Biomedical subjects

C Donnini

Publications and source records attributed to C Donnini.

At least 19 recordsLinked to original sources

PubMed2007

Perceived parenting behavior in the childhood of cocaine users: relationship with genotype and personality traits.

Low parental care during childhood, a pattern characteristic of an "affectionless control" rearing style was frequently reported in the history of addicted individuals. Parents' childrearing regimes and children's genetic predispositions, with their own behavioral characteristics, have been seen to be closely interwoven, probably affecting children's development and addictive behavior susceptibility. In the present study, parents care perception, aggressive personality traits, and genotype (serotonin transporter promoter gene--5-HTTLPR) have been investigated in cocaine users and healthy control subjects. PBI scores (maternal and paternal care) were lower and BDHI scores (aggressiveness) higher in cocaine users in comparison with controls and significant differences in the perception of either paternal or maternal care were observed between cocaine users and non-users. The short-short (SS) genotype frequency was significantly higher among cocaine users compared with control subjects (P = 0.04). Logistic regression proves that persons bearing the SS genotype have a risk of becoming cocaine user almost three times higher than those having the LL genotype. Estimations of the effects of other factors potentially affecting the risk of being cocaine addicted clearly prove the significant impact of aggressiveness: the highest the score, the highest the risk of becoming cocaine user. Moreover, paternal and maternal care perception significantly improve the fit of the model (the log likelihood decreases passing from -105.9 to -89.8, LR test = 32.17, P-value = 0.0000). Each unit increase in the PBI score yields a significant 12% and 10% decrease of the risk of becoming cocaine user, respectively for paternal and maternal care. Interestingly, once controlled for the PBI score, the relative risk associated to the SS genotype drops strikingly and becomes no longer statistically significant. On the whole, our preliminary data suggest that the association between 5-HT transporter polymorphism and psycho-stimulant use may be mediated by mother-child relationship and parental attachment perception, both being environmental and genetic factors involved in the proneness to substance use disorders, particularly in aggressive-antisocial individuals.

Adolescent↗

PubMed2005

Association of the serotonin transporter promoter polymorphism with smoking behavior among adolescents.

Serotonin transporter promoter polymorphism (5-HTTLPR) genotype was previously found associated with smoking behavior, difficulty in quitting smoking, and nicotine addiction; with non-replicated findings and contrasting results. Aim of the present study was to evaluate the possible association between 5-HTTLPR genotype and smoking behavior among adolescents, in relationship with psychological characteristics. Two hundred and ten Caucasian high school students (aged 14-19 years); 103 non-smokers, who have never smoked nicotine; and 107 tobacco smokers have been genotyped. Aggressiveness levels and temperamental traits were measured in both smokers and non-smokers, respectively, utilizing Buss-Durkee Hostility Inventory (BDHI) and Cloninger Three-Dimensional Personality Questionnaire (TPQ). Data about school performance have been also collected. The short-short (SS) genotype frequency was significantly higher among smokers compared with non-smokers (P = 0.023). The odds ratio for the SS genotype versus the long-long (LL) genotype frequency was 1.17 [95% CL (0.30-2.05)], when smokers were compared with non-smokers. The SS genotype frequency was significantly higher among heavy smokers with early onset, compared with moderate smokers with late onset (P = 0.042). BDHI irritability scores, NS scores at TPQ, and school failure frequency were significantly higher in smokers than in non-smokers. Multivariate model-fitting analysis evidenced a significantly greater relationship of genotype with irritability levels (BDHI scores) (0.34, P < 0.001) and temperament traits (NS scores) (0.36, P < 0.001), than with school performance (rate of school under-achievements) (0.18, P < 0.05) and nicotine smoking (number of cigarettes) (0.24, P < 0.01). Accordingly, factor-analysis showed that gene polymorphism contributes more directly to BDHI scores and NS scores (0.73; 0.71) than to smoking behavior and school under-achievement (0.54; 0.51). Our data suggest that a decreased expression of the gene encoding the 5-HTT transporter, due to "S" promoter polymorphism, may be associated with smoking behavior among adolescents and increased risk to develop nicotine dependence, possibly in relationship to personality traits, temperamental characteristics, and school under-achievements.

Achievement↗

PubMed2005

Serotonin transporter promoter polymorphism genotype is associated with temperament, personality traits and illegal drugs use among adolescents.

