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PubMed2001

Gene-environment interaction between an aldehyde dehydrogenase-2 (ALDH2) polymorphism and alcohol consumption for the risk of esophageal cancer.

Aldehyde dehydrogenase-2 (ALDH2) degrades acetaldehyde metabolized from ethanol. Its encoding gene ALDH2 has a functional polymorphism: ALDH2 Glu487LYS: An association between this polymorphism and esophageal cancer among alcoholics has been reported. To further evaluate the gene-environment interaction, a hospital-based case-control study was conducted. Cases were 102 patients with histologically confirmed esophageal cancer and controls were 241 non-cancer outpatients of Aichi Cancer Center. ALDH2 genotypes were examined by a PCR-CTPP method developed in our laboratory, which does not require a digestion stage. Logistic regression analysis was employed for estimation of relative risk and gene-environment interaction. The allele frequency for ALDH2 Lys487 was 0.28, consistent with previous reports. The age, sex, smoking and drinking status adjusted odds ratio for the ALDH2 Glu/Lys and Lys/Lys genotypes as compared with the Glu/Glu genotype was 3.43 (95% CI 1.74-6.75). The odds ratio for heavy drinking was 49.6 (14.5-169.4) among Lys487 carriers and 7.84 (2.77-22.2) for the Glu/Glu genotype. The gene-environment interaction between alcohol drinking and the ALDH2 Lys487 allele was 6.84 (2.39-19.6), whereas no significant interaction was obtained with smoking status. Although limited because of its prevalent case-control design, our study revealed a strong gene-environment interaction between ALDH2 polymorphism and heavy alcohol consumption. Taking the observed high risk of esophageal cancer in association with the ALDH2 Lys487 allele into consideration, reducing alcohol intake may be most protective among Lys487 allele carriers of this polymorphism.

Adult↗

PubMed1992

Word frequency effects in associative and item recognition.

The word frequency effect (WFE) has been taken as evidence that recall and recognition are in some way fundamentally different. Consequently, most models assume that recall and recognition operate via very different retrieval mechanisms. Experiment 1 showed that the WFE reverses for associative recognition, which requires discrimination between intact test pairs and recombinations of study list words from different study pairs. Experiment 2, in which word triples were used, revealed an interaction between word frequency and test type: for item recognition, performance was better for low-frequency words; however, for associative recognition and free recall, performance was better for high-frequency words. In Experiment 3, item recognition was tested: although overall performance was better for low-frequency words, the recognition advantage for items in intact pairs was larger for high-frequency words, suggesting two components in recognition memory. These results imply common mechanisms in recall and recognition. Theoretical implications are discussed within the framework of the SAM model.

Adult↗

PubMed1998

Individual variation in male vocal traits and female mating preferences in Bufo americanus.

We investigated the amount of variation in mating behaviour between and within individual male and female American toads, because both sources of trait variation can influence the course of sexual selection. Males varied in all four call parameters investigated (dominant call frequency, pulse rate, call rate and call duration). Individual males lowered the dominant frequency of their call when they interacted vocally with nearby males. Dominant call frequency was more highly correlated with body size in vocally interacting males than in non-interacting males. Pulse rate of calls primarily varied with water temperature. Call rate and call duration showed the most variation of the four call properties, but this variation was unrelated to male morphology or social interactions. Females varied in three aspects of mating behaviour: two measures of pair formation and their preference for dominant frequency of male calls. The body size of paired males varied between females both in pairings initiated by either sex and in pairings initiated only by females. Males chosen by females were usually larger than average, although age and prior breeding experience of females did not affect mate choice. Playback experiments indicated that female preference for calls of low dominant frequency depended on the temporal patterning of alternative calls presented. Each of the four male vocal properties showed significant repeatability, but only one of the three aspects of female mating behaviour was repeatable. We discuss how different degrees of repeatability in sexual traits of males and females may influence the action and detection of sexual selection in this and other species. Copyright 1998 The Association for the Study of Animal Behaviour. Copyright 1998 The Association for the Study of Animal Behaviour.

Journal Article↗

PubMed2001

Structural determinants of cold adaptation and stability in a large protein.

