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PubMedDate not supplied

Metabolism of N-nitrosodimethyl- and N-nitrosodiethylamine by rat hepatocytes: effects of pretreatment with ethanol.

Hepatocytes were isolated from the livers of ethanol-pretreated rats, and the relationship between the generation of CO2 and the loss of N-nitrosodimethylamine (NDMA) and N-nitrosodiethylamine (NDEA) from the incubation mixtures was examined. The evolution of CO2 by hepatocytes isolated from untreated, control rats was compared with the evolution of CO2 by hepatocytes isolated from rats treated with 10% EtOH in their drinking water. The CO2 generated from either NDMA or NDEA represented only a fraction of the parent compound that was metabolized during the incubation period. Therefore, the measurement of CO2 evolution as an indication of the metabolism of these simple dialkylnitrosamines is inadequate, and the actual loss of the parent compound must be measured directly when utilizing isolated hepatocytes as a model system to study the metabolism of nitrosamines. The liver microsomal metabolism of NDMA and NDEA was also examined. Pretreatment of the rats with ethanol resulted in a marked increase in the microsomal metabolism of NDMA but had a relatively small effect on NDEA metabolism. Phenobarbital pretreatment did not result in any increase in NDMA metabolism whereas there was a very significant (6-fold) increase in NDEA metabolism. These results suggest that different isozymes of cytochrome P-450 may be primarily responsible for the metabolism of the two nitrosamines. The inhibition patterns observed when an antibody inhibitory to cytochrome P-450j was added to microsomes derived from control and ethanol- and phenobarbital-pretreated rats conclusively demonstrate that NDMA and NDEA are preferentially metabolized by distinct isozymes of cytochrome P-450.

Alkylation↗
PubMed2005

A high-resolution whole-genome cattle-human comparative map reveals details of mammalian chromosome evolution.

Approximately 3,000 cattle bacterial artificial chromosome (BAC)-end sequences were added to the Illinois-Texas 5,000-rad RH (RH, radiation hybrid) map. The BAC-end sequences selected for mapping are approximately 1 Mbp apart on the human chromosomes as determined by blastn analysis. The map has 3,484 ordered markers, of which 3,204 are anchored in the human genome. Two hundred-and-one homologous synteny blocks (HSBs) were identified, of which 27 are previously undiscovered, 79 are extended, 26 were formed by previously unrecognized breakpoints in 18 previously defined HSBs, and 23 are the result of fusions. The comparative coverage relative to the human genome is approximately 91%, or 97% of the theoretical maximum. The positions of 64% of all cattle centromeres and telomeres were reassigned relative to their positions on the previous map, thus facilitating a more detailed comparative analysis of centromere and telomere evolution. As an example of the utility of the high-resolution map, 22 cattle BAC fingerprint contigs were directly anchored to cattle chromosome 19 [Bos taurus, (BTA) 19]. The order of markers on the cattle RH and fingerprint maps of BTA19 and the sequence-based map of human chromosome 17 [Homo sapiens, (HSA) 17] were found to be highly consistent, with only two minor ordering discrepancies between the RH map and fingerprint contigs. The high-resolution Illinois-Texas 5,000-rad RH and comparative maps will facilitate identification of candidate genes for economically important traits, the phylogenomic analysis of mammalian chromosomes, proofing of the BAC fingerprint map and, ultimately, aid the assembly of cattle whole-genome sequence.

Animals↗
PubMed2005

Evolution of a microbial nitrilase gene family: a comparative and environmental genomics study.

BACKGROUND: Completed genomes and environmental genomic sequences are bringing a significant contribution to understanding the evolution of gene families, microbial metabolism and community eco-physiology. Here, we used comparative genomics and phylogenetic analyses in conjunction with enzymatic data to probe the evolution and functions of a microbial nitrilase gene family. Nitrilases are relatively rare in bacterial genomes, their biological function being unclear. RESULTS: We examined the genetic neighborhood of the different subfamily genes and discovered conserved gene clusters or operons associated with specific nitrilase clades. The inferred evolutionary transitions that separate nitrilases which belong to different gene clusters correlated with changes in their enzymatic properties. We present evidence that Darwinian adaptation acted during one of those transitions and identified sites in the enzyme that may have been under positive selection. CONCLUSION: Changes in the observed biochemical properties of the nitrilases associated with the different gene clusters are consistent with a hypothesis that those enzymes have been recruited to a novel metabolic pathway following gene duplication and neofunctionalization. These results demonstrate the benefits of combining environmental genomic sampling and completed genomes data with evolutionary and biochemical analyses in the study of gene families. They also open new directions for studying the functions of nitrilases and the genes they are associated with.

