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PubMed1977

Some observations on biodegradation of pollutants in aquatic systems.

The biodegradability of pollutants introduced into aquatic environments is subject to many variabilities characteristic of microbial processes. Some observations have been reported on studies with p-cresol, methyl parathion, benzo[b]thiophene, dibenzothiophene, 9H-carbazole, quinoline, benzo[f]quinoline, benz[a]anthracene, benzo[a]pyrene, 7H-dibenzo[c,g]carbazole, Mirex, 2,4-dichlorophenoxyacetic acid, Lindane and 1,1-bis(p-chlorophenyl)-2,2,2-trichloroethane analogs. Water reservoirs included a eutrophic stream, a eutrophic pond, an oligotrophic lake and effluents from waste-water treatment plants. The first ten of the above compounds were studied only in aerobic mixed-culture systems, and Mirex was studied with mixed cultures under both aerobic and anaerobic conditions. Examples were presented of the significance of cometabolism, diauxic processes, film fermentations and microbial interactions in biodegradation studies. Caution is advised in protocols regarding biodegradability of pollutants in aquatic environments.

Bacteria↗

PubMed1998

Physiological characterization of mBSA antigen induced arthritis in the rat. I. Vascular leakiness and pannus growth.

OBJECTIVE: To study the temporal relation between vascular inflammatory activity and synovial hyperplasia during the development of methylated bovine serum albumin (mBSA) antigen induced arthritis (AIA) in the rat, and to correlate these variables to changes in knee diameter. The influence of a single dose of indomethacin and methotrexate (MTX) on these measures was also determined. METHODS: Vascular inflammatory activity was assessed as extravasation of radiolabelled albumin. Synovial hyperplasia was followed by measurements of the increases in wet and dry weight of the anterior part of the periarticular soft tissue and by routine histology. RESULTS: The vascular inflammation peaked on Day 3 after antigen challenge. The pannus weight increased at a slower pace, peaking on Day 7. No major difference between the sexes was found in these responses. Both variables were attenuated by MTX or indomethacin, suggesting a dependence between them. The water content of the pannus increased in tandem with the tissue growth but did not correlate to vascular leakiness, and is thus explained by the structural properties of the pannus rather than by the formation of inflammatory edema. In histological sections, ingrowth of pannus and destruction of cartilage was visible from Day 3 until the end of the experiment. CONCLUSION: Proliferative response follows the inflammatory vascular inflammation over time. The knee diameter, which is the most commonly used clinical measurement, seems mainly to be a reflection of the former variable. The effects of MTX and indomethacin suggest that the pannus formation is induced by the inflammatory activity in this model.

Animals↗

PubMed1997

Structural characterization of the lipids A of three Bordetella bronchiseptica strains: variability of fatty acid substitution.

The structures of lipids A isolated from the lipopolysaccharides (LPSs; endotoxins) of three different pathogenic Bordetella bronchiseptica strains were investigated by chemical composition and methylation analysis, gas chromatography-mass spectrometry, nuclear magnetic resonance, and plasma desorption mass spectrometry (PDMS). The analyses revealed that the LPSs contain the classical lipid A bisphosphorylated beta-(1-->6)-linked D-glucosamine disaccharide with hydroxytetradecanoic acid in amide linkages. Their structures differ from that of the lipid A of Bordetella pertussis endotoxin by the replacement of hydroxydecanoic acid on the C-3 position with hydroxydodecanoic acid or dodecanoic acid and the presence of variable amounts of hexadecanoic acid. The dodecanoic acid is the first nonhydroxylated fatty acid to be found directly linked to a lipid A glucosamine. The lipids A were heterogeneous and composed of one to three major and several minor molecular species. The fatty acids in ester linkage were localized by PDMS of chemically modified lipids A. B. pertussis lipids A are usually hypoacylated with respect to those of enterobacterial lipids A. However, one of the three B. bronchiseptica strains had a major hexaacylated molecular species. C-4 and C-6' hydroxyl groups of the backbone disaccharide were unsubstituted, the latter being the proposed attachment site of the polysaccharide. The structural variability seen in these three lipids A was unusual for a single species and may have consequences for the pathogenicity of this Bordetella species.

