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PubMed2006

Effects of the trinucleotide preceding the self-cleavage site on eggplant latent viroid hammerheads: differences in co- and post-transcriptional self-cleavage may explain the lack of trinucleotide AUC in most natural hammerheads.

Eggplant latent viroid (ELVd) can form stable hammerhead structures in its (+) and (-) strands. These ribozymes have the longest helices I reported in natural hammerheads, with that of the ELVd (+) hammerhead being particularly stable (5/7 bp are G-C). Moreover, the trinucleotide preceding the self-cleavage site of this hammerhead is AUA, which together with GUA also found in some natural hammerheads, deviate from the GUC present in most natural hammerheads including the ELVd (-) hammerhead. When the AUA trinucleotide preceding the self-cleavage site of the ELVd (+) hammerhead was substituted by GUA and GUC, as well as by AUC (essentially absent in natural hammerheads), the values of the self-cleavage rate constants at low magnesium of the purified hammerheads were: ELVd-(+)-AUC approximately ELVd-(+)-GUC>ELVd-(+)-GUA> ELVd-(+)-AUA. However, the ELVd-(+)-AUC hammerhead was the catalytically less efficient during in vitro transcription, most likely because of the transient adoption of catalytically-inactive metastable structures. These results suggest that natural hammerheads have been evolutionary selected to function co-transcriptionally, and provide a model explaining the lack of trinucleotide AUC preceding the self-cleavage site of most natural hammerheads. Comparisons with other natural hammerheads showed that the ELVd-(+)-GUC and ELVd-(+)-AUC hammerheads are the catalytically most active in a post-transcriptional context with low magnesium.

Base Sequence↗

PubMed2003

Heterogeneity of antigen expression explains controversy over glomerular macrophage accumulation in mouse glomerulonephritis.

BACKGROUND: Many antibody labelling studies have suggested that there are few or no glomerular macrophages in mouse models of glomerulonephritis, despite the presence of a prominent interstitial macrophage infiltrate. These findings conflict with studies of human and rat glomerulonephritis. Therefore, we examined whether heterogeneity of macrophage antigen expression could explain this apparent discrepancy. METHODS: Kidneys were collected from normal mice and mice killed at 2 and 10 days after induction of accelerated anti-glomerular basement membrane (GBM) glomerulonephritis. Following fixation, macrophages were detected by immunoperoxidase staining in serial kidney sections using antibodies recognising CD11b, F4/80 and CD68. RESULTS: Induction of anti-GBM nephritis caused a progressive increase in glomerular and interstitial leukocytes. At days 2 and 10, there were more CD68+ macrophages in glomeruli than macrophages expressing CD11b or F4/80. At day 10, CD68+ macrophages accounted for almost all glomerular CD45+ total leukocytes. In contrast, CD11b+ and F4/80+ macrophages at day 10 accounted for only 65 and 13% of glomerular leukocytes, respectively. However, in the interstitium the number of macrophages expressing CD68, CD11b and F4/80 were not different. CONCLUSION: Antibody detection of mouse CD68 identifies all glomerular macrophages in mouse anti-GBM nephritis, indicating a similar infiltrate to that seen in human and rat anti-GBM nephritis. Our finding of substantial heterogeneity in glomerular macrophage antigen expression in this model suggests that previous studies of mouse glomerulonephritis may have underestimated glomerular macrophages and their role in glomerular injury.

Animals↗

PubMed1997

Explaining the relation between education and postmenopausal breast cancer.

The authors examined the relation between socioeconomic status, as defined by education level, and postmenopausal breast cancer incidence using data from the National Health and Nutrition Examination Survey I Epidemiologic Followup Study. Female participants in the study were followed from 1971-1974 to 1992-1993. Cox proportional hazards modeling was used to determine the relation between breast cancer incidence and education level. There was a direct dose-response association between education level and postmenopausal breast cancer risk. Several breast cancer risk factors, including height and reproductive-related risks such as nulliparity, were found to mediate this relation. Adjustment for these factors reduced, but did not eliminate, the positive relation between education level and risk of postmenopausal breast cancer; however, the association was no longer statistically significant. The association between higher education and increased risk of breast cancer appears to be largely explained by differences in the known risk factors for breast cancer.

