Search results for "Metabolite"
showing 10 items of 551 documents
First mitochondrial genome-wide association study with metabolomics.
2021
AbstractIn the era of personalized medicine with more and more patient-specific targeted therapies being used, we need reliable, dynamic, faster and sensitive biomarkers both to track the causes of disease and to develop and evolve therapies during the course of treatment. Metabolomics recently has shown substantial evidence to support its emerging role in disease diagnosis and prognosis. Aside from biomarkers and development of therapies, it is also an important goal to understand the involvement of mitochondrial DNA (mtDNA) in metabolic regulation, aging and disease development. Somatic mutations of the mitochondrial genome are also heavily implicated in age-related disease and aging. The…
Natural Genetic Variation of Freezing Tolerance in Arabidopsis
2006
Abstract Low temperature is a primary determinant of plant growth and survival. Using accessions of Arabidopsis (Arabidopsis thaliana) originating from Scandinavia to the Cape Verde Islands, we show that freezing tolerance of natural accessions correlates with habitat winter temperatures, identifying low temperature as an important selective pressure for Arabidopsis. Combined metabolite and transcript profiling show that during cold exposure, global changes of transcripts, but not of metabolites, correlate with the ability of Arabidopsis to cold acclimate. There are, however, metabolites and transcripts, including several transcription factors, that correlate with freezing tolerance, indica…
Physiology and genetics of antibiotic production and resistance.
1993
Actinomycetes have the genetic capability to synthesize many different biologically active secondary metabolites and of these compounds, antibiotics predominate in therapeutic and commercial importance. Intensive research often centres on the use of molecular techniques to investigate the physiology and genetics of antibiotic biosynthesis with a view to improving production. The isolation of clones of Streptomyces hygroscopicus, the producer of geldanamycin, which synthesizes geldanamycin in S. lividans, is reported. Molecular approaches using genes for elongation factors (tuf) were used in attempts to increase the fermentation yield of kirromycin, whilst probes for aphD and sph, genes for …
Spectrum of styrene-induced DNA adducts: the relationship to other biomarkers and prospects in human biomonitoring.
2002
Styrene is an important industrial chemical that has shown genotoxicity in many toxicology assays. This is believed to be related to the DNA-binding properties of styrene-7,8-oxide (SO), a major metabolite of styrene. In this review, we have summarized knowledge on various aspects of styrene genotoxicity, especially in order to understand the formation and removal of primary DNA lesions, and the usefulness of biomarkers for risk assessment. Biological significances of specific DNA adducts and their role in the cascade of genotoxic events are discussed. Links between markers of external and internal exposure are evaluated, as well as metabolic aspects leading to the formation of DNA adducts …
Excretion and metabolism of phenol, 4-nitrophenol and 2-methylphenol by the frogs Rana temporaria and Xenopus laevis.
1987
1. Rana and Xenopus excrete 90-95% dose, and metabolize 50-65% dose of phenol, 4-nitrophenol and 2-methylphenol within 24 h, to about the same extent. 2. Kinetic data for the excretion of phenols from both species fit a two-compartment model. The elimination constants of Rana and Xenopus are not significantly different. 3. Metabolism is mostly conjugation by glucuronidation and sulphation of the original phenols. Additionally, oxidations leading to dihydroxyphenols and benzoic acid from 2-methylphenol, and reduction of 4-nitrophenol occur, followed by conjugation. 4. There is an important difference between the metabolite patterns of Rana and Xenopus in that the latter is unable to glucuron…
Artificial Chromosomes to Explore and to Exploit Biosynthetic Capabilities of Actinomycetes
2012
Actinomycetes are an important source of biologically active compounds, like antibiotics, antitumor agents, and immunosuppressors. Genome sequencing is revealing that this class of microorganisms has larger genomes relative to other bacteria and uses a considerable fraction of its coding capacity (5–10%) for the production of mostly cryptic secondary metabolites. To access actinomycetes biosynthetic capabilities or to improve the pharmacokinetic properties and production yields of these chemically complex compounds, genetic manipulation of the producer strains can be performed. Heterologous expression in amenable hosts can be useful to exploit and to explore the genetic potential of actinom…
Wide-scope screening of pharmaceuticals, illicit drugs and their metabolites in the Amazon River.
2021
Only a limited number of households in the Amazon are served by sewage collection or treatment facili- ties, suggesting that there might be a significant emission of pharmaceuticals and other wastewater contaminants into freshwater ecosystems. In this work, we performed a wide-scope screening to assess the occurrence of pharmaceuticals, illicit drugs and their metabolites in freshwater ecosystems of the Brazilian Amazon. Our study included 40 samples taken along the Amazon River, in three of its major tributaries, and in small tributaries crossing four important urban areas (Manaus, Santarém, Macapá, Belém). More than 900 compounds were investigated making use of target and suspect screenin…
Sequence of lethal events in HeLa cells exposed to the G2 blocking cytolethal distending toxin
2000
The bacterial cytolethal distending toxin (CDT) was previously shown to block the cell cycle of several cell lines at stage G2 through inactivation of the cyclin-dependent kinase Cdkl and without induction of DNA strand breaks. In the present study, we have analyzed, using various methods of analytical cytometry, the progressive transformation and delayed lethal events in the tumor-derived HeLa cell line temporarily exposed to CDT. The cell proliferation arrest induced by CDT was irreversible but, starting about two days after exposure, the G2 block released partially, concomitantly with a decline in the level of Cdkl phosphorylation. This partial release resulted in endoreduplication, lead…
An efficient synthesis of new fluorinated uracil derivatives.
2003
A series of potentially biologically active fluorinated uracil derivatives has been prepared in three steps from oxazolines and fluorinated nitriles with good chemical yields. Fustero Lardies, Santos, Santos.Fustero@uv.es ; Sanz Cervera, Juan Francisco, Juan.F.Sanz@uv.es ; Asensio Martinez, Amparo, Amparo.Asensio@uv.es
Reduction of clozapine-induced hypersalivation by pirenzepine is safe.
2004
Introduction Hypersalivation is known as a frequent, disturbing, and socially stigmatizing side effect of therapy with the atypical antipsychotic clozapine. It has been shown that the addition of the anticholinergic pirenzepine is able to reduce clozapine-induced hypersalivation, probably by blocking M4-receptors. Nevertheless, a pharmacokinetic interaction between both compounds cannot be excluded. Methods In this pilot study, 29 schizophrenic patients (ICD-10; 51.7 % female; age: 36.7 +/- 8.7 years [mean +/- SD]) were included. Serum concentrations of clozapine and its pharmacologically active metabolite N-desmethylclozapine were determined under steady-state conditions by automated HPLC …