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PubMed1990

Localization of a series of RNA-protein cross-link sites in the 23S and 5S ribosomal RNA from Escherichia coli, induced by treatment of 50S subunits with three different bifunctional reagents.

50S ribosomal subunits were reacted with bis-(2-chloroethyl)methylamine, 2-iminothiolane or methyl p-azidophenyl acetimidate, and RNA-protein cross-link sites on the RNA were localised using our published procedures. The degree of precision with which these sites could be determined was variable, depending on the particular protein or RNA region concerned. The following positions in the 23S RNA were identified as encompassing the individual cross-link sites (numbered from the 5'-end, with asterisks denoting sites previously reported): L1, 1864-67, 1876-78, 2119-33, 2163-72*, L2, 1819-20*; L3, 2832-34; L4, 320-25*; 613-17*; L5, 2307; L6, 2473-81*; L9, 1484-91; L11, 1060-62; L13, 547-50; L14, 1993-2002; L17, 1260-95; L18, 2307-20; L19, 1741-58; L21, 544-48*; 1198-1248; L23, 63-65, 137-41*; L24, 99-107*; L27, 2272-83, 2320-23*; 2332-37*; L28, 195-242, 368-424; L29, 101-02*; L30, 931-38; L32, 2878-90; L33, 2422-24. Cross-links to 5S RNA were observed with L5 (positions 34-41), and L18 (precise site not localised).

Base Sequence↗

PubMed1993

Excitatory amino acid receptors in schizophrenia.

Growing evidence suggests an involvement of excitatory amino acid (EAA) systems in schizophrenia. Precedent exists for changes in binding to kainate, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, N-methyl-D-aspartate subtypes of EAA receptors. Current evidence indicates that in schizophrenia, EAA receptor levels can be decreased, unchanged, or even increased in certain brain regions and certain cases. It is likely that variability may arise from different drug histories of patients, other coexistent and undetected disease states, and the inherent heterogeneity of schizophrenia. On the other hand, it is possible that schizophrenia reflects a pattern of imbalances, not a simple unidirectional change. If so, even subtle changes may contribute significantly to the overall status of ongoing circuitry function in key brain areas implicated in schizophrenia. Together with other neurotransmitter systems, for example, dopaminergic, the net effect of EAA receptor imbalances may be greater than changes in the individual receptors and their neurotransmitters.

Amino Acids↗

PubMed1995

The effect of recombinant human IGF-I on protein metabolism in post-operative patients without nutrition compared to effects in experimental animals.

This study has evaluated the effects of recombinant human insulin-like growth factor I (rhIGF-I) to moderately stressed post-operative patients provided with dextrose as the only exogeneous substrate. Thirty patients who underwent elective colorectal surgery were randomized to receive either rhIGF-I (80 micrograms kg-1 bw) subcutaneously twice daily or placebo injections in a double-blind parallel group design. Nitrogen balance, urinary 3-methyl-histidine excretion plasma growth hormone (GH), serum cortisol, IGF-I binding proteins (IGFBP-1,3), glomerular filtration rate, plasma amino acid concentrations and whole-body energy expenditures were measured as effector variables during days 1-5 post-operatively. Animal and isolated tissue experiments were performed as additional control experiments to confirm cellular effectiveness of the recombinant material. rhIGF-I increased significantly the glomerular filtration rate and prevented the adaptive decrease in whole-body energy expenditure in response to partial starvation in the postoperative period. Serum and plasma concentrations of IGFBP-1,3 cortisol, blood glucose and amino acids were not significantly influenced by rhIGF-I administration, while plasma GH levels decreased significantly as expected. rhIGF-I had no effect on either nitrogen balance or protein breakdown (3-methylhistidine excretion) in post-operative patients on dextrose supplementation only, although plasma concentrations of IGF-I increased from 130-140 ng mL-1 to a range of 300-450 ng mL-1. In contrast, IGF-I stimulated the synthesis of both globular and myofibrillar proteins (+50%, P < 0.01), when given as a single dose (100 micrograms kg-1) 2 h before measurements of protein synthesis in skeletal muscles of overnight fasted adult mice. This stimulatory effect by IGF-I (1 microgram mL-1) was also confirmed by measurements of skeletal muscle protein synthesis in vitro (+40%, P < 0.05). Orally re-fed mice had a normal transcription of IGF-I mRNA in skeletal muscle cells, while overnight fasted mice showed a trend to down-regulated transcription. Our results demonstrate that rhIGF-I has several significant physiological effects, without major side-effects, when supplied to partially starved patients in the post-operative phase. The lack of a whole-body nitrogen sparing effect by rhIGF-I alone to post-operative patients is not clear, but was most likely explained by subnormal plasma concentrations of amino acids.