The heat-labile alpha-amylase from an antarctic bacterium is the largest known protein that unfolds reversibly according to a two-state transition as shown by differential scanning calorimetry. Mutants of this enzyme were produced, carrying additional weak interactions found in thermostable alpha-amylases. It is shown that single amino acid side chain substitutions can significantly modify the melting point T(m), the calorimetric enthalpy Delta H(cal), the cooperativity and reversibility of unfolding, the thermal inactivation rate constant, and the kinetic parameters k(cat) and K(m). The correlation between thermal inactivation and unfolding reversibility displayed by the mutants also shows that stabilizing interactions increase the frequency of side reactions during refolding, leading to intramolecular mismatches or aggregations typical of large proteins. Although all mutations were located far from the active site, their overall trend is to decrease both k(cat) and K(m) by rigidifying the molecule and to protect mutants against thermal inactivation. The effects of these mutations indicate that the cold-adapted alpha-amylase has lost a large number of weak interactions during evolution to reach the required conformational plasticity for catalysis at low temperatures, thereby producing an enzyme close to the lowest stability allowing maintenance of the native conformation.

Bacterial Proteins↗

PubMed1992

Danazol increases the anticoagulant effect of warfarin.

OBJECTIVE: To report two cases demonstrating an interaction between danazol and warfarin, resulting in the potentiation of warfarin's effect and bleeding complications. DATA SOURCES: Case reports, review articles, and studies identified by MEDLINE. STUDY SELECTION: All published English-language reports involving danazol and warfarin interactions were reviewed. DATA SYNTHESIS: Danazol, a synthetic testosterone derivative, is used in the treatment of endometriosis, fibrocystic breast disease, menorrhagia protein C deficiency, and hemophilia. We describe two cases including an interaction between danazol and warfarin, resulting in bleeding complications. There are at least two other reported cases of this interaction. This interaction may be attributable to several mechanisms. Danazol may inhibit the metabolism of warfarin and/or it may have a direct effect on the coagulation and fibrinolytic systems. CONCLUSIONS: Based on this report and other published cases, clinicians must be aware that danazol may increase the anticoagulant effect of warfarin. Patients receiving warfarin who are prescribed danazol must be monitored closely to prevent excessive anticoagulation and subsequent bleeding. Studies are needed to determine the frequency of this interaction and its underlying mechanisms.

Adult↗

PubMed1982

Effect of species pool size on species occurrence frequencies: Musical chairs on islands.

If species interactions affect species distributions, then species occurrence frequencies (nu(i)), defined as the fraction of an archipelago's islands that species i inhabits, should vary with species pool size. A "natural experiment" approximating this test is provided by the Bismarck, Solomon, and New Hebrides archipelagoes, whose bird species pools decrease in that order, the species of each archipelago being mostly a subset of those of the next richer archipelago. The average nu for an archipelago's species decreases with archipelago pool size. In the archipelago with the largest pool, most species are on few islands and few species are on most islands, whereas the reverse is true in the archipelago with the smallest pool. For species shared between two or more archipelagoes, nu(i) decreases with pool size or number of species in the same guild. These interarchipelagal differences in nu(i) or average nu reflect differences in level of interspecific competition, which reduces nus in species-rich archipelagoes in two ways: usually, by reducing a species' incidence on small islands and restricting the species to larger islands; less often (for so-called supertramps), by restricting a species to small islands.

Journal Article↗

PubMed2003

Pathogen frequency in an age-structured population of Plantago lanceolata.

Life-history traits can play important roles in determining the course of ecological species interactions. We explored the consequences of host age on a host-pathogen interaction by quantifying pathogen frequency in an age-structured host population. Our project was motivated by an interest in whether the demographic structure of a host population has consequences for species interactions. In 2 successive years, we planted large cohorts of the perennial herb Plantago lanceolata in its natural environment and observed infection by Fusarium moniliforme, a non-lethal floral fungal pathogen, over 3 years. We documented substantial variation of pathogen frequency across years and between cohorts. Logistic regression revealed that pathogen frequency increased with the number of inflorescences produced and with evidence of prior pathogen presence, whereas it decreased with increasing plant longevity. In addition, interannual variation and an age-year interaction contributed to the observed pathogen frequencies. There was a significant positive effect of age on pathogen frequency overall, but this was not consistent over all ages. Pathogen frequency was higher in 2-year-old plants than in 1-year-olds, suggesting that age-structure can influence the host-pathogen interaction. This pattern did not continue into 3-year-old plants. A possible explanation for this is that selective mortality allows only generally robust plants, and consequently the most resistant plants, to survive to the oldest ages.

Ecology↗

PubMed2003

Effects of suckling frequency and breed on productive performance, follicular dynamics and postpartum interval in beef cows.

