Several reports have suggested the involvement of brain adenosine and dopamine receptors in different actions produced by ethanol such as motor incoordination or anxiolytic, hypnotic and reinforcing ...effects. The co-localization and interaction between adenosine and dopamine receptors in different brain regions has also been well documented. However, few studies have demonstrated the involvement of these mechanisms in the tolerance induced by ethanol.
The aim of the present study was to evaluate the role of adenosine and dopamine receptors in the development of rapid tolerance to ethanol-induced motor incoordination in mice.
In connection with the rota-rod apparatus, the effects of acute administration of the adenosine receptor antagonists caffeine (non-selective), 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, adenosine A1 receptor antagonist) and 4-(2-7-amino-2-{2-furyl}{1,2,4}triazolo-{2,3-a}{1,3,5}triazin-5-yl-aminoethyl)phenol (ZM241385, adenosine A2A receptor antagonist), together with R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine (SCH23390, dopamine D1 receptor antagonist) and sulpiride (dopamine D2 receptor antagonist), alone or in combination with ethanol (2.25 g/kg, i.p.), were studied. Twenty-four hours after, all animals were re-tested on the rota-rod after receiving the same dose of ethanol.
The repeated administration of ethanol promoted a significant reduction of motor impairment on day 2 (i.e. rapid tolerance). This effect was blocked by caffeine (3.0-30.0 mg/kg, i.p.), DPCPX (3.0-6.0 mg/kg, i.p.) or SCH23390 (0.01-0.03 mg/kg, s.c.), but not with ZM241385 (0.5-1.0 mg/kg, i.p.) or sulpiride (1.0-3.0 mg/kg, i.p.).
Our results suggest that the rapid tolerance to ethanol-induced motor impairment in mice may be modulated by adenosine A1 receptors and dopamine D1 receptors.
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First, this study examined genetic and environmental sources of variation in performance on a standardised test of academic achievement, the Queensland Core Skills Test (QCST) (Queensland Studies ...Authority, 2003a). Second, it assessed the genetic correlation among the QCST score and Verbal and Performance IQ measures using the Multidimensional Aptitude Battery (MAB), Jackson, D. N. (1984) Multidimensional Aptitude Battery manual. Port Huron, MI:Research Psychologist Press, Inc.. Participants were 256 monozygotic twin pairs and 326 dizygotic twin pairs aged from 15 to 18 years (mean 17 years+/-0.4 SD) when achievement tested, and from 15 to 22 years (mean 16 years+/-0.4 SD) when IQ tested. Univariate analysis indicated a heritability for the QCST of 0.72. Adjustment to this estimate due to truncate selection (downward adjustment) and positive phenotypic assortative mating (upward adjustment) suggested a heritability of 0.76 The phenotypic (0.81) and genetic (0.91) correlations between the QCST and Verbal IQ (VIQ) were significantly stronger than the phenotypic (0.57) and genetic (0.64) correlations between the QCST and Performance IQ (PIQ). The findings suggest that individual variation in QCST performance is largely due to genetic factors and that common environmental effects may be substantially accounted for by phenotypic assortative mating. Covariance between academic achievement on the QCST and psychometric IQ (particularly VIQ) is to a large extent due to common genetic influences.
Apolipoprotein A-I amyloidosis is a rare, late-onset, autosomal dominant condition characterized by systemic deposition of amyloid in tissues, the major clinical problems being related to renal, ...hepatic, and cardiac involvement. Described is the clinical and histologic picture of renal involvement as a result of apolipoprotein A-I amyloidosis in five families of Italian ancestry. In all of the affected family members, the disease was caused by the Leu75Pro heterozygous mutation in exon 4 of apolipoprotein A-I gene, as demonstrated by direct sequencing and RFLP analysis. Immunohistochemistry confirmed that amyloid deposits were specifically stained with an anti-apolipoprotein A-I antibody. The clinical phenotype was mainly characterized by a variable combination of kidney and liver disturbance. The occurrence of renal involvement seemed to be almost universal, although its severity varied greatly ranging from subclinical organ damage to overt, slowly progressive renal dysfunction. The renal presentation was consistent with a tubulointerstitial disease, as suggested by the findings of defective urine-concentrating capacity, moderate polyuria, negative urinalysis, and mild tubular proteinuria. Histology confirmed tubulointerstitial nephritis. Surprising, amyloid was restricted to nonglomerular regions and limited to the renal medulla. This location of apolipoprotein A-I amyloid differs sharply from other systemic amyloidoses that are mainly characterized by glomerular and vascular deposits. The tubulointerstitial nephritis as a result of hereditary apolipoprotein A-I amyloidosis is a rare disease and a challenging diagnosis to recognize. Patients who present with familial tubulointerstitial nephritis associated with liver disease require a high index of suspicion for apolipoprotein A-I amyloidosis.
