial training. This type of amnesia was specific to the CS we used at initial training, since long-term memory for another kind of CS could be formed in the same snails. The attained results suggest that disruption of memory reconsolidation using antagonists of serotonin or NMDA glutamate receptors induced amnesias with different abilities to form long-term memory during the late period of development. Copyright © 2018 Elsevier B.V. All rights reserved.

  16. Evidence for Heterodimerization and Functional Interaction of the Angiotensin Type 2 Receptor and the Receptor MAS.

    Science.gov (United States)

    Leonhardt, Julia; Villela, Daniel C; Teichmann, Anke; Münter, Lisa-Marie; Mayer, Magnus C; Mardahl, Maibritt; Kirsch, Sebastian; Namsolleck, Pawel; Lucht, Kristin; Benz, Verena; Alenina, Natalia; Daniell, Nicholas; Horiuchi, Masatsugu; Iwai, Masaru; Multhaup, Gerhard; Schülein, Ralf; Bader, Michael; Santos, Robson A; Unger, Thomas; Steckelings, Ulrike Muscha

    2017-06-01

    The angiotensin type 2 receptor (AT2R) and the receptor MAS are receptors of the protective arm of the renin-angiotensin system. They mediate strikingly similar actions. Moreover, in various studies, AT2R antagonists blocked the effects of MAS agonists and vice versa. Such cross-inhibition may indicate heterodimerization of these receptors. Therefore, this study investigated the molecular and functional interplay between MAS and the AT2R. Molecular interactions were assessed by fluorescence resonance energy transfer and by cross correlation spectroscopy in human embryonic kidney-293 cells transfected with vectors encoding fluorophore-tagged MAS or AT2R. Functional interaction of AT2R and MAS was studied in astrocytes with CX3C chemokine receptor-1 messenger RNA expression as readout. Coexpression of fluorophore-tagged AT2R and MAS resulted in a fluorescence resonance energy transfer efficiency of 10.8 ± 0.8%, indicating that AT2R and MAS are capable to form heterodimers. Heterodimerization was verified by competition experiments using untagged AT2R and MAS. Specificity of dimerization of AT2R and MAS was supported by lack of dimerization with the transient receptor potential cation channel, subfamily C-member 6. Dimerization of the AT2R was abolished when it was mutated at cysteine residue 35. AT2R and MAS stimulation with the respective agonists, Compound 21 or angiotensin-(1-7), significantly induced CX3C chemokine receptor-1 messenger RNA expression. Effects of each agonist were blocked by an AT2R antagonist (PD123319) and also by a MAS antagonist (A-779). Knockout of a single of these receptors made astrocytes unresponsive for both agonists. Our results suggest that MAS and the AT2R form heterodimers and that-at least in astrocytes-both receptors functionally depend on each other. © 2017 American Heart Association, Inc.

  17. Function of the cytoplasmic tail of human calcitonin receptor-like receptor in complex with receptor activity-modifying protein 2

    Energy Technology Data Exchange (ETDEWEB)

    Kuwasako, Kenji, E-mail: kuwasako@fc.miyazaki-u.ac.jp [Frontier Science Research Center, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692 (Japan); Kitamura, Kazuo; Nagata, Sayaka; Hikosaka, Tomomi [Division of Circulation and Body Fluid Regulation, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692 (Japan); Kato, Johji [Frontier Science Research Center, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692 (Japan)

    2010-02-12

    Receptor activity-modifying protein 2 (RAMP2) enables calcitonin receptor-like receptor (CRLR) to form an adrenomedullin (AM)-specific receptor. Here we investigated the function of the cytoplasmic C-terminal tail (C-tail) of human (h)CRLR by co-transfecting its C-terminal mutants into HEK-293 cells stably expressing hRAMP2. Deleting the C-tail from CRLR disrupted AM-evoked cAMP production or receptor internalization, but did not affect [{sup 125}I]AM binding. We found that CRLR residues 428-439 are required for AM-evoked cAMP production, though deleting this region had little effect on receptor internalization. Moreover, pretreatment with pertussis toxin (100 ng/mL) led to significant increases in AM-induced cAMP production via wild-type CRLR/RAMP2 complexes. This effect was canceled by deleting CRLR residues 454-457, suggesting Gi couples to this region. Flow cytometric analysis revealed that CRLR truncation mutants lacking residues in the Ser/Thr-rich region extending from Ser{sup 449} to Ser{sup 467} were unable to undergo AM-induced receptor internalization and, in contrast to the effect on wild-type CRLR, overexpression of GPCR kinases-2, -3 and -4 failed to promote internalization of CRLR mutants lacking residues 449-467. Thus, the hCRLR C-tail is crucial for AM-evoked cAMP production and internalization of the CRLR/RAMP2, while the receptor internalization is dependent on the aforementioned GPCR kinases, but not Gs coupling.

  18. An 8-item short form of the Eating Disorder Examination-Questionnaire adapted for children (ChEDE-Q8).

    Science.gov (United States)

    Kliem, Sören; Schmidt, Ricarda; Vogel, Mandy; Hiemisch, Andreas; Kiess, Wieland; Hilbert, Anja

    2017-06-01

    Eating disturbances are common in children placing a vulnerable group of them at risk for full-syndrome eating disorders and adverse health outcomes. To provide a valid self-report assessment of eating disorder psychopathology in children, a short form of the child version of the Eating Disorder Examination (ChEDE-Q) was psychometrically evaluated. Similar to the EDE-Q, the ChEDE-Q provides assessment of eating disorder psychopathology related to anorexia nervosa, bulimia nervosa, and binge-eating disorder; however, the ChEDE-Q does not assess symptoms of avoidant/restrictive food intake disorder, pica, or rumination disorder. In 1,836 participants ages 7 to 18 years, recruited from two independent population-based samples, the factor structure of the recently established 8-item short form EDE-Q8 for adults was examined, including measurement invariance analyses on age, gender, and weight status derived from objectively measured weight and height. For convergent validity, the ChEDE-Q global score, body esteem scale, strengths and difficulties questionnaire, and sociodemographic characteristics were used. Item characteristics and age- and gender-specific norms were calculated. Confirmatory factor analysis revealed good model fit for the 8-item ChEDE-Q. Measurement invariance analyses indicated strict invariance for all analyzed subgroups. Convergent validity was provided through associations with well-established questionnaires and age, gender, and weight status, in expected directions. The newly developed ChEDE-Q8 proved to be a psychometrically sound and economical self-report assessment tool of eating disorder psychopathology in children. Further validation studies are needed, particularly concerning discriminant and predictive validity. © 2017 Wiley Periodicals, Inc.

  19. Samuel Beckett and music an absurd essay about the idea of musicality and musical form in Samuel Beckett’s short pieces - influences and possibilities

    Directory of Open Access Journals (Sweden)

    Mosusova Nadežda

    2004-01-01

    Full Text Available The premise of musicality of Beckett’s short dramas contains more questions than answers. Is the musicality of text present only in the work of Samuel Beckett? Do only the (musical stage remarks in Beckett’s dramas suggest the idea of musicality? Can the absurdity of his output be expressed with music and through music? Some short musical compositions, especially by Alexandre Scriabine, can be in some way compared with Beckett’s "dramaticules", but only in form not in the meaning and musical language. The question of hidden influences remains to be developed.

  20. Measuring resilience after spinal cord injury: Development, validation and psychometric characteristics of the SCI-QOL Resilience item bank and short form.

    Science.gov (United States)

    Victorson, David; Tulsky, David S; Kisala, Pamela A; Kalpakjian, Claire Z; Weiland, Brian; Choi, Seung W

    2015-05-01

    To describe the development and psychometric properties of the Spinal Cord Injury--Quality of Life (SCI-QOL) Resilience item bank and short form. Using a mixed-methods design, we developed and tested a resilience item bank through the use of focus groups with individuals with SCI and clinicians with expertise in SCI, cognitive interviews, and item-response theory based analytic approaches, including tests of model fit and differential item functioning (DIF). We tested a 32-item pool at several medical institutions across the United States, including the University of Michigan, Kessler Foundation, the Rehabilitation Institute of Chicago, the University of Washington, Craig Hospital and the James J. Peters/Bronx Department of Veterans Affairs medical center. A total of 717 individuals with SCI completed the Resilience items. A unidimensional model was observed (CFI=0.968; RMSEA=0.074) and measurement precision was good (theta range between -3.1 and 0.9). Ten items were flagged for DIF, however, after examination of effect sizes we found this to be negligible with little practical impact on score estimates. The final calibrated item bank resulted in 21 retained items. This study indicates that the SCI-QOL Resilience item bank represents a psychometrically robust measurement tool. Short form items are also suggested and computer adaptive tests are available.

  1. Genome-Wide Profiling of Liver X Receptor, Retinoid X Receptor, and Peroxisome Proliferator-Activated Receptor α in Mouse Liver Reveals Extensive Sharing of Binding Sites

    DEFF Research Database (Denmark)

    Boergesen, Michael; Pedersen, Thomas Åskov; Gross, Barbara

    2012-01-01

    and correlate with an LXR-dependent hepatic induction of lipogenic genes. To further investigate the roles of RXR and LXR in the regulation of hepatic gene expression, we have mapped the ligand-regulated genome-wide binding of these factors in mouse liver. We find that the RXR agonist bexarotene primarily......The liver X receptors (LXRs) are nuclear receptors that form permissive heterodimers with retinoid X receptor (RXR) and are important regulators of lipid metabolism in the liver. We have recently shown that RXR agonist-induced hypertriglyceridemia and hepatic steatosis in mice are dependent on LXRs...

  2. Prognostic significance of circulating intact and cleaved forms of urokinase plasminogen activator receptor in inoperable chemotherapy treated cholangiocarcinoma patients

    DEFF Research Database (Denmark)

    Grunnet, Mie; Christensen, I J; Lassen, Ulrik

    2014-01-01

    BACKGROUND: High levels of intact and cleaved forms of the urokinase-type plasminogen activator receptor (uPAR) in both tissue and blood are associated with poor survival in several cancer diseases. The prognostic significance of uPAR in cholangiocarcinoma is unknown. The aims of this study were...... to determine if pre-treatment serum levels of uPAR forms and a decrease in levels during chemotherapy are predictive of survival in patients with inoperable cholangiocarcinoma. DESIGN AND METHODS: Patients with inoperable cholangiocarcinoma were consecutively included in the training set (n=108). A test set......PAR(I-III)+uPAR(II-III) after 2cycles of chemotherapy was associated with poor survival (HR=1.79, 95% CI:1.08-2.97, p=0.023, n=57). This predictor, however, was not significant in the test set (p=0.21, 26 events in 27 patients). CONCLUSION: The baseline level of uPAR(I-III)+uPAR(II-III) is a predictor of survival in inoperable...

  3. Intact and cleaved forms of the urokinase receptor enhance discrimination of cancer from non-malignant conditions in patients presenting with symptoms related to colorectal cancer

    DEFF Research Database (Denmark)

    Lomholt, A F; Høyer-Hansen, G; Nielsen, H J

    2009-01-01

    plasminogen activator receptor (suPAR) was proposed as a marker in CRC patients. This study was undertaken to evaluate the individual molecular forms of suPAR as discriminators in a group of patients undergoing endoscopical examination following symptoms related to colorectal cancer. METHODS: In a case......-control study comprising 308 patients undergoing endoscopical examination following CRC-related symptoms, 77 CRC patients with adenocarcinoma were age and gender matched to: 77 patients with adenomas; 77 with other non-malignant findings, and 77 with no findings. The different uPAR forms were measured...

  4. Measurement Equivalence of the Patient Reported Outcomes Measurement Information System® (PROMIS®) Pain Interference Short Form Items: Application to Ethnically Diverse Cancer and Palliative Care Populations.

    Science.gov (United States)

    Teresi, Jeanne A; Ocepek-Welikson, Katja; Cook, Karon F; Kleinman, Marjorie; Ramirez, Mildred; Reid, M Carrington; Siu, Albert

    2016-01-01

    Reducing the response burden of standardized pain measures is desirable, particularly for individuals who are frail or live with chronic illness, e.g., those suffering from cancer and those in palliative care. The Patient Reported Outcome Measurement Information System ® (PROMIS ® ) project addressed this issue with the provision of computerized adaptive tests (CAT) and short form measures that can be used clinically and in research. Although there has been substantial evaluation of PROMIS item banks, little is known about the performance of PROMIS short forms, particularly in ethnically diverse groups. Reviewed in this article are findings related to the differential item functioning (DIF) and reliability of the PROMIS pain interference short forms across diverse sociodemographic groups. DIF hypotheses were generated for the PROMIS short form pain interference items. Initial analyses tested item response theory (IRT) model assumptions of unidimensionality and local independence. Dimensionality was evaluated using factor analytic methods; local dependence (LD) was tested using IRT-based LD indices. Wald tests were used to examine group differences in IRT parameters, and to test DIF hypotheses. A second DIF-detection method used in sensitivity analyses was based on ordinal logistic regression with a latent IRT-derived conditioning variable. Magnitude and impact of DIF were investigated, and reliability and item and scale information statistics were estimated. The reliability of the short form item set was excellent. However, there were a few items with high local dependency, which affected the estimation of the final discrimination parameters. As a result, the item, "How much did pain interfere with enjoyment of social activities?" was excluded in the DIF analyses for all subgroup comparisons. No items were hypothesized to show DIF for race and ethnicity; however, five items showed DIF after adjustment for multiple comparisons in both primary and sensitivity

  5. Measurement Equivalence of the Patient Reported Outcomes Measurement Information System® (PROMIS®) Pain Interference Short Form Items: Application to Ethnically Diverse Cancer and Palliative Care Populations

    Science.gov (United States)

    Teresi, Jeanne A.; Ocepek-Welikson, Katja; Cook, Karon F.; Kleinman, Marjorie; Ramirez, Mildred; Reid, M. Carrington; Siu, Albert

    2017-01-01

    Reducing the response burden of standardized pain measures is desirable, particularly for individuals who are frail or live with chronic illness, e.g., those suffering from cancer and those in palliative care. The Patient Reported Outcome Measurement Information System® (PROMIS®) project addressed this issue with the provision of computerized adaptive tests (CAT) and short form measures that can be used clinically and in research. Although there has been substantial evaluation of PROMIS item banks, little is known about the performance of PROMIS short forms, particularly in ethnically diverse groups. Reviewed in this article are findings related to the differential item functioning (DIF) and reliability of the PROMIS pain interference short forms across diverse sociodemographic groups. Methods DIF hypotheses were generated for the PROMIS short form pain interference items. Initial analyses tested item response theory (IRT) model assumptions of unidimensionality and local independence. Dimensionality was evaluated using factor analytic methods; local dependence (LD) was tested using IRT-based LD indices. Wald tests were used to examine group differences in IRT parameters, and to test DIF hypotheses. A second DIF-detection method used in sensitivity analyses was based on ordinal logistic regression with a latent IRT-derived conditioning variable. Magnitude and impact of DIF were investigated, and reliability and item and scale information statistics were estimated. Results The reliability of the short form item set was excellent. However, there were a few items with high local dependency, which affected the estimation of the final discrimination parameters. As a result, the item, “How much did pain interfere with enjoyment of social activities?” was excluded in the DIF analyses for all subgroup comparisons. No items were hypothesized to show DIF for race and ethnicity; however, five items showed DIF after adjustment for multiple comparisons in both primary and

  6. Blocking opioid receptors alters short-term feed intake and oro-sensorial preferences in weaned calves.

    Science.gov (United States)

    Montoro, C; Ipharraguerre, I R; Bach, A

    2012-05-01

    during the first 4 h after feeding and tended to prefer SF only after 6 h from feeding. Plasma glucose, insulin, and cholecystokinin concentrations were greater in FED than in FAS calves. Injection of naloxone decreased plasma glucagon-like peptide-1 (GLP-1) in NAL calves. Blocking opioid receptors reduced intake the first 2 h after naloxone injection in FED calves, altered oro-sensorial preferences, and reduced plasma GLP-1 concentration. In conclusion, the opioid peptide system may control short-term feed intake by modulating the oro-sensorial response triggered by feed consumption, especially when calves are fed ad libitum. Copyright © 2012 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  7. Intravenous siRNA of brain cancer with receptor targeting and avidin-biotin technology.

    Science.gov (United States)

    Xia, Chun-Fang; Zhang, Yufeng; Zhang, Yun; Boado, Ruben J; Pardridge, William M

    2007-12-01

    The effective delivery of short interfering RNA (siRNA) to brain following intravenous administration requires the development of a delivery system for transport of the siRNA across the brain capillary endothelial wall, which forms the blood-brain barrier in vivo. siRNA was delivered to brain in vivo with the combined use of a receptor-specific monoclonal antibody delivery system, and avidin-biotin technology. The siRNA was mono-biotinylated on either terminus of the sense strand, in parallel with the production of a conjugate of the targeting MAb and streptavidin. Rat glial cells (C6 or RG-2) were permanently transfected with the luciferase gene, and implanted in the brain of adult rats. Following the formation of intra-cranial tumors, the rats were treated with a single intravenous injection of 270 microg/kg of biotinylated siRNA attached to a transferrin receptor antibody via a biotin-streptavidin linker. The intravenous administration of the siRNA caused a 69-81% decrease in luciferase gene expression in the intracranial brain cancer in vivo. Brain delivery of siRNA following intravenous administration is possible with siRNAs that are targeted to brain with the combined use of receptor specific antibody delivery systems and avidin-biotin technology.

  8. Effects of a novel bradykinin B1 receptor antagonist and angiotensin II receptor blockade on experimental myocardial infarction in rats.

    Directory of Open Access Journals (Sweden)

    Dongmei Wu

    Full Text Available The aim of the present study was to evaluate the cardiovascular effects of the novel bradykinin B1 receptor antagonist BI-113823 following myocardial infarction (MI and to determine whether B1 receptor blockade alters the cardiovascular effects of an angiotensin II type 1 (AT1 receptor antagonist after MI in rats.Sprague Dawley rats were subjected to permanent occlusion of the left descending coronary artery. Cardiovascular function was determined at 7 days post MI. Treatment with either B1 receptor antagonist (BI-113823 or AT1 receptor antagonist (irbesartan alone or in combination improved post-MI cardiac function as evidenced by attenuation of elevated left ventricular end diastolic pressure (LVEDP; greater first derivative of left ventricular pressure (± dp/dt max, left ventricle ejection fraction, fractional shorting, and better wall motion; as we as reductions in post-MI up-regulation of matrix metalloproteinases 2 (MMP-2 and collagen III. In addition, the cardiac up-regulation of B1 receptor and AT1 receptor mRNA were markedly reduced in animals treated with BI 113823, although bradykinin B2 receptor and angiotensin 1 converting enzyme (ACE1 mRNA expression were not significantly affected by B1 receptor blockade.The present study demonstrates that treatment with the novel B1 receptor antagonist, BI-113823 improves post-MI cardiac function and does not influence the cardiovascular effects of AT1 receptor antagonist following MI.

  9. Adaptation and Validation of the Foot Function Index-Revised Short Form into Polish

    Directory of Open Access Journals (Sweden)

    Radosław Rutkowski

    2017-01-01

    Full Text Available Purpose. The aim of the present study was to adapt the Foot Function Index-Revised Short Form (FFI-RS questionnaire into Polish and verify its reliability and validity in a group of patients with rheumatoid arthritis (RA. Methods. The study included 211 patients suffering from RA. The FFI-RS questionnaire underwent standard linguistic adaptation and its psychometric parameters were investigated. The enrolled participants had been recruited for seven months as a convenient sample from the rheumatological hospital in Śrem (Poland. They represented different sociodemographic characteristics and were characterized as rural and city environments residents. Results. The mean age of the patients was 58.9±10.2 years. The majority of patients (85% were female. The average final FFI-RS score was 62.9±15.3. The internal consistency was achieved at a high level of 0.95 in Cronbach’s alpha test, with an interclass correlation coefficient ranging between 0.78 and 0.84. A strong correlation was observed between the FFI-RS and Health Assessment Questionnaire-Disability Index (HAQ-DI questionnaires. Conclusion. The Polish version of FFI-RS-PL indicator is an important tool for evaluating the functional condition of patients’ feet and can be applied in the diagnosis and treatment of Polish-speaking patients suffering from RA.

  10. Adaptation and Validation of the Foot Function Index-Revised Short Form into Polish.

    Science.gov (United States)

    Rutkowski, Radosław; Gałczyńska-Rusin, Małgorzata; Gizińska, Małgorzata; Straburzyński-Lupa, Marcin; Zdanowska, Agata; Romanowski, Mateusz Wojciech; Romanowski, Wojciech; Budiman-Mak, Elly; Straburzyńska-Lupa, Anna

    2017-01-01

    The aim of the present study was to adapt the Foot Function Index-Revised Short Form (FFI-RS) questionnaire into Polish and verify its reliability and validity in a group of patients with rheumatoid arthritis (RA). The study included 211 patients suffering from RA. The FFI-RS questionnaire underwent standard linguistic adaptation and its psychometric parameters were investigated. The enrolled participants had been recruited for seven months as a convenient sample from the rheumatological hospital in Śrem (Poland). They represented different sociodemographic characteristics and were characterized as rural and city environments residents. The mean age of the patients was 58.9 ± 10.2 years. The majority of patients (85%) were female. The average final FFI-RS score was 62.9 ± 15.3. The internal consistency was achieved at a high level of 0.95 in Cronbach's alpha test, with an interclass correlation coefficient ranging between 0.78 and 0.84. A strong correlation was observed between the FFI-RS and Health Assessment Questionnaire-Disability Index (HAQ-DI) questionnaires. The Polish version of FFI-RS-PL indicator is an important tool for evaluating the functional condition of patients' feet and can be applied in the diagnosis and treatment of Polish-speaking patients suffering from RA.

  11. Complete relaxation and conformational exchange matrix (CORCEMA) analysis of intermolecular saturation transfer effects in reversibly forming ligand-receptor complexes.

    Science.gov (United States)

    Jayalakshmi, V; Krishna, N Rama

    2002-03-01

    A couple of recent applications of intermolecular NOE (INOE) experiments as applied to biomolecular systems involve the (i) saturation transfer difference NMR (STD-NMR) method and (ii) the intermolecular cross-saturation NMR (ICS-NMR) experiment. STD-NMR is a promising tool for rapid screening of a large library of compounds to identify bioactive ligands binding to a target protein. Additionally, it is also useful in mapping the binding epitopes presented by a bioactive ligand to its target protein. In this latter application, the STD-NMR technique is essentially similar to the ICS-NMR experiment, which is used to map protein-protein or protein-nucleic acid contact surfaces in complexes. In this work, we present a complete relaxation and conformational exchange matrix (CORCEMA) theory (H. N. B. Moseley et al., J. Magn. Reson. B 108, 243-261 (1995)) applicable for these two closely related experiments. As in our previous work, we show that when exchange is fast on the relaxation rate scale, a simplified CORCEMA theory can be formulated using a generalized average relaxation rate matrix. Its range of validity is established by comparing its predictions with those of the exact CORCEMA theory which is valid for all exchange rates. Using some ideal model systems we have analyzed the factors that influence the ligand proton intensity changes when the resonances from some protons on the receptor protein are saturated. The results show that the intensity changes in the ligand signals in an intermolecular NOE experiment are very much dependent upon: (1) the saturation time, (2) the location of the saturated receptor protons with respect to the ligand protons, (3) the conformation of the ligand-receptor interface, (4) the rotational correlation times for the molecular species, (5) the kinetics of the reversibly forming complex, and (6) the ligand/receptor ratio. As an example of a typical application of the STD-NMR experiment we have also simulated the STD effects for a

  12. Modulation of neuroplasticity pathways and antidepressant-like behavioural responses following the short-term (3 and 7 days) administration of the 5-HT₄ receptor agonist RS67333.

    Science.gov (United States)

    Pascual-Brazo, Jesús; Castro, Elena; Díaz, Alvaro; Valdizán, Elsa M; Pilar-Cuéllar, Fuencisla; Vidal, Rebeca; Treceño, Begoña; Pazos, Angel

    2012-06-01

    It has been recently suggested that activation of 5-HT₄ receptors might exert antidepressant-like effects in rats after 3 d treatment, suggesting a new strategy for developing faster-acting antidepressants. We studied the effects of 3 d and 7 d treatment with the 5-HT₄ receptor partial agonist RS67333 (1.5 mg/kg.d) in behavioural tests of chronic efficacy and on neuroplastic-associated changes, such as adult hippocampal neurogenesis, expression of CREB, BDNF, β-catenin, AKT and 5-HT₄ receptor functionality. RS67333 treatment up-regulated hippocampal cell proliferation, β-catenin expression and pCREB/CREB ratio after 3 d treatment. This short-term treatment also reduced immobility time in the forced swim test (FST), together with a partial reversion of the anhedonic-like state (sucrose consumption after chronic corticosterone). Administration of RS67333 for 7 d resulted in a higher increase in the rate of hippocampal cell proliferation, a significant desensitization of 5-HT₄ receptor-coupled adenylate cyclase activity and a more marked increase in the expression of neuroplasticity-related proteins (BDNF, CREB, AKT): these changes reached the same magnitude as those observed after 3 wk administration of classical antidepressants. Consistently, a positive behavioural response in the novelty suppressed feeding (NSF) test and a complete reversion of the anhedonic-like state (sucrose consumption) were also observed after 7 d treatment. These results support the antidepressant-like profile of RS67333 with a shorter onset of action and suggest that this time period of administration (3-7 d) could be a good approximation to experimentally predict the onset of action of this promising strategy.

  13. Properties of the intracellular transient receptor potential (TRP) channel in yeast, Yvc1.

    Science.gov (United States)

    Chang, Yiming; Schlenstedt, Gabriel; Flockerzi, Veit; Beck, Andreas

    2010-05-17

    Transient receptor potential (TRP) channels are found among mammals, flies, worms, ciliates, Chlamydomonas, and yeast but are absent in plants. These channels are believed to be tetramers of proteins containing six transmembrane domains (TMs). Their primary structures are diverse with sequence similarities only in some short amino acid sequence motifs mainly within sequences covering TM5, TM6, and adjacent domains. In the yeast genome, there is one gene encoding a TRP-like sequence. This protein forms an ion channel in the vacuolar membrane and is therefore called Yvc1 for yeast vacuolar conductance 1. In the following we summarize its prominent features. Copyright 2009 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  14. Simple construct evaluation with latent class analysis: An investigation of Facebook addiction and the development of a short form of the Facebook Addiction Test (F-AT).

    Science.gov (United States)

    Dantlgraber, Michael; Wetzel, Eunike; Schützenberger, Petra; Stieger, Stefan; Reips, Ulf-Dietrich

    2016-09-01

    In psychological research, there is a growing interest in using latent class analysis (LCA) for the investigation of quantitative constructs. The aim of this study is to illustrate how LCA can be applied to gain insights on a construct and to select items during test development. We show the added benefits of LCA beyond factor-analytic methods, namely being able (1) to describe groups of participants that differ in their response patterns, (2) to determine appropriate cutoff values, (3) to evaluate items, and (4) to evaluate the relative importance of correlated factors. As an example, we investigated the construct of Facebook addiction using the Facebook Addiction Test (F-AT), an adapted version of the Internet Addiction Test (I-AT). Applying LCA facilitates the development of new tests and short forms of established tests. We present a short form of the F-AT based on the LCA results and validate the LCA approach and the short F-AT with several external criteria, such as chatting, reading newsfeeds, and posting status updates. Finally, we discuss the benefits of LCA for evaluating quantitative constructs in psychological research.

  15. Relationship between expression of leptin receptors mRNA in breast tissue, plasma leptin level in breast cancer patients with obesity and clinical pathologic data

    International Nuclear Information System (INIS)

    Li Chunrui; Liu Wenli; Sun Hanying; Zhou Jianfeng

    2007-01-01

    In order to investigate the expression of leptin receptors mRNA in breast tissue and plasma leptin levels in breast cancer patients with obesity and their relationship with clinical pathologic data, 124 subjects who were either obesity or had suffered from breast benign disease with obesity, or breast cancer with obesity were entered into this study. The levels of plasma leptin in all subjects were determined and leptin receptors mRNA expression levels were measured by RT-PCR in breast tissue of breast cancer patients with obesity and breast benign disease with obesity. The results showed that plasma leptin levels in breast cancer patients with obesity were significantly higher than those in breast benign disease with obesity and obesity patients alone (P<0.05). The expression of the leptin receptor long form [-Lep-R(L)-] mRNA and the leptin receptor short form [-Lep-R(S)-] mRNA in breast tissue of breast cancer patients with obesity were significantly higher than that in breast tissue of breast benign disease patients with obesity (P<0.05). The plasma leptin level had remarkable positive correlation with the expressions of the Lep-R(L) mRNA and the Lep-R(S) mRNA. The plasma leptin level and leptin receptors mRNA expression levels in patients were not correlated with the axillary node metastasis, menopause, the TNM stage or pathological type. Therefore, leptin may have a promoting effect on the carcinogenesis of breast cancer. (authors)

  16. Comparison of the antiviral potential among soluble forms of herpes simplex virus type-2 glycoprotein D receptors, herpes virus entry mediator A, nectin-1 and nectin-2, in transgenic mice.

    Science.gov (United States)

    Fujimoto, Yoshikazu; Tomioka, Yukiko; Ozaki, Kinuyo; Takeda, Keiko; Suyama, Haruka; Yamamoto, Sayo; Takakuwa, Hiroki; Morimatsu, Masami; Uede, Toshimitsu; Ono, Etsuro

    2017-07-01

    Herpesvirus entry mediator A (HVEM), nectin-1 and nectin-2 are cellular receptors of glycoprotein D (gD) of herpes simplex virus type-2 (HSV-2). It has been shown that soluble forms of HSV gD receptors have the antiviral potential in cultured cells and transgenic mice. Here, to compare antiviral potential of soluble forms of HVEM, nectin-1 and nectin-2 against HSV-2 infections in vivo, transgenic mice expressing fusion proteins consisting of the entire ectodomain of HVEM, nectin-1 or nectin-2 and the Fc portion of human IgG (HVEMIg, nectin-1Ig and nectin-2Ig, respectively) were intraperitoneally infected with HSV-2. In the infection with 3 MLD50 (50 % mouse lethal dose), effective resistance was not observed in transgenic mice expressing nectin-2Ig. In a transgenic mouse line with high expression of nectin-1Ig, significant protection from the infection with 30 and 300 MLD50 was observed (survival rate of 100 and 71 %, respectively). On the other hand, transgenic mice expressing HVEMIg showed a complete resistance to the lethal infection even with 300 MLD50 (survival rate of 100 %). These results demonstrated that HVEMIg could exert effective antiviral activities against HSV-2 infections in vivo as compared with other soluble forms of HSV gD receptors.

  17. Cocaine Inhibits Dopamine D2 Receptor Signaling via Sigma-1-D2 Receptor Heteromers

    Science.gov (United States)

    Navarro, Gemma; Moreno, Estefania; Bonaventura, Jordi; Brugarolas, Marc; Farré, Daniel; Aguinaga, David; Mallol, Josefa; Cortés, Antoni; Casadó, Vicent; Lluís, Carmen; Ferre, Sergi

    2013-01-01

    Under normal conditions the brain maintains a delicate balance between inputs of reward seeking controlled by neurons containing the D1-like family of dopamine receptors and inputs of aversion coming from neurons containing the D2-like family of dopamine receptors. Cocaine is able to subvert these balanced inputs by altering the cell signaling of these two pathways such that D1 reward seeking pathway dominates. Here, we provide an explanation at the cellular and biochemical level how cocaine may achieve this. Exploring the effect of cocaine on dopamine D2 receptors function, we present evidence of σ1 receptor molecular and functional interaction with dopamine D2 receptors. Using biophysical, biochemical, and cell biology approaches, we discovered that D2 receptors (the long isoform of the D2 receptor) can complex with σ1 receptors, a result that is specific to D2 receptors, as D3 and D4 receptors did not form heteromers. We demonstrate that the σ1-D2 receptor heteromers consist of higher order oligomers, are found in mouse striatum and that cocaine, by binding to σ1 -D2 receptor heteromers, inhibits downstream signaling in both cultured cells and in mouse striatum. In contrast, in striatum from σ1 knockout animals these complexes are not found and this inhibition is not seen. Taken together, these data illuminate the mechanism by which the initial exposure to cocaine can inhibit signaling via D2 receptor containing neurons, destabilizing the delicate signaling balance influencing drug seeking that emanates from the D1 and D2 receptor containing neurons in the brain. PMID:23637801

  18. Short- and long-term cognitive effects of chronic cannabinoids administration in late-adolescence rats.

    Directory of Open Access Journals (Sweden)

    Hila Abush

    Full Text Available The use of cannabis can impair cognitive function, especially short-term memory. A controversial question is whether long-term cannabis use during the late-adolescence period can cause irreversible deficits in higher brain function that persist after drug use stops. In order to examine the short- and long-term effects of chronic exposure to cannabinoids, rats were administered chronic i.p. treatment with the CB1/CB2 receptor agonist WIN55,212-2 (WIN; 1.2 mg/kg for two weeks during the late adolescence period (post-natal days 45-60 and tested for behavioral and electrophysiological measures of cognitive performance 24 hrs, 10 and 30 days after the last drug injection. The impairing effects of chronic WIN on short-term memory in the water maze and the object recognition tasks as well as long-term potentiation (LTP in the ventral subiculum (vSub-nucleus accumbens (NAc pathway were temporary as they lasted only 24 h or 10 d after withdrawal. However, chronic WIN significantly impaired hippocampal dependent short-term memory measured in the object location task 24 hrs, 10, 30, and 75 days after the last drug injection. Our findings suggest that some forms of hippocampal-dependent short-term memory are sensitive to chronic cannabinoid administration but other cognitive impairments are temporary and probably result from a residue of cannabinoids in the brain or acute withdrawal effects from cannabinoids. Understanding the effects of cannabinoids on cognitive function may provide us with tools to overcome these impairments and for cannabinoids to be more favorably considered for clinical use.

  19. Epilepsy, E/I balance and GABAA receptor plasticity

    Directory of Open Access Journals (Sweden)

    Jean-Marc Fritschy

    2008-03-01

    Full Text Available GABAA receptors mediate most of the fast inhibitory transmission in the CNS. They form heteromeric complexes assembled from a large family of subunit genes. The existence of multiple GABAA receptor subtypes differing in subunit composition, localization and functional properties underlies their role for fi ne-tuning of neuronal circuits and genesis of network oscillations. The differential regulation of GABAA receptor subtypes represents a major facet of homeostatic synaptic plasticity and contributes to the excitation/inhibition (E/I balance under physiological conditions and upon pathological challenges. The purpose of this review is to discuss recent fi ndings highlighting the signifi cance of GABAA receptor heterogeneity for the concept of E/I balance and its relevance for epilepsy. Specifi cally, we address the following issues: (1 role for tonic inhibition, mediated by extrasynaptic GABAA receptors, for controlling neuronal excitability; (2 signifi cance of chloride ion transport for maintenance of the E/I balance in adult brain; and (3 molecular mechanisms underlying GABAA receptor regulation (traffi cking, posttranslational modifi cation, gene transcription that are important for homoeostatic plasticity. Finally, the relevance of these fi ndings is discussed in light of the involvement of GABAA receptors in epileptic disorders, based on recent experimental studies of temporal lobe epilepsy (TLE and absence seizures and on the identifi cation of mutations in GABAA receptor subunit genes underlying familial forms of epilepsy.

  20. Reconstruction of the Chemotaxis Receptor-Kinase Assembly

    International Nuclear Information System (INIS)

    Park, S.; Borbat, P.; Gonzalez-Bonet, G.; Bhatnagar, J.; Pollard, A.; Freed, J.; Bilwes, A.; Crane, B.

    2006-01-01

    In bacterial chemotaxis, an assembly of transmembrane receptors, the CheA histidine kinase and the adaptor protein CheW processes environmental stimuli to regulate motility. The structure of a Thermotoga maritima receptor cytoplasmic domain defines CheA interaction regions and metal ion-coordinating charge centers that undergo chemical modification to tune receptor response. Dimeric CheA-CheW, defined by crystallography and pulsed ESR, positions two CheWs to form a cleft that is lined with residues important for receptor interactions and sized to clamp one receptor dimer. CheW residues involved in kinase activation map to interfaces that orient the CheW clamps. CheA regulatory domains associate in crystals through conserved hydrophobic surfaces. Such CheA self-contacts align the CheW receptor clamps for binding receptor tips. Linking layers of ternary complexes with close-packed receptors generates a lattice with reasonable component ratios, cooperative interactions among receptors and accessible sites for modification enzymes

  1. Simultaneous Activation of Induced Heterodimerization between CXCR4 Chemokine Receptor and Cannabinoid Receptor 2 (CB2) Reveals a Mechanism for Regulation of Tumor Progression*

    Science.gov (United States)

    Coke, Christopher J.; Scarlett, Kisha A.; Chetram, Mahandranauth A.; Jones, Kia J.; Sandifer, Brittney J.; Davis, Ahriea S.; Marcus, Adam I.

