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Allozyme variation in bumble bees (Hymenoptera: Apidae).

Allozyme variation at an average of 37.3 loci was assessed in queens of 16 Bombus and 2 Psithyrus bumble bee species from North America. The mean expected heterozygosity (H) for the Bombus species was 0.008 +/- 0.006 (95% confidence limits) and that for the Psithyrus was 0.007 +/- 0.007. These levels are significantly lower than found in other Hymenoptera but are comparable to those found in previous studies of bumble bees based on far fewer loci. Neutral mutation and random genetic drift can account for the observed variation, but this implies a very small effective population size for species of bumble bees.

Alleles↗

Adjustments in hydraulic architecture of Pinus palustris maintain similar stomatal conductance in xeric and mesic habitats.

We investigated relationships between whole-tree hydraulic architecture and stomatal conductance in Pinus palustris Mill. (longleaf pine) across habitats that differed in soil properties and habitat structure. Trees occupying a xeric habitat (characterized by sandy, well-drained soils, higher nitrogen availability and lower overstory tree density) were shorter in stature and had lower sapwood-to-leaf area ratio (A(S):A(L)) than trees in a mesic habitat. The soil-leaf water potential gradient (psiS - psiL) and leaf-specific hydraulic conductance (kL) were similar between sites, as was tissue-specific hydraulic conductivity (Ks) of roots. Leaf and canopy stomatal conductance (gs and Gs, respectively) were also similar between sites, and they tended to be somewhat higher at the xeric site during morning hours when vapour pressure deficit (D) was low. A hydraulic model incorporating tree height, A(S):A(L) and psiS-psiL accurately described the observed variation in individual tree G(Sref) (G(S) at D = 1 kPa) across sites and indicated that tree height was an important determinant of G(Sref) across sites. This, combined with a 42% higher root-to-leaf area ratio (A(R):A(L)) at the xeric site, suggests that xeric site trees are hydraulically well equipped to realize equal--and sometimes higher potential for conductance compared with trees on mesic sites. However, a slightly more sensitive stomatal closure response to increasing D observed in xeric site trees suggests that this potential for higher conductance may only be reached when D is low and when the capacity of the hydraulic system to supply water to foliage is not greatly challenged.

Adaptation, Physiological↗

Lack of clinical significance of variability in the internal ribosome entry site of hepatitis C virus.

The extreme 5'-proximal sequence of the hepatitis C virus (HCV) genome including the 5' non-coding region (5'NCR) of 341 nucleotide long and the first 30 nucleotides of the core region is highly conserved among different HCV genotypes. It contains a segment termed Internal Ribosome Entry Site (IRES) that regulates the cap-independent translation of HCV-RNA to polyprotein. Sequence variability in this region has important implications for structural organisation and function of the IRES element and could correlate with HCV RNA concentration or response to antiviral therapy. Fourteen patients (seven women, seven men) with chronic hepatitis C were separated into two groups according to their response to antiviral therapy. Seven of these were sustained responders to treatment by Interferon alpha 2b and Ribavirin and seven were non-responders. After cloning-sequencing, the IRES (nt 21 to 374) appears to be structurally highly conserved. However some variability was found between the different isolates obtained: 209 substitutions with a median of four variants/patients. Comparison of the number of variants present in the viral population of the sustained responders and non-responders patients do not show any difference. Positioning of the mutations on the predicted IRES secondary structure showed that the distribution of the mutations and their apparition frequency were different between the two groups. The translation initiator AUG-4 codon, located in the stem-loop IV, is never modified. Variations observed in the IRES are not a parameter of response to antiviral therapy, but the integrity of this region is a necessary condition to maintain its activity.

5' Untranslated Regions↗

Small area analysis of hospital discharges for musculoskeletal diseases in Michigan: the influence of socioeconomic factors.