Adult↗

PubMed1983

Familial aggregation of blood pressure and weight in adoptive families. III. Analysis of the role of shared genes and shared household environment in explaining family resemblance for height, weight and selected weight/height indices.

This study presents an analysis of the role of genetic and household environment in explaining the familial aggregation of height (HT), weight (WT), and body mass indices (WT/HT1.2 and WT/HT2.0). The biologic model used for the analysis partitions the covariances between family members into the contributions of genetic and environmental variability shared within and across generations, including a variance component shared only by a mother and her natural children. Tests of hypotheses suggest that shared genes and shared household environmental factors make significant contributions to the familial aggregation of WT (adjusted for age and sex) and of HT (adjusted for age and sex), whereas family resemblance of WT adjusted for age and HT can be attributed mostly to the effects of shared genes. The familial aggregation of selected WT/HT indices is attributed to the effects of shared household environment only, suggesting that these variables measure a characteristic of stature that is independent of height and weight.

Adolescent↗

PubMed1986

The role of behavioral variables and fat patterning in explaining ethnic differences in serum lipids and lipoproteins.

Mexican Americans have been previously reported to have greater adiposity, higher triglyceride levels, and lower high density lipoprotein (HDL) cholesterol levels than Anglos. This study investigated the relationship between behavioral variables (caloric balance, cigarette and alcohol consumption, exercise, postmenopausal estrogen or oral contraceptive use) and fat patterning (central vs. peripheral distribution of adiposity) in the San Antonio Heart Study (1979-1982) (n = 2,102) to explain the ethnic difference in lipids and lipoproteins. Adjustment for caloric balance (as reflected by body mass index) narrowed the ethnic difference in triglyceride and HDL levels for both sexes, while adjustment for smoking widened the ethnic difference. For females, the ethnic difference was also decreased by adjustment for alcohol and estrogen use. However, adjustment for these behavioral variables did not completely eliminate the ethnic difference in lipids and lipoproteins in either sex. Increased central adiposity, more characteristic of Mexican Americans than Anglos, was positively associated with triglycerides and negatively associated with HDL levels, especially in females. Fat patterning made a more important contribution to the prediction of triglyceride and HDL levels than did the other behavioral variables (except for caloric balance) and, in general, eliminated ethnic differences in lipids and lipoproteins. Epidemiologists should consider the use of a centrality index to distinguish different types of adiposity since it is easy and inexpensive to measure.

Adipose Tissue↗

PubMed1992

How much of the recent rise in breast cancer incidence can be explained by increases in mammography utilization? A dynamic population model approach.

Largely unexplained increases in breast cancer incidence of about 1% per year have been documented back to the 1940s. Since 1982, breast cancer incidence in women aged 40 years and above has been increasing at a faster rate than this long-term secular trend, especially in women aged 60 years and above. Increases in the use of mammography since 1982 (which have been documented in population surveys of women) provide the most plausible explanation for the incidence increase over the long-term secular trend. A study by White et al. (J Natl Cancer Inst 1990;82:1546-52) found that, for women aged 45-64 years, the increase in mammography utilization could explain the incidence increase, while for women aged 65-74 years, it could account for only half the increase. The authors have developed an alternative model to that of White et al. that incorporates estimates of differential lead time (time from screen detection to clinical detection in the absence of screening) by age group. Using this model, the authors show that if older women have longer lead times, than similar increases in mammography utilization across age groups will lead to a larger incidence increase in older women. Thus, the observed increases in mammography utilization are generally concordant with increases in incidence, even in the older age groups.

Adult↗

PubMed1992

Socioeconomic factors in the community fail to explain the high coronary mortality in cold parts of Sweden.