Serotonin transporter promoter polymorphism (5-HTTLPR) genotype was previously found associated with substance use disorders, particularly in the subjects with comorbid antisocial behavior, and with temperament and personality traits at risk for substance abuse. Aim of the present study was to evaluate the possible association between 5-HTTLPR genotype and the availability to experiment illegal drugs among adolescents, in relationship with psychological characteristics. 216 caucasian high school students (aged 14-19 ys), 125 abstinent subjects, who have never experimented psychotropic drugs, and 91 experimenters of illegal drugs have been genotyped. Aggressiveness levels and temperamental traits were measured in both abstinent subjects and experimenters utilizing respectively Buss-Durkee-Hostility-Inventory (BDHI) and Cloninger Three-dimensional Personality Questionnaire (TPQ). Data about school performance have been also collected. The short-short (SS) genotype frequency was significantly higher among experimenters compared with abstinent subjects (p = 0.001). The odds ratio for the SS genotype vs the long-long (LL) genotype frequency was 4.67, 95% Cl (1.97-11.04), when experimenters were compared with abstinent students. The SS genotype frequency was significantly higher among aggressive/novelty seeker (NS) experimenters with poor school achievements, compared with drugs experimenters without aggressiveness and school failure (p = 0.02). When evaluated on the entire sample, BDHI mean total scores, NS scores at TPQ and school failure frequency were significantly higher in SS individuals, in comparison with LL subjects. Our data suggest that a decreased expression of the gene encoding the 5-HTT transporter, due to "S" promoter polymorphism, may be associated with an increased availability to experiment illegal drugs among adolescents, particularly in the subjects with more consistent aggressiveness, NS temperament and learning disabilities.

Adolescent↗

PubMed2004

Association between low-activity serotonin transporter genotype and heroin dependence: behavioral and personality correlates.

In previous studies, serotonin (5-HT) system disturbance was found involved in a variety of behavioral disorders, psychopathologies, and substance use disorders. A functional polymorphism in the promoter region of the human serotonin transporter gene (5-HTTLPR) was recently identified and the presence of the short (S) allele found to be associated with a lower level of expression of the gene, lower levels of 5-HT uptake, type 2 alcoholism, violence and suicidal behavior. In the present study, 101 heroin addicts (males, West European, Caucasians) and 101 healthy control subjects matched for race and gender, with no history of substance use disorder, have been genotyped. Aggressiveness levels were measured in both heroin addicts and controls utilizing Buss-Durkee-Hostility-Inventory (BDHI). Data about suicide attempt and violent criminal behavior in subject history have been collected. The short-short (SS) genotype frequency was significantly higher among heroin dependent individuals compared with control subjects (P = 0.025). The odds ratio for the SS genotype versus the long-long (LL) genotype frequency was 0.69, 95% Cl (0.49-0.97), when heroin addicts were compared with healthy controls. The SS genotype frequency was significantly higher among violent heroin dependent individuals compared with addicted individuals without aggressive behavior (P = 0.02). BDHI mean total scores and suspiciousness and negativism subscales scores were significantly higher in SS individuals, in comparison with LL subjects, among heroin addicts. No association was found between SS genotype and suicide history. Our data suggest that a decreased expression of the gene encoding the 5-HTT transporter, due to "S" promoter polymorphism, may be associated with an increased risk for substance use disorders, particularly in the subjects with more consistent aggressiveness and impulsiveness.

Adult↗

PubMed2004

Analysis of monoamine oxidase A (MAO-A) promoter polymorphism in male heroin-dependent subjects: behavioural and personality correlates.

The promoter of the monoamine oxidase A (MAO-A) gene was analysed to test whether length variation of the repeat polymorphism contributes to variation in individual vulnerability to aggressive-criminal behaviour, and liability to heroin dependence. The repeat number of the MAO-A polymorphism was assessed in 199 male subjects of Italian descent, a sample comprising 95 healthy subjects and 104 heroin-dependent subjects including 52 addicted individuals with violent behaviour and antisocial personality disorder. The frequency of the low-activity 3-repeat allele was significantly higher in violent offenders among heroin addicts, compared to addicted individuals without antisocial behaviour (34.6 vs. 15.4%; p<0.03) and controls (18.9%; p<0.05). No significant difference was evidenced in the frequencies of the MAO-A alleles between heroin-dependent subjects in general and control subjects. High activity 4-repeat allele frequency was significantly higher in addicted individuals without antisocial behavior compared to antisocial-aggressive heroin-dependent subjects (76.9 vs. 55.8%; p<0.02). Buss Durkee Hostility Inventory (BDHI) mean total scores were significantly higher in heroin addicts than in controls (p<0.001), and in antisocial-violent heroin addicts in comparison with addicted individuals without antisocial behaviour (p<0.005). Among heroin addicts BDHI irritability, suspiciousness and resentment subscales scores were found significantly higher in low activity 3-repeat allele subjects than in high activity alleles subjects (p<0.001; p<0.05; p<0.05, respectively). No association was found between MAO-A polymorphism and suicide history. Our findings suggest that the low-activity 3-repeat allele of the MAO-A promoter polymorphism confers increased susceptibility to antisocial-violent behavior and aggressiveness, rather than drug dependence per se, in heroin-dependent males.