Aged↗

PubMed1995

Biochemical and functional properties of photosystem II in agranal membranes from maize mesophyll and bundle sheath chloroplasts.

We have studied the occurrence and organization of photosystem II (PSII) in bundle sheath thylakoids and stroma lamellae from maize. As shown by non-denaturing lauryl beta-D- iminopropionidate (Deriphat)/PAGE, PSII exists in a dimeric form in grana membranes. In bundle sheath and stroma lamellae, however, only a monomeric form was found. Based on immunotitration data, we estimated the stoichiometry of the individual components of the PSII core complex and antenna systems. In stroma lamellae, all PSII antenna complexes had a stoichiometry similar to that in grana membranes, with the exception of light-harvesting complex II (LHCII) that was somewhat over-represented, while the minor antenna complexes CP26 and CP29 were under-represented. In bundle sheath, the amount of LHCII was approximately eight times higher than expected with respect to D1. The 33-kDa protein of the oxygen-evolving enhancer polypeptides was not detectable nor was the ferredoxin-NADP+ reductase, thus strongly suggesting that no significant linear electron transport occurs in bundle sheath thylakoids. Fluorescence induction data suggest that most of the PSII reaction centers in bundle sheath and stroma lamellae sustain electron transport towards a secondary acceptor pool. Stromal PSII centers are only weakly inhibited by 3-(3,4-dichlorophenyl)-1,1-dimethylurea (diuron), whereas, unexpectedly, dichlorobenzoquinone and methyl viologen had a pronounced inhibitory effect of the QA- reoxidation. An additional specificity of these centers is the slow rate (50-ms range) of the QA to QB electron transfer. The amplitude of variable fluorescence found in stroma lamellae can only account for a small fraction (1-2%) of the variable fluorescence of whole thylakoids. This suggests that stromal PSII cannot be solely responsible for the slow beta-phase of the induction kinetics.

Chlorophyll↗

PubMed1980

Headspace analysis of volatile metabolites of Pseudomonas aeruginosa and related species by gas chromatography-mass spectrometry.

Gas chromatographic-mass spectrometric analysis of headspace volatiles was performed on cultures of 11 strains of Pseudomonas aeruginosa and 1 strain each of Pseudomonas cepacia, Pseudomonas putida, Pseudomonas putrefaciens, Pseudomonas fluorescens, and Pseudomonas maltophilia. All strains of Pseudomonas aeruginosa produced a distinctive series of odd-carbon methyl ketones, particularly 2-nonanone and 2-undecanone, and 2-aminoacetophenone. The other strains failed to produce 2-aminoacetophenone. Two sulfur compounds, dimethyldisulfide and dimethyltrisulfide, were present in strains of P. aeruginosa and in variable amounts in other species. Butanol, 2-butanone, 1-undecene, and isopentanol were also detected in P. aeruginosa cultures.

Alcohols↗

PubMed2007

Carbon conversion efficiency and limits of productive bacterial degradation of methyl tert-butyl ether and related compounds.