Bordetella bronchiseptica↗

PubMed2025

Prenatal organophosphate ester exposure and epigenetic changes at birth: a characterization of the methylome in the ECHO cohort.

BACKGROUND: Prenatal exposure to organophosphate esters (OPEs) affects multiple child health domains. Alterations to the DNA methylome are a plausible mechanism through which these changes occur. This study characterized DNA methylation signatures at birth associated with prenatal OPE biomarkers. METHODS: We included 736 mother-infant pairs from 7 sites in the Environmental influences on Child Health Outcomes (ECHO) Cohort. Five OPE biomarkers were quantified in maternal urine samples collected during the second and third trimesters and modeled as log2-transformed continuous variables. Using covariate-adjusted linear regression, we tested associations between OPE biomarkers and locus-specific, regional, and global cord blood DNA methylation changes measured by Illumina 450 K and EPIC arrays, and gestational epigenetic age measured by the Knight gestational age epigenetic clock generated with measures from the 27 K, 450 K, and EPIC arrays. When feasible, we examined relationships by sex. FINDINGS: Global hypomethylation at multiple regions was associated with BDCPP concentrations (p = 0.003 to 0.02, coef = -0.002). Differentially methylated regions annotated to PCDHGB1 and SLC43A2 were associated with BDCPP and DPHP concentrations, respectively (FDR q < 0.05). In sex-specific analyses, global hypomethylation was associated with prenatal BDCPP (p = 0.006 to 0.03, coef = -0.0003 to -0.0002) and DBUP_DIBP (p = 0.01, coef = -0.0007 to -0.0006) concentrations in females; and global hypermethylation was associated with DBUP_DIBP concentrations in males (p < 0.05, coef = 0.0004). BCETP concentrations were significantly associated with decelerated epigenetic aging at birth in females (p < 0.05, coef = -0.05). INTERPRETATION: Prenatal exposure to OPEs impacts child methylation at birth, suggesting a potential mechanism for the association between prenatal OPE exposure and child health outcomes.

Humans↗

PubMed2026

Methylation profiling in CNS tumor diagnostics: a single-centre real-world experience from Central Europe.

Genome-wide DNA methylation profiling has transformed neuro-oncology by providing an objective, machine learning-based taxonomy that mitigates interobserver variability and refines the histo-molecular criteria of the current WHO classification. We evaluate the real-world diagnostic performance and clinical utility of this modality in a prospective, consecutively accrued three-year cohort of 291 central nervous system (CNS) tumors across a mixed adult-pediatric population. Successful profiling was completed in 95.9% of cases. Using the Epignostix classifier, a high-confidence diagnostic match (calibrated score [CS] ≥ 0.84) was achieved in 70.3% of analyzable samples, while 26.5% returned lower-confidence scores (≥ 0.3 to < 0.84) and only 3.2% remained completely unclassifiable (CS < 0.3). When integrated into a comprehensive diagnostic framework, methylation profiling provided clinically useful results in 81.1% of cases, establishing diagnoses in 70 cases submitted for molecular subclassification and resolving diagnostic uncertainty or prompting major revisions in 149 histologically challenging tumors. Within truly ambiguous lesions, integration of methylome data dictated tumor grade modifications in 38.8% of cases (upgrading in 29.4% and downgrading in 9.4%), shifting patient risk stratification. Crucially, over half (52.7%) of the lower-confidence cases yielded meaningful clinical integration when supported by histomorphology and ancillary genetic or immunohistochemical markers, demonstrating that rigid score cutoffs should not dictate assay failure. Discrepant or misleading classifications occurred in 1.9%. Updating bioinformatic pipelines from version 11b4 to 12.8 rescued multiple ambiguous entries, increasing overall clinical utility to 84.1%. These findings demonstrate that integrating computational epigenomics with classical neuropathology enhances diagnostic precision, while highlighting the ongoing need for careful clinical-pathological correlation.