    2016-01-01

    The G-protein-coupled chemokine receptor CXCR4 generates signals that lead to cell migration, cell proliferation, and other survival mechanisms that result in the metastatic spread of primary tumor cells to distal organs. Numerous studies have demonstrated that CXCR4 can form homodimers or can heterodimerize with other G-protein-coupled receptors to form receptor complexes that can amplify or decrease the signaling capacity of each individual receptor. Using biophysical and biochemical approaches, we found that CXCR4 can form an induced heterodimer with cannabinoid receptor 2 (CB2) in human breast and prostate cancer cells. Simultaneous, agonist-dependent activation of CXCR4 and CB2 resulted in reduced CXCR4-mediated expression of phosphorylated ERK1/2 and ultimately reduced cancer cell functions such as calcium mobilization and cellular chemotaxis. Given that treatment with cannabinoids has been shown to reduce invasiveness of cancer cells as well as CXCR4-mediated migration of immune cells, it is plausible that CXCR4 signaling can be silenced through a physical heterodimeric association with CB2, thereby inhibiting subsequent functions of CXCR4. Taken together, the data illustrate a mechanism by which the cannabinoid system can negatively modulate CXCR4 receptor function and perhaps tumor progression. PMID:26841863

  2. Radiolabelled GLP-1 receptor antagonist binds to GLP-1 receptor-expressing human tissues

    International Nuclear Information System (INIS)

    Waser, Beatrice; Reubi, Jean Claude

    2014-01-01

    Radiolabelled glucagon-like peptide 1 (GLP-1) receptor agonists have recently been shown to successfully image benign insulinomas in patients. For the somatostatin receptor targeting of tumours, however, it was recently reported that antagonist tracers were superior to agonist tracers. The present study therefore evaluated various forms of the 125 iodinated-Bolton-Hunter (BH)-exendin(9-39) antagonist tracer for the in vitro visualization of GLP-1 receptor-expressing tissues in rats and humans and compared it with the agonist tracer 125 I-GLP-1(7-36)amide. Receptor autoradiography studies with 125 I-GLP-1(7-36)amide agonist or 125 I-BH-exendin(9-39) antagonist radioligands were performed in human and rat tissues. The antagonist 125 I-BH-exendin(9-39) labelled at lysine 19 identifies all human and rat GLP-1 target tissues and GLP-1 receptor-expressing tumours. Binding is of high affinity and is comparable in all tested tissues in its binding properties with the agonist tracer 125 I-GLP-1(7-36)amide. For comparison, 125 I-BH-exendin(9-39) with the BH labelled at lysine 4 did identify the GLP-1 receptor in rat tissues but not in human tissues. The GLP-1 receptor antagonist exendin(9-39) labelled with 125 I-BH at lysine 19 is an excellent GLP-1 radioligand that identifies human and rat GLP-1 receptors in normal and tumoural tissues. It may therefore be the molecular basis to develop suitable GLP-1 receptor antagonist radioligands for in vivo imaging of GLP-1 receptor-expressing tissues in patients. (orig.)

  3. The Relationship of Erythropoietin Receptor Expression and ...

    African Journals Online (AJOL)

    2018-04-04

    Apr 4, 2018 ... brain tumor characterized with poor prognosis and short survival. In addition to the standard treatment protocols, targeted molecular treatment options are under trial. In the recent trials, erythropoietin and erythropoietin receptor were found to be linked with the progression of GBM cells. Aim: In this study, we.

  4. Short-lived positron emitter labeled radiotracers - present status

    International Nuclear Information System (INIS)

    Fowler, J.S.; Wolf, A.P.

    1982-01-01

    The preparation of labelled compounds is important for the application of positron emission transaxial tomography (PETT) in biomedical sciences. This paper describes problems and progress in the synthesis of short-lived positron emitter ( 11 C, 18 F, 13 N) labelled tracers for PETT. Synthesis of labelled sugars, amino acids, and neurotransmitter receptors (pimozide and spiroperidol tagged with 11 C) is discussed in particular

  5. Structural validity of a 16-item abridged version of the Cervantes Health-Related Quality of Life scale for menopause: the Cervantes Short-Form Scale.

    Science.gov (United States)

    Coronado, Pluvio J; Borrego, Rafael Sánchez; Palacios, Santiago; Ruiz, Miguel A; Rejas, Javier

    2015-03-01

    The Cervantes Scale is a specific health-related quality of life questionnaire that was originally developed in Spanish to be used in Spain for women through and beyond menopause. It contains 31 items and is time-consuming. The aim of this study was to produce an abridged version with the same dimensional structure and with similar psychometric properties. A representative sample of 516 postmenopausal women (mean [SD] age, 57 [4.31] y) seen in outpatient gynecology clinics and extracted from an observational cross-sectional study was used. Item analysis, internal consistency reliability, item-total and item-dimension correlations, and item correlation with the 12-item Medical Outcomes Study Short Form Health Survey Version 2.0 were studied. Dimensional and full-model confirmatory factor analyses were used to check structure stability. A threefold cross-validation method was used to obtain stable estimates by means of multigroup analysis. The scale was reduced to a 16-item version, the Cervantes Short-Form Scale, containing four main dimensions (Menopause and Health, Psychological, Sexuality, and Couple Relations), with the first dimension composed of three subdimensions (Vasomotor Symptoms, Health, and Aging). Goodness-of-fit statistics were better than those of the extended version (χ(2)/df = 2.493; adjusted goodness-of-fit index, 0.802; parsimony comparative fit index, 0.749; root mean standard error of approximation, 0.054). Internal consistency was good (Cronbach's α = 0.880). Correlations between the extended and the reduced dimensions were high and significant in all cases (P < 0.001; r values ranged from 0.90 for Sexuality to 0.969 for Vasomotor Symptoms). The Cervantes Scale can be reduced to a 16-item abridged version (Cervantes Short-Form Scale) that maintains the original dimensional structure and psychometric properties. At 51% of the original length, this version can be administered faster, making it especially suitable for routine medical practice.

  6. Development and validation of the short-form Adolescent Health Promotion Scale.

    Science.gov (United States)

    Chen, Mei-Yen; Lai, Li-Ju; Chen, Hsiu-Chih; Gaete, Jorge

    2014-10-26

    Health-promoting lifestyle choices of adolescents are closely related to current and subsequent health status. However, parsimonious yet reliable and valid screening tools are scarce. The original 40-item adolescent health promotion (AHP) scale was developed by our research team and has been applied to measure adolescent health-promoting behaviors worldwide. The aim of our study was to examine the psychometric properties of a newly developed short-form version of the AHP (AHP-SF) including tests of its reliability and validity. The study was conducted in nine middle and high schools in southern Taiwan. Participants were 814 adolescents randomly divided into two subgroups with equal size and homogeneity of baseline characteristics. The first subsample (calibration sample) was used to modify and shorten the factorial model while the second subsample (validation sample) was utilized to validate the result obtained from the first one. The psychometric testing of the AHP-SF included internal reliability of McDonald's omega and Cronbach's alpha, convergent validity, discriminant validity, and construct validity with confirmatory factor analysis (CFA). The results of the CFA supported a six-factor model and 21 items were retained in the AHP-SF with acceptable model fit. For the discriminant validity test, results indicated that adolescents with lower AHP-SF scores were more likely to be overweight or obese, skip breakfast, and spend more time watching TV and playing computer games. The AHP-SF also showed excellent internal consistency with a McDonald's omega of 0.904 (Cronbach's alpha 0.905) in the calibration group. The current findings suggest that the AHP-SF is a valid and reliable instrument for the evaluation of adolescent health-promoting behaviors. Primary health care providers and clinicians can use the AHP-SF to assess these behaviors and evaluate the outcome of health promotion programs in the adolescent population.

  7. Ghrelin receptor mutations--too little height and too much hunger

    DEFF Research Database (Denmark)

    Holst, Birgitte; Schwartz, Thue W

    2006-01-01

    The ghrelin receptor is known from in vitro studies to signal in the absence of the hormone ghrelin at almost 50% of its maximal capacity. But, as for many other 7-transmembrane receptors, the in vivo importance of this ligand-independent signaling has remained unclear. In this issue of the JCI......, Pantel et al. find that a natural mutation in the ghrelin receptor, Ala204Glu, which is associated with a selective loss of constitutive activity without affecting ghrelin affinity, potency, or efficacy, segregates in 2 families with the development of short stature (see the related article beginning...... on page 760). By combination of the observations from this study with those related to the phenotype of subjects carrying another natural ghrelin receptor mutation, Phe279Leu, having identical molecular-pharmacological properties, it is proposed that selective lack of ghrelin receptor constitutive...

  8. [QOL questionnaire for pediatric patients with bronchial asthma and their parents or caregivers. Preparation and evaluation of the short form version 2008 (Gifu)].

    Science.gov (United States)

    Kondo, Naomi; Hirayama, Koichiro; Matsui, Eiko; Teramoto, Takahide; Kaneko, Hideo; Fukao, Toshiyuki; Orii, Kenji; Kawamoto, Minako; Funato, Michinori; Ohnishi, Hidenori; Kawamoto, Norio; Morita, Hideyuki; Kimura, Takeshi; Nada, Masatoshi; Tokumi, Tetsuji; Hori, Tomohiro; Watanabe, Rinko

    2008-08-01

    The QOL questionnaire version 2001 for pediatric patients with bronchial asthma and their parents or caregivers includes 15 questions for patients under the age of 4 years and 20 questions for patients over the age of 4 years. We have already reported that the QOL questionnaire version 2001 reflects reliability (including reproducibility), factorial validity, and changes in paroxysmal attacks of asthma. In this study, we revised the questionnaire for use in routine medical practice. In this study, based on the data of a previous report, the number of questions was reduced further and it was revised to the questionnaire the short form by integrated data. The revised version 2008 (Gifu) consisted of emotional burden, asthma attack, instability of symptoms and proper acceptance of asthma as a common factor, moreover 4 or more years old added load of exercise factor which consisted of two questions in each factor. This QOL short form questionnaire version 2008 (Gifu) is a disease specific questionnaire in comparison with health control, bronchial asthma and non-asthmatic patients, such as atopic dermatitis and allergic rhinitis. Although Cronbach's alpha fell with reduction of the number of questions, we conclude that it was acceptable in the clinical practice.

  9. Time perspective in hereditary cancer: psychometric properties of a short form of the Zimbardo Time Perspective Inventory in a community and clinical sample.

    Science.gov (United States)

    Wakefield, Claire E; Homewood, Judi; Taylor, Alan; Mahmut, Mehmet; Meiser, Bettina

    2010-10-01

    We aimed to assess the psychometric properties of a 25-item short form of the Zimbardo Time Perspective Inventory in a community sample (N = 276) and in individuals with a strong family history of cancer, considering genetic testing for cancer risk (N = 338). In the community sample, individuals with high past-negative or present-fatalistic scores had higher levels of distress, as measured by depression, anxiety, and aggression. Similarly, in the patient sample, past-negative time perspective was positively correlated with distress, uncertainty, and postdecision regret when making a decision about genetic testing. Past-negative-oriented individuals were also more likely to be undecided about, or against, genetic testing. Hedonism was associated with being less likely to read the educational materials they received at their clinic, and fatalism was associated with having lower knowledge levels about genetic testing. The assessment of time perspective in individuals at increased risk of cancer can provide valuable clinical insights. However, further investigation of the psychometric properties of the short form of this scale is warranted, as it did not meet the currently accepted criteria for psychometric validation studies.

  10. The role of GluN2B-containing NMDA receptors in short- and long-term fear recall.

    Science.gov (United States)

    Mikics, Eva; Toth, Mate; Biro, Laszlo; Bruzsik, Biborka; Nagy, Boglarka; Haller, Jozsef

    2017-08-01

    N-methyl-d-aspartate (NMDA) receptors are crucial synaptic elements in long-term memory formation, including the associative learning of fearful events. Although NMDA blockers were consistently shown to inhibit fear memory acquisition and recall, the clinical use of general NMDA blockers is hampered by their side effects. Recent studies revealed significant heterogeneity in the distribution and neurophysiological characteristics of NMDA receptors with different GluN2 (NR2) subunit composition, which may have differential role in fear learning and recall. To investigate the specific role of NMDA receptor subpopulations with different GluN2 subunit compositions in the formation of lasting traumatic memories, we contrasted the effects of general NMDA receptor blockade with GluN2A-, GluN2B-, and GluN2C/D subunit selective antagonists (MK-801, PEAQX, Ro25-6981, PPDA, respectively). To investigate acute and lasting consequences, behavioral responses were investigated 1 and 28days after fear conditioning. We found that MK-801 (0.05 and 0.1mg/kg) decreased fear recall at both time points. GluN2B receptor subunit blockade produced highly similar effects, albeit efficacy was somewhat smaller 28days after fear conditioning. Unlike MK-801, Ro25-6981 (3 and 10mg/kg) did not affect locomotor activity in the open-field. In contrast, GluN2A and GluN2C/D blockers (6 and 20mg/kg PEAQX; 3 and 10mg/kg PPDA, respectively) had no effect on conditioned fear recall at any time point and dose. This sharp contrast between GluN2B- and other subunit-containing NMDA receptor function indicates that GluN2B receptor subunits are intimately involved in fear memory formation, and may provide a novel pharmacological target in post-traumatic stress disorder or other fear-related disorders. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Structure and assembly mechanism for heteromeric kainate receptors.

    Science.gov (United States)

    Kumar, Janesh; Schuck, Peter; Mayer, Mark L

    2011-07-28

    Native glutamate receptor ion channels are tetrameric assemblies containing two or more different subunits. NMDA receptors are obligate heteromers formed by coassembly of two or three divergent gene families. While some AMPA and kainate receptors can form functional homomeric ion channels, the KA1 and KA2 subunits are obligate heteromers which function only in combination with GluR5-7. The mechanisms controlling glutamate receptor assembly involve an initial step in which the amino terminal domains (ATD) assemble as dimers. Here, we establish by sedimentation velocity that the ATDs of GluR6 and KA2 coassemble as a heterodimer of K(d) 11 nM, 32,000-fold lower than the K(d) for homodimer formation by KA2; we solve crystal structures for the GluR6/KA2 ATD heterodimer and heterotetramer assemblies. Using these structures as a guide, we perform a mutant cycle analysis to probe the energetics of assembly and show that high-affinity ATD interactions are required for biosynthesis of functional heteromeric receptors. Copyright © 2011 Elsevier Inc. All rights reserved.

  12. Facial morphometry of Ecuadorian patients with growth hormone receptor deficiency/Laron syndrome.

    Science.gov (United States)

    Schaefer, G B; Rosenbloom, A L; Guevara-Aguirre, J; Campbell, E A; Ullrich, F; Patil, K; Frias, J L

    1994-01-01

    Facial morphometry using computerised image analysis was performed on patients with growth hormone receptor deficiency (Laron syndrome) from an inbred population of southern Ecuador. Morphometrics were compared for 49 patients, 70 unaffected relatives, and 14 unrelated persons. Patients with growth hormone receptor deficiency showed significant decreases in measures of vertical facial growth as compared to unaffected relatives and unrelated persons with short stature from other causes. This report validates and quantifies the clinical impression of foreshortened facies in growth hormone receptor deficiency. Images PMID:7815422

  13. Receptor binding studies of the living heart

    International Nuclear Information System (INIS)

    Syrota, A.

    1988-01-01

    Receptors form a class of intrinsic membrane proteins (or glycoproteins) defined by the high affinity and specificity with which they bind ligands. Many receptors are associated directly or indirectly with membrane ion channels that open or close after a conformational change of the receptor induced by the binding of the neurotransmitter. Changes in number and/or affinity of cardiac neurotransmitter receptors have been associated with myocardial ischemia and infarction, congestive heart failure, and cardiomyopathy as well as diabetes or thyroid-induced heart muscle disease. These alterations of cardiac receptors have been demonstrated in vitro on membrane homogenates from samples collected mainly during surgery or postmortem. The disadvantage of these in vitro binding techniques is that receptors lose their natural environment and their relationships with the other components of the tissue

  14. Sulfhydryl group content of chicken progesterone receptor: effect of oxidation on DNA binding activity

    International Nuclear Information System (INIS)

    Peleg, S.; Schrader, W.T.; O'Malley, B.W.

    1988-01-01

    DNA binding activity of chicken progesterone receptor B form (PRB) and A form (PRA) has been examined. This activity is strongly dependent upon the presence of thiols in the buffer. Stability studies showed that PRB was more sensitive to oxidation that was PRA. Receptor preparations were fractionated by DNA-cellulose chromatography to DNA-positive and DNA-negative subpopulations, and sulfhydryl groups were quantified on immunopurified receptor by labeling with [ 3 H]-N-ethylmaleimide. Labeling of DNA-negative receptors with [ 3 H]-N-ethylmaleimide showed 21-23 sulfhydryl groups on either PRA or PRB form when the proteins were reduced and denatured. A similar number was seen without reduction if denatured DNA-positive receptor species were tested. In contrast, the DNA-negative PRB had only 10-12 sulfhydryl groups detectable without reduction. A similar number (12-13 sulfhydryl groups) was found for PRA species that lost DNA binding activity after exposure to a nonreducing environment in vitro. The authors conclude that the naturally occurring receptor forms unable to bind to DNA, as well as receptor forms that have lost DNA binding activity due to exposure to nonreducing environment in vitro, contain 10-12 oxidized cysteine residues, likely present as disulfide bonds. Since they were unable to reduce the disulfide bonds when the native DNA-negative receptor proteins were treated with dithiothreitol (DTT), they speculate that irreversible loss of DNA binding activity of receptor in vitro is due to oxidation of cysteine residues that are not accessible to DTT in the native state

  15. Dim light at night disrupts the short-day response in Siberian hamsters.

    Science.gov (United States)

    Ikeno, Tomoko; Weil, Zachary M; Nelson, Randy J

    2014-02-01

    Photoperiodic regulation of physiology, morphology, and behavior is crucial for many animals to survive seasonally variable conditions unfavorable for reproduction and survival. The photoperiodic response in mammals is mediated by nocturnal secretion of melatonin under the control of a circadian clock. However, artificial light at night caused by recent urbanization may disrupt the circadian clock, as well as the photoperiodic response by blunting melatonin secretion. Here we examined the effect of dim light at night (dLAN) (5lux of light during the dark phase) on locomotor activity rhythms and short-day regulation of reproduction, body mass, pelage properties, and immune responses of male Siberian hamsters. Short-day animals reduced gonadal and body mass, decreased spermatid nuclei and sperm numbers, molted to a whiter pelage, and increased pelage density compared to long-day animals. However, animals that experienced short days with dLAN did not show these short-day responses. Moreover, short-day specific immune responses were altered in dLAN conditions. The nocturnal activity pattern was blunted in dLAN hamsters, consistent with the observation that dLAN changed expression of the circadian clock gene, Period1. In addition, we demonstrated that expression levels of genes implicated in the photoperiodic response, Mel-1a melatonin receptor, Eyes absent 3, thyroid stimulating hormone receptor, gonadotropin-releasing hormone, and gonadotropin-inhibitory hormone, were higher in dLAN animals than those in short-day animals. These results suggest that dLAN disturbs the circadian clock function and affects the molecular mechanisms of the photoperiodic response. Copyright © 2013 Elsevier Inc. All rights reserved.

  16. Endometrial changes from short-term therapy with CDB-4124, a selective progesterone receptor modulator.

    Science.gov (United States)

    Ioffe, Olga B; Zaino, Richard J; Mutter, George L

    2009-03-01

    Selective progesterone receptor modulators are a class of drugs with progesterone antagonist activity that may confer therapeutic benefit for reproductive disorders in premenopausal women. Endometrial structure, which is dynamically controlled by circulating sex hormones, is likely to be perturbed by progesterone receptor modulators through their progesterone antagonist properties. We examined endometrial histology in 58 premenopausal women treated with the progesterone receptor modulator CDB-4124 (also known as Proellex) for endometriosis or uterine leiomyomata in two clinical trials. Endometrial biopsies obtained after 3 or 6 months with doses of 12.5, 25, or 50 mg daily oral CDB-4124 were reviewed independently by three pathologists. Consensus diagnoses using the World Health Organization hyperplasia scoring system, comments on specific histologic features, and clinical annotation were collected and analyzed. The majority of the endometrial biopsies (103 of 174 biopsies) contained histologic changes that are not seen during normal menstrual cycles. The histology of CDB-4124-treated patients was generally inactive or atrophic, and less frequently, proliferative or secretory, superimposed upon which were novel changes including formation of cystically dilated glands, and secretory changes coexisting with mitoses and apoptotic bodies. With increasing treatment dose and duration, the cysts became predominant and their lining inactive or atrophic. Cystic glands in the CDB-4124-treated subjects correlated with increased endometrial thickness by ultrasound. None of the CDB-4124-treated patients developed endometrial carcinoma or hyperplasia while on therapy. CDB-4124 therapy for 3-6 months produces histologic changes that are sufficiently novel that they might easily be misinterpreted by pathologists, particularly as disordered proliferative or hyperplastic endometrium. Knowledge of the constellation of endometrial changes associated with this agent and other

  17. Short latency compound action potentials from mammalian gravity receptor organs

    Science.gov (United States)

    Jones, T. A.; Jones, S. M.

    1999-01-01

    Gravity receptor function was characterized in four mammalian species using far-field vestibular evoked potentials (VsEPs). VsEPs are compound action potentials of the vestibular nerve and central relays that are elicited by linear acceleration ramps applied to the cranium. Rats, mice, guinea pigs, and gerbils were studied. In all species, response onset occurred within 1.5 ms of the stimulus onset. Responses persisted during intense (116 dBSPL) wide-band (50 to 50 inverted question mark omitted inverted question mark000 Hz) forward masking, whereas auditory responses to intense clicks (112 dBpeSPL) were eliminated under the same conditions. VsEPs remained after cochlear extirpation but were eliminated following bilateral labyrinthectomy. Responses included a series of positive and negative peaks that occurred within 8 ms of stimulus onset (range of means at +6 dBre: 1.0 g/ms: P1=908 to 1062 micros, N1=1342 to 1475 micros, P2=1632 to 1952 micros, N2=2038 to 2387 micros). Mean response amplitudes at +6 dBre: 1.0 g/ms ranged from 0.14 to 0.99 microV. VsEP input/output functions revealed latency slopes that varied across peaks and species ranging from -19 to -51 micros/dB. Amplitude-intensity slopes also varied ranging from 0.04 to 0.08 microV/dB for rats and mice. Latency values were comparable to those of birds although amplitudes were substantially smaller in mammals. VsEP threshold values were considerably higher in mammals compared to birds and ranged from -8.1 to -10.5 dBre 1.0 g/ms across species. These results support the hypothesis that mammalian gravity receptors are less sensitive to dynamic stimuli than are those of birds.

  18. Construction of a short form of the healthy eating behaviour inventory for the Japanese population.

    Science.gov (United States)

    Shimazaki, Takashi; Iio, Misa; Lee, Ying-Hua; Suzuki, Akiko; Konuma, Kayo; Teshima, Yoko; Takenaka, Koji

    2016-09-01

    The present study constructed a short form of the Healthy Eating Behavior Inventory suitable for use in the Japanese culture (HEBI-J) and confirmed the scale's preliminary reliability and validity. In Study 1, Japanese adults (N=75) completed a free-response questionnaire about healthy eating behaviours. Thematic analysis was used to identify three factors-balance, pattern, and restriction-associated with healthy eating behaviours and 12 items related to these healthy eating behaviours. In Study 2, Japanese office workers (N=784) completed two questionnaires regarding 12 items of healthy eating behaviours and the dietary stages of change. Confirmatory factor analysis demonstrated that the three-factor model was appropriate (GFI=.94, AGFI=.90, CFI=.90, RMSEA=.08, SRMR=.53). Reliability was confirmed by alpha coefficients and the Spearman-Brown formula. Concurrent validity was confirmed by the relationship between the healthy eating stages. This study demonstrated the preliminary reliability and validity of the HEBI-J. Copyright © 2015 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.

  19. Serotonin mediation of early memory formation via 5HT2B receptor-induced glycogenolysis in the day-old chick

    Directory of Open Access Journals (Sweden)

    Marie Elizabeth Gibbs

    2014-04-01

    Full Text Available Investigation of the effects of serotonin on memory formation in the chick revealed an action on at least two 5HT receptors. Serotonin injected intracerebrally produced a biphasic effect on memory consolidation with enhancement at low doses and inhibition at higher doses. The non-selective 5HT receptor antagonist methiothepin and the selective 5HT2B/C receptor antagonist SB221284 both inhibited memory, suggesting actions of serotonin on at least 2 different receptor subtypes. The 5HT2B/C and astrocyte-specific 5-HT receptor agonists, fluoxetine and paroxetine, enhanced memory and the effect was attributed to glycogenolysis. Inhibition of glycogenolysis with a low dose of DAB prevented both serotonin and fluoxetine from enhancing memory during short-term memory but not during intermediate memory. The role of serotonin on the 5HT2B/C receptor appears to involve glycogen breakdown in astrocytes during short-term memory, whereas other published evidence attributes the second period of glycogenolysis to noradrenaline.

  20. Radiolabelled GLP-1 receptor antagonist binds to GLP-1 receptor-expressing human tissues

    Energy Technology Data Exchange (ETDEWEB)

    Waser, Beatrice; Reubi, Jean Claude [University of Berne, Division of Cell Biology and Experimental Cancer Research, Institute of Pathology, PO Box 62, Berne (Switzerland)

    2014-06-15

    Radiolabelled glucagon-like peptide 1 (GLP-1) receptor agonists have recently been shown to successfully image benign insulinomas in patients. For the somatostatin receptor targeting of tumours, however, it was recently reported that antagonist tracers were superior to agonist tracers. The present study therefore evaluated various forms of the {sup 125}iodinated-Bolton-Hunter (BH)-exendin(9-39) antagonist tracer for the in vitro visualization of GLP-1 receptor-expressing tissues in rats and humans and compared it with the agonist tracer {sup 125}I-GLP-1(7-36)amide. Receptor autoradiography studies with {sup 125}I-GLP-1(7-36)amide agonist or {sup 125}I-BH-exendin(9-39) antagonist radioligands were performed in human and rat tissues. The antagonist {sup 125}I-BH-exendin(9-39) labelled at lysine 19 identifies all human and rat GLP-1 target tissues and GLP-1 receptor-expressing tumours. Binding is of high affinity and is comparable in all tested tissues in its binding properties with the agonist tracer {sup 125}I-GLP-1(7-36)amide. For comparison, {sup 125}I-BH-exendin(9-39) with the BH labelled at lysine 4 did identify the GLP-1 receptor in rat tissues but not in human tissues. The GLP-1 receptor antagonist exendin(9-39) labelled with {sup 125}I-BH at lysine 19 is an excellent GLP-1 radioligand that identifies human and rat GLP-1 receptors in normal and tumoural tissues. It may therefore be the molecular basis to develop suitable GLP-1 receptor antagonist radioligands for in vivo imaging of GLP-1 receptor-expressing tissues in patients. (orig.)

  1. Psychometric properties of the Polish version of the Trait Emotional Intelligence Questionnaire-Short Form

    Directory of Open Access Journals (Sweden)

    Szczygieł Dorota

    2015-09-01

    Full Text Available The study was aimed at validating the Polish version of the Trait Emotional Intelligence Questionnaire-Short Form (TEIQue-SF. Our findings confirm the reliability and validity of the scale. With respect to reliability, internal consistency coefficients of the TEIQue-SF were comparable to those obtained using the original English version. The evidence of the validity of the TEIQue-SF came from the pattern of relations with the other self-report measure of EI, personality measures, as well as affective and social correlates. We demonstrated that the TEIQue-SF score correlated positively with scores on the Emotional Intelligence Questionnaire (INTE (Jaworowska & Matczak, 2001. The TEIQue- SF score correlated negatively with Neuroticism and positively with Extraversion, Openness, Agreeableness, and Conscientiousness. In addition, scores on the TEIQue-SF were related to dispositional affect, i.e., correlated positively with positive affectivity and negatively with negative affectivity. The TEIQue-SF score correlated positively with social competencies as measured with the Social Competencies Questionnaire (Matczak, 2001. We also found that trait EI, as measured with the TEIQue-SF, was positively related to the richness of one’s supportive social network and this relationship remained statistically significant even after controlling for Big Five variance. We also demonstrated that scoring on the TEIQue-SF was positively related to satisfaction with life and negatively related to perceived stress and these relationships remained significant, even after controlling for positive and negative affectivity. Taken together, these findings suggest that the Polish version of the TEIQue-SF is a reliable and valid measure that inherits the network of associations both from the original version of the TEIQue-SF and the full form of the Polish TEIQue (Wytykowska & Petrides, 2007.

  2. Ionotropic glutamate receptors mediate inducible defense in the water flea Daphnia pulex.

    Directory of Open Access Journals (Sweden)

    Hitoshi Miyakawa

    Full Text Available Phenotypic plasticity is the ability held in many organisms to produce different phenotypes with a given genome in response to environmental stimuli, such as temperature, nutrition and various biological interactions. It seems likely that environmental signals induce a variety of mechanistic responses that influence ontogenetic processes. Inducible defenses, in which prey animals alter their morphology, behavior and/or other traits to help protect against direct or latent predation threats, are among the most striking examples of phenotypic plasticity. The freshwater microcrustacean Daphnia pulex forms tooth-like defensive structures, "neckteeth," in response to chemical cues or signals, referred to as "kairomones," in this case released from phantom midge larvae, a predator of D. pulex. To identify factors involved in the reception and/or transmission of a kairomone, we used microarray analysis to identify genes up-regulated following a short period of exposure to the midge kairomone. In addition to identifying differentially expressed genes of unknown function, we also found significant up-regulation of genes encoding ionotropic glutamate receptors, which are known to be involved in neurotransmission in many animal species. Specific antagonists of these receptors strongly inhibit the formation of neckteeth in D. pulex, although agonists did not induce neckteeth by themselves, indicating that ionotropic glutamate receptors are necessary but not sufficient for early steps of neckteeth formation in D. pulex. Moreover, using co-exposure of D. pulex to antagonists and juvenile hormone (JH, which physiologically mediates neckteeth formation, we found evidence suggesting that the inhibitory effect of antagonists is not due to direct inhibition of JH synthesis/secretion. Our findings not only provide a candidate molecule required for the inducible defense response in D. pulex, but also will contribute to the understanding of complex mechanisms

  3. Reactivation of desensitized formyl peptide receptors by platelet activating factor: a novel receptor cross talk mechanism regulating neutrophil superoxide anion production.

    Directory of Open Access Journals (Sweden)

    Huamei Forsman

    Full Text Available Neutrophils express different chemoattractant receptors of importance for guiding the cells from the blood stream to sites of inflammation. These receptors communicate with one another, a cross talk manifested as hierarchical, heterologous receptor desensitization. We describe a new receptor cross talk mechanism, by which desensitized formyl peptide receptors (FPRdes can be reactivated. FPR desensitization is induced through binding of specific FPR agonists and is reached after a short period of active signaling. The mechanism that transfers the receptor to a non-signaling desensitized state is not known, and a signaling pathway has so far not been described, that transfers FPRdes back to an active signaling state. The reactivation signal was generated by PAF stimulation of its receptor (PAFR and the cross talk was uni-directional. LatrunculinA, an inhibitor of actin polymerization, induced a similar reactivation of FPRdes as PAF while the phosphatase inhibitor CalyculinA inhibited reactivation, suggesting a role for the actin cytoskeleton in receptor desensitization and reactivation. The activated PAFR could, however, reactivate FPRdes also when the cytoskeleton was disrupted prior to activation. The receptor cross talk model presented prophesies that the contact on the inner leaflet of the plasma membrane that blocks signaling between the G-protein and the FPR is not a point of no return; the receptor cross-talk from the PAFRs to the FPRdes initiates an actin-independent signaling pathway that turns desensitized receptors back to a signaling state. This represents a novel mechanism for amplification of neutrophil production of reactive oxygen species.

  4. Simultaneous Activation of Induced Heterodimerization between CXCR4 Chemokine Receptor and Cannabinoid Receptor 2 (CB2) Reveals a Mechanism for Regulation of Tumor Progression.

    Science.gov (United States)

    Coke, Christopher J; Scarlett, Kisha A; Chetram, Mahandranauth A; Jones, Kia J; Sandifer, Brittney J; Davis, Ahriea S; Marcus, Adam I; Hinton, Cimona V

    2016-05-06

    The G-protein-coupled chemokine receptor CXCR4 generates signals that lead to cell migration, cell proliferation, and other survival mechanisms that result in the metastatic spread of primary tumor cells to distal organs. Numerous studies have demonstrated that CXCR4 can form homodimers or can heterodimerize with other G-protein-coupled receptors to form receptor complexes that can amplify or decrease the signaling capacity of each individual receptor. Using biophysical and biochemical approaches, we found that CXCR4 can form an induced heterodimer with cannabinoid receptor 2 (CB2) in human breast and prostate cancer cells. Simultaneous, agonist-dependent activation of CXCR4 and CB2 resulted in reduced CXCR4-mediated expression of phosphorylated ERK1/2 and ultimately reduced cancer cell functions such as calcium mobilization and cellular chemotaxis. Given that treatment with cannabinoids has been shown to reduce invasiveness of cancer cells as well as CXCR4-mediated migration of immune cells, it is plausible that CXCR4 signaling can be silenced through a physical heterodimeric association with CB2, thereby inhibiting subsequent functions of CXCR4. Taken together, the data illustrate a mechanism by which the cannabinoid system can negatively modulate CXCR4 receptor function and perhaps tumor progression. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  5. Pathophysiological consequences of receptor mistraffic: Tales from the platelet P2Y12 receptor.

    Science.gov (United States)

    Cunningham, Margaret R; Aungraheeta, Riyaad; Mundell, Stuart J

    2017-07-05

    Genetic variations in G protein-coupled receptor (GPCR) genes can disrupt receptor function in a wide variety of human genetic diseases, including platelet bleeding disorders. Platelets are critical for haemostasis with inappropriate platelet activation leading to the development of arterial thrombosis, which can result in heart attack and stroke whilst decreased platelet activity is associated with an increased risk of bleeding. GPCRs expressed on the surface of platelets play key roles in regulating platelet activity and therefore function. Receptors include purinergic receptors (P2Y 1 and P2Y 12 ), proteinase-activated receptor (PAR1 and PAR4) and thromboxane receptors (TPα), among others. Pharmacological blockade of these receptors forms a powerful therapeutic tool in the treatment and prevention of arterial thrombosis. With the advance of genomic technologies, there has been a substantial increase in the identification of naturally occurring rare and common GPCR variants. These variants include single-nucleotide polymorphisms (SNPs) and insertion or deletions that have the potential to alter GPCR expression or function. A number of defects in platelet GPCRs that disrupt receptor function have now been characterized in patients with mild bleeding disorders. This review will focus on rare, function-disrupting variants of platelet GPCRs with particular emphasis upon mutations in the P2Y 12 receptor gene that affect receptor traffic to modulate platelet function. Further this review will outline how the identification and characterization of function-disrupting GPCR mutations provides an essential link in translating our detailed understanding of receptor traffic and function in cell line studies into relevant human biological systems. Copyright © 2017. Published by Elsevier B.V.

  6. Assessment of Physical Self-Concept in Adolescents with Intellectual Disability: Content and Factor Validity of the Very Short Form of the Physical Self-Inventory

    Science.gov (United States)

    Maiano, Christophe; Begarie, Jerome; Morin, Alexandre J. S.; Ninot, Gregory

    2009-01-01

    The purpose of this study was to test the factor validity and reliability of the Very Short Form of the Physical Self-Inventory- (PSI-VSF) within a sample of adolescents with mild to moderate Intellectual Disability (ID). A total of 362 ID adolescents were involved in two studies. In Study 1, the content and format scale response of the PSI-VSF…

  7. Molecular analysis of the nerve growth factor receptor

    International Nuclear Information System (INIS)

    Hempstead, B.; Patil, N.; Olson, K.; Chao, M.

    1988-01-01

    An essential molecule in the translocation of information by nerve growth factor (NGF) to responsive cells is the cell-surface receptor for NGF. This paper presents information on the genomic structure of the NGF receptor gene, NGF receptor models, and transfection of NGF receptors. Equilibrium binding of [ 125 I]NGF to cells reveals two distinct affinity states for the NGF receptor. The human NGF receptor gene is a single-copy gene, consisting of six exons that span 23 kb. The receptor gene is capable of being transferred to fibroblast cells from human genomic DNA and expressed at high levels. The constitutive nature of the receptor promoter sequence is a partial explanation of why this tissue-specific gene is expressed efficiently in a variety of nonneuronal cells after genomic gene transfer. The two kinetic forms of the NGF receptor appear to be encoded by the same protein, which is the product of a single gene

  8. How may short-duration GRBs form? A review of progenitor theories.

    Czech Academy of Sciences Publication Activity Database

    Szécsi, Dorottya

    2017-01-01

    Roč. 47, č. 2 (2017), s. 108-115 ISSN 1335-1842. [INTEGRAL/BART Workshop /14./. Karlovy Vary, 03.04.2017-07.04.2017] R&D Projects: GA ČR GA13-10589S Institutional support: RVO:67985815 Keywords : short GRB progenitor * TWUIN stars * chemically homogeneous evolution Subject RIV: BN - Astronomy, Celestial Mechanics, Astrophysics OBOR OECD: Astronomy (including astrophysics,space science) Impact factor: 0.336, year: 2016

  9. Structure of short-range-ordered iron(III)-precipitates formed by iron(II) oxidation in water containing phosphate, silicate, and calcium

    Science.gov (United States)

    Voegelin, A.; Frommer, J.; Vantelon, D.; Kaegi, R.; Hug, S. J.