The utilization of the fuel oxygenate methyl tert-butyl ether (MTBE) and related compounds by microorganisms was investigated in a mainly theoretical study based on the Y(ATP) concept. Experiments were conducted to derive realistic maintenance coefficients and K(s) values needed to calculate substrate fluxes available for biomass production. Aerobic substrate conversion and biomass synthesis were calculated for different putative pathways. The results suggest that MTBE is an effective heterotrophic substrate that can sustain growth yields of up to 0.87 g g(-1), which contradicts previous calculation results (N. Fortin et al., Environ. Microbiol. 3:407-416, 2001). Sufficient energy equivalents were generated in several of the potential assimilatory routes to incorporate carbon into biomass without the necessity to dissimilate additional substrate, efficient energy transduction provided. However, when a growth-related kinetic model was included, the limits of productive degradation became obvious. Depending on the maintenance coefficient m(s) and its associated biomass decay term b, growth-associated carbon conversion became strongly dependent on substrate fluxes. Due to slow degradation kinetics, the calculations predicted relatively high threshold concentrations, S(min), below which growth would not further be supported. S(min) strongly depended on the maximum growth rate mu(ma)(x), and b and was directly correlated with the half maximum rate-associated substrate concentration K(s), meaning that any effect impacting this parameter would also change S(min). The primary metabolic step, catalyzing the cleavage of the ether bond in MTBE, is likely to control the substrate flux in various strains. In addition, deficits in oxygen as an external factor and in reduction equivalents as a cellular variable in this reaction should further increase K(s) and S(min) for MTBE.

Bacteria↗

PubMed1998

Nitric oxide suppresses bFGF- and IL-1-alpha-mediated but not VEGF165-mediated angiogenesis in natively vascularized mammalian tissue.

Using the rat mesenteric window angiogenesis assay, we studied the systemic effect of the nitric oxide synthase inhibitor Nw-nitro-L-arginine methyl ester, L-NAME, on angiogenesis induced by basic fibroblast growth factor (bFGF), interleukin-1-alpha (IL-1) or vascular endothelial growth factor (VEGF165). Using technically independent morphometric and image analysis methods, the angiogenic response was quantified in variables related to (i) microvascular spatial extension and (ii) microvascular density. The test tissue, which is natively vascularized and lacks significant angiogenesis physiologically, was unaffected by surgical intervention. Two daily intraperitoneal injections of bFGF (2.20 nmole), IL-1 (1.18 nmole) and VEGF165 (480 pmole) for 5 days elicited significant angiogenesis in the mesenteric windows. L-NAME (0.5 g/L in drinking water) caused further enhancement of the angiogenic response produced by human recombinant bFGF (p<0.001), bovine purified bFGF (p<0.05) or murine recombinant IL-1 (p<0.05). In contrast, the L-NAME treatment did not affect the angiogenic response produced by human and murine recombinant VEGF165. These data suggest that nitric oxide can act as an endogenous suppressor of mammalian de novo angiogenesis, which is a new finding, and, moreover, that angiogenesis induced by VEGF165 on the one hand and by bFGF and IL-1 on the other in the rat mesenteric window depends on different pathways.

Animals↗

PubMed2003

Folate status, metabolic genotype, and biomarkers of genotoxicity in healthy subjects.

