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PubMed1999

Substrate recognition by class I lysyl-tRNA synthetases: a molecular basis for gene displacement.

Lysyl-tRNA synthetases (LysRSs) are unique amongst the aminoacyl-tRNA synthetases in being composed of unrelated class I and class II enzymes. To allow direct comparison between the two types of LysRS, substrate recognition by class I LysRSs was examined. Genes encoding both an archaeal and a bacterial class I enzyme were able to rescue an Escherichia coli strain deficient in LysRS, indicating their ability to functionally substitute for a class II LysRS in vivo. In vitro characterization showed lysine activation and recognition to be tRNA-dependent, an attribute of several class I, but not class II, aminoacyl-tRNA synthetases. Examination of tRNA recognition showed that class I LysRSs recognize the same elements in tRNALys as their class II counterparts, namely the discriminator base (N73) and the anticodon. This sequence-specific recognition of the same nucleotides in tRNALys by the two unrelated types of enzyme suggests that tRNALys predates at least one of the LysRSs in the evolution of the translational apparatus. The only observed variation in recognition was that the G2.U71 wobble pair of spirochete tRNALys acts as antideterminant for class II LysRS but does not alter class I enzyme recognition. This difference in tRNA recognition strongly favors the use of a class I-type enzyme to aminoacylate particular tRNALys species and provides a molecular basis for the observed displacement of class II by class I LysRSs in certain bacteria.

Amino Acyl-tRNA Synthetases↗

PubMed2003

Nonstochastic variation of species-level diversification rates within angiosperms.

Variations in the origination and extinction rates of species over geological time often are linked with a range of factors, including the evolution of key innovations, changes in ecosystem structure, and environmental factors such as shifts in climate and physical geography. Before hypothesizing causality of a single factor, it is critical to demonstrate that the observed variation in diversification is significantly greater than one would expect due to natural stochasticity in the evolutionary branching process. Here, we use a likelihood-ratio test to compare taxonomic rate heterogeneity to a neutral birth-death model, using data on well-supported sister pairs of taxa and their species richness. We test the likelihood that the distribution of extant species among angiosperm genera and families could be the result of constant diversification rates. Results strongly support the conclusion that there is significantly more heterogeneity in diversity at the species level within angiosperms than would be expected due to stochastic processes. This result is consistent in datasets of genus pairs and family pairs and is not affected significantly by degrading pairs to simulate inaccuracy in the assumption of simultaneous origin of sister taxa. When we parse taxon pairs among higher groups of angiosperms, results indicate that a constant rates model is not rejected by rosid and basal eudicot pairs but is rejected by asterid and eumagnoliid pairs. These results provide strong support for the hypothesis that species-level rates of origination and/or extinction have varied nonrandomly within angiosperms and that the magnitude of heterogeneity varies among major groups within angiosperms.

Biological Evolution↗

PubMed1991

Parkinson's disease occurrence in Europe.

Parkinson's disease (PD) surveys and death-record studies in European populations were reviewed. Particular attention was given to methodological aspects. Two sets of quality criteria were used. Four door-to-door surveys revealed underdiagnosis of prevalent idiopathic parkinsonism ranging from 30% to 71%. Quality surveys based on medical records were scarce. The analysis of a) the time relationships between the diagnostic process and the study period for measurements, and b) a variation observed in the shape of the curve for age-specific prevalences, suggested that both incidence and prevalence were underestimated by these surveys, especially among the elderly. In the UK, Denmark and Sweden, mortality from parkinsonism increased over time for ages over 70 years, but decreased for the younger age groups. A two-fold variation in mortality was found between countries. It is concluded that PD is widely distributed in Europe, and that most geographical differences in reported disease occurrence can be explained by methodological variations in measurements. The pattern of variation of age-specific figures was similar for mortality and prevalence. This might reflect decreasing prevalences among those aged under 70 years and increasing ascertainment in the elderly. There is a need for research methods for specific purposes in this field to be developed.

Adult↗

PubMed1982

Heterogeneity of the sympathetic innervation of rat interscapular brown adipose tissue via intercostal nerves.

