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Sample records for adaptive response radio-protection

  1. Tissue responses to low protracted doses of high let radiations or photons - Early and late damage relevant to radio-protective countermeasures

    NASA Technical Reports Server (NTRS)

    Ainsworth, E. J.; Afzal, S. M. J.; Crouse, D. A.; Hanson, W. R.; Fry, R. J. M.

    1989-01-01

    Early and late murine tissue responses to single or fractionated low doses of heavy charged particles, fission-spectrum neutrons or gamma rays are considered. Damage to the hematopoietic system is emphasized, but results on acute lethality, host response to challenge with transplanted leukemia cells and life-shortening are presented. Recent studies on protection against early and late effects by aminothiols, prostaglandins, and other compounds are discussed.

  2. Tissue responses to low protracted doses of high LET radiations or photons: Early and late damage relevant to radio-protective countermeasures

    NASA Astrophysics Data System (ADS)

    Ainsworth, E. J.; Afzal, S. M. J.; Crouse, D. A.; Hanson, W. R.; Fry, R. J. M.

    Early and late murine tissue responses to single or fractionated low doses of heavy charged particles, fission-spectrum neutrons or gamma rays are considered. Damage to the hematopoietic system is emphasized, but results on acute lethality, host response to challenge with transplanted leukemia cells and life-shortening are presented. Low dose rates per fraction were used in some neutron experiments. Split-dose lethality studies (LD 50/30) with fission neutrons indicated greater accumulation of injury during a 9 fraction course (over 17 days) than was the case for γ-radiation. When total doses of 96 or 247 cGy of neutrons or γ rays were given as a single dose or in 9 fractions, a significant sparing effect on femur CFU-S depression was observed for both radiation qualities during the first 11 days, but there was not an earlier return to normal with dose fractionation. During the 9 fraction sequence, a significant sparing effect of low dose rate on CFU-S depression was observed in both neutron and γ-irradiated mice. CFU-S content at the end of the fractionation sequence did not correlate with measured LD 50/30. Sustained depression of femur and spleen CFU-S and a significant thrombocytopenia were observed when a total neutron dose of 240 cGy was given in 72 fractions over 24 weeks at low dose rates. The temporal aspects of CFU-S repopulation were different after a single versus fractionated neutron doses. The sustained reduction in the size of the CFU-S population was accompanied by an increase in the fraction in DNA synthesis. The proliferation characteristics and effects of age were different for radial CFU-S population closely associated with bone, compared with the axial population that can be readily aspirated from the femur. In aged irradiated animals, the CFU-S proliferation/redistribution response to typhoid vaccine showed both an age and radiation effect. After high single doses of neutrons or γ rays, a significant age- and radiation-related deficiency

  3. Tissue responses to low protracted doses of high let radiations or photons: Early and late damage relevant to radio-protective countermeasures

    SciTech Connect

    Ainsworth, E.J.; Afzal, S.M.J.; Crouse, D.A.; Hanson, W.R.; Fry, R.J.M.

    1988-01-01

    Early and late murine tissue responses to single or fractionated low doses of heavy charged particles, fission-spectrum neutrons or gamma rays are considered. Damage to the hematopoietic system is emphasized, but results on acute lethality, host response to challenge with transplanted leukemia cells and life-shortening are presented. Low dose rates per fraction were used in some neutron experiments. Split-dose lethality studies (LD 50/30) with fission neutrons indicated greater accumulation of injury during a 9 fraction course (over 17 days) than was the case for ..gamma..-radiation. When total doses of 96 or 247 cGy of neutrons or ..gamma.. rays were given as a single dose or in 9 fractions, a significant sparing effect on femur CFU-S depression was observed for both radiation qualities during the first 11 days, but there was not an earlier return to normal with dose fractionation. During the 9 fraction sequence, a significant sparing effect of low dose rate on CFU-S depression was observed in both neutron and ..gamma..-irradiated mice. CFU-S content at the end of the fractionation sequence did not correlate with measured LD 50/30. Sustained depression of femur and spleen CFU-S and a significant thrombocytopenia were observed when a total neutron dose of 240 cGy was given in 72 fractions over 24 weeks at low dose rates. The temporal aspects of CFU-S repopulation were different after a single versus fractionated neutron doses. The sustained reduction in the size of the CFU-S population was accompanied by an increase in the fraction in DNA synthesis. The proliferation characteristics and effects of age were different for radial CFU-S population closely associated with bone, compared with the axial population that can be readily aspirated from the femur. In aged irradiated animals, the CFU-S proliferation/redistribution response to typhoid vaccine showed both an age and radiation effect. 63 refs., 6 figs., 7 tabs.

  4. Adaptive response modelling

    NASA Astrophysics Data System (ADS)

    Campa, Alessandro; Esposito, Giuseppe; Belli, Mauro

    Cellular response to radiation is often modified by a previous delivery of a small "priming" dose: a smaller amount of damage, defined by the end point being investigated, is observed, and for this reason the effect is called adaptive response. An improved understanding of this effect is essential (as much as for the case of the bystander effect) for a reliable radiation risk assessment when low dose irradiations are involved. Experiments on adaptive response have shown that there are a number of factors that strongly influence the occurrence (and the level) of the adaptation. In particular, priming doses and dose rates have to fall in defined ranges; the same is true for the time interval between the delivery of the small priming dose and the irradiation with the main, larger, dose (called in this case challenging dose). Different hypotheses can be formulated on the main mechanism(s) determining the adaptive response: an increased efficiency of DNA repair, an increased level of antioxidant enzymes, an alteration of cell cycle progression, a chromatin conformation change. An experimental clearcut evidence going definitely in the direction of one of these explanations is not yet available. Modelling can be done at different levels. Simple models, relating the amount of damage, through elementary differential equations, to the dose and dose rate experienced by the cell, are relatively easy to handle, and they can be modified to account for the priming irradiation. However, this can hardly be of decisive help in the explanation of the mechanisms, since each parameter of these models often incorporates in an effective way several cellular processes related to the response to radiation. In this presentation we show our attempts to describe adaptive response with models that explicitly contain, as a dynamical variable, the inducible adaptive agent. At a price of a more difficult treatment, this approach is probably more prone to give support to the experimental studies

  5. Systematic identification of genes and transduction pathways involved in radio-adaptive response

    SciTech Connect

    Wu, Honglu

    2015-05-22

    Low doses of radiation have been shown to protect against the biological effects of later exposure to toxic levels of radiation. In this study, we propose to identify the molecular mechanisms of this adaptive response by systematically identifying the genes that play a role in radio-protection. In the original proposal, a human cell line that is well-documented to exhibit the radio-adaptive effect was to be used. In this revised study plan, we will use a mouse model, C57BL/6, which has also been well investigated for radio-adaptation. The goal of the proposed study is to enhance our understanding of cellular responses to low doses of radiation exposure at the molecular level.

  6. Human Lung Cancer Risks from Radon – Part III - Evidence of Influence of Combined Bystander and Adaptive Response Effects on Radon Case-Control Studies - A Microdose Analysis

    PubMed Central

    Leonard, Bobby E.; Thompson, Richard E.; Beecher, Georgia C.

