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Hsp27 protects the cytoskeleton and nucleus from the effects of 42 degrees C at pH 6.7 in CHO cells adapted to growth at pH 6.7.

CHO cells are normally sensitized to hyperthermia by acidic pH. However, CHO cells adapted to growth in pH 6.7 medium become less sensitive to heat killing at the reduced pH. The adapted cells maintain their ability to develop thermotolerance at pH 6.7 and their steady state intracellular pH is elevated. Furthermore, the small molecular weight stress chaperone, hsp27, is elevated in unheated cells maintained at pH 6.7. This report documents that the cytoskeletal and nuclear components of the low pH adapted CHO cells are resistant to 42 degrees C-induced collapse and protein accretion, respectively. Hyperthermia induced a perinuclear collapse of the microtubular cytoskeleton and an increase in the amount of insoluble protein associated with the nuclei and nuclear matrix fractions in the control cells heated at pH 7.3 or heated after acute acidification to pH 6.7. Protection from these effects was observed in the low pH adapted cells heated at pH 6.7. Hsp70 does not appear to play a dominant role in the response of the adapted cells to 42 degrees C. The induction of hsp70 during heating is abrogated by pH 6.7 in cells cultured at either pH 7.3 or pH 6.7. The resistance of the microtubular cytoskeleton to perinuclear collapse and the absence of protein aggregation in the nucleus during 42 degrees C may be due to the elevated levels of hsp27 both before heating and during the heat treatment. In summary, the phenotype of CHO cells adapted to growth at low pH includes resistance of the cytoskeleton to 42 degrees C-induced perinuclear collapse and resistance to 42 degrees C-induced aggregation of nuclear proteins, in addition to the reduction in heat cytotoxicity, upregulation of intracellular pH and upregulation of hsp27.

Adaptation, Physiological↗

The effect of a beta-adrenoceptor antagonist on accommodative adaptation in Hong Kong children.

PURPOSE: Increased susceptibility to nearwork-induced accommodative adaptation has been suggested as a risk factor for myopia development. We investigated whether accommodative adaptation may explain in part the high prevalence of myopia in Hong Kong children and examined the effect of beta-antagonism with topical timolol maleate on accommodative adaptation. METHODS: Thirty children (10 emmetropes and 20 myopes) aged between 8 and 12 years were recruited. Tonic accommodation was measured before and after 5 min of video game-playing using an open-field Shin-Nippon autorefractor. Measurements were repeated 30 min after timolol instillation. RESULTS: Children with progressing myopia demonstrated accommodative adaptation following the near task, whereas stable myopes showed counter-adaptive, hyperopic accommodative changes. Timolol increased the magnitude of accommodative adaptation in the stable myopes but had little effect on responses of the progressing myopes or emmetropes. CONCLUSIONS: Neuropharmacological modulation of the accommodative system may have a possible etiological role in the progression of myopia.

Accommodation, Ocular↗

Physiological variation and adaptability in human populations.

This review traces some of the developments in population physiology based on contributions to the Annals over the last 25 years. Two broad themes are evident, physiological systems variation and adaptation, and by way of introduction an historical perspective of their relationship within human ecology is explored. Studies of physical fitness and work capacity, and the efforts to create standardized field procedures make up a number of the early papers. Longitudinal studies have provided reliable reference standards for Westernized populations, but are virtually non-existent for primitive groups. The relative importance of phenotypic and genotypic variations in working capacity have yet to be clearly defined. The level of habitual activity during childhood contributes to the development of ventilatory capacity though constitutional influences are of major importance. Variability in strength and motor performance of skeletal muscles are shown to have a direct bearing on aspects of growth, development and biological maturation. Physical and psychological stress in communities have been investigated. These and other studies contribute valuable data on the issue of stress, hypertension and cardiovascular morbidity and mortality. On the theme of human adaptability, high altitude populations, variations in thermal tolerance and adaptations in ageing populations have all received recent investigation. Highland people of all ages have considerably larger lung volumes than coastal dwellers. Haematological, biochemical and pulmonary function show adaptive phenomena that vary in different highland groups. In the tropical biome, more recent work includes the functional consequences of malnutrition, ethnic and cultural differences in work capacity, and the effects of endemic disease on physical performance. Annals of Human Biology papers have more recently contributed to investigations on morphological and physiological changes with human ageing. Though there is a decline in the ability to adapt to environmental stresses with age this may be met by changes in adaptational strategy in physiological systems.