A regional association between cold climate and coronary mortality in Sweden has already been described. This study aimed to investigate whether this association can be explained by differences in socioeconomic factors and found that there was a regional association between coronary mortality and the following socioeconomic factors: prevalence of manual workers (D = 0.22), unemployment rates (D = 0.19), and proportion of low income earners (D = 0.17). However, these associations were substantially weaker than that between cold climate and coronary mortality (D = 0.39), and when cold climate was introduced into the statistical model the explanatory power of the socioeconomic factors diminished substantially and only the percentage of manual workers enhanced the explanatory power of cold climate. Regional variation in coronary mortality could not be attributed to long distance to emergency hospital. To conclude, the strong association between cold climate and coronary mortality could not be attributed to the influence of socioeconomic factors.

Adult↗

PubMed1988

A predicted tertiary structure of a thrombin inhibitor-trypsin complex explains the mechanisms of the selective inhibition of thrombin, factor Xa, plasmin, and trypsin.

The tertiary structure of a thrombin inhibitor-trypsin complex has been predicted by a molecular modelling considering the van der Waals interactions between the inhibitor and the enzyme. The selective inhibition of trypsin, thrombin, factor Xa, and plasmin exhibited by arginine and lysine derivatives has been clearly explained based on the predicted structure and the homology in the amino acid sequences of these enzymes. The differences in the amino acid sequences at the positions corresponding to Ile63, Leu99, and Ser190 of trypsin give each enzyme different binding affinities toward inhibitors and result in the selective inhibition. The X-ray analysis of the inhibitor-trypsin complex is in progress to prove the predicted structure.

Amino Acid Sequence↗

PubMed2000

Distribution and abundance of microsatellites in the yeast genome can Be explained by a balance between slippage events and point mutations.

We fit a Markov chain model of microsatellite evolution introduced by Kruglyak et al. to data on all di-, tri-, and tetranucleotide repeats in the yeast genome. Our results suggest that many features of the distribution of abundance and length of microsatellites can be explained by this simple model, which incorporates a competition between slippage events and base pair substitutions, with no need to invoke selection or constraints on the lengths. Our results provide some new information on slippage rates for individual repeat motifs, which suggest that AT-rich trinucleotide repeats have higher slippage rates. As our model predicts, we found that many repeats were adjacent to shorter repeats of the same motif. However, we also found a significant tendency of microsatellites of different motifs to cluster.

Base Sequence↗

PubMed2001

Magnesium is more efficient than calcium in alleviating aluminum rhizotoxicity in soybean and its ameliorative effect is not explained by the Gouy-Chapman-Stern model.

The mechanistic basis for cation amelioration of Al rhizotoxicity in soybean was investigated through a series of studies comparing protective effects of Ca and Mg against Al inhibition of root elongation in a background 0.8 mM CaSO4 solution (pH 4.3). A modified Gouy-Chapman-Stern model was used to evaluate the effect of cations on electrical potential and Al3+ activity at root plasma membrane surfaces. Activities of Al3+ up to 4.6 microM in the background solution inhibited soybean tap root elongation by more than 80%. There was little or no response in root elongation when Ca and Mg were added to background solutions in the absence of AL: When added to Al-toxic solutions in the micromolar concentration range, Mg was 100-fold more effective than Ca in alleviating Al toxicity, whereas both cations were equally effective when added in the millimolar concentration range. The protective effect of micromolar additions of Mg on root elongation was specific for Al and it failed to alleviate La rhizotoxicity. In contrast to wheat, Mg amelioration of Al toxicity to soybean root elongation at low Mg concentration could not be explained by changes in potential and Al3+ activity at the root plasma membrane surfaces as predicted by a Gouy-Chapman-Stern model. These results suggest that Mg is not acting as an indifferent cation when present at low concentration and implies the involvement of a mechanism other than pure electrostatic effects at the root surface.

Absorption↗

PubMed2005

Explaining social inequalities in health by sleep: the Japanese civil servants study.