    2012-01-01

    Since the publication of the BEIR VI (1999) report on health risks from radon, a significant amount of new data has been published showing various mechanisms that may affect the ultimate assessment of radon as a carcinogen, in particular the potentially deleterious Bystander Effect (BE) and the potentially beneficial Adaptive Response radio-protection (AR). The case-control radon lung cancer risk data of the pooled 13 European countries radon study (Darby et al 2005, 2006) and the 8 North American pooled study (Krewski et al 2005, 2006) have been evaluated. The large variation in the odds ratios of lung cancer from radon risk is reconciled, based on the large variation in geological and ecological conditions and variation in the degree of adaptive response radio-protection against the bystander effect induced lung damage. The analysis clearly shows Bystander Effect radon lung cancer induction and Adaptive Response reduction in lung cancer in some geographical regions. It is estimated that for radon levels up to about 400 Bq m−3 there is about a 30% probability that no human lung cancer risk from radon will be experienced and a 20% probability that the risk is below the zero-radon, endogenic spontaneous or perhaps even genetically inheritable lung cancer risk rate. The BEIR VI (1999) and EPA (2003) estimates of human lung cancer deaths from radon are most likely significantly excessive. The assumption of linearity of risk, by the Linear No-Threshold Model, with increasing radon exposure is invalid. PMID:22942874

  7. Adaptive Responses Limited by Intrinsic Noise

    PubMed Central

    Shankar, Prabhat; Nishikawa, Masatoshi; Shibata, Tatsuo

    2015-01-01

    Sensory systems have mechanisms to respond to the external environment and adapt to them. Such adaptive responses are effective for a wide dynamic range of sensing and perception of temporal change in stimulus. However, noise generated by the adaptation system itself as well as extrinsic noise in sensory inputs may impose a limit on the ability of adaptation systems. The relation between response and noise is well understood for equilibrium systems in the form of fluctuation response relation. However, the relation for nonequilibrium systems, including adaptive systems, are poorly understood. Here, we systematically explore such a relation between response and fluctuation in adaptation systems. We study the two network motifs, incoherent feedforward loops (iFFL) and negative feedback loops (nFBL), that can achieve perfect adaptation. We find that the response magnitude in adaption systems is limited by its intrinsic noise, implying that higher response would have higher noise component as well. Comparing the relation of response and noise in iFFL and nFBL, we show that whereas iFFL exhibits adaptation over a wider parameter range, nFBL offers higher response to noise ratio than iFFL. We also identify the condition that yields the upper limit of response for both network motifs. These results may explain the reason of why nFBL seems to be more abundant in nature for the implementation of adaption systems. PMID:26305221

  8. Response-Adaptive Allocation for Circular Data.

    PubMed

    Biswas, Atanu; Dutta, Somak; Laha, Arnab Kumar; Bakshi, Partho K

    2015-01-01

    Response-adaptive designs are used in phase III clinical trials to allocate a larger proportion of patients to the better treatment. Circular data is a natural outcome in many clinical trial setup, e.g., some measurements in opthalmologic studies, degrees of rotation of hand or waist, etc. There is no available work on response-adaptive designs for circular data. With reference to a dataset on cataract surgery we provide some response-adaptive designs where the responses are of circular nature and propose some test statistics for treatment comparison under adaptive data allocation procedure. Detailed simulation study and the analysis of the dataset, including redesigning the cataract surgery data, are carried out.

  9. Mechanisms of radio-protection by catecholamines in the hamster /Mesocricetus auratus/

    NASA Technical Reports Server (NTRS)

    Prewitt, R. L.; Musacchia, X. J.

    1975-01-01

    Experiments were conducted on normal and splenectomized male and female hamsters between 2 and 3 months old subjected to a whole-body exposure of 1000 or 2000 rads in a Co-60 source with a view toward evaluating their radio-protection by norepinephrine, isoproterenol, and phenylephrine. Vasoconstriction hypoxia mechanism of radio-protection is examined along with the hypothesis that isoproterenol protects by hypercalcemia-induced cell proliferation. Radiation experiment results are found to be consistent with the hypothesis that stimulation of alpha receptors results in radio-protection through a tissue hypoxia mechanism. Beta agonists seem to protect by a hypotensive-hypoxia mechanism. The catecholamines protect against the hematopoietic syndrome, but show no evidence of protection against the gastrointestinal syndrome.

  10. Monitoring adaptive genetic responses to environmental change.

    PubMed

    Hansen, Michael M; Olivieri, Isabelle; Waller, Donald M; Nielsen, Einar E

    2012-03-01

    Widespread environmental changes including climate change, selective harvesting and landscape alterations now greatly affect selection regimes for most organisms. How animals and plants can adapt to these altered environments via contemporary evolution is thus of strong interest. We discuss how to use genetic monitoring to study adaptive responses via repeated analysis of the same populations over time, distinguishing between phenotypic and molecular genetics approaches. After describing monitoring designs, we develop explicit criteria for demonstrating adaptive responses, which include testing for selection and establishing clear links between genetic and environmental change. We then review a few exemplary studies that explore adaptive responses to climate change in Drosophila, selective responses to hunting and fishing, and contemporary evolution in Daphnia using resurrected resting eggs. We further review a broader set of 44 studies to assess how well they meet the proposed criteria, and conclude that only 23% fulfill all criteria. Approximately half (43%) of these studies failed to rule out the alternative hypothesis of replacement by a different, better-adapted population. Likewise, 34% of the studies based on phenotypic variation did not test for selection as opposed to drift. These shortcomings can be addressed via improved experimental designs and statistical testing. We foresee monitoring of adaptive responses as a future valuable tool in conservation biology, for identifying populations unable to evolve at sufficiently high rates and for identifying possible donor populations for genetic rescue. Technological advances will further augment the realization of this potential, especially next-generation sequencing technologies that allow for monitoring at the level of whole genomes.

  11. Response-adaptive regression for longitudinal data.

    PubMed

    Wu, Shuang; Müller, Hans-Georg

    2011-09-01

    We propose a response-adaptive model for functional linear regression, which is adapted to sparsely sampled longitudinal responses. Our method aims at predicting response trajectories and models the regression relationship by directly conditioning the sparse and irregular observations of the response on the predictor, which can be of scalar, vector, or functional type. This obliterates the need to model the response trajectories, a task that is challenging for sparse longitudinal data and was previously required for functional regression implementations for longitudinal data. The proposed approach turns out to be superior compared to previous functional regression approaches in terms of prediction error. It encompasses a variety of regression settings that are relevant for the functional modeling of longitudinal data in the life sciences. The improved prediction of response trajectories with the proposed response-adaptive approach is illustrated for a longitudinal study of Kiwi weight growth and by an analysis of the dynamic relationship between viral load and CD4 cell counts observed in AIDS clinical trials. PMID:21133880

  12. Adaptive immune responses to Candida albicans infection.

    PubMed

    Richardson, Jonathan P; Moyes, David L

    2015-01-01

    Fungal infections are becoming increasingly prevalent in the human population and contribute to morbidity and mortality in healthy and immunocompromised individuals respectively. Candida albicans is the most commonly encountered fungal pathogen of humans, and is frequently found on the mucosal surfaces of the body. Host defense against C. albicans is dependent upon a finely tuned implementation of innate and adaptive immune responses, enabling the host to neutralise the invading fungus. Central to this protection are the adaptive Th1 and Th17 cellular responses, which are considered paramount to successful immune defense against C. albicans infections, and enable tissue homeostasis to be maintained in the presence of colonising fungi. This review will highlight the recent advances in our understanding of adaptive immunity to Candida albicans infections.

  13. Adaptive neural control of aeroelastic response

    NASA Astrophysics Data System (ADS)

    Lichtenwalner, Peter F.; Little, Gerald R.; Scott, Robert C.

    1996-05-01

    The Adaptive Neural Control of Aeroelastic Response (ANCAR) program is a joint research and development effort conducted by McDonnell Douglas Aerospace (MDA) and the National Aeronautics and Space Administration, Langley Research Center (NASA LaRC) under a Memorandum of Agreement (MOA). The purpose of the MOA is to cooperatively develop the smart structure technologies necessary for alleviating undesirable vibration and aeroelastic response associated with highly flexible structures. Adaptive control can reduce aeroelastic response associated with buffet and atmospheric turbulence, it can increase flutter margins, and it may be able to reduce response associated with nonlinear phenomenon like limit cycle oscillations. By reducing vibration levels and loads, aircraft structures can have lower acquisition cost, reduced maintenance, and extended lifetimes. Phase I of the ANCAR program involved development and demonstration of a neural network-based semi-adaptive flutter suppression system which used a neural network for scheduling control laws as a function of Mach number and dynamic pressure. This controller was tested along with a robust fixed-gain control law in NASA's Transonic Dynamics Tunnel (TDT) utilizing the Benchmark Active Controls Testing (BACT) wing. During Phase II, a fully adaptive on-line learning neural network control system has been developed for flutter suppression which will be tested in 1996. This paper presents the results of Phase I testing as well as the development progress of Phase II.