Central nervous system tumors↗

PubMed2006

Dynamic reprogramming of DNA methylation at an epigenetically sensitive allele in mice.

There is increasing evidence in both plants and animals that epigenetic marks are not always cleared between generations. Incomplete erasure at genes associated with a measurable phenotype results in unusual patterns of inheritance from one generation to the next, termed transgenerational epigenetic inheritance. The Agouti viable yellow (A(vy)) allele is the best-studied example of this phenomenon in mice. The A(vy) allele is the result of a retrotransposon insertion upstream of the Agouti gene. Expression at this locus is controlled by the long terminal repeat (LTR) of the retrotransposon, and expression results in a yellow coat and correlates with hypomethylation of the LTR. Isogenic mice display variable expressivity, resulting in mice with a range of coat colours, from yellow through to agouti. Agouti mice have a methylated LTR. The locus displays epigenetic inheritance following maternal but not paternal transmission; yellow mothers produce more yellow offspring than agouti mothers. We have analysed the DNA methylation in mature gametes, zygotes, and blastocysts and found that the paternally and maternally inherited alleles are treated differently. The paternally inherited allele is demethylated rapidly, and the maternal allele is demethylated more slowly, in a manner similar to that of nonimprinted single-copy genes. Interestingly, following maternal transmission of the allele, there is no DNA methylation in the blastocyst, suggesting that DNA methylation is not the inherited mark. We have independent support for this conclusion from studies that do not involve direct analysis of DNA methylation. Haplo-insufficiency for Mel18, a polycomb group protein, introduces epigenetic inheritance at a paternally derived A(vy) allele, and the pedigrees reveal that this occurs after zygotic genome activation and, therefore, despite the rapid demethylation of the locus.

Alleles↗

PubMed1989

Phenotypic variability of chemically induced primary rat mammary tumors.

Rat mammary tumors induced by DMBA (7,12-dimethylbenz(a)anthracene) or MNU (N-methyl-N-nitrosourea) were compared for frequency of histological types. Total tumor incidence in 50-day-old rats (Groups 3, 4, 5) was about 100% independently of the rat strain and carcinogen. There were found no distinct histological tumor types between DMBA and MNU carcinogenesis, although the distribution of fibroadenomas, adenocarcinomas and sarcomas varied markedly among rat groups. In 300-day-old female Wistar rats (Group 1) treated with DMBA, fibroadenomas and adenocarcinomas showed an incidence of 58% and 42% respectively. In 50-day-old rats (Group 3) the proportion of adenocarcinomas increased up to 72% of total DMBA tumors. MNU carcinogenesis induced adenocarcinomas in 98% of total tumors in the Lewis rat strain (Group 5), while only 53% in Wistar rats (Group 4). The rest of tumors were sarcomas occurring in opposite ratio to adenocarcinomas. The relatively high susceptibility of connective tissue to MNU as compared with mammary epithelium was due to the mode of MNU administration and seemed to be strain dependent. Both DMBA and MNU carcinogenic systems are valuable experimental models of mammary tumor. The cell phenotypes of the resulting tumors can be predicted with high probability by the choice of dose regimen of carcinogen and the route of its application.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1997

A genetic and functional analysis of the unusually large variable region in the M.AluI DNA-(cytosine C5)-methyltransferase.

The M.AluI DNA-(cytosine C5)-methyltransferase (5mC methylase) acts on the sequence 5'-AGCT-3'. The amino acid sequences of known 5mC methylases contain ten conserved motifs, with a variable region between Motifs VIII and IX that contains one or more "target-recognizing domains" (TRDs) responsible for DNA sequence specificity. Monospecific 5mC methylases are believed to have only one TRD, while multispecific 5mC methylases have as many as five. M.AluI has the second-largest variable region of all known 5mC methylases, and sequence analysis reveals five candidate TRDs. In testing whether M.AluI is in fact monospecific it was found that AGCT methylation represents only 80-90% of the methylating activity of this enzyme, while control experiments with the enzyme M.HhaI gave no unexplained activity. Because individual TRDs can be deleted from multispecific methylases without general loss of activity, a series of insertion and deletion mutants of the M.AluI variable region were prepared. All deletions that removed more than single amino acids from the variable region caused significant loss of activity; a sensitive in vivo assay for methylase activity based on McrBC restriction suggested that the central portion of the variable region is particularly important. In some cases, multispecific methylases can accommodate a TRD from another multispecific methylase, thereby acquiring an additional specificity. When TRDs were moved from a multispecific methylase into two different locations in the variable region of M.AluI, all hybrid enzymes had greatly reduced activity and no new specificities. M.AluI thus behaves in most respects as a monospecific methylase despite the remarkable size of its variable region.