BACKGROUND: Individuals of low socioeconomic status (SES) are likely to have poor sleep and poor health. This study aims to evaluate whether and how much of the socioeconomic differences in health are explained by sleep. METHODS: The subjects were 3684 (2471 males and 1213 females) employees aged 20-65 working in local government in Japan. A questionnaire survey was conducted in January 2003. Analysis of covariance (ANCOVA) was performed to examine the association of employment-grade with sleep, measured by the Pittsburgh Sleep Quality Index (PSQI), and with health, measured by the Physical and Mental Component Summary Scales (PCS and MCS) of the Short Form-36 (SF-36). RESULTS: In men, higher grade employees had better sleep and better health. The age-adjusted difference between the highest and the lowest grade employees was 1.9 points (95% confidence interval = 1.0-3.0) in the PCS and 3.4 points (1.8-4.9) in the MCS. The grade difference in health reduced to 1.5 points (0.5-2.5) in the PCS (21.1% reduction) and 2.0 points (0.6-3.4) in the MCS (41.2% reduction), when the PSQI global score was adjusted for. The grade differences in sleep quality contributed more to the health inequalities than sleep quantity. Among women, no significant grade differences were observed in the PSQI global score. The grade differences in the PCS and MCS were weaker and less consistent than those of men, and the differences hardly changed when the PSQI global score was adjusted for. CONCLUSION: Sleep quality may mediate the relationship between SES and physical and, in particular, mental health in men.

Adult↗

PubMed1994

Vegetarian diet for patients with rheumatoid arthritis: can the clinical effects be explained by the psychological characteristics of the patients?

In a controlled, single blind clinical trial we have demonstrated recently a beneficial effect of fasting and vegetarian diet in RA. In the present study we compared 53 patients who participated in this clinical trial with 71 other RA patients with regard to some psychological parameters. The patients who participated in the clinical trial differed significantly from other RA patients. Firstly, they had a higher internal score and a lower chance score on the Multi-dimensional Health Locus of Control Scale (MHLCS). Secondly, their belief in the effect of ordinary medical treatment, evaluated by a 10-cm visual analogue scale, was lower, and their belief in the effect of 'alternative', unconventional forms of treatment was higher. Of the patients who were randomized to a vegetarian diet, there was no significant difference between diet responders and diet non-responders with regard to the MHLCS scores. But, diet responders had a significantly lower belief in the effect of ordinary medical treatment compared with diet non-responders. The psychological distress imposed on the patients by changing from an omnivorous diet to a vegetarian diet was monitored during the clinical trial by means of the General Health Questionnaire. Throughout the clinical trial, this variable favoured the vegetarians compared with the omnivorous and the diet responders vs the diet non-responders. We conclude, firstly, that patients with certain psychological characteristics were selected to the clinical trial; secondly, that the MHLCS scores could not explain the clinical improvement, but it may have been influenced by the patients' beliefs in ordinary and 'alternative' forms of treatment; and thirdly, that dietary treatment decreased psychological distress.

Adult↗

PubMed1997

Sleep disturbances in a young adult population: can gender differences be explained by differences in psychological status?

To study the prevalence of reported sleep disturbances and the association between these complaints and psychological status, 529 randomly selected subjects aged 20-45 years were questioned about their sleep symptoms and psychological status by means of questionnaires. In this young population, feeling refreshed in the morning almost every day was reported by only 15.3%. Females reported a significantly longer mean total sleep time (TST) than males (F: 425 +/- 58 minutes, M: 403 +/- 50 minutes; p < 0.01). Despite this, the difference compared with the reported need of sleep was greater in females (56 +/- 62 minutes) than in males (40 +/- 51 minutes) (p < 0.05). Difficulties maintaining sleep (DMS, > or = 3/week) (F: 20.1%, M: 10.4%; p < 0.01), the absence of feeling refreshed in the morning (F: 36.2%, M: 26.8%; p < 0.05), and excessive daytime sleepiness (EDS) (F: 23.3%, M: 15.9%; p < 0.05) were significantly more common among females. According to the Hospital Anxiety and Depression scale, females suffered from anxiety more frequently than males (F: 32.8%, M: 18.9%; p < 0.001). An association was found between anxiety and many sleep disturbances. After making adjustments for age, smoking, snoring, gender and psychological status by means of multiple regression, the gender differences mentioned above remained significant. We conclude that despite a longer TST, females report insufficient sleep, EDS, DMS, and the absence of feeling refreshed in the morning more frequently than males. The higher prevalence of anxiety among females alone cannot explain the gender differences in sleep disturbances seen in this population.