  14. Regulated cell death and adaptive stress responses.

    PubMed

    Galluzzi, Lorenzo; Bravo-San Pedro, José Manuel; Kepp, Oliver; Kroemer, Guido

    2016-06-01

    Eukaryotic cells react to potentially dangerous perturbations of the intracellular or extracellular microenvironment by activating rapid (transcription-independent) mechanisms that attempt to restore homeostasis. If such perturbations persist, cells may still try to cope with stress by activating delayed and robust (transcription-dependent) adaptive systems, or they may actively engage in cellular suicide. This regulated form of cell death can manifest with various morphological, biochemical and immunological correlates, and constitutes an ultimate attempt of stressed cells to maintain organismal homeostasis. Here, we dissect the general organization of adaptive cellular responses to stress, their intimate connection with regulated cell death, and how the latter operates for the preservation of organismal homeostasis.

  15. Radio protective effects of the Ayurvedic medicinal plant Ocimum sanctum Linn. (Holy Basil): A memoir.

    PubMed

    Baliga, Manjeshwar Shrinath; Rao, Suresh; Rai, Manoj P; D'souza, Prema

    2016-01-01

    The use of compounds which can selectively protect normal tissues against radiation injury is of immense use because in addition to it protecting the normal tissue, will also permits use of higher doses of radiation to obtain better cancer control and possible cure. However, most of the radio protective compounds investigated possess inadequate clinical application principally due to their inherent systemic toxicity at their optimal protective concentrations. Plants commonly used as medicinal and dietary agents have recently been the focus of attention and studies have shown that Ocimum sanctum Linn. commonly known as the Holy Basil and its water soluble flavonoids, orientin and vicenin protects experimental animals against the radiation-induced sickness and mortality at nontoxic concentrations. Studies with tumor bearing mice have also shown that both Tulsi extract and its flavonoids selectively protect the normal tissues against the tumoricidal effects of radiation. Preclinical studies have also shown that the aqueous extract of the Tulsi leaves; its flavanoids orientin and vicenin, and eugenol, the principal nonpolar constituent present in Tulsi prevent radiation-induced clastogenesis. Mechanistic studies have indicated that free radical scavenging, antioxidant, metal chelating and anti-inflammatory effects may contribute toward the observed protection. In addition, clinical studies with a small number of patients have shown that Tulsi was effective as a radio protective agent. This review summarizes the results related to the radio protective properties of Tulsi and its phytochemicals and also emphasizes the aspects that warrant future research to establish its use as a radio protective agent. PMID:27072205

  16. [Radio protective drug production from fresh leaves of Aloe arborescens Mill].

    PubMed

    Bakuridze, A Dzh; Nikolaev, S M; Berashvili, D T; Bakuridze, K A; Tsomaia, I V

    2009-06-01

    Nowadays, phytogenous drugs are wildly used as radio protective substances. The aim of the research was to study radio protective characteristics of aloe juice fraction and to develop new technology for radio protective drug production. Technological scheme for getting the drug in two stages. The first stage - extraction of juice from fresh leaves; the second stage - extracting bagasse have been developed and optimal environment for bagasse extraction are defined: Infusion of bagasse with 96 % ethyl spirit (1:1) during 30 minutes, continuation of extracting with water on correlation to raw materials 10:1 at temperature of 70 degrees C during 30 minutes. For the basis of the first series of balanced loading there are taken the optimal parameters of extracting process, on the basis of which in its turn was developed technological scheme of getting dry extract of aloe. Dry extract is a fine-dispersed reddish-yellow (brownish-yellow) powder, which can be easily dissolved in warm (40-60 degrees C) water. Pharmacological researches were conducted in the Institute of General and Experimental Biology, Siberian Branch, Russian. Academy of Sciences. The remarkable radio protective effect of the drug was revealed.

  17. The Adaptive Calibration Model of stress responsivity

    PubMed Central

    Ellis, Bruce J.; Shirtcliff, Elizabeth A.

    2010-01-01

    This paper presents the Adaptive Calibration Model (ACM), an evolutionary-developmental theory of individual differences in the functioning of the stress response system. The stress response system has three main biological functions: (1) to coordinate the organism’s allostatic response to physical and psychosocial challenges; (2) to encode and filter information about the organism’s social and physical environment, mediating the organism’s openness to environmental inputs; and (3) to regulate the organism’s physiology and behavior in a broad range of fitness-relevant areas including defensive behaviors, competitive risk-taking, learning, attachment, affiliation and reproductive functioning. The information encoded by the system during development feeds back on the long-term calibration of the system itself, resulting in adaptive patterns of responsivity and individual differences in behavior. Drawing on evolutionary life history theory, we build a model of the development of stress responsivity across life stages, describe four prototypical responsivity patterns, and discuss the emergence and meaning of sex differences. The ACM extends the theory of biological sensitivity to context (BSC) and provides an integrative framework for future research in the field. PMID:21145350

  18. Resistance Training: Physiological Responses and Adaptations (Part 3 of 4).

    ERIC Educational Resources Information Center

    Fleck, Steven J.; Kraemer, William J.

    1988-01-01

    The physiological responses and adaptations which occur as a result of resistance training, such as cardiovascular responses, serum lipid count, body composition, and neural adaptations are discussed. Changes in the endocrine system are also described. (JL)

  19. Is the bitter rejection response always adaptive?

    PubMed

    Glendinning, J I

    1994-12-01

    The bitter rejection response consists of a suite of withdrawal reflexes and negative affective responses. It is generally assumed to have evolved as a way to facilitate avoidance of foods that are poisonous because they usually taste bitter to humans. Using previously published studies, the present paper examines the relationship between bitterness and toxicity in mammals, and then assesses the ecological costs and benefits of the bitter rejection response in carnivorous, omnivorous, and herbivorous (grazing and browsing) mammals. If the bitter rejection response accurately predicts the potential toxicity of foods, then one would expect the threshold for the response to be lower for highly toxic compounds than for nontoxic compounds. The data revealed no such relationship. Bitter taste thresholds varied independently of toxicity thresholds, indicating that the bitter rejection response is just as likely to be elicited by a harmless bitter food as it is by a harmful one. Thus, it is not necessarily in an animal's best interest to have an extremely high or low bitter threshold. Based on this observation, it was hypothesized that the adaptiveness of the bitter rejection response depends upon the relative occurrence of bitter and potentially toxic compounds in an animal's diet. Animals with a relatively high occurrence of bitter and potentially toxic compounds in their diet (e.g., browsing herbivores) were predicted to have evolved a high bitter taste threshold and tolerance to dietary poisons. Such an adaptation would be necessary because a browser cannot "afford" to reject all foods that are bitter and potentially toxic without unduly restricting its dietary options. At the other extreme, animals that rarely encounter bitter and potentially toxic compounds in their diet (e.g., carnivores) were predicted to have evolved a low bitter threshold. Carnivores could "afford" to utilize such a stringent rejection mechanism because foods containing bitter and potentially

  20. Is the bitter rejection response always adaptive?

    PubMed

    Glendinning, J I

    1994-12-01

    The bitter rejection response consists of a suite of withdrawal reflexes and negative affective responses. It is generally assumed to have evolved as a way to facilitate avoidance of foods that are poisonous because they usually taste bitter to humans. Using previously published studies, the present paper examines the relationship between bitterness and toxicity in mammals, and then assesses the ecological costs and benefits of the bitter rejection response in carnivorous, omnivorous, and herbivorous (grazing and browsing) mammals. If the bitter rejection response accurately predicts the potential toxicity of foods, then one would expect the threshold for the response to be lower for highly toxic compounds than for nontoxic compounds. The data revealed no such relationship. Bitter taste thresholds varied independently of toxicity thresholds, indicating that the bitter rejection response is just as likely to be elicited by a harmless bitter food as it is by a harmful one. Thus, it is not necessarily in an animal's best interest to have an extremely high or low bitter threshold. Based on this observation, it was hypothesized that the adaptiveness of the bitter rejection response depends upon the relative occurrence of bitter and potentially toxic compounds in an animal's diet. Animals with a relatively high occurrence of bitter and potentially toxic compounds in their diet (e.g., browsing herbivores) were predicted to have evolved a high bitter taste threshold and tolerance to dietary poisons. Such an adaptation would be necessary because a browser cannot "afford" to reject all foods that are bitter and potentially toxic without unduly restricting its dietary options. At the other extreme, animals that rarely encounter bitter and potentially toxic compounds in their diet (e.g., carnivores) were predicted to have evolved a low bitter threshold. Carnivores could "afford" to utilize such a stringent rejection mechanism because foods containing bitter and potentially