    2009-04-01

    The oxidation of Fe(II) in water leads to the formation of Fe(III)-precipitates that strongly affect the fate of nutrients and contaminants in natural and engineered systems. Examples include the cycling of As in rice fields irrigated with As-rich groundwater or the treatment of drinking water for As removal. Knowledge of the types of Fe(III)-precipitates forming in such systems is essential for the quantitative modeling of nutrient and contaminant dynamics and for the optimization of water purification techniques on the basis of a mechanistic understanding of the relevant biogeochemical processes. In this study, we investigated the local coordination of Fe, P, and Ca in Fe(III)-precipitates formed by aeration of synthetic Fe(II)-containing groundwater with variable composition (pH 7, 2-30 mg/L Fe(II), 2-20 mg/L phosphate-P, 2-20 mg/L silicate-Si, 8 mM Na-bicarbonate or 2.5 mM Ca-&1.5 mM Mg-bicarbonate). After 4 hours of oxidation, Fe(III)-precipitates were collected on 0.2 µm nylon filters and dried. The precipitates were analyzed by Fe K-edge EXAFS (XAS beamline, ANKA, Germany) and by P and Ca K-edge XANES spectroscopy (LUCIA beamline, SLS, Switzerland). The Fe K-edge EXAFS spectra indicated that local Fe coordination in the precipitates systematically shifted with water composition. As long as water contained P, mainly short-range-ordered Fe(III)-phosphate formed (with molar P/Fe ~0.5). In the absence of P, Fe(III) precipitated as hydrous ferric oxide at high Si/Fe>0.5, as ferrihydrite at intermediate Si/Fe, and mainly as lepidocrocite at Si/Fe<0.2. Analysis of the EXAFS by shell-fitting indicated that Fe(III)-phosphates mainly contained mono- or oligomeric (edge- or corner-sharing) Fe and that the linkage between neighboring Fe(III)-octahedra changed from predominantly edge-sharing in Si-rich hydrous ferric oxide to edge- and corner-sharing in ferrihydrite. Electron microscopic data showed that changes in local precipitate structure were systematically

  10. Magnetic short range order in Gd

    International Nuclear Information System (INIS)

    Child, H.R.

    1976-01-01

    Quasielastic neutron scattering has been used to investigate magnetic short range order in Gd for 80 0 K 0 K. Short range order exists throughout this range from well below T/sub C/ = 291 0 K to well above it and can be reasonably well described by an anisotropic Orstein-Zernike form for chi

  11. Prediction and analysis of near-road concentrations using a reduced-form emission/dispersion model

    Directory of Open Access Journals (Sweden)

    Kononowech Robert

    2010-06-01

    Full Text Available Abstract Background Near-road exposures of traffic-related air pollutants have been receiving increased attention due to evidence linking emissions from high-traffic roadways to adverse health outcomes. To date, most epidemiological and risk analyses have utilized simple but crude exposure indicators, most typically proximity measures, such as the distance between freeways and residences, to represent air quality impacts from traffic. This paper derives and analyzes a simplified microscale simulation model designed to predict short- (hourly to long-term (annual average pollutant concentrations near roads. Sensitivity analyses and case studies are used to highlight issues in predicting near-road exposures. Methods Process-based simulation models using a computationally efficient reduced-form response surface structure and a minimum number of inputs integrate the major determinants of air pollution exposures: traffic volume and vehicle emissions, meteorology, and receptor location. We identify the most influential variables and then derive a set of multiplicative submodels that match predictions from "parent" models MOBILE6.2 and CALINE4. The assembled model is applied to two case studies in the Detroit, Michigan area. The first predicts carbon monoxide (CO concentrations at a monitoring site near a freeway. The second predicts CO and PM2.5 concentrations in a dense receptor grid over a 1 km2 area around the intersection of two major roads. We analyze the spatial and temporal patterns of pollutant concentration predictions. Results Predicted CO concentrations showed reasonable agreement with annual average and 24-hour measurements, e.g., 59% of the 24-hr predictions were within a factor of two of observations in the warmer months when CO emissions are more consistent. The highest concentrations of both CO and PM2.5 were predicted to occur near intersections and downwind of major roads during periods of unfavorable meteorology (e.g., low wind

  12. Analysis of Circulating Vascular Endothelial Growth Factor and Its Soluble Receptors in Patients with Different Forms of Chronic Urticaria

    Directory of Open Access Journals (Sweden)

    Julia Jagodzinska

    2015-01-01

    Full Text Available Background. Vascular endothelial growth factor (VEGF is a powerful enhancer of vascular permeability and inflammatory response; however its significance in chronic urticaria is poorly recognised. Aim. To compare free circulating levels of VEGF and its soluble receptors (sVEGFR1 and VEGFR2 in patients with different forms of chronic urticaria. Methods. The concentrations of VEGF and its receptors in plateletpoor plasma (PPP/plasma were measured using enzyme-linked immunosorbent assay in chronic urticaria: (1 chronic spontaneous urticaria (CSU with positive autologous serum skin test (ASST, (2 CSU with negative response to ASST, (3 CSU with concomitant euthyroid Hashimoto’s thyroiditis (CSU/Hashimoto, (4 delayed pressure urticaria (DPU, and the healthy subjects. Results. There were no significant differences in VEGF concentration in PPP between CSU groups and the healthy subjects. Contrary, VEGF concentration was significantly higher in DPU and CSU/Hashimoto patients as compared with the healthy subjects and CSU groups. Furthermore, VEGF value in CSU/Hashimoto patients during the remission was similar to that of the active period and significantly higher than the healthy subjects; VEGF concentration was significantly correlated with TSH. Plasma concentrations of sVEGF1 and sVEGF2 were similar in chronic urticaria patients and the healthy subjects. Conclusions. Increased free circulating VEGF concentration may result from the urticarial process itself as well as concomitant Hashimoto’s thyroiditis.

  13. Evaluation of a modified version of the Posttraumatic Growth Inventory-Short Form

    Directory of Open Access Journals (Sweden)

    Navjot Kaur

    2017-04-01

    Full Text Available Abstract Background Posttraumatic growth is the positive change resulting from traumatic experiences and is typically assessed with retrospective measures like the Posttraumatic Growth Inventory (PTGI. The PTGI was designed to include reference to a specific traumatic event, making it difficult to implement, without change, in prospective survey studies. Thus, a modified Posttraumatic Growth Inventory–Short Form (PTGI-SF was included in a large prospective study of current and former U.S. military personnel. The current study provides preliminary psychometric data for this modified measure and its ability to assess psychological well-being at a single time point. Methods The study population (N = 135,843 was randomly and equally split into exploratory and confirmatory samples that were proportionately balanced on trauma criterion. Exploratory factor analysis and confirmatory factor analysis (CFA were performed to assess the psychometric validity of the modified measure. The final model was also assessed in a subset of the confirmatory sample with a history of trauma using CFA. Results Results supported a single-factor model with two additional correlations between items assessing spirituality and items assessing compassion/appreciation for others. This model also fits among the subset with a history of trauma. The resulting measure was strongly associated with social support and personal mastery. Conclusions The modified PTGI-SF in this study captures psychological well-being in cross-sectional assessments, in addition to being able to measure posttraumatic growth with multiple assessments. Results indicate that the modified measure is represented by a single factor, but that items assessing spirituality and compassion/appreciation for others may be used alone to better capture these constructs.

  14. Substrate coated with receptor and labelled ligand for assays

    International Nuclear Information System (INIS)

    1980-01-01

    Improvements in the procedures for assaying ligands are described. The assay consists of a polystyrene tube on which receptors are present for both the ligand to be assayed and a radioactively labelled form of the ligand. The receptors on the bottom portion of the tube are also coated with labelled ligands, thus eliminating the necessity for separate addition of the labelled ligand and sample during an assay. Examples of ligands to which this method is applicable include polypeptides, nucleotides, nucleosides and proteins. Specific examples are given in which the ligand to be assayed is digoxin, the labelled form of the ligand is 3-0-succinyl digoxyigenin tyrosine ( 125 I) and the receptor is digoxin antibody. (U.K.)

  15. Expression of Plant Receptor Kinases in Tobacco BY-2 Cells.

    Science.gov (United States)

    Shinohara, Hidefumi; Matsubayashi, Yoshikatsu

    2017-01-01

    Although more than 600 single-transmembrane receptor kinase genes have been found in the Arabidopsis genome, only a few of them have known physiological functions, and even fewer plant receptor kinases have known specific ligands. Ligand-binding analysis must be operated using the functionally expressed receptor form. However, the relative abundance of native receptor kinase molecules in the plasma membrane is often quite low. Here, we present a method for stable and functional expression of plant receptor kinases in tobacco BY-2 cells that allows preparation of microsomal fractions containing the receptor. This procedure provides a sufficient amount of receptor proteins while maintaining its ligand-binding activities.

  16. Family C 7TM receptor dimerization and activation

    DEFF Research Database (Denmark)

    Bonde, Marie Mi; Sheikh, Søren P; Hansen, Jakob Lerche

    2006-01-01

    The family C seven transmembrane (7TM) receptors constitutes a small and especially well characterized subfamily of the large 7TM receptor superfamily. Approximately 50% of current prescription drugs target 7TM receptors, this biologically important family represents the largest class of drug...... to be fully defined. This review presents the biochemical support for family C 7TM receptor dimerization and discusses its importance for receptor biosynthesis, surface expression, ligand binding and activation, since lessons learnt here may well be applicable to the whole superfamily of 7TM receptors.......-targets today. It is well established that family C 7TM receptors form homo- or hetero-dimers on the cell surface of living cells. The large extra-cellular domains (ECD) have been crystallized as a dimer in the presence and absence of agonist. Upon agonist binding, the dimeric ECD undergoes large conformational...

  17. Untangling dopamine-adenosine receptor-receptor assembly in experimental parkinsonism in rats

    Directory of Open Access Journals (Sweden)

    Víctor Fernández-Dueñas

    2015-01-01

    Full Text Available Parkinson’s disease (PD is a dopaminergic-related pathology in which functioning of the basal ganglia is altered. It has been postulated that a direct receptor-receptor interaction – i.e. of dopamine D2 receptor (D2R with adenosine A2A receptor (A2AR (forming D2R-A2AR oligomers – finely regulates this brain area. Accordingly, elucidating whether the pathology prompts changes to these complexes could provide valuable information for the design of new PD therapies. Here, we first resolved a long-standing question concerning whether D2R-A2AR assembly occurs in native tissue: by means of different complementary experimental approaches (i.e. immunoelectron microscopy, proximity ligation assay and TR-FRET, we unambiguously identified native D2R-A2AR oligomers in rat striatum. Subsequently, we determined that, under pathological conditions (i.e. in a rat PD model, D2R-A2AR interaction was impaired. Collectively, these results provide definitive evidence for alteration of native D2R-A2AR oligomers in experimental parkinsonism, thus conferring the rationale for appropriate oligomer-based PD treatments.

  18. GABAB receptor phosphorylation regulates KCTD12-induced K+ current desensitization

    DEFF Research Database (Denmark)

    Adelfinger, L; Turecek, R; Ivankova, K

    2014-01-01

    released from the G-protein. Receptor-activated K+ currents desensitize in the sustained presence of agonist to avoid excessive effects on neuronal activity. Desensitization of K+ currents integrates distinct mechanistic underpinnings. GABAB receptor activity reduces protein kinase-A activity, which...... reduces phosphorylation of serine-892 in GABAB2 and promotes receptor degradation. This form of desensitization operates on the time scale of several minutes to hours. A faster form of desensitization is induced by the auxiliary subunit KCTD12, which interferes with channel activation by binding to the G......-protein βγ subunits. Here we show that the two mechanisms of desensitization influence each other. Serine-892 phosphorylation in heterologous cells rearranges KCTD12 at the receptor and slows KCTD12-induced desensitization. Likewise, protein kinase-A activation in hippocampal neurons slows fast...

  19. Validación de una escala reducida de capacidad funcional del cuestionario WOMAC Validation of a short form of the function dimension of the WOMAC questionnaire

    Directory of Open Access Journals (Sweden)

    Antonio Escobar

    2011-12-01

    Full Text Available Objetivos: El objetivo del estudio fue evaluar la validez, la fiabilidad y la sensibilidad al cambio de la versión española de la dimensión reducida de 7 ítems de capacidad funcional del Western Ontario McMaster Universities Osteoarthritis Index (WOMAC. Métodos: Estudio prospectivo con seguimiento de 1 año realizado con 459 pacientes en lista de espera para prótesis de cadera o rodilla. Se enviaron los cuestionarios WOMAC y EQ-5D en cuatro tiempos: basal, 3, 6 y 12 meses postintervencion. Se realizó el proceso de validación, análisis Rasch y acuerdo medido por el gráfico de Bland-Altman. Resultados: Los valores de los coeficientes rho de Spearman y de concordancia de Lin entre la versión completa y la reducida estuvieron entre 0,96 y 0,98. Se encontraron diferencias estadísticamente significativas (pObjective: The aim of this prospective study was to evaluate the validity, reliability and responsiveness of the Spanish version of the 7-item short-form of the function dimension of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC. Methods: We conducted a prospective 1-year cohort study that included 459 patients on the waiting list for total knee or hip replacement. The WOMAC and EQ-5D questionnaires were sent at four time points: baseline and at 3, 6 and 12 months post-surgery. Based on a previously shortened scale, we performed a validation process with Rasch analysis and agreement measured by Bland-Altman plots. Results: The values of Spearman's rho and Lin concordance coefficients between the full and short-form ranged from 0.96 to 0.98. Differences were statistically significant (p<0.001 among the three groups of severity measured by a item in the EQ-5D. The two Bland-Altman plots showed no systematic differences and agreement was not dependent on the severity score. The short form fitted the Rasch model. Cronbach's α coefficients were higher than 0.85. Responsiveness was higher than 1.27 and 1.72 in knee

  20. Metformin and insulin receptors

    International Nuclear Information System (INIS)

    Vigneri, R.; Gullo, D.; Pezzino, V.

    1984-01-01

    The authors evaluated the effect of metformin (N,N-dimethylbiguanide), a biguanide known to be less toxic than phenformin, on insulin binding to its receptors, both in vitro and in vivo. Specific 125 I-insulin binding to cultured IM-9 human lymphocytes and MCF-7 human breast cancer cells was determined after preincubation with metformin. Specific 125 I-insulin binding to circulating monocytes was also evaluated in six controls, eight obese subjects, and six obese type II diabetic patients before and after a short-term treatment with metformin. Plasma insulin levels and blood glucose were also measured on both occasions. Metformin significantly increased insulin binding in vitro to both IM-9 lymphocytes and MCF-7 cells; the maximum increment was 47.1% and 38.0%, respectively. Metformin treatment significantly increased insulin binding in vivo to monocytes of obese subjects and diabetic patients. Scatchard analysis indicated that the increased binding was mainly due to an increase in receptor capacity. Insulin binding to monocytes of normal controls was unchanged after metformin as were insulin levels in all groups; blood glucose was significantly reduced after metformin only in diabetic patients. These data indicate that metformin increases insulin binding to its receptors in vitro and in vivo. The effect in vivo is observed in obese subjects and in obese type II diabetic patients, paralleling the clinical effectiveness of this antidiabetic agent, and is not due to receptor regulation by circulating insulin, since no variation in insulin levels was recorded

  1. Unsplit bipolar pulse forming line

    Science.gov (United States)

    Rhodes, Mark A [Pleasanton, CA

    2011-05-24

    A bipolar pulse forming transmission line module and system for linear induction accelerators having first, second, third, and fourth planar conductors which form a sequentially arranged interleaved stack having opposing first and second ends, with dielectric layers between the conductors. The first and second planar conductors are connected to each other at the first end, and the first and fourth planar conductors are connected to each other at the second end via a shorting plate. The third planar conductor is electrically connectable to a high voltage source, and an internal switch functions to short at the first end a high voltage from the third planar conductor to the fourth planar conductor to produce a bipolar pulse at the acceleration axis with a zero net time integral. Improved access to the switch is enabled by an aperture through the shorting plate and the proximity of the aperture to the switch.

  2. Nuclear Receptors in atherosclerosis: a superfamily with many 'Goodfellas'

    NARCIS (Netherlands)

    Kurakula, Kondababu; Hamers, Anouk A. J.; de Waard, Vivian; de Vries, Carlie J. M.

    2013-01-01

    Nuclear Receptors form a superfamily of 48 transcription factors that exhibit a plethora of functions in steroid hormone signaling, regulation of metabolism, circadian rhythm and cellular differentiation. In this review, we describe our current knowledge on the role of Nuclear Receptors in

  3. FIM-Minimum Data Set Motor Item Bank: Short Forms Development and Precision Comparison in Veterans.

    Science.gov (United States)

    Li, Chih-Ying; Romero, Sergio; Simpson, Annie N; Bonilha, Heather S; Simpson, Kit N; Hong, Ickpyo; Velozo, Craig A

    2018-03-01

    To improve the practical use of the short forms (SFs) developed from the item bank, we compared the measurement precision of the 4- and 8-item SFs generated from a motor item bank composed of the FIM and the Minimum Data Set (MDS). The FIM-MDS motor item bank allowed scores generated from different instruments to be co-calibrated. The 4- and 8-item SFs were developed based on Rasch analysis procedures. This article compared person strata, ceiling/floor effects, and test SE plots for each administration form and examined 95% confidence interval error bands of anchored person measures with the corresponding SFs. We used 0.3 SE as a criterion to reflect a reliability level of .90. Veterans' inpatient rehabilitation facilities and community living centers. Veterans (N=2500) who had both FIM and the MDS data within 6 days during 2008 through 2010. Not applicable. Four- and 8-item SFs of FIM, MDS, and FIM-MDS motor item bank. Six SFs were generated with 4 and 8 items across a range of difficulty levels from the FIM-MDS motor item bank. The three 8-item SFs all had higher correlations with the item bank (r=.82-.95), higher person strata, and less test error than the corresponding 4-item SFs (r=.80-.90). The three 4-item SFs did not meet the criteria of SE bank composed of existing instruments across the continuum of care in veterans. We also found that the number of items, not test specificity, determines the precision of the instrument. Copyright © 2017 American Congress of Rehabilitation Medicine. All rights reserved.

  4. Bipolar pulse forming line

    Science.gov (United States)

    Rhodes, Mark A.

    2008-10-21

    A bipolar pulse forming transmission line module for linear induction accelerators having first, second, third, fourth, and fifth planar conductors which form an interleaved stack with dielectric layers between the conductors. Each conductor has a first end, and a second end adjacent an acceleration axis. The first and second planar conductors are connected to each other at the second ends, the fourth and fifth planar conductors are connected to each other at the second ends, and the first and fifth planar conductors are connected to each other at the first ends via a shorting plate adjacent the first ends. The third planar conductor is electrically connectable to a high voltage source, and an internal switch functions to short a high voltage from the first end of the third planar conductor to the first end of the fourth planar conductor to produce a bipolar pulse at the acceleration axis with a zero net time integral. Improved access to the switch is enabled by an aperture through the shorting plate and the proximity of the aperture to the switch.

  5. Molecular mechanisms in the selective basal activation of pyrabactin receptor 1: Comparative analysis of mutants.

    Science.gov (United States)

    Dorosh, Lyudmyla; Rajagopalan, Nandhakishore; Loewen, Michele C; Stepanova, Maria

    2014-01-01

    Pyrabactin receptors (PYR) play a central role in abscisic acid (ABA) signal transduction; they are ABA receptors that inhibit type 2C protein phosphatases (PP2C). Molecular aspects contributing to increased basal activity of PYR against PP2C are studied by molecular dynamics (MD) simulations. An extensive series of MD simulations of the apo-form of mutagenized PYR1 as a homodimer and in complex with homology to ABA-insensitive 1 (HAB1) phosphatase are reported. In order to investigate the detailed molecular mechanisms mediating PYR1 activity, the MD data was analyzed by essential collective dynamics (ECD), a novel approach that allows the identification, with atomic resolution, of persistent dynamic correlations based on relatively short MD trajectories. Employing the ECD method, the effects of select mutations on the structure and dynamics of the PYR1 complexes were investigated and considered in the context of experimentally determined constitutive activities against HAB1. Approaches to rationally design constitutively active PYR1 constructs to increase PP2C inhibition are discussed.

  6. Modeling the receptor pharmacology, pharmacokinetics, and pharmacodynamics of NKTR-214, a kinetically-controlled interleukin-2 (IL2 receptor agonist for cancer immunotherapy.

    Directory of Open Access Journals (Sweden)

    Deborah Charych

    Full Text Available Cytokines are potent immune modulating agents but are not ideal medicines in their natural form due to their short half-life and pleiotropic systemic effects. NKTR-214 is a clinical-stage biologic that comprises interleukin-2 (IL2 protein bound by multiple releasable polyethylene glycol (PEG chains. In this highly PEG-bound form, the IL2 is inactive; therefore, NKTR-214 is a biologic prodrug. When administered in vivo, the PEG chains slowly release, creating a cascade of increasingly active IL2 protein conjugates bound by fewer PEG chains. The 1-PEG-IL2 and 2-PEG-IL2 species derived from NKTR-214 are the most active conjugated-IL2 species. Free-IL2 protein is undetectable in vivo as it is eliminated faster than formed. The PEG chains on NKTR-214 are located at the region of IL2 that contacts the alpha (α subunit of the heterotrimeric IL2 receptor complex, IL2Rαβγ, reducing its ability to bind and activate the heterotrimer. The IL2Rαβγ complex is constitutively expressed on regulatory T cells (Tregs. Therefore, without the use of mutations, PEGylation reduces the affinity for IL2Rαβγ to a greater extent than for IL2Rβγ, the receptor complex predominant on CD8 T cells. NKTR-214 treatment in vivo favors activation of CD8 T cells over Tregs in the tumor microenvironment to provide anti-tumor efficacy in multiple syngeneic models. Mechanistic modeling based on in vitro and in vivo kinetic data provides insight into the mechanism of NKTR-214 pharmacology. The model reveals that conjugated-IL2 protein derived from NKTR-214 occupy IL-2Rβγ to a greater extent compared to free-IL2 protein. The model accurately describes the sustained in vivo signaling observed after a single dose of NKTR-214 and explains how the properties of NKTR-214 impart a unique kinetically-controlled immunological mechanism of action.

  7. Modeling the receptor pharmacology, pharmacokinetics, and pharmacodynamics of NKTR-214, a kinetically-controlled interleukin-2 (IL2) receptor agonist for cancer immunotherapy.

    Science.gov (United States)

    Charych, Deborah; Khalili, Samira; Dixit, Vidula; Kirk, Peter; Chang, Thomas; Langowski, John; Rubas, Werner; Doberstein, Stephen K; Eldon, Michael; Hoch, Ute; Zalevsky, Jonathan

    2017-01-01

    Cytokines are potent immune modulating agents but are not ideal medicines in their natural form due to their short half-life and pleiotropic systemic effects. NKTR-214 is a clinical-stage biologic that comprises interleukin-2 (IL2) protein bound by multiple releasable polyethylene glycol (PEG) chains. In this highly PEG-bound form, the IL2 is inactive; therefore, NKTR-214 is a biologic prodrug. When administered in vivo, the PEG chains slowly release, creating a cascade of increasingly active IL2 protein conjugates bound by fewer PEG chains. The 1-PEG-IL2 and 2-PEG-IL2 species derived from NKTR-214 are the most active conjugated-IL2 species. Free-IL2 protein is undetectable in vivo as it is eliminated faster than formed. The PEG chains on NKTR-214 are located at the region of IL2 that contacts the alpha (α) subunit of the heterotrimeric IL2 receptor complex, IL2Rαβγ, reducing its ability to bind and activate the heterotrimer. The IL2Rαβγ complex is constitutively expressed on regulatory T cells (Tregs). Therefore, without the use of mutations, PEGylation reduces the affinity for IL2Rαβγ to a greater extent than for IL2Rβγ, the receptor complex predominant on CD8 T cells. NKTR-214 treatment in vivo favors activation of CD8 T cells over Tregs in the tumor microenvironment to provide anti-tumor efficacy in multiple syngeneic models. Mechanistic modeling based on in vitro and in vivo kinetic data provides insight into the mechanism of NKTR-214 pharmacology. The model reveals that conjugated-IL2 protein derived from NKTR-214 occupy IL-2Rβγ to a greater extent compared to free-IL2 protein. The model accurately describes the sustained in vivo signaling observed after a single dose of NKTR-214 and explains how the properties of NKTR-214 impart a unique kinetically-controlled immunological mechanism of action.

  8. Perspectives on the Trypanosoma cruzi–host cell receptor interactions

    Science.gov (United States)

    Villalta, Fernando; Scharfstein, Julio; Ashton, Anthony W.; Tyler, Kevin M.; Guan, Fangxia; Mukherjee, Shankar; Lima, Maria F.; Alvarez, Sandra; Weiss, Louis M.; Huang, Huan; Machado, Fabiana S.

    2009-01-01

    Chagas disease is caused by the parasite Trypanosoma cruzi. The critical initial event is the interaction of the trypomastigote form of the parasite with host receptors. This review highlights recent observations concerning these interactions. Some of the key receptors considered are those for thromboxane, bradykinin, and for the nerve growth factor TrKA. Other important receptors such as galectin-3, thrombospondin, and laminin are also discussed. Investigation into the molecular biology and cell biology of host receptors for T. cruzi may provide novel therapeutic targets. PMID:19283409

  9. Mutations increasing exposure of a receptor binding site epitope in the soluble and oligomeric forms of the caprine arthritis-encephalitis lentivirus envelope glycoprotein

    International Nuclear Information System (INIS)

    Hoetzel, Isidro; Cheevers, William P.

    2005-01-01

    The caprine arthritis-encephalitis (CAEV) and ovine maedi-visna (MVV) viruses are resistant to antibody neutralization, a feature shared with all other lentiviruses. Whether the CAEV gp135 receptor binding site(s) (RBS) in the functional surface envelope glycoprotein (Env) is protected from antibody binding, allowing the virus to resist neutralization, is not known. Two CAEV gp135 regions were identified by extrapolating a gp135 structural model that could affect binding of antibodies to the RBS: the V1 region and a short sequence analogous in position to the human immunodeficiency virus type 1 gp120 loop B postulated to be located between two major domains of CAEV gp135. Mutation of isoleucine-166 to alanine in the putative loop B of gp135 increased the affinity of soluble gp135 for the CAEV receptor(s) and goat monoclonal antibody (Mab) F7-299 which recognizes an epitope overlapping the gp135 RBS. The I166A mutation also stabilized or exposed the F7-299 epitope in anionic detergent buffers, indicating that the I166A mutation induces conformational changes and stabilizes the RBS of soluble gp135 and enhances Mab F7-299 binding. In contrast, the affinity of a V1 deletion mutant of gp135 for the receptor and Mab F7-299 and its structural stability did not differ from that of the wild-type gp135. However, both the I166A mutation and the V1 deletion of gp135 increased cell-to-cell fusion activity and binding of Mab F7-299 to the oligomeric Env. Therefore, the CAEV gp135 RBS is protected from antibody binding by mechanisms both dependent and independent of Env oligomerization which are disrupted by the V1 deletion and the I166A mutation, respectively. In addition, we found a correlation between side-chain β-branching at amino acid position 166 and binding of Mab F7-299 to oligomeric Env and cell-to-cell fusion, suggesting local secondary structure constraints in the region around isoleucine-166 as one determinant of gp135 RBS exposure and antibody binding

  10. Loss of the ability to generate large burst-forming unit-like megakaryocytic colonies from thawed cord blood in semisolid cultures after short term suspension culture.

    Science.gov (United States)

    Eskola, M; Bäckman, S; Möttönen, S; Kekomäki, R

    2015-04-01

    Total colony-forming cells from thawed cord blood units (CBUs) include megakaryocytic colony-forming units (CFU-Mks), which survive the freezing process. The aim of this study was to evaluate whether different megakaryocytic progenitors from unseparated CBUs survive the freezing process and a short-term liquid culture. Thawed samples of CBUs were cultured in liquid medium. During the cultures, serial samples were drawn to assess the growth of different megakaryocytic progenitors in a semisolid collagen medium with identical cytokines as in the liquid medium. Megakaryocytic cells were detected using immunohistochemistry and flow cytometry. In suspension culture, the megakaryocytic progenitors almost completely lost the ability to generate large (burst-forming unit-like, BFU-like) megakaryocytic colonies in semisolid cultures (large colonies, median count per chamber d0: 7.25 vs. d7: 1.5; P culture in suspension resulted in the decline of small colonies as well (d7: 16.0 vs. d14: 5.75; P = 0.0088). Total CFU-Mk count declined from 23.3 (range 12.5-34.0) at d0 to 7.25 (range 1.0-13.5) at d14 (P culture after a short suspension culture. Small CFU-Mks were observed throughout the cultures. It may be that the BFU-Mk colonies matured and acquired CFU-Mk behaviour. © 2014 International Society of Blood Transfusion.

  11. Ciproxifan, an H3 receptor antagonist, improves short-term recognition memory impaired by isoflurane anesthesia.

    Science.gov (United States)

    Ding, Fang; Zheng, Limin; Liu, Min; Chen, Rongfa; Leung, L Stan; Luo, Tao

    2016-08-01

    Exposure to volatile anesthetics has been reported to cause temporary or sustained impairments in learning and memory in pre-clinical studies. The selective antagonists of the histamine H3 receptors (H3R) are considered to be a promising group of novel therapeutic agents for the treatment of cognitive disorders. The aim of this study was to evaluate the effect of H3R antagonist ciproxifan on isoflurane-induced deficits in an object recognition task. Adult C57BL/6 J mice were exposed to isoflurane (1.3 %) or vehicle gas for 2 h. The object recognition tests were carried at 24 h or 7 days after exposure to anesthesia to exploit the tendency of mice to prefer exploring novel objects in an environment when a familiar object is also present. During the training phase, two identical objects were placed in two defined sites of the chamber. During the test phase, performed 1 or 24 h after the training phase, one of the objects was replaced by a new object with a different shape. The time spent exploring each object was recorded. A robust deficit in object recognition memory occurred 1 day after exposure to isoflurane anesthesia. Isoflurane-treated mice spent significantly less time exploring a novel object at 1 h but not at 24 h after the training phase. The deficit in short-term memory was reversed by the administration of ciproxifan 30 min before behavioral training. Isoflurane exposure induces reversible deficits in object recognition memory. Ciproxifan appears to be a potential therapeutic agent for improving post-anesthesia cognitive memory performance.

  12. The purinergic P2X7 ion channel receptor — a ‘repair’ receptor in bone

    DEFF Research Database (Denmark)

    Jørgensen, Niklas Rye

    2018-01-01

    A strong skeleton relies on adaptation to varying physical demands and on maintenance of the bone tissue in order to avoid accumulation of micro-damage. In bone, the purinergic P2X7 ion channel receptor is expressed on both cells of the stromal lineage such as the bone forming osteoblasts...... and the mechano-sensing osteocytes and on cells belonging to the immune-related monocyte–macrophage lineage, the bone resorbing osteoclasts. Recent studies have demonstrated that the receptor plays important roles in the anabolic responses to mechanical loading on bone and, together with the pannexin1 hemi......-channel, in the process of initiating bone remodeling in response to micro-damage. Thus, the receptor is crucial in skeletal mechano-transduction and in the continuous repair process. However, under pathophysiological conditions such as diabetes with high glucose concentrations or glucocorticoid-treatment the receptor...

  13. Quality of life assessed with the medical outcomes study short form 36-item health survey of patients on renal replacement therapy: A systematic review and meta-analysis

    NARCIS (Netherlands)

    Y.S. Liem (Ylian Serina); J.L. Bosch (Johanna); L.R. Arends (Lidia); M.H. Heijenbrok-Kal (Majanka); M.G.M. Hunink (Myriam)

    2007-01-01

    textabstractObjectives: The Medical Outcomes Study Short Form 36-Item Health Survey (SF-36) is the most widely used generic instrument to estimate quality of life of patients on renal replacement therapy. Purpose of this study was to summarize and compare the published literature on quality of

  14. Free fatty acid receptor 3 is a key target of short chain fatty acid. What is the impact on the sympathetic nervous system?

    Science.gov (United States)

    López Soto, Eduardo Javier; Gambino, Luisina Ongaro; Mustafá, Emilio Román

    2014-01-01

    Nervous system (NS) activity participates in metabolic homeostasis by detecting peripheral signal molecules derived from food intake and energy balance. High quality diets are thought to include fiber-rich foods like whole grain rice, breads, cereals, and grains. Several studies have associated high consumption of fiber-enriched diets with a reduced risk of diabetes, obesity, and gastrointestinal disorders. In the lower intestine, anaerobic fermentation of soluble fibers by microbiota produces short chain fatty acids (SCFAs), key energy molecules that have a recent identified leading role in the intestinal gluconeogenesis, promoting beneficial effects on glucose tolerance and insulin resistance. SCFAs are also signaling molecules that bind to specific G-protein coupled receptors (GPCRs) named Free Fatty Acid Receptor 3 (FFA3, GPR41) and 2 (FFA2, GPR43). However, how SCFAs impact NS activity through their GPCRs is poorly understood. Recently, studies have demonstrated the presence of FFA2 and FFA3 in the sympathetic NS of rat, mouse and human. Two studies have showed that FFA3 activation by SCFAs increases firing and norepinephrine (NE) release from sympathetic neurons. However, the recent study from the Ikeda Laboratory revealed that activation of FFA3 by SCFAs impairs N-type calcium channel (NTCC) activity, which contradicts the idea of FFA3 activation leading to increased action potential evoked NE release. Here we will discuss the scope of the latter study and the putative physiological role of SCFAs and FFAs in the sympathetic NS.

  15. Early vertebrate chromosome duplications and the evolution of the neuropeptide Y receptor gene regions

    Directory of Open Access Journals (Sweden)

    Brenner Sydney

    2008-06-01

    Full Text Available Abstract Background One of the many gene families that expanded in early vertebrate evolution is the neuropeptide (NPY receptor family of G-protein coupled receptors. Earlier work by our lab suggested that several of the NPY receptor genes found in extant vertebrates resulted from two genome duplications before the origin of jawed vertebrates (gnathostomes and one additional genome duplication in the actinopterygian lineage, based on their location on chromosomes sharing several gene families. In this study we have investigated, in five vertebrate genomes, 45 gene families with members close to the NPY receptor genes in the compact genomes of the teleost fishes Tetraodon nigroviridis and Takifugu rubripes. These correspond to Homo sapiens chromosomes 4, 5, 8 and 10. Results Chromosome regions with conserved synteny were identified and confirmed by phylogenetic analyses in H. sapiens, M. musculus, D. rerio, T. rubripes and T. nigroviridis. 26 gene families, including the NPY receptor genes, (plus 3 described recently by other labs showed a tree topology consistent with duplications in early vertebrate evolution and in the actinopterygian lineage, thereby supporting expansion through block duplications. Eight gene families had complications that precluded analysis (such as short sequence length or variable number of repeated domains and another eight families did not support block duplications (because the paralogs in these families seem to have originated in another time window than the proposed genome duplication events. RT-PCR carried out with several tissues in T. rubripes revealed that all five NPY receptors were expressed in the brain and subtypes Y2, Y4 and Y8 were also expressed in peripheral organs. Conclusion We conclude that the phylogenetic analyses and chromosomal locations of these gene families support duplications of large blocks of genes or even entire chromosomes. Thus, these results are consistent with two early vertebrate

  16. Validation of the Kidney Disease Quality of Life-Short Form: a cross-sectional study of a dialysis-targeted health measure in Singapore

    OpenAIRE

    Joshi, Veena D; Mooppil, Nandakumar; Lim, Jeremy FY

    2010-01-01

    Abstract Background In Singapore, the prevalence of end-stage renal disease (ESRD) and the number of people on dialysis is increasing. The impact of ESRD on patient quality of life has been recognized as an important outcome measure. The Kidney Disease Quality Of Life-Short Form (KDQOL-SF™) has been validated and is widely used as a measure of quality of life in dialysis patients in many countries, but not in Singapore. We aimed to determine the reliability and validity of the KDQOL-SF™ for h...

  17. 5-HT7 receptor activation: procognitive and antiamnesic effects.

    Science.gov (United States)

    Meneses, A; Perez-Garcia, G; Liy-Salmeron, G; Ponce-López, T; Lacivita, E; Leopoldo, M

    2015-02-01

    The serotonin (5-hydroxytryptamine (5-HT)) 5-HT7 receptor is localized in brain areas mediating memory; however, the role of this receptor on memory remains little explored. First, demonstrating the associative nature of Pavlovian/instrumental autoshaping (P/I-A) task, rats were exposed (three sessions) to CS-US (Pavlovian autoshaping), truly random control, free operant, and presentations of US or CS, and they were compared with rats trained-tested for one session to the P/I-A procedure. Also, effects of the 5-HT7 receptor agonist LP-211 administered intraperitoneally after training was determined on short- (1.5 h) and long-term memory 24 and 48 h) and on scopolamine-induced memory impairment and cAMP production. Autoshaping and its behavioral controls were studied. Other animals were subjected to an autoshaping training session and immediately afterwards were given (intraperitoneal) vehicle or LP-211 (0.1-10 mg/kg) and/or scopolamine (0.2 mg/kg) and tested for short-term memory (STM) and long-term memory (LTM); their brains were extracted for the cAMP ELISA immunoassay. P/I-A group produced the higher %CR. LP-211 did not affect STM; nonetheless, at 0.5 and 1.0 mg/kg, it improved LTM. The 5-HT7 receptor antagonist SB-269970 (SB; 10.0 mg/kg) alone had no effect; nevertheless, the LP-211 (1.0 mg/kg) LTM facilitation was reversed by SB. The scopolamine (0.2 mg/kg) induced-decrement in CR was accompanied by significant increased cAMP production. The scopolamine-induced decrement in CR and increments in cAMP were significantly attenuated by LP-211. Autoshaping is a reliable associative learning task whose consolidation is facilitated by the 5-HT7 receptor agonist LP-211.

  18. Psychometric Characteristics of a Vocational Preference Inventory Short Form.

    Science.gov (United States)

    Lowman, Rodney L.; Schurman, Susan J.

    1982-01-01

    The psychometric properties of a revised version of Holland's Vocational Preference Inventory were assessed using federal government employees. Factor analyses, interscale correlations, measures of internal consistency, and criterion group profiles are presented. Evidence was supportive of the validity of the revised form. (Author/BW)

  19. Neutral tripodal receptors towards efficient trapping of oxalate

    Indian Academy of Sciences (India)

    Interestingly most of the receptors tend to form dimeric capsular assembly upon encapsulation of anionic guests like sulphate, phosphates and carbonate.8p,r,s In our ongoing effort for anion recognition chemistry, we have recently reported recognition of C2O2−. 4 by two structurally analogous tripodal urea receptors in ...