Adult↗

PubMed2001

Three target genes for the transcriptional activator Cat8p of Kluyveromyces lactis: acetyl coenzyme A synthetase genes KlACS1 and KlACS2 and lactate permease gene KlJEN1.

The aerobic yeast Kluyveromyces lactis and the predominantly fermentative Saccharomyces cerevisiae share many of the genes encoding the enzymes of carbon and energy metabolism. The physiological features that distinguish the two yeasts appear to result essentially from different organization of regulatory circuits, in particular glucose repression and gluconeogenesis. We have isolated the KlCAT8 gene (a homologue of S. cerevisiae CAT8, encoding a DNA binding protein) as a multicopy suppressor of a fog1 mutation. The Fog1 protein is a homologue of the Snf1 complex components Gal83p, Sip1p, and Sip2p of S. cerevisiae. While CAT8 controls the key enzymes of gluconeogenesis in S. cerevisiae, KlCAT8 of K. lactis does not (I. Georis, J. J. Krijger, K. D. Breunig, and J. Vandenhaute, Mol. Gen. Genet. 264:193-203, 2000). We therefore examined possible targets of KlCat8p. We found that the acetyl coenzyme A synthetase genes, KlACS1 and KlACS2, were specifically regulated by KlCAT8, but very differently from the S. cerevisiae counterparts. KlACS1 was induced by acetate and lactate, while KlACS2 was induced by ethanol, both under the control of KlCAT8. Also, KlJEN1, encoding the lactate-inducible and glucose-repressible lactate permease, was found under a tight control of KlCAT8.

Acetate-CoA Ligase↗

PubMed1996

FOG1 and FOG2 genes, required for the transcriptional activation of glucose-repressible genes of Kluyveromyces lactis, are homologous to GAL83 and SNF1 of saccharomyces cerevisiae.

The fog1 and fog2 mutants of the yeast Kluyveromyces lactis were identified by inability to grow on a number of both fermentable and non-fermentable carbon sources. Genetic and physiological evidences suggest a role for FOG1 and FOG2 in the regulation of glucose-repressible gene expression in response to a glucose limitation. The regulatory effect appears to be at the transcriptional level, at least for beta-galactosidase. Both genes have been cloned by complementation and sequenced. FOG1 is a unique gene homologous to GAL83, SIP1 and SIP2, a family of regulatory genes affecting glucose repression of the GAL system in Saccharomyces cerevisiae. However, major differences exist between fog1 and gal83 mutants. FOG2 is structurally and functionally homologous to SNF1 of S. cerevisiae and shares with SNF1 a role also in sporulation.

Amino Acid Sequence↗

PubMed1995

IMP2, a gene involved in the expression of glucose-repressible genes in Saccharomyces cerevisiae.

Two mutants carrying different deletions of the IMP2 coding sequence of Saccharomyces cerevisiae, delta T1, which encodes a protein lacking the last 26 C-terminal amino acids, and delta T2, which completely lacks the coding region, were analysed for derepression of glucose-repressible maltose, galactose, raffinose and ethanol utilization pathways in response to glucose limitation. The role of the IMP2 gene product in the regulation of carbon catabolite repressible enzymes maltase, invertase, alcohol dehydrogenase, NAD-dependent glutamate dehydrogenase (NAD-GDH) and L-lactate:ferricytochrome-c oxidoreductase (L-LCR) was also analysed. The IMP2 gene product is required for the rapid glucose derepression of all above-mentioned carbon source utilization pathways and of all the enzymes except for L-LCR. NAD-GDH is regulated by IMP2 in the opposite way and, in fact, this enzyme was released at higher levels in both imp2 mutants than in the wild-type strain. Therefore, the product of IMP2 appears to be involved in positive and negative regulation. Both deletions result in growth and catalytic defects; in some cases partial modification of the gene product yielded more dramatic effects than its complete absence. Moreover, evidence is provided that the IMP2 gene product regulates galactose- and maltose-inducible genes at the transcriptional level and is a positive regulator of maltase, maltose permease and galactose permease gene expression.

Alleles↗

PubMed1992

IMP2, a nuclear gene controlling the mitochondrial dependence of galactose, maltose and raffinose utilization in Saccharomyces cerevisiae.