Amino Acid Sequence↗

PubMed2005

Blood pressure variability, cardiac baroreflex sensitivity and organ damage in experimentally hypertensive rats.

1. The present study was designed to investigate the haemodynamic features and morphological changes in experimentally hypertensive rat models. 2. Sprague-Dawley rats were used to prepare the experimentally hypertensive models, including two-kidney, one-clip renovascular hypertensive (2K1C) rats, deoxycorticosterone acetate salt hypertensive (DOCA) rats and N(G)-nitro-l-arginine methyl ester-induced hypertensive (l-NAME) rats. Six weeks after the induction of hypertension, 24 h blood pressure was recorded and blood pressure variability (BPV) expressed by 24 h (or 12 h in the daytime and night-time study) standard deviation of the variables was calculated. Then, cardiac baroreflex sensitivity (BRS) was determined and four endogenous factors (tumour necrosis factor-alpha, interleukin-1beta, angiotensin II and endothelin-1) were measured. Finally, morphological changes were examined. 3. It was found that an increase in BPV and a decrease in BRS were accompanied by an elevation of blood pressure in all three hypertensive models. The DOCA rats had the highest BPV, whereas the l-NAME rats had the lowest BRS. 4. Morphological changes were similar in DOCA and l-NAME rats and the cardiac changes were relatively slight in 2K1C rats. Tumour necrosis factor-alpha was increased in all the three models, especially in DOCA rats. Endothelin-1 was higher in DOCA rats and angiotensin II was increased in 2K1C rats and decreased in DOCA rats. 5. In conclusion, increased BPV and decreased BRS accompanied the elevation of blood pressure in all three hypertensive models. The DOCA rats had the highest BPV and the l-NAME rats had the lowest BRS. Obvious organ damage was seen in all three hypertensive models 6 weeks after the induction of hypertension.

Angiotensin II↗

PubMed1980

Lipid epoxide hydrolase in rat lung preparations.

The activity of rat lung epoxide hydrolase (epoxide hydrolase, EC 3.3.2.3) was studied using two lipid epoxides which can be isolated from lung tissue. These epoxides displayed different Km,app and hydration rates. Methyl cis-9,10-epoxystearate was hydrated 20-times more rapidly than cholest-5 alpha,6 alpha-epoxy-3 beta-ol. The Km for the lung microsomal enzyme was variable and dependent on the microsome concentration in the medium. A soluble epoxide hydrolase was also detected in both lung and liver. This enzyme appears similar to the microsomal enzyme in its activity toward methyl epoxystearate. The measured activities for liver microsomal epoxide hydrolase were over 8-times those for lung microsomes; activity against cholesterol epoxide was 40-times greater for liver. In spite of the slow rates measured with cholesterol epoxide in lung preparations, this compound was an effective competitive inhibitor against methyl epoxystearate over a wide concentration range. This suggests that cholesterol epoxide readily binds to epoxide hydrolase and is an effective competitive inhibitor against a much more actively metabolized substrate, methyl epoxystearate. Such circumstances indicate that cholesterol epoxide binds with a high degree of nonproductivity to lung microsomal epoxide hydrolase. This attribute of lung epoxide hydrolase may relate to the relatively high concentrations of cholesterol epoxide found in lung tissue.