The interscapular brown adipose tissue (IBAT) of cold-acclimated white rats was partially denervated by cutting in most cases four of the five intercostal nerves going to one of its two bilaterally located, lobular pads. After 24 h the functional ability and the degree of residual sympathetic innervation of the pads and of their lobes were assessed (in separate groups of rats): the former by measuring tissue blood flow as an index of sympathetically mediated calorigenesis during exposure of the animals to -6 degrees C, the latter by measuring the residual noradrenaline (NA) content of the tissue. Only the four anterior intercostal nerves contributed significantly to the sympathetic innervation of IBAT pads. On average their contributions were unequal, but there was considerable variation between rats in the relative contribution of each nerve. The measurements on lobes of the pads indicated that the sympathetic fibers supplied by a given intercostal nerve were not distributed uniformly throughout the pad. For example, measurements of NA indicated that on average the fibers of the fourth nerve were four times as abundant in the lateral lobe as in the posterior lobe. But at this level of analysis also there was wide variation between rats. The variation in the participation of each intercostal nerve in the sympathetic innervation of rat IBAT and in the distribution of each nerve's fibers to different parts of the IBAT pad could be of genetic origin or it could reflect a considerable degree of flexibility during development of the innervation of IBAT. Because of the observation variation, it is suggested that if functional responses of IBAT evoked by electrical stimulation of intercostal nerves are to be recorded from a highly localized area of tissue, stimulation of all the nerves probably would be required to obtain responses that are consistent between animals.

Adipose Tissue, Brown↗

PubMed1989

[Radiographic examination of the thorax, fluoroscopy and echocardiography in cardiac calcification].

The value of radiographic examination of the thorax, fluoroscopy and echocardiography in demonstration and localization of intracardiac calcifications were compared in an investigation of 40 patients with valvular heart disease prior to planned cardiac catheterization or operation. Radiographic examination of the thorax revealed only the most severe calcifications. By means of echocardiography it proved possible to undertake a simple semi-quantitative characterisation of the calcified tissue with acceptable intra- and inter-observer variation. Echocardiography and fluoroscopy were found to be of equal value in demonstration of the degree of calcification of the heart. Echocardiography was, however, superior to fluoroscopy in fine localization of the calcifications. The relative and additive values of the methods could be illustrated employing Bayes' theorem and could be represented graphically provided that the observations carried out with the three methods could be considered independent of one another. It is concluded that radiographic examinations of the thorax is unsuitable for screening for cardiac calcifications. Fluoroscopy can no longer be considered to be the method of choice in assessing lesions of this type but should be employed in cases where echocardiography does not provide sufficient information or is not available. The greatest certainty in demonstration of calcifications is obtained with combined employment of fluoroscopy and echocardiography.

Adult↗

PubMed1988

The mechanisms of force enhancement during constant velocity lengthening in tetanized single fibres of frog muscle.

The present paper deals with the mechanism responsible for the force enhancement in response to constant velocity lengthenings imposed at the plateau of isometric tetanic contractions. Experiments were performed at 3.5-5.6 degrees C on single fibres isolated from the tibialis anterior muscle of the frog. The resting sarcomere length was about 2.15 microns. The large variation observed in the characteristics of the force responses to lengthening and therefore in the shape of the force-lengthening velocity relations is mainly determined by the degree of longitudinal dishomogenities of muscle fibres. "Homogeneous" fibres and individual "tendon-free segments" selected along them exhibited superimposable force-lengthening velocity relations with negligible shape variation. Stiffness and force increased with lengthening, reaching, approximately steady values, respectively 10-15% and 60-70% greater than at the isometric tetanus plateau, at velocities of about 0.1 micron/s per half-sarcomere (hs). At higher lengthening velocities stiffness remained practically unvaried, whereas the steady component of the force responses continued to increase, reaching asymptotically a maximum value, about 100% greater than at the isometric tetanus plateau, at velocities between about 0.5 and 1 micron/s per hs. The amount of lengthening required to attain the peak value was smaller for stiffness (10 nm per hs) than for force (12-14 nm per hs). In terms of 1957 model of A. F. Huxley, the results indicate that lengthening (i) potentiates the mechanical output of muscle by increasing the number and the degree of extension of attached cross-bridges, (ii) enhances the speed of cross-bridge attachment and detachment.

Animals↗

PubMed1997

Genetic diversity between hepatitis G virus isolates: analysis of nucleotide variation in the NS-3 and putative 'core' peptide genes.