Adaptation, Physiological↗

The structure of post-retirement adaptation for recent and longer-term women retirees.

A review of the literature on adjustment to retirement reveals that many investigators have studied retirees together as a group, regardless of the amount of time they have been retired. The present study questions the validity of that approach. The post-retirement adaptation of a group of 59 relatively recent (3-6 years) and 122 longer-term (7 + years) retirees was compared via canonical correlation analyses. The results showed that the structure of post-retirement adaptation differed for the two groups. The relatively recent retirees' adaptational variate emphasized satisfaction with retirement (.990) and showed weaker loadings on self-esteem (.475) and happiness (.374). Corresponding factor loadings for the longer-term retirees were -.340, .827 and .494, respectively. Thus, retirement satisfaction (or job deprivation) was a more salient aspect of the recent retirees' adaptation while longer-term adaptation was a more general phenomenon. These results suggest that the inclusion of longer-term retirees in retirement research may obscure the important correlates of adaptation to this life change.

Adaptation, Psychological↗

Decoupling functional mechanisms of adaptive encoding.

In a natural setting, adaptive mechanisms constantly modulate the encoding properties of sensory neurons in response to changes in the external environment. Recent experiments have revealed that adaptation affects both the spatiotemporal integration properties and baseline membrane potential of sensory neurons. However, the precise functional role of adaptation remains an open question, due in part to contradictory experimental results. Here, we develop a framework to characterize adaptive encoding, including a cascade model with a time-varying receptive field (reflecting spatiotemporal integration properties) and offset (reflecting baseline membrane potential), and a recursive technique for tracking changes in the model parameters during a single stimulus/response trial. Simulated and experimental responses from retinal neurons are used to track adaptive changes in receptive field structure and offset during nonstationary stimulation. Due to the nonlinear nature of spiking neurons, the parameters of the receptive field and offset must be estimated simultaneously, or changes in the offset (or even in the statistical distribution of the stimulus) can mask, confound, or create the illusion of adaptive changes in the receptive field. Our analysis suggests that these confounding effects may be at the root of the inconsistency in the literature and shows that seemingly conflicting experimental results can be reconciled within our framework.

Adaptation, Physiological↗

Implication of PBP74/mortalin/GRP75 in the radio-adaptive response.

PURPOSE: To investigate the relationship between expression of the human peptide-binding protein PBP74 and the occurrence of an adaptive response to ionizing radiation. MATERIALS AND METHODS: Human tumour cell lines HT29 and MCF-7 were transfected with a PBP74 or PBP74 antisense construct. For demonstration of an adaptive response, cells lines were irradiated with a conditioning dose of 0.25 Gy cobalt-60 gamma-rays followed by a second dose of 4.0 Gy after an interval of 4.5 h. Response was measured in terms of clonogenic survival. RESULTS: Transfection of a PBP74 plasmid caused transient overexpression of PBP74 mRNA in both cell lines. The optimal dose for the induction of PBP74 in the cell lines investigated was 0.1-0.25Gy and PBP74 induction occurred within 30 min of irradiation. For both cell lines, the adaptive response was repressed when cells were transfected with the anti-PBP plasmid. However, the converse, an enhancement of the adaptive response in cell lines transfected with the PBP74 construct, was seen only for HT29 cells under certain experimental conditions. CONCLUSIONS: The results support the view that while PBP74 is necessary to the adaptive response, it may not by itself be sufficient for the adaptive response to occur.

Adaptation, Physiological↗

AROS-29 is involved in adaptive response to oxidative stress.

