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PubMed1988

Monthly variations in the pharmacokinetics of antipyrine in the rat: circannual rhythm or random variation?

We examined the pharmacokinetics of antipyrine in the rat over an 18 month period to determine whether or not the variations in pharmacokinetic parameters previously reported exhibited a circannual rhythm. While the clearance of antipyrine varied over the study period, no discernible rhythmic pattern was found. Comparing this data with previously published work also failed to demonstrate a rhythmic pattern of variability. Unlike previous investigations, we found only relatively small variations in antipyrine volume of distribution and half-life from month to month. These data indicate that the monthly variability in the pharmacokinetics of antipyrine in the rat are random and do not exhibit a circannual rhythm.

Animals↗

PubMed1986

Quantitative genetic variation in the skeleton of the mouse: II. Description of variation within and between inbred strains.

Variation in the skeletons of over 400 male and female mice from 12 genotypes was investigated by using multivariate statistical methods. A series of discriminant functions explains the differences in the shape of six bones: mandible, os coxae, femur, tibia-fibula, scapula, and humerus. The anatomical features of bone shape described by these functions are summarized together with illustrations of the typical shapes of each bone from the 12 genotypes. Variability within genotypes was investigated by using the Mahalanobis D2 distance--a measure of the difference between two points representing multivariate data--from the group mean. A series of variants were detected ranging from grossly abnormal bones to bones showing subtle differences localized to specific regions. Examples of the variants found are illustrated.

Animals↗

PubMed1990

Repeat unit sequence variation in minisatellites: a novel source of DNA polymorphism for studying variation and mutation by single molecule analysis.

Variation in internal minisatellite structure can be analyzed by mapping variant repeat units within amplified alleles. A system capable of distinguishing greater than 10(70) allelic states at the human hypervariable locus D1S8 has been developed. Population surveys of internal allelic structure indicate that D1S8 alleles evolve rapidly along haploid chromosome lineages. Internal mapping of deletion mutant alleles physically selected from genomic DNA provides further evidence that germline and somatic mutations altering the number of allelic repeat units seldom if ever arise by unequal exchange between alleles. The existence of low level germline mosaicism for new mutants further indicates that many germline mutation events are premeiotic. Physical selection of new mutants also allows minisatellite mutation rates to be estimated directly in human DNA.

Alleles↗

PubMed1996

Contingent negative variation (CNV) and determinants of the post-imperative negative variation (PINV) in schizophrenic patients and healthy controls.

A slowly rising cortical potential shift with negative polarity following the imperative stimulus of a forewarned reaction time task, the 'post-imperative negative variation' (PINV), is regularly observed in schizophrenic patients but not in controls. The topography of the PINV suggests that it may originate in frontal cortical regions. We used a task designed to test two putative prefrontal cortical functions: working memory and processing of ambiguity. Nineteen patients with a chronic schizophrenic disorder and 19 control subjects matched for age, sex, and education participated in two experimental sessions. The EEG was recorded from frontal, central, temporal, and parietal leads over both hemispheres using a DC amplifier. PINV amplitudes were generally larger in patients than in controls. If the result of comparing physical features of the two successively presented stimuli (warning and imperative stimulus) was ambiguous rather than clear, an augmentation of the PINV amplitudes was seen in both groups. If this comparison required high rather than low involvement of working memory functions, PINV amplitudes were augmented in schizophrenic patients only. Scalp distribution of the PINV indicated a left-hemisphere fronto-central PINV maximum in patients, and a right-hemisphere predominance in controls, which was larger following ambiguous stimulus comparisons. These results suggest that ambiguity during the comparison of physical features of successively presented stimuli may be a general factor of the PINV in schizophrenic patients and healthy controls. Augmented involvement of working memory functions, presumably subserved by the prefrontal cortex, specifically affected the fronto-centrally predominant PINV in schizophrenic patients. This result is compatible with the hypothesis of prefrontal cortical dysfunctions in schizophrenia.

