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Subunit Levels (subunit + level)

Distribution by Scientific Domains

Medical Sciences	33%

Selected Abstracts

The Weighted Generalized Estimating Equations Approach for the Evaluation of Medical Diagnostic Test at Subunit Level

BIOMETRICAL JOURNAL, Issue 5 2006
Carol Y. Lin
Abstract Sensitivity and specificity are common measures used to evaluate the performance of a diagnostic test. A diagnostic test is often administrated at a subunit level, e.g. at the level of vessel, ear or eye of a patient so that the treatment can be targeted at the specific subunit. Therefore, it is essential to evaluate the diagnostic test at the subunit level. Often patients with more negative subunit test results are less likely to receive the gold standard tests than patients with more positive subunit test results. To account for this type of missing data and correlation between subunit test results, we proposed a weighted generalized estimating equations (WGEE) approach to evaluate subunit sensitivities and specificities. A simulation study was conducted to evaluate the performance of the WGEE estimators and the weighted least squares (WLS) estimators (Barnhart and Kosinski, 2003) under a missing at random assumption. The results suggested that WGEE estimator is consistent under various scenarios of percentage of missing data and sample size, while the WLS approach could yield biased estimators due to a misspecified missing data mechanism. We illustrate the methodology with a cardiology example. (© 2006 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source]

Loss of zolpidem efficacy in the hippocampus of mice with the GABAA receptor ,2 F77I point mutation

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2005
D. W. Cope
Abstract Zolpidem is a hypnotic benzodiazepine site agonist with some ,-aminobutyric acid (GABA)A receptor subtype selectivity. Here, we have tested the effects of zolpidem on the hippocampus of ,2 subunit (,2F77I) point mutant mice. Analysis of forebrain GABAA receptor expression with immunocytochemistry, quantitative [3H]muscimol and [35S] t-butylbicyclophosphorothionate (TBPS) autoradiography, membrane binding with [3H]flunitrazepam and [3H]muscimol, and comparison of miniature inhibitory postsynaptic current (mIPSC) parameters did not reveal any differences between homozygous ,2I77/I77 and ,2F77/F77 mice. However, quantitative immunoblot analysis of ,2I77/I77 hippocampi showed some increased levels of ,2, ,1, ,4 and , subunits, suggesting that differences between strains may exist in unassembled subunit levels, but not in assembled receptors. Zolpidem (1 µm) enhanced the decay of mIPSCs in CA1 pyramidal cells of control (C57BL/6J, ,2F77/F77) mice by ,,60%, and peak amplitude by ,,20% at 33,34 °C in vitro. The actions of zolpidem (100 nm or 1 µm) were substantially reduced in ,2I77/I77 mice, although residual effects included a 9% increase in decay and 5% decrease in peak amplitude. Similar results were observed in CA1 stratum oriens/alveus interneurons. At network level, the effect of zolpidem (10 µm) on carbachol-induced oscillations in the CA3 area of ,2I77/I77 mice was significantly different compared with controls. Thus, the ,2F77I point mutation virtually abolished the actions of zolpidem on GABAA receptors in the hippocampus. However, some residual effects of zolpidem may involve receptors that do not contain the ,2 subunit. [source]

Utp25p, a nucleolar Saccharomyces cerevisiae protein, interacts with U3 snoRNP subunits and affects processing of the 35S pre-rRNA

FEBS JOURNAL, Issue 13 2010
Mauricio B. Goldfeder
In eukaryotes, pre-rRNA processing depends on a large number of nonribosomal trans -acting factors that form intriguingly organized complexes. Two intermediate complexes, pre-40S and pre-60S, are formed at the early stages of 35S pre-rRNA processing and give rise to the mature ribosome subunits. Each of these complexes contains specific pre-rRNAs, some ribosomal proteins and processing factors. The novel yeast protein Utp25p has previously been identified in the nucleolus, an indication that this protein could be involved in ribosome biogenesis. Here we show that Utp25p interacts with the SSU processome proteins Sas10p and Mpp10p, and affects 18S rRNA maturation. Depletion of Utp25p leads to accumulation of the pre-rRNA 35S and the aberrant rRNA 23S, and to a severe reduction in 40S ribosomal subunit levels. Our results indicate that Utp25p is a novel SSU processome subunit involved in pre-40S maturation. Structured digital abstract ,,MINT-7889901: SAS10 (uniprotkb:Q12136) physically interacts (MI:0915) with Utp25p (uniprotkb:P40498) by pull down (MI:0096) ,,MINT-7889915: NIP7 (uniprotkb:Q08962) physically interacts (MI:0915) with RRP43 (uniprotkb:P25359) by two hybrid (MI:0018) ,,MINT-7889852: Utp25p (uniprotkb:P40498) physically interacts (MI:0915) with MPP10 (uniprotkb:P47083) by two hybrid (MI:0018) ,,MINT-7890065: NOP1 (uniprotkb:P15646) and Utp25p (uniprotkb:P40498) colocalize (MI:0403) by fluorescence microscopy (MI:0416) ,,MINT-7889865: Utp25p (uniprotkb:P40498) physically interacts (MI:0915) with SAS10 (uniprotkb:Q12136) by two hybrid (MI:0018) [source]