Transient adaptation to mild oxidative stress was induced in human osteosarcoma cells chronically grown in sub-toxic concentrations of diethylmaleate (DEM), a glutathione (GSH) depleting agent. The adapted cells, compared to untreated cells, contain increased concentrations of GSH (4-6 fold) which, upon DEM withdrawal from the culture medium, return to normal values and are more resistant to subsequent oxidizing stress induced either by toxic concentrations of the same agent or by (H(2)O(2)) treatment. To investigate the molecular mechanisms involved in the adaptive response to oxidative stress, we analyzed the gene expression profiles of DEM-adapted cells by differential display. The expression of adaptive response to oxidative stress (AROS)-29 gene, coding for a transmembrane protein of unknown function, as well as of some known genes involved in energy metabolism, protein folding and membrane traffic is up-regulated in adapted cells. The increased resistance to both DNA damage and apoptosis, in cells stably overexpressing AROS-29, demonstrated its functional role in the protection against oxidative stress.

Adaptation, Physiological↗

A quantitative comparison of the effects of intracellular calcium injection and light adaptation on the photoresponse of Limulus ventral photoreceptors.

Calcium ions were iontophoretically injected into ventral photoreceptors of Limulus by passing current between two intracellular pipettes. Changes in sensitivity and photoresponse time course were measured for both light adaptation and Ca++ injection. We found for some photoreceptors that there was no significant difference in the photoresponse time course for desensitization produced by light adaptation or by Ca++ injection. In other photoreceptors, the time delay of photoresponse for Ca++ injection was slightly longer than for light adaptation. The variability of threshold response amplitude and time delay decreases when the photoreceptor is desensitized by either light adaptation or Ca++ injection. The peak amplitude versus log stimulus intensity relationships for controls, light adaptation, and Ca++ injection all could be described very closely by a single template curve shifted along the log intensity axis. A 40- to 50-fold change in sensitivity is associated with a 2-fold change in photoresponse time delay for both light adaptation and Ca++ injection.

Adaptation, Ocular↗

Electrical and adaptive properties of rod photoreceptors in Bufo marinus. II. Effects of cyclic nucleotides and prostaglandins.

Substances known to alter cyclic nucleotide levels in cells were applied to the isolated toad retina and effects on rod electrical and adaptive behavior were studied. The retina was continually superfused in control ringer's or ringer's containing one or a combination of drugs, and rod activity was recorded intracellularly. Superfusion with cGMP, Bu(2)GMP, isobutylmethylxanthine (IBMX; a phosphodiesterase inhibitor), or PGF(2alpha) (a prostaglandin) caused effects in rods that closely match those observed when extracellular Ca(2+) levels were lowered. For example, short exposures (up to 6 min) of the retina to these substances caused depolarization of the membrane potential, increase in response amplitudes, and some changes in waveform; but under dark-adapted or partially light-adapted conditions receptor sensitivity was virtually unaffected. That is, the position of the V-log I curve on the intensity axis was determined by the prevailing light level, not by drug level. These drugs, like lowered extracellular Ca(2+), also decreased the period of receptor saturation after a bright-adapting flash, resulting in an acceleration of the onset of membrane and sensitivity recovery during dark adaptation. Long-term (6-15 min) exposure of a dark-adapted retina to 5 mM IBMX or a combination of IBMX and cGMP caused a loss of response amplitude and a desensitization of the rods that was similar to that observed in rods after a long-term low Ca(2+) (10(-9)M) treatment. Application of high (3.2 mM) Ca(2+) to the retina blocked the effects of applied Bu(2)cGMP. PGE(1) superfusion mimicked the effects of increasing extracellular Ca(2+). The results show that increased cGMP and lowered Ca(2+) produce similar alterations in the electrical activity of rods. These findings suggest that Ca(2+) and cGMP are interrelated messengers. We speculate that low Ca(2+) may lead to increased intracellular cGMP, and/or that applied cGMP, and/or that applied cGMP may lower cytosol Ca(2+), perhaps by stimulating Ca(2+)- ATPase pumps in the outer segment.