Adult↗

PubMed1984

Distribution of REM latencies and other sleep phenomena in depression as explained by a single ultradian rhythm disturbance.

The McCarley-Hobson model, describing the alternation of NREM and REM sleep in the cat, was applied to human electroencephalographic data. The influence of initial conditions on oscillatory behavior was especially emphasized. It appears that the distribution of REM latency in depression, the abnormal accumulation of REM sleep, the variability of NREM-REM cycle duration, the frequent stage shifts, and frequent awakenings can be explained in this model by means of a decrease in the initial value of a single variable, which may be regarded as representing the strength of REM inhibition. The observation of slow wave sleep deficiency in depression may well be another reflection of this parameter.

Biological Clocks↗

PubMed2002

Photosynthetic responses to water deficit in six Mediterranean sclerophyll species: possible factors explaining the declining distribution of Rhamnus ludovici-salvatoris, an endemic Balearic species.

We sought to explain the declining distribution in the Balearic Islands of the endemic shrub Rhamnus ludovici-salvatoris R. Chodat, by comparing its photosynthetic response to drought with that of several widely distributed, competing Mediterranean species (R. alaternus L., Quercus ilex L., Pistacia lentiscus L., Q. humilis Mill. and P. terebinthus L.). All of the study species, except for the two Rhamnus species, avoided desiccation by rapidly adjusting their stomatal conductance at the onset of drought, and maintaining constant leaf relative water content. The two Rhamnus species showed desiccation-tolerant behavior; i.e., as drought progressed, their predawn leaf relative water content decreased simultaneously with stomatal closure. All four desiccation-avoiding species showed a significant positive correlation between leaf thermal dissipation (estimated by the fluorescence parameter NPQ (non-photochemical quenching)) and the de-epoxidation state of the xanthophyll cycle (DPS). The two Rhamnus species exhibited maximum DPS regardless of treatment, but only R. alaternus increased NPQ in response to drought. Rhamnus ludovici-salvatoris had a high ratio of photorespiration to photosynthesis and a low intrinsic water-use efficiency; traits that are likely to be unfavorable for plant productivity under arid conditions. It also had the lowest DPS and thermal dissipation among the six species. We conclude that the photosynthetic traits of R. ludovici-salvatoris account for its limited ability to compete with other species in the Mediterranean region.

Carbon Dioxide↗

PubMed2005

Does rainfall explain variation in leaf morphology and physiology among populations of red ironbark (Eucalyptus sideroxylon subsp. tricarpa) grown in a common garden?

We investigated adaptation of leaf morphology and physiology of red ironbark (Eucalyptus sideroxylon Cunn. Ex. Wools subsp. tricarpa L.A.S. Johnson) in a common garden experiment. Fifteen populations, representing a rainfall range of 500 to 1055 mm per annum at the sites of seed collection, were grown at the same site. Because environmental variables other than rainfall did not vary significantly among populations, we were able to test if leaf morphology and physiology were related to seed-source rainfall. There were large differences among and within populations in all measured variables. Most univariate relationships with seed-source rainfall were not significant. Notable exceptions were the weak positive correlation of specific leaf area with seed-source rainfall-consistent with expectations-and the weak negative correlation of photosynthesis and stomatal conductance with seed-source rainfall-the opposite of what we predicted. In many cases, populations collected from sites of similar rainfall differed greatly in leaf morphology and physiology. Principal component analysis (PCA) reduced the 13 input variables to five principal components (PC) explaining 73.0% of the total variance in the original data. Some of the PC axes could be interpreted in terms of adaptation to drought (i.e., to seed-source rainfall), but relationships of accumulated variables (the PC axes) with seed-source rainfall were significant for only one PC axis. Hence, among red ironbark populations grown in a common garden, there was significant genetic variation in leaf morphology and physiology, but for most traits, this variation was unrelated to rainfall at the site of seed collection. This study adds to a growing body of common garden literature showing weak within-species relationships of leaf morphology and physiology with seed-source rainfall, in contrast to the consistently stronger relationships among species growing at different points along broad environmental gradients.