  20. Comparison of the Mini-Nutritional Assessment short and long form and serum albumin as prognostic indicators of hip fracture outcomes.

    Science.gov (United States)

    Helminen, Heli; Luukkaala, Tiina; Saarnio, Juha; Nuotio, Maria

    2017-04-01

    Malnutrition is common among older hip fracture patients and associated with adverse outcomes. We examined Mini Nutritional Assessment short (MNA-SF) and long form (MNA-LF) and serum albumin as prognostic indicators of mobility, living arrangements and mortality after hip fracture. Population-based prospective data were collected on 594 hip fracture patients aged 65 and over. MNA-SF, MNA-LF and serum albumin were assessed on admission. Outcomes were poorer mobility; transfer to more assisted living accommodation and mortality one month, four months and one year post fracture. Logistic regression analyses for mobility and living arrangements with odds ratios (OR) and Cox proportional hazards model for mortality with hazard ratios (HR) and 95% confidence intervals (CI) were used, adjusted for age, gender, ASA grade and fracture type. All measures predicted mortality at all time-points. Risk of malnutrition and malnutrition measured by MNA-LF predicted mobility and living arrangements within four months of hip fracture. At one year, risk of malnutrition predicted mobility and malnutrition predicted living arrangements, when measured by MNA-LF. Malnutrition, but not risk thereof, measured by MNA-SF predicted living arrangements at all time-points. None of the measures predicted one-month mobility. All measures were strong indicators of short- and long-term mortality after hip fracture. MNA-LF was superior in predicting mobility and living arrangements, particularly at four months. All measures were relatively poor in predicting short-term outcomes of mobility and living arrangements. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Adrenomedullin increases the short-circuit current in the rat prostate: Receptors, chloride channels, the effects of cAMP and calcium ions and implications on fluid secretion.

    Science.gov (United States)

    Liao, S B; Cheung, K H; Cheung, M P L; Wong, P F; O, W S; Tang, F

    2014-05-01

    In this study, we have investigated the effects of adrenomedullin on chloride and fluid secretion in the rat prostate. The presence of adrenomedullin (ADM) in rat prostate was confirmed using immunostaining, and the molecular species was determined using gel filtration chromatography coupled with an enzyme-linked assay for ADM. The effects of ADM on fluid secretion were studied by short-circuit current technique in a whole mount preparation of the prostate in an Ussing chamber. The results indicated that the ADM level was higher in the ventral than the dorso-lateral prostate and the major molecular species was the active peptide. ADM increased the short-circuit current through both the cAMP- and calcium-activated chloride channels in the ventral lobe, but only through the calcium-activated channels in the dorso-lateral lobe. These stimulatory effects were blocked by the calcitonin gene-related peptide (CGRP) receptor antagonist, hCGRP8-37. We conclude that ADM may regulate prostatic fluid secretion through the chloride channels, which may affect the composition of the seminal plasma bathing the spermatozoa and hence fertility. © 2014 American Society of Andrology and European Academy of Andrology.

  2. Molecular cloning and characterization of a short peptidoglycan recognition protein from silkworm Bombyx mori.

    Science.gov (United States)

    Yang, P-J; Zhan, M-Y; Ye, C; Yu, X-Q; Rao, X-J

    2017-12-01

    Peptidoglycan is the major bacterial component recognized by the insect immune system. Peptidoglycan recognition proteins (PGRPs) are a family of pattern-recognition receptors that recognize peptidoglycans and modulate innate immune responses. Some PGRPs retain N-acetylmuramoyl-L-alanine amidase (Enzyme Commission number: 3.5.1.28) activity to hydrolyse bacterial peptidoglycans. Others have lost the enzymatic activity and work only as immune receptors. They are all important modulators for innate immunity. Here, we report the cloning and functional analysis of PGRP-S4, a short-form PGRP from the domesticated silkworm, Bombyx mori. The PGRP-S4 gene encodes a protein of 199 amino acids with a signal peptide and a PGRP domain. PGRP-S4 was expressed in the fat body, haemocytes and midgut. Its expression level was significantly induced by bacterial challenges in the midgut. The recombinant PGRP-S4 bound bacteria and different peptidoglycans. In addition, it inhibited bacterial growth and hydrolysed an Escherichia coli peptidoglycan in the presence of Zn 2+ . Scanning electron microscopy showed that PGRP-S4 disrupted the bacterial cell surface. PGRP-S4 further increased prophenoloxidase activation caused by peptidoglycans. Taken together, our data suggest that B. mori PGRP-S4 has multiple functions in immunity. © 2017 The Royal Entomological Society.

  3. Psychometrics properties of early trauma inventory self report - short form (ETISR-SR) for the Brazilian context.

    Science.gov (United States)

    Osório, Flávia L; Salum, Giovanni Abrahão; Donadon, Mariana Fortunata; Forni-Dos-Santos, Larissa; Loureiro, Sonia Regina; Crippa, José Alexandre S

    2013-01-01

    This study aims to translate and validate Early Trauma Inventory Self Report -Short Form (ETISR-SF) to Brazilian Portuguese. 253 adult subjects answered the ETISR-SF, Beck Anxiety Inventory (BAI), Fagerström Test for Nicotine Dependence (FTND), Patient Health Questionnaire (PHQ-9) and Fast Alcohol Screening Test (FAST). The instrument showed good internal consistency (0.83). Correlations with the PHQ-9 and BAI were moderate (r=0.26-0.47) and showed the expected associations with psychiatric constructs. No associations were found for FTND and FAST. Confirmatory Factor Analysis revealed that a correlated four-factor model as well as a second order model subsuming four lower order components presented the best model fit. Test-retest reliability was also excellent (ICC=0.78-0.90). ETISR-SF is suitable for assessing traumatic experiences in a Brazilian community sample. Given the importance of trauma as a public health problem, tools such as ETISR-SF may help clinicians/ researchers to better evaluate and measure such events and further advance clinical care of trauma victims.

  4. Psychometric properties of the Social Problem Solving Inventory-Revised Short-Form in a South African population.

    Science.gov (United States)

    Sorsdahl, Katherine; Stein, Dan J; Myers, Bronwyn

    2017-04-01

    The Social Problem Solving Inventory-Revised Short-Form (SPSI-R:SF) has been used in several countries to identify problem-solving deficits among clinical and general populations in order to guide cognitive-behavioural interventions. Yet, very few studies have evaluated its psychometric properties. Three language versions of the questionnaire were administered to a general population sample comprising 1000 participants (771 English-, 178 Afrikaans- and 101 Xhosa-speakers). Of these participants, 210 were randomly selected to establish test-retest reliability (70 in each language). Principal component analysis was performed to examine the applicability of the factor structure of the original questionnaire to the South African data. Supplementary psychometric analyses were performed, including internal consistency and test-retest reliability. Collectively, results provide initial evidence of the reliability and validity of the SPSI-R:SF for the assessment of problem solving deficits in South Africa. Further studies that explore how the Afrikaans language version of the SPSI-R:SF can be improved and that establish the predictive validity of scores on the SPSI-R:SF are needed. © 2015 International Union of Psychological Science.

  5. Generation of truncated recombinant form of tumor necrosis factor ...

    African Journals Online (AJOL)

    Purpose: To produce truncated recombinant form of tumor necrosis factor receptor 1 (TNFR1), cysteine-rich domain 2 (CRD2) and CRD3 regions of the receptor were generated using pET28a and E. coli/BL21. Methods: DNA coding sequence of CRD2 and CRD3 was cloned into pET28a vector and the corresponding ...

  6. Psychometric Evaluation and Cultural Correlates of the Mate Retention Inventory–Short Form (MRI-SF in Iran

    Directory of Open Access Journals (Sweden)

    Mohammad Atari

    2017-02-01

    Full Text Available The current study investigated the psychometric properties of the Persian translation of the Mate Retention Inventory–Short Form (MRI-SF in Iran. We also investigated sex differences in the use of mate retention tactics and investigated the relationships between mate retention behaviors and a number of related cultural constructs. Participants (N = 308 ranged in age from 18 to 57 years. All participants were in a committed romantic relationship, with mean relationship length of 63.5 months (SD = 73.8. Participants completed the Persian translation of the MRI-SF and measures of religiosity, relationship satisfaction, self-esteem, and socioeconomic status. Cultural measures specific to Iran were also included, such as Mahr (for married individuals, self-perceived Qeiratiness (for men, and self-perceived jealousy (for women. Mahr is a mandatory amount of money or possessions paid or promised to be paid by the groom to the bride at the time of the marriage contract. Qeirati is a male-specific adjective in Persian meaning protective against unwanted attention toward a man’s romantic partner. Female jealousy is usually regarded the counterpart of male Qeiratiness in Iranian culture. The 19 mate retention tactics formed a two-component structure, consistent with previous research. Results demonstrate adequate internal consistency of 2-item assessments of mate retention tactics. Observed sex differences accorded with previous mate retention research and are discussed in reference to evolutionary perspectives on human mating. Several significant associations emerged between mate retention tactics and Iranian culture-specific variables and are discussed from a cross-cultural perspective.

  7. GluA2-dependent AMPA receptor endocytosis and the decay of early and late long-term potentiation: possible mechanisms for forgetting of short- and long-term memories.

    Science.gov (United States)

    Hardt, Oliver; Nader, Karim; Wang, Yu-Tian

    2014-01-05

    The molecular processes involved in establishing long-term potentiation (LTP) have been characterized well, but the decay of early and late LTP (E-LTP and L-LTP) is poorly understood. We review recent advances in describing the mechanisms involved in maintaining LTP and homeostatic plasticity. We discuss how these phenomena could relate to processes that might underpin the loss of synaptic potentiation over time, and how they might contribute to the forgetting of short-term and long-term memories. We propose that homeostatic downscaling mediates the loss of E-LTP, and that metaplastic parameters determine the decay rate of L-LTP, while both processes require the activity-dependent removal of postsynaptic GluA2-containing AMPA receptors.

  8. Development of a Short Form of the Abridged Big Five-Dimensional Circumplex Model to Aid with the Organization of Personality Traits.

    Science.gov (United States)

    Bucher, Meredith A; Samuel, Douglas B

    2018-02-01

    Although there has been widespread consensus on the use of the Five-Factor Model (FFM) of general personality functioning in personality research, there are various, diverse models of the lower order traits of the FFM domains. Given the usefulness of these finer grained traits, it is imperative to integrate facets proposed across a variety of models and eventually reach consensus on the lower level traits of the FFM. Due to its depth and coverage, the Abridged Big Five-Dimensional Circumplex (AB5C) model potentially provides a useful framework for organizing various faceted models due to its conceptual organization and inclusiveness. The only measure of this model-the IPIP-AB5C-has shown promise, but is limited by its length (i.e., 485 items). This study developed an abbreviated version of the IPIP-AB5C using an iterative process including item response theory methods. The shorter version maintained key features of the long form including a factor structure that matched the full form as well as facets that correlated in expected ways with other FFM measures. Building on this support, the short form was used to contextualize and organize the facets from 2 commonly used measures.

  9. Long-term failure of alveologenesis after an early short-term exposure to a PDGF-receptor antagonist.

    Science.gov (United States)

    Lau, Mandy; Masood, Azhar; Yi, Man; Belcastro, Rosetta; Li, Jun; Tanswell, A Keith

    2011-04-01

    Survivors of moderate-to-severe bronchopulmonary dysplasia have impaired alveologenesis lasting at least into early adult life. The mechanisms underlying this long-term effect are unknown. We hypothesized that short-term inhibition of growth factor-mediated early alveolar formation would result in a long-term impairment of subsequent alveologenesis. Neonatal rats were injected daily with the platelet-derived growth factor (PDGF) receptor antagonist, imatinib mesylate, from day 1-7 of life, to inhibit the early alveolar formation occurring by in-growth of secondary crests into precursor saccules. The pups were then allowed to recover for 7, 14, 21, or 58 days. In imatinib-treated pups, DNA synthesis in total lung cells, and specifically in cells of secondary crests, was reduced at day 8 of life, had rebounded on day 14 of life but was then again reduced by day 28 of life. At day 8 of life, imatinib-treated pups had impaired alveologenesis as reflected by a decrease in secondary crests, an increase in alveolar size, and an overall decrease in both estimated alveolar number and generations compared with age-matched controls. No meaningful recovery was observed, even after a 21- or 58-day recovery period. The lungs of imatinib-treated pups had increased fibulin-5 content and an abnormal deposition of elastin. We conclude that reduced signaling through the PDGF pathways, at an early stage of alveologenesis, can result in long-lasting changes in lung architecture. A likely mechanism is through impaired formation of the elastin scaffold required for alveolarization.

  10. Impairments of exploration and memory after systemic or prelimbic D1-receptor antagonism in rats

    DEFF Research Database (Denmark)

    Clausen, Bettina; Schachtman, Todd R.; Mark, Louise T.

    2011-01-01

    to examine the effects on memory: cross-maze and object recognition task. Systemic administration reduced spatial exploration in cross-maze as well as in an open field test, and also reduced object exploration. Spatial (hippocampus-dependent) short-term memory was inhibited in the cross-maze and non......-spatial short-term object retention was also impaired. In contrast to these systemic effects, bilateral injections of SCH23390 into the prelimbic cortices altered neither spatial nor object exploration, but did inhibit short-term memory in both cross-maze and object recognition task. Therefore, the inhibiting......D1-receptor antagonism is known to impair rodent memory but also inhibits spontaneous exploration of stimuli to be remembered. Hypo-exploration could contribute to impaired memory by influencing event processing. In order to explore this effect, the D1 receptor antagonist, SCH23390...

  11. Signal transduction by the platelet-derived growth factor receptor

    International Nuclear Information System (INIS)

    Williams, L.T.; Escobedo, J.A.; Keating, M.T.; Coughlin, S.R.

    1988-01-01

    The mitogenic effects of platelet-derived growth factor (PDGF) are mediated by the PDGF receptor. The mouse PDGF receptor was recently purified on the basis of its ability to become tyrosine phosphorylated in response to the A-B human platelet form of PDGF, and the receptor amino acid sequence was determined from a full-length cDNA clone. Both the human and mouse receptor cDNA sequences have been expressed in Chinese hamster ovary fibroblast (CHO) cells that normally lack PDGF receptors. This paper summarizes recent results using this system to study signal transduction by the PDGF receptor. Some of the findings show that the KI domain of the PDGF receptor plays an important role in the stimulation of DNA synthesis by PDGF. Surprisingly, the kinase insert region is not essential for PDGF stimulation of PtdIns turnover, pH change, increase in cellular calcium, and receptor autophosphorylation. In addition, PDGF stimulates a conformational change in the receptor

  12. G protein-coupled receptor 30 (GPR30) forms a plasma membrane complex with membrane-associated guanylate kinases (MAGUKs) and protein kinase A-anchoring protein 5 (AKAP5) that constitutively inhibits cAMP production.

    Science.gov (United States)

    Broselid, Stefan; Berg, Kelly A; Chavera, Teresa A; Kahn, Robin; Clarke, William P; Olde, Björn; Leeb-Lundberg, L M Fredrik

    2014-08-08

    GPR30, or G protein-coupled estrogen receptor, is a G protein-coupled receptor reported to bind 17β-estradiol (E2), couple to the G proteins Gs and Gi/o, and mediate non-genomic estrogenic responses. However, controversies exist regarding the receptor pharmacological profile, effector coupling, and subcellular localization. We addressed the role of the type I PDZ motif at the receptor C terminus in receptor trafficking and coupling to cAMP production in HEK293 cells and CHO cells ectopically expressing the receptor and in Madin-Darby canine kidney cells expressing the native receptor. GPR30 was localized both intracellularly and in the plasma membrane and subject to limited basal endocytosis. E2 and G-1, reported GPR30 agonists, neither stimulated nor inhibited cAMP production through GPR30, nor did they influence receptor localization. Instead, GPR30 constitutively inhibited cAMP production stimulated by a heterologous agonist independently of Gi/o. Moreover, siRNA knockdown of native GPR30 increased cAMP production. Deletion of the receptor PDZ motif interfered with inhibition of cAMP production and increased basal receptor endocytosis. GPR30 interacted with membrane-associated guanylate kinases, including SAP97 and PSD-95, and protein kinase A-anchoring protein (AKAP) 5 in the plasma membrane in a PDZ-dependent manner. Knockdown of AKAP5 or St-Ht31 treatment, to disrupt AKAP interaction with the PKA RIIβ regulatory subunit, decreased inhibition of cAMP production, and St-Ht31 increased basal receptor endocytosis. Therefore, GPR30 forms a plasma membrane complex with a membrane-associated guanylate kinase and AKAP5, which constitutively attenuates cAMP production in response to heterologous agonists independently of Gi/o and retains receptors in the plasma membrane. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  13. The short isoform of the CEACAM1 receptor in intestinal T cells regulates mucosal immunity and homeostasis via Tfh cell induction.

    Science.gov (United States)

    Chen, Lanfen; Chen, Zhangguo; Baker, Kristi; Halvorsen, Elizabeth M; da Cunha, Andre Pires; Flak, Magdalena B; Gerber, Georg; Huang, Yu-Hwa; Hosomi, Shuhei; Arthur, Janelle C; Dery, Ken J; Nagaishi, Takashi; Beauchemin, Nicole; Holmes, Kathryn V; Ho, Joshua W K; Shively, John E; Jobin, Christian; Onderdonk, Andrew B; Bry, Lynn; Weiner, Howard L; Higgins, Darren E; Blumberg, Richard S

    2012-11-16

    Carcinoembryonic antigen cell adhesion molecule like I (CEACAM1) is expressed on activated T cells and signals through either a long (L) cytoplasmic tail containing immune receptor tyrosine based inhibitory motifs, which provide inhibitory function, or a short (S) cytoplasmic tail with an unknown role. Previous studies on peripheral T cells show that CEACAM1-L isoforms predominate with little to no detectable CEACAM1-S isoforms in mouse and human. We show here that this was not the case in tissue resident T cells of intestines and gut associated lymphoid tissues, which demonstrated predominant expression of CEACAM1-S isoforms relative to CEACAM1-L isoforms in human and mouse. This tissue resident predominance of CEACAM1-S expression was determined by the intestinal environment where it served a stimulatory function leading to the regulation of T cell subsets associated with the generation of secretory IgA immunity, the regulation of mucosal commensalism, and defense of the barrier against enteropathogens. Copyright © 2012 Elsevier Inc. All rights reserved.

  14. Similarities and differences between the responses induced in human phagocytes through activation of the medium chain fatty acid receptor GPR84 and the short chain fatty acid receptor FFA2R.

    Science.gov (United States)

    Sundqvist, Martina; Christenson, Karin; Holdfeldt, André; Gabl, Michael; Mårtensson, Jonas; Björkman, Lena; Dieckmann, Regis; Dahlgren, Claes; Forsman, Huamei

    2018-05-01

    GPR84 is a recently de-orphanized member of the G-protein coupled receptor (GPCR) family recognizing medium chain fatty acids, and has been suggested to play important roles in inflammation. Due to the lack of potent and selective GPR84 ligands, the basic knowledge related to GPR84 functions is very limited. In this study, we have characterized the GPR84 activation profile and regulation mechanism in human phagocytes, using two recently developed small molecules that specifically target GPR84 agonistically (ZQ16) and antagonistically (GLPG1205), respectively. Compared to our earlier characterization of the short chain fatty acid receptor FFA2R which is functionally expressed in neutrophils but not in monocytes, GPR84 is expressed in both cell types and in monocyte-derived macrophages. In neutrophils, the GPR84 agonist had an activation profile very similar to that of FFA2R. The GPR84-mediated superoxide release was low in naïve cells, but the response could be significantly primed by TNFα and by the actin cytoskeleton disrupting agent Latrunculin A. Similar to that of FFA2R, a desensitization mechanism bypassing the actin cytoskeleton was utilized by GPR84. All ZQ16-mediated cellular responses were sensitive to GLPG1205, confirming the GPR84-dependency. Finally, our data of in vivo transmigrated tissue neutrophils indicate that both GPR84 and FFA2R are involved in neutrophil recruitment processes in vivo. In summary, we show functional similarities but also some important differences between GPR84 and FFA2R in human phagocytes, thus providing some mechanistic insights into GPR84 regulation in blood neutrophils and cells recruited to an aseptic inflammatory site in vivo. Copyright © 2018 Elsevier B.V. All rights reserved.

  15. Lactate Transport and Receptor Actions in Retina

    DEFF Research Database (Denmark)

    Kolko, Miriam; Vosborg, Fia; Henriksen, Jens Ulrik Lütken

    2016-01-01

    known as HCAR1, may contribute importantly to the control of retinal cell functions in health and disease. GPR81, a G-protein coupled receptor, is known to downregulate cAMP both in adipose and nervous tissue. The receptor also acts through other down-stream mechanisms to control functions......In retina, like in brain, lactate equilibrates across cell membranes via monocarboxylate transporters and in the extracellular space by diffusion, forming a basis for the action of lactate as a transmitter of metabolic signals. In the present paper, we argue that the lactate receptor GPR81, also...

  16. Influence of allelic variations in relation to norepinephrine and mineralocorticoid receptors on psychopathic traits: a pilot study

    Directory of Open Access Journals (Sweden)

    Guillaume Durand

    2018-03-01

    Full Text Available Background Past findings support a relationship between abnormalities in the amygdala and the presence of psychopathic traits. Among other genes and biomarkers relevant to the amygdala, norepinephrine and mineralocorticoid receptors might both play a role in psychopathy due to their association with traits peripheral to psychopathy. The purpose is to examine if allelic variations in single nucleotide polymorphisms related to norepinephrine and mineralocorticoid receptors play a role in the display of psychopathic traits and executive functions. Methods Fifty-seven healthy participants from the community provided a saliva sample for SNP sampling of rs5522 and rs5569. Participants then completed the Psychopathic Personality Inventory–Short Form (PPI-SF and the Tower of Hanoi. Results Allelic variations of both rs5522 and rs5569 were significant when compared to PPI-SF total score and the fearless dominance component of the PPI-SF. A significant result was also obtained between rs5522 and the number of moves needed to complete the 5-disk Tower of Hanoi. Conclusion This pilot study offers preliminary results regarding the effect of allelic variations in SNPs related to norepinephrine and mineralocorticoid receptors on the presence of psychopathic traits. Suggestions are provided to enhance the reliability and validity of a larger-scale study.

  17. Association between level of personality organization as assessed with theory-driven profiles of the Dutch Short Form of the MMPI and outcome of inpatient treatment for personality disorder

    NARCIS (Netherlands)

    Scholte, W.R.; Eurelings-Bontekoe, E.H.M.; Tiemens, B.G.; Verheul, R.; Meerman, A.; Hutschemaekers, G.J.M.

    2014-01-01

    The association between level of personality organization as assessed by theory-driven profile interpretation of the MMPI (Hathaway & McKinley, 1943) Dutch Short Form and treatment outcome was investigated in a naturalistic follow-up study among 121 psychotherapy inpatients who had been treated for

  18. Psychometric properties of the Bulgarian translation of noise sensitivity scale short form (NSS-SF): implementation in the field of noise control.

    Science.gov (United States)

    Dzhambov, Angel M; Dimitrova, Donka D

    2014-01-01

    The Noise Sensitivity Scale Short Form (NSS-SF), developed in English as a more practical form of the classical Weinstein NSS, has not to date been validated in other cultures, and its validity and reliability have not yet been confirmed. This study aimed to validate NSS-SF in Bulgarian and to demonstrate its applicability. The study comprised test-retest (n = 115) and a field-testing (n = 71) of the newly validated scale. Its construct validity was examined with confirmatory factor analysis, and very good model-fit was observed. Temporal stability was assessed in a test-retest (r = 0.990), convergent validity was examined with single-item susceptibility to the noise scale (r = 0.906) and discriminant validity was confirmed with single-item noise annoyance scale (r = 0.718). The lowest observed McDonald's omega across the studies was 0.923. The cross-cultural validation of NSS-SF was successful but it proved to be somewhat problematic with respect to its annoyance-based items.

  19. Transcriptional activation by the thyroid hormone receptor through ligand-dependent receptor recruitment and chromatin remodelling

    DEFF Research Database (Denmark)

    Grøntved, Lars; Waterfall, Joshua J; Kim, Dong Wook

    2015-01-01

    A bimodal switch model is widely used to describe transcriptional regulation by the thyroid hormone receptor (TR). In this model, the unliganded TR forms stable, chromatin-bound complexes with transcriptional co-repressors to repress transcription. Binding of hormone dissociates co...

  20. Preliminary Molecular Dynamic Simulations of the Estrogen Receptor Alpha Ligand Binding Domain from Antagonist to Apo

    Directory of Open Access Journals (Sweden)

    Adrian E. Roitberg

    2008-06-01

    Full Text Available Estrogen receptors (ER are known as nuclear receptors. They exist in the cytoplasm of human cells and serves as a DNA binding transcription factor that regulates gene expression. However the estrogen receptor also has additional functions independent of DNA binding. The human estrogen receptor comes in two forms, alpha and beta. This work focuses on the alpha form of the estrogen receptor. The ERα is found in breast cancer cells, ovarian stroma cells, endometrium, and the hypothalamus. It has been suggested that exposure to DDE, a metabolite of DDT, and other pesticides causes conformational changes in the estrogen receptor. Before examining these factors, this work examines the protein unfolding from the antagonist form found in the 3ERT PDB crystal structure. The 3ERT PDB crystal structure has the estrogen receptor bound to the cancer drug 4-hydroxytamoxifen. The 4-hydroxytamoxifen ligand was extracted before the simulation, resulting in new conformational freedom due to absence of van der Waals contacts between the ligand and the receptor. The conformational changes that result expose the binding clef of the co peptide beside Helix 12 of the receptor forming an apo conformation. Two key conformations in the loops at either end of the H12 are produced resulting in the antagonist to apo conformation transformation. The results were produced over a 42ns Molecular Dynamics simulation using the AMBER FF99SB force field.

  1. Differential trafficking of AMPA receptors following activation of NMDA receptors and mGluRs

    Directory of Open Access Journals (Sweden)

    Sanderson Thomas M

    2011-07-01

    Full Text Available Abstract The removal of AMPA receptors from synapses is a major component of long-term depression (LTD. How this occurs, however, is still only partially understood. To investigate the trafficking of AMPA receptors in real-time we previously tagged the GluA2 subunit of AMPA receptors with ecliptic pHluorin and studied the effects of NMDA receptor activation. In the present study we have compared the effect of NMDA receptor and group I mGluR activation, using GluA2 tagged with super ecliptic pHluorin (SEP-GluA2 expressed in cultured hippocampal neurons. Surprisingly, agonists of the two receptors, which are both able to induce chemical forms of LTD, had clearly distinct effects on AMPA receptor trafficking. In agreement with our previous work we found that transient NMDA receptor activation results in an initial decrease in surface GluA2 from extrasynaptic sites followed by a delayed reduction in GluA2 from puncta (putative synapses. In contrast, transient activation of group I mGluRs, using DHPG, led to a pronounced but more delayed decrease in GluA2 from the dendritic shafts. Surprisingly, there was no average change in the fluorescence of the puncta. Examination of fluorescence at individual puncta, however, indicated that alterations did take place, with some puncta showing an increase and others a decrease in fluorescence. The effects of DHPG were, like DHPG-induced LTD, prevented by treatment with a protein tyrosine phosphatase (PTP inhibitor. The electrophysiological correlate of the effects of DHPG in the SEP-GluA2 infected cultures was a reduction in mEPSC frequency with no change in amplitude. The implications of these findings for the initial mechanisms of expression of both NMDA receptor- and mGluR-induced LTD are discussed.

  2. Signaling cross-talk between peroxisome proliferator-activated receptor/retinoid X receptor and estrogen receptor through estrogen response elements.

    Science.gov (United States)

    Keller, H; Givel, F; Perroud, M; Wahli, W

    1995-07-01

    Peroxisome proliferator-activated receptors (PPARs) and retinoid X receptors (RXRs) are nuclear hormone receptors that are activated by fatty acids and 9-cis-retinoic acid, respectively. PPARs and RXRs form heterodimers that activate transcription by binding to PPAR response elements (PPREs) in the promoter of target genes. The PPREs described thus far consist of a direct tandem repeat of the AGGTCA core element with one intervening nucleotide. We show here that the vitellogenin A2 estrogen response element (ERE) can also function as a PPRE and is bound by a PPAR/RXR heterodimer. Although this heterodimer can bind to several other ERE-related palindromic response elements containing AGGTCA half-sites, only the ERE is able to confer transactivation of test reporter plasmids, when the ERE is placed either close to or at a distance from the transcription initiation site. Examination of natural ERE-containing promoters, including the pS2, very-low-density apolipoprotein II and vitellogenin A2 genes, revealed considerable differences in the binding of PPAR/RXR heterodimers to these EREs. In their natural promoter context, these EREs did not allow transcriptional activation by PPARs/RXRs. Analysis of this lack of stimulation of the vitellogenin A2 promoter demonstrated that PPARs/RXRs bind to the ERE but cannot transactivate due to a nonpermissive promoter structure. As a consequence, PPARs/RXRs inhibit transactivation by the estrogen receptor through competition for ERE binding. This is the first example of signaling cross-talk between PPAR/RXR and estrogen receptor.

  3. Short-Term Sleep Disturbance-Induced Stress Does not Affect Basal Pain Perception, but Does Delay Postsurgical Pain Recovery.

    Science.gov (United States)

    Wang, Po-Kai; Cao, Jing; Wang, Hongzhen; Liang, Lingli; Zhang, Jun; Lutz, Brianna Marie; Shieh, Kun-Ruey; Bekker, Alex; Tao, Yuan-Xiang

    2015-11-01

    Chronic sleep disturbance-induced stress is known to increase basal pain sensitivity. However, most surgical patients frequently report short-term sleep disturbance/deprivation during the pre- and postoperation periods and have normal pain perception presurgery. Whether this short-term sleep disturbance affects postsurgical pain is elusive. Here, we report that pre- or postexposure to rapid eye movement sleep disturbance (REMSD) for 6 hours daily for 3 consecutive days did not alter basal responses to mechanical, heat, and cold stimuli, but did delay recovery in incision-induced reductions in paw withdrawal threshold to mechanical stimulation and paw withdrawal latencies to heat and cold stimuli on the ipsilateral side of male or female rats. This short-term REMSD led to stress shown by an increase in swim immobility time, a decrease in sucrose consumption, and an increase in the level of corticosterone in serum. Blocking this stress via intrathecal RU38486 or bilateral adrenalectomy abolished REMSD-caused delay in recovery of incision-induced reductions in behavioral responses to mechanical, heat, and cold stimuli. Moreover, this short-term REMSD produced significant reductions in the levels of mu opioid receptor and kappa opioid receptor, but not Kv1.2, in the ipsilateral L4/5 spinal cord and dorsal root ganglia on day 9 after incision (but not after sham surgery). Our findings show that short-term sleep disturbance either pre- or postsurgery does not alter basal pain perception, but does exacerbate postsurgical pain hypersensitivity. The latter may be related to the reductions of mu and kappa opioid receptors in the spinal cord and dorsal root ganglia caused by REMSD plus incision. Prevention of short-term sleep disturbance may help recovery from postsurgical pain in patients. Copyright © 2015 American Pain Society. Published by Elsevier Inc. All rights reserved.

  4. Atypical chemokine receptors in cancer: friends or foes?

    Science.gov (United States)

    Massara, Matteo; Bonavita, Ornella; Mantovani, Alberto; Locati, Massimo; Bonecchi, Raffaella

    2016-06-01

    The chemokine system is a fundamental component of cancer-related inflammation involved in all stages of cancer development. It controls not only leukocyte infiltration in primary tumors but also angiogenesis, cancer cell proliferation, and migration to metastatic sites. Atypical chemokine receptors are a new, emerging class of regulators of the chemokine system. They control chemokine bioavailability by scavenging, transporting, or storing chemokines. They can also regulate the activity of canonical chemokine receptors with which they share the ligands by forming heterodimers or by modulating their expression levels or signaling activity. Here, we summarize recent results about the role of these receptors (atypical chemokine receptor 1/Duffy antigen receptor for chemokine, atypical chemokine receptor 2/D6, atypical chemokine receptor 3/CXC-chemokine receptor 7, and atypical chemokine receptor 4/CC-chemokine receptor-like 1) on the tumorigenesis process, indicating that their effects are strictly dependent on the cell type on which they are expressed and on their coexpression with other chemokine receptors. Indeed, atypical chemokine receptors inhibit tumor growth and progression through their activity as negative regulators of chemokine bioavailability, whereas, on the contrary, they can promote tumorigenesis when they regulate the signaling of other chemokine receptors, such as CXC-chemokine receptor 4. Thus, atypical chemokine receptors are key components of the regulatory network of inflammation and immunity in cancer and may have a major effect on anti-inflammatory and immunotherapeutic strategies. © Society for Leukocyte Biology.

  5. Differences in muscarinic acetylcholine receptor subtypes in the central nervous system of long sleep and short sleep mice

    International Nuclear Information System (INIS)

    Watson, M.; Ming, X.; McArdle, J.J.

    1989-01-01

    Differences in voluntary ethanol consumption have been noted in various inbred strains of mice and pharmacogenetic approaches have been used to study the mechanisms of action of many drugs such as ethanol. Long-sleep (LS) and short-sleep (SS) mice, selectively bred for differences in ethanol induced narcosis, provide a method by which a relationship between the differential responsiveness of these geno-types and muscarinic acetylcholine receptors (mAChR) may be evaluated. Sleep times after injection of 3ml ethanol/kg (i.p.) verified the higher sensitivity of LS vs. SS. Mean body weights of LS (26.5g) vs. SS (22g) were also significantly (p 3 H](-) quinuclidinylbenzilate ([ 3 H](-)QNB), a specific but nonsubtype selective mAChR antagonist, [ 3 H]pirenzepine ([ 3 H]PZ), a specific M1 mAChR antagonist and [ 3 H]11-2-[[2-[(diethylamino) methyl]-1-piperidinyl] acetyl]-5,11-dihydro-6H-pyrido (2,3-b) (1,4) benzodiazepine-6-one, ([ 3 H]AF-DX 116), an M2 selective antagonist were performed to determine mAChR affinity (K d ) and density (B max ) in CNS regions such as the cerebral cortex, hippocampus, corpus striatum and other areas. Significantly lower (30-40%) [ 3 H](-)QNB binding suggests that SS have fewer mAChR's than LS in many areas. These differences may relate to their differential ethanol sensitivity

  6. Global Developmental Gene Programing Involves a Nuclear Form of Fibroblast Growth Factor Receptor-1 (FGFR1.

    Directory of Open Access Journals (Sweden)

    Christopher Terranova

    Full Text Available Genetic studies have placed the Fgfr1 gene at the top of major ontogenic pathways that enable gastrulation, tissue development and organogenesis. Using genome-wide sequencing and loss and gain of function experiments the present investigation reveals a mechanism that underlies global and direct gene regulation by the nuclear form of FGFR1, ensuring that pluripotent Embryonic Stem Cells differentiate into Neuronal Cells in response to Retinoic Acid. Nuclear FGFR1, both alone and with its partner nuclear receptors RXR and Nur77, targets thousands of active genes and controls the expression of pluripotency, homeobox, neuronal and mesodermal genes. Nuclear FGFR1 targets genes in developmental pathways represented by Wnt/β-catenin, CREB, BMP, the cell cycle and cancer-related TP53 pathway, neuroectodermal and mesodermal programing networks, axonal growth and synaptic plasticity pathways. Nuclear FGFR1 targets the consensus sequences of transcription factors known to engage CREB-binding protein, a common coregulator of transcription and established binding partner of nuclear FGFR1. This investigation reveals the role of nuclear FGFR1 as a global genomic programmer of cell, neural and muscle development.

  7. [Application of the concetrations ratio of soluble receptor tyrosine kinase type 1, and placental growth factor for short-term prediction and diagnosis of preeclampsia].

    Science.gov (United States)

    Bubeníková, Š; Cíchová, A; Roubalová, L; Durdová, V; Vlk, R

    Bring a comprehensive overview of the available information about applications of the concetration ratio of soluble receptor tyrosine kinase type 1 (sFlt-1), and placental growth factor for short-term prediction and diagnosis of preeclampsia. Overview study. Department of Midwifery, Faculty of Health Sciences, Olomouc; Department of Clinical Biochemistry, University Hospital Olomouc; Department of Obstetrics and Gynecology, University Hospital Olomouc; Department of Obstetrics and Gynecology, 2nd Faculty of Medicine, Charles University in Prague and Motol University Hospital. Analysis of literary sources and databases Ovid, Medline (2001-2016). Preeclampsia is a multisystem disease with not fully understood etiology. This disease occurs in 2-5% of pregnant women. Preeclampsia is one of the main causes of global maternal and perinatal morbidity and mortality. It manifests itself as a newborn hypertension and proteinuria after 20 weeks of pregnancy in previously normotensive women. The only effective treatment is the delivery of the child. Diagnosis of preeclampsia comprises measuring blood pressure and proteinuria. These indicators have low diagnostic sensitivity and specificity. In preeclampsia, there is a decrease of serum levels of placental growth factor (PlGF). Soluble receptor tyrosine kinase type 1 (sFlt-1) is an antagonist of PlGF. Increased levels of sFlt-1 in proportion to the reduced level of PlGF are associated with an increased risk of preeclampsia. The sFlt-1/PlGF ratio can be a better predictive marker in the diagnosis of pre-eclampsia after 20 weeks of gestation.

  8. Different pathways of [3H]inositol phosphate formation mediated by α 1a- and α 1b-adrenergic receptors

    International Nuclear Information System (INIS)

    Wilson, K.M.; Minneman, K.P.