Adaptation, Ocular↗

Constraints on adaptive evolution: the functional trade-off between reproduction and fast-start swimming performance in the Trinidadian guppy (Poecilia reticulata).

The empirical study of natural selection reveals that adaptations often involve trade-offs between competing functions. Because natural selection acts on whole organisms rather than isolated traits, adaptive evolution may be constrained by the interaction between traits that are functionally integrated. Yet, few attempts have been made to characterize how and when such constraints are manifested or whether they limit the adaptive divergence of populations. Here we examine the consequences of adaptive life-history evolution on locomotor performance in the live-bearing guppy. In response to increased predation from piscivorous fish, Trinidadian guppies evolve an increased allocation of resources toward reproduction. These populations are also under strong selection for rapid fast-start swimming performance to evade predators. Because embryo development increases a female's wet mass as she approaches parturition, an increased investment in reproductive allocation should impede fast-start performance. We find evidence for adaptive but constrained evolution of fast-start swimming performance in laboratory trials conducted on second-generation lab-reared fish. Female guppies from high-predation localities attain a faster acceleration and velocity and travel a greater distance during fast-start swimming trials. However, velocity and distance traveled decline more rapidly over the course of pregnancy in these same females, thus reducing the magnitude of divergence in swimming performance between high- and low-predation populations. This functional trade-off between reproduction and swimming performance reveals how different aspects of the phenotype are integrated and highlights the complexity of adaptation at the whole-organism level.

Adaptation, Physiological↗

On adaptive accuracy and precision in natural populations.

Adaptation is usually conceived as the fit of a population mean to a fitness optimum. Natural selection, however, does not act only to optimize the population mean. Rather, selection normally acts on the fitness of individual organisms in the population. Furthermore, individual genotypes do not produce invariant phenotypes, and their fitness depends on how precisely they are able to realize their target phenotypes. For these reasons we suggest that it is better to conceptualize adaptation as accuracy rather than as optimality. The adaptive inaccuracy of a genotype can be measured as a function of the expected distance of its associated phenotype from a fitness optimum. The less the distance, the more accurate is the adaptation. Adaptive accuracy has two components: the deviance of the genotypically set target phenotype from the optimum and the precision with which this target phenotype can be realized. The second component, the adaptive precision, has rarely been quantified as such. We survey the literature to quantify how much of the phenotypic variation in wild populations is due to imprecise development. We find that this component is often substantial and highly variable across traits. We suggest that selection for improved precision may be important for many traits.

Adaptation, Physiological↗

Internal models in sensorimotor integration: perspectives from adaptive control theory.

Internal models and adaptive controls are empirical and mathematical paradigms that have evolved separately to describe learning control processes in brain systems and engineering systems, respectively. This paper presents a comprehensive appraisal of the correlation between these paradigms with a view to forging a unified theoretical framework that may benefit both disciplines. It is suggested that the classic equilibrium-point theory of impedance control of arm movement is analogous to continuous gain-scheduling or high-gain adaptive control within or across movement trials, respectively, and that the recently proposed inverse internal model is akin to adaptive sliding control originally for robotic manipulator applications. Modular internal models' architecture for multiple motor tasks is a form of multi-model adaptive control. Stochastic methods, such as generalized predictive control, reinforcement learning, Bayesian learning and Hebbian feedback covariance learning, are reviewed and their possible relevance to motor control is discussed. Possible applicability of a Luenberger observer and an extended Kalman filter to state estimation problems-such as sensorimotor prediction or the resolution of vestibular sensory ambiguity-is also discussed. The important role played by vestibular system identification in postural control suggests an indirect adaptive control scheme whereby system states or parameters are explicitly estimated prior to the implementation of control. This interdisciplinary framework should facilitate the experimental elucidation of the mechanisms of internal models in sensorimotor systems and the reverse engineering of such neural mechanisms into novel brain-inspired adaptive control paradigms in future.