There is ongoing debate whether the efficiency of local cognitive processes leads to global cognitive ability or whether global ability feeds the efficiency of basic processes. A prominent example is ...the well-replicated association between inspection time (IT), a measure of perceptual discrimination speed, and intelligence (IQ), where it is not known whether increased speed is a cause or consequence of high IQ. We investigated the direction of causation between IT and IQ in 2012 genetically related subjects from Australia and The Netherlands. Models in which the reliable variance of each observed variable was specified as a latent trait showed IT correlations of −0.44 and −0.33 with respective Performance and Verbal IQ; heritabilities were 57% (IT), 83% (PIQ) and 77% (VIQ). Directional causation models provided poor fits to the data, with covariation best explained by pleiotropic genes (influencing variation in both IT and IQ). This finding of a common genetic factor provides a better target for identifying genes involved in cognition than genes which are unique to specific traits.
Information processing speed, as measured by elementary cognitive tasks, is correlated with higher order cognitive ability so that increased speed relates to improved cognitive performance. The ...question of whether the genetic variation in Inspection Time (IT) and Choice Reaction Time (CRT) is associated with IQ through a unitary factor was addressed in this multivariate genetic study of IT, CRT, and IQ subtest scores. The sample included 184 MZ and 206 DZ twin pairs with a mean age of 16.2 years (range 15-18 years). They were administered a visual (pi-figure) IT task, a two-choice RT task, five computerized subtests of the Multidimensional Aptitude Battery, and the digit symbol substitution subtest from the WAIS-R. The data supported a factor model comprising a general, three group (verbal ability, visuospatial ability, broad speediness), and specific genetic factor structure, a shared environmental factor influencing all tests but IT, plus unique environmental factors that were largely specific to individual measures. The general genetic factor displayed factor loadings ranging between 0.35 and 0.66 for the IQ subtests, with IT and CRT loadings of -0.47 and -0.24, respectively. Results indicate that a unitary factor is insufficient to describe the entire relationship between cognitive speed measures and all IQ subtests, with independent genetic effects explaining further covariation between processing speed (especially CRT) and Digit Symbol.
Purpose We report that primary infertility and hypergonadotropic hypogonadism in young patients may be caused by testicular amyloidosis and it is associated with the presence of a mutation in the ...apoA-I gene, resulting in the replacement of proline for leucine at residue 75 of the protein. Materials and Methods Ten patients presenting with infertility, gynecomastia, decreased libido, erectile dysfunction or a family history of amyloidosis underwent clinical evaluation, hormone assays, semen analysis, ultrasonographic investigation of the testicles, testicular biopsy and DNA sequencing of the apoA-I gene. Results All patients showed azoospermia and 9 had increased testicular volume. Massive amyloid deposition was observed in all testicular biopsies and the apoA-I mutation of replacement of proline for leucine at residue 75 of the protein was noted. Five patients showed hypergonadotropic hypogonadism and 5 had normal testosterone values with high gonadotropin levels. Conclusions Nonobstructive azoospermia and macro-orchidism with or without hypogonadism may be caused by hereditary apoA-I amyloidosis in young patients. Testicular amyloidosis can be the first manifestation of this systemic disease. Specific staining for amyloid deposits and genetic analysis of apoA-I mutations are recommended in young, infertile patients with macro-orchidism. Finally, surveillance in asymptomatic mutation carriers is suggested to evaluate the opportunity to implement sperm retrieval and start androgen replacement therapy when necessary.