  1. Radio-protective effect of some new curcumin analogues.

    PubMed

    El-Gazzar, Marwa G; Zaher, Nashwa H; El-Hossary, Ebaa M; Ismail, Amel F M

    2016-09-01

    In the present study, novel symmetrical curcumin analogues (2-7) have been synthesized by substituting the phenolic OH of curcumin with different linkers providing additional keto-enol tautomerism, very essential for radioprotective activity. The structures of the synthesized compounds (2-7) were elucidated by elemental analysis, IR, (1)H-NMR, (13)C-NMR and mass spectral data and were found consistent with the assigned structures. The curative effect of these new compounds, against the oxidative stress due to exposure of rats to the whole body γ-irradiation (7Gy) was investigated. Gamma-irradiated rats exhibited elevations of ALT, AST activities, urea, creatinine, triglycerides, total cholesterol, malondialdehyde (MDA), nitric oxide (NO), Interleukin-6 (IL-6), Tumor Necrosis Factor-α (TNF-α) and Nuclear Factor-kappa B (NF-κB) levels. Contrariwise, the total protein, albumin, total calcium level, SOD, CAT, GSH-Px, GST activities and GSH content were decreased. Treatment of gamma-irradiated rats with the new curcumin analogues (2-7) showed significant amelioration in the in-vivo antioxidant status, liver and kidney functions, as well as the anti-inflammatory markers (IL-6, TNF-α and NF-κB). Inhibition of NF-κB could be responsible for the improvement of the antioxidant and anti-inflammatory status in gamma-irradiated animals, by down-regulation of IL-1β and TNF-α level. In conclusion, the new curcumin analogues (2-7) exhibited post-protective effect on gamma-irradiation, by NF-κB inhibition. PMID:27505300

  2. Improving Adaptive Learning Technology through the Use of Response Times

    ERIC Educational Resources Information Center

    Mettler, Everett; Massey, Christine M.; Kellman, Philip J.

    2011-01-01

    Adaptive learning techniques have typically scheduled practice using learners' accuracy and item presentation history. We describe an adaptive learning system (Adaptive Response Time Based Sequencing--ARTS) that uses both accuracy and response time (RT) as direct inputs into sequencing. Response times are used to assess learning strength and…

  3. Green light signaling and adaptive response

    PubMed Central

    Zhang, Tingting; Folta, Kevin M.

    2012-01-01

    To a plant, the sun’s light is not exclusively energy for photosynthesis, it also provides a package of data about time and prevailing conditions. The plant’s surroundings may dampen or filter solar energies, altering spectral profiles of their light environment. Plants use this information to adjust form and physiology, tailoring gene expression to best match ambient conditions. Extensive literature exists on how blue, red and far-red light contribute to plant adaptive responses. A growing body of work identifies discrete effects of green light (500–565 nm) that also shape plant biology. Green light responses are known to be either mediated through, or independent of, the cryptochrome blue light receptors. Responses to green light share a general tendency to oppose blue- or red-light-induced responses, including stem growth rate inhibition, anthocyanin accumulation or chloroplast gene expression. Recent evidence demonstrates a role for green light in sensing a shaded environment, independent from far-red shade responses. PMID:22301972

  4. Local adaptation in transgenerational responses to predators.

    PubMed

    Walsh, Matthew R; Castoe, Todd; Holmes, Julian; Packer, Michelle; Biles, Kelsey; Walsh, Melissa; Munch, Stephan B; Post, David M

    2016-01-27

    Environmental signals can induce phenotypic changes that span multiple generations. Along with phenotypic responses that occur during development (i.e. 'within-generation' plasticity), such 'transgenerational plasticity' (TGP) has been documented in a diverse array of taxa spanning many environmental perturbations. New theory predicts that temporal stability is a key driver of the evolution of TGP. We tested this prediction using natural populations of zooplankton from lakes in Connecticut that span a large gradient in the temporal dynamics of predator-induced mortality. We reared more than 120 clones of Daphnia ambigua from nine lakes for multiple generations in the presence/absence of predator cues. We found that temporal variation in mortality selects for within-generation plasticity while consistently strong (or weak) mortality selects for increased TGP. Such results provide us the first evidence for local adaptation in TGP and argue that divergent ecological conditions select for phenotypic responses within and across generations. PMID:26817775

  5. Covariate-adjusted response-adaptive designs for binary response.

    PubMed

    Rosenberger, W F; Vidyashankar, A N; Agarwal, D K

    2001-11-01

    An adaptive allocation design for phase III clinical trials that incorporates covariates is described. The allocation scheme maps the covariate-adjusted odds ratio from a logistic regression model onto [0, 1]. Simulations assume that both staggered entry and time to response are random and follow a known probability distribution that can depend on the treatment assigned, the patient's response, a covariate, or a time trend. Confidence intervals on the covariate-adjusted odds ratio is slightly anticonservative for the adaptive design under the null hypothesis, but power is similar to equal allocation under various alternatives for n = 200. For similar power, the net savings in terms of expected number of treatment failures is modest, but enough to make this design attractive for certain studies where known covariates are expected to be important and stratification is not desired, and treatment failures have a high ethical cost.

  6. Plant Cell Adaptive Responses to Microgravity

    NASA Astrophysics Data System (ADS)

    Kordyum, Elizabeth; Kozeko, Liudmyla; Talalaev, Alexandr

    simulated microgravity and temperature elevation have different effects on the small HSP genes belonging to subfamilies with different subcellular localization: cytosol/nucleus - PsHSP17.1-СІІ and PsHSP18.1-СІ, cloroplasts - PsHSP26.2-Cl, endoplasmatic reticulum - PsHSP22.7-ER and mitochondria - PsHSP22.9-M: unlike high temperature, clinorotation does not cause denaturation of cell proteins, that confirms the sHSP chaperone function. Dynamics of investigated gene expression in pea seedlings growing 5 days after seed germination under clinorotation was similar to that in the stationary control. Similar patterns in dynamics of sHSP gene expression in the stationary control and under clinorotation may be one of mechanisms providing plant adaptation to simulated microgravity. It is pointed that plant cell responses in microgravity and under clinorotation vary according to growth phase, physiological state, and taxonomic position of the object. At the same time, the responses have, to some degree, a similar character reflecting the changes in cell organelle functional load. Thus, next certain changes in the structure and function of plant cells may be considered as adaptive: 1) an increase in the unsaturated fatty acid content in the plasmalemma, 2) rearrangements of organelle ultrastructure and an increase in their functional load, 3) an increase in cortical F-actin under destabilization of tubulin microtubules, 4) the level of gene expression and synthesis of heat shock proteins, 5) alterations of the enzyme and antioxidant system activity. The dynamics of these patterns demonstrated that the adaptation occurs on the principle of self-regulating systems in the limits of physiological norm reaction. The very importance of changed expression of genes involved in different cellular processes, especially HSP genes, in cell adaptation to altered gravity is discussed.

  7. Radio-Adaptive Responses of Mouse Myocardiocytes

    NASA Technical Reports Server (NTRS)

    Seawright, John W.; Westby, Christian M.