Eucalyptus↗

PubMed2005

Sperm mobility: deduction of a model explaining phenotypic variation in roosters (Gallus domesticus).

In previous work, variation in sperm mobility phenotype was attributed to the proportion of ejaculated fowl sperm containing dysfunctional mitochondria. In the present work, latent mitochondrial dysfunction was inferred from patterns of sperm egress from the oviduct's sperm-storage tubules. In addition, experiments were performed to help explain how mitochondrial function could be compromised in viable sperm cells. Confocal microscopy demonstrated that sperm Ca2+ content differed between low and high sperm-mobility phenotypes when sperm were stained with rhod-2 AM, a Ca2+ -specific dye. Fluorescence was associated with the nuclear envelope, a variant of the endoplasmic reticulum, and greater fluorescence was observed in sperm from low sperm-mobility males. Fluorescence was reduced by 50% when motile sperm were rendered immotile by incubation with a Ca2+ chelator. Thus, a relationship was established between a dynamic intracellular Ca2+ pool and sperm motility. Sperm N-methy-D-aspartic acid (NMDA) receptors were inferred by the action of D-homocysteinesulfinic acid, a potent NMDA receptor agonist. Seminal plasma from low sperm mobility males was characterized by an elevated glutamate concentration. Thapsigargin, which inhibits the smooth endoplasmic reticulum Ca2+ pump and thereby promotes Ca2+ efflux, rendered sperm immotile. This effect was blocked by cyclosporin A, which prevents the formation of the mitochondrial permeability transition pore (PTP) in response to elevated mitochondrial Ca2+ content. In summary, we propose that 1) glutamate enables Ca2+ uptake into sperm before ejaculation, 2) excessive Ca2+ uptake triggers formation of the PTP in a subpopulation of sperm, and 3) sperm mobility is decreased in proportion.

Animals↗

PubMed2005

Selective activation of AMPK-PGC-1alpha or PKB-TSC2-mTOR signaling can explain specific adaptive responses to endurance or resistance training-like electrical muscle stimulation.

Endurance training induces a partial fast-to-slow muscle phenotype transformation and mitochondrial biogenesis but no growth. In contrast, resistance training mainly stimulates muscle protein synthesis resulting in hypertrophy. The aim of this study was to identify signaling events that may mediate the specific adaptations to these types of exercise. Isolated rat muscles were electrically stimulated with either high frequency (HFS; 6x10 repetitions of 3 s-bursts at 100 Hz to mimic resistance training) or low frequency (LFS; 3 h at 10 Hz to mimic endurance training). HFS significantly increased myofibrillar and sarcoplasmic protein synthesis 3 h after stimulation 5.3- and 2.7-fold, respectively. LFS had no significant effect on protein synthesis 3 h after stimulation but increased UCP3 mRNA 11.7-fold, whereas HFS had no significant effect on UCP3 mRNA. Only LFS increased AMPK phosphorylation significantly at Thr172 by approximately 2-fold and increased PGC-1alpha protein to 1.3 times of control. LFS had no effect on PKB phosphorylation but reduced TSC2 phosphorylation at Thr1462 and deactivated translational regulators. In contrast, HFS acutely increased phosphorylation of PKB at Ser473 5.3-fold and the phosphorylation of TSC2, mTOR, GSK-3beta at PKB-sensitive sites. HFS also caused a prolonged activation of the translational regulators p70 S6k, 4E-BP1, eIF-2B, and eEF2. These data suggest that a specific signaling response to LFS is a specific activation of the AMPK-PGC-1alpha signaling pathway which may explain some endurance training adaptations. HFS selectively activates the PKB-TSC2-mTOR cascade causing a prolonged activation of translational regulators, which is consistent with increased protein synthesis and muscle growth. We term this behavior the "AMPK-PKB switch." We hypothesize that the AMPK-PKB switch is a mechanism that partially mediates specific adaptations to endurance and resistance training, respectively.

Adaptation, Physiological↗