PURPOSE: The rise in health care costs has occasioned a number of initiatives in an attempt to reduce the rate of increase. Despite the growth of health maintenance organizations and preferred provider organizations and the introduction of Medicare's prospective payment system, health care costs have continued to increase. Coincident with these efforts, a number of researchers have shown that there exists wide variation in age-adjusted hospital discharge rates, which translate into significant variation in per capita expenditures. Much of the focus on the reasons for hospital admission variability has been on physician practice variation. If most of the variation in hospital discharge rates is due to physician practice style, then payment systems can be developed (e.g., capitation) that limit physician practice variation without harming patients. We examined socioeconomic factors in Michigan communities to assess their association with hospital discharge rates for patients with musculoskeletal diseases. PATIENTS AND METHODS: Data on hospital discharges from 1980 and 1987 were taken from the Michigan Inpatient Data Base. All admissions from the major diagnostic category 8, diagnosis-related group (DRG) 209-256 were included. Zip code-specific hospitalization data were grouped into small geographic areas or hospital market communities (HMCs). Discharge rates were calculated, and profiles of the socioeconomic characteristics of each of the HMCs were developed. A Poisson regression model with an extrasystematic component of variance was used to analyze the association of HMC socioeconomic characteristics with age-adjusted hospital use. RESULTS: We found that four socioeconomic variables, average annual income per capita, percent of the population with four years of college, percent of the population living in an urban area, and percent of families with incomes below the poverty line, explained 26.6% (R2) of the variation in overall hospital discharge rates (p less than 0.001). Moreover, we found that the ability of the model to explain variability was influenced by the type of disease, and that these socioeconomic variables had a consistent effect across the range of DRGs. Finally, we noted that, over the period of 1980 to 1987, socioeconomic factors remained important in explaining hospital use despite the dramatic changes in the delivery of care over this period. CONCLUSION: Socioeconomic factors play a significant role in explaining the observed variation in hospital discharge rates for musculoskeletal diseases. Models utilizing only physician practice variation to account for the population-based differences in discharge rates are overly simplistic. In order to ensure that vulnerable subsets of the population are not harmed by the introduction of cost-containment strategies based on simplistic models, more attention must be paid to the socioeconomic and epidemiologic factors related to hospital use.

Bone Diseases↗

Clinical relevance of nonsteroidal anti-inflammatory drug pharmacokinetics.

Only recently have the pharmacokinetic characteristics of nonsteroidal anti-inflammatory drugs (NSAIDs) been recognized as decisive factors in understanding the effects and side effects of these drugs. The accumulation of NSAIDs in inflamed tissue is central to the anti-inflammatory action, whereas high drug concentrations in the gastrointestinal tract wall, kidneys, blood, and liver may be major contributing factors to the incidence and severity of side effects. Also, variations in pharmacokinetic handling of NSAIDs by different patients may contribute considerably to differences in therapeutic response. An evaluation of the response-related pharmacokinetics of the three most widely used NSAIDs, diclofenac, indomethacin, and piroxicam, shows some obvious reasons for these differences: The onset of absorption and the bioavailability of diclofenac can vary considerably, and relevant inter-patient differences are found in the terminal plasma half-life of indomethacin and piroxicam. The variability in these parameters may contribute significantly to the observed variations in clinical response and to the incidence of unwanted drug effects.

Absorption↗

The kinetic mechanism of cation-catalyzed phosphatidylglycerol transbilayer migration implies close contact between vesicles as an intermediate state.

We have investigated variations in the rate of Mn2+-catalyzed phosphatidylglycerol transbilayer migration [Lentz, Madden, & Alford (1982) Biochemistry 21, 6799] with changes in phospholipid and cation concentration over more than a 100-fold range of both parameters. The slope of a double logarithmic plot of the rate of transbilayer lipid migration versus lipid concentration was 1.7, suggesting that lipid redistribution was dependent on vesicle aggregation or collision. A model involving transitory dimerization of vesicles was able to account for the concentration dependence of the transbilayer redistribution rate. The observed variation in rate with the logarithm of Mn2+ concentration was complex: linear above 0.4 microM (corresponding to roughly 2.5 Mn2+ per vesicle) but involving a steeper dependence on Mn2+ below 0.04 microM (roughly four vesicles per Mn2+). The rate of transbilayer redistribution increased substantially between 37 and 56 degrees C, yielding a nonlinear Arrhenius plot. There was no evidence of either fusion or lipid exchange between vesicles at the low concentrations of Mn2+ needed for transbilayer redistribution. The data are consistent with a model suggesting transitory "micro-domains" of a dehydrated, interbilayer complex as involved in the transition state and are inconsistent with a model involving an inverted micelle-type structure for the transition state.