Animals↗

PubMed2006

Survival of adult Tiphia vernalis (Hymenoptera: Tiphiidae) after insecticide, fungicide, and herbicide exposure in laboratory bioassays.

Tiphia vernalis Rohwer is a hymenopteran ectoparasitoid of Japanese beetle, Popillia japonica Newman, larvae. The adult wasps feed on nectar or honeydew between mid-April and late June. Adults may contact pesticides when landing on foliage or when females hunt for grubs in the soil. The lethal effect of nursery, turf, and landscape pesticides was determined by exposing wasps to treated foliage in the laboratory. Pesticides tested at labeled rates were the insecticides bifenthrin, carbaryl, chlorpyrifos, halofenozide, and imidacloprid; the herbicides oryzalin, pendimethalin, and a combination product with 2,4-D, dicamba, and mecoprop (multiherbicide); and the fungicides chlorothalonil and thiophanate-methyl. During 2001 and 2002, male and female T. vernalis were exposed to pesticides by using turf cores. For both years, bifenthrin, chlorpyrifos, and imidacloprid treatments lowered adult survival relative to the control, but halofenozide had minimal effect on mortality of males and females. More males than females died after exposure to carbaryl treatments. Survival of females was not reduced by exposure to herbicides or fungicides. Females were apparently more tolerant of pesticides than males. Mortality of males in response to herbicides and fungicides was more variable than for females; in 2002 trials, male mortality was higher after exposure to multiherbicide, oryzalin, pendimethalin, and thiophanate-methyl than the control. The fungicide chlorothalonil did not increase mortality of males or females in either year. Sublethal effects were not evaluated. The study indicates the choice of pesticide may be important for conserving T. vernalis in nursery, landscape, and turf settings.

Animals↗

PubMed1998

The role of intracellular Na+ and mitochondria in buffering of kainate-induced intracellular free Ca2+ changes in rat forebrain neurones.

1. We have examined the mechanisms by which cultured central neurones from embryonic rat brain buffer intracellular Ca2+ loads following kainate receptor activation using fluorescent indicators of [Ca2+]i and [Na+]i. 2. Stimulation of cultured forebrain neurones with 100 microM kainate produced a rapid increase in [Ca2+]i that displayed a variable rate of recovery. Kainate also increased [Na+]i with a response that was slightly slower in onset and markedly slower in recovery. 3. The recovery of [Ca2+]i to baseline was not very sensitive to the [Na+]i. The magnitude of the increase in [Na+]i in response to kainate did not correlate well with the [Ca2+]i recovery time, and experimental manipulations that altered [Na+]i did not have a large impact on the rate of recovery of [Ca2+]i. 4. The recovery of [Ca2+]i to baseline was accelerated by the mitochondrial Na+-Ca2+ exchange inhibitor CGP-37157, suggesting that the recovery rate is influenced by release of Ca2+ from a mitochondrial pool and also that variation in the recovery rate is related to the extent of mitochondrial Ca2+ loading. Kainate did not alter the mitochondrial membrane potential. 5. These studies reveal that mitochondria have a central role in buffering neuronal [Ca2+]i changes mediated by non-N-methyl-D-aspartate (NMDA) glutamate receptors, and that the variation in recovery times following kainate receptor activation reflects a variable degree of mitochondrial Ca2+ loading. However, unlike NMDA receptor-mediated Ca2+ loads, kainate receptor activation has minimal effects on mitochondrial function.

Animals↗

PubMed2005

Protamine after heparin produces hypotension resulting from decreased sympathetic outflow secondary to increased nitric oxide in the central nervous system.

