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SOS mutator DNA polymerase IV functions in adaptive mutation and not adaptive amplification.

Adaptive point mutation and amplification are induced responses to environmental stress, promoting genetic changes that can enhance survival. A specialized adaptive mutation mechanism has been documented in one Escherichia coli assay, but its enzymatic basis remained unclear. We report that the SOS-inducible, error-prone DNA polymerase (pol) IV, encoded by dinB, is required for adaptive point mutation in the E. coli lac operon. A nonpolar dinB mutation reduces adaptive mutation frequencies by 85% but does not affect adaptive amplification, growth-dependent mutation, or survival after oxidative or UV damage. We show that pol IV, together with the major replicase, pol III, can account for all adaptive point mutations at lac. The results identify a role for pol IV in inducible genetic change.

Adaptation, Physiological↗

Bright light treatment used for adaptation to night work and re-adaptation back to day life. A field study at an oil platform in the North Sea.

Night workers complain of sleepiness, reduced performance and disturbed sleep due to lack of adjustment of the circadian rhythm. In simulated night-work experiments scheduled exposure to bright light has been shown to reduce these complaints. Here we studied the effects of bright light treatment on the adaptation to 14 days of consecutive night work at an oil platform in the North Sea, and the subsequent readaptation to day life at home, using the Karolinska sleep/wake diary. Bright light treatment of 30 min per exposure was applied during the first 4 nights of the night-shift period and the first 4 days at home following the shift period. The bright light exposure was scheduled individually to phase delay the circadian rhythm. Bright light treatment modestly facilitated the subjective adaptation to night work, but the positive effect of bright light was especially pronounced during the re-adaptation back to day life following the return home. Sleepiness was reduced and the quality of day was rated better after exposure to bright light. The modest effect of bright light at the platform was, possibly, related to the finding that the workers seemed to adapt to night work within a few days even without bright light. These results suggest that short-term bright light treatment may help the adaptation to an extended night-work period, and especially the subsequent re-adaptation to day life.

Adaptation, Physiological↗

Mutators, population size, adaptive landscape and the adaptation of asexual populations of bacteria.

Selection of mutator alleles, increasing the mutation rate up to 10, 000-fold, has been observed during in vitro experimental evolution. This spread is ascribed to the hitchhiking of mutator alleles with favorable mutations, as demonstrated by a theoretical model using selective parameters corresponding to such experiments. Observations of unexpectedly high frequencies of mutators in natural isolates suggest that the same phenomenon could occur in the wild. But it remains questionable whether realistic in natura parameter values could also result in selection of mutators. In particular, the main parameters of adaptation, the size of the adapting population and the height and steepness of the adaptive peak characterizing adaptation, are very variable in nature. By simulation approach, we studied the effect of these parameters on the selection of mutators in asexual populations, assuming additive fitness. We show that the larger the population size, the more likely the fixation of mutator alleles. At a large population size, at least four adaptive mutations are needed for mutator fixation; moreover, under stronger selection stronger mutators are selected. We propose a model based on multiple mutations to illustrate how second-order selection can optimize population fitness when few favorable mutations are required for adaptation.

Adaptation, Physiological↗

Spectral sensitivity and adaptation characteristics of cone mechanisms under white-light adaptation.

Increment-threshold spectral-sensitivity (ITSS) functions and threshold-versus-intensity (tvi) curves were measured under white-light adaptation in rhesus monkeys. The tvi curves showed shape and test wavelength invariance, implying that three cone mechanisms were mediating detection. In general, the results were in agreement with the differential adaptation hypothesis proposed by Stiles that predicted spectral shape invariance of the cone mechanisms but overall changes in the shape of the spectral-sensitivity function with increases in the intensity of the adapting field. The principal changes occurring in the ITSS function as the level of adaptation increased involved a smaller loss in sensitivity of the short-wavelength and the long-wavelength peaks compared with the corresponding loss in sensitivity of the middle-wavelength peak. A three-channel model with an opponent L-M mechanism and a nonopponent L-M mechanism (both with S-cone input) and an independent S-cone mechanism described the ITSS data as well as other increment-threshold and suprathreshold data. The model values for the ITSS functions, along with parameters derived from the transformation of these data to cone-contrast coordinates, permitted the factoring out of first-site adaptation, second-site adaptation, and the relative strengths of contribution of the L and M cones within the opponent and nonopponent L-M channels.

Adaptation, Ocular↗

Mucosal irritation, adaptive cytoprotection, and adaptation to topical ammonia in the rat stomach.