Adult↗

PubMed1997

Bacterial pathogenesis: a variation on variation in Lyme disease.

The discovery of antigenic variation in Borrelia burgdorferi, the bacterium that causes Lyme disease, provides a potential explanation for the chronic nature of infection as well as new insights into the genetic structure of highly recombinogenic loci responsible for combinatorial genetic diversification.

Antigenic Variation↗

PubMed2002

Variation in the vasopressin V1a receptor promoter and expression: implications for inter- and intraspecific variation in social behaviour.

Instability in highly repetitive microsatellite DNA located in the regulatory regions of genes may be a major factor producing diversity in both region-specific gene expression and the resulting phenotypes. Polymorphisms in promoter regions affecting expression of genes involved in regulating behaviour may play a role in generating individual variation in behaviour, including psychopathologies in humans, and probably are also important for the evolution of behaviour. Here we discuss the prairie vole vasopressin V1a receptor gene as a model that may be useful for understanding the evolution of promoter sequences and the relationship between gene sequence, expression and behavioural phenotype.

Animals↗

PubMed2001

Frequency variations of discrete cranial traits in major human populations. III. Hyperostotic variations.

Seven discrete cranial traits usually categorised as hyperostotic characters, the medial palatine canal, hypoglossal canal bridging, precondylar tubercle, condylus tertius, jugular foramen bridging, auditory exostosis, and mylohyoid bridging were investigated in 81 major human population samples from around the world. Significant asymmetric occurrences of the bilateral traits were detected in the medial palatine canal and jugular foramen bridging in several samples. Significant intertrait associations were found between some pairs of the traits, but not consistently across the large geographical samples. The auditory exostosis showed a predominant occurrence in males. With the exception of the auditory exostosis and mylohyoid bridging in a few samples, significant sex differences were slight. The frequency distributions of the traits (except for the auditory exostosis) showed some interregional clinality and intraregional discontinuity, suggesting that genetic drift could have contributed to the observed pattern of variation.

Cephalometry↗

PubMed1993

Retrovirus variation and reverse transcription: abnormal strand transfers result in retrovirus genetic variation.

Human immunodeficiency virus variation is extensive and is based on numerous mistakes in reverse transcription. All retrovirus replication requires two strand transfers (growing point jumps) to synthesize the complete provirus. I propose that the numerous mistakes in reverse transcription are the result of this requirement for the two strand transfers needed to form the provirus.

Genetic Variation↗

PubMed2001

Phenotypic variation in molecular mimicry between Helicobacter pylori lipopolysaccharides and human gastric epithelial cell surface glycoforms. Acid-induced phase variation in Lewis(x) and Lewis(y) expression by H. Pylori lipopolysaccharides.

Helicobacter pylori is an important gastroduodenal pathogen of humans whose survival in the gastric environment below pH 4 is dependent on bacterial production of urease, whereas above pH 4 urease-independent mechanisms are involved in survival, but that remain to be elucidated fully. Previous structural investigations on the lipopolysaccharides (LPSs) of H. pylori have shown that the majority of these surface glycolipids express partially fucosylated, glucosylated, or galactosylated N-acetyllactosamine (LacNAc) O-polysaccharide chains containing Lewis(x) (Le(x)) and/or Lewis(y) (Le(y)), although some strains also express type 1 determinants, Lewis(a), Lewis(b), and H-1 antigen. In this study, we investigated acid-induced changes in the structure and composition of LPS and cellular lipids of the genome-sequenced strain, H. pylori 26695. When grown in liquid medium at pH 7, the O-chain consisted of a type 2 LacNAc polysaccharide, which was glycosylated with alpha-1-fucose at O-3 of the majority of N-acetylglucosamine residues forming Le(x) units, including chain termination by a Le(x) unit. However, growth in liquid medium at pH 5 resulted in production of a more complex O-chain whose backbone of type 2 LacNAc units was partially glycosylated with alpha L-fucose, thus forming Le(x), whereas the majority of the nonfucosylated N-acetylglucosamine residues were substituted at O-6 by alpha-D-galactose residues, and the chain was terminated by a Le(y) unit. In contrast, detailed chemical analysis of the core and lipid A components of LPS and analysis of cellular lipids did not show significant differences between H. pylori 26695 grown at pH 5 and 7. Although putative molecular mechanisms affecting Le(x) and Le(y) expression have been investigated previously, this is the first report identifying an environmental trigger inducing phase variation of Le(x) and Le(y) in H. pylori that can aid adaptation of the bacterium to its ecological niche.