Biological Transport↗

Identification and characterization of (GA/CT)n-microsatellite loci from Quercus petraea.

In this study a size selected genomic library from Quercus petraea was screened for (GA/CT)n-microsatellite sequences. The resulting loci were analysed by PCR for their usefulness as molecular markers in Q. petraea and Q. robur. 17 out of 52 tested primer pairs resulted in the amplification of a polymorphic single-locus pattern. The number of alleles found per locus varied from 6 to 16. Combining the genetic variation observed for the characterized loci provides a unique genotype for all the individuals tested. Using intraspecific controlled crosses of Q. robur trees Mendelian inheritance could be shown for five loci.

Base Sequence↗

Heat stress and age induced maternal effects on wing size and shape in parthenogenetic Drosophila mercatorum.

Maternal effects on progeny wing size and shape in a homozygous parthenogenetic strain of Drosophila mercatorum were investigated. The impact of external maternal factors (heat stress) and the impact of internal maternal factors (different maternal and grand maternal age) were studied. The offspring developed under identical environmental conditions, and due to lack of genetic variation any phenotypic difference among offspring could be ascribed to maternal effects. Wing size was estimated by centroid size, shape was analysed with the Procrustes geometric morphometric method and variation in landmark displacement was visualized by principal component analysis. Both kinds of maternal effects had a significant impact on progeny wing size and shape. Maternal heat stress led to the same pattern of response in size and shape among the progeny, with increased difference between the control group and progeny from heat stressed flies in both size and shape with increased maternal heat stress temperature. The effects of maternal age, however, led to different responses in size and shape between the different progeny groups. The observed variation in landmark displacements was similar, and in both cases mainly associated with shape differences of the posterior part of the wing. Finally, our results suggest that maternal effect has some evolutionary implications by altering the genetic correlations among traits, which can affect the response to selective pressures.

Age Factors↗

Intralitter variation of neonatal rat lung morphology following prenatal maternal hypervitaminosis A.

Prenatal exposure to excess vitamin A (160,000 USP units/day) from days 15 through 19 of gestation results in altered lung morphology, characterized by thickened septal walls and/or large areas of atelectasis and an associated high neonatal mortality. Marked variability in both morphological and physiological expression from this prenatal insult is commonly seen between litters and littermates, making analyses difficult. The present study documents morphological intralitter variation observed in vitamin A-exposed 2-day-old rats as compared to controls. Representative midhilar coronal histological sections of each lung were examined by two methods and the results compared. The first method, although less sensitive, demonstrated that five out of eight experimental rat lungs had a significantly greater percentage of tissue to airway space as compared with undisturbed controls (greater than 43%). The second method, using several morphological criteria and a grid system to score parenchyma into classifications based on the degree of morphological variation and projected functional capability, clearly found significantly increased percentages of poor or nonfunctional lung tissue (P greater than 0.01) in seven out of eight pups exposed to excess vitamin A. This method of ranking the severity of adverse effects on tissue morphology allowed identification of drug-affected newborn and provided a means to quantify the alterations. Such a means for identifying affected individuals from littermates is essential to research methodologies for detecting substances which, when administered during fetal life, produce decrements of postnatal function but no gross structural abnormalities.

Animals↗

Comparison of bacterial toxicity tests based on growth, dehydrogenase activity, and esterase activity of Pseudomonas fluorescens.

Bacterial test systems that are used to assess the environmental risk of chemicals show considerable differences in sensitivity to toxic chemicals. This variation may be caused by differences in sensitivity between species and test parameters of the test systems. In this study, the differences in sensitivity of three test parameters, growth, esterase activity, and dehydrogenase activity, using Pseudomonas fluorescens as the test organism, were studied. The effect of eight substances was tested: pentachlorophenol, 2,4-dichlorophenol, aniline, trichloroethylene, nonylphenolethoxylate, tetrapropylene benzene sulphonate, copper, and nickel. None of the three test parameters was the most sensitive to all substances, although dehydrogenase activity showed a high sensitivity in most cases. The observed differences in sensitivity among the three test parameters were of the same order of magnitude as those previously observed for different strains of bacteria. It was concluded that the choice of test parameter is just as important as the choice of test species to the sensitivity of a test system. The differences in sensitivity between test parameters and between species may account for a great deal of the observed variation between test results obtained with different methods.