BACKGROUND: The urease-ammonia (NH4OH) system has been proposed to play a major role in the pathogenesis of the Helicobacter pylori-associated gastritis, but the mechanism of the mucosal damage has not been fully explained. This study was designed to examine possible adaptive cytoprotection and the adaptation of rat gastric mucosa to the irritant action of NH4OH and urease. METHODS AND RESULTS: Single application of NH4OH alone in various concentrations (15-500 mM) caused concentration-dependent mucosal damage starting with 30 mM and reaching a maximum at 250 mM NH4OH, similar to that obtained with 100% ethanol; it was accompanied by a decrease in gastric blood flow (GBF) to approximately 30% of the normal value. When the mucosa was first exposed to the low, non-damaging concentration (15 mM) of NH4OH and then insulted with 100% ethanol, the extent of ethanol damage was greatly attenuated as compared with that caused by ethanol alone. This adaptive cytoprotection was accompanied by the rise in GBF and reversed, in part, by the pretreatment with indomethacin, an inhibitor of prostaglandin (PG)-cyclooxygenase; with L-NAME, a blocker of NO-synthase; or with capsaicin deactivating the sensory nerves. Damaging concentrations of NH4OH (125 mM) caused widespread mucosal damage after the first application, but with repeated insults with 125 mM NH4OH a gradual reduction in the mucosal lesions, accompanied by enhanced mucosal cell proliferation and over-expression of epidermal growth factor (EGF) (using immunocytochemistry) and mRNA of EGF (using trans-reverse polymerase chain reaction), were observed. CONCLUSIONS: NH4OH alone damages gastric mucosa only at the concentration exceeding that found in H. pylori-infected stomachs, whereas at lower concentrations it acts as 'mild' irritant to induce adaptive cytoprotection. This adaptive cytoprotection appears to be mediated, in part, by endogenous PG, sensory nerves, and an arginine-NO-dependent pathway, and repeated applications of NH4OH induce gastric adaptation, probably mediated by enhanced expression of EGF and its receptors and by an increased cell proliferation.

Adaptation, Physiological↗

Wheelchair users' experience of non-adapted and adapted clothes during sailing, quad rugby or wheel-walking.

The purpose of the present quasi-experimental post-test-design study was to compare 32 wheelchair users' (mostly para/tetraplegics) experience of wearing specially adapted clothes and non-adapted clothes for sailing, quad rugby or wheel-walking. Four existing assessment instruments were used: the Klein-Bell Activities of Daily Living Scale; a two-part Basic Information Questionnaire eliciting experience of effort, comfort and feeling of physical condition; the Experience Sampling Form for investigating the individuals' attitudes in terms of involvement and affective and activity mood states, and the Occupational Therapy Assessment of Leisure Time interview framework for collecting data about experience of leisure time. The wheelchair users all associated significantly greater comfort with use of the adapted clothes and, particularly the 'sailors', better physical condition. Overall, significantly greater involvement and more positive affect states were associated with the adapted clothes than with conventional garments, and mood state changed for the better. The wheelchair users set a higher priority upon work or leisure activities than upon independence in activities of daily living, and for this reason the Klein-Bell ratings showed great variation between the 'sailors' and the 'quad rugby players' (range 57%-93%), though these groups demonstrated more independence than the 'wheel-walkers'. The results of the study confirm the value of adapting sportswear for handicapped people. Such adaptations should also be of benefit for other activities than those studied.

Adaptation, Physiological↗

Individualized adaptation of clothes for impaired persons. A comparison of two groups with and without experience of adapted clothes.

Impaired persons often have difficulties in obtaining suitable clothing. Questionnaires on this subject were sent to a consecutive series of impaired persons. Group 1 (n = 50) had received adapted clothes and group 2 (n = 81) had not. Questionnaire A (both groups) contained general questions on clothes and questionnaire B (Group 1) contained questions on adapted clothes. The result of the study shows a significant difference (p less than 0.01) between the need for adapted clothing in group 1 and group 2. No significant difference was found between the groups regarding the reason for obtaining and using adapted clothes. It was difficult for 94% in group 1 and 85% in group 2 to obtain clothes which were suitable for the individual's impairment and which made their daily activities easier. In group 1 the adapted garments were of most value when dressing and undressing (86%). They also reduced the time needed, by 31% for the individual, by 43% for a helper; and by 62% when going to the toilet. The adapted garments were considered smarter and more comfortable by 64%. Eighteen per cent considered that wearing them had increased their self-confidence.