Carbohydrate Conformation↗

PubMed2002

Naturally occurring indel variation in the Brassica nigra COL1 gene is associated with variation in flowering time.

Previous QTL mapping identified a Brassica nigra homolog to Arabidopsis thaliana CO as a candidate gene affecting flowering time in B. nigra. Transformation of an A. thaliana co mutant with two different alleles of the B. nigra CO (Bni COa) homolog, one from an early-flowering B. nigra plant and one from a late one, did not show any differential effect of the two alleles on flowering time. The DNA sequence of the coding region of the two alleles was also identical, showing that nucleotide variation influencing flowering time must reside outside the coding region of Bni COa. In contrast, the nucleotide sequence of the B. nigra COL1 (Bni COL1) gene located 3.5 kb upstream of Bni COa was highly diverged between the alleles from early and late plants. One indel polymorphism in the Bni COL1 coding region, present in several natural populations of B. nigra, displayed a significant association with flowering time within a majority of these populations. These data indicate that a quantitative trait nucleotide (QTN) affecting flowering time is located within or close to the Bni COL1 gene. The intergenic sequence between Bni COL1 and Bni COa displayed a prominent peak of divergence 1 kb downstream of the Bni COL1 coding region. This region could contain regulatory elements for the downstream Bni COa gene. Our data suggest that a naturally occurring QTN for flowering time affects the function or expression of either Bni COL1 or Bni COa.

Base Sequence↗

PubMed1996

Analysis of germline variation at the FMR1 CGG repeat shows variation in the normal-premutated borderline range.

In order to characterize the dynamics of CGG repeat instability at the fragile X syndrome locus (FMR1 gene), we have used small pool PCR to estimate the mutation rate within germline (sperm) and somatic tissue (leukocytes) of two normal males, one carrying the most common 29 CGG repeats allele, the other carrying a borderline normal-premutated allele of 55 repeats. Large contractions and moderate expansions of the repeat were found in sperm and blood for the 55 repeat allele while almost no variation was found in sperm or blood with the 29 repeat allele. Somatic blood DNA exhibited fewer expansions and contractions than sperm. Contractions were more frequent than expansions, and all the expansions were found in the +4 to +10 repeats range, while most of the contractions were found in the -10 to -30 range, suggesting that a subset of contractions results from a distinct mechanism. These results also suggest that the dynamics of the CGG repeat could be partly due to germline instability within the high normal or premutated ranges.

Fragile X Messenger Ribonucleoprotein 1↗

PubMed1997

Variation in the ribosomal internal transcribed spacers and 5.8S rDNA among five species of Acropora (Cnidaria; Scleractinia): patterns of variation consistent with reticulate evolution.

The ITS sequences of Acropora spp. are the shortest so far identified in any metazoan and are among the shortest seen in eukaryotes; ITS1 was 70-80 bases, and ITS2 was 100-112 bases. The ITS sequences were also highly variable, but base composition and secondary structure prediction indicate that divergent sequence variants are unlikely to be pseudogenes. The pattern of variation was unusual in several other respects: (1) two distinct ITS2 types were detected in both A. hyacinthus and A. cytherea, species known to hybridize in vitro with high success rates, and a putative intermediate ITS2 form was also detected in A. cytherea; (2) A. valida was found to contain highly (29%) diverged ITS1 variants; and (3) A. longicyathus contained two distinct 5.8S rDNA types. These data are consistent with a reticulate evolutionary history for the genus Acropora.