Hippocampal N -Methyl- d -Aspartate Receptor Subunit Expression Profiles in a Mouse Model of Prenatal Alcohol Exposure

ALCOHOLISM, Issue 2 2010
Sabrina L. Samudio-Ruiz
Background:, Although several reports have been published showing prenatal ethanol exposure is associated with alterations in N -methyl- d- aspartate (NMDA) receptor subunit levels and, in a few cases, subcellular distribution, results of these studies are conflicting. Methods:, We used semi-quantitative immunoblotting techniques to analyze NMDA receptor NR1, NR2A, and NR2B subunit levels in the adult mouse hippocampal formation isolated from offspring of dams who consumed moderate amounts of ethanol throughout pregnancy. We employed subcellular fractionation and immunoprecipitation techniques to isolate synaptosomal membrane- and postsynaptic density protein-95 (PSD-95)-associated pools of receptor subunits. Results:, We found that, compared to control animals, fetal alcohol-exposed (FAE) adult mice had: (i) increased synaptosomal membrane NR1 levels with no change in association of this subunit with PSD-95 and no difference in total NR1 expression in tissue homogenates; (ii) decreased NR2A subunit levels in hippocampal homogenates, but no alterations in synaptosomal membrane NR2A levels and no change in NR2A-PSD-95 association; and (iii) no change in tissue homogenate or synaptosomal membrane NR2B levels but a reduction in PSD-95-associated NR2B subunits. No alterations were found in mRNA levels of NMDA receptor subunits suggesting that prenatal alcohol-associated differences in subunit protein levels are the result of differences in post-transcriptional regulation of subunit localization. Conclusions:, Our results demonstrate that prenatal alcohol exposure induces selective changes in NMDA receptor subunit levels in specific subcellular locations in the adult mouse hippocampal formation. Of particular interest is the finding of decreased PSD-95-associated NR2B levels, suggesting that synaptic NR2B-containing NMDA receptor concentrations are reduced in FAE animals. This result is consistent with various biochemical, physiological, and behavioral findings that have been linked with prenatal alcohol exposure. [source]

Circulating IGF-I levels are associated with increased biventricular contractility in top-level rowers

CLINICAL ENDOCRINOLOGY, Issue 2 2008
Giovanni Vitale
Summary Background, The intensive physical activity is often associated with cardiac changes. Objectives, (i) To evaluate the IGF-I system and myocardial structure and function by standard Doppler echocardiography and Tissue Doppler in athletes and sedentary controls; and (ii) to determine any relationship between IGF-I system and echocardiographic parameters. Methods, Nineteen male top-level rowers and 19 age-matched healthy sedentary male controls underwent blood determination of fasting serum IGF-I, IGFBP-3 and acid-labile subunit levels and standard Doppler echocardiography combined with pulsed Tissue Doppler of posterior septal wall, left ventricular (LV) lateral mitral annulus and right ventricular (RV) tricuspid annulus. Myocardial presystolic (PSm), systolic (Sm), the ratio of early diastolic (Em) to atrial (Am) velocities as well as myocardial time intervals were calculated. Results, Rowers had higher serum IGF-I levels (P = 0·04), higher biventricular cavity dimensions and wall thicknesses compared to controls. They also had better LV and RV myocardial function than controls. In the rowers, IGF-I was associated with LV ejection fraction (r = 0·50, P = 0·03), RV PSm velocity (r = 0·55, P = 0·01) and with RV myocardial precontraction time (r = ,0·57, P = 0·01). These associations remained significant after adjusting for age and heart rate. Conclusions, Top-level athletes showed higher IGF-I levels and a better myocardial performance than controls, particularly for the RV systolic activity. The independent correlations between IGF-I and systolic parameters of the left (ejection fraction) and right (PSm velocity and precontraction time) ventricles may possibly indicate a role of IGF-I system in the modulation of myocardial inotropism in athletes. Further studies are needed to confirm this hypothesis. [source]