Activities of Daily Living↗

Olfactory self- and cross-adaptation: effects of time of adaptation on perceived odor intensity.

The time-course of self- and cross-adaptation of the olfactory system was investigated for two constant concentrations of three odorous substances. The substances (hydrogen sulfide, dimethyl disulfide, and pyridine) were matched, in a pilot experiment, with regard to perceived odor intensity. The time of adaptation was controlled by the number of inhalations (1-10). A two-step scaling method, involving cross-modality matching and numerical scaling of the matching continuum, was used for measuring perceived odor intensity during adaptation. The results show that the time-course function for self-adaptation seems to be an exponential function for two of the substances (H2S, DMDS), while for the third (pyridine) the form of the function is less distinct. Cross-adaptation between substances was found for the high concentrations, while for the low concentrations, hydrogen sulfide and dimethyl disulfide gave rise to pronounced cross-facilitation. The latter effect increased with time of adaptation.

Adaptation, Physiological↗

[The biphasic nature of the phenomenon of structural adaptational stabilization during the long-term adaptation of the body to stress].

During long-term (28 days) adaptation of the body to stress, the structural adaptational stabilization phenomenon (SASP) has a marked two-phase pattern: (1) SASP formation during nearly 14 days when protein transcription in heat shock was activated, hsp 70 was substantially accumulated and cardiac resistance to reperfusion damage drastically increased and (2) SASP reduction occurring despite continuous adaptation. By day 28 myocardial adaptation showed only two hsp 70 isoforms of the five revealed on day 14 of stress adaptation. Correspondingly, by day 28, the anticontractural effect of adaptation and its capacity of retaining the high contraction amplitude turned out to vanish in reperfusion. Moreover, ventricular fibrillation and ventricular tachycardia were observed in the control animal hearts during reperfusion, whereas these arrhythmias were seen only in 25 and 50% cases on days 14 and 28, respectively.

Adaptation, Physiological↗

Laboratory properties of cold-adapted influenza B live vaccine strains developed in the US and USSR, and their B/Ann Arbor/1/86 cold-adapted reassortant vaccine candidates.

The adaptation of two influenza B strains (B/Leningrad/14/55 and B/Ann Arbor/1/66) to replication at 25 degrees C is described. Comparison of the two viruses indicates that both also exhibit temperature sensitive phenotypes, although that of the virus B/Leningrad/14/55 is less pronounced. When inoculated into ferrets both viruses replicate well in the trachea, but only the B/Leningrad/14/55 cold-adapted virus replicates in the lungs. This virus exhibited a moderate level of attenuation in the animals, in contrast to the B/Ann Arbor/1/66 cold-adapted virus, which was fully attenuated. Reassortant viruses deriving the surface antigens of the contemporary wild type virus B/Ann Arbor/1/86 and most or all of their other genes, from one or other cold-adapted parent, were virtually indistinguishable from their respective cold-adapted parents. The B/Leningrad/14/55 reassortant was slightly more attenuated than its cold-adapted parent in ferrets. These studies extend knowledge of the properties of viruses used to prepare experimental live influenza B human vaccines.

Animals↗

Time course of adaptation and recovery from adaptation in the cat auditory-nerve neurophonic.

The auditory-nerve neurophonic (ANN) reflects the ensemble response of phase-locked firing in single auditory-nerve fibers to sustained signals. Consequently, neural response properties such as adaptation and recovery from adaptation can be observed. In this study, ANN responses to 800-Hz, 100-ms tones presented at 10-30-dB SL were recorded using bipolar platinum-iridium electrodes placed on the auditory nerve of the cat. The cat ANN adaptation properties were determined and fit to the equation: A(tp) = Yre(-tp/tau Ar) + Yse(-tp/tau As) + Ass. The rapid time constant of adaptation (tau Ar) was invariant across stimulus level, with a mean value of 4.8 (+/- 2.1) ms. The short-term time constant (tau As) decreased approximately 21 ms for each 10-dB increase in probe amplitude. The mean tau As was 116 ms at 10 dB SL, 83.2 ms at 20 dB SL, and 73.5 ms at 30 dB SL. The ANN recovery from adaptation data was analyzed and fit to the equation: A(delta t) = Amax - Yre(-delta t/tau Rr) - Yse(-delta t/tau Rs). Here, tau Rr, the rapid time constant of recovery, and tau Rs, the short-term time constant, were independent of masker intensity in the studied range, with values of 16.2(+/- 9.8) and 125(+/- 50.1) ms, respectively. The results of this study indicate that ANN time constants are comparable to those measured for single units and that the adaptation behavior of phase-locked and nonphase-locked activity appears to be similar.