Gene-environment interactions play an important role in folate metabolism, with a potential impact on human health. Deficiencies in the uptake of key micronutrients and variant genotypes can affect the folic acid cycle, modulating methyl group transfer in key processes and leading to increased cancer risk and Down syndrome incidence. So far, the significance of folate status and metabolic genotypes on baseline levels of DNA damage in normal individuals has not been fully elucidated. In this study, the possible modulation of SCE, micronuclei and tail moment values in peripheral lymphocytes by plasma levels of folic acid, homocysteine and vitamin B12, and by the methylenetetrahydrofolate reductase (MTHFR) C677T and methionine synthase reductase (MTRR) A66G polymorphisms was investigated in 191 healthy subjects. The results obtained show a highly significant (P = 0.001) positive association between plasma levels of vitamin B12 and frequencies of both SCE and high frequency cells (HFC, above 90 degrees percentile) in smokers. No significant effect was observed in non-smokers. Moreover, after correction for age, gender and GSTM1 genotype, a significant association (P = 0.026) between the MTRR 66GG variant genotype and higher micronucleus rates was observed. Tail moment values were not affected by any of the independent variables considered. Overall, the results obtained suggest that both folate status and relevant metabolic genotype can influence background levels of DNA damage in normal subjects. The significant association observed in smokers between plasma vitamin B12 and SCE frequencies may highlight the effect of methylation status on DNA damage and repair, although the role of other, unidentified dietary factors cannot be ruled out. At the same time, micronucleus data indicate that the MTRR 66GG variant may represent another individual trait of relative genomic instability, thus supporting epidemiological data on increased risk of Down syndrome conception in MTRR 66GG subjects.

Adult↗

PubMed1998

Synthesis and inhibitory action on HMG-CoA synthase of racemic and optically active oxetan-2-ones (beta-lactones).

A homologous series of both C3-unsubstituted and C3-methyl substituted oxetan-2-ones (beta-lactones) was investigated as potential inhibitors of yeast 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) synthase. Several reported methods for racemic beta-lactone synthesis were studied for preparation of the target series. In addition, a novel aluminum-based Lewis acid obtained by combination of Et2AlCl with (1R,2R)-2-[(diphenyl)hydroxymethyl] cyclohexan-1-ol was studied for the asymmetric [2 + 2] cycloaddition of aldehydes and trimethylsilylketene. This Lewis acid exhibited good reactivity but variable enantioselectivity (22-85% ee). In in vitro assays using both native and recombinant HMG-CoA synthase from Saccharomyces cerevisiae, oxetan-2-ones mono-substituted at C4 with linear alkyl chains gave IC50s that decreased monotonically with chain length up to 10 carbons and then rose rapidly for longer chains. The trans isomers of 3-methyl-4-alkyl-oxetan-2-ones showed a similar trend but had 1.3- to 5.6-fold lower IC50s. The results imply a substantial hydrophobic pocket in this enzyme that interacts with both C-3 and C-4 substituents of oxetan-2-one inhibitors.

Enzyme Inhibitors↗

PubMed2005

Androgen receptor CAGn repeat length influences phenotype of 47,XXY (Klinefelter) syndrome.

CONTEXT: Klinefelter syndrome (KS; 47,XXY karyotype and variants) is characterized by tall stature and testicular failure, with marked variation in severity of the phenotype. Previous studies have proposed that genetic factors including mosaicism, parental origin of the supernumerary X-chromosome, skewed X inactivation, and androgen receptor (AR) polyglutamine repeat length may contribute to phenotypic variability in KS. OBJECTIVE: The objective of this study was to investigate the roles of these genetic factors in the variability of the KS phenotype. DESIGN: This was a cross-sectional study. SETTING: The study was performed at a pediatric endocrinology referral clinic. PATIENTS: Thirty-five KS boys and men, aged 0.1-39 yr, were studied. INTERVENTIONS: There were no interventions. MAIN OUTCOME MEASURES: Auxological measurements, biological indices of testicular function, and clinical assessment of muscle tone were the main outcome measures. Genetic studies included karyotyping to detect mosaicism, genotyping of microsatellite markers to determine parental origin of the supernumerary X-chromosome, and genotyping and methylation studies to measure AR polyglutamine (AR CAGn) repeat length and X inactivation ratio. RESULTS: The only genetic factor that significantly influenced the KS phenotype was the AR CAGn repeat length, which was inversely correlated with penile length, a biological indicator of early androgen action. Mosaicism, imprinting, and skewed X inactivation did not account for the variability of the KS phenotype. CONCLUSIONS: Normal genetic variation in the AR coding sequence may be clinically significant in the setting of early testicular failure and subnormal circulating testosterone levels, as occur in KS.