Animals↗

PubMed2001

Antigenic variation among isolates of infectious salmon anaemia virus correlates with genetic variation of the viral haemagglutinin gene.

Infectious salmon anaemia virus (ISAV), an orthomyxovirus-like virus, is an important fish pathogen in marine aquaculture. Virus neutralization of 24 ISAV isolates in the TO cell line using rabbit antisera to the whole virus and comparative sequence analysis of their haemagglutinin (HA) genes have allowed elaboration on the variation of ISAV isolates. The 24 viruses were neutralized to varying degrees, revealing two major antigenic groups, one American and one European. Sequence analysis of the HA gene also revealed two groups of viruses (genotypes) that correlated with the antigenic groupings. The two HA subtypes had nucleotide sequence identity of only < or =79.4% and amino acid sequence identity of < or =84.5% whereas, within each subtype, the sequence identities were 90.7% or higher. This grouping was also evident upon phylogenetic analysis, which revealed two distinct phylogenetic families. Between the two groups, the amino acid sequence was most variable in the C-terminal region and included deletions of 4-16 amino acids in all isolates relative to ISAV isolate RPC/NB-980 280-2. In order to view the relationships among these sequences and the HA sequences of the established orthomyxoviruses, a second phylogenetic tree was constructed which showed the ISAV sequences to be more closely related to sequences from Influenzavirus A and Influenzavirus B than to sequences from Influenzavirus C and Thogotovirus. The extensive deletions in the gene of European ISAV isolates lead us to speculate that the archetypal ISAV was probably of Canadian origin.

Amino Acid Sequence↗

PubMed2001

Genetic variation in 16S-23S rDNA internal transcribed spacer regions and the possible use of this genetic variation for molecular diagnosis of Bacteroides species.

The structural variation in 16S-23S rDNA internal transcribed spacer regions (ITS) among Bacteroides species was assessed by PCR amplification and sequencing analysis, and its possible use for molecular diagnosis of these species was evaluated. Ninety strains of the genus Bacteroides, including the species B. distasonis, B. eggerthii, B. fragilis, B. ovatus, B. thetaiotaomicron, B. uniformis and B. vulgatus, produced one to three ITS amplification products with sizes ranging from 615 to 810 bp. Some Bacteroides strains could be differentiated at species level on the basis of ITS amplification patterns and restriction fragment length polymorphism (RFLP) analysis using a four-nucleotide-recognizing enzyme, Msp I. The results of sequence analysis of ITS amplification products revealed genes for Ile-tRNA and Ala-tRNA in all strains tested. The nucleotide sequence, except for that in tRNA-coding regions, was highly variable and characteristic for each species, but a common sequence among B. fragilis, B. thetaiotaomicron and B. ovatus was observed. A digoxigenin-labeled oligonucleotide probe (named FOT1), which was designed from this conserved sequence, specifically hybridized to the ITS amplification products from B. fragilis, B. thetaiotaomicron and B. ovatus. These results suggest that the ITS region is a useful target for the development of rapid and accurate techniques for identification of Bacteroides species.

Bacteroides↗

PubMed2004

Hereditary variation and genetic recombination in Koji-molds (Aspergillus oryzae and Asp. sojae). I. Natural variation.

Natural variation in monospore lines of Koji-molds (Asp. oryzae and Asp. sojae), isolated from commercial Koji material or soil and from laboratory stock cultures, has been observed. We can divide the 58 strains of Koji-molds investigated into two groups; one group consists of inconstant strains which are very liable to produce natural variants, and the other consists of strains which remain constant through successive single spore culture. The inconstant strains develop colonies bearing various proportions of conidia and aerial mycelium (X-type). They generally form large conidia (Asp. oryzae var. magnasporus) but sometimes medium sized conidia (Asp. oryzae s. str.), which produce large conidia occasionally. The colonies of the constant strains show abundant conidial formation and smooth surfaces (C-type). The conidia are mostly small (Asp. oryzae var. microsporus) but sometimes medium in size (Asp. oryzae s. str.). The colony types of the variants are as follows: C (Conidial type, whole colony covered with conidia), M (mycelial type), R (restricted in growth rate), St (sterile type, little sporulation on all media tested), Nit (requiring reduced nitrate, very faint growth on Czapek's agar), and LS (semi lethal, growth cease immediately after germination). Pedigree cultures of the 8 inconstant strains have been made, but no definite segregation ratios for each variant type have been recognized through successive generations. The LS and N types commonly occur spontaneously from the M-type.