Adaptation, Physiological↗

Adaptation in iron metabolism.

Humans can adapt successfully to a wide range of iron requirements and intakes. The lower limit of the adapted state is best defined by serum ferritin greater than or equal to 12 micrograms/L, because lower values indicate that iron stores are fully depleted. Successful adaptation is achieved by modifying the rate of gastrointestinal absorption according to body iron needs. Several dietary variables, including total intake, content of heme, and bioavailability of nonheme iron, determine the ceiling of the adaptive response when iron demands are high. With lesser demands the nature of the diet has a limited influence on body iron reserves, although there is some evidence that the adaptive response to variations in heme iron intake is less complete than the response to differences in nonheme bioavailability. How the intestinal mucosal cell achieves adaptation is one of the most important unsolved questions in iron metabolism.

Adaptation, Physiological↗

Cryptic serpentine divergence and substrate adaptation of Cardamine glauca in the Balkan Peninsula.

BACKGROUND AND AIMS: Serpentine soils represent one of the most challenging substrates for plant life due to skewed ratios of essential nutrients and toxic concentrations of metals. Plant adaptation to such conditions may lead to locally adapted edaphic ecotypes or, when reproductive barriers evolve, to distinct serpentine endemics. However, a third scenario may occur: cryptic edaphic divergence, where phenotypically similar lineages adapted to contrasting substrates exhibit deep genetic divergence. Here, we tested whether substrate-associated divergence reflects repeated serpentine adaptation or cryptic edaphic lineage divergence in Cardamine glauca (Brassicaceae) in Balkan peninsula - a hotspot of serpentine endemism in Europe. METHODS: We sampled and sequenced genomes of 43 individuals of C. glauca together with four individuals representing closely related taxa, C. plumieri and C. pancicii, from variable substrates across the Balkans. We combined phylogenomics, population genomic analyses of selection and a reciprocal transplant experiment to infer the most likely evolutionary scenario. KEY RESULTS: Phylogenomic analysis of 941 loci confirmed monophyly of C. glauca, including the local endemic C. pancicii, but revealed deep splits (∼2.2-3.2 Mya) between co-occurring serpentine and non-serpentine lineages. Population genomic analyses of replicated geographically proximate serpentine-non-serpentine population pairs demonstrated strong genome-wide differentiation and limited gene flow between edaphic types. Window-based analyses of local genomic divergence and tests for positive selection revealed candidate genes involved in ion transport, membrane transporter activity and metal homeostasis, consistent with the hypothesis of substrate-driven ecological adaptation. This was further supported by a significant substrate-of-origin fitness advantage in a reciprocal transplant experiment. CONCLUSIONS: Altogether, our results demonstrate that edaphic preferences may correspond with deep genetic divergence between similar-looking yet differently adapted lineages. The presence of cryptic edaphic lineages suggests that plant diversity may still be underestimated in genomically underexplored but edaphically diverse hotspots such as the Balkans.

Cardamine glauca↗

Involvement of heme oxygenase-1 (HO-1) in the adaptive protection of human lymphocytes after hyperbaric oxygen (HBO) treatment.

Accumulating evidence suggests that HO-1 plays an important role in cellular protection against oxidant-mediated cell injury. Our previous studies on hyperbaric oxygen (HBO; i.e. exposure to pure oxygen under high ambient pressure) indicated clearly increased levels of HO-1 in lymphocytes of volunteers 24 h after HBO treatment (1 h at 1.5 bar). Experiments with the comet assay (alkaline single cell gel electrophoresis) revealed that the same cells were almost completely protected against the induction of DNA damage by a repeated exposure or in vitro treatment with H(2)O(2) 24 h after the first HBO. In order to further investigate the role of HO-1 in HBO-induced adaptive response, we now performed experiments with isolated human lymphocytes exposed to HBO in vitro (2 h at 3 bar). Our results show that also under cell culture conditions, lymphocytes exhibit an adaptive protection similar to that observed in our previous work with healthy human subjects. The time-course of HO-1 induction proceeds in parallel to the development of an adaptive protection against the induction of oxidative DNA damage. A comparable protection was not seen in V79 cells, indicating a specific difference between the two investigated cell systems. Treatment with the specific HO-1 inhibitor tin-mesoporphyrin IX (SnMP) led to a complete abrogation of HBO-induced adaptive protection in human lymphocytes. Our results indicate a functional involvement of HO-1 in the adaptive protection of human lymphocytes against the induction of oxidative DNA damage. The exact mechanism by which HO-1 contributes to an adaptive response remains to be elucidated.