    2011-01-01

    One of the most significant occupational hazards to an astronaut is the frequent exposure to radiation. Commonly associated with increased risk for cancer related morbidity and mortality, radiation is also known to increase the risk for cardiovascular related disorders including: pericarditis, hypertension, and heart failure. It is believed that these radiation-induced disorders are a result of abnormal tissue remodeling. It is unknown whether radiation exposure promotes remodeling through fibrotic changes alone or in combination with programmed cell death. Furthermore, it is not known whether it is possible to mitigate the hazardous effects of radiation exposure. As such, we assessed the expression and mechanisms of radiation-induced tissue remodeling and potential radio-adaptive responses of p53-mediated apoptosis and fibrosis pathways along with markers for oxidative stress and inflammation in mice myocardium. 7 week old, male, C57Bl/6 mice were exposed to 6Gy (H) or 5cGy followed 24hr later with 6Gy (LH) Cs-137 gamma radiation. Mice were sacrificed and their hearts extirpated 4, 24, or 72hr after final irradiation. Real Time - Polymerase Chain Reaction was used to evaluate target genes. Pro-apoptotic genes Bad and Bax, pro-cell survival genes Bcl2 and Bcl2l2, fibrosis gene Vegfa, and oxidative stress genes Sod2 and GPx4 showed a reduced fold regulation change (Bad,-6.18; Bax,-6.94; Bcl2,-5.09; Bcl2l2,-4.03; Vegfa, -11.84; Sod2,-5.97; GPx4*,-28.72; * = Bonferroni adjusted p-value . 0.003) 4hr after H, but not after 4hr LH when compared to control. Other p53-mediated apoptosis genes Casp3, Casp9, Trp53, and Myc exhibited down-regulation but did not achieve a notable level of significance 4hr after H. 24hr after H, genetic down-regulation was no longer present compared to 24hr control. These data suggest a general reduction in genetic expression 4hrs after a high dose of gamma radiation. However, pre-exposure to 5cGy gamma radiation appears to facilitate a radio-adaptive

  8. Adaptation of health care for migrants: whose responsibility?

    PubMed Central

    2014-01-01

    Background In a context of increasing ethnic diversity, culturally competent strategies have been recommended to improve care quality and access to health care for ethnic minorities and migrants; their implementation by health professionals, however, has remained patchy. Most programs of cultural competence assume that health professionals accept that they have a responsibility to adapt to migrants, but this assumption has often remained at the level of theory. In this paper, we surveyed health professionals’ views on their responsibility to adapt. Methods Five hundred-and-sixty-nine health professionals from twenty-four inpatient and outpatient health services were selected according to their geographic location. All health care professionals were requested to complete a questionnaire about who should adapt to ethnic diversity: health professionals or patients. After a factorial analysis to identify the underlying responsibility dimensions, we performed a multilevel regression model in order to investigate individual and service covariates of responsibility attribution. Results Three dimensions emerged from the factor analysis: responsibility for the adaptation of communication, responsibility for the adaptation to the negotiation of values, and responsibility for the adaptation to health beliefs. Our results showed that the sense of responsibility for the adaptation of health care depended on the nature of the adaptation required: when the adaptation directly concerned communication with the patient, health professionals declared that they should be the ones to adapt; in relation to cultural preferences, however, the responsibility felt on the patient’s shoulders. Most respondents were unclear in relation to adaptation to health beliefs. Regression indicated that being Belgian, not being a physician, and working in a primary-care service were associated with placing the burden of responsibility on the patient. Conclusions Health care professionals do not

  9. Linear ubiquitination signals in adaptive immune responses

    PubMed Central

    Ikeda, Fumiyo

    2015-01-01

    Summary Ubiquitin can form eight different linkage types of chains using the intrinsic Met 1 residue or one of the seven intrinsic Lys residues. Each linkage-type of ubiquitin chain has a distinct three-dimensional topology, functioning as a tag to attract specific signaling molecules, which are so-called ubiquitin readers, and regulates various biological functions. Ubiquitin chains linked via Met 1 in a head-to-tail manner are called linear ubiquitin chains. Linear ubiquitination plays an important role in the regulation of cellular signaling, including the best-characterized Tumor Necrosis Factor (TNF) -induced canonical nuclear factor-kappa B (NF-κB) pathway. Linear ubiquitin chains are specifically generated by an E3 ligase complex called the linear ubiquitin chain assembly complex (LUBAC) and hydrolyzed by a deubiquitinase (DUB) called ovarian tumor (OTU) DUB with linear linkage specificity (OTULIN). LUBAC linearly ubiquitinates critical molecules in the TNF pathway, such as NEMO and RIPK1. The linear ubiquitin chains are then recognized by the ubiquitin readers, including NEMO, which control the TNF pathway. Accumulating evidence indicates an importance of the LUBAC complex in the regulation of apoptosis, development, and inflammation in mice. In this article, I focus on the role of linear ubiquitin chains in adaptive immune responses with an emphasis on the TNF-induced signaling pathways. PMID:26085218

  10. Bayesian response adaptive randomization using longitudinal outcomes.

    PubMed

    Hatayama, Tomoyoshi; Morita, Satoshi; Sakamaki, Kentaro

    2015-01-01

    The response adaptive randomization (RAR) method is used to increase the number of patients assigned to more efficacious treatment arms in clinical trials. In many trials evaluating longitudinal patient outcomes, RAR methods based only on the final measurement may not benefit significantly from RAR because of its delayed initiation. We propose a Bayesian RAR method to improve RAR performance by accounting for longitudinal patient outcomes (longitudinal RAR). We use a Bayesian linear mixed effects model to analyze longitudinal continuous patient outcomes for calculating a patient allocation probability. In addition, we aim to mitigate the loss of statistical power because of large patient allocation imbalances by embedding adjusters into the patient allocation probability calculation. Using extensive simulation we compared the operating characteristics of our proposed longitudinal RAR method with those of the RAR method based only on the final measurement and with an equal randomization method. Simulation results showed that our proposed longitudinal RAR method assigned more patients to the presumably superior treatment arm compared with the other two methods. In addition, the embedded adjuster effectively worked to prevent extreme patient allocation imbalances. However, our proposed method may not function adequately when the treatment effect difference is moderate or less, and still needs to be modified to deal with unexpectedly large departures from the presumed longitudinal data model.

  11. How Language Supports Adaptive Teaching through a Responsive Learning Culture

    ERIC Educational Resources Information Center

    Johnston, Peter; Dozier, Cheryl; Smit, Julie

    2016-01-01

    For students to learn optimally, teachers must design classrooms that are responsive to the full range of student development. The teacher must be adaptive, but so must each student and the learning culture itself. In other words, adaptive teaching means constructing a responsive learning culture that accommodates and even capitalizes on diversity…

  12. A Sharing Item Response Theory Model for Computerized Adaptive Testing

    ERIC Educational Resources Information Center

    Segall, Daniel O.

    2004-01-01

    A new sharing item response theory (SIRT) model is presented that explicitly models the effects of sharing item content between informants and test takers. This model is used to construct adaptive item selection and scoring rules that provide increased precision and reduced score gains in instances where sharing occurs. The adaptive item selection…

  13. Using Response Times for Item Selection in Adaptive Testing

    ERIC Educational Resources Information Center

    van der Linden, Wim J.

    2008-01-01

    Response times on items can be used to improve item selection in adaptive testing provided that a probabilistic model for their distribution is available. In this research, the author used a hierarchical modeling framework with separate first-level models for the responses and response times and a second-level model for the distribution of the…

  14. Exposure to stressful environments - Strategy of adaptive responses

    NASA Technical Reports Server (NTRS)

    Farhi, Leon E.

    1991-01-01

    Stresses such as hypoxia, water lack, and heat exposure can produce strains in more than a single organ system, in turn stimulating the body to adapt in multiple ways. Nevertheless, a general strategy of the various adaptive responses emerges when the challenges are divided into three groups: (1) conditions that affect the supply of essential molecules, (2) stresses that prevent the body from regulating properly the output of waste products such as CO2 and heat, and (3) environments that disrupt body transport systems. Problems may arise when there is a conflict between two stresses requiring conflicting adaptive changes. An alternative to adaptation, creation of microenvironment, is often favored by the animal.