To elucidate whether there are linkages among protamine-induced hypotension, nitric oxide (NO), and sympathetic nerve activity, we administered 3 mg/kg protamine sulfate after 300 U/kg heparin after 20 mg/kg of N(G)-nitro-D-arginine methyl ester (D-NAME) or N(G)-nitro-L-arginine methyl ester (L-NAME) as a pretreatment to baroreceptor-denervated rabbits and compared changes in hemodynamic variables and renal sympathetic nerve activity (RSNA). In the D-NAME group, heart rate (HR), mean arterial blood pressure (MAP), and RSNA significantly decreased to 93.7% +/- 0.7%, 75.0% +/- 5.1% and 65.2% +/- 4.6% (mean +/- SE), respectively. In the L-NAME group, the pretreatment of L-NAME significantly inhibited the depressant effects of protamine on these variables. Because the animals were totally baroreceptor-denervated, decreased RSNA was attributable to the central depressant effect of protamine, and decreased sympathetic outflow could have contributed to the reduction of HR and MAP. The depressant effect of protamine on sympathetic outflow was inhibited by the pretreatment with L-NAME, a NO synthase inhibitor, suggesting that decreased sympathetic outflow secondary to a protamine-induced increase in NO concentration in the central nervous system may contribute to protamine-induced cardiovascular depression.

Animals↗

PubMed2006

Modulation of cellular and synaptic variability in the lamprey spinal cord.

Variability is increasingly recognized as a characteristic feature of cellular, synaptic, and network properties. While studies have traditionally focused on mean values, significant effects can result from changes in variance. This study has examined cellular and synaptic variability in the lamprey spinal cord and its modulation by the neuropeptide substance P. Cellular and synaptic variability differed in different types of cell and synapse. Substance P reduced the variability of subthreshold locomotor-related depolarizations and spiking in motor neurons during network activity. These effects were associated with a reduction in the variability of spiking in glutamatergic excitatory network interneurons and with a reduction in the variance of excitatory interneuron-evoked excitatory postsynaptic potentials (EPSPs). Substance P also reduced the variance of postsynpatic potentials (PSPs) from crossing inhibitory and excitatory interneurons, but it increased the variance of inhibitory postsynpatic potentials (IPSPs) from ipsilateral inhibitory interneurons. The effects on the variance of different PSPs could occur with or without changes in the PSP amplitude. The reduction in the variance of excitatory interneuron-evoked EPSPs was protein kinase A, calcium, and N-methyl-d-aspartate (NMDA) dependent. The NMDA dependence suggested that substance P was acting postsynaptically. This was supported by the reduced variability of postsynaptic responses to glutamate by substance P. However, ultrastructural analyses suggested that there may also be a presynaptic component to the modulation, because substance P reduced the variability of synaptic vesicle diameters in putative glutamatergic terminals. These results suggest that cellular and synaptic variability can be targeted for modulation, making it an additional source of spinal cord plasticity.

Action Potentials↗

PubMedDate not supplied

Mechanisms underlying chaotic vasomotion in isolated resistance arteries: roles of calcium and EDRF.

Nonlinear mathematical techniques now make it possible to quantify the complexity of an irregular time series through calculation of a parameter known as fractal dimension. In the present study, we use such an analysis to provide evidence that histamine-induced pressure oscillations in an isolated rabbit ear resistance artery are generated by deterministic rather than stochastic mechanisms, and that a minimum of 3 independent control variables is necessary to account for the complexity of the dynamics of these oscillations. The fractal dimension of the responses was independent both of the concentration of histamine used to induce rhythmic behavior, and the level of activity of the endogenous nitrovasodilator, EDRF. While both superficially influenced the form of the oscillations, it follows that neither are key control variables involved in their genesis. Nonlinear analysis of data obtained in the presence of NG-nitro-L-arginine methyl ester (L-NAME), which blocks EDRF synthesis, provided insights into the intrinsic smooth muscle control mechanisms responsible for generating rhythmic activity. The oscillations exhibited distinct "fast" and "slow" components (periods of 5-20 secs and 1-5 min. respectively). The former involved ion movements at the cell membrane and was inhibited by low [Ca2+]o, verapamil (which blocks voltage-dependent Ca2+ influx) and tetraethylammonium (which blocks Ca(2+)-activated outward K+ channels), whereas the latter involved Ca(2+)-induced Ca2+ release from intracellular stores and was inhibited by ryanodine. All such interventions decreased the overall fractal dimension of the responses to a value < 2, thus removing one degree of complexity (and hence control variable) from the dynamics. We conclude that the nonlinear interaction between a fast membrane oscillator and a slow intracellular oscillator generates chaos in vascular smooth muscle and that exogenous constrictor agonists and EDRF may be regarded as permissive and modulatory influences, respectively.