Adolescent↗

PubMed1992

Teratological examination of the insecticide methyl-parathion (Wofatox 50 EC) on pheasant embryos. 2. Biochemical study.

Fertile pheasant's eggs were treated with the insecticide Wofatox 50 EC (50% methyl-parathion) by injection technique on day 12 of the hatching period. Treatment consisted of inoculation of 0.1 ml of different concentrations of the insecticide into the air space of embryonated eggs. The following dose levels were employed: 0.00, 1.35, 13.5 and 135.0 mg/kg egg of active ingredient. Biochemical changes in the plasma were evaluated by micro (photometric) methods which rendered possible the determination of several blood plasma variables of the embryos. At the highest dose level applied, serum alkaline phosphatase (SAP) enzyme activity and inorganic P concentration of the treated embryos showed statistically differences (reduction) as compared to the control data. Macroscopic alterations were detected at necropsy.

Animals↗

PubMed2003

The neuroendocrinology of posttraumatic stress disorder: new directions.

Studies of the hypothalamic-pituitary-adrenal (HPA) axis in persons with posttraumatic stress disorder (PTSD) have produced variable findings. This review focuses on the factors likely to have affected the outcome of these studies, including population characteristics and experimental design. Also discussed is a possible role for the adrenal neurosteroid dehydroepiandrosterone (DHEA) as a mediator of HPA axis adaptation to extreme stress and the psychiatric symptoms associated with PTSD. The antiglucocorticoid properties of DHEA may contribute to an upregulation of HPA axis responses as well as mitigate possible deleterious effects of high cortisol levels on the brain in some PTSD subpopulations. The neuromodulatory effects of DHEA and its metabolite DHEAS at gamma-aminobutyric acid and N-methyl-D-aspartate receptors in the brain may contribute to psychiatric symptoms associated with PTSD. The possible importance of other neurohormone systems in modulating HPA axis and symptom responses to traumatic stress is also discussed. Understanding the complex interactions of these stress-responsive neurosteroid and peptide systems may help explain the variability in patterns of HPA axis adaptation, brain changes, and psychiatric symptoms observed in PTSD and lead to better targeting of preventive and therapeutic interventions.

Adaptation, Psychological↗

PubMed2002

Disruption of the lineage restriction of TCR beta gene rearrangements.

Despite a common lymphoid recombinase, assembly of Ig genes is restricted to B cells, whereas TCR loci rearrange in T cells. Transcriptional promoters and enhancers are critical for the regulation of the recombination process. However, the specific function of such elements in conferring the lineage-restriction of V(D)J recombination remains poorly understood. To gain further insights into the mechanism restricting TCR beta-chain rearrangements to T cells, we generated mice in which an 11 kb region--containing the beta-chain constant region 2 and the TCR beta enhancer (E beta)--was replaced with the B cell specific Ig heavy-chain enhancer (E mu). Unlike the simple E mu to E beta replacement, this mutation allowed significant levels of D beta to J beta as well as V beta to DJ beta rearrangements in both T and B cells. Although the lineage restriction was disrupted, TCR beta allelic exclusion was still efficient in mutated T cells. Together these results demonstrate that changes in the activity of regulatory elements located at the TCR beta constant regions are sufficient to redirect the recombination pattern of TCR beta variable gene segments.

Acetylation↗

PubMed2000

CYP2D6 is involved in O-demethylation of diltiazem. An in vitro study with transfected human liver cells.