Significant variation was found, between 46 isolates of hepatitis G virus (HGV), following direct sequencing of subgenomic PCR fragments from either or both the NS-3 and putative 'core' peptide. Nucleotide sequences of most HGV NS-3 fragments varied by 10-30% and of most putative 'core' peptide fragments by 2-20%. HGV was therefore shown to be much less variable than hepatitis C virus (HCV) and pairwise comparisons of HGV sequences demonstrated a single distinct distribution of evolutionary distances. Construction of phylogenetic trees, bootstrap analysis and calculation of mean distances between possible subtypes also indicated one level of variation between HGV NS-3 and putative 'core' peptide sequences, and the suggested degree of variation between isolates was similar to that between HCV subtypes. No evidence for clustering of sequences into multiple subtypes or genotypes was found. Although very small subgenomic fragments of HCV are indicative of the viral genotype it seems that the assignment of genetic groups is not possible for HGV using such small subgenomic fragments. The relatively limited genetic variation observed in HGV may reflect a relatively low level of host selection pressure stemming from the low level of host immunity stimulated by this virus.

DNA Primers↗

PubMed1989

Comparison of fetotoxic effects of a dermally applied complex organic mixture in rats and mice.

A high-boiling (288-454 degrees C), coal-derived complex organic mixture (COM) has been shown to be teratogenic in rats following inhalation and oral routes of exposure. To determine whether similar changes also occur after dermal exposure to this COM, pregnant rats and mice were exposed during periods of organogenesis (Days 11 to 15 of gestation). Shaved backs were painted with 0, 500, or 1500 mg/kg of the COM (control, low, or high dose, respectively); the exposed area was not occluded. Maternal weight gain during the gestation period decreased with increasing dose in rats but not in mice. Examination of rat fetuses on Day 20 of gestation showed that resorptions had occurred in more than 90% of low- and high-dose litters (vs 6% in the control group). In mice, fetal examinations on Day 18 of gestation showed that resorptions occurred in 71% of litters from both exposure groups (vs 14% in the controls). Fetal measurements indicated that both the weight and the length of rat fetuses decreased with increasing dose, but mouse fetuses were unaffected. Cleft palates, absent in the control groups, were observed in 50 to 55% of the high-dose group and 5 to 8% of the low-dose fetuses of both species. Small fetal lungs occurred in nearly 100% of the exposed rat fetuses and in 25% of the high-dose mice; the incidence of small lungs was 1% in control animals. Other variations observed in exposed groups included edema and reduced ossification in the rat and renal pelvic cavitation in the mouse.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Topical↗

PubMed2001

A study of occlusal variation in the primary dentition of Australian twins and singletons.

In this study, we quantified the extent of variation in different occlusal features of Australian children of European descent with complete primary dentitions, but no permanent teeth present in the mouth. The study group consisted of 412 individuals, aged between 3 and 7 years, including 70 monozygous (MZ) twin pairs, 68 same-sexed dizygous (DZ) twin pairs, 11 opposite-sexed DZ twin pairs, and 114 singletons. Occlusal traits, including inter-dental spacing, incisal overbite and overjet, arch breadth and arch depth, were obtained directly from dental casts or indirectly from photocopies or impressions of the casts. Descriptive statistics summarised the data and indicated that distributions were similar to those published for other populations. Univariate genetic analysis, using the structural equation modelling package Mx, was carried out on the quantitative data using the normal assumptions of the twin model. Genetic modelling indicated that a model incorporating additive genetic (A) and unique environmental variation (E) was the most parsimonious for interdental spacing, overbite, overjet and arch dimensions. Estimates of heritability for interdental spacing ranged from 0.62 to 0.81. Estimates for overbite and overjet were 0.53 and 0.28, respectively, and estimates for arch dimensions ranged from 0.69 to 0.89. These results indicated a moderate to relatively high genetic contribution to observed variation.

Australia↗

PubMed2006

Are the distributions of variations of circle of Willis different in different populations? - Results of an anatomical study and review of literature.