Background The P3(00) event-related potential is an index of processing capacity (P3 amplitude) and stimulus evaluation (P3 latency) as well as a phenotypic marker of various forms of psychopathology ...where P3 abnormalities have been reported. Methods A genome-wide linkage scan of 400–761 autosomal markers, at an average spacing of 5–10 centimorgans (cM), was completed in 647 twins/siblings (306 families mostly comprising dizygotic twins), mean age 16.3, range 15.4–20.1 years, for whom P3 amplitude and latency data were available. Results Significant linkage for P3 amplitude was observed on chromosome 7q for the central recording site (logarithm-of-odds LOD = 3.88, p = .00002) and in the same region for both frontal (LOD = 2.19, p = .0015) and parietal (LOD = 1.67, p = .0053) sites, with multivariate analysis also identifying linkage in this region (LOD = 2.14, p = .0017). Suggestive linkage was also identified on 6p (LODmax = 2.49) and 12q (LODmax = 2.24), with other promising regions identified on 9q (LODmax = 2.14) and 10p (LODmax = 2.18). Less striking were the results for P3 latency; LOD > 1.5 were found on chromosomes 1q, 9q, 10q, 12q, and 19p. Conclusions This is a first step in the identification of genes for normal variation in the P3. Loci identified here for P3 amplitude suggest the possible importance of neurodevelopmental genes in addition to those influencing neurotransmitters, fitting with the evidence that P3 amplitude is sensitive to diverse types of brain abnormalities.
The mode of binding of sperm and somatic H1 histones to DNA has been investigated by analyzing the effect of their addition on the electrophoretic mobility of linear and circular plasmid molecules. ...Low concentrations of sperm histones do not appear to alter the electrophoretic mobility of DNA, whereas at increasing concentrations, an additional DNA band is observed near the migration origin. This band then becomes the only component at higher values. In contrast, somatic histones cause a gradual retardation in the mobility of the DNA band at low concentrations and aggregated structures are observed only at higher values. Experiments on the H1 globular domain obtained by limited proteolysis indicate that the mode of binding to DNA depends on the H1 globular domain. The arginine residues appear to be relevant for the different effects as indicated by experiments on sperm histone and on protamine with arginines deguanidinated to ornithines. The modified molecules influence DNA mobility like somatic H1s, indicating that the positive guanidino groups of arginines cannot be substituted by the positive amino groups of ornithines. Modifications of the amino groups of lysines show that these residues are necessary for the binding of H1 histones to DNA but they have no influence on the binding mode.
In this study, we examined genetic and environmental influences on covariation among two reading tests used in neuropsychological assessment (Cambridge Contextual Reading Test CCRT, Beardsall, L., ...and Huppert, F. A. (1994). J. Clin. Exp. Neuropsychol. 16:232-242, Schonell Graded Word Reading Test SGWRT, Schonell, F. J., and Schonell, P. E. (1960). Diagnostic and attainment testing. Edinburgh: Oliver and Boyd.) and among a selection of IQ subtests from the Multidimensional Aptitude Battery (MAB), Jackson, D. N. (1984). Multidimensional aptitude battery, Ontario: Research Psychologists Press. and the Wechsler Adult Intelligence Scale-Revised (WAIS-R) Wechsler, D. (1981). Manual for the Wechsler Adult Intelligence Scale-Revised (WAIS-R). San Antonio: The Psychological Corporation. Participants were 225 monozygotic and 275 dizygotic twin pairs aged from 15 years to 18 years (mean, 16 years). For Verbal IQ subtests, phenotypic correlations with the reading tests ranged from 0.44 to 0.65. For Performance IQ subtests, phenotypic correlations with the reading tests ranged from 0.23 to 0.34. Results of Structural Equation Modeling (SEM) supported a model with one genetic General factor and three genetic group factors (Verbal, Performance, Reading). Reading performance was influenced by the genetic General factor (accounting for 13% and 20% of the variance for the CCRT and SGWRT, respectively), the genetic Verbal factor (explaining 17% and 19% of variance for the CCRT and SGWRT), and the genetic Reading factor (explaining 21% of the variance for both the CCRT and SGWRT). A common environment factor accounted for 25% and 14% of the CCRT and SGWRT variance, respectively. Genetic influences accounted for more than half of the phenotypic covariance between the reading tests and each of the IQ subtests. The heritabilities of the CCRT and SGWRT were 0.54 and 0.65, respectively. Observable covariance between reading assessments used by neuropsychologists to estimate IQ and IQ subtests appears to be largely due to genetic effects.
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