One experiment was conducted to determine the influence of suckling frequency (restricted suckling (RS) versus ad libitum suckling (AS)) and breed (Brown Swiss versus Pirenaica) on productive performance, follicular dynamics and postpartum cyclicity resumption in beef cows. Twenty-four spring-calving cows (12 Brown Swiss and 12 Pirenaica) were used. After calving cows were assigned, within breed, to the two suckling frequencies (RS versus AS). During the postpartum period, cows were fed 100% of the daily energy estimated requirements. The study was conducted from calving to either day 90 postpartum or to detection of the second ovulation whenever it came later. The pattern of follicular development was monitored daily by transrectal ultrasonography, and blood samples were collected three times a week to analyse progesterone concentrations by RIA. Body condition score at calving was 2.5 (from 1 to 5). Productive parameters were not significantly affected by suckling frequency. Pirenaica cows gained more weight (P<0.001), while Brown Swiss cows had higher milk yield (P<0.001) and thus their calves grew faster (P<0.05). In the present moderate conditions of nutrition, either suckling frequency or breed did not affect follicular dynamics (on average there were 6.5 follicles in emergence, growth rate of dominant follicle (DF) was 1.3mm per day and maximum diameter of dominant follicle was 13.9mm). There were gradual increases in maximum diameter and growth rate of dominant follicle related to the proximity of the ovulatory waves, and they were defined by third order polynomial equations. Postpartum anoestrous interval (PPI) was markedly affected by the interaction between suckling frequency and breed (P<0.001): ad libitum suckling prolonged significantly the interval from calving to first ovulation in Brown Swiss cows (31.8 day versus 82.7 day, in RS and AS groups, respectively, P<0.05), but not in Pirenaica cows (43.5 day versus 32.6 day, in RS and AS groups, respectively, not statistically significant). It is concluded that in moderate pre- and postpartum nutritional conditions Brown Swiss cows were more susceptible to the suppressor effect of ad libitum suckling on postpartum anoestrous interval than Pirenaica cows, although this breed difference did not seem to be mediated by differences in energy balance or in ovarian follicular dynamics.

Animal Nutritional Physiological Phenomena↗

PubMed1991

Model inferences on baroreceptor & sinus wall responses.

Mechanical associations between sinus wall elements and those between wall and baroreceptor were modeled with differential equations. Viscoelastic relationships were tested using frequency domain analysis (TUTSIM, FANSIM). Two wall models were examined. The first had a single degree of freedom (df) and the second was a cascade system with two df. Component of the cascade model represented adventitia and media layers of the wall. This wall model had little deviation in gain between 0.1 and 10 Hz; regardless of a 100 fold difference in component damping. Properties of a wall-receptor model were in part estimated from myelinated baroreceptor responses (Brown et al., Circ. Res. 42:694-702, 1978). The wall-receptor model was designed with a natural frequency (omega b) of 12.7 Hz and damping ratio (zeta b) of 0.2 for the receptor and omega w of 50 Hz and zeta w of 1.2 for the wall component. Analysis of receptor responses, with respect to input forcing function, resulted in a omega b of 12.6 Hz. Analysis of responses with respect to those of the wall, resulted in a omega b of 16.0 Hz. These results are indicative of the complexity involved with interactive systems. If frequency analysis is used to estimate mechanical associations between sinus wall elements and baroreceptors, modeling can provide comparative data for interpretation of experimental responses.

Animals↗

PubMed1988

Inhibition of carcinoma formation and of vascular invasion in grafts of radiation-initiated thyroid clonogens by unirradiated thyroid cells.

Quantitative transplantation techniques have been employed to study radiogenic cancer initiation frequency and cell interactions during promotion/progression in grafted clonogenic rat thyroid epithelial cells. The graft recipients were surgically thyroidectomized and maintained on a diet containing less than 50 ng iodine per g. The results confirm that radiogenic initiation is a common cellular event; one of approximately 32 surviving 5-Gy-irradiated thyroid clonogens gave rise to cancer in grafts initially containing approximately 11 clonogens per transplantation site. The data demonstrate that the efficiency of promotion/progression is inversely related to grafted irradiated cell number. As the number of transplanted surviving irradiated clonogens was increased progressively from approximately 11 to approximately 720 clonogens per graft site, the carcinoma frequency per grafted clonogen progressively decreased to one per approximately 920. Addition of unirradiated thyroid cells to the transplant inocula further suppressed promotion/progression of radiation-initiated thyroid clonogens. Furthermore, the probability of vascular invasion, a reflection of metastatic potential in carcinomas which arose from irradiated grafted thyroid clonogens, was reduced by addition of unirradiated thyroid cells to the transplant inocula. Assays of thyroid stimulating hormone (TSH) titers in the sera of thyroidectomized rats 44 weeks after transplantation of clonogenic thyroid cells indicate that the suppression of neoplastic promotion/progression observed with increased numbers of cells per graft site is due at least in part to feed-back inhibition of TSH production by thyroid hormone of graft origin. Whether local cellular interactions are also involved in this inhibitory process is currently under investigation.