    1990-01-01

    The types of inositol phosphates (InsPs) formed in response to activation of alpha 1-adrenergic receptor subtypes were determined in collagenase-dispersed renal cells and hepatocytes by high pressure liquid chromatography separation. In hepatocytes, which contain only the alpha 1b subtype, norepinephrine stimulated rapid (10-s) formation of [3H]Ins(1,4,5)P3 and [3H]Ins(1,3,4)P3 and slower (5-min) formation of Ins(1,4)P2 and Ins(1)P. Selective inactivation of alpha 1b receptors by chloroethylclonidine almost completely blocked the effects of norepinephrine in hepatocytes. In renal cells, which contain both alpha 1a and alpha 1b receptors in a 60:40 ratio, norepinephrine did not significantly increase the size of any peaks until 5 min after agonist activation. At this time, only a peak eluting with Ins(1)P and one eluting shortly after Ins(1,4)P2 were significantly elevated. Incubation with norepinephrine for 2 h caused small but significant increases in peaks co-eluting with Ins(1)P and Ins(1,4,5)P3 in renal cells; however, only the increase in Ins(1)P was inhibited by chloroethylclonidine pretreatment. Extraction under neutral conditions suggested that cyclic InsPs may be the primary compounds formed in response to norepinephrine in renal cells. Removal of extracellular Ca2+ caused a 60% reduction in the InsP response to norepinephrine in renal cells but had no effect in hepatocytes. These results suggest that activation of alpha 1a and alpha 1b receptor subtypes results in formation of different InsPs and that the response to alpha 1a activation may require influx of extracellular Ca2+

  9. Short-term sleep deprivation impairs spatial working memory and modulates expression levels of ionotropic glutamate receptor subunits in hippocampus.

    Science.gov (United States)

    Xie, Meilan; Yan, Jie; He, Chao; Yang, Li; Tan, Gang; Li, Chao; Hu, Zhian; Wang, Jiali

    2015-06-01

    Hippocampus-dependent learning memory is sensitive to sleep deprivation (SD). Although the ionotropic glutamate receptors play a vital role in synaptic plasticity and learning and memory, however, whether the expression of these receptor subunits is modulated by sleep loss remains unclear. In the present study, western blotting was performed by probing with specific antibodies against the ionotropic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunits GluA1, GluA2, GluA3, and against the N-methyl-d-aspartate (NMDA) glutamate receptor subunits GluN1, GluN2A, GluN2B. In hippocampus, down regulation of surface GluA1 and GluN2A surface expression were observed in both SD groups. However, surface expression level of GluA2, GluA3, GluN1 and GluN2B was significantly up-regulated in 8h-SD rats when compared to the 4h-SD rats. In parallel with the complex changes in AMPA and NMDA receptor subunit expressions, we found the 8h-SD impaired rat spatial working memory in 30-s-delay T-maze task, whereas no impairment of spatial learning was observed in 4h-SD rats. These results indicate that sleep loss alters the relative expression levels of the AMPA and NMDA receptors, thus affects the synaptic strength and capacity for plasticity and partially contributes to spatial memory impairment. Copyright © 2015. Published by Elsevier B.V.

  10. Improving the measurement of health-related quality of life in adolescent with idiopathic scoliosis: the SRS-7, a Rasch-developed short form of the SRS-22 questionnaire.

    Science.gov (United States)

    Caronni, Antonio; Zaina, Fabio; Negrini, Stefano

    2014-04-01

    Scoliosis Research Society-22 (SRS-22) questionnaire was developed to evaluate health-related quality of life (HRQL) in adolescent idiopathic scoliosis (AIS) patients. Rasch analysis (RA) is a statistical procedure which turns questionnaire ordinal scores into interval measures. Measures from Rasch-compatible questionnaires can be used, similar to body temperature or blood pressure, to quantify disease severity progression and treatment efficacy. Purpose of the current work is to present Rasch analysis (RA) of the SRS-22 questionnaire and to develop an SRS-22 Rasch-approved short form. 300 SRS-22 were randomly collected from 2447 consecutive IS adolescents at their first evaluation (229 females; 13.9 ± 1.9 years; 26.9 ± 14.7 Cobb°) in a scoliosis outpatient clinic. RA showed both disordered thresholds and overall misfit of the SRS-22. Sixteen items were re-scored and two misfitting items (6 and 14) removed to obtain a Rasch-compatible questionnaire. Participants HRQL measured too high with the rearranged questionnaire, indicating a severe SRS-22 ceiling effect. RA also highlighted SRS-22 multidimensionality, with pain/function not merging with self-image/mental health items. Item 3 showed differential item functioning (DIF) for both curve and hump amplitude. A 7-item questionnaire (SRS-7) was prepared by selecting single items from the original SRS-22. SRS-7 showed fit to the model, unidimensionality and no DIF. Compared with the SRS-22, the short form scale shows better targeting of the participants' population. RA shows that SRS-22 has poor clinimetric properties; moreover, when used with AIS at first evaluation, SRS-22 is affected by a severe ceiling effect. SRS-7, an SRS-22 7-item short form questionnaire, provides an HRQL interval measure better tailored to these participants. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. The Structural Basis for Endotoxin-induced Allosteric Regulation of the Toll-like Receptor 4 (TLR4) Innate Immune Receptor*

    Science.gov (United States)

    Paramo, Teresa; Piggot, Thomas J.; Bryant, Clare E.; Bond, Peter J.

    2013-01-01

    As part of the innate immune system, Toll-like receptor 4 (TLR4) recognizes bacterial cell surface lipopolysaccharide (LPS) by forming a complex with a lipid-binding co-receptor, MD-2. In the presence of agonist, TLR4·MD-2 dimerizes to form an active receptor complex, leading to initiation of intracellular inflammatory signals. TLR4 is of great biomedical interest, but its pharmacological manipulation is complicated because even subtle variations in the structure of LPS can profoundly impact the resultant immunological response. Here, we use atomically detailed molecular simulations to gain insights into the nature of the molecular signaling mechanism. We first demonstrate that MD-2 is extraordinarily flexible. The “clamshell-like” motions of its β-cup fold enable it to sensitively match the volume of its hydrophobic cavity to the size and shape of the bound lipid moiety. We show that MD-2 allosterically transmits this conformational plasticity, in a ligand-dependent manner, to a phenylalanine residue (Phe-126) at the cavity mouth previously implicated in TLR4 activation. Remarkably, within the receptor complex, we observe spontaneous transitions between active and inactive signaling states of Phe-126, and we confirm that Phe-126 is indeed the “molecular switch” in endotoxic signaling. PMID:24178299

  12. The structural basis for endotoxin-induced allosteric regulation of the Toll-like receptor 4 (TLR4) innate immune receptor.

    Science.gov (United States)

    Paramo, Teresa; Piggot, Thomas J; Bryant, Clare E; Bond, Peter J

    2013-12-20

    As part of the innate immune system, Toll-like receptor 4 (TLR4) recognizes bacterial cell surface lipopolysaccharide (LPS) by forming a complex with a lipid-binding co-receptor, MD-2. In the presence of agonist, TLR4·MD-2 dimerizes to form an active receptor complex, leading to initiation of intracellular inflammatory signals. TLR4 is of great biomedical interest, but its pharmacological manipulation is complicated because even subtle variations in the structure of LPS can profoundly impact the resultant immunological response. Here, we use atomically detailed molecular simulations to gain insights into the nature of the molecular signaling mechanism. We first demonstrate that MD-2 is extraordinarily flexible. The "clamshell-like" motions of its β-cup fold enable it to sensitively match the volume of its hydrophobic cavity to the size and shape of the bound lipid moiety. We show that MD-2 allosterically transmits this conformational plasticity, in a ligand-dependent manner, to a phenylalanine residue (Phe-126) at the cavity mouth previously implicated in TLR4 activation. Remarkably, within the receptor complex, we observe spontaneous transitions between active and inactive signaling states of Phe-126, and we confirm that Phe-126 is indeed the "molecular switch" in endotoxic signaling.

  13. Metabotropic glutamate receptor 2 and corticotrophin-releasing factor receptor-1 gene expression is differently regulated by BDNF in rat primary cortical neurons

    DEFF Research Database (Denmark)

    Jørgensen, Christinna V; Klein, Anders B; El-Sayed, Mona

    2013-01-01

    Brain-derived neurotrophic factor (BDNF) is important for neuronal survival and plasticity. Incorporation of matured receptor proteins is an integral part of synapse formation. However, whether BDNF increases synthesis and integration of receptors in functional synapses directly is unclear. We...... are particularly interested in the regulation of the 5-hydroxytryptamine receptor 2A (5-HT2A R). This receptor form a functional complex with the metabotropic glutamate receptor 2 (mGluR2) and is recruited to the cell membrane by the corticotrophin-releasing factor receptor 1 (CRF-R1). The effect of BDNF on gene...... expression for all these receptors, as well as a number of immediate-early genes, was pharmacologically characterized in primary neurons from rat frontal cortex. BDNF increased CRF-R1 mRNA levels up to fivefold, whereas mGluR2 mRNA levels were proportionally downregulated. No effect on 5-HT2A R mRNA was seen...

  14. Uncompetitive antagonism of AMPA receptors

    DEFF Research Database (Denmark)

    Andersen, Trine F; Tikhonov, Denis B; Bølcho, Ulrik

    2006-01-01

    Philanthotoxins are uncompetitive antagonists of Ca2+-permeable AMPA receptors presumed to bind to the pore-forming region, but a detailed molecular mechanism for this interaction is missing. Here a small library of novel philanthotoxins was designed and synthesized using a solid-phase strategy. ...

  15. Validation of the Italian Tinnitus Questionnaire Short Form (TQ 12-I as a Brief Test for the Assessment of Tinnitus-Related Distress: Results of a Cross-Sectional Multicenter-Study

    Directory of Open Access Journals (Sweden)

    Roland Moschen

    2018-01-01

    Full Text Available Objectives: The use of reliable and valid psychometric tools to assess subjectively experienced distress due to tinnitus is broadly recommended. The purpose of the study was the validation of the Italian version of Tinnitus Questionnaire 12 item short form (TQ 12-I as a brief test for the assessment of patient reported tinnitus-related distress.Design: Cross-sectional multicenter questionnaire study.Setting: Tinnitus Center, European Hospital (Rome, the Department of Otorhinolaryngology, “Guglielmo da Saliceto” Hospital (Piacenza, and the Department of Audiology and Phoniatry, “Mater Domini” University Hospital (Catanzaro.Participants: One hundred and forty-three outpatients with tinnitus treated at one of the participating medical centers.Main Outcome Measures: Tinnitus Questionnaire Short Form (TQ 12-I, compared to the Tinnitus Handicap Inventory (THI, Brief Symptom Inventory (BSI, and Short Form (SF-36 Health Survey.Results: Our factor analysis revealed a two-factor solution (health anxiety, cognitive distress, accounting for 53.5% of the variance. Good internal consistency for the total score (α = 0.86 and both factors (α = 0.79–0.87 was found. Moderate correlations with the THI (r = 0.65, p < 0.001 indicated good convergent validity. Tinnitus distress was further correlated to increased psychological distress (r = 0.31, p < 0.001 and reduced emotional well-being (r = -0.34, p < 0.001.Conclusion: The study clearly showed that the TQ 12-I is a reliable and valid instrument to assess tinnitus-related distress which can be used in clinical practice as well as for research.

  16. Antibodies to a soluble form of a tumor necrosis factor (TNF) receptor have TNF-like activity

    DEFF Research Database (Denmark)

    Engelmann, H; Holtmann, H; Brakebusch, C

    1990-01-01

    Immunological cross-reactivity between tumor necrosis factor (TNF) binding proteins which are present in human urine (designated TBPI and TBPII) and two molecular species of the cell surface receptors for TNF is demonstrated. The two TNF receptors are shown to be immunologically distinct, to differ....... These antibodies are cytotoxic to cells which are sensitive to TNF toxicity, induce resistance to TNF toxicity, enhance the incorporation of thymidine into normal fibroblasts, inhibit the growth of chlamydiae, and induce the synthesis of prostaglandin E2. Monovalent F(ab) fragments of the polyclonal antibodies...

  17. Validity and reliability of International Physical Activity Questionnaire-Short Form in Chinese youth.

    Science.gov (United States)

    Wang, Chao; Chen, Peijie; Zhuang, Jie

    2013-12-01

    The psychometric profiles of the widely used International Physical Activity Questionnaire-Short Form (IPAQ-SF) in Chinese youth have not been reported. The purpose of this study was to examine the validity and reliability of the IPAQ-SF using a sample of Chinese youth. One thousand and twenty-one youth (M(age) = 14.26 +/- 1.63 years, 52.8% boys) from 11 cities in China wore accelerometers for 7 consecutive days and completed the IPAQ-SF on the 8th day to recall their physical activity (PA) during accelerometer-wearing days. A subsample of 92 youth (M(age) = 15.90 +/- 1.35 years, 46.7% boys) completed the IPAQ-SF again a week later to recall their PA during accelerometer-wearing days. Differences in PA estimated by the IPAQ-SF and accelerometer were examined by paired-sample t test. Spearman correlation coefficients were used to examine the correlation between the IPAQ-SF and accelerometer. Test-retest reliability of the IPAQ-SF was determined by the intraclass correlation coefficient (ICC). Compared with accelerometer, the IPAQ-SF overestimated sedentary time, moderate PA (MPA), vigorous PA (VPA), and moderate-to-vigorous PA (MVPA). Correlations between PA (total PA, MPA, VPA, and MVPA) and sedentary time measured by 2 instruments ranged from "none" to "low" (p = .08-.31). Test-retest ICC of the IPAQ-SF ranged from "moderate" to "high" (ICC = .43-.83), except for sitting in boys (ICC = .06), sitting for the whole sample (ICC = .32), and VPA in girls (ICC = .35). The IPAQ-SF was not a valid instrument for measuring PA and sedentary behavior in Chinese youth.

  18. Measurement Development and Validation of the Family Supportive Supervisor Behavior Short-Form (FSSB-SF)

    Science.gov (United States)

    Hammer, Leslie B.; Kossek, Ellen Ernst; Bodner, Todd; Crain, Tori

    2013-01-01

    Recently, scholars have demonstrated the importance of Family Supportive Supervisor Behaviors (FSSB), defined as behaviors exhibited by supervisors that are supportive of employees’ family roles, in relation to health, well-being, and organizational outcomes. FSSB was originally conceptualized as a multidimensional, superordinate construct with four subordinate dimensions assessed with 14 items: emotional support, instrumental support, role modeling behaviors, and creative work-family management. Retaining one item from each dimension, two studies were conducted to support the development and use of a new FSSB-Short Form (FSSB-SF). Study 1 draws on the original data from the FSSB validation study of retail employees to determine if the results using the 14-item measure replicate with the shorter 4-item measure. Using data from a sample of 823 information technology professionals and their 219 supervisors, Study 2 extends the validation of the FSSB-SF to a new sample of professional workers and new outcome variables. Results from multilevel confirmatory factor analyses and multilevel regression analyses provide evidence of construct and criterion-related validity of the FSSB-SF, as it was significantly related to work-family conflict, job satisfaction, turnover intentions, control over work hours, obligation to work when sick, perceived stress, and reports of family time adequacy. We argue that it is important to develop parsimonious measures of work-family specific support to ensure supervisor support for work and family is mainstreamed into organizational research and practice. PMID:23730803

  19. Short-term increases in transient receptor potential vanilloid-1 mediate stress-induced enhancement of neuronal excitation.

    Science.gov (United States)

    Weitlauf, Carl; Ward, Nicholas J; Lambert, Wendi S; Sidorova, Tatiana N; Ho, Karen W; Sappington, Rebecca M; Calkins, David J

    2014-11-12

    Progression of neurodegeneration in disease and injury is influenced by the response of individual neurons to stressful stimuli and whether this response includes mechanisms to counter declining function. Transient receptor potential (TRP) cation channels transduce a variety of disease-relevant stimuli and can mediate diverse stress-dependent changes in physiology, both presynaptic and postsynaptic. Recently, we demonstrated that knock-out or pharmacological inhibition of the TRP vanilloid-1 (TRPV1) capsaicin-sensitive subunit accelerates degeneration of retinal ganglion cell neurons and their axons with elevated ocular pressure, the critical stressor in the most common optic neuropathy, glaucoma. Here we probed the mechanism of the influence of TRPV1 on ganglion cell survival in mouse models of glaucoma. We found that induced elevations of ocular pressure increased TRPV1 in ganglion cells and its colocalization at excitatory synapses to their dendrites, whereas chronic elevation progressively increased ganglion cell Trpv1 mRNA. Enhanced TRPV1 expression in ganglion cells was transient and supported a reversal of the effect of TRPV1 on ganglion cells from hyperpolarizing to depolarizing, which was also transient. Short-term enhancement of TRPV1-mediated activity led to a delayed increase in axonal spontaneous excitation that was absent in ganglion cells from Trpv1(-/-) retina. In isolated ganglion cells, pharmacologically activated TRPV1 mobilized to discrete nodes along ganglion cell dendrites that corresponded to sites of elevated Ca(2+). These results suggest that TRPV1 may promote retinal ganglion cell survival through transient enhancement of local excitation and axonal activity in response to ocular stress. Copyright © 2014 the authors 0270-6474/14/3415369-13$15.00/0.

  20. Class I Cytokine Receptors: Structure and function in the Membrane

    DEFF Research Database (Denmark)

    Bugge, Katrine Østergaard

    bilayer via structural characterizations of TMD representatives. To enable structural studies of these domains, an organic-extraction based strategy for efficient production of isotope-labeled TMDs with or without short intrinsically disordered regions was developed. This strategy successfully provided...... of these challenging domains. Supplemented by a review of the current collection of TMD structures from single-pass transmembrane receptors, the thesis as a whole provides important insights on the structure and function in the membrane as well as highlight the open questions to be addressed in the years to come.......Class I cytokine receptors are involved in important biological functions of both physiological and pathological nature in mammals. However, the molecular details of the cross-membrane signal transduction through these receptors remain obscure. One of the major reasons for this is the lack...

  1. An exemplar-familiarity model predicts short-term and long-term probe recognition across diverse forms of memory search.

    Science.gov (United States)

    Nosofsky, Robert M; Cox, Gregory E; Cao, Rui; Shiffrin, Richard M

    2014-11-01

    Experiments were conducted to test a modern exemplar-familiarity model on its ability to account for both short-term and long-term probe recognition within the same memory-search paradigm. Also, making connections to the literature on attention and visual search, the model was used to interpret differences in probe-recognition performance across diverse conditions that manipulated relations between targets and foils across trials. Subjects saw lists of from 1 to 16 items followed by a single item recognition probe. In a varied-mapping condition, targets and foils could switch roles across trials; in a consistent-mapping condition, targets and foils never switched roles; and in an all-new condition, on each trial a completely new set of items formed the memory set. In the varied-mapping and all-new conditions, mean correct response times (RTs) and error proportions were curvilinear increasing functions of memory set size, with the RT results closely resembling ones from hybrid visual-memory search experiments reported by Wolfe (2012). In the consistent-mapping condition, new-probe RTs were invariant with set size, whereas old-probe RTs increased slightly with increasing study-test lag. With appropriate choice of psychologically interpretable free parameters, the model accounted well for the complete set of results. The work provides support for the hypothesis that a common set of processes involving exemplar-based familiarity may govern long-term and short-term probe recognition across wide varieties of memory- search conditions. PsycINFO Database Record (c) 2014 APA, all rights reserved.

  2. Novel Functional Properties of Drosophila CNS Glutamate Receptors

    Energy Technology Data Exchange (ETDEWEB)

    Li, Yan; Dharkar, Poorva; Han, Tae-Hee; Serpe, Mihaela; Lee, Chi-Hon; Mayer, Mark L.

    2016-12-01

    Phylogenetic analysis reveals AMPA, kainate, and NMDA receptor families in insect genomes, suggesting conserved functional properties corresponding to their vertebrate counterparts. However, heterologous expression of the Drosophila kainate receptor DKaiR1D and the AMPA receptor DGluR1A revealed novel ligand selectivity at odds with the classification used for vertebrate glutamate receptor ion channels (iGluRs). DKaiR1D forms a rapidly activating and desensitizing receptor that is inhibited by both NMDA and the NMDA receptor antagonist AP5; crystallization of the KaiR1D ligand-binding domain reveals that these ligands stabilize open cleft conformations, explaining their action as antagonists. Surprisingly, the AMPA receptor DGluR1A shows weak activation by its namesake agonist AMPA and also by quisqualate. Crystallization of the DGluR1A ligand-binding domain reveals amino acid exchanges that interfere with binding of these ligands. The unexpected ligand-binding profiles of insect iGluRs allows classical tools to be used in novel approaches for the study of synaptic regulation.

  3. Structural and Molecular Modeling Features of P2X Receptors

    Directory of Open Access Journals (Sweden)

    Luiz Anastacio Alves

    2014-03-01

    Full Text Available Currently, adenosine 5'-triphosphate (ATP is recognized as the extracellular messenger that acts through P2 receptors. P2 receptors are divided into two subtypes: P2Y metabotropic receptors and P2X ionotropic receptors, both of which are found in virtually all mammalian cell types studied. Due to the difficulty in studying membrane protein structures by X-ray crystallography or NMR techniques, there is little information about these structures available in the literature. Two structures of the P2X4 receptor in truncated form have been solved by crystallography. Molecular modeling has proven to be an excellent tool for studying ionotropic receptors. Recently, modeling studies carried out on P2X receptors have advanced our knowledge of the P2X receptor structure-function relationships. This review presents a brief history of ion channel structural studies and shows how modeling approaches can be used to address relevant questions about P2X receptors.

  4. Evaluation of the Satisfaction with Appearance Scale and Its Short Form in Systemic Sclerosis: Analysis from the UCLA Scleroderma Quality of Life Study.

    Science.gov (United States)

    Mills, Sarah D; Fox, Rina S; Merz, Erin L; Clements, Philip J; Kafaja, Suzanne; Malcarne, Vanessa L; Furst, Daniel E; Khanna, Dinesh

    2015-09-01

    Changes in appearance are common in patients with systemic sclerosis (SSc) and can significantly affect well-being. The Satisfaction with Appearance Scale (SWAP) measures body image dissatisfaction in persons with visible disfigurement; the Brief-Satisfaction with Appearance Scale (Brief-SWAP) is its short form. The present study evaluated the reliability and validity of SWAP and Brief-SWAP scores in SSc. A sample of 207 patients with SSc participating in the University of California, Los Angeles Scleroderma Quality of Life Study completed the SWAP. Brief-SWAP scores were derived from the SWAP. The structural validity of both measures was investigated using confirmatory factor analysis. Internal consistency reliability of total and subscale scores was assessed with Cronbach's alpha coefficients. Convergent and divergent validity was evaluated using the Center for Epidemiological Studies Depression Scale, the Health Assessment Questionnaire-Disability Index, and the Medical Outcomes Study Short Form-36 questionnaire. SWAP and Brief-SWAP total scores were highly correlated (r = 0.97). The 4-factor structure of the SWAP fit well descriptively; the 2-factor structure of the Brief-SWAP fit well descriptively and statistically. Internal consistencies for total and subscale scores were good, and results supported convergent and divergent validity. Both versions are suitable for use in patients with SSc. The Brief-SWAP is most efficient; the full SWAP yields additional subscales that may be informative in understanding body image issues in patients with SSc.

  5. Designing of an artificial light energy converter in the form of short-chain dyad when combined with core-shell gold/silver nanocomposites.

    Science.gov (United States)

    Dutta Pal, Gopa; Paul, Somnath; Bardhan, Munmun; De, Asish; Ganguly, Tapan

    2017-06-05

    UV-vis absorption, steady state and time resolved fluorescence and absorption spectroscopic investigations demonstrate that the short chain dyad MNTMA when combined with gold-silver core-shell (Au@Ag) nanocomposite , forms elongated conformers in the excited state whereas for the dyad - Ag (spherical) system the majority of dyads remains in a folded conformation. In the dyad-core-shell nanocomposite system, energy wasting charge recombination rate slows down primarily due to elongated conformation and thus it may be anticipated that this hybrid nanocomposite system may serve as a better light energy conversion device. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Effects of arginine vasotocin and mesotocin on the activation and development of amiloride-blockable short-circuit current across larval, adult, and cultured larval bullfrog skins.

    Science.gov (United States)

    Takada, Makoto; Fujimaki-Aoba, Kayo; Hokari, Shigeru

    2010-03-01

    Amphibian skin has osmoregulatory functions, with Na(+) crossing from outside to inside. Na(+) transport can be measured as the short-circuit current (SCC). We investigated the short-term and long-term effects of arginine vasotocin (AVT) and mesotocin (MT) (which modulate Na(+) transport) on the activation and development of an amiloride-blockable SCC (adult-type feature) in larval, adult, and corticoid-cultured larval bullfrog skins. We found: (1) AVT-receptor (AVT-R) and MT-receptor (MT-R) mRNAs could be detected in both larval and adult skins, (2) in the short term (within 60 min), the larval SCC (amiloride-stimulated SCC) was increased by AVT, forskolin, and MT, suggesting that AVT and MT did not activate the inactive ENaC (epithelial sodium channel) protein thought to be expressed in larval skin, (3) in the short term (within 90 min), AVT, forskolin, and MT stimulated the adult SCC (amiloride-blockable SCC), (4) AVT and MT increased both the larval and adult SCC via receptors insensitive to OPC-21268 (an antagonist of the V(1)-type receptor), OPC-31260 (an antagonist of the V(2)-type receptor), and ([d(CH(2))(5),Tyr(Me)(2),Thr(4),Orn(8),des-Gly-NH (2) (9) ]VT) (an antagonist of the oxytocin receptor), (5) culturing EDTA-treated larval skin with corticoids supplemented with AVT (1 microM) or MT (1 microM) for 2 weeks (long-term effects of AVT and MT) did not alter the corticoid-induced development of an amiloride-blockable SCC (adult-type feature). AVT and MT thus have the potential to stimulate SCC though channels that are already expressed, but they may not influence the development of the amiloride-blockable SCC (an adult-type feature) in larval skin.

  7. Cross-Cultural Adaptation of a Farsi Version of the Impulsive Behavior Scale‎-Short Form in Iran

    Directory of Open Access Journals (Sweden)

    Omid Shokri

    2016-12-01

    Full Text Available Background: The aim of the present study was to investigate psychometric properties of the Impulsive Behavior Scale-Short Form (IBS-SF among undergraduate Farsi-speaking Iranian students. In this study, 201 individuals (95 men, 106 women answered to the IBS-SF and the Problematic and Risky Internet Use Screening Scale‎ (PRIUSS.Methods: The confirmatory factor analysis and internal consistency methods were used to compute the factorial validity and reliability of the IBS-SF, respectively. In order to examine the construct validity of the IBS-SF, the correlation of different dimensions of IBS-SF with PRIUSS was determined.Results: The results of confirmatory factor analysis showed that a 5-factor structure of the negative urgency, lack of perseverance, lack of premeditation, sensation seeking, and positive urgency was replicated in the Iranian sample. The IBS-SF convergent validity was confirmed by a correlation between different features of impulsivity trait and problematic and risky internet use behavior. The internal consistency of the different subscales of impulsivity trait ranged from 0.67 to 0.80.Conclusion: The present study revealed that the IBS-SF is a valid and reliable scale for measuring impulsivity trait among undergraduate Farsi-speaking Iranian students.

  8. Usefulness of the Wechsler Intelligence Scale short form for assessing functional outcomes in patients with schizophrenia.

    Science.gov (United States)

    Sumiyoshi, Chika; Fujino, Haruo; Sumiyoshi, Tomiki; Yasuda, Yuka; Yamamori, Hidenaga; Ohi, Kazutaka; Fujimoto, Michiko; Takeda, Masatoshi; Hashimoto, Ryota

    2016-11-30

    The Wechsler Adult Intelligence Scale (WAIS) has been widely used to assess intellectual functioning not only in healthy adults but also people with psychiatric disorders. The purpose of the study was to develop an optimal WAIS-3 short form (SF) to evaluate intellectual status in patients with schizophrenia. One hundred and fifty patients with schizophrenia and 221 healthy controls entered the study. To select subtests for SFs, following criteria were considered: 1) predictability for the full IQ (FIQ), 2) representativeness for the IQ structure, 3) consistency of subtests across versions, 4) sensitivity to functional outcome measures, 5) conciseness in administration time. First, exploratory factor analysis (EFA) and multiple regression analysis were conducted to select subtests satisfying the first and the second criteria. Then, candidate SFs were nominated based on the third criterion and the coverage of verbal IQ and performance IQ. Finally, the optimality of candidate SFs was evaluated in terms of the fourth and fifth criteria. The results suggest that the dyad of Similarities and Symbol Search was the most optimal satisfying the above criteria. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  9. Extracellular loop 2 of the free Fatty Acid receptor 2 mediates allosterism of a phenylacetamide ago-allosteric modulator

    DEFF Research Database (Denmark)

    Smith, Nicola J; Ward, Richard J; Stoddart, Leigh A

    2011-01-01

    Allosteric agonists are powerful tools for exploring the pharmacology of closely related G protein-coupled receptors that have nonselective endogenous ligands, such as the short chain fatty acids at free fatty acid receptors 2 and 3 (FFA2/GPR43 and FFA3/GPR41, respectively). We explored the molec...

  10. Identification of Receptor Ligands and Receptor Subtypes Using Antagonists in a Capillary Electrophoresis Single-Cell Biosensor Separation System

    Science.gov (United States)

    Fishman, Harvey A.; Orwar, Owe; Scheller, Richard H.; Zare, Richard N.

    1995-08-01

    A capillary electrophoresis system with single-cell biosensors as a detector has been used to separate and identify ligands in complex biological samples. The power of this procedure was significantly increased by introducing antagonists that inhibited the cellular response from selected ligand-receptor interactions. The single-cell biosensor was based on the ligand-receptor binding and G-protein-mediated signal transduction pathways in PC12 and NG108-15 cell lines. Receptor activation was measured as increases in cytosolic free calcium ion concentration by using fluorescence microscopy with the intracellular calcium ion indicator fluo-3 acetoxymethyl ester. Specifically, a mixture of bradykinin (BK) and acetylcholine (ACh) was fractionated and the components were identified by inhibiting the cellular response with icatibant (HOE 140), a selective antagonist to the BK B_2 receptor subtype (B_2BK), and atropine, an antagonist to muscarinic ACh receptor subtypes. Structurally related forms of BK were also identified based on inhibiting B_2BK receptors. Applications of this technique include identification of endogenous BK in a lysate of human hepatocellular carcinoma cells (Hep G2) and screening for bioactivity of BK degradation products in human blood plasma. The data demonstrate that the use of antagonists with a single-cell biosensor separation system aids identification of separated components and receptor subtypes.

  11. Urolinin: The First Linear Peptidic Urotensin-II Receptor Agonist.

    Science.gov (United States)

    Bandholtz, Sebastian; Erdmann, Sarah; von Hacht, Jan Lennart; Exner, Samantha; Krause, Gerd; Kleinau, Gunnar; Grötzinger, Carsten

    2016-11-23

    This study investigated the role of individual U-II amino acid positions and side chain characteristics important for U-IIR activation. A complete permutation library of 209 U-II variants was studied in an activity screen that contained single substitution variants of each position with one of the other 19 proteinogenic amino acids. Receptor activation was measured using a cell-based high-throughput fluorescence calcium mobilization assay. We generated the first complete U-II substitution map for U-II receptor activation, resulting in a detailed view into the structural features required for receptor activation, accompanied by complementary information from receptor modeling and ligand docking studies. On the basis of the systematic SAR study of U-II, we created 33 further short and linear U-II variants from eight to three amino acids in length, including d- and other non-natural amino acids. We identified the first high-potency linear U-II analogues. Urolinin, a linear U-II agonist (nWWK-Tyr(3-NO 2 )-Abu), shows low nanomolar potency as well as improved metabolic stability.

  12. mGlu5 Receptor Functional Interactions and Addiction

    Directory of Open Access Journals (Sweden)

    Robyn eBrown

    2012-05-01

    Full Text Available The idea of ‘receptor mosaics’ suggests that proteins can form complex and dynamic networks, with respect to time and protein make up, which has the potential to make significant contributions to the diversity and specificity of GPCR signalling, particularly in neuropharmacology, where a few key receptors have been implicated in multiple neurological and psychiatric disorders such as addiction. Metabotropic glutamate type 5 receptors (mGlu5 have been shown to heterodimerise and form complexes with other GPCRs including adenosine A2A and dopamine D2 receptors. mGlu5-containing complexes are found in the striatum, a region of the brain known to be critical for mediating the rewarding and incentive motivational properties of drugs of abuse. Indeed, initial studies indicate a role for mGlu5-containing complexes in rewarding and conditioned effects of drugs, as well as drug-seeking behaviour. This is consistent with the substantial influence that mGlu5 complexes appear to have on striatal function, regulating both GABAergic output of striatopallidal neurons and glutamatergic input from corticostriatal afferents. Given their discrete localization, mGlu5-containing complexes represent a novel way in which to minimize the off-target effects and therefore provide us with an exciting therapeutic avenue for drug discovery efforts. Indeed, the therapeutic targeting of receptor mosaics in a tissue specific or temporal manner (for example, a sub-population of receptors in a ‘pathological state’ has the potential to dramatically reduce detrimental side effects that may otherwise impair vital brain function.

  13. Sphingosine-1-phosphate (S1P) displays sustained S1P1 receptor agonism and signaling through S1P lyase-dependent receptor recycling.

    Science.gov (United States)

    Gatfield, John; Monnier, Lucile; Studer, Rolf; Bolli, Martin H; Steiner, Beat; Nayler, Oliver

    2014-07-01

    The sphingosine-1-phosphate (S1P) type 1 receptor (S1P1R) is a novel therapeutic target in lymphocyte-mediated autoimmune diseases. S1P1 receptor desensitization caused by synthetic S1P1 receptor agonists prevents T-lymphocyte egress from secondary lymphoid organs into the circulation. The selective S1P1 receptor agonist ponesimod, which is in development for the treatment of autoimmune diseases, efficiently reduces peripheral lymphocyte counts and displays efficacy in animal models of autoimmune disease. Using ponesimod and the natural ligand S1P, we investigated the molecular mechanisms leading to different signaling, desensitization and trafficking behavior of S1P1 receptors. In recombinant S1P1 receptor-expressing cells, ponesimod and S1P triggered Gαi protein-mediated signaling and β-arrestin recruitment with comparable potency and efficiency, but only ponesimod efficiently induced intracellular receptor accumulation. In human umbilical vein endothelial cells (HUVEC), ponesimod and S1P triggered translocation of the endogenous S1P1 receptor to the Golgi compartment. However, only ponesimod treatment caused efficient surface receptor depletion, receptor accumulation in the Golgi and degradation. Impedance measurements in HUVEC showed that ponesimod induced only short-lived Gαi protein-mediated signaling followed by resistance to further stimulation, whereas S1P induced sustained Gαi protein-mediated signaling without desensitization. Inhibition of S1P lyase activity in HUVEC rendered S1P an efficient S1P1 receptor internalizing compound and abrogated S1P-mediated sustained signaling. This suggests that S1P lyase - by facilitating S1P1 receptor recycling - is essential for S1P-mediated sustained signaling, and that synthetic agonists are functional antagonists because they are not S1P lyase substrates. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Structural Insights into Selective Ligand-Receptor Interactions Leading to Receptor Inactivation Utilizing Selective Melanocortin 3 Receptor Antagonists.

    Science.gov (United States)

    Cai, Minying; Marelli, Udaya Kiran; Mertz, Blake; Beck, Johannes G; Opperer, Florian; Rechenmacher, Florian; Kessler, Horst; Hruby, Victor J

    2017-08-15

    Systematic N-methylated derivatives of the melanocortin receptor ligand, SHU9119, lead to multiple binding and functional selectivity toward melanocortin receptors. However, the relationship between N-methylation-induced conformational changes in the peptide backbone and side chains and melanocortin receptor selectivity is still unknown. We conducted comprehensive conformational studies in solution of two selective antagonists of the third isoform of the melanocortin receptor (hMC3R), namely, Ac-Nle-c[Asp-NMe-His 6 -d-Nal(2') 7 -NMe-Arg 8 -Trp 9 -Lys]-NH 2 (15) and Ac-Nle-c[Asp-His 6 -d-Nal(2') 7 -NMe-Arg 8 -NMe-Trp 9 -NMe-Lys]-NH 2 (17). It is known that the pharmacophore (His 6 -DNal 7 -Arg 8 -Trp 9 ) of the SHU-9119 peptides occupies a β II-turn-like region with the turn centered about DNal 7 -Arg 8 . The analogues with hMC3R selectivity showed distinct differences in the spatial arrangement of the Trp 9 side chains. In addition to our NMR studies, we also carried out molecular-level interaction studies of these two peptides at the homology model of hMC3R. Earlier chimeric human melanocortin 3 receptor studies revealed insights regarding the binding and functional sites of hMC3R selectivity. Upon docking of peptides 15 and 17 to the binding pocket of hMC3R, it was revealed that Arg 8 and Trp 9 side chains are involved in a majority of the interactions with the receptor. While Arg 8 forms polar contacts with D154 and D158 of hMC3R, Trp 9 utilizes π-π stacking interactions with F295 and F298, located on the transmembrane domain of hMC3R. It is hypothesized that as the frequency of Trp 9 -hMC3R interactions decrease, antagonistic activity increases. The absence of any interactions of the N-methyl groups with hMC3R suggests that their primary function is to modulate backbone conformations of the ligands.

  15. Differential treatment response of subtypes of patients with borderline personality organization, as assessed with theory-driven profiles of the Dutch short form of the MMPI: a naturalistic follow-up study

    NARCIS (Netherlands)

    Eurelings-Bontekoe, E.H.M.; Peen, J.; Noteboom, A.; Alkema, M.; Dekker, J.J.M.