BACKGROUND: Previous studies have proposed correlation between variants of the cerebral arterial circle (also known as circle of Willis) and some cerebrovascular diseases. Differences in the incidence of these diseases in different populations have also been investigated. The study of variations in the anatomy of the cerebral arterial circle may partially explain differences in the incidence of some of the cerebrovascular diseases in different ethnic or racial groups. While many studies have investigated the variations in the anatomy of each segment of the cerebral arterial circle, few have addressed the variants of the cerebral arterial circle as a whole. Similarly, the frequency of occurrence of such variants in different ethnic or racial groups has not been compared. METHODS: 102 brains of recently deceased Iranian males were dissected, in order to observe variations in the anatomy of the cerebral arterial circle. The dissection process was recorded on film and digitized. One resized picture from each dissection, showing complete circle has been made available online. The variations of the circle as whole and segmental variations were compared with previous studies. RESULTS: On the whole, the frequencies of the different variants of the entire cerebral arterial circle and segmental variations were comparable with previous studies.More specifically variants with uni- and bilateral hypoplasia of posterior communicating arteries were the most common in our study, similar to the previous works. No hypoplasia of the precommunicating part of the left anterior cerebral artery (A1), aplasia of A1 or the precommunicating part of the posterior cerebral artery (P1) was seen. In 3% both right and left posterior communcating arteries were absent. CONCLUSION: The anatomical variations found in the cerebral arterial circle of the Iranian males in the current study were not significantly different to those of more diverse populations reported in the literature. While taking into account potential confounding factors, the authors conclude that based on available studies, there is no evidence suggesting that the distributions of the variations of cerebral arterial circle differ in different populations.

Adolescent↗

PubMed2003

Laser-induced incandescence for soot diagnostics at high pressures.

The influence of pressure on laser-induced incandescence (LII) is investigated systematically in premixed, laminar sooting ethylene/air flames at 1-15 bar with wavelength-, laser fluence-, and time-resolved detection. In the investigated pressure range the LII signal decay rate is proportional to pressure. This observation is consistent with the prediction of heat-transfer models in the free-molecular regime. Pressure does not systematically affect the relationship between LII signal and laser fluence. With appropriate detection timing the pressure influence on LII signal's proportionality to soot volume faction obtained by extinction measurements is only minor compared with the variation observed in different flames at fixed pressures. The implications for particle sizing and soot volume fraction measurements using LII techniques at elevated pressures are discussed.

Journal Article↗

PubMed2004

Natural variation of drug susceptibility in wild-type human immunodeficiency virus type 1.

Wild-type viruses from the ViroLogic phenotype-genotype database were evaluated to determine the upper confidence limit of the drug susceptibility distributions, or "biological cutoffs," for the PhenoSense HIV phenotypic drug susceptibility assay. Definition of the natural variation in drug susceptibility in wild-type human immunodeficiency virus (HIV) type 1 isolates is necessary to determine the prevalence of innate drug resistance and to assess the capability of the PhenoSense assay to reliably measure subtle reductions in drug susceptibility. The biological cutoffs for each drug, defined by the 99th percentile of the fold change in the 50% inhibitory concentration distributions or the mean fold change plus 2 standard deviations, were lower than those previously reported for other phenotypic assays and lower than the clinically relevant cutoffs previously defined for the PhenoSense assay. The 99th percentile fold change values ranged from 1.2 (tenofovir) to 1.8 (zidovudine) for nucleoside reverse transcriptase RT inhibitors (RTIs), from 3.0 (efavirenz) to 6.2 (delavirdine) for nonnucleoside RTIs, and from 1.6 (lopinavir) to 3.6 (nelfinavir) for protease inhibitors. To evaluate the potential role of intrinsic assay variability in the observed variations in the drug susceptibilities of wild-type isolates, 10 reference viruses with different drug susceptibility patterns were tested 8 to 30 times each. The median coefficients of variation in fold change for the reference viruses ranged from 12 to 18% for all drugs except zidovudine (32%), strongly suggesting that the observed differences in wild-type virus susceptibility to the different drugs is related to intrinsic virus variability rather than assay variability. The low biological cutoffs and assay variability suggest that the PhenoSense HIV assay may assist in defining clinically relevant susceptibility cutoffs for resistance to antiretroviral drugs.

Anti-HIV Agents↗

PubMed1976

[Variation of the 9-keto-2-decenoic acid content as a function of age in virgin queen-bees (Apis mellifica ligustica S.)].