OBJECTIVE: In a previous study of diltiazem (DTZ) pharmacokinetics in renal transplant patients, we speculated that a polymorphic enzyme could be involved in O-demethylation of diltiazem. The aim of this in vitro study was to investigate whether O-demethylation of DTZ is mediated by cytochrome P450-2D6 (CYP2D6). METHODS: DTZ was incubated with transfected human liver epithelial (THLE) cells expressing CYP2D6 (T5-2D6 clone). Metabolism of DTZ was studied over a concentration range of 12.5-400 microM and in the presence of quinidine (a CYP2D6 inhibitor) or erythromycin (a CYP3A4 inhibitor). THLE cells lacking CYP2D6 activity (T5-neo clone) were used as control. The culture medium of the cells, in which DTZ was dissolved, was analysed for DTZ and metabolites prior to and after 8 h of incubation using high-performance liquid chromatography (HPLC, UV detection). Authentic O-demethyl-DTZ (Mx) was not available, and this metabolite was therefore not identifiable. RESULTS: Desacetyl-O-demethyl-DTZ (M4) was exclusively produced during incubations of DTZ with THLE cells expressing CYP2D6. The rate of M4 formation was described using Michaelis Menten kinetics in the concentration range of DTZ used. Production of M4 was inhibited by quinidine, but not erythromycin. An unidentified chromatographic peak, which was interpreted to be Mx, showed the same pattern of formation as M4 both in absence and presence of inhibitors. N-demethylated metabolites, formed by CYP3A4, were not observed in any of the cell lines. CONCLUSION: Evidence was provided in vitro that O-demethylation of DTZ is mediated by the polymorphic isoenzyme CYP2D6. Involvement of CYP2D6 in the metabolism of DTZ may have clinical implications regarding pharmacokinetic variability and interactions.

Acetylation↗

PubMed1995

Effects of sevoflurane on the middle latency auditory evoked response and the electroencephalographic power spectrum.

We investigated the effects of sevoflurane on the middle latency auditory evoked response (MLR) and the power spectrum of the electroencephalogram (EEG) in 10 elective surgical patients. The MLR and the EEG power spectrum were recorded with a surface electrode placed at the central (Cz) scalp location. End-tidal sevoflurane concentrations of 0%, 0.25%, 0.5%, 0.75%, 1.0%, and 1.5% in 50% nitrous oxide and oxygen were studied. The Na, Pa, and Nb components of the MLR increased in latency and decreased in amplitude in a dose-dependent manner at increasing concentrations of sevoflurane. The latencies for Na, Pa, and Nb increased in a linear fashion (correlation coefficients: r = 0.81, r = 0.81, and r = 0.89, respectively). The EEG delta power was dominant with increasing sevoflurane concentration, and was significantly increased at sevoflurane concentrations of 1.0%-1.5%. The beta power, median power frequency (MPF), and 95% spectral edge frequency (SEF) decreased significantly according to the increases by 0.5% sevoflurane. Regarding the changes evoked by 0.25% sevoflurane, the Nb latency of the MLR responded significantly under 0.75% of sevoflurane. At these low concentrations of sevoflurane, the MLR seemed to be more sensitive to changes in anesthetic concentration than the various EEG variables.

Anesthetics↗

PubMed1999

Effect of base analog substitutions in the specific GATC site on binding and methylation of oligonucleotide duplexes by the bacteriophage T4 Dam DNA-[N6-adenine] methyltransferase.