Adaptation, Physiological↗

The cellular and molecular basis of odor adaptation.

An important recent advance in the understanding of odor adaptation has come from the discovery that complex mechanisms of odor adaptation already take place at the earliest stage of the olfactory system, in the olfactory cilia. At least two rapid forms and one persistent form of odor adaptation coexist in vertebrate olfactory receptor neurons. These three different adaptation phenomena can be dissected on the basis of their different onset and recovery time courses and their pharmacological properties, indicating that they are controlled, at least in part, by separate molecular mechanisms. Evidence is provided for the involvement of distinct molecular steps in these forms of odor adaptation, including Ca(2+) entry through cyclic nucleotide-gated (CNG) channels, Ca(2+)-dependent CNG channel modulation, Ca(2+)/calmodulin kinase II-dependent attenuation of adenylyl cyclase, and the activity of the carbon monoxide/cyclic GMP second messenger system. Identification of these molecular steps may help to elucidate how the olfactory system extracts temporal and intensity information and to which extent odor perception is influenced by the different mechanisms underlying adaptation.

Adaptation, Physiological↗

The G-protein gamma subunit gpc-1 of the nematode C.elegans is involved in taste adaptation.

Caenorhabditis elegans has two heterotrimeric G-protein gamma subunits, gpc-1 and gpc-2. Although GPC-1 is specifically expressed in sensory neurons, it is not essential for the detection of odorants or salts. To test whether GPC-1 is involved in sensory plasticity, we developed a water soluble compound adaptation assay. The behaviour of wild-type animals in this assay confirms that prolonged exposure to salts can abolish chemo-attraction to these compounds. This process is time and concentration dependent, partly salt specific and reversible. In contrast, gpc-1 mutant animals show clear deficits in their ability to adapt to NaAc, NaCl and NH4Cl, but normal wild-type adaptation to odorants. Two other loci previously implicated in odorant adaptation, adp-1 and osm-9, are also involved in adaptation to salts. Our finding that G proteins, OSM-9 and ADP-1 are involved in taste adaptation offer the first molecular insight into this process.

Acetates↗

Museum genomics links MC1R alleles to adaptive winter coat color polymorphism in the long-tailed weasel.

Understanding the architecture of biological adaptations is a major endeavor of evolutionary biology. Using Natural History collections, we study the genetic basis and evolution of white/brown winter coat color variation in the long-tailed weasel (Neogale frenata), a crucial phenological adaptation for camouflage in habitats with seasonal snow. We produced whole-genome sequencing data for museum specimens, along two winter color morph transition areas in North America, at the West and East coasts. Genome-wide association scans identified a single genomic region linked to color variation polymorphism with approximately 300 kb and 200 kb in the West and East regions, respectively, which included the pigmentation gene MC1R. We identified three MC1R alleles, two of which with deletions of nine or eight amino acids, alternatively associated with the winter brown morphs in the West and East, respectively. These deletions affect the second transmembrane domain, and in one case also the first extracellular loop, which in silico analyses predicted to impact the protein's function. Our findings show alternative intraspecific evolutionary solutions for environmental adaptation in long-tailed weasels, building on the evidence that major genes of the melanin production pathway are hotspots for recurrent and independent evolution of winter camouflage adaptation. This adaptive variation may be crucial to anchor adaptive responses facing future environmental change.

Receptor, Melanocortin, Type 1↗