  15. How Neutrophils Shape Adaptive Immune Responses

    PubMed Central

    Leliefeld, Pieter H. C.; Koenderman, Leo; Pillay, Janesh

    2015-01-01

    Neutrophils are classically considered as cells pivotal for the first line of defense against invading pathogens. In recent years, evidence has accumulated that they are also important in the orchestration of adaptive immunity. Neutrophils rapidly migrate in high numbers to sites of inflammation (e.g., infection, tissue damage, and cancer) and are subsequently able to migrate to draining lymph nodes (LNs). Both at the site of inflammation as well as in the LNs, neutrophils can engage with lymphocytes and antigen-presenting cells. This crosstalk occurs either directly via cell–cell contact or via mediators, such as proteases, cytokines, and radical oxygen species. In this review, we will discuss the current knowledge regarding locations and mechanisms of interaction between neutrophils and lymphocytes in the context of homeostasis and various pathological conditions. In addition, we will highlight the complexity of the microenvironment that is involved in the generation of suppressive or stimulatory neutrophil phenotypes. PMID:26441976

  16. How Neutrophils Shape Adaptive Immune Responses.

    PubMed

    Leliefeld, Pieter H C; Koenderman, Leo; Pillay, Janesh

    2015-01-01

    Neutrophils are classically considered as cells pivotal for the first line of defense against invading pathogens. In recent years, evidence has accumulated that they are also important in the orchestration of adaptive immunity. Neutrophils rapidly migrate in high numbers to sites of inflammation (e.g., infection, tissue damage, and cancer) and are subsequently able to migrate to draining lymph nodes (LNs). Both at the site of inflammation as well as in the LNs, neutrophils can engage with lymphocytes and antigen-presenting cells. This crosstalk occurs either directly via cell-cell contact or via mediators, such as proteases, cytokines, and radical oxygen species. In this review, we will discuss the current knowledge regarding locations and mechanisms of interaction between neutrophils and lymphocytes in the context of homeostasis and various pathological conditions. In addition, we will highlight the complexity of the microenvironment that is involved in the generation of suppressive or stimulatory neutrophil phenotypes. PMID:26441976

  17. Incorporating adaptive responses into future projections of coral bleaching.

    PubMed

    Logan, Cheryl A; Dunne, John P; Eakin, C Mark; Donner, Simon D

    2014-01-01

    Climate warming threatens to increase mass coral bleaching events, and several studies have projected the demise of tropical coral reefs this century. However, recent evidence indicates corals may be able to respond to thermal stress though adaptive processes (e.g., genetic adaptation, acclimatization, and symbiont shuffling). How these mechanisms might influence warming-induced bleaching remains largely unknown. This study compared how different adaptive processes could affect coral bleaching projections. We used the latest bias-corrected global sea surface temperature (SST) output from the NOAA/GFDL Earth System Model 2 (ESM2M) for the preindustrial period through 2100 to project coral bleaching trajectories. Initial results showed that, in the absence of adaptive processes, application of a preindustrial climatology to the NOAA Coral Reef Watch bleaching prediction method overpredicts the present-day bleaching frequency. This suggests that corals may have already responded adaptively to some warming over the industrial period. We then modified the prediction method so that the bleaching threshold either permanently increased in response to thermal history (e.g., simulating directional genetic selection) or temporarily increased for 2-10 years in response to a bleaching event (e.g., simulating symbiont shuffling). A bleaching threshold that changes relative to the preceding 60 years of thermal history reduced the frequency of mass bleaching events by 20-80% compared with the 'no adaptive response' prediction model by 2100, depending on the emissions scenario. When both types of adaptive responses were applied, up to 14% more reef cells avoided high-frequency bleaching by 2100. However, temporary increases in bleaching thresholds alone only delayed the occurrence of high-frequency bleaching by ca. 10 years in all but the lowest emissions scenario. Future research should test the rate and limit of different adaptive responses for coral species across latitudes and

  18. Plasticity versus Adaptation of Ambient-Temperature Flowering Response.

    PubMed

    Pajoro, Alice; Verhage, Leonie; Immink, Richard G H

    2016-01-01

    It is challenging to understand how plants adapt flowering time to novel environmental conditions, such as global warming, while maintaining plasticity in response to daily fluctuating temperatures. A recent study shows a role for transposons and highlights the need to investigate how these different responses evolved. PMID:26698930

  19. Plasticity versus Adaptation of Ambient-Temperature Flowering Response.

    PubMed

    Pajoro, Alice; Verhage, Leonie; Immink, Richard G H

    2016-01-01

    It is challenging to understand how plants adapt flowering time to novel environmental conditions, such as global warming, while maintaining plasticity in response to daily fluctuating temperatures. A recent study shows a role for transposons and highlights the need to investigate how these different responses evolved.

  20. Intracellular recordings of rod responses during dark-adaptation.

    PubMed Central

    Grabowski, S R; Pak, W L

    1975-01-01

    1. Dark-adaptation of rod photoreceptors has been studied in the isolated axolotl (Ambystoma mexicanum) retina by intracellular recordings. Rod responsiveness was greatly reduced immediately after a 30 sec partial bleach, but partially recovered with time in the dark. 2. In parallel spectrophotometric measurements using isolated retinas, regeneration of the rod pigment could not be detected after a 30 sec bleach. 3. During rod dark-adaptation, the response of a rod to a given stimulus increased in amplitude, duration, and rate of rise but did not recover completely to the dark-adapted values. Response latency was lengthened immediately after a bleach but ultimately returned to the dark-adapted level. 4. The time courses of dark-adaptation determined on the basis of the intensity of a stimulus needed to evoke a response having a criterion amplitude, a criterion duration, or a criterion rate of rise were similar. On the other hand changes in latency of the response and magnitude of the saturated amplitude followed different time courses. Change in log threshold was found to be related to change in saturated amplitude by an exponential function during dark-adaptation. 5. After bleaching 10% or less of the rod pigment, the kinetics of both recovery of log threshold and decrease in absorbance at 400 nm (metarhodopsin II+free retinal) could be described by two concurrent first-order processes having similar time constants. However, after bleaching more than 10% of the rod pigment, changes in sensitivity and absorbance did not follow parallel time courses. 6. Metarhodopsin III cannot be solely responsible for setting the axolotl rod sensitivity since rod thresholds decrease monotonically during dark-adaptation whereas meta III concentration reaches a peak 3 min after the bleach and decreases thereafter. PMID:1151778

  1. Exposure to Stressful Environments: Strategy of Adaptive Responses

    NASA Technical Reports Server (NTRS)

    Farhi, Leon E.

    1991-01-01

    Any new natural environment may generate a number of stresses (such as hypoxia, water lack, and heat exposure), each of which can produce strains in more than a single organ system. Every strain may in turn stimulate the body to adapt in multiple ways. Nevertheless, a general strategy of the various adaptive responses emerges when the challenges are divided into three groups. The first category includes conditions that affect the supply of essential molecules, while the second is made up by those stresses that prevent the body from regulating properly the output of waste products, such as CO2 and heat. In both classes, there is a small number of responses, similar in principle, regardless of the specific situation. The third unit is created by environments that disrupt body transport systems. Problems may arise when there is a conflict between two stresses requiring conflicting adaptive changes. An alternative to adaptation, creation of micro-environment, is often favored by the animal.

  2. An adaptive response surface method for crashworthiness optimization

    NASA Astrophysics Data System (ADS)

    Shi, Lei; Yang, Ren-Jye; Zhu, Ping

    2013-11-01

    Response surface-based design optimization has been commonly used for optimizing large-scale design problems in the automotive industry. However, most response surface models are built by a limited number of design points without considering data uncertainty. In addition, the selection of a response surface in the literature is often arbitrary. This article uses a Bayesian metric to systematically select the best available response surface among several candidates in a library while considering data uncertainty. An adaptive, efficient response surface strategy, which minimizes the number of computationally intensive simulations, was developed for design optimization of large-scale complex problems. This methodology was demonstrated by a crashworthiness optimization example.