The IMP2 gene of Saccharomyces cerevisiae is involved in the nucleo-mitochondrial control of maltose, galactose and raffinose utilization as shown by the inability of imp2 mutants to grow on these carbon sources in respiratory-deficient conditions or in the presence of ethidium bromide and erythromycin. The negative phenotype cannot be scored in the presence of inhibitors of respiration and oxidative phosphorylation, indicating that the role of the mitochondria in the utilization of the above-mentioned carbon sources in imp2 mutants is not at the energetical level. Mutations in the IMP2 gene also confer many phenotypic alterations in respiratory-sufficient conditions, e.g. leaky phenotype on oxidizable carbon sources, sensitivity to heat shock and sporulation deficiency. The IMP2 gene has been cloned, sequenced and disrupted. The phenotype of null imp2 mutants is indistinguishable from that of the originally isolated mutant.

Amino Acid Sequence↗

PubMed1992

Allelism of IMP1 and GAL2 genes of Saccharomyces cerevisiae.

Cloning and characterization of the previously described Saccharomyces cerevisiae IMP1 gene, which was assumed to be a nuclear determinant involved in the nucleomitochondrial control of the utilization of galactose, demonstrate allelism to the GAL2 gene. Galactose metabolism does not necessarily involve the induction of the specific transport system coded by GAL2/IMP1, because a null mutant takes up galactose and grows on it. Data on galactose uptake are presented, and the dependence on ATP for constitutive and inducible galactose transport is discussed. These results can account for the inability of imp1/gal2 mutants to grow on galactose in a respiration-deficient background. Under these conditions, uptake was affected at the functional level but not at the biosynthetic level.

Alleles↗

PubMed1991

Catabolite repression by galactose in overexpressed GAL4 strains of Saccharomyces cerevisiae.

Catabolite repression by galactose was investigated in several strains of Saccharomyces cerevisiae grown on different carbon sources. Galactose repressed as much as glucose; raffinose was less effective. Full derepression was achieved with lactate. The functions tested were L-lactate ferricytochrome c oxidoreductase, NAD-glutamate dehydrogenase, and respiration. Galactose repression was observed only in the GAL4 but not in the gal4 strain. The presence of multiple copies of the GAL4 gene enhanced the repression by galactose. Different alleles of the GAL4 gene and the copy number did not affect glucose repression.

Alleles↗

PubMed1990

Isolation and characterization of carbon catabolite repression mutants in Saccharomyces cerevisiae.

Two carbon catabolite repression mutants of S. cerevisiae were isolated and characterized. In spite of the selection procedure (red colonies after tetrazolium overlay at high glucose concentration) the mutants exhibited a respiration which was as repressed as that of the parental strain or even more repressed. When grown at high glucose concentration the mutants display hyper-repression of cytochrome aa3 and of certain mitochondrial enzymes (L- and D-lactate dehydrogenases) but not of others (malate dehydrogenase, succinate dehydrogenase), indicating the existence of separate control sites for the different genes involved in the mitochondrial biogenesis. The data obtained pointed out that the same mutation affects both repression and derepression. In addition, the mutation(s) give rise to the complete derepression of the cytoplasmic enzyme NAD-glutamate dehydrogenase at 10% glucose whereas the enzyme is normally repressed at 3% glucose. The results of the genetic analysis indicate the mitochondrial nature of the mutation(s).

Carbon↗

PubMed1988

Germination of Saccharomyces cerevisiae ascospores without trehalose mobilization as revealed by in vivo 13C nuclear magnetic resonance spectroscopy.

Saccharomyces cerevisiae ascospores germinate in the presence of acetate without any detectable trehalose degradation, as revealed by high-resolution nuclear magnetic resonance spectroscopy and by a standard colorimetric assay. The results presented here substantiate the hypothesis that in S. cerevisiae trehalose supplies energy during dormancy of the spores and not during the germination process.

Acetates↗

PubMed1986

Germination conditions that require mitochondrial function in Saccharomyces cerevisiae: utilization of acetate and galactose.

Ascospores of Saccharomyces cerevisiae inherited at least one functioning mitochondrion as shown by their ability to germinate on nonfermentable carbon sources. After transfer to germination medium, the optical density of the culture at 600 nm decreased (phase-dark), reaching a minimum within 60 min in the presence of glucose and within 180 min after transfer to acetate medium; thereafter, the optical density increased. Budding cells first appeared 90 min after transfer to glucose and 150 min after transfer to acetate. Augmentation of respiratory components, respiratory activity, and macromolecular synthesis (except for DNA synthesis) started at about the same time on glucose and on acetate, although the highest values for all these processes were reached in the presence of glucose. Mitochondrial inhibitors which affected germination on acetate did not arrest germination on glucose. However, mitochondrial activity was required for germination on galactose in a strain carrying the mutated allele imp1 of the nucleomitochondrion-connecting gene IMP1.