Aminohydrolases↗
PubMed2004

Quantifying myocardial deformation throughout the cardiac cycle: a comparison of ultrasound strain rate, grey-scale M-mode and magnetic resonance imaging.

Strain rate imaging (SRI) is a new ultrasound (US) approach to the quantification of regional myocardial deformation. It previously has been validated in vitro and in vivo against other imaging techniques. However, in all such studies, only peak strain values were compared, and the temporal evolution of the strain curve was not studied. Yet, it is the temporal evolution of the strain curves that contains the more important clinical information (e.g., asynchrony, viability, etc). Thus, the aim of this study was to compare the evolution of strain during the complete cardiac cycle as measured by US SRI, US grey-scale M-mode and magnetic resonance imaging (MRI). In 10 healthy volunteers and 20 patients with chronic ischaemic heart disease, radial deformation of the inferolateral segment of the left ventricle was measured by US SRI, US M-mode and MRI. The correspondence of the temporal characteristics of these strain curves were compared by defining an intraclass correlation coefficient (ICC). In healthy volunteers, an overall good agreement (mean ICC: 0.75 and 0.63 for systole and diastole) was found between the different methods. However, in patients with abnormal segmental deformation and low peak strain values, the agreement was less (mean ICC: 0.42 and 0.32), but remained within acceptable limits for clinical decision making. Myocardial deformation measurements using SRI correlated well with MRI and US M-mode measurements throughout the complete cardiac cycle.

Coronary Stenosis↗
PubMed2026

Genome evolution and long-term demographic history in true crocodiles.

Reference-quality genomes remain scarce for true crocodiles (Crocodylus), limiting comparative analyses of genome evolution and demographic history. Here, we generated and analyzed 2 long-read genomes, 1 for Crocodylus intermedius and 1 for C. niloticus, to investigate genome architecture, coalescent effective population size (Ne), and patterns of molecular evolution across crocodilians. Comparative analyses revealed broadly similar repeat landscapes in both species and extensive macro-synteny with Alligator sinensis, indicating strong structural conservation across crocodilian genomes. Using phased diploid assemblies and MSMC2, we reconstructed historical Ne trajectories and found marked differences between species. Crocodylus intermedius exhibited persistently low Ne throughout most of the late Quaternary, with a pronounced decline during the Late Pleistocene-early Holocene transition. In contrast, C. niloticus showed substantially larger Ne over comparable time intervals. Genome-wide codon-based analyses identified significant heterogeneity in dN/dS (ω) among crocodilian lineages. Crocodylus niloticus showed the lowest genome-wide ω, whereas elevated values in C. intermedius and other lineages were consistent with reduced long-term efficacy of purifying selection under smaller historical population sizes. Branch-site tests identified candidate genes under positive selection in both focal species, with functional categories related to ion transport, endocrine regulation, and cellular signaling. Together, these results provide genomic resources for Crocodylus and support an association between long-term demographic history and genome-wide patterns of molecular evolution across crocodilians.

Animals↗
PubMed1996

Region-specific YAC banding and painting probes for comparative genome mapping: implications for the evolution of human chromosome 2.

To date, several hundred nonchimeric yeast artificial chromosomes (YACs) from the Centre d'Etude du Polymorphisme Humain containing polymorphic sequence-tagged sites have been mapped by fluoresence in situ hybridization (FISH) on human metaphase chromosomes. Because they carry an average of 1 Mb of human genomic DNA, CEPH YACs generate high-intensity in situ hybridization signals. The available set of cytogenetically and genetically anchored YACs, approximately one every 5-10 cM evenly spaced over almost the entire human genome, provides complex region-specific probes for molecular cytogenetics. YAC probes can be adapted with unlimited flexibility to specific FISH applications such as the study of chromosomal evolution. We have generated representational probes for YAC banding and painting of human chromosome 2 and its great ape homologs. Convergent inversions were found in the pericentric region of the gorilla and orangutan homologs of chromosome 2p.