  3. Adaptation responses of crops to climate change

    SciTech Connect

    Seino, Hiroshi

    1993-12-31

    Appreciable global climatic responses to increasing levels of atmospheric CO{sub 2} and other trace gases are expected to take place over the next 50 to 80 years. Increasing atmospheric concentrations of carbon dioxide and other greenhouse gases are producing or will produce changes in the climate of the Earth. In particular, numerous efforts of climate modeling project very substantial increase of surface air temperature. In addition to a general warming of the atmosphere, the possibility of increased summer dryness in the continental mid-latitudes has been suggested on the basis of both historical analogues and some General Circulation Model (GCM) studies. There are three types of effect of climatic change on agriculture: (1) the physiological (direct) effect of elevated levels of atmospheric CO{sub 2} on crop plants and weeds, (2) the effect of changes in parameters of climate (e.g., temperature, precipitation, and solar radiation) on plants and animals, and (3) the effects of climate-related rises in sea-level on land use. The direct effects of elevated CO{sub 2} are on photosynthesis and respiration and thereby on growth, and there are additional effects of increased CO{sub 2} on development, yield quality and stomatal aperture and water use. A doubling of CO{sub 2} increases the instantaneous photosynthetic rate by 30% to 100%, depending on the other environmental conditions, and reduce water requirements of plants by reducing transpiration (per unit leaf area) through reductions in stomatal aperture. A doubling of CO{sub 2} causes partial stomatal closure on both C{sub 3} and C{sub 4} plants (approximately a 40% decrease in aperture). In many experiments this results in reductions of transpiration of about 23% to 46%. However. there is considerable uncertainty over the magnitude of this in natural conditions.

  4. Stimuli-Responsive Mechanically Adaptive Polymer Nanocomposites

    PubMed Central

    Shanmuganathan, Kadhiravan; Capadona, Jeffrey R.; Rowan, Stuart J.; Weder, Christoph

    2010-01-01

    A new series of biomimetic stimuli-responsive nanocomposites, which change their mechanical properties upon exposure to physiological conditions, was prepared and investigated. The materials were produced by introducing percolating networks of cellulose nanofibers or “whiskers” derived from tunicates into poly(vinyl acetate) (PVAc), poly(butyl methacrylate) (PBMA), and blends of these polymers, with the objective of determining how the hydrophobicity and glass-transition temperature (Tg) of the polymer matrix affect the water-induced mechanically dynamic behavior. Below the Tg (~60–70 °C), the incorporation of whiskers (15.1 – 16.5% v/v) modestly increased the tensile storage moduli (E′) of the neat polymers from 0.6 to 3.8 GPa (PBMA) and from 2 to 5.2 GPa (PVAc). The reinforcement was much more dramatic above Tg, where E′ increased from 1.2 to 690 MPa (PVAc) and ~1 to 1.1 GPa (PBMA). Upon exposure to physiological conditions (immersion in artificial cerebrospinal fluid, ACSF, at 37 °C) all materials displayed a decrease of E′. The most significant contrast was seen in PVAc; for example the E′ of a 16.5% v/v PVAc/whisker nanocomposite decreased from 5.2 GPa to 12.7 MPa. Only a modest modulus decrease was measured for PBMA/whisker nanocomposite; here the E′ of a 15.1% v/v PBMA/whisker nanocomposite decreased from 3.8 to 1.2 GPa. A systematic investigation revealed that the magnitude of the mechanical contrast was related to the degree of swelling with ACSF, which was shown to increase with whisker content, temperature, and polarity of the matrix (PVAc > PBMA). The mechanical morphing of the new materials can be described in the framework of both the percolation and Halpin-Kardos models for nanocomposite reinforcement, and is the result of changing interactions among the nanoparticles and plasticization of the matrix upon swelling. PMID:20305827

  5. Genetic erosion impedes adaptive responses to stressful environments

    PubMed Central

    Bijlsma, R; Loeschcke, Volker

    2012-01-01

    Biodiversity is increasingly subjected to human-induced changes of the environment. To persist, populations continually have to adapt to these often stressful changes including pollution and climate change. Genetic erosion in small populations, owing to fragmentation of natural habitats, is expected to obstruct such adaptive responses: (i) genetic drift will cause a decrease in the level of adaptive genetic variation, thereby limiting evolutionary responses; (ii) inbreeding and the concomitant inbreeding depression will reduce individual fitness and, consequently, the tolerance of populations to environmental stress. Importantly, inbreeding generally increases the sensitivity of a population to stress, thereby increasing the amount of inbreeding depression. As adaptation to stress is most often accompanied by increased mortality (cost of selection), the increase in the ‘cost of inbreeding’ under stress is expected to severely hamper evolutionary adaptive processes. Inbreeding thus plays a pivotal role in this process and is expected to limit the probability of genetically eroded populations to successfully adapt to stressful environmental conditions. Consequently, the dynamics of small fragmented populations may differ considerably from large nonfragmented populations. The resilience of fragmented populations to changing and deteriorating environments is expected to be greatly decreased. Alleviating inbreeding depression, therefore, is crucial to ensure population persistence. PMID:25568035

  6. Beyond Adapting to Climate Change: Embedding Adaptation in Responses to Multiple Threats and Stresses

    SciTech Connect

    Wilbanks, Thomas J; Kates, Dr. Robert W.

    2010-01-01

    Climate change impacts are already being experienced in every region of the United States and every part of the world most severely in Arctic regions and adaptation is needed now. Although climate change adaptation research is still in its infancy, significant adaptation planning in the United States has already begun in a number of localities. This article seeks to broaden the adaptation effort by integrating it with broader frameworks of hazards research, sustainability science, and community and regional resilience. To extend the range of experience, we draw from ongoing case studies in the Southeastern United States and the environmental history of New Orleans to consider the multiple threats and stresses that all communities and regions experience. Embedding climate adaptation in responses to multiple threats and stresses helps us to understand climate change impacts, themselves often products of multiple stresses, to achieve community acceptance of needed adaptations as co-benefits of addressing multiple threats, and to mainstream the process of climate adaptation through the larger envelope of social relationships, communication channels, and broad-based awareness of needs for risk management that accompany community resilience.

  7. Adaptation responses to climate change differ between global megacities

    NASA Astrophysics Data System (ADS)

    Georgeson, Lucien; Maslin, Mark; Poessinouw, Martyn; Howard, Steve

    2016-06-01

    Urban areas are increasingly at risk from climate change, with negative impacts predicted for human health, the economy and ecosystems. These risks require responses from cities to improve their resilience. Policymakers need to understand current adaptation spend to plan comprehensively and effectively. Through the measurement of spend in the newly defined `adaptation economy', we analyse current climate change adaptation efforts in ten megacities. In all cases, the adaptation economy remains a small part of the overall economy, representing a maximum of 0.33% of a city's gross domestic product (here referred to as GDPc). Differences in total spend are significant between cities in developed, emerging and developing countries, ranging from #15 million to #1,600 million. Comparing key subsectors, we demonstrate the differences in adaptation profiles. Developing cities have higher proportional spend on health and agriculture, whereas developed cities have higher spend on energy and water. Spend per capita and percentage of GDPc comparisons more clearly show disparities between cities. Developing country cities spend half the proportion of GDPc and significantly less per capita, suggesting that adaptation spend is driven by wealth rather than the number of vulnerable people. This indicates that current adaptation activities are insufficient in major population centres in developing and emerging economies.

  8. The Pupillary Orienting Response Predicts Adaptive Behavioral Adjustment after Errors

    PubMed Central

    Murphy, Peter R.; van Moort, Marianne L.; Nieuwenhuis, Sander

    2016-01-01

    Reaction time (RT) is commonly observed to slow down after an error. This post-error slowing (PES) has been thought to arise from the strategic adoption of a more cautious response mode following deployment of cognitive control. Recently, an alternative account has suggested that PES results from interference due to an error-evoked orienting response. We investigated whether error-related orienting may in fact be a pre-cursor to adaptive post-error behavioral adjustment when the orienting response resolves before subsequent trial onset. We measured pupil dilation, a prototypical measure of autonomic orienting, during performance of a choice RT task with long inter-stimulus intervals, and found that the trial-by-trial magnitude of the error-evoked pupil response positively predicted both PES magnitude and the likelihood that the following response would be correct. These combined findings suggest that the magnitude of the error-related orienting response predicts an adaptive change of response strategy following errors, and thereby promote a reconciliation of the orienting and adaptive control accounts of PES. PMID:27010472

  9. Neural Basis of Adaptive Response Time Adjustment during Saccade Countermanding

    PubMed Central

    Pouget, Pierre; Logan, Gordon D.; Palmeri, Thomas J.; Boucher, Leanne; Paré, Martin; Schall, Jeffrey D.