Animals↗

Cyclical effects of triiodothyronine on blood-free fatty acid and glucose concentrations in warm-adapted and cold-adapted rats.

Effects of triiodothyronine (T3) (100 mug/100 g, sc) on blood-free fatty acid (FFA) and glucose concentrations were investigated in warm- and cold-adapted rats. Blood specimens were obtained from the tail locally anesthetized with lidocaine. In warm-adapted rats FFA rose 3 to 6 hr after administration of T3, but returned to the pre-injection level 12 hr later. Thereafter, blood FFA level showed a repeated cyclical rise and fall every 12 hr for up to 60 hr, while blood glucose level did not increase until 12 hr later and this level was maintained for up to 36 hr. After that time it also showed a repeated rise and fall every 12 hr for up to 60 hr. Both FFA and glucose levels returned to the initial values after 72 hr. Changes induced by T3 in blood levels of these metabolites were reciprocal. In cold-adapted rats the patterns of responses to T3 were essentially the same as those observed in warm-adapted ones, except that T3 provoked a simultaneous rise in blood glucose as well as FFA 6 hr after injection, although an extent of FFA increment was less than in warm-adapted rats. Reserpine pre-treatment caused a considerable reduction in the FFA mobilizing action of T3. The FFA and glucose mobilizing action of T3 was also observed at dosages of 25 and 6.25 mug/100 g, although to lesser extent. These results indicated for the first time the cyclical action of T3 on blood FFA and glucose concentrations, and a changed sensitivity to T3 in cold-adapted animals.

Acclimatization↗

In vivo lipolytic effect of glucagon in warm-adapted and cold-adapted rats.

In vivo effect of glucagon on blood-free fatty acid (FFA) concentration was investigated in rats adapted to 25 degree C and to 5 degree C. Intraperitoneal injection of glucagon in 100 or 25 mug/100 g body weight doses was followed by a triphasic response in blood FFA concentration: an immediate and marked rise at 5 min, a secondary depression at 60 min and a final rise at 120 to 240 min after the injectionss. For the 12.5 and 6.25 mug/100 g body weight injections, an initial increment was significantly lowered and no elevation at 240 min was observed. Concomitant elevations of blood glucose concentration were shown 5 min after glucagon injection of 100, 25, 12.5, and 6.25 mug/100 g body weight doses and their extents were not significantly different each other between these doses. However, rise in blood glucose level at 60 min was not seen at the 12.5 and 6.25 mug/100 g body weight doses. Blood lactate concentrations did not show any significant variations by the injections of glucagon. In fasting rats, glucagon at the 100 mug/100 g body weight dose caused similar increase in blood FFA as that in fed ones. In fed cold-adapted rats at 5 degree C glucagon at the dose of 100 mug/100 g body weight brought about similar effects in elevation of blood FFA level and its time-course as those in fed rats adapted to 25 degree C. However, under fasting condition cold-adapted animals exhibited greater increment in blood FFA level at 5 min than those adapted to 25 degree C, while an elevation of blood FFA at 240 min was not observed in the former animals. These results indicate for the first time an in vivo lipolytic action of glucagon in rats and further suggest an enhanced sensitivity to lipolytic action of glucagon in cold adaptation.

Acclimatization↗

Toll-like receptor 4 and Toll-IL-1 receptor domain-containing adapter protein (TIRAP)/myeloid differentiation protein 88 adapter-like (Mal) contribute to maximal IL-6 expression in macrophages.

Previous studies have shown that engagement of Toll-like receptors (TLR) 2 and 4 can induce macrophages to express a variety of proinflammatory cytokines. We have recently demonstrated that TLR2 agonists poorly induce a subset of TLR4-inducible proinflammatory genes (e.g., inducible protein (IP)-10, inducible NO synthase (iNOS), monocyte chemoattractant protein-5, IL-12p40), due in part to differential activation of IFN-beta production and phosphorylation of the transcription factor STAT1. TLR4, but not TLR2, agonists can induce IFN-beta expression via a mechanism that requires the adapter protein Toll-IL-1R domain-containing adapter protein (TIRAP)/myeloid differentiation protein 88 (MyD88) adapter-like (Mal), but not the adapter protein MyD88. Thus, the failure of TLR2 agonists to induce STAT1-dependent genes results, in part, from their failure to induce the expression of IFN-beta. In this study, we show that IL-6 expression is also preferentially induced by activation of TLR4. TLR4-dependent induction of IL-6 expression did require Toll-IL-1R domain-containing adapter protein (TIRAP)/MyD88 adapter-like (Mal), but unlike iNOS and IP-10, it did not require the expression of IFN-beta. Although exogenous IFN-beta and IFN-gamma could synergize with TLR2 agonists to restore high levels of iNOS expression and NO production, these IFNs could not synergize with TLR2 agonists to induce high levels of IL-6. Similarly, neutralizing anti-IFN Abs could block iNOS gene expression in LPS-stimulated murine macrophages, whereas these Abs had little effect on IL-6 gene expression in these cells. Together, these studies demonstrate that IL-6, like iNOS and IP-10, is differentially expressed in macrophages stimulated via TLR2 vs TLR4, although these differences appear to arise from distinct signaling mechanisms.