Aspergillus↗

PubMed1997

Variation of bcl-2 expression in breast ducts and lobules in relation to plasma progesterone levels: overexpression and absence of variation in fibroadenomas.

Some women with benign breast disease eventually develop breast cancer. The mammary gland undergoes tissue remodelling according to hormonal influences, involving a balance between quiescence, proliferation, and mechanisms of cell death. Proliferation and/or apoptotic events could therefore be investigated to help understand the mechanisms of benign lesion formation and identify mastopathies with a poor prognosis. bcl-2 expression was analysed by immunohistochemistry in 75 benign mastopathies. Protein levels were quantitated with an image analyser in various epithelial structures on frozen sections, including adenoses, fibroadenomas, ductal epithelial hyperplasias, cysts, and apparently normal surrounding lobules and ducts. bcl-2 levels were equivalent in apparently normal lobules and ducts, as well as in cysts and ductal hyperplasias. bcl-2 staining was significantly higher in fibroadenomas, known to be of lobular origin [mean = 10.1, quantitative immunochemistry score (QIC) arbitrary units (AU), n = 19], than in normal lobules (mean = 5.1 AU, n = 43, P = 7 x 10(-5). bcl-2 levels in normal lobules and ducts varied according to the menstrual cycle, being higher during the follicular than the luteal phase (P = 1.8 x 10(-2) and P = 1.7 x 10(-2), respectively). This was further supported by a statistical link (P = 5 x 10(-3) between high levels of circulating progesterone and weak bcl-2 staining in lobules and ducts. This progesterone-dependent variation was absent in fibroadenomas. No statistical correlation was found between bcl-2 expression and circulating levels of oestradiol, and follicle-stimulating or luteotrophic hormones. Although these are only preliminary results, they suggest an influence of progesterone on bcl-2 expression which might be lost in fibroadenomas. A hypothesis is proposed concerning the potential involvement of altered regulation of the apoptotic process in the formation of such benign lesions.

Breast Neoplasms↗

PubMed1985

Bite-force variation related to occlusal variation in rural and urban Punjabis (North India).

Occlusal variation from defined norms was much less in traditional rural youths eating a rough unprocessed diet. Bite forces were significantly higher in the rural youths; their habitual harder chewing may help to being about their better occlusal development. Rural youths showed stronger increase with age and sex dimorphism than urban youths in bite force; thus, rurally the development of masticatory and facial structures may depend on functional masticatory demand.

Adolescent↗

PubMed1977

Daily variations of various parameters of serotonin metabolism in the rat brain. I. Circadian variations of tryptophan-5-hydroxylase in the raphe nuclei and the striatum.

Daily changes in tryptophan-5-hydroxylase (TrH) activity have been studied in six different 5-HT-containing cell groups (B3, B4, B5, B6, B7, B8,) in the brain stem of rats maintained in a regular cycle of 12 h of light and 12 h of darkness. Significant circadian alternations of TrH activity were observed in most of the raphe nuclei tested, although the changes were not identical from one structure to another. The striatum showed daily variations in TrH activity in opposite phase to the nucleus raphe dorsalis which projects specific terminals into this area. Monoamine oxidase (MAO) activity was simultaneously estimated in these nuclei but did not exhibit and significant rhythm, suggesting a specific regulation of TrH. Total protein levels were also subject to daily changes.

Animals↗