Animals↗

PubMed2006

Mass spectrometric mapping of linker histone H1 variants reveals multiple acetylations, methylations, and phosphorylation as well as differences between cell culture and tissue.

Posttranslational modifications of histones are involved in regulation of chromatin structure and gene activity. Whereas the modifications of the core histones H2A, H2B, H3, and H4 have been extensively studied, our knowledge of H1 modifications remained mainly limited to its phosphorylation. Here we analyzed the composition of histone H1 variants and their modifications in two human cell lines and nine mouse tissues. Use of a hybrid linear ion trap-orbitrap mass spectrometer facilitated assignment of modifications by high resolution and low ppm mass accuracy for both the precursor and product mass spectra. Across different tissues we identified a range of phosphorylation, acetylation, and methylation sites. We also mapped sites of ubiquitination and report identification of formylated lysine residues. Interestingly many of the mapped modifications are located within the globular domain of the histones at sites that are thought to be involved in binding to nucleosomal DNA. Investigation of mouse tissue in addition to cell lines uncovered a number of interesting differences. For example, whereas methylation sites are frequent in tissues, this type of modification was much less abundant in cultured cells and escaped detection. Our study significantly extends the known spectrum of linker histone variability.

Acetylation↗

PubMed1998

The evolution of grass genome organisation and function.

New cloning technologies and more efficient DNA sequencing now permit comprehensive structural studies of complex eukaryotic genomes. Previous global investigations of genome organisation in plants had shown that abundant repetitive DNAs were intermixed with genes. However, the nature of the major repeats, their possible biological roles, their origins, and their precise patterns of organisation were not clearly defined. My laboratory has used large clones derived from homologous regions of the maize, sorghum and rice genomes to investigate the nature, functional properties and evolution of grass genome organisation. Unexpectedly simple patterns of genome composition and arrangement have been seen, and these appear to be similar in different grasses. Our detailed studies of the maize genome indicate that short (2-20 kb) blocks of gene-containing DNA alternate with large (2-200 kb) blocks of intermixed middle and highly repetitive DNAs. Most of the highly repetitive sequences, and many of the middle repetitive DNAs, are retrotransposons that have inserted within each other. These repetitive DNAs are usually methylated and mostly inactive, but they are homologous to transcripts found in many different tissues. The unmethylated DNA is composed primarily of genes interspersed with lower-copy-number retroelements and inverted-repeat transposable elements. Gene order and sequence are highly conserved, but the mobile DNAs between genes appear to be different due to their rapid evolution and their variable presence or locations in different grasses.

Chromosome Mapping↗

PubMed2001

Intestinal uptake of betaine in vitro and the distribution of methyl groups from betaine, choline, and methionine in the body of broiler chicks.

The efficiency of betaine absorption into small intestinal slices of broiler chicks was studied in vitro with 14C-labeled betaine. The relative proportion of Na+-coupled betaine uptake, as well as the total uptake capacity was larger in the duodenum than in the jejunum. Dietary betaine increased the Na+-coupled uptake in the duodenum. In in vivo-experiments, methyl-14C-labeled betaine, methionine, or choline was fed to broiler chicks. Betaine appeared in the blood more rapidly, and reached a higher total concentration than choline or methionine. The data suggest that choline and methionine were associated with plasma lipoproteins whereas betaine remained free in the plasma. The label distribution in liver, kidney, and intestinal tissues was studied 24 h after label ingestion. Most of the label from betaine was found in the aquaeous phase in the muscle, while in the liver and jejunum the label from betaine was distributed more evenly between the aquaeous, lipid, and protein phases. Label from choline accumulated in the lipid fraction, particularly so in the liver, whereas label from methionine showed a more variable distribution pattern. The distribution results are interpreted in terms of specific roles of betaine, choline, and methionine in methyl group metabolism.

Animals↗