Animals↗
PubMed1996

Inefficacy of collagen shields in the rabbit corneal wound-healing process.

A controlled study in the rabbit eye was performed to clarify the suitability of collagen shields in accelerating the wound healing process in damaged cornea. After a standardized bilateral keratectomy, the spontaneous evolution of the healing process in the right eye (control eye) was compared with the evolution in the left eye, treated with a collagen shield (a shield of the 12- or 24-h type). The healing area was measured by planimetry after fluorescein staining at 0, 24, 48, and 72 h after keratectomy. Histological and immunohistochemical analysis of the healing process was also performed. Reepithelization of the damaged cornea was almost complete at 72 h, and there were no differences in the time course of the healing process between control and treated eyes. There was an important polymorphonuclear infiltration in treated eyes, mainly composed of eosinophiles, which was not present in control eyes. This indicates a subacute inflammatory immunological reaction. It is concluded that the usefulness of collagen shields should be reappraised, especially in injured corneas.

Animals↗
PubMed2000

[Thomas H.Huxley--the naval doctor who became Darwin's bulldog].

Thomas H. Huxley (1825-1895) was an English physician and biologist who had a deep impact on the Victorian age. More than any other at his time he introduced scientifically based values. As a member of London's school board he brought science into the curriculum, encouraging school-children to ask questions and to make their own observations. Huxley came from a lower middle class family with little money. By sheer determination and hard work he managed to get a medical education at Charing Cross Hospital Medical School. He then obtained a posting on H.M.S. Rattlesnake, which gave him a chance to explore the southern seas and to study marine species. The results were published by the Royal Society of which Huxley became a member at the age of 26, and later its president. After several years of uncertainty he secured a position at the Royal School of Mines, which he transformed into the Imperial College of Science. He was a prolific scientist with wide interests, doing valuable work in paleontology, taxonomy and ethnology. Huxley wrote numerous essays on philosophy and scientific subjects. He coined the word agnostic to explain his attitude to Christian dogma. His style was clear and direct, and his essays still read very well. However, Huxley is now mostly, perhaps unfairly, remembered for his defence of Darwin's theory of evolution. In his book Evidence as to man's place in nature, Huxley, in contrast to Darwin, deals with the evolution of humans, mainly based on comparative anatomy. Huxley advocated a firmly held belief that scientific truths will have a liberating effect on the minds of men. His lectures on scientific subjects attracted large audiences of people who had not had the benefit of a higher education.

Anatomy, Comparative↗
PubMed2024

Comparative genomics illuminates karyotype and sex chromosome evolution of sharks.

Chondrichthyes is an important lineage to reconstruct the evolutionary history of vertebrates. Here, we analyzed genome synteny for six chondrichthyan chromosome-level genomes. Our comparative analysis reveals a slow evolutionary rate of chromosomal changes, with infrequent but independent fusions observed in sharks, skates, and chimaeras. The chondrichthyan common ancestor had a proto-vertebrate-like karyotype, including the presence of 18 microchromosome pairs. The X chromosome is a conversed microchromosome shared by all sharks, suggesting a likely common origin of the sex chromosome at least 181 million years ago. We characterized the Y chromosomes of two sharks that are highly differentiated from the X except for a small young evolutionary stratum and a small pseudoautosomal region. We found that shark sex chromosomes lack global dosage compensation but that dosage-sensitive genes are locally compensated. Our study on shark chromosome evolution enhances our understanding of shark sex chromosomes and vertebrate chromosome evolution.

Animals↗
PubMed1977

[A comparative study of the difference in the evolution of refraction in the two eyes in patients with convergent strabismus (author's transl)].

In 329 cases of concomitant convergent strabismus, the alterations of refraction in the two eyes were compared over periods ranging from 10 to 30 years. In the group with unilateral strabismus (245 cases), a significant difference between the two eyes was observed. The change of refraction, if any, in the non-fixing eye (emmetropization or myopization) clearly lagged behind that in the fixing eye. This difference was particularly pronounced in the cases showing myopization. In the group with equivalent function of both eyes--alternating strabismus and cases with complete normalization, including functional normalization--a total of 84 cases, any emmetropization or myopization was found to run practically parallel in the two eyes. This shows that it is true of refraction, also that the genetically determined evolutive pattern may be modified by a functional abnormality.

Aging↗