Acetates↗

PubMed1983

The role of the nuclear gene "mitochondrial mutability control" (MMC1) in the process of mutability of the mitochondrial genome by different mutagens in Saccharomyces cerevisiae.

The accumulation of respiratory deficient (RD) mutants in Saccharomyces cerevisiae depended upon the mutagens used and upon the presence of the nuclear gene previously identified as MMC1 (one) which we showed to control the spontaneous and the erythromycin-induced RD mutability. In this paper data are reported about the accumulation of RD mutants in the presence of manganous ions (Mn++) and UV which was higher in the mmc1 (one) than in MMC1 strains. We found that the characters 'low spontaneous' and 'low induced' RD mutability by erythromycin, manganous ions and UV, were controlled by the same genetic determinant. In the presence of manganous ions, also the frequency of antibiotic resistant mutants capR and eryR was higher in the mmc1 strains. Moreover, the accumulation of RD mutants in the presence of berenil, 5-fluorouracil and basic fuchsin was higher in the mmc1 than in MMC1 strains. In contrast, RD mutants accumulation by acriflavine and ethidium bromide treatments did not appear affected by the MMC1 genetic constitution.

Acriflavine↗

PubMed1983

The role of glucose and aminoacid starvation in the sensitivity of protein and RNA synthesis to cycloheximide and erythromycin in the yeast Saccharomyces cerevisiae.

In Saccharomyces cerevisiae dependence of ribonucleic acid synthesis on protein synthesis occurring during nutritional shift down conditions was evidenced. The results obtained indicated that yeast had "stringent control" of ribonucleic acid synthesis and that this control was reversed by cycloheximide only under glucose starvation or ammonia starvation in the presence of acetate as carbon source (phenotypic relaxation). Therefore, it appeared that the "phenotypic relaxation" of RNA synthesis depended on the carbon source present in the medium suggesting that the process could be negatively controlled by glucose or by some glucose catabolite(s). Such a phenotypic relaxation was sensitive to erythromycin treatment. On the other hand, total protein synthesis carried out during amino-acid starvation in the presence of glucose or ammonia starvation in the presence of acetate was 30%-40% inhibited by erythromycin, showing that in these conditions sensitivity to a non legitimate inhibitor could be triggered off in an haploid strain, and that such sensitivity did not depend on the presence of glucose in the medium.

Amino Acids↗

PubMed1981

Effect of chloramphenicol, antimycin A and hydroxamate on the morphogenetic development of the dimorphic ascomycete Endomycopsis capsularis.

Mitochondrial protein synthesis, primary (antimycin-sensitive) respiration and secondary (antimycin-insensitive, salicyl-hydroxamate-sensitive) respiration, have been characterized in the dimorphic yeast Endomycopsis capsularis. The inhibition by chloramphenicol (CAP) of the morphogenetic development from the yeast-like form to the mycelial structure in this yeast could represent the intervention in the morphogenetic process of mitochondrial protein synthesis, since chloramphenicol blocks in vivo and in vitro mitochondrial protein synthesis. In fact, other functions such as primary and secondary respiration, do not seem to play a role in the morphogenetic development since their inhibition by antimycin A (AA) or by salicyl-hydroxamic acid (SHAM) does not affect the process. In addition, mitochondrial protein synthesis has been shown to be uninhibited by the two respiratory inhibitors.

Antimycin A↗

PubMed1980

Analysis of rho mutability in Saccharomyces cerevisiae. I. Effects of mmc and pet-ts alleles.

Two additional types of nuclear determinants involved in the control of spontaneous mutability of rho in S. cerevisiae have been identified: mmc and the pet-ts 1, 2, 10, 52 and 53 genes. These genes in their mutated recessive form increase at various extents the number of respiratory deficient cytoplasmic "petite" mutants accumulated. The gene mmc does not affect the respiratory activity and is not temperature-dependent whereas the pet-ts genes determine at the non permissive temperature a respiratory deficient phenotypes even if they affect the mutability of rho at the permissive and at the non permissive temperature. The data here reported suggest that a "replicative complex" exists for the mitochondrial DNA. It is in the purpose of this paper to deal with the relative contribution that mmc and pet-ts gene products have in ensuring the fidelity of this "replicative complex".

Alleles↗