We measured the amount of 9-oxodec-2-enoic acid in virgin Honeybee queens 1 to 50 days old. We chose 4 age ranges: from 1 to 6, from 16 to 20, from 26 to 30, from 40 to 50 days. Queens 16 to 20 days old contain most 9-oxodec-2-enoic acid (average : 1 107 mug). The observed variations in amounts should partly depend on the physiology of attending workers. The authors discuss the mechanisms responsible for the action of 9-oxodec-2-enoic-acid.

Aging↗

PubMed1994

Comparative effects of hepatocyte growth factor and epidermal growth factor on motility, morphology, mitogenesis, and signal transduction of primary rat hepatocytes.

Hepatocyte growth factor (HGF) and epidermal growth factor (EGF) are major hepatocyte mitogens, but HGF, also known as scatter factor (SF), has also been shown as a potent motogen for epithelial and endothelial cells. The mechanisms by which HGF is a stronger motogen compared to other mitogens are not understood. Here we report a comparative study of the effect of the two growth factors on cultured primary rat hepatocytes regarding their differential effects on morphology, mitogenicity, and motility as well as the phosphorylation of cytoskeletal-associated proteins. Using three different motility assays, both HGF and EGF increased the motility of hepatocytes, but HGF consistently elicited a significantly greater motility response than EGF. Additionally, HGF induced a more flattened, highly spread morphology compared to EGF. To examine if HGF and EGF phosphorylated different cytoskeletal elements as signal transduction targets in view of the observed variation in morphology and motility, primary cultures of 32P-loaded rat hepatocytes were stimulated by either HGF or EGF for up to 60 min. Both mitogens rapidly stimulated four isoforms of MAP kinase with similar kinetics and also rapidly facilitated the phosphorylation of cytoskeletal-associated F-actin. Two cytoskeletal-associated proteins, however, were observed to undergo rapid phosphorylation by HGF and not EGF during the time points described. One protein of 28 kDa was observed to become phosphorylated fivefold over controls, while the EGF-stimulated cells showed only a slight increase in the phosphorylation of this protein. Another protein with an apparent mwt of 42 kDa was phosphorylated 20-fold at 1 min and remained phosphorylated over 50-fold over control up to the 60 min time point. This protein was observed to become phosphorylated by EGF only after 10 min, and to a lesser extent (20-fold). Taken together, the data suggest that HGF and EGF stimulate divergent as well as redundant signal transduction pathways in the hepatocyte cytoskeleton, and this may result in unique HGF- or EGF-specific motility, morphology, and mitogenicity in hepatocytes.

Animals↗

PubMed2006

Femtosecond fluorescence dynamics of porphyrin in solution and solid films: the effects of aggregation and interfacial electron transfer between porphyrin and TiO2.

The excited-state relaxation dynamics of a synthetic porphyrin, ZnCAPEBPP, in solution, coated on a glass substrate as solid films, mixed with PMMA and coated on a glass substrate as solid films, and sensitized on nanocrystalline TiO2 films were investigated by using femtosecond fluorescence up-conversion spectroscopy with excitation in the Soret band, S2. We found that the S2--> S1 electronic relaxation of ZnCAPEBPP in solution and on PMMA films occurs in 910 and 690 fs, respectively, but it becomes extremely rapid, <100 fs, in solid films and TiO2 films due to formation of porphyrin aggregates. When probed in the S1 state of porphyrin, the fluorescence transients of the solid films show a biphasic kinetic feature with the rapid and slow components decaying in 1.9-2.4 and 19-26 ps, respectively. The transients in ZnCAPEBPP/TiO2 films also feature two relaxation processes but they occur on different time scales, 100-300 fs and 0.8-4.1 ps, and contain a small offset. According to the variation of relaxation period as a function of molecular density on a TiO2 surface, we assigned the femtosecond component of the TiO2 films as due to indirect interfacial electron transfer through a phenylethynyl bridge attached to one of four meso positions of the porphyrin ring, and the picosecond component arising from intermolecular energy transfer among porphyrins. The observed variation of aggregate-induced relaxation periods between solid and TiO2 films is due mainly to aggregation of two types: J-type aggregation is dominant in the former case whereas H-type aggregation prevails in the latter case.