    2012-01-01

    We investigated the validity of different subtypes of borderline personality organization (BPO) as assessed by theory-driven profiles of the Minnesota Multiphasic Personality Disorder (MMPI; Hathaway & McKinley, 1943) Dutch Short Form (DSFM; Eurelings-Bontekoe, Onnink, Williams, & Snellen, 2008) in

  16. G Protein-coupled Receptor Kinases of the GRK4 Protein Subfamily Phosphorylate Inactive G Protein-coupled Receptors (GPCRs).

    Science.gov (United States)

    Li, Lingyong; Homan, Kristoff T; Vishnivetskiy, Sergey A; Manglik, Aashish; Tesmer, John J G; Gurevich, Vsevolod V; Gurevich, Eugenia V

    2015-04-24

    G protein-coupled receptor (GPCR) kinases (GRKs) play a key role in homologous desensitization of GPCRs. It is widely assumed that most GRKs selectively phosphorylate only active GPCRs. Here, we show that although this seems to be the case for the GRK2/3 subfamily, GRK5/6 effectively phosphorylate inactive forms of several GPCRs, including β2-adrenergic and M2 muscarinic receptors, which are commonly used as representative models for GPCRs. Agonist-independent GPCR phosphorylation cannot be explained by constitutive activity of the receptor or membrane association of the GRK, suggesting that it is an inherent ability of GRK5/6. Importantly, phosphorylation of the inactive β2-adrenergic receptor enhanced its interactions with arrestins. Arrestin-3 was able to discriminate between phosphorylation of the same receptor by GRK2 and GRK5, demonstrating preference for the latter. Arrestin recruitment to inactive phosphorylated GPCRs suggests that not only agonist activation but also the complement of GRKs in the cell regulate formation of the arrestin-receptor complex and thereby G protein-independent signaling. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  17. DYNAMICS OF THE ANXIETY DISORDERS IN THE COURSE OF SHORT-TERM PSYCHOTHERAPY

    Directory of Open Access Journals (Sweden)

    T.N. Hmylova

    2008-06-01

    Full Text Available The tendency of psychotherapy modern concepts referring to the short-term forms having been taken into account, we carried out the research aimed at the study of short-term form personality-oriented psychotherapy effect on the anxiety disorder dynamics. 103 patients with neurotic disorders were examined in the neurosis and psychotherapy department of the Bekhterev Psychoneurological Research Institute. The findings revealed the situational and personal anxiety level to be objectively decreased in the short-term group psychotherapy course. The short-term group psychotherapy was proved to bean effective method in anxiety disorders treatment considering indications and limitations.

  18. Assembly and activation of neurotrophic factor receptor complexes.

    Science.gov (United States)

    Simi, Anastasia; Ibáñez, Carlos F

    2010-04-01

    Neurotrophic factors play important roles in the development and function of both neuronal and glial elements of the central and peripheral nervous systems. Their functional diversity is in part based on their ability to interact with alternative complexes of receptor molecules. This review focuses on our current understanding of the mechanisms that govern the assembly and activation of neurotrophic factor receptor complexes. The realization that many, if not the majority, of these complexes exist in a preassembled form at the plasma membrane has forced the revision of classical ligand-mediated oligomerization models, and led to the discovery of novel mechanisms of receptor activation and generation of signaling diversity which are likely to be shared by many different classes of receptors.

  19. Psychometric Evaluation of a Coping Strategies Inventory Short-Form (CSI-SF in the Jackson Heart Study Cohort

    Directory of Open Access Journals (Sweden)

    Herman Taylor

    2007-12-01

    Full Text Available This study sought to establish the psychometric properties of a Coping Strategies Inventory Short Form (CSISF by examining coping skills in the Jackson Heart Study cohort. We used exploratory and confirmatory factor analysis, Pearson’s correlation, and Cronbach Alpha to examine reliability and validity in the CSI-SF that solicited responses from 5302 African American men and women between the ages of 35 and 84. One item was dropped from the 16-item CSI-SF, making it a 15-item survey. No significant effects were found for age and gender, strengthening the generalizability of the CSI-SF. The internal consistency reliability analysis revealed reliability between alpha = 0.58-0.72 for all of the scales, and all of the fit indices used to examine the CSI-SF provided support for its use as an adequate measure of coping. This study provides empirical support for utilizing this instrument in future efforts to understand the role of coping in moderating health outcomes.

  20. Structural complementarity of Toll/interleukin-1 receptor domains in Toll-like receptors and the adaptors Mal and MyD88.

    Science.gov (United States)

    Dunne, Aisling; Ejdeback, Mikael; Ludidi, Phumzile L; O'Neill, Luke A J; Gay, Nicholas J

    2003-10-17

    The Toll/interleukin 1 receptor (TIR) domain is a region found in the cytoplasmic tails of members of the Toll-like receptor/interleukin-1 receptor superfamily. The domain is essential for signaling and is also found in the adaptor proteins Mal (MyD88 adaptor-like) and MyD88, which function to couple activation of the receptor to downstream signaling components. Experimental structures of two Toll/interleukin 1 receptor domains reveal a alpha-beta-fold similar to that of the bacterial chemotaxis protein CheY, and other evidence suggests that the adaptors can make heterotypic interactions with both the receptors and themselves. Here we show that the purified TIR domains of Mal and MyD88 can form stable heterodimers and also that Mal homodimers and oligomers are dissociated in the presence of ATP. To identify structural features that may contribute to the formation of signaling complexes, we produced models of the TIR domains from human Toll-like receptor 4 (TLR4), Mal, and MyD88. We found that although the overall fold is conserved the electrostatic surface potentials are quite distinct. Docking studies of the models suggest that Mal and MyD88 bind to different regions in TLRs 2 and 4, a finding consistent with a cooperative role of the two adaptors in signaling. Mal and MyD88 are predicted to interact at a third non-overlapping site, suggesting that the receptor and adaptors may form heterotetrameric complexes. The theoretical model of the interactions is supported by experimental data from glutathione S-transferase pull-downs and co-immunoprecipitations. Neither theoretical nor experimental data suggest a direct role for the conserved proline in the BB-loop in the association of TLR4, Mal, and MyD88. Finally we show a sequence relationship between the Drosophila protein Tube and Mal that may indicate a functional equivalence of these two adaptors in the Drosophila and vertebrate Toll pathways.

  1. The short short story as a teaching resource for the acquisition of grammar in SFL

    Directory of Open Access Journals (Sweden)

    María Nayra Rodríguez Rodríguez

    2016-07-01

    Full Text Available In the present article we intend to make a reflection on the introduction of target language literature in foreign language classrooms. We will analyze the use of short-short stories as a didactic resource in Spanish as Foreign Language classrooms. To this end, we will research different teaching methodologies that have been implemented and investigate the validity of this genre as a suitable material for teaching grammar. We will make an approximation to Focus on Form as an effective approach, which integrates grammar teaching within a communicative context.

  2. Point mutation in FGF receptor eliminates phosphatidylinositol hydrolysis without affecting mitogenesis.

    Science.gov (United States)

    Mohammadi, M; Dionne, C A; Li, W; Li, N; Spivak, T; Honegger, A M; Jaye, M; Schlessinger, J

    1992-08-20

    Stimulation of growth factor receptors with tyrosine kinase activity is followed by rapid receptor dimerization, tyrosine autophosphorylation and phosphorylation of signalling molecules such as phospholipase C gamma (PLC gamma) and the ras GTPase-activating protein. PLC gamma and GTPase-activating protein bind to specific tyrosine-phosphorylated regions in growth factor receptors through their src-homologous SH2 domains. Growth factor-induced tyrosine phosphorylation of PLC gamma is essential for stimulation of phosphatidylinositol hydrolysis in vitro and in vivo. We have shown that a short phosphorylated peptide containing tyrosine at position 766 from a conserved region of the fibroblast growth factor (FGF) receptor is a binding site for the SH2 domain of PLC gamma (ref. 8). Here we show that an FGF receptor point mutant in which Tyr 766 is replaced by a phenylalanine residue (Y766F) is unable to associate with and tyrosine-phosphorylate PLC gamma or to stimulate hydrolysis of phosphatidylinositol. Nevertheless, the Y766F FGF receptor mutant can be autophosphorylated, and can phosphorylate several cellular proteins and stimulate DNA synthesis. Our data show that phosphorylation of the conserved Tyr 766 of the FGF receptor is essential for phosphorylation of PLC gamma and for hydrolysis of phosphatidylinositol, but that elimination of this hydrolysis does not affect FGF-induced mitogenesis.

  3. Regulation of formyl peptide receptor binding to rabbit neutrophil plasma membranes. Use of monovalent cations, guanine nucleotides, and bacterial toxins to discriminate among different states of the receptor

    International Nuclear Information System (INIS)

    Feltner, D.E.; Marasco, W.A.

    1989-01-01

    The regulation by monovalent cations, guanine nucleotides, and bacterial toxins of [3H]FMLP binding to rabbit neutrophil plasma membranes was studied by using dissociation techniques to identify regulatory effects on separate receptor states. Under conditions of low receptor occupancy (1 nM [3H]FMLP) and in both Na+ and K+ buffers, dissociation is heterogenous, displaying two distinct, statistically significant off rates. [3H]FMLP binding was enhanced by substituting other monovalent cations for Na+. In particular, enhanced binding in the presence of K+ relative to Na+ was caused by additional binding to both rapidly and slowly dissociating receptors. Three receptor dissociation rates, two of which appear to correspond to the two affinity states detected in equilibrium binding studies, were defined by specific GTP and pertussis toxin (PT) treatments. Neither GTP, nor PT or cholera toxins (CT) had an effect on the rate of dissociation of [3H]FMLP from the rapidly dissociating form of the receptor. Both 100 microM GTP and PT treatments increased the percentage of rapidly dissociating receptors, correspondingly decreasing the percentage of slowly dissociating receptors. The observed changes in the rapidly and slowly dissociating receptors after GTP, PT, and CT treatments were caused by an absolute decrease in the amount of binding to the slowly dissociating receptors. However, complete inhibition of slowly dissociating receptor binding by GTP, PT, or both was never observed. Both GTP and PT treatments, but not CT treatment, increased by two-fold the rate of dissociation of 1 nM [3H]FMLP from the slowly dissociating form of the receptor, resulting in a third dissociation rate. Thus, slowly dissociating receptors comprise two different receptor states, a G protein-associated guanine nucleotide and PT-sensitive state and a guanine nucleotide-insensitive state

  4. Application of GPCR Structures for Modelling of Free Fatty Acid Receptors.

    Science.gov (United States)

    Tikhonova, Irina G

    2017-01-01

    Five G protein-coupled receptors (GPCRs) have been identified to be activated by free fatty acids (FFA). Among them, FFA1 (GPR40) and FFA4 (GPR120) bind long-chain fatty acids, FFA2 (GPR43) and FFA3 (GPR41) bind short-chain fatty acids and GPR84 binds medium-chain fatty acids. Free fatty acid receptors have now emerged as potential targets for the treatment of diabetes, obesity and immune diseases. The recent progress in crystallography of GPCRs has now enabled the elucidation of the structure of FFA1 and provided reliable templates for homology modelling of other FFA receptors. Analysis of the crystal structure and improved homology models, along with mutagenesis data and structure activity, highlighted an unusual arginine charge-pairing interaction in FFA1-3 for receptor modulation, distinct structural features for ligand binding to FFA1 and FFA4 and an arginine of the second extracellular loop as a possible anchoring point for FFA at GPR84. Structural data will be helpful for searching novel small-molecule modulators at the FFA receptors.

  5. Differential functions of NR2A and NR2B in short-term and long-term memory in rats.

    Science.gov (United States)

    Jung, Ye-Ha; Suh, Yoo-Hun

    2010-08-23

    N-methyl-D-aspartate receptors (NMDARs) are glutamate receptors implicated in synaptic plasticity and memory function. The specific functions of NMDA receptor subunits NR2A and NR2B have not yet been fully determined in the different types of memory. Nine Wistar rats (8-weeks-old) were subjected to the Morris water maze task to evaluate the memory behaviorally. Quantitative analysis of NR1, NR2A, and NR2B levels in the right and left forebrain of rats was performed and subunit associations with different types of memory were investigated using the Morris water maze task. Right forebrain NR2A expression was significantly increased and correlated with faster escape time onto a hidden platform, indicating involvement of short-term memory, because of the training time interval. Right forebrain NR2B expression was positively associated with long-term memory lasting 24-h (h). In the left forebrain, NR2B expression was positively related to 72-h long-term memory. In conclusion, the functions of NR2A and NR2B receptors were differentially specialized in short-term and long-term memory, depending on the right or left forebrain.

  6. Conception, synthesis and evaluation of fluorescent probes and PET radioligands for the oxytocin and vasopressin receptors

    International Nuclear Information System (INIS)

    Karpenko, Iuliia

    2014-01-01

    In order to better understand the role of OTR and AVPR in ASD, to reveal new features in its pharmacology and signaling and to establish high-throughput screening method on wild-type G protein-coupled receptors, we developed imaging probes for the oxytocin-vasopressin receptors family, namely radiotracers for positron emission tomography and optical probes for fluorescence detection and imaging. The fluorescent ligands have been used to establish TR-FRET binding assay for OTR and to initiate the development the screening assay for the wild-type oxytocin receptor. The PET radiotracers will be shortly tested in mice and monkeys to evaluate their potency in detecting the central oxytocin receptors. (author)

  7. The importance of the adenosine A(2A) receptor-dopamine D(2) receptor interaction in drug addiction.

    Science.gov (United States)

    Filip, M; Zaniewska, M; Frankowska, M; Wydra, K; Fuxe, K

    2012-01-01

    Drug addiction is a serious brain disorder with somatic, psychological, psychiatric, socio-economic and legal implications in the developed world. Illegal (e.g., psychostimulants, opioids, cannabinoids) and legal (alcohol, nicotine) drugs of abuse create a complex behavioral pattern composed of drug intake, withdrawal, seeking and relapse. One of the hallmarks of drugs that are abused by humans is that they have different mechanisms of action to increase dopamine (DA) neurotransmission within the mesolimbic circuitry of the brain and indirectly activate DA receptors. Among the DA receptors, D(2) receptors are linked to drug abuse and addiction because their function has been proven to be correlated with drug reinforcement and relapses. The recognition that D(2) receptors exist not only as homomers but also can form heteromers, such as with the adenosine (A)(2A) receptor, that are pharmacologically and functionally distinct from their constituent receptors, has significantly expanded the range of potential drug targets and provided new avenues for drug design in the search for novel drug addiction therapies. The aim of this review is to bring current focus on A(2A) receptors, their physiology and pharmacology in the central nervous system, and to discuss the therapeutic relevance of these receptors to drug addiction. We concentrate on the contribution of A(2A) receptors to the effects of different classes of drugs of abuse examined in preclinical behavioral experiments carried out with pharmacological and genetic tools. The consequences of chronic drug treatment on A(2A) receptor-assigned functions in preclinical studies are also presented. Finally, the neurochemical mechanism of the interaction between A(2A) receptors and drugs of abuse in the context of the heteromeric A(2A)-D(2) receptor complex is discussed. Taken together, a significant amount of experimental analyses provide evidence that targeting A(2A) receptors may offer innovative translational strategies

  8. The aryl hydrocarbon receptor and glucocorticoid receptor interact to activate human metallothionein 2A

    Energy Technology Data Exchange (ETDEWEB)

    Sato, Shoko, E-mail: satosho@rs.tus.ac.jp [Laboratory of Nutrition, Graduate School of Agricultural Science, Tohoku University, Sendai 981-8555 (Japan); Shirakawa, Hitoshi, E-mail: shirakah@m.tohoku.ac.jp [Laboratory of Nutrition, Graduate School of Agricultural Science, Tohoku University, Sendai 981-8555 (Japan); Tomita, Shuhei, E-mail: tomita@med.tottori-u.ac.jp [Division of Molecular Pharmacology, Department of Pathophysiological and Therapeutic Science, Yonago 683-8503 (Japan); Tohkin, Masahiro, E-mail: tohkin@phar.nagoya-cu.ac.jp [Department of Medical Safety Science, Graduate School of Pharmaceutical Science, Nagoya City University, Nagoya 267-8603 (Japan); Gonzalez, Frank J., E-mail: gonzalef@mail.nih.gov [Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States); Komai, Michio, E-mail: mkomai@m.tohoku.ac.jp [Laboratory of Nutrition, Graduate School of Agricultural Science, Tohoku University, Sendai 981-8555 (Japan)

    2013-11-15

    Although the aryl hydrocarbon receptor (AHR) and glucocorticoid receptor (GR) play essential roles in mammalian development, stress responses, and other physiological events, crosstalk between these receptors has been the subject of much debate. Metallothioneins are classic glucocorticoid-inducible genes that were reported to increase upon treatment with AHR agonists in rodent tissues and cultured human cells. In this study, the mechanism of human metallothionein 2A (MT2A) gene transcription activation by AHR was investigated. Cotreatment with 3-methylcholanthrene and dexamethasone, agonists of AHR and GR respectively, synergistically increased MT2A mRNA levels in HepG2 cells. MT2A induction was suppressed by RNA interference against AHR or GR. Coimmunoprecipitation experiments revealed a physical interaction between AHR and GR proteins. Moreover, chromatin immunoprecipitation assays indicated that AHR was recruited to the glucocorticoid response element in the MT2A promoter. Thus, we provide a novel mechanism whereby AHR modulates expression of human MT2A via the glucocorticoid response element and protein–protein interactions with GR. - Highlights: • Aryl hydrocarbon receptor forms a complex with glucocorticoid receptor in cells. • Human metallothionein gene is regulated by the AHR and GR interaction. • AHR–GR complex binds to glucocorticoid response element in metallothionein gene. • We demonstrated a novel transcriptional mechanism via AHR and GR interaction.

  9. The aryl hydrocarbon receptor and glucocorticoid receptor interact to activate human metallothionein 2A

    International Nuclear Information System (INIS)

    Sato, Shoko; Shirakawa, Hitoshi; Tomita, Shuhei; Tohkin, Masahiro; Gonzalez, Frank J.; Komai, Michio

    2013-01-01

    Although the aryl hydrocarbon receptor (AHR) and glucocorticoid receptor (GR) play essential roles in mammalian development, stress responses, and other physiological events, crosstalk between these receptors has been the subject of much debate. Metallothioneins are classic glucocorticoid-inducible genes that were reported to increase upon treatment with AHR agonists in rodent tissues and cultured human cells. In this study, the mechanism of human metallothionein 2A (MT2A) gene transcription activation by AHR was investigated. Cotreatment with 3-methylcholanthrene and dexamethasone, agonists of AHR and GR respectively, synergistically increased MT2A mRNA levels in HepG2 cells. MT2A induction was suppressed by RNA interference against AHR or GR. Coimmunoprecipitation experiments revealed a physical interaction between AHR and GR proteins. Moreover, chromatin immunoprecipitation assays indicated that AHR was recruited to the glucocorticoid response element in the MT2A promoter. Thus, we provide a novel mechanism whereby AHR modulates expression of human MT2A via the glucocorticoid response element and protein–protein interactions with GR. - Highlights: • Aryl hydrocarbon receptor forms a complex with glucocorticoid receptor in cells. • Human metallothionein gene is regulated by the AHR and GR interaction. • AHR–GR complex binds to glucocorticoid response element in metallothionein gene. • We demonstrated a novel transcriptional mechanism via AHR and GR interaction

  10. Adenosine A(2A) receptors are necessary and sufficient to trigger memory impairment in adult mice.

    Science.gov (United States)

    Pagnussat, N; Almeida, A S; Marques, D M; Nunes, F; Chenet, G C; Botton, P H S; Mioranzza, S; Loss, C M; Cunha, R A; Porciúncula, L O

    2015-08-01

    Caffeine (a non-selective adenosine receptor antagonist) prevents memory deficits in aging and Alzheimer's disease, an effect mimicked by adenosine A2 A receptor, but not A1 receptor, antagonists. Hence, we investigated the effects of adenosine receptor agonists and antagonists on memory performance and scopolamine-induced memory impairment in mice. We determined whether A2 A receptors are necessary for the emergence of memory impairments induced by scopolamine and whether A2 A receptor activation triggers memory deficits in naïve mice, using three tests to assess short-term memory, namely the object recognition task, inhibitory avoidance and modified Y-maze. Scopolamine (1.0 mg·kg(-1) , i.p.) impaired short-term memory performance in all three tests and this scopolamine-induced amnesia was prevented by the A2 A receptor antagonist (SCH 58261, 0.1-1.0 mg·kg(-1) , i.p.) and by the A1 receptor antagonist (DPCPX, 0.2-5.0 mg·kg(-1) , i.p.), except in the modified Y-maze where only SCH58261 was effective. Both antagonists were devoid of effects on memory or locomotion in naïve rats. Notably, the activation of A2 A receptors with CGS 21680 (0.1-0.5 mg·kg(-1) , i.p.) before the training session was sufficient to trigger memory impairment in the three tests in naïve mice, and this effect was prevented by SCH 58261 (1.0 mg·kg(-1) , i.p.). Furthermore, i.c.v. administration of CGS 21680 (50 nmol) also impaired recognition memory in the object recognition task. These results show that A2 A receptors are necessary and sufficient to trigger memory impairment and further suggest that A1 receptors might also be selectively engaged to control the cholinergic-driven memory impairment. © 2015 The British Pharmacological Society.

  11. Characterization of Odorant Receptors from a Non-ditrysian Moth, Eriocrania semipurpurella Sheds Light on the Origin of Sex Pheromone Receptors in Lepidoptera.

    Science.gov (United States)

    Yuvaraj, Jothi Kumar; Corcoran, Jacob A; Andersson, Martin N; Newcomb, Richard D; Anderbrant, Olle; Löfstedt, Christer

    2017-11-01

    Pheromone receptors (PRs) are essential in moths to detect sex pheromones for mate finding. However, it remains unknown from which ancestral proteins these specialized receptors arose. The oldest lineages of moths, so-called non-ditrysian moths, use short-chain pheromone components, secondary alcohols, or ketones, so called Type 0 pheromones that are similar to many common plant volatiles. It is, therefore, possible that receptors for these ancestral pheromones evolved from receptors detecting plant volatiles. Hence, we identified the odorant receptors (ORs) from a non-ditrysian moth, Eriocrania semipurpurella (Eriocraniidae, Lepidoptera), and performed functional characterization of ORs using HEK293 cells. We report the first receptors that respond to Type 0 pheromone compounds; EsemOR3 displayed highest sensitivity toward (2S, 6Z)-6-nonen-2-ol, whereas EsemOR5 was most sensitive to the behavioral antagonist (Z)-6-nonen-2-one. These receptors also respond to plant volatiles of similar chemical structures, but with lower sensitivity. Phylogenetically, EsemOR3 and EsemOR5 group with a plant volatile-responding receptor from the tortricid moth Epiphyas postvittana (EposOR3), which together reside outside the previously defined lepidopteran PR clade that contains the PRs from more derived lepidopteran families. In addition, one receptor (EsemOR1) that falls at the base of the lepidopteran PR clade, responded specifically to β-caryophyllene and not to any other additional plant or pheromone compounds. Our results suggest that PRs for Type 0 pheromones have evolved from ORs that detect structurally-related plant volatiles. They are unrelated to PRs detecting pheromones in more derived Lepidoptera, which, in turn, also independently may have evolved a novel function from ORs detecting plant volatiles. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  12. Ligand binding to G protein-coupled receptors in tethered cell membranes

    DEFF Research Database (Denmark)

    Martinez, Karen L.; Meyer, Bruno H.; Hovius, Ruud

    2003-01-01

    for the surface immobilization of membrane proteins was developed using the prototypic seven transmembrane neurokinin-1 receptor. The receptor was expressed as a biotinylated protein in mammalian cells. Membranes from cell homogenates were selectively immobilized on glass surfaces covered with streptavidin. TIRF...... measurements showed that a fluorescent agonist binds to the receptor on the sensor surface with similar affinity as to the receptor in live cells. This approach offers the possibility to investigate minute amounts of membrane protein in an active form and in its native environment without purification....

  13. Women's health status in urban Ghana: dimensions and differentials using short form 36.

    Science.gov (United States)

    Frempong-Ainguah, Faustina; Bailey, Claire E; Hill, Allan G

    2018-04-24

    Global discourse on population, health and development have placed women's health issues at the top of development agenda. Women's reproductive health has received some attention in Ghana since the mid-1990s. However, studies on women's general health status, dimensions and the differentials in a rapidly growing urban setting is poorly understood and under-researched. This study sought to examine the various pathways in which individual socio-demographic factors, economic characteristics and endowment influence self-assessed health status among women living in the city of Accra, Ghana. The paper draws on a cross-sectional study carried out in 2008 and 2009 using a representative sample of urban women 20 years and older (n = 2814). Multivariate stepwise linear regression models were performed to investigate the influence of socio-demographic, economic and health indicators on health-related quality of life, measured by eight sub-scales of the Short Form-36 (SF-36). Interaction effects between some demographic and socio-economic variables were also performed. The analyses show diverse relationships between demographic, socio-economic and health indicators and health outcomes assessed using eight SF-36 sub-scales. Education, disease symptoms and age of the respondent were the most significant factors influencing good overall health status. Interestingly, age has no significant effect on mental health after controlling for all other explanatory variables. The findings show that health issues are multi-faceted requiring socio-cultural, health and economic policy interventions. Investing in women's education is important to improve health status. There is also the need for more effective collaboration across various sectors to improve the health and well-being of women in general. Ageing has increasing relationship with poor physical health status and the elderly should be given needed attention and support.

  14. A soluble form of the high affinity IgE receptor, Fc-epsilon-RI, circulates in human serum.

    Directory of Open Access Journals (Sweden)

    Eleonora Dehlink

    Full Text Available Soluble IgE receptors are potential in vivo modulators of IgE-mediated immune responses and are thus important for our basic understanding of allergic responses. We here characterize a novel soluble version of the IgE-binding alpha-chain of Fc-epsilon-RI (sFcεRI, the high affinity receptor for IgE. sFcεRI immunoprecipitates as a protein of ∼40 kDa and contains an intact IgE-binding site. In human serum, sFcεRI is found as a soluble free IgE receptor as well as a complex with IgE. Using a newly established ELISA, we show that serum sFcεRI levels correlate with serum IgE in patients with elevated IgE. We also show that serum of individuals with normal IgE levels can be found to contain high levels of sFcεRI. After IgE-antigen-mediated crosslinking of surface FcεRI, we detect sFcεRI in the exosome-depleted, soluble fraction of cell culture supernatants. We further show that sFcεRI can block binding of IgE to FcεRI expressed at the cell surface. In summary, we here describe the alpha-chain of FcεRI as a circulating soluble IgE receptor isoform in human serum.

  15. Short-Form Science

    Science.gov (United States)

    Murphy, Beth; Hedwall, Melissa; Dirks, Andrew; Stretch, Elizabeth

    2017-01-01

    Reading provides a unique window into the history and nature of science and the norms of scientific communication and supports students in developing critical-reading skills in engaging ways. Effective use of reading promotes a spirit of inquiry and an understanding of science concepts while also addressing expectations of the Common Core State…

  16. Long-term activation upon brief exposure to xanomleline is unique to M1 and M4 subtypes of muscarinic acetylcholine receptors.

    Directory of Open Access Journals (Sweden)

    Eva Šantrůčková

    Full Text Available Xanomeline is an agonist endowed with functional preference for M1/M4 muscarinic acetylcholine receptors. It also exhibits both reversible and wash-resistant binding to and activation of these receptors. So far the mechanisms of xanomeline selectivity remain unknown. To address this question we employed microfluorometric measurements of intracellular calcium levels and radioligand binding to investigate differences in the short- and long-term effects of xanomeline among muscarinic receptors expressed individually in Chinese hamster ovary cells. 1/One-min exposure of cells to xanomeline markedly increased intracellular calcium at hM1 and hM4, and to a lesser extent at hM2 and hM3 muscarinic receptors for more than 1 hour. 2/Unlike the classic agonists carbachol, oxotremorine, and pilocarpine 10-min exposure to xanomeline did not cause internalization of any receptor subtype. 3/Wash-resistant xanomeline selectively prevented further increase in intracellular calcium by carbachol at hM1 and hM4 receptors. 4/After transient activation xanomeline behaved as a long-term antagonist at hM5 receptors. 5/The antagonist N-methylscopolamine (NMS reversibly blocked activation of hM1 through hM4 receptors by xanomeline. 6/NMS prevented formation of xanomeline wash-resistant binding and activation at hM2 and hM4 receptors and slowed them at hM1, hM3 and hM5 receptors. Our results show commonalities of xanomeline reversible and wash-resistant binding and short-time activation among the five muscarinic receptor subtypes. However long-term receptor activation takes place in full only at hM1 and hM4 receptors. Moreover xanomeline displays higher efficacy at hM1 and hM4 receptors in primary phasic intracellular calcium release. These findings suggest the existence of particular activation mechanisms specific to these two receptors.

  17. Crystal structure of a prolactin receptor antagonist bound to the extracellular domain of the prolactin receptor

    DEFF Research Database (Denmark)

    Svensson, L Anders; Bondensgaard, Kent; Nørskov-Lauritsen, Leif

    2008-01-01

    The crystal structure of the complex between an N-terminally truncated G129R human prolactin (PRL) variant and the extracellular domain of the human prolactin receptor (PRLR) was determined at 2.5A resolution by x-ray crystallography. This structure represents the first experimental structure...... studies, the structural data imply that the definition of PRL binding site 1 should be extended to include residues situated in the N-terminal part of loop 1 and in the C terminus. Comparison of the structure of the receptor-bound PRL variant with the structure reported for the unbound form of a similar...... scale rearrangements and structuring occur in the flexible N-terminal part of loop 1. Hydrogen exchange mass spectrometry data imply that the dynamics of the four-helix bundle in solution generally become stabilized upon receptor interaction at binding site 1....

  18. Unsaturated free fatty acids increase benzodiazepine receptor agonist binding depending on the subunit composition of the GABAA receptor complex.

    Science.gov (United States)

    Witt, M R; Westh-Hansen, S E; Rasmussen, P B; Hastrup, S; Nielsen, M

    1996-11-01

    It has been shown previously that unsaturated free fatty acids (FFAs) strongly enhance the binding of agonist benzodiazepine receptor ligands and GABAA receptor ligands in the CNS in vitro. To investigate the selectivity of this effect, recombinant human GABAA/benzodiazepine receptor complexes formed by different subunit compositions (alpha x beta y gamma 2, x = 1, 2, 3, and 5; y = 1, 2, and 3) were expressed using the baculovirus-transfected Sf9 insect cell system. At 10(-4) M, unsaturated FFAs, particularly arachidonic (20:4) and docosahexaenoic (22:6) acids, strongly stimulated (> 200% of control values) the binding of [3H]flunitrazepam ([3H]FNM) to the alpha 3 beta 2 gamma 2 receptor combination in whole cell preparations. No effect or small increases in levels of unsaturated FFAs on [3H]FNM binding to alpha 1 beta x gamma 2 and alpha 2 beta x gamma 2 receptor combinations were observed, and weak effects (130% of control values) were detected using the alpha 5 beta 2 gamma 2 receptor combination. The saturated FFAs, stearic and palmitic acids, were without effect on [3H]FNM binding to any combination of receptor complexes. The hydroxylated unsaturated FFAs, ricinoleic and ricinelaidic acids, were shown to decrease the binding of [3H]FNM only if an alpha 1 beta 2 gamma 2 receptor combination was used. Given the heterogeneity of the GABAA/ benzodiazepine receptor subunit distribution in the CNS, the effects of FFAs on the benzodiazepine receptor can be assumed to vary at both cellular and regional levels.

  19. Additive manufacturing of short and mixed fibre-reinforced polymer

    Science.gov (United States)

    Lewicki, James; Duoss, Eric B.; Rodriguez, Jennifer Nicole; Worsley, Marcus A.; King, Michael J.

    2018-01-09

    Additive manufacturing of a fiber-reinforced polymer (FRP) product using an additive manufacturing print head; a reservoir in the additive manufacturing print head; short carbon fibers in the reservoir, wherein the short carbon fibers are randomly aligned in the reservoir; an acrylate, methacrylate, epoxy, cyanate ester or isocyanate resin in the reservoir, wherein the short carbon fibers are dispersed in the acrylate, methacrylate, epoxy, cyanate ester or isocyanate resin; a tapered nozzle in the additive manufacturing print head operatively connected to the reservoir, the tapered nozzle produces an extruded material that forms the fiber-reinforced polymer product; baffles in the tapered nozzle that receive the acrylate, methacrylate, epoxy, cyanate ester or isocyanate resin with the short carbon fibers dispersed in the acrylate, methacrylate, epoxy, cyanate ester or isocyanate resin; and a system for driving the acrylate, methacrylate, epoxy, cyanate ester or isocyanate resin with the short carbon fibers dispersed in the acrylate, methacrylate, epoxy, cyanate ester or isocyanate resin from the reservoir through the tapered nozzle wherein the randomly aligned short carbon fibers in the acrylate, methacrylate, epoxy, cyanate ester or isocyanate resin are aligned by the baffles and wherein the extruded material has the short carbon fibers aligned in the acrylate, methacrylate, epoxy, cyanate ester or isocyanate resin that forms the fiber-reinforced polymer product.

  20. Hebb learning, verbal short-term memory, and the acquisition of phonological forms in children.

    Science.gov (United States)

    Mosse, Emma K; Jarrold, Christopher

    2008-04-01

    Recent work using the Hebb effect as a marker for implicit long-term acquisition of serial order has demonstrated a functional equivalence across verbal and visuospatial short-term memory. The current study extends this observation to a sample of five- to six-year-olds using verbal and spatial immediate serial recall and also correlates the magnitude of Hebb learning with explicit measures of word and nonword paired-associate learning. Comparable Hebb effects were observed in both domains, but only nonword learning was significantly related to the magnitude of Hebb learning. Nonword learning was also independently related to individuals' general level of verbal serial recall. This suggests that vocabulary acquisition depends on both a domain-specific short-term memory system and a domain-general process of learning through repetition.

  1. miR-137 forms a regulatory loop with nuclear receptor TLX and LSD1 in neural stem cells.

    Science.gov (United States)

    Sun, GuoQiang; Ye, Peng; Murai, Kiyohito; Lang, Ming-Fei; Li, Shengxiu; Zhang, Heying; Li, Wendong; Fu, Chelsea; Yin, Jason; Wang, Allen; Ma, Xiaoxiao; Shi, Yanhong

    2011-11-08

    miR-137 is a brain-enriched microRNA. Its role in neural development remains unknown. Here we show that miR-137 has an essential role in controlling embryonic neural stem cell fate determination. miR-137 negatively regulates cell proliferation and accelerates neural differentiation of embryonic neural stem cells. In addition, we show that the histone lysine-specific demethylase 1 (LSD1), a transcriptional co-repressor of nuclear receptor TLX, is a downstream target of miR-137. In utero electroporation of miR-137 in embryonic mouse brains led to premature differentiation and outward migration of the transfected cells. Introducing a LSD1 expression vector lacking the miR-137 recognition site rescued miR-137-induced precocious differentiation. Furthermore, we demonstrate that TLX, an essential regulator of neural stem cell self-renewal, represses the expression of miR-137 by recruiting LSD1 to the genomic regions of miR-137. Thus, miR-137 forms a feedback regulatory loop with TLX and LSD1 to control the dynamics between neural stem cell proliferation and differentiation during neural development.

  2. Kupffer cell complement receptor clearance function and host defense.

    Science.gov (United States)

    Loegering, D J

    1986-01-01

    Kupffer cells are well known to be important for normal host defense function. The development of methods to evaluate the in vivo function of specific receptors on Kupffer cells has made it possible to assess the role of these receptors in host defense. The rationale for studying complement receptors is based on the proposed important role of these receptors in host defense and on the observation that the hereditary deficiency of a complement receptor is associated with recurrent severe bacterial infections. The studies reviewed here demonstrate that forms of injury that are associated with depressed host defense including thermal injury, hemorrhagic shock, trauma, and surgery also cause a decrease in complement receptor clearance function. This decrease in Kupffer cell receptor clearance function was shown not to be the result of depressed hepatic blood flow or depletion of complement components. Complement receptor function was also depressed following the phagocytosis of particulates that are known to depress Kupffer cell host defense function. Endotoxemia and bacteremia also were associated with a depression of complement receptor function. Complement receptor function was experimentally depressed in uninjured animals by the phagocytosis of IgG-coated erythrocytes. There was a close association between the depression of complement receptor clearance function and increased susceptibility to the lethal effects of endotoxin and bacterial infection. These studies support the hypotheses that complement receptors on Kupffer cells are important for normal host defense and that depression of the function of these receptors impairs host defense.

  3. Olfactory bulb short axon cell release of GABA and dopamine produces a temporally biphasic inhibition-excitation response in external tufted cells.

    Science.gov (United States)

    Liu, Shaolin; Plachez, Celine; Shao, Zuoyi; Puche, Adam; Shipley, Michael T

    2013-02-13

    Evidence for coexpression of two or more classic neurotransmitters in neurons has increased, but less is known about cotransmission. Ventral tegmental area (VTA) neurons corelease dopamine (DA), the excitatory transmitter glutamate, and the inhibitory transmitter GABA onto target cells in the striatum. Olfactory bulb (OB) short axon cells (SACs) form interglomerular connections and coexpress markers for DA and GABA. Using an optogenetic approach, we provide evidence that mouse OB SACs release both GABA and DA onto external tufted cells (ETCs) in other glomeruli. Optical activation of channelrhodopsin specifically expressed in DAergic SACs produced a GABA(A) receptor-mediated monosynaptic inhibitory response, followed by DA-D(1)-like receptor-mediated excitatory response in ETCs. The GABA(A) receptor-mediated hyperpolarization activates I(h) current in ETCs; synaptically released DA increases I(h), which enhances postinhibitory rebound spiking. Thus, the opposing actions of synaptically released GABA and DA are functionally integrated by I(h) to generate an inhibition-to-excitation "switch" in ETCs. Consistent with the established role of I(h) in ETC burst firing, we show that endogenous DA release increases ETC spontaneous bursting frequency. ETCs transmit sensory signals to mitral/tufted output neurons and drive intraglomerular inhibition to shape glomerulus output to downstream olfactory networks. GABA and DA cotransmission from SACs to ETCs may play a key role in regulating output coding across the glomerular array.