Animals↗

PubMed2000

Dogs as catalysts for social interactions: robustness of the effect.

It is known that pet dogs can act as catalysts for human social interactions, and it has been suggested that this may enhance feelings of well-being. Two studies were carried out to establish the robustness of this effect. In Study 1, a highly trained dog was used to ensure that the dog itself did not solicit attention from passers-by, and data were collected across a range of normal daily activities in which a dog could be included, not confined to conventional dog walking areas as in previous studies. Being accompanied by a dog increased the frequency of social interactions, especially interactions with strangers. In Study 2, also using a trained dog, a different (male) participant observer was dressed either smartly or scruffily. Although there were significantly more interactions when he was smartly dressed, the greatest effect was between the Dog present and No Dog conditions irrespective of the handler's dress. It is concluded that the social catalysis effect is very robust, which opens the way for investigating possible consequences of the effect for well-being and health.

Adult↗

PubMed2007

Cerebral haemorrhage induced by warfarin - the influence of drug-drug interactions.

PURPOSE: To evaluate the frequency, severity and preventability of warfarin-induced cerebral haemorrhages due to warfarin and warfarin-drug interactions in patients living in the county of Ostergötland, Sweden. METHODS: All patients with a diagnosed cerebral haemorrhage at three hospitals during the period 2000-2002 were identified. Medical records were studied retrospectively to evaluate whether warfarin and warfarin-drug interactions could have caused the cerebral haemorrhage. The proportion of possibly avoidable cases due to drug interactions was estimated. RESULTS: Among 593 patients with cerebral haemorrhage, 59 (10%) were assessed as related to warfarin treatment. This imply an incidence of 1.7/100,000 treatment years. Of the 59 cases, 26 (44%) had a fatal outcome, compared to 136 (25%) among the non-warfarin patients (p < 0.01). A warfarin-drug interaction could have contributed to the haemorrhage in 24 (41%) of the warfarin patients and in 7 of these (12%) the bleeding complication was considered being possible to avoid. CONCLUSIONS: Warfarin-induced cerebral haemorrhages are a major clinical problem with a high fatality rate. Almost half of the cases was related to a warfarin-drug interaction. A significant proportion of warfarin-related cerebral haemorrhages might have been prevented if greater caution had been taken when prescribing drugs known to interact with warfarin.

Adolescent↗

PubMed2002

Direct evidence for excitonically coupled chlorophylls a and b in LHC II of higher plants by nonlinear polarization spectroscopy in the frequency domain.

Occurrence of excitonic interactions in light-harvesting complex II (LHC II) was investigated by nonlinear polarization spectroscopy in the frequency domain (NLPF) at room temperature. NLPF spectra were obtained upon probing in the chlorophyll (Chl) a/b Soret region and pumping in the Q(y) region. The lowest energy Chl a absorbing at 678 nm is strongly excitonically coupled to Chl b.

Circular Dichroism↗

PubMed2001

The human oculomotor response to simultaneous visual and physical movements at two different frequencies.

In order to investigate interactions in the visual and vestibular systems' oculomotor response to linear movement, we developed a two-frequency stimulation technique. Thirteen subjects lay on their backs and were oscillated sinusoidally along their z-axes at between 0.31 and 0.81 Hz. During the oscillation subjects viewed a large, high-contrast, visual pattern oscillating in the same direction as the physical motion but at a different, non-harmonically related frequency. The evoked eye movements were measured by video-oculography and spectrally analysed. We found significant signal level at the sum and difference frequencies as well as at other frequencies not present in either stimulus. The emergence of new frequencies indicates non-linear processing consistent with an agreement-detector system that have previously proposed.

Eye Movements↗

PubMed2002

Correlational selection and the evolution of genomic architecture.

We review and discuss the importance of correlational selection (selection for optimal character combinations) in natural populations. If two or more traits subject to multivariate selection are heritable, correlational selection builds favourable genetic correlations through the formation of linkage disequilibrium at underlying loci governing the traits. However, linkage disequilibria built up by correlational selection are expected to decay rapidly (ie, within a few generations), unless correlational selection is strong and chronic. We argue that frequency-dependent biotic interactions that have 'Red Queen dynamics' (eg, host-parasite interactions, predator-prey relationships or intraspecific arms races) often fuel chronic correlational selection, which is strong enough to maintain adaptive genetic correlations of the kind we describe. We illustrate these processes and phenomena using empirical examples from various plant and animal systems, including our own recent work on the evolutionary dynamics of a heritable throat colour polymorphism in the side-blotched lizard Uta stansburiana. In particular, male and female colour morphs of side-blotched lizards cycle on five- and two-generation (year) timescales under the force of strong frequency-dependent selection. Each morph refines the other morph in a Red Queen dynamic. Strong correlational selection gradients among life history, immunological and morphological traits shape the genetic correlations of the side-blotched lizard polymorphism. We discuss the broader evolutionary consequences of the buildup of co-adapted trait complexes within species, such as the implications for speciation processes.