Journal Article↗

PubMed2002

The effect of selection on a long wavelength-sensitive (LWS) opsin gene of Lake Victoria cichlid fishes.

In East African Lake Victoria >200 endemic species of haplochromine fishes have been described on the basis of morphological and behavioral differences. Yet molecular analysis has failed to reveal any species-specific differences among these fishes in either mitochondrial or nuclear genes. Although the genes could be shown to vary, the variations represent trans-species polymorphisms not yet assorted along species lines. Nevertheless, fixed genetic differences must exist between the species at loci responsible for the adaptive characters distinguishing the various forms from one another. Here we describe variation and fixation at the long wavelength-sensitive (LWS) opsin locus, which is selection-driven, adaptive, and if not species- then at least population-specific. Because color is one of the characters distinguishing species of haplochromine fishes and color perception plays an important part in food acquisition and mate choice, we suggest that the observed variation and fixation at the LWS opsin locus may have been involved in the process that has led to the spectacular species divergence of haplochromine fishes in Lake Victoria.

Adaptation, Physiological↗

PubMed1987

An abasic site in DNA. Solution conformation determined by proton NMR and molecular mechanics calculations.

We have determined the three-dimensional structure of a non-selfcomplementary nonanucleotide duplex which contains an abasic (apyrimidinic) site in the centre, i.e. a deoxyribose residue opposite an adenosine. The majority of the base and sugar proton resonances were assigned by NOESY, COSY and 2DQF spectra in D2O and H2O. We have measured the initial slope of buildup of NOEs in NOESY spectra at very short mixing times (25 to 50 ms), and from these were able to establish interproton distances for the central part of the duplex. We propose a different strategy for proton-proton distance determinations which takes into account the observed variations in correlation times for particular proton-proton vectors. A set of 31 measured interproton distances was incorporated into the refinement of the oligonucleotide structure by molecular mechanics calculations. Two structures were obtained which retain all aspects of a classical B DNA in which the unpaired adenine and the abasic deoxyribose lie inside the helix. We observe that the non-hydrogen bonded adenine is held well in the helix, the Tm of this base being the same as that of the A.T base pairs in the same duplex.

Algorithms↗

PubMed1999

Influence of microbial phytase on apparent ileal amino acid digestibility of feedstuffs for broilers.

The influence of microbial phytase on the ileal amino acid digestibilities in three cereals (corn, sorghum, and wheat), four oilseed meals (soybean meal, canola meal, cottonseed meal, and sunflower meal) and two cereal by-products (wheat middlings and rice polishings) was determined using 5-wk-old broilers. Supplementation of microbial phytase (1,200 FTU/kg) improved (P < 0.001 to 0.10) the digestibilities of protein and amino acids in all feedstuffs, but the magnitude of response varied depending on the feedstuff and the amino acid considered. Mean digestibility of the 15 amino acids in the feedstuffs without and with phytase were: corn, 78.0 and 80.4%; sorghum, 74.7 and 79.4%; wheat, 77.7 and 84.6%; soybean meal, 82.2 and 85.5%; canola meal, 78.7 and 80.7%; cottonseed meal, 70.8 and 74.2%; sunflower meal, 76.7 and 80.2%; wheat middlings, 70.8 and 73.4%; and rice polishings 62.1 and 66.9%, respectively. When individual amino acids were considered, the increments in digestibility were relatively higher for threonine and valine. This effect was consistent across all feedstuffs. The observed variations in response among feedstuffs were influenced by the inherent protein digestibility, but not by dietary phytic acid concentration. No correlations were determined between the dietary concentrations of phytic acid and phytase responses in terms of protein digestibility (r = 0.20; P > 0.31) and mean amino acid digestibility (r = 0.12; P > 0.51); however a significant negative correlation was observed between inherent protein digestibility and phytase responses in protein digestibility (r = -0.42; P < 0.03). It appears that solubilities of phytate salts and protein, and their influence on the degree of phytate-protein complexing in different feedstuffs, may be more relevant than total phytic acid concentrations. Interestingly, dietary phytic acid concentrations were negatively correlated with inherent protein (r = -0.81; P < 0.001) and mean amino acid (r = -0.85; P < 0.001) digestibilities of the feedstuffs evaluated in this study.

6-Phytase↗