Bacteriological Techniques↗

Quantitative succinate-dehydrogenase histochemistry. III. Variations in histochemical succinatedehydrogenase activity in different cross-sections of the same muscle fibre.

The variation in histochemical SDH-activity at different levels in the same muscle fibre was determined in muscle fibre cross-sections both by visual classification and quantitative determination of the formazan-deposits. This work resulted in a confirmation of the earlier micro-biochemical studies of Spamer AND Pette (1977, 1979) and Lowrey et al. (1978) that the activity of enzymes of the citric acid cycle is not homogeneously distributed in a muscle fibre over its entire length. In addition it is shown that the observed variations in histochemical SDH-activity strongly interfere with the visual muscle fibre typing. Some of the possible causes for these variations in histochemical SDH-activity (section-thickness, presence of the motor-endplate) and the implications of these findings for the relation between histochemical characteristics and functional properties of the muscle fibres are briefly discussed.

Animals↗

Life span variations in 128 successive generations of D. melanogaster. I. Evidence that the phenomenon exists and analysis of the variations mode.

Survival of Drosophila melanogaster was estimated in 128 successive generations for 5 years. The resultant 116 samples (58 for females and 58 for males) containing series of individual values of life span (LS; 50-90 values in each series) were analyzed. Each of 58 pairs of samples belonged to a definite generation in a continuous succession where every next generation was an offspring of the preceding one. In total, 10180 Drosophila flies (5100 females and 5080 males) were studied. The mean life span (MLS) was found to be considerably heterogeneous in the series of generations: in many pairs of consecutive generations, MLSs significantly differed within two errors of the mean (P<0.05), and the minimum and maximum MLSs in the series differed from each other almost twofold. The use of the nonparametric Kruskal-Wallis test made it possible to conclusively demonstrate highly significant (P<0.001) differences between LS distributions and their medians in the series of successive generations of D. melanogaster. Highly significant (P<0.0001) positive correlations (from 0.61 to 0.91) between the parameters characterizing the minimum (t(10)), mean, and maximum (t(90)) LSs were found. This indicates considerable consistency of the LS variations in successive generations of the same population, with the proportions of individuals with low and high LSs remaining about the same irrespective of the MLS. It was demonstrated with the use of mathematical simulation that the MLS changes in successive generations may be regarded as an oscillatory process and described as a sum of several (three to five) harmonic components. The calculated determination coefficients were high (93.51 and 88.93% for females and males, respectively). This indicates that the mathematical model used for simulation adequately described the observed variations in MLS. The results are discussed in terms of population gerontology and the problem of geroprotector effectiveness.

Aging↗

Classical swine fever virus diversity and evolution.

By analysing the nucleotide sequence data generated from both the E2 (gp55) and the NS5B genes of classical swine fever virus (CSFV), in addition to previously published data from the 5'NCR, we were able to divide 115 CSFV isolates into two major groups, five subgroups and two disparate isolates. Further discrimination was possible by analysis of sequence data from the E2 region. The three sequencing based methods were compared to monoclonal antibody (MAb) typing and to limited restriction enzyme (RE) mapping. Although both MAb and RE methods confirmed the previous classification the resolution was inferior. We estimated an approximate evolution rate for CSFV from an analysis of the virus variation observed in a single geographical area over a 6 year period. Applying this proposed rate to each of our deduced CSFV subgroups enabled us to calculate the approximate dates of divergence for each subgroup.

Animals↗

Plasmodium falciparum CS protein--prime malaria vaccine candidate: definition of the human CTL domain and analysis of its variation.

Studies in mice have shown that immunity to malaria sporozoites is mediated primarily by cytotoxic T lymphocytes (CTL) specific for epitopes within the circumsporozoite (CS) protein. Humans, however, had never been shown to generate CTL against any malaria or other parasite protein. The design of a sub-unit vaccine for humans relies on the epitopes recognized by CTL being identified and polymorphisms therein being defined. We have developed a novel technique using an entire series of overlapping synthetic peptides to define the epitopes of the Plasmodium falciparum CS protein recognized by human CTL and have analyzed the sequence variation of the protein with respect to the identified CTL epitopic domain. We have demonstrated that some humans can indeed generate CTL against the P. falciparum CS protein. Furthermore, the extent of variation observed for the CTL recognition domain is finite and the combination of peptides necessary for inclusion in a polyvalent vaccine may be small. If ways can be found to increase immune responsiveness, then a vaccine designed to stimulate CS protein-specific CTL activity may prevent malaria.