The interaction of the phage T4 Dam DNA-[N6-adenine] methyltransferase with 24mer synthetic oligonucleotide duplexes having different purine base substitutions in the palindromic recognition sequence, GATC, was investigated by means of gel shift and methyl transfer assays. The substitutions were introduced in either the upper or lower strand: guanine by 7-deazaguanine (G-->D) or 2-aminopurine (G-->N) and target adenine by purine (A-->P) or 2-aminopurine (A-->N). The effects of each base modification on binding/methylation were approximately equivalent for both strands. G-->D and G-->N substitutions resulted in a sharp decrease in binary complex formation. This suggests that T4 Dam makes hydrogen bonds with either the N7- or O6-keto groups (or both) in forming the complex. In contrast, A-->P and A-->N substitutions were much more tolerant for complex formation. This confirms our earlier observations that the presence of intact 5'-G:C base pairs at both ends of the methylation site is critical, but that base substitutions within the central A:T base pairs show less inhibition of complex formation. Addition of T4 Dam to a complete substrate mixture resulted in a burst of [3H]methylated product. In all cases the substrate dependencies of bursts and methylation rates were proportional to each other. For the perfect 24mer k cat = 0.014/s and K m = 7.7 nM was obtained. In contrast to binary complex formation the two guanine substitutions exerted relatively minor effects on catalytic turnover (the k cat was reduced at most 2. 5-fold), while the two adenine substitutions showed stronger effects (5- to 15-fold reduction in k cat). The effects of base analog substitutions on K m(DNA) were more variable: A-->P (decreased); A-->N and G-->D (unchanged); G-->N (increased).

2-Aminopurine↗

PubMed2006

The role of nitric oxide and GluR1 in presynaptic and postsynaptic components of neocortical potentiation.

In this study, we investigated the mechanisms underlying synaptic plasticity at the layer IV to II/III pathway in barrel cortex of mice aged 6-13 weeks. This pathway is one of the likely candidates for expression of experience-dependent plasticity in the barrel cortex and may serve as a model for other IV to II/III synapses in the neocortex. We found that postsynaptic autocamtide-2-inhibitory peptide is sufficient to block long-term potentiation (LTP) (IC50 of 500 nm), implicating postsynaptic calcium/calmodulin-dependent kinase II in LTP induction. AMPA receptor subunit 1 (GluR1) knock-out mice also showed LTP in this pathway, but potentiation was predominantly presynaptic in origin as determined by paired-pulse analysis, coefficient of variation analysis, and quantal analysis, whereas wild types showed a mixed presynaptic and postsynaptic locus. Quantal analysis at this synapse was validated by measuring uniquantal events in the presence of strontium. The predominantly presynaptic LTP in the GluR1 knock-outs was blocked by postsynaptic antagonism of nitric oxide synthase (NOS), either with intracellular N-omega-nitro-L-arginine methyl ester or N-nitro-L-arginine, providing the first evidence for a retrograde transmitter role for NO at this synapse. Antagonism of NOS in wild types significantly reduced but did not eliminate LTP (group average reduction of 50%). The residual LTP formed a variable proportion of the total LTP in each cell and was found to be postsynaptic in origin. We found no evidence for silent synapses in this pathway at this age. Finally, application of NO via a donor induced potentiation in layer II/III cells and caused an increase in frequency but not amplitude of miniature EPSPs, again implicating NO in presynaptic plasticity.

Action Potentials↗

PubMed1993

Differences in DNA-methylation are associated with a paramutation phenomenon in transgenic petunia.

The transgenic petunia line 17-R contains one copy of the maize A1 gene which mediates brick-red pelargonidin pigmentation of the flower. A white derivative, 17-W, was isolated from homozygous progeny of this line in which no pelargonidin pigmentation was observed. In 17-W the 35S promoter driving the A1 gene was hypermethylated, in contrast to its hypomethylated state in 17-R. Progeny plants carrying both the 17-R and 17-W allele did not show the expected A1 phenotype. Predominantly white progeny and variable plants were observed which showed a continuous change in pattern and intensity of pelargonidin pigmentation. This reduction of A1 activity argues for a semidominant effect of the 17-W allele which inhibits the activity of its homologue, 17-R. This system shows striking similarities to some paramutation phenomena in plants which represent a heritable change in gene function of a paramutable allele directed by a paramutagenic homologue. The analysis of the methylation patterns of the A1 alleles suggests that interactions between differentially methylated alleles are responsible for the paramutation-like effect which is mediated by somatic pairing. The analogy of this system to other phenomena based on homology-dependent interlocus trans-inactivation supports the assumption that those may be based on a related mechanism which includes an interaction between ectopic homologues.

Alleles↗