  4. Human eosinophils - potential pharmacological model applied in human histamine H4 receptor research.

    Science.gov (United States)

    Grosicki, Marek; Kieć-Kononowicz, Katarzyna

    2015-01-01

    Histamine and histamine receptors are well known for their immunomodulatory role in inflammation. In this review we describe the role of histamine and histamine H4 receptor on human eosinophils. In the first part of article we provide short summary of histamine and histamine receptors role in physiology and histamine related therapeutics used in clinics. We briefly describe the human histamine receptor H4 and its ligands, as well as human eosinophils. In the second part of the review we provide detailed description of known histamine effects on eosinophils including: intracellular calcium concentration flux, actin polymerization, cellular shape change, upregulation of adhesion proteins and cellular chemotaxis. We provide proofs that these effects are mainly connected with the activation of histamine H4 receptor. When examining experimental data we discuss the controversial results and limitations of the studies performed on isolated eosinophils. In conclusion we believe that studies on histamine H4 receptor on human eosinophils can provide interesting new biomarkers that can be used in clinical studies of histamine receptors, that in future might result in the development of new strategies in the treatment of chronic inflammatory conditions like asthma or allergy, in which eosinophils are involved.

  5. Signaling assemblies formed in mast cells activated via Fce receptor I dimers

    Czech Academy of Sciences Publication Activity Database

    Dráberová, Lubica; Lebduška, Pavel; Hálová, Ivana; Tolar, Pavel; Štokrová, Jitka; Tolarová, Helena; Korb, Jan; Dráber, Petr

    2004-01-01

    Roč. 34, č. 8 (2004), s. 2209-2219 ISSN 0014-2980 R&D Projects: GA MŠk LN00A026; GA ČR GA204/03/0594; GA ČR GA301/03/0596; GA ČR GA204/00/0204; GA ČR GA310/00/0205; GA AV ČR IAA5052005; GA AV ČR IAA7052006; GA AV ČR IAA5052310 Institutional research plan: CEZ:AV0Z5052915 Keywords : mast cell * protein kinase * IgE receptor Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.005, year: 2004

  6. Measurement Equivalence of the Patient Reported Outcomes Measurement Information System® (PROMIS®) Applied Cognition - General Concerns, Short Forms in Ethnically Diverse Groups.

    Science.gov (United States)

    Fieo, Robert; Ocepek-Welikson, Katja; Kleinman, Marjorie; Eimicke, Joseph P; Crane, Paul K; Cella, David; Teresi, Jeanne A

    2016-01-01

    The goals of these analyses were to examine the psychometric properties and measurement equivalence of a self-reported cognition measure, the Patient Reported Outcome Measurement Information System ® (PROMIS ® ) Applied Cognition - General Concerns short form. These items are also found in the PROMIS Cognitive Function (version 2) item bank. This scale consists of eight items related to subjective cognitive concerns. Differential item functioning (DIF) analyses of gender, education, race, age, and (Spanish) language were performed using an ethnically diverse sample ( n = 5,477) of individuals with cancer. This is the first analysis examining DIF in this item set across ethnic and racial groups. DIF hypotheses were derived by asking content experts to indicate whether they posited DIF for each item and to specify the direction. The principal DIF analytic model was item response theory (IRT) using the graded response model for polytomous data, with accompanying Wald tests and measures of magnitude. Sensitivity analyses were conducted using ordinal logistic regression (OLR) with a latent conditioning variable. IRT-based reliability, precision and information indices were estimated. DIF was identified consistently only for the item, brain not working as well as usual. After correction for multiple comparisons, this item showed significant DIF for both the primary and sensitivity analyses. Black respondents and Hispanics in comparison to White non-Hispanic respondents evidenced a lower conditional probability of endorsing the item, brain not working as well as usual. The same pattern was observed for the education grouping variable: as compared to those with a graduate degree, conditioning on overall level of subjective cognitive concerns, those with less than high school education also had a lower probability of endorsing this item. DIF was also observed for age for two items after correction for multiple comparisons for both the IRT and OLR-based models: "I have had

  7. GPR41/FFAR3 and GPR43/FFAR2 as Cosensors for Short-Chain Fatty Acids in Enteroendocrine Cells vs FFAR3 in Enteric Neurons and FFAR2 in Enteric Leukocytes

    DEFF Research Database (Denmark)

    Nøhr, Mark K; Pedersen, Maria H; Gille, Andreas

    2013-01-01

    The expression of short-chain fatty acid receptors GPR41/FFAR3 and GPR43/ free fatty acid receptor 2 (FFAR2) was studied in the gastrointestinal tract of transgenic monomeric red fluorescent protein (mRFP) reporter mice. In the stomach free fatty acid receptor 3 (FFAR3)-mRFP was expressed...... for the majority of enteroendocrine cells of the small and large intestine and that FFAR3 and FFAR2 both act as sensors for short-chain fatty acids in enteroendocrine cells, whereas FFAR3 apparently has this role alone in enteric neurons and FFAR2 in enteric leukocytes....

  8. Thiazide diuretic receptors: Autoradiographic localization in rat kidney with [3H]metolazone

    International Nuclear Information System (INIS)

    Beaumont, K.; Vaughn, D.A.; Healy, D.P.

    1989-01-01

    The localization of binding sites for [ 3 H]metolazone, a quinazolinesulfonamide diuretic with thiazide-like actions, was determined by in vitro autoradiography. [ 3 H]Metolazone bound saturably to rat kidney sections incubated in vitro with a dissociation constant (Kd) = 3.4 nM and binding site density = 0.14 pmol/mg of protein. Incubation conditions were used that excluded binding to low affinity sites and carbonic anhydrase. Pharmacological specificity of binding was consistent with labeling of physiologically relevant thiazide diuretic receptors, as identified in previous studies of [ 3 H]metolazone binding to renal membranes. Autoradiographs obtained with tritium-sensitive film demonstrated that binding sites were limited to the renal cortex and were relatively sparsely distributed. Higher resolution autoradiography indicated that [ 3 H] metolazone binding sites were localized in a highly specific manner over short lengths of tubular segments, which by their morphology and distribution most likely represented distal convoluted tubules. In the short sections of tubule that contained receptors, labeling was very dense and appeared to be more prevalent over luminal than peritubular surfaces. The intrarenal distribution of [ 3 H]metolazone binding sites provides further evidence for their identity as thiazide diuretic receptors. These results are consistent with physiological studies demonstrating that the early distal tubule is the location of thiazide-sensitive sodium chloride cotransport

  9. Microdomain forming proteins in oncogenesis

    Directory of Open Access Journals (Sweden)

    I. B. Zborovskaya

    2016-01-01

    Full Text Available Lipid rafts are lateral assembles of cholesterol, sphingomyelin, glicosphingolipids and specific proteins within cell plasma membrane. These microdomains are involved into a number of important cellular processes including membrane rearrangement, protein internalization, signal transduction, entry of viruses into the cell. Some of lipid rafts are stabilized by special microdomain-forming proteins such as caveolins, SPFH domain containing superfamily, tetraspanins, galectins, which maintain integrity of rafts and regulate signal transduction via forming of “signalosomes”. Involvement of the different lipid rafts is necessary in many situations such as binding of growth factors with their receptors, integrin regulation, cytoskeleton and extracellular matrix rearrangements, vesicular transport, etc. However, such classes of microdomain-forming proteins are still considered separately from each other. In this review we tried to perform complex analysis of microdomain-forming proteins in regulation of cancer assotiated processes.

  10. Scavenger Receptor CD163 and Its Biological Functions

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    Gabriela Onofre

    2009-01-01

    Full Text Available CD163 is a member of scavenger receptor super family class B of the first subgroup. It is mapped to the region p13 on chromosome 12. Five different isoforms of CD163 have been described, which differ in the structure of their cytoplasmic domains and putative phosporylation sites. This scavenger receptor is selectively expressed on cells of monocytes and macrophages lineage exclusively. CD163 immunological function is essentially homeostatic. It also has other functions because participates in adhesion to endothelial cells, in tolerance induction and tissues regeneration. Other very important function of CD163 is the clearance of hemoglobin in its cell-free form and participation in anti-inflammation in its soluble form, exhibiting cytokine-like functions. We review the biological functions of CD163 which have been discovered until now. It seems apparent from this review that CD163 scavenger receptor can be used as biomarker in different diseases and as a valuable diagnostic parameter for prognosis of many diseases especially inflammatory disorders and sepsis.

  11. Non-peptidic antagonists of the CGRP receptor, BIBN4096BS and MK-0974, interact with the calcitonin receptor-like receptor via methionine-42 and RAMP1 via tryptophan-74.

    Science.gov (United States)

    Miller, Philip S; Barwell, James; Poyner, David R; Wigglesworth, Mark J; Garland, Stephen L; Donnelly, Dan

    2010-01-01

    The receptor for calcitonin gene-related peptide (CGRP) has been the target for the development of novel small molecule antagonists for the treatment of migraine. Two such antagonists, BIBN4096BS and MK-0974, have shown great promise in clinical trials and hence a deeper understanding of the mechanism of their interaction with the receptor is now required. The structure of the CGRP receptor is unusual since it is comprised of a hetero-oligomeric complex between the calcitonin receptor-like receptor (CRL) and an accessory protein (RAMP1). Both the CLR and RAMP1 components have extracellular domains which interact with each other and together form part of the peptide-binding site. It seems likely that the antagonist binding site will also be located on the extracellular domains and indeed Trp-74 of RAMP1 has been shown to form part of the binding site for BIBN4096BS. However, despite a chimeric study demonstrating the role of the N-terminal domain of CLR in antagonist binding, no specific residues have been identified. Here we carry out a mutagenic screen of the extreme N-terminal domain of CLR (residues 23-63) and identify a mutant, Met-42-Ala, which displays 48-fold lower affinity for BIBN4096BS and almost 900-fold lower affinity for MK-0974. In addition, we confirm that the Trp-74-Lys mutation at human RAMP1 reduces BIBN4096BS affinity by over 300-fold and show for the first time a similar effect for MK-0974 affinity. The data suggest that the non-peptide antagonists occupy a binding site close to the interface of the N-terminal domains of CLR and RAMP1. Copyright 2009 Elsevier Inc. All rights reserved.

  12. Comparative Geometrical Analysis of Leucine-Rich Repeat Structures in the Nod-Like and Toll-Like Receptors in Vertebrate Innate Immunity

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    Norio Matsushima

    2015-08-01

    Full Text Available The NOD-like receptors (NLRs and Toll-like receptors (TLRs are pattern recognition receptors that are involved in the innate, pathogen pattern recognition system. The TLR and NLR receptors contain leucine-rich repeats (LRRs that are responsible for ligand interactions. In LRRs short β-strands stack parallel and then the LRRs form a super helical arrangement of repeating structural units (called a coil of solenoids. The structures of the LRR domains of NLRC4, NLRP1, and NLRX1 in NLRs and of TLR1-5, TLR6, TLR8, TLR9 in TLRs have been determined. Here we report nine geometrical parameters that characterize the LRR domains; these include four helical parameters from HELFIT analysis. These nine parameters characterize well the LRR structures in NLRs and TLRs; the LRRs of NLR adopts a right-handed helix. In contrast, the TLR LRRs adopt either a left-handed helix or are nearly flat; RP105 and CD14 also adopt a left-handed helix. This geometrical analysis subdivides TLRs into four groups consisting of TLR3/TLR8/TLR9, TLR1/TLR2/TRR6, TLR4, and TLR5; these correspond to the phylogenetic tree based on amino acid sequences. In the TLRs an ascending lateral surface that consists of loops connecting the β-strand at the C-terminal side is involved in protein, protein/ligand interactions, but not the descending lateral surface on the opposite side.

  13. Integrating TRPV1 Receptor Function with Capsaicin Psychophysics

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    Gregory Smutzer

    2016-01-01

    Full Text Available Capsaicin is a naturally occurring vanilloid that causes a hot, pungent sensation in the human oral cavity. This trigeminal stimulus activates TRPV1 receptors and stimulates an influx of cations into sensory cells. TRPV1 receptors function as homotetramers that also respond to heat, proinflammatory substances, lipoxygenase products, resiniferatoxin, endocannabinoids, protons, and peptide toxins. Kinase-mediated phosphorylation of TRPV1 leads to increased sensitivity to both chemical and thermal stimuli. In contrast, desensitization occurs via a calcium-dependent mechanism that results in receptor dephosphorylation. Human psychophysical studies have shown that capsaicin is detected at nanomole amounts and causes desensitization in the oral cavity. Psychophysical studies further indicate that desensitization can be temporarily reversed in the oral cavity if stimulation with capsaicin is resumed at short interstimulus intervals. Pretreatment of lingual epithelium with capsaicin modulates the perception of several primary taste qualities. Also, sweet taste stimuli may decrease the intensity of capsaicin perception in the oral cavity. In addition, capsaicin perception and hedonic responses may be modified by diet. Psychophysical studies with capsaicin are consistent with recent findings that have identified TRPV1 channel modulation by phosphorylation and interactions with membrane inositol phospholipids. Future studies will further clarify the importance of capsaicin and its receptor in human health and nutrition.

  14. Dopamine D2 receptors photolabeled by iodo-azido-clebopride.

    Science.gov (United States)

    Niznik, H B; Dumbrille-Ross, A; Guan, J H; Neumeyer, J L; Seeman, P

    1985-04-19

    Iodo-azido-clebopride, a photoaffinity compound for dopamine D2 receptors, had high affinity for canine brain striatal dopamine D2 receptors with a dissociation constant (Kd) of 14 nM. Irradiation of striatal homogenate with iodo-azido-clebopride irreversibly inactivated 50% of dopamine D2 receptors at 20 nM (as indicated by subsequent [3H]spiperone binding). Dopamine agonists and antagonists prevented this photo-inactivation with the appropriate rank-order of potency. Striatal dopamine D1, serotonin (S2), alpha 1- and beta-adrenoceptors were not significantly inactivated following irradiation with iodo-azido-clebopride. Thus, iodo-azido-clebopride is a selective photoaffinity probe for dopamine D2 receptors, the radiolabelled form of which may aid in the molecular characterization of these proteins.

  15. Designer lipid-like peptides: a class of detergents for studying functional olfactory receptors using commercial cell-free systems.

    Science.gov (United States)

    Corin, Karolina; Baaske, Philipp; Ravel, Deepali B; Song, Junyao; Brown, Emily; Wang, Xiaoqiang; Wienken, Christoph J; Jerabek-Willemsen, Moran; Duhr, Stefan; Luo, Yuan; Braun, Dieter; Zhang, Shuguang

    2011-01-01

    A crucial bottleneck in membrane protein studies, particularly G-protein coupled receptors, is the notorious difficulty of finding an optimal detergent that can solubilize them and maintain their stability and function. Here we report rapid production of 12 unique mammalian olfactory receptors using short designer lipid-like peptides as detergents. The peptides were able to solubilize and stabilize each receptor. Circular dichroism showed that the purified olfactory receptors had alpha-helical secondary structures. Microscale thermophoresis suggested that the receptors were functional and bound their odorants. Blot intensity measurements indicated that milligram quantities of each olfactory receptor could be produced with at least one peptide detergent. The peptide detergents' capability was comparable to that of the detergent Brij-35. The ability of 10 peptide detergents to functionally solubilize 12 olfactory receptors demonstrates their usefulness as a new class of detergents for olfactory receptors, and possibly other G-protein coupled receptors and membrane proteins.

  16. Designer lipid-like peptides: a class of detergents for studying functional olfactory receptors using commercial cell-free systems.

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    Karolina Corin

    Full Text Available A crucial bottleneck in membrane protein studies, particularly G-protein coupled receptors, is the notorious difficulty of finding an optimal detergent that can solubilize them and maintain their stability and function. Here we report rapid production of 12 unique mammalian olfactory receptors using short designer lipid-like peptides as detergents. The peptides were able to solubilize and stabilize each receptor. Circular dichroism showed that the purified olfactory receptors had alpha-helical secondary structures. Microscale thermophoresis suggested that the receptors were functional and bound their odorants. Blot intensity measurements indicated that milligram quantities of each olfactory receptor could be produced with at least one peptide detergent. The peptide detergents' capability was comparable to that of the detergent Brij-35. The ability of 10 peptide detergents to functionally solubilize 12 olfactory receptors demonstrates their usefulness as a new class of detergents for olfactory receptors, and possibly other G-protein coupled receptors and membrane proteins.

  17. Transcriptional activation by the thyroid hormone receptor through ligand-dependent receptor recruitment and chromatin remodelling.

    Science.gov (United States)

    Grøntved, Lars; Waterfall, Joshua J; Kim, Dong Wook; Baek, Songjoon; Sung, Myong-Hee; Zhao, Li; Park, Jeong Won; Nielsen, Ronni; Walker, Robert L; Zhu, Yuelin J; Meltzer, Paul S; Hager, Gordon L; Cheng, Sheue-yann

    2015-04-28

    A bimodal switch model is widely used to describe transcriptional regulation by the thyroid hormone receptor (TR). In this model, the unliganded TR forms stable, chromatin-bound complexes with transcriptional co-repressors to repress transcription. Binding of hormone dissociates co-repressors and facilitates recruitment of co-activators to activate transcription. Here we show that in addition to hormone-independent TR occupancy, ChIP-seq against endogenous TR in mouse liver tissue demonstrates considerable hormone-induced TR recruitment to chromatin associated with chromatin remodelling and activated gene transcription. Genome-wide footprinting analysis using DNase-seq provides little evidence for TR footprints both in the absence and presence of hormone, suggesting that unliganded TR engagement with repressive complexes on chromatin is, similar to activating receptor complexes, a highly dynamic process. This dynamic and ligand-dependent interaction with chromatin is likely shared by all steroid hormone receptors regardless of their capacity to repress transcription in the absence of ligand.

  18. Validation of a culturally modified short form of the McCarthy Scales of Children’s Abilities in 6 to 8 year old Zimbabwean school children: a cross section study

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    Kandawasvika Gwendoline Q

    2012-11-01

    Full Text Available Abstract Background The burden of cognitive impairment among school children from developing communities is under reported due to lack of culturally appropriate screening tools. The objective of this study was to validate a culturally modified short form of the McCarthy Scales of Children Abilities (MSCA in school children aged 6–8 years from varied backgrounds. Methods One hundred and one children aged 6–8 years attending mainstream classes were enrolled cross-sectionally from three schools: one rural and two urban. Two assessments were conducted on each child and the Short form MSCA was compared to an independent assessment by the educational psychologist. Results When comparing the results of the MSCA to local standard at -2SD, -1.5 SD and -1SD the sensitivity rates ranged from 17 to 50% with lower sensitivity at -2SD cut-off point. Specificity rates had less variation ranging from 95% to 100%. The number of children identified with cognitive impairment using -2SD, -1.5SD and -1SD below the mean for MSCA as a cut-off point were 3(3%, 7(7% and 13(13% respectively while the psychologist identified 18 (18%. The overall mean score on MSCA was 103 (SD 15. The rural children tended to score significantly lower marks compared to their peers from urban areas, mean (SD 98(15 and 107(15 respectively, p=0.006. There was no difference in the mean (SD scores between boys and girls, 103(17 and 103(15 respectively, p=0.995. Conclusion The culturally modified short form MSCA showed high specificity but low sensitivity. Prevalence of cognitive impairment among 6 to 8 year children was 3%. This figure is high when compared to developed communities.

  19. The Pseudo signal peptide of the corticotropin-releasing factor receptor type 2A prevents receptor oligomerization.

    Science.gov (United States)

    Teichmann, Anke; Rutz, Claudia; Kreuchwig, Annika; Krause, Gerd; Wiesner, Burkhard; Schülein, Ralf

    2012-08-03

    N-terminal signal peptides mediate the interaction of native proteins with the translocon complex of the endoplasmic reticulum membrane and are cleaved off during early protein biogenesis. The corticotropin-releasing factor receptor type 2a (CRF(2(a))R) possesses an N-terminal pseudo signal peptide, which represents a so far unique domain within the large protein family of G protein-coupled receptors (GPCRs). In contrast to a conventional signal peptide, the pseudo signal peptide remains uncleaved and consequently forms a hydrophobic extension at the N terminus of the receptor. The functional consequence of the presence of the pseudo signal peptide is not understood. Here, we have analyzed the significance of this domain for receptor dimerization/oligomerization in detail. To this end, we took the CRF(2(a))R and the homologous corticotropin-releasing factor receptor type 1 (CRF(1)R) possessing a conventional cleaved signal peptide and conducted signal peptide exchange experiments. Using single cell and single molecule imaging methods (fluorescence resonance energy transfer and fluorescence cross-correlation spectroscopy, respectively) as well as biochemical experiments, we obtained two novel findings; we could show that (i) the CRF(2(a))R is expressed exclusively as a monomer, and (ii) the presence of the pseudo signal peptide prevents its oligomerization. Thus, we have identified a novel functional domain within the GPCR protein family, which plays a role in receptor oligomerization and which may be useful to study the functional significance of this process in general.

  20. Quaternary structure of a G-protein-coupled receptor heterotetramer in complex with Gi and Gs.

    Science.gov (United States)

    Navarro, Gemma; Cordomí, Arnau; Zelman-Femiak, Monika; Brugarolas, Marc; Moreno, Estefania; Aguinaga, David; Perez-Benito, Laura; Cortés, Antoni; Casadó, Vicent; Mallol, Josefa; Canela, Enric I; Lluís, Carme; Pardo, Leonardo; García-Sáez, Ana J; McCormick, Peter J; Franco, Rafael

    2016-04-05

    G-protein-coupled receptors (GPCRs), in the form of monomers or homodimers that bind heterotrimeric G proteins, are fundamental in the transfer of extracellular stimuli to intracellular signaling pathways. Different GPCRs may also interact to form heteromers that are novel signaling units. Despite the exponential growth in the number of solved GPCR crystal structures, the structural properties of heteromers remain unknown. We used single-particle tracking experiments in cells expressing functional adenosine A1-A2A receptors fused to fluorescent proteins to show the loss of Brownian movement of the A1 receptor in the presence of the A2A receptor, and a preponderance of cell surface 2:2 receptor heteromers (dimer of dimers). Using computer modeling, aided by bioluminescence resonance energy transfer assays to monitor receptor homomerization and heteromerization and G-protein coupling, we predict the interacting interfaces and propose a quaternary structure of the GPCR tetramer in complex with two G proteins. The combination of results points to a molecular architecture formed by a rhombus-shaped heterotetramer, which is bound to two different interacting heterotrimeric G proteins (Gi and Gs). These novel results constitute an important advance in understanding the molecular intricacies involved in GPCR function.

  1. The receptor RAGE: Bridging inflammation and cancer

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    Hess Jochen

    2009-05-01

    Full Text Available Abstract The receptor for advanced glycation end products (RAGE is a single transmembrane receptor of the immunoglobulin superfamily that is mainly expressed on immune cells, neurons, activated endothelial and vascular smooth muscle cells, bone forming cells, and a variety of cancer cells. RAGE is a multifunctional receptor that binds a broad repertoire of ligands and mediates responses to cell damage and stress conditions. It activates programs responsible for acute and chronic inflammation, and is implicated in a number of pathological diseases, including diabetic complications, stroke, atheriosclerosis, arthritis, and neurodegenerative disorders. The availability of Rage knockout mice has not only advanced our knowledge on signalling pathways within these pathophysiological conditions, but also on the functional importance of the receptor in processes of cancer. Here, we will summarize molecular mechanisms through which RAGE signalling contributes to the establishment of a pro-tumourigenic microenvironment. Moreover, we will review recent findings that provide genetic evidence for an important role of RAGE in bridging inflammation and cancer.

  2. MELATONIN DAN MELATONIN RECEPTOR AGONIST SEBAGAI PENANGANAN INSOMNIA PRIMER KRONIS

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    Ni Luh Putu Ayu Maha Iswari

    2013-04-01

    Full Text Available Melatonin is a hormone that has an important role in the mechanism of sleep. Hypnotic effects of melatonin and melatonin receptor agonist are mediated via MT1 and MT2 receptors, especially in circadian rhythm pacemaker, suprachiasmatic nucleus, which is worked on the hypothalamic sleep switch. This mechanism is quite different with the GABAergic drugs such as benzodiazepine. Agonist melatonin triggers the initiation of sleep and normalize circadian rhythms so that makes it easier to maintain sleep. The main disadvantage of melatonin in helping sleep maintenance on primary insomnia is that the half life is very short. The solution to this problem is the use of prolonged-release melatonin and melatonin receptor agonist agents such as ramelteon. Melatoninergic agonist does not cause withdrawal effects, dependence, as well as cognitive and psychomotor disorders as often happens on the use of benzodiazepine.  

  3. The Herdecke questionnaire on quality of life (HLQ: Validation of factorial structure and development of a short form within a naturopathy treated in-patient collective

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    Beer Andre-Michael

    2005-07-01

    Full Text Available Abstract Background Quality of life (QoL of patients has become a central evaluation parameter that also acts as an aid for decisions related to treatment strategies particularly for patients with chronic illnesses. In Germany, one of the newer instruments attempting to measure distinct QoL aspects is the "Herdecke Questionnaire for Quality of Life" (HLQ. In this study, we aimed to validate the HLQ with respect to its factorial structure, and to develop a short form. The validation has been carried out in relation to other questionnaires including the SF-36 Health Survey, the Mood-Scale Bf-S, the Giessen Physical Complaints Questionnaire GBB-24 and McGill's Pain Perception Scale SES. Methods Data for this study derived from a model project on the treatment of patients using naturopathy methods in Blankenstein Hospital, Hattingen. In total, 2,461 patients between the ages of 16 and 92 years (mean age: 58.0 ± 13.4 years were included in this study. Most of the patients (62% suffered from rheumatic diseases. Factorial validation of the HLQ, it's reliability and external consistency analysis and the development of a short form were carried out using the SPSS software. Results Structural analysis of the HLQ-items pointed to a 6-factor model. The internal consistency of both the long and the short version is excellent (Cronbach's α is 0.935 for the HLQ-L and 0.862 for the HLQ-S. The highest reliability in the HLQ-L was obtained for the "Initiative Power and Interest" scale, the lowest for the 2-item scales "Digestive Well-Being" and the "Physical Complaints". However, the scales found by factor analysis herein were only in part congruent with the original 5-scale model which was approved a multitrait analysis approach. The new instrument shows good correlations with several scales of other relevant QoL instruments. The scales "Initiative Power and Interest", "Social Interaction", "Mental Balance", "Motility", "Physical Complaints", "Digestive Well

  4. Criterion validity of a Wechsler-III scale short form in a sample of Brazilian Elderly

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    Eliane Ferreira Carvalho Banhato

    Full Text Available Abstract Although a normative process, changes in cognitive functioning vary among older adults. The differential diagnosis between normal and pathological aging must be made early using psychometrically adequate measures. Objectives: To assess the evidence of criterion validity of a Short Form (SF of the Wechsler-III Scale containing eight subtests (SF8 by determining its sensitivity, specificity, positive and negative predictive values and cut-off points for Brazilian elderly from different age groups. Methods: 168 individuals, aged 60 years or above, living in the community or in an institution, were assigned to case and control groups, and investigated according to age range. Measures included a sociodemographic questionnaire, the Mini-Mental State Examination (MMSE, Verbal Fluency Test, Clock-Drawing Test and the SF8. Results: More than two thirds of the sample was women (73.8%, mean age was 74.5 years (SD=8.9, mean education was 6.2 years (SD=4.8 and 40.5% were widows/widowers. In the total sample, the best cut-off point for the SF8 was 142 while cut offs among individuals aged 60 to 69 years, 70 to 79 years, and more than 80 years were 160, 129 and 129, respectively. Conclusions: The results demonstrated the importance of different cut-off points for different age ranges. Sensitivity and specificity values of the SF8 were sufficiently high to warrant the use of the SF8 as an instrument to identify cognitive impairment in the elderly.

  5. Criterion validity of a Wechsler-III Scale Short Form in a sample of brazilian elderly.

    Science.gov (United States)

    Banhato, Eliane Ferreira Carvalho; Leite, Isabel Cristina Gonçalves; Guedes, Danielle Viveiros; Chaoubah, Alfredo

    2010-01-01

    Although a normative process, changes in cognitive functioning vary among older adults. The differential diagnosis between normal and pathological aging must be made early using psychometrically adequate measures. To assess the evidence of criterion validity of a Short Form (SF) of the Wechsler-III Scale containing eight subtests (SF8) by determining its sensitivity, specificity, positive and negative predictive values and cut-off points for Brazilian elderly from different age groups. 168 individuals, aged 60 years or above, living in the community or in an institution, were assigned to case and control groups, and investigated according to age range. Measures included a sociodemographic questionnaire, the Mini-Mental State Examination (MMSE), Verbal Fluency Test, Clock-Drawing Test and the SF8. More than two thirds of the sample was women (73.8%), mean age was 74.5 years (SD=8.9), mean education was 6.2 years (SD=4.8) and 40.5% were widows/widowers. In the total sample, the best cut-off point for the SF8 was 142 while cut offs among individuals aged 60 to 69 years, 70 to 79 years, and more than 80 years were 160, 129 and 129, respectively. The results demonstrated the importance of different cut-off points for different age ranges. Sensitivity and specificity values of the SF8 were sufficiently high to warrant the use of the SF8 as an instrument to identify cognitive impairment in the elderly.

  6. MesonNet Workshop on Meson Transition Form Factors

    CERN Document Server

    Eidelman, S; Hanhart, C; Kubis, B; Kupsc, A; Leupold, S; Moskal, P; Schadmand, S

    2012-01-01

    The mini-proceedings of the Workshop on Meson Transition Form Factors held in Cracow from May 29th to 30th, 2012 introduce the meson transition form factor project with special emphasis on the interrelations between the various form factors (on-shell, single off-shell, double off-shell). Short summaries of the talks presented at the workshop follow.

  7. Korean version of mini mental status examination for dementia screening and its' short form.

    Science.gov (United States)

    Kim, Tae Hui; Jhoo, Jin Hyeong; Park, Joon Hyuk; Kim, Jeong Lan; Ryu, Seung Ho; Moon, Seok Woo; Choo, Il Han; Lee, Dong Woo; Yoon, Jong Chul; Do, Yeon Ja; Lee, Seok Bum; Kim, Moon Doo; Kim, Ki Woong

    2010-06-01

    We developed a Korean version of Mini-Mental Status Examination (MMSE) optimized for screening dementia (MMSE-DS) and its' short form (SMMSE-DS). We constructed the MMSE-DS using the items of the two current Korean versions of MMSE and then construct the SMMSE-DS consisted of 13 items from the MMSE-DS based on the diagnostic accuracy of individual items for dementia. We investigated reliability and validity of MMSE-DS and SMMSE-DS on 1,555 subjects (1,222 nondemented controls, 333 dementia patients). We compared the diagnostic accuracy of the SMMSE-DS with that of the three full Korean versions of MMSE, and examined its' age- and education-specific optimal cutoff scores for dementia. The internal consistency obtained by Cronbach's coefficient alpha was 0.826. The inter-rater reliability and test-retest reliability were 0.968 (p<0.001) and 0.825 (p<0.001), respectively. It showed significant correlation with the Clinical Dementia Rating (CDR) (r=-0.698, p<0.05) and the three full Korean versions of MMSE (r=0.839-0.938, p<0.001). The area under the receiver operator curve for dementia of the SMMSE-DS was larger than those of the three full Korean versions of MMSE (p<0.001). Age, education and gender explained 19.4% of the total variance of SMMSE-DS scores. The optimal cutoff scores for dementia of the SMMSE-DS were estimated differently by age and educational attainment of the subjects. The SMMSE-DS was found to be accurate, brief and portable instrument for screening dementia in Korean elders, and may be particularly useful for screening dementia in elderly populations with wide variation in educational levels.

  8. Translation, cross-cultural adaptation and validation of the Diabetes Empowerment Scale - Short Form.

    Science.gov (United States)

    Chaves, Fernanda Figueredo; Reis, Ilka Afonso; Pagano, Adriana Silvina; Torres, Heloísa de Carvalho

    2017-03-23

    To translate, cross-culturally adapt and validate the Diabetes Empowerment Scale - Short Form for assessment of psychosocial self-efficacy in diabetes care within the Brazilian cultural context. Assessment of the instrument's conceptual equivalence, as well as its translation and cross-cultural adaptation were performed following international standards. The Expert Committee's assessment of the translated version was conducted through a web questionnaire developed and applied via the web tool e-Surv. The cross-culturally adapted version was used for the pre-test, which was carried out via phone call in a group of eleven health care service users diagnosed with type 2 diabetes mellitus. The pre-test results were examined by a group of experts, composed by health care consultants, applied linguists and statisticians, aiming at an adequate version of the instrument, which was subsequently used for test and retest in a sample of 100 users diagnosed with type 2 diabetes mellitus via phone call, their answers being recorded by the web tool e-Surv. Internal consistency and reproducibility of analysis were carried out within the statistical programming environment R. Face and content validity were attained and the Brazilian Portuguese version, entitled Escala de Autoeficácia em Diabetes - Versão Curta, was established. The scale had acceptable internal consistency with Cronbach's alpha of 0.634 (95%CI 0.494- 0.737), while the correlation of the total score in the two periods was considered moderate (0.47). The intraclass correlation coefficient was 0.50. The translated and cross-culturally adapted version of the instrument to spoken Brazilian Portuguese was considered valid and reliable to be used for assessment within the Brazilian population diagnosed with type 2 diabetes mellitus. The use of a web tool (e-Surv) for recording the Expert Committee responses as well as the responses in the validation tests proved to be a reliable, safe and innovative method. Traduzir

  9. The evolution of the class A scavenger receptors

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    Whelan Fiona J

    2012-11-01

    Full Text Available Abstract Background The class A scavenger receptors are a subclass of a diverse family of proteins defined based on their ability to bind modified lipoproteins. The 5 members of this family are strikingly variable in their protein structure and function, raising the question as to whether it is appropriate to group them as a family based on their ligand binding abilities. Results To investigate these relationships, we defined the domain architecture of each of the 5 members followed by collecting and annotating class A scavenger receptor mRNA and amino acid sequences from publicly available databases. Phylogenetic analyses, sequence alignments, and permutation tests revealed a common evolutionary ancestry of these proteins, indicating that they form a protein family. We postulate that 4 distinct gene duplication events and subsequent domain fusions, internal repeats, and deletions are responsible for the diverse protein structures and functions of this family. Despite variation in domain structure, there are highly conserved regions across all 5 members, indicating the possibility that these regions may represent key conserved functional motifs. Conclusions We have shown with significant evidence that the 5 members of the class A scavenger receptors form a protein family. We have indicated that these receptors have a common origin which may provide insight into future functional work with these proteins.

  10. Confined Diffusion Without Fences of a G-Protein-Coupled Receptor as Revealed by Single Particle Tracking

    Science.gov (United States)

    Daumas, Frédéric; Destainville, Nicolas; Millot, Claire; Lopez, André; Dean, David; Salomé, Laurence

    2003-01-01

    Single particle tracking is a powerful tool for probing the organization and dynamics of the plasma membrane constituents. We used this technique to study the μ-opioid receptor belonging to the large family of the G-protein-coupled receptors involved with other partners in a signal transduction pathway. The specific labeling of the receptor coupled to a T7-tag at its N-terminus, stably expressed in fibroblastic cells, was achieved by colloidal gold coupled to a monoclonal anti T7-tag antibody. The lateral movements of the particles were followed by nanovideomicroscopy at 40 ms time resolution during 2 min with a spatial precision of 15 nm. The receptors were found to have either a slow or directed diffusion mode (10%) or a walking confined diffusion mode (90%) composed of a long-term random diffusion and a short-term confined diffusion, and corresponding to a diffusion confined within a domain that itself diffuses. The results indicate that the confinement is due to an effective harmonic potential generated by long-range attraction between the membrane proteins. A simple model for interacting membrane proteins diffusion is proposed that explains the variations with the domain size of the short-term and long-term diffusion coefficients. PMID:12524289

  11. α7 and β2 Nicotinic Acetylcholine Receptor Subunits Form Heteromeric Receptor Complexes that Are Expressed in the Human Cortex and Display Distinct Pharmacological Properties

    DEFF Research Database (Denmark)

    Thomsen, Morten Skøtt; Zwart, Ruud; Ursu, Daniel

    2015-01-01

    The existence of α7β2 nicotinic acetylcholine receptors (nAChRs) has recently been demonstrated in both the rodent and human brain. Since α7-containing nAChRs are promising drug targets for schizophrenia and Alzheimer's disease, it is critical to determine whether α7β2 nAChRs are present in the h......The existence of α7β2 nicotinic acetylcholine receptors (nAChRs) has recently been demonstrated in both the rodent and human brain. Since α7-containing nAChRs are promising drug targets for schizophrenia and Alzheimer's disease, it is critical to determine whether α7β2 nAChRs are present...