Animals↗

PubMed1984

Resolving 20 years of inconsistent interactions between lexical familiarity and orthography, concreteness, and polysemy.

Numerous word recognition studies conducted over the past 2 decades are examined. These studies manipulated lexical familiarity by presenting words of high versus low printed frequency and most reported an interaction between printed frequency and one of several second variables, namely, orthographic regularity, semantic concreteness, or polysemy. However, the direction of these interactions was inconsistent from study to study. Six new experiments clarify these discordant results. The first two demonstrate that words of the same low printed frequency are not always equally familiar to subjects. Instead, subjects' ratings of "experimental familiarity" suggest that many of the low-printed-frequency words used in prior studies varied along this dimension. Four lexical decision experiments reexamine the prior findings by orthogonally manipulating lexical familiarity, as assessed by experiential familiarity ratings, with bigram frequency, semantic concreteness, and number of meanings. The results suggest that of these variables, only experiential familiarity reliably affects word recognition latencies. This in turn suggests that previous inconsistent findings are due to confounding experiential familiarity with a second variable.

Humans↗

PubMed2002

Effect of energy density in the diet and milking frequency on hepatic long chain fatty acid oxidation in early lactating dairy cows.

The objective of this study was to examine the effects of diet energy density (high versus low) and increased milk yield, induced by increased milking frequency (two versus three times daily), on the hepatic status of triacylglycerol (TAG) and glycogen content and hepatic long chain fatty acid (LCFA) oxidation capacity in early lactation in a 2 x 2 factorial design. Forty multiparous Danish-Holstein dairy cows were used from 8 weeks before to 8 weeks after calving. Liver biopsies and blood samples were taken in weeks -2, 2, and 7 from calving. The cows fed the high energy density diet, compared with the cows fed the low energy density diet, had an 18 and 28% higher milk production and net energy intake, respectively. Milk yield was increased by 10% when the cows were milked three times compared with twice daily. Complete (CO2 production) and incomplete (ketone body production) LCFA oxidation capacity in the liver were 35 and 32% higher, respectively, and liver TAG content was 48% lower for the cows fed the high energy density diet compared with the low energy density diet. Overall there was no effect of milking frequency on liver parameters. However, a significant interaction between diet and milking frequency showed that the cows milked three times daily and fed the low energy density diet had the lowest liver LCFA oxidation (CO2 and ketone body) capacity. Furthermore, these cows had the numerically highest liver TAG content. The results for liver LCFA metabolism are discussed in relation to the plasma concentration of metabolites and insulin. In conclusion, cows in early lactation given a high energy density diet will, in general, have a lower risk of high TAG infiltration in the liver.

Animals↗

PubMed1998

Simplification of the quasiperiodic route to chaos in agonist-induced vasomotion by iterative circle maps.

We have shown that the patterns of vasomotion induced by histamine in isolated rabbit ear resistance arteries can be described in terms of iterative circle maps that model the dynamics of coupled nonlinear oscillators. Cyclopiazonic acid (CPA), an inhibitor of the sarcoplasmic reticulum Ca(2+)-adenosinetriphosphatase pump, consistently transformed chaotic behavior into characteristic periodic oscillations known as mixed-mode responses, which consist of mixtures of large- and small-amplitude excursions and represent frequency-locked states. Quasiperiodicity, which reflects the interaction of oscillators with incommensurate frequencies, was also observed, although in a smaller number of experiments. The patterns of mixed-mode complexes found at different CPA concentrations allowed the derivation of firing numbers, i.e., number of large oscillations/sum of number of small and large oscillations, and the sequences in which they emerged conformed to Farey arithmetic. Two-dimensional return maps derived by Poincaré section of phase space representations of the dynamics were used to compute the mean number of rotations per iteration on the circle, i.e., the winding number. Plots of winding number against firing number revealed a devil's staircase-type structure. Experiments with verapamil, a voltage-operated L-type Ca(2+)-channel antagonist, confirmed that influx of extracellular Ca2+ was essential to sustain chaos, quasiperiodicity, and mixed-mode responses. Nonlinear coupling between cytosolic and membrane events in rabbit ear arteries thus results in a self-organized dynamics that collapses to that predicted by the theory of simple circle maps.

Animals↗