Animals↗

The effects of feeding and fasting on gastrointestinal sounds in adult horses.

The effect of changes in feed intake on auscultatable gastrointestinal sounds has not been systematically studied. Disagreement also is present in the literature about variation in sounds according to the quadrant of auscultation. Gastrointestinal sounds were recorded over the center of the left dorsal, left ventral, right ventral, and right dorsal quadrants and over the middle of the right abdominal flank. During 24 hours (n = 4) or 48 hours (n = 5) of fasting, there was a reduction in the intensity of gastrointestinal sounds as assessed by analysis of sound recordings. There was also a reduction in the number of mixing-like and propulsive-like sounds heard by 2 blinded observers. After refeeding, there was a marked increase in sound. Sound intensity varied among abdominal quadrants, but blinded observers did not notice significant differences in the number of mixing-like sounds. The left dorsal quadrant was quieter than others during fasting and refeeding. The right ventral quadrant appeared to be least affected by fasting, and sounds were louder over the right ventral and right middle quadrants than over the others. The blinded observers' perceptions of sound correlated poorly with one another and with objective measures of sound intensity. This experiment demonstrates the effectiveness of computerized analysis of abdominal sound in detecting a reduction in the intensity of gastrointestinal sounds during fasting and their return during refeeding. The left dorsal quadrant was quieter than other quadrants, likely because of its position over the small colon. There was considerable observer variation in the number of intestinal sounds heard.

Animals↗

Variation in the relationship between serum and saliva lithium levels.

This study has been carried out to find out the reasons for the wide variations observed in the correlation between serum and saliva lithium levels. Serum/saliva lithium levels were monitored in 10 individuals on 6 occasions. The correlation coefficient (r) varied within individuals from 0.19 to 0.91 (p less than 0.025) whereas when all the individuals were considered simultaneously, it was 0.59 (p less than 0.005). It was concluded that prediction of serum lithium levels from salivary lithium levels would only be possible in those individuals showing good correlation. The variability in this correlation could be mainly due to inter-individual variations in the particular sample of individuals studied.

Humans↗

Selected lessons learned from the Dialysis Outcomes and Practice Patterns Study (DOPPS).

The Dialysis Outcomes and Practice Patterns Study (DOPPS) is a prospective, observational study of the relationships between hemodialysis (HD) patient outcomes and HD treatment practices. The DOPPS began in 1996 in the United States, expanding to France, Germany, Italy, Japan, Spain, and the United Kingdom in 1998-1999, and then to Australia, Belgium, Canada, New Zealand, and Sweden in 2002. More than 300 dialysis units have participated in the DOPPS since 1996, with mortality data collected from nearly 90,000HD patients and detailed longitudinal data from nearly 30,000 HD patients. Large sample size and the large treatment practice variation observed in the DOPPS--given its international scope of participation--provide strong statistical power to investigate many different HD practices. Furthermore, the detailed patient data collected in the DOPPS allow relationships to account for differences in a large number of patient characteristics. More than 55 papers have been published from the DOPPS; here we provide a summary of selected DOPPS findings regarding nutrition, mineral metabolism, anemia management, vascular access, depression, and use of multivitamins and statins.

Anemia↗

Genetic variation among Malaysian isolates of Salmonella typhi as detected by ribosomal RNA gene restriction patterns.

Genetic variation among Malaysian isolates of Salmonella typhi was determined by analysis of ribosomal RNA gene restriction patterns. Of the 20 isolates analyzed, eight different pattern combinations were detected. The amount of variation observed was also dependent upon the restriction endonuclease used; PstI produced more different patterns than did SmaI. The results suggested that disease activity was due to a number of different clones circulating simultaneously rather than a single strain. Further implications of the data are discussed.

DNA, Ribosomal↗