Adaptor Proteins, Signal Transducing↗

Changes in sensitivity of the dark-adapted eye during concurrent light adaptation of the other eye.

Thresholds for detection of light by a dark-adapted test eye were measured while the other, non-test eye was either similarly dark adapted or while it was exposed to an intense red adapting field. An interocular effect that depends on the retinal location of the test was found: compared to the threshold during binocular dark adaptation, sensitivity decreased during contralateral light adaptation when the test was presented to the foveola and up to 4 deg above it; but sensitivity increased when the test was between 7 and 12 deg, showing a reversal at 5 deg.

Adaptation, Ocular↗

A physiological model of dark-adapted and light-adapted photoreceptors of the honeybee.

A physiological model of dark-adapted and light-adapted photoreceptors in the honeybee worker (Apis mellifera) has been developed. Almost all of the electrophysiological components of photoreceptors known up to date, e.g. the phototransduction cascade, the ion channels of the membrane, phototransduction gain and optical adaptation mechanisms, are adequately described by simple biophysical and biochemical models. The connections of these components were tried out in synthetic simulations for best fits of simulated to intracellularly recorded membrane potentials. Although the parameters of the best model were determined exclusively for the measured membrane potentials of dark-adapted photoreceptors, the model also accurately describes the light-adapted photoreceptor membrane potentials. Furthermore, the model correctly predicts the time-courses of measured photoreceptor responses with respect to squared-modulated flicker lights up to 200 Hz. This clearly demonstrates that the presented photoreceptor model is indeed a physiologically adequate description of the essential components of the phototransduction and the electrical membrane processes in the photoreceptors of the honeybee worker.

Adaptation, Physiological↗

Effect of activation and adaptation on the sensitivity of slowly adapting cutaneous mechanoreceptors.

The effect of adaptation on the sensitivity of type I and type II cutaneous mechanoreceptors was evaluated with test stimuli applied before, during and after a persistent indentation (offset) of the skin. It was found that the offset initially lowered the threshold to both high (100-200 Hz) and low (1-20 Hz) frequency sinusoidal stimuli, as compared with the preoffset condition. This lowered threshold increased for both stimuli as adaptation progressed. When adaptation was nearly complete, there was an appreciable residual reduction of threshold, as compared with preoffset values, for the low frequency stimuli but not for high frequency stimuli. For a time after the offset was removed, the threshold was increased above preoffset levels for both stimuli. Suprathreshold ramp displacements superimposed on an offset caused higher maximal frequencies and a larger change in frequency than before the offset was applied. This difference often was considerable (20-40 impulses/sec) even though the discharge produced by the offset had adapted to only 2-4 impulses/sec above the preoffset level. Shortly after removal of the offset, the ramp responses typically were less than before the offset was applied. Thus, these receptors are not "reset" to the preoffset condition by adaptation nor is their sensitivity reduced. On the contrary, they respond more vigorously to superimposed stimuli except for near threshold displacements that are brief and rapid.

Adaptation, Physiological↗

Adaptation mechanisms in spatial vision--II. Flash thresholds and background adaptation.

To examine how the mechanisms of light adaptation affect spatial pattern vision, contrast detection thresholds were measured for sinusoidal (increment-Gabor) probes on flashed backgrounds in the presence of steady adapting backgrounds. The thresholds for all spatial frequencies (1-12 c/deg), flashed-background intensities (dark to 4 log td) and adapting-background intensities (dark to 4 log td) were adequately described by a simple model consisting of a compressive nonlinearity (a modified Naka-Rushton function), a subtractive adaptation factor, and a multiplicative adaptation factor. For all five subjects the compressive nonlinearity was found to vary systematically with spatial frequency; for all but one subject, the subtractive and multiplicative factors were found to be relatively constant.

Adaptation, Ocular↗