  12. Simulating the Effects of Short-Term Synaptic Plasticity on Postsynaptic Dynamics in the Globus Pallidus

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    Moran eBrody

    2013-08-01

    Full Text Available The rat globus pallidus (GP is one of the nuclei of the basal ganglia and plays an important role in a variety of motor and cognitive processes. In vivo studies have shown that repetitive stimulation evokes complex modulations of GP activity. In vitro and computational studies have suggested that short-term synaptic plasticity (STP could be one of the underlying mechanisms. The current study used simplified single compartment modeling to explore the possible effect of STP on the activity of GP neurons during low and high frequency stimulation. To do this we constructed a model of a GP neuron connected to a small network of neurons from the three major input sources to GP neurons: striatum (Str, subthalamic nucleus (STN and GP collaterals. All synapses were implemented with a kinetic model of STP. The in vitro recordings of responses to low frequency repetitive stimulation were highly reconstructed, including rate changes and locking to the stimulus. Mainly involved were fast forms of plasticity which have been found at these synapses. . The simulations were qualitatively compared to a data set previously recorded in vitro in our lab. Reconstructions of experimental responses to high frequency stimulation required adding slower forms of plasticity to the STN and GP collateral synapses, as well as adding metabotropic receptors to the STN-GP synapses. These finding suggest the existence of as yet unreported slower short-term dynamics in the GP. The computational model made additional predictions about GP activity during low and high frequency stimulation that may further our understanding of the mechanisms underlying repetative stimulation of the GP.

  13. Regulation of ion transport via apical purinergic receptors in intact rabbit airway epithelium

    DEFF Research Database (Denmark)

    Poulsen, Asser Nyander; Klausen, Thomas Levin; Pedersen, Peter Steen

    2005-01-01

    and unidirectional Cl- fluxes decreased significantly. The results suggest that nucleotides released to the airway surface liquid exert an autocrine regulation of epithelial NaCl absorption mainly by inhibiting the amiloride-sensitive epithelial Na+ channel (ENaC) and paracellular anion conductance via a P2Y......We investigated purinergic receptors involved in ion transport regulation in the intact rabbit nasal airway epithelium. Stimulation of apical membrane P2Y receptors with ATP or UTP (200 microM) induced transient increases in short-circuit current (Isc) of 13 and 6% followed by sustained inhibitions...

  14. Harvard-MIT research program in short-lived radiopharmaceuticals. Progress report, March 1, 1983-February 29, 1984

    International Nuclear Information System (INIS)

    Adelstein, S.J.; Brownell, G.L.

    1984-02-01

    This report describes research efforts towards the achievement of a clearer understanding of the solution chemistry of technetium in order to facilitate the design of future clinical agents labeled with Tc-99m, the development of new receptor binding radiopharmaceuticals for the in vivo assessment of insulin receptors and for imaging the adrenal medulla and the brain, the examination of the utility of monoclonal antibodies and liposomes in the design of radiopharmaceuticals for diagnosis and therapy, and the synthesis of short-lived positron-emitting radiopharmaceuticals for transverse imaging of regional physiological processes

  15. Synthesis of the possible receptor Ligand [125I]-spiperone for D2-dopamine receptor and in-vivo biodistribution

    International Nuclear Information System (INIS)

    Amin, A.M.; Shoukry, M.; Abd EL-Bary, A.

    2009-01-01

    The spiperone is a selective D2-dopamine receptor antagonist radioiodination of spiperone is of interest for dopamine (DA) receptor studies both in vivo and in vitro. The labeling of spiperone with iodine-125 was extremely done in a neutral ph 7, using chloramine-T as oxidizing agent via heating the reaction mixture at 70 C (degree) for 10 - 15 minutes producing radiochemical yield of 97 %. In vivo biodistribution studies showed that the initial brain uptake correlated fairly well with the brain uptake index and that the kinetics of the radioactivity specifically bound to the striatum were strongly influenced by the dopamine receptor binding affinity of the compound. The brain uptake of 125 I-Spiperone was high and equal to 3.5, 3.25,2.75 and 1.7 % per gram tissue at 5, 30, 60 and 120 minutes post injection, respectively. 125 I-Spiperone binds with high affinity to dopamine receptors in vivo. Specific binding is about 65% of the total binding as is displaced stereo-specifically by clozapine. 125 I-spiperone may prove to be a useful ligand in studies examining D2-dopamine receptors. Furthermore iodinated spiperone may be useful in radioreceptor assays of neuroleptic drug levels and, in a 123 I-labeled form, for imaging of dopamine receptors, in vivo, using single photon tomography.

  16. Personal receptor repertoires: olfaction as a model

    Directory of Open Access Journals (Sweden)

    Olender Tsviya

    2012-08-01

    Full Text Available Abstract Background Information on nucleotide diversity along completely sequenced human genomes has increased tremendously over the last few years. This makes it possible to reassess the diversity status of distinct receptor proteins in different human individuals. To this end, we focused on the complete inventory of human olfactory receptor coding regions as a model for personal receptor repertoires. Results By performing data-mining from public and private sources we scored genetic variations in 413 intact OR loci, for which one or more individuals had an intact open reading frame. Using 1000 Genomes Project haplotypes, we identified a total of 4069 full-length polypeptide variants encoded by these OR loci, average of ~10 per locus, constituting a lower limit for the effective human OR repertoire. Each individual is found to harbor as many as 600 OR allelic variants, ~50% higher than the locus count. Because OR neuronal expression is allelically excluded, this has direct effect on smell perception diversity of the species. We further identified 244 OR segregating pseudogenes (SPGs, loci showing both intact and pseudogene forms in the population, twenty-six of which are annotatively “resurrected” from a pseudogene status in the reference genome. Using a custom SNP microarray we validated 150 SPGs in a cohort of 468 individuals, with every individual genome averaging 36 disrupted sequence variations, 15 in homozygote form. Finally, we generated a multi-source compendium of 63 OR loci harboring deletion Copy Number Variations (CNVs. Our combined data suggest that 271 of the 413 intact OR loci (66% are affected by nonfunctional SNPs/indels and/or CNVs. Conclusions These results portray a case of unusually high genetic diversity, and suggest that individual humans have a highly personalized inventory of functional olfactory receptors, a conclusion that might apply to other receptor multigene families.

  17. Cultural adaptation and validation of the Filipino version of Kidney Disease Quality of Life--Short Form (KDQOL-SF version 1.3).

    Science.gov (United States)

    Bataclan, Rommel P; Dial, Ma Antonietta D

    2009-10-01

    Chronic kidney disease is the 10th leading cause of death among Filipinos. Those with chronic kidney disease are exposed to stressors which effect their daily lives. Therefore, assessment of health-related quality of life is important in these patients. The objective of the present study was to translate the Kidney Disease Quality of Life--Short Form version 1.3 (KDQOL-SF ver. 1.3) into Filipino and measure its validity and reliability. Translation and cultural adaptation began with two translations into Filipino, with reconciliation of the forward translators. Pretesting with 10 renal patients, review by experts (nephrologist, translator and dialysis nurse) and back-translation was also done. The final questionnaire was administered to 80 patients with chronic renal disease undergoing haemodialysis for at least 3 months, who could understand Filipino, and were without life-threatening or terminal conditions at the time of the test. A convenience sample of 30 patients from the group had a repeat test 10-14 days after to determine test-retest reliability. Test-retest reliability was assessed by intraclass correlation coefficient and internal consistency reliability was measured by determining the Cronbach's alpha value. Validity was measured using Pearson's correlation between the overall health rating scale and the items from the questionnaire. All of the items showed good test-retest reliability (intraclass correlation coefficient >0.40), ranging from 0.58 (social interaction) to 0.98 (role--emotional). Internal consistency reliability values were acceptable, with Cronbach's alpha ranging from 0.60 (cognitive function) to 0.80 (physical functioning and role--physical). Regarding construct validity, overall health rating in kidney disease-targeted scales was significantly correlated with symptoms/problems, effects of kidney disease and burden of kidney disease. All items in the SF 36 scales had significant correlation with overall health rating (P < 0.05) except

  18. Assessing appearance-related disturbances in HIV-infected men who have sex with men (MSM): psychometrics of the body change and distress questionnaire-short form (ABCD-SF).

    Science.gov (United States)

    Blashill, Aaron J; Wilson, Johannes M; Baker, Joshua S; Mayer, Kenneth H; Safren, Steven A

    2014-06-01

    Appearance-related disturbances are common among HIV-infected MSM; however, to date, there have been limited options in the valid assessment of this construct. The aim of the current study was to assess the structural, internal, and convergent validity of the assessment of body change distress questionnaire (ABCD) and its short version. Exploratory and confirmatory factor analyses indicated that both versions fit the data well. Four subfactors were revealed measuring the following body disturbance constructs: (1) negative affect about appearance, (2) HIV health-related outcomes and stigma, (3) eating and exercise confusion, and (4) ART non-adherence. The subfactors and total scores revealed bivariate associations with salient health outcomes, including depressive symptoms, HIV sexual transmission risk behaviors, and ART non-adherence. The ABCD and its short form, offer valid means to assess varied aspects of body image disturbance among HIV-infected MSM, and require modest participant burden.

  19. Corneal epithelium expresses a variant of P2X(7 receptor in health and disease.

    Directory of Open Access Journals (Sweden)

    Courtney Mankus

    Full Text Available Improper wound repair of the corneal epithelium can alter refraction of light resulting in impaired vision. We have shown that ATP is released after injury, activates purinergic receptor signaling pathways and plays a major role in wound closure. In many cells or tissues, ATP activates P2X(7 receptors leading to cation fluxes and cytotoxicity. The corneal epithelium is an excellent model to study the expression of both the full-length P2X(7 form (defined as the canonical receptor and its truncated forms. When Ca(2+ mobilization is induced by BzATP, a P2X(7 agonist, it is attenuated in the presence of extracellular Mg(2+ or Zn(2+, negligible in the absence of extracellular Ca(2+, and inhibited by the competitive P2X7 receptor inhibitor, A438079. BzATP enhanced phosphorylation of ERK. Together these responses indicate the presence of a canonical or full-length P2X(7 receptor. In addition BzATP enhanced epithelial cell migration, and transfection with siRNA to the P2X(7 receptor reduced cell migration. Furthermore, sustained activation did not induce dye uptake indicating the presence of truncated or variant forms that lack the ability to form large pores. Reverse transcription-polymerase chain reaction and Northern blot analysis revealed a P2X(7 splice variant. Western blots identified a full-length and truncated form, and the expression pattern changed as cultures progressed from monolayer to stratified. Cross-linking gels demonstrated the presence of homo- and heterotrimers. We examined epithelium from age matched diabetic and non-diabetic corneas patients and detected a 4-fold increase in P2X(7 mRNA from diabetic corneal epithelium compared to non-diabetic controls and an increased trend in expression of P2X(7variant mRNA. Taken together, these data indicate that corneal epithelial cells express full-length and truncated forms of P2X(7, which ultimately allows P2X(7 to function as a multifaceted receptor that can mediate cell proliferation and

  20. Comparison Review of Short-Acting and Long-Acting Glucagon-like Peptide-1 Receptor Agonists

    OpenAIRE

    Uccellatore, Annachiara; Genovese, Stefano; Dicembrini, Ilaria; Mannucci, Edoardo; Ceriello, Antonio

    2015-01-01

    Glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1 RAs) are useful tools for treating type 2 diabetes mellitus. In their recent position statement, the American Diabetes Association and European Association for the Study of Diabetes recommend GLP1-RAs as add-on to metformin when therapeutic goals are not achieved with monotherapy, particularly for patients who wish to avoid weight gain or hypoglycemia. GLP1-RAs differ substantially in their duration of action, frequency of administratio...

  1. Growth form and seasonal variation in leaf gas exchange of Colophospermum mopane savanna trees in northwest Botswana.

    Science.gov (United States)

    Veenendaal, Elmar M; Mantlana, Khanyisa B; Pammenter, Norman W; Weber, Piet; Huntsman-Mapila, Phillipa; Lloyd, Jon

    2008-03-01

    We investigated differences in physiological and morphological traits between the tall and short forms of mopane (Colophospermum mopane (Kirk ex Benth.) Kirk ex J. Léonard) trees growing near Maun, Botswana on a Kalahari sandveld overlying an impermeable calcrete duricrust. We sought to determine if differences between the two physiognomic types are attributable to the way they exploit available soil water. The tall form, which was located on deeper soil than the short form (5.5 versus 1.6 m), had a lower leaf:fine root biomass ratio (1:20 versus 1:6), but a similar leaf area index (0.9-1.0). Leaf nitrogen concentrations varied between 18 and 27 mg g(-1) and were about 20% higher in the tall form than in the short form. Maximum net assimilation rates (A sat) occurred during the rainy seasons (March-April 2000 and January-February 2001) and were similar in the tall and short forms (15-22 micromol m(-2) s(-1)) before declining to less than 10 micromol m(-2) s(-1) at the end of the rainy season in late April. As the dry season progressed, A sat, soil water content, predawn leaf water potential (Psi pd) and leaf nitrogen concentration declined rapidly. Before leaf abscission, Psi pd was more negative in the short form (-3.4 MPa) than in the tall form (-2.7 MPa) despite the greater availability of soil water beneath the short form trees. This difference appeared attributable to differences in root depth and density between the physiognomic types. Stomatal regulation of water use and carbon assimilation differed between years, with the tall form having a consistently more conservative water-use strategy as the dry season progressed than the short form.

  2. The Iranian version of 12-item Short Form Health Survey (SF-12: factor structure, internal consistency and construct validity

    Directory of Open Access Journals (Sweden)

    Mousavi Sayed

    2009-09-01

    Full Text Available Abstract Background The 12-item Short Form Health Survey (SF-12 as a shorter alternative of the SF-36 is largely used in health outcomes surveys. The aim of this study was to validate the SF-12 in Iran. Methods A random sample of the general population aged 15 years and over living in Tehran, Iran completed the SF-12. Reliability was estimated using internal consistency and validity was assessed using known groups comparison and convergent validity. In addition, the factor structure of the questionnaire was extracted by performing both exploratory factor analysis (EFA and confirmatory factor analysis (CFA. Results: In all, 5587 individuals were studied (2721 male and 2866 female. The mean age and formal education of the respondents were 35.1 (SD = 15.4 and 10.2 (SD = 4.4 years respectively. The results showed satisfactory internal consistency for both summary measures, that are the Physical Component Summary (PCS and the Mental Component Summary (MCS; Cronbach's α for PCS-12 and MCS-12 was 0.73 and 0.72, respectively. Known-groups comparison showed that the SF-12 discriminated well between men and women and those who differed in age and educational status (P Conclusion In general the findings suggest that the SF-12 is a reliable and valid measure of health related quality of life among Iranian population. However, further studies are needed to establish stronger psychometric properties for this alternative form of the SF-36 Health Survey in Iran.

  3. Possible Relevance of Receptor-Receptor Interactions between Viral- and Host-Coded Receptors for Viral-Induced Disease

    Directory of Open Access Journals (Sweden)

    Luigi F. Agnati

    2007-01-01

    Full Text Available It has been demonstrated that some viruses, such as the cytomegalovirus, code for G-protein coupled receptors not only to elude the immune system, but also to redirect cellular signaling in the receptor networks of the host cells. In view of the existence of receptor-receptor interactions, the hypothesis is introduced that these viral-coded receptors not only operate as constitutively active monomers, but also can affect other receptor function by interacting with receptors of the host cell. Furthermore, it is suggested that viruses could also insert not single receptors (monomers, but clusters of receptors (receptor mosaics, altering the cell metabolism in a profound way. The prevention of viral receptor-induced changes in host receptor networks may give rise to novel antiviral drugs that counteract viral-induced disease.

  4. AmTAR2: Functional characterization of a honeybee tyramine receptor stimulating adenylyl cyclase activity.

    Science.gov (United States)

    Reim, Tina; Balfanz, Sabine; Baumann, Arnd; Blenau, Wolfgang; Thamm, Markus; Scheiner, Ricarda

    2017-01-01

    The biogenic monoamines norepinephrine and epinephrine regulate important physiological functions in vertebrates. Insects such as honeybees do not synthesize these neuroactive substances. Instead, they employ octopamine and tyramine for comparable physiological functions. These biogenic amines activate specific guanine nucleotide-binding (G) protein-coupled receptors (GPCRs). Based on pharmacological data obtained on heterologously expressed receptors, α- and β-adrenergic-like octopamine receptors are better activated by octopamine than by tyramine. Conversely, GPCRs forming the type 1 tyramine receptor clade (synonymous to octopamine/tyramine receptors) are better activated by tyramine than by octopamine. More recently, receptors were characterized which are almost exclusively activated by tyramine, thus forming an independent type 2 tyramine receptor clade. Functionally, type 1 tyramine receptors inhibit adenylyl cyclase activity, leading to a decrease in intracellular cAMP concentration ([cAMP] i ). Type 2 tyramine receptors can mediate Ca 2+ signals or both Ca 2+ signals and effects on [cAMP] i . We here provide evidence that the honeybee tyramine receptor 2 (AmTAR2), when heterologously expressed in flpTM cells, exclusively causes an increase in [cAMP] i . The receptor displays a pronounced preference for tyramine over octopamine. Its activity can be blocked by a series of established antagonists, of which mianserin and yohimbine are most efficient. The functional characterization of two tyramine receptors from the honeybee, AmTAR1 (previously named AmTYR1) and AmTAR2, which respond to tyramine by changing cAMP levels in opposite direction, is an important step towards understanding the actions of tyramine in honeybee behavior and physiology, particularly in comparison to the effects of octopamine. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Human Complement Receptor Type 1/CD35 Is an Epstein-Barr Virus Receptor

    Directory of Open Access Journals (Sweden)

    Javier G. Ogembo

    2013-02-01

    Full Text Available Epstein-Barr virus (EBV attachment to primary B cells initiates virus entry. Although CD21 is the only known receptor for EBVgp350/220, a recent report documents EBV-infected B cells from a patient genetically deficient in CD21. On normal resting B cells, CD21 forms two membrane complexes: one with CD19 and another with CD35. Whereas the CD21/CD19 complex is widely retained on immortalized and B cell tumor lines, the related complement-regulatory protein CD35 is lost. To determine the role(s of CD35 in initial infection, we transduced a CD21-negative pre-B cell and myeloid leukemia line with CD35, CD21, or both. Cells expressing CD35 alone bound gp350/220 and became latently infected when the fusion receptor HLA II was coexpressed. Temporal, biophysical, and structural characteristics of CD35-mediated infection were distinct from CD21. Identification of CD35 as an EBV receptor uncovers a salient role in primary infection, addresses unsettled questions of virus tropism, and underscores the importance of EBVgp350/220 for vaccine development.

  6. PROSE FICTION--SHORT STORY, NOVEL. LITERATURE CURRICULUM V, TEACHER AND STUDENT VERSIONS.

    Science.gov (United States)

    KITZHABER, ALBERT R.

    THE BASIC CONVENTIONS THAT SHAPE THE CREATION OF THE SHORT STORY AND THE NOVEL ARE EXAMINED IN THIS 11TH-GRADE LITERATURE UNIT. THE SECTION ON THE SHORT STORY ILLUSTRATES NARRATIVE FICTION FORM THROUGH THE SHORT STORIES OF FORSTER, JACKSON, STEINBECK, THURBER, POE, MCCULLERS, HAWTHORNE, MANSFIELD, SALINGER, STEELE, AND COLLIER. EMPHASIZED IN EACH…

  7. Psychometric properties of the Ruminative Response Scale-short form in a clinical sample of patients with major depressive disorder

    Directory of Open Access Journals (Sweden)

    Parola N

    2017-05-01

    Full Text Available Nathalie Parola,1,2,* Xavier Yves Zendjidjian,1,3,* Marine Alessandrini,1 Karine Baumstarck,1 Anderson Loundou,1 Guillaume Fond,4,5 Fabrice Berna,4,6 Christophe Lançon,1–3 Pascal Auquier,1 Laurent Boyer1 1Public Health, Chronic Diseases and Quality of Life – Research Unit EA 3279, Aix-Marseille University, Marseille, 2Department of Psychiatry, Sainte-Marguerite University Hospital, Marseille, 3Department of Psychiatry, La Conception University Hospital, Marseille, 4Fondation FondaMental, Créteil, 5Department of Psychiatry and Addictology, Henri Mondor University Hospital, INSERM U955, Eq 15 Genetic Psychiatry and Psychopathology, Paris Est-Créteil University, Créteil, 6Department of Psychiatry, INSERM U1114, Fédération de Médecine Translationnelle de Strasbourg, Strasbourg University Hospital, Strasbourg, France *These authors contributed equally to this work Background: The Ruminative Response Scale (RRS-short form is one of the most widely used measures of rumination, comprising ten items and two components: reflection and brooding. The aim of this study was to investigate RRS validity and reliability in a clinical sample of French patients with major depressive disorder (MDD.Subjects and methods: Outpatients with a DSM-IV-TR diagnosis of MDD were recruited from a public academic hospital in France. Depressive symptoms were evaluated by the Beck Depression Inventory, anxiety by the State-Trait Anxiety Inventory – state scale, and quality of life by the 36-Item Short Form Health Survey (SF-36 questionnaire. Confirmatory factor analyses, item-dimension correlations, Cronbach’s α-coefficients, Rasch statistics, and external validity were tested. Differential item functioning analyses were performed for sex.Results: A total of 109 patients participated. The final reflection–brooding two-factor model of the RRS showed a good fit (root-mean-square error of approximation 0.041, comparative fit index 0.987, standardized root

  8. Effects of Acute Exercise on Circulating Soluble Form of the Urokinase Receptor in Patients With Major Depressive Disorder

    Directory of Open Access Journals (Sweden)

    Anna Gustafsson

    2017-04-01

    Full Text Available Inflammation has been proposed to play a role in the generation of depressive symptoms. Previously, we demonstrated that patients with major depressive disorder (MDD have increased plasma levels of the soluble form of the urokinase receptor (suPAR, a marker for low-grade inflammation. The aim of this study was to test the hypothesis that acute exercise would induce inflammatory response characterized by increased suPAR and elucidate whether patients with MDD display altered levels of suPAR in response to acute exercise. A total of 17 patients with MDD and 17 controls were subjected to an exercise challenge. Plasma suPAR (P-suPAR was analyzed before, during, and after exercise. There was a significantly higher baseline P-suPAR in the patients with MDD, and the dynamic changes of P-suPAR during the exercise were significantly lower in the patients with MDD, compared with the controls. This study supports the hypothesis that an activation of systemic inflammatory processes, measured as elevated P-suPAR, is involved in the pathophysiology of depression. The study concludes that P-suPAR is influenced by acute exercise, most likely due to release from activated neutrophils.

  9. A dearth of short-period massive binaries in the young massive star forming region M 17. Evidence for a large orbital separation at birth?

    Science.gov (United States)

    Sana, H.; Ramírez-Tannus, M. C.; de Koter, A.; Kaper, L.; Tramper, F.; Bik, A.

    2017-03-01

    Aims: The formation of massive stars remains poorly understood and little is known about their birth multiplicity properties. Here, we aim to quantitatively investigate the strikingly low radial-velocity dispersion measured for a sample of 11 massive pre- and near-main-sequence stars (σ1D= 5.6 ± 0.2 km s-1) in the very young massive star forming region M 17, in order to obtain first constraints on the multiplicity properties of young massive stellar objects. Methods: We compute the radial-velocity dispersion of synthetic populations of massive stars for various multiplicity properties and we compare the obtained σ1D distributions to the observed value. We specifically investigate two scenarios: a low binary fraction and a dearth of short-period binary systems. Results: Simulated populations with low binary fractions () or with truncated period distributions (Pcutoff > 9 months) are able to reproduce the low σ1D observed within their 68%-confidence intervals. Furthermore, parent populations with fbin > 0.42 or Pcutoff < 47 d can be rejected at the 5%-significance level. Both constraints are in stark contrast with the high binary fraction and plethora of short-period systems in few Myr-old, well characterized OB-type populations. To explain the difference in the context of the first scenario would require a variation of the outcome of the massive star formation process. In the context of the second scenario, compact binaries must form later on, and the cut-off period may be related to physical length-scales representative of the bloated pre-main-sequence stellar radii or of their accretion disks. Conclusions: If the obtained constraints for the M 17's massive-star population are representative of the multiplicity properties of massive young stellar objects, our results may provide support to a massive star formation process in which binaries are initially formed at larger separations, then harden or migrate to produce the typical (untruncated) power-law period

  10. Dopamine D2L receptor-interacting proteins regulate dopaminergic signaling

    Directory of Open Access Journals (Sweden)

    Norifumi Shioda

    2017-10-01

    Full Text Available Dopamine receptor family proteins include seven transmembrane and trimeric GTP-binding protein-coupled receptors (GPCRs. Among them, the dopamine D2 receptor (D2R is most extensively studied. All clinically used antipsychotic drugs serve as D2R antagonists in the mesolimbic dopamine system, and their ability to block D2R signaling is positively correlated with antipsychotic efficiency. Human genetic studies also show a significant association of DRD2 polymorphisms with disorders including schizophrenia and Parkinson's disease. D2R exists as two alternatively spliced isoforms, the long isoform (D2LR and the short isoform (D2SR, which differ in a 29-amino acid (AA insert in the third cytoplasmic loop. Importantly, previous reports demonstrate functional diversity between the two isoforms in humans. In this review, we focus on binding proteins that specifically interact with the D2LR 29AA insert. We discuss how D2R activities are mediated not only by heterotrimeric G proteins but by D2LR-interacting proteins, which in part regulate diverse D2R activities. Keywords: Dopamine D2L receptor, Antipsychotic drugs, DRD2 polymorphisms, Alternatively spliced isoforms, D2LR-interacting proteins

  11. Determination of some histamine H1-receptor antagonists in dosage forms.

    Science.gov (United States)

    Gazy, Azza A; Mahgoub, Hoda; El-Yazbi, F A; El-Sayed, M A; Youssef, Rasha M

    2002-10-15

    Three simple and accurate methods are presented for determination of Cetirizine, Fexofenadine, Loratadine and Acrivastine in pure form and commercial dosage forms. The first method is based on the reaction of the above cited drugs with bromocresol purple dye to form ion-pair complex extractable with chloroform and subsequently measured spectrophotometrically. Secondly, eosin gives with these drugs ion-pair complex, measurable directly without extraction both spectrophotometrically and spectrofluorimetrically. The last method involves the base-catalysed condensation of mixed anhydrides of organic acids (citric acid/acetic anhydride) where as the tertiary amino group in the above-cited drugs acts as the basic catalyst. The product of condensation is measured spectrophotometrically. All the reaction conditions for the proposed methods have been studied. Copyright 2002 Elsevier Science B.V.

  12. Killer Cell Immunoglobulin-like Receptors and their Ligands

    Directory of Open Access Journals (Sweden)

    Tajik N.

    2010-09-01

    Full Text Available The Natural killer (NK cells are a subset of lymphocytes comprising around 10% of total lymphocytes in peripheral blood. Due to their role in the innate response, NK cells provide a ‘first line of defense’ against infectious agents and cancer and are also thought to play a role in autoimmunity. The killer cell immunoglobulin-like receptors (KIR are regulatory surface molecules, found on NK cells and on a subset of T lymphocytes. The genes for KIR are present on chromosome 19 in the leukocyte receptor complex and show a major difference for both the type and number of KIR genes present among different ethnic groups. They have been divided into two groups of 2D or 3D, depending on the number of external immunoglobulin domains. The presence of a long cytoplasmic tail with two immune tyrosine-based inhibitory motifs (ITIM allows the transduction of inhibitory signals and characterizes the inhibitory KIRs (2DL and 3DL, whereas the presence of short cytoplasmic tails corresponds to the activating KIR receptors (2DS and 3DS.These polymorphic receptors interact with specific motifs on human leukocyte antigen (HLA class I molecules, modulate NK cytolytic activity. Some KIRs are known to interact with HLA-C molecules of target cells, HLA-Bw4 molecules and HLA-A3/11. For some KIRs the corresponding ligands are still unknown.

  13. Increased Circulating and Urinary Levels of Soluble TAM Receptors in Diabetic Nephropathy

    NARCIS (Netherlands)

    Ochodnicky, Peter; Lattenist, Lionel; Ahdi, Mohamed; Kers, Jesper; Uil, Melissa; Claessen, Nike; Leemans, Jaklien C.; Florquin, Sandrine; Meijers, Joost C. M.; Gerdes, Victor E. A.; Roelofs, Joris J. T. H.

    2017-01-01

    TAM receptors (Tyro3, Axl, and Mer) have been implicated in innate immunity. Circulating TAM receptor soluble forms (sTyro3, sAxl, sMer) are related to autoimmune disorders. We investigated TAM and their ligand protein S in patients with diabetes. Urinary and plasma levels of protein S, sTyro3,

  14. Generating "fragment-based virtual library" using pocket similarity search of ligand-receptor complexes.

    Science.gov (United States)

    Khashan, Raed S

    2015-01-01

    As the number of available ligand-receptor complexes is increasing, researchers are becoming more dedicated to mine these complexes to aid in the drug design and development process. We present free software which is developed as a tool for performing similarity search across ligand-receptor complexes for identifying binding pockets which are similar to that of a target receptor. The search is based on 3D-geometric and chemical similarity of the atoms forming the binding pocket. For each match identified, the ligand's fragment(s) corresponding to that binding pocket are extracted, thus forming a virtual library of fragments (FragVLib) that is useful for structure-based drug design. The program provides a very useful tool to explore available databases.

  15. Role of free fatty acid receptors in the regulation of energy metabolism.

    Science.gov (United States)

    Hara, Takafumi; Kashihara, Daiji; Ichimura, Atsuhiko; Kimura, Ikuo; Tsujimoto, Gozoh; Hirasawa, Akira

    2014-09-01

    Free fatty acids (FFAs) are energy-generating nutrients that act as signaling molecules in various cellular processes. Several orphan G protein-coupled receptors (GPCRs) that act as FFA receptors (FFARs) have been identified and play important physiological roles in various diseases. FFA ligands are obtained from food sources and metabolites produced during digestion and lipase degradation of triglyceride stores. FFARs can be grouped according to ligand profiles, depending on the length of carbon chains of the FFAs. Medium- and long-chain FFAs activate FFA1/GPR40 and FFA4/GPR120. Short-chain FFAs activate FFA2/GPR43 and FFA3/GPR41. However, only medium-chain FFAs, and not long-chain FFAs, activate GPR84 receptor. A number of pharmacological and physiological studies have shown that these receptors are expressed in various tissues and are primarily involved in energy metabolism. Because an impairment of these processes is a part of the pathology of obesity and type 2 diabetes, FFARs are considered as key therapeutic targets. Here, we reviewed recently published studies on the physiological functions of these receptors, primarily focusing on energy homeostasis. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Autoinactivation of the stargazin-AMPA receptor complex: subunit-dependency and independence from physical dissociation.

    Directory of Open Access Journals (Sweden)

    Artur Semenov

    Full Text Available Agonist responses and channel kinetics of native α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA receptors are modulated by transmembrane accessory proteins. Stargazin, the prototypical accessory protein, decreases desensitization and increases agonist potency at AMPA receptors. Furthermore, in the presence of stargazin, the steady-state responses of AMPA receptors show a gradual decline at higher glutamate concentrations. This "autoinactivation" has been assigned to physical dissociation of the stargazin-AMPA receptor complex and suggested to serve as a protective mechanism against overactivation. Here, we analyzed autoinactivation of GluA1-A4 AMPA receptors (all flip isoform expressed in the presence of stargazin. Homomeric GluA1, GluA3, and GluA4 channels showed pronounced autoinactivation indicated by the bell-shaped steady-state dose response curves for glutamate. In contrast, homomeric GluA2i channels did not show significant autoinactivation. The resistance of GluA2 to autoinactivation showed striking dependence on the splice form as GluA2-flop receptors displayed clear autoinactivation. Interestingly, the resistance of GluA2-flip containing receptors to autoinactivation was transferred onto heteromeric receptors in a dominant fashion. To examine the relationship of autoinactivation to physical separation of stargazin from the AMPA receptor, we analyzed a GluA4-stargazin fusion protein. Notably, the covalently linked complex and separately expressed proteins expressed a similar level of autoinactivation. We conclude that autoinactivation is a subunit and splice form dependent property of AMPA receptor-stargazin complexes, which involves structural rearrangements within the complex rather than any physical dissociation.

  17. Microsomal receptor for steroid hormones: functional implications for nuclear activity.

    Science.gov (United States)

    Muldoon, T G; Watson, G H; Evans, A C; Steinsapir, J

    1988-01-01

    Target tissues for steroid hormones are responsive by virtue of and to the extent of their content of functional intracellular receptors. Recent years have seen a shift in considerations of the cellular dynamics and distribution of these receptors, with current views favoring predominant intranuclear localization in the intact cell. This paper summarizes our analyses of the microsomal estrogen and androgen binding capability of rat uterine and ventral prostate tissue, respectively; these studies have revealed a set of high affinity sites that may act as a conduit for estrogen traversing the cell en route to the nucleus. These sites have many properties in common with cytosolic receptors, with the salient difference of a failure to activate to a more avid DNA-binding form under conditions which permit such activation of cytosolic receptors. The microsomal estrogen-binding proteins also have appreciable affinity for progesterone, another distinction from other known cellular estrogen receptor species. Various experimental approaches were employed to demonstrate that the microsomal receptors were not simply cytosol contaminants; the most convincing evidence is the recent successful separation of the cytosolic and microsomal forms by differential ammonium sulfate precipitation. Discrete subfractionation of subcellular components on successive sucrose gradients, with simultaneous assessments of binding capability and marker enzyme concentrations, indicates that the major portion of the binding is localized within the vesicles of the endoplasmic reticulum free of significant plasma membrane contamination. The microsomal receptors are readily solubilized by extraction with high- or low-salt-containing buffers or with steroid. The residual microsomes following such extraction have the characteristics of saturable acceptor sites for cytosolic estrogen-receptor complexes. The extent to which these sites will accept the cytosolic complexes is equal to the concentration of

  18. The Structure of the Mouse Serotonin 5-HT3 Receptor in Lipid Vesicles.

    Science.gov (United States)

    Kudryashev, Mikhail; Castaño-Díez, Daniel; Deluz, Cédric; Hassaine, Gherici; Grasso, Luigino; Graf-Meyer, Alexandra; Vogel, Horst; Stahlberg, Henning

    2016-01-05

    The function of membrane proteins is best understood if their structure in the lipid membrane is known. Here, we determined the structure of the mouse serotonin 5-HT3 receptor inserted in lipid bilayers to a resolution of 12 Å without stabilizing antibodies by cryo electron tomography and subtomogram averaging. The reconstruction reveals protein secondary structure elements in the transmembrane region, the extracellular pore, and the transmembrane channel pathway, showing an overall similarity to the available X-ray model of the truncated 5-HT3 receptor determined in the presence of a stabilizing nanobody. Structural analysis of the 5-HT3 receptor embedded in a lipid bilayer allowed the position of the membrane to be determined. Interactions between the densely packed receptors in lipids were visualized, revealing that the interactions were maintained by the short horizontal helices. In combination with methodological improvements, our approach enables the structural analysis of membrane proteins in response to voltage and ligand gating. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Glycosylation as a Main Regulator of Growth and Death Factor Receptors Signaling

    Directory of Open Access Journals (Sweden)

    Inês Gomes Ferreira

    2018-02-01

    Full Text Available Glycosylation is a very frequent and functionally important post-translational protein modification that undergoes profound changes in cancer. Growth and death factor receptors and plasma membrane glycoproteins, which upon activation by extracellular ligands trigger a signal transduction cascade, are targets of several molecular anti-cancer drugs. In this review, we provide a thorough picture of the mechanisms bywhich glycosylation affects the activity of growth and death factor receptors in normal and pathological conditions. Glycosylation affects receptor activity through three non-mutually exclusive basic mechanisms: (1 by directly regulating intracellular transport, ligand binding, oligomerization and signaling of receptors; (2 through the binding of receptor carbohydrate structures to galectins, forming a lattice thatregulates receptor turnover on the plasma membrane; and (3 by receptor interaction with gangliosides inside membrane microdomains. Some carbohydrate chains, for example core fucose and β1,6-branching, exert a stimulatory effect on all receptors, while other structures exert opposite effects on different receptors or in different cellular contexts. In light of the crucial role played by glycosylation in the regulation of receptor activity, the development of next-generation drugs targeting glyco-epitopes of growth factor receptors should be considered a therapeutically interesting goal.

  20. Fibroblast growth factor 10-fibroblast growth factor receptor 2b mediated signaling is not required for adult glandular stomach homeostasis.

    Directory of Open Access Journals (Sweden)

    Allison L Speer

    Full Text Available The signaling pathways that are essential for gastric organogenesis have been studied in some detail; however, those that regulate the maintenance of the gastric epithelium during adult homeostasis remain unclear. In this study, we investigated the role of Fibroblast growth factor 10 (FGF10 and its main receptor, Fibroblast growth factor receptor 2b (FGFR2b, in adult glandular stomach homeostasis. We first showed that mouse adult glandular stomach expressed Fgf10, its receptors, Fgfr1b and Fgfr2b, and most of the other FGFR2b ligands (Fgf1, Fgf7, Fgf22 except for Fgf3 and Fgf20. Fgf10 expression was mesenchymal whereas FGFR1 and FGFR2 expression were mostly epithelial. Studying double transgenic mice that allow inducible overexpression of Fgf10 in adult mice, we showed that Fgf10 overexpression in normal adult glandular stomach increased epithelial proliferation, drove mucous neck cell differentiation, and reduced parietal and chief cell differentiation. Although a similar phenotype can be associated with the development of metaplasia, we found that Fgf10 overexpression for a short duration does not cause metaplasia. Finally, investigating double transgenic mice that allow the expression of a soluble form of Fgfr2b, FGF10's main receptor, which acts as a dominant negative, we found no significant changes in gastric epithelial proliferation or differentiation in the mutants. Our work provides evidence, for the first time, that the FGF10-FGFR2b signaling pathway is not required for epithelial proliferation and differentiation during adult glandular stomach homeostasis.