    2011-01-01

    Humans and macaque monkeys adjust their response time adaptively in stop signal (countermanding) tasks, responding slower after stop-signal trials than after control trials with no stop signal. We investigated the neural mechanism underlying this adaptive response time adjustment in macaque monkeys performing a saccade countermanding task. Earlier research showed that movements are initiated when the random accumulation of presaccadic movement-related activity reaches a fixed threshold. We found that a systematic delay in response time after stop signal trials was accomplished not through a change of threshold, baseline, or accumulation rate, but instead through a change in the time when activity first began to accumulate. The neurons underlying movement initiation have been identified with mathematical accumulator models of response time performance. Therefore, this new result provides surprising new insights into the neural instantiation of stochastic accumulator models and the mechanisms through which executive control can be exerted. PMID:21880921

  10. Adaptive Patterns of Stress Responsivity: A Preliminary Investigation

    ERIC Educational Resources Information Center

    Del Giudice, Marco; Hinnant, J. Benjamin; Ellis, Bruce J.; El-Sheikh, Mona

    2012-01-01

    The adaptive calibration model (ACM) is an evolutionary-developmental theory of individual differences in stress responsivity. In this article, we tested some key predictions of the ACM in a middle childhood sample (N = 256). Measures of autonomic nervous system activity across the sympathetic and parasympathetic branches validated the 4-pattern…

  11. Adaptation of extrapulmonary responses to ozone exposure in conscious rats.

    PubMed

    Iwasaki, T; Takahashi, M; Saito, H; Arito, H

    1998-01-01

    The adaptation of cardiovascular and thermoregulatory responses to ozone (O3) was examined by repeated exposure of electrocardiographic (ECG) electrode- and thermistor sensor-implanted rats to O3 for 4 consecutive days (8 hrs/day). Circadian rhythms of heart rate (HR) and abdominal core temperature (Tco) were disrupted on the first and second O3 exposure days in a concentration dependent manner. The 8-hr and 12-hr averaged values of HR and Tco during the exposure period and the dark post-exposure period, respectively, decreased significantly on the first and second exposure days. The decreased HR and Tco recovered to respective control values after small but significant rebound increases on the third and fourth days of O3 exposure. The adaptation of the extrapulmonary responses to O3 exposure was discussed in light of the previously reported time periods required to abolish the spontaneous breathing, biochemical, cellular, and morphological responses to O3.

  12. [Adaptive immune response of people living near chemically hazardous object].

    PubMed

    Petlenko, S V; Ivanov, M B; Goverdovskiĭ, Iu B; Bogdanova, E G; Golubkov, A V

    2011-10-01

    The article presents data dynamics of adaptive immune responses of people for a long time living in adverse environmental conditions caused by pollution of the environment by industrial toxic waste. It is shown that in the process of adaptation to adverse environmental factors, changes in the immune system are in the phase fluctuations of immunological parameters that are accompanied by changes in the structure of immunodependent pathology. Most sensitive to prolonged exposure to toxic compounds are the cellular mechanisms of immune protection. Violations of the structural and quantitative and functional parameters of the link of the immune system are leading to the formation of immunopathological processes.

  13. Infinite impulse response modal filtering in visible adaptive optics

    NASA Astrophysics Data System (ADS)

    Agapito, G.; Arcidiacono, C.; Quirós-Pacheco, F.; Puglisi, A.; Esposito, S.

    2012-07-01

    Diffraction limited resolution adaptive optics (AO) correction in visible wavelengths requires a high performance control. In this paper we investigate infinite impulse response filters that optimize the wavefront correction: we tested these algorithms through full numerical simulations of a single-conjugate AO system comprising an adaptive secondary mirror with 1127 actuators and a pyramid wavefront sensor (WFS). The actual practicability of the algorithms depends on both robustness and knowledge of the real system: errors in the system model may even worsen the performance. In particular we checked the robustness of the algorithms in different conditions, proving that the proposed method can reject both disturbance and calibration errors.

  14. Adaptive optics and phase diversity imaging for responsive space applications.

    SciTech Connect

    Smith, Mark William; Wick, David Victor

    2004-11-01

    The combination of phase diversity and adaptive optics offers great flexibility. Phase diverse images can be used to diagnose aberrations and then provide feedback control to the optics to correct the aberrations. Alternatively, phase diversity can be used to partially compensate for aberrations during post-detection image processing. The adaptive optic can produce simple defocus or more complex types of phase diversity. This report presents an analysis, based on numerical simulations, of the efficiency of different modes of phase diversity with respect to compensating for specific aberrations during post-processing. It also comments on the efficiency of post-processing versus direct aberration correction. The construction of a bench top optical system that uses a membrane mirror as an active optic is described. The results of characterization tests performed on the bench top optical system are presented. The work described in this report was conducted to explore the use of adaptive optics and phase diversity imaging for responsive space applications.

  15. BYSTANDERS, ADAPTIVE RESPONSES AND GENOMIC INSTABILITY - POTENTIAL MODIFIERS OF LOW-DOSE CANCER RESPONSES.

    EPA Science Inventory

    Bystanders, Adaptive Responses and Genomic Instability -Potential Modifiers ofLow-Dose
    Cancer Responses
    .
    There has been a concerted effort in the field of radiation biology to better understand cellular
    responses that could have an impact on the estin1ation of cancer...

  16. Seed Pubescence and Shape Modulate Adaptive Responses to Fire Cues

    PubMed Central

    Gómez-González, Susana; Ojeda, Fernando; Torres-Morales, Patricio; Palma, Jazmín E.

    2016-01-01

    Post-fire recruitment by seeds is regarded as an adaptive response in fire-prone ecosystems. Nevertheless, little is known about which heritable seed traits are functional to the main signals of fire (heat and smoke), thus having the potential to evolve. Here, we explored whether three seed traits (pubescence, dormancy and shape) and fire regime modulate seed response to fire cues(heat and smoke). As a model study system, we used Helenium aromaticum (Asteraceae), a native annual forb from the Chilean matorral, where fires are anthropogenic. We related seed trait values with fitness responses (germination and survival) after exposure to heat-shock and smoke experimental treatments on seeds from 10 H. aromaticum wild populations. We performed a phenotypic selection experiment to examine the relationship of seed traits with post-treatment fitness within a population (adaptive hypothesis). We then explored whether fire frequency in natural habitats was associated with trait expression across populations, and with germination and survival responses to experimental fire-cues. We found that populations subjected to higher fire frequency had, in average, more rounded and pubescent seeds than populations from rarely burned areas. Populations with more rounded and pubescent seeds were more resistant to 80°C heat-shock and smoke treatments.There was correlated selection on seed traits: pubescent-rounded or glabrouscent-elongated seeds had the highest probability of germinating after heat-shock treatments. Seed pubescence and shape in H. aromaticum are heritable traits that modulate adaptive responses to fire. Our results provide new insights into the process of plant adaptation to fire and highlight the relevance of human-made fires as a strong evolutionary agent in the Anthropocene. PMID:27438267

  17. Seed Pubescence and Shape Modulate Adaptive Responses to Fire Cues.

    PubMed

    Gómez-González, Susana; Ojeda, Fernando; Torres-Morales, Patricio; Palma, Jazmín E

    2016-01-01

    Post-fire recruitment by seeds is regarded as an adaptive response in fire-prone ecosystems. Nevertheless, little is known about which heritable seed traits are functional to the main signals of fire (heat and smoke), thus having the potential to evolve. Here, we explored whether three seed traits (pubescence, dormancy and shape) and fire regime modulate seed response to fire cues(heat and smoke). As a model study system, we used Helenium aromaticum (Asteraceae), a native annual forb from the Chilean matorral, where fires are anthropogenic. We related seed trait values with fitness responses (germination and survival) after exposure to heat-shock and smoke experimental treatments on seeds from 10 H. aromaticum wild populations. We performed a phenotypic selection experiment to examine the relationship of seed traits with post-treatment fitness within a population (adaptive hypothesis). We then explored whether fire frequency in natural habitats was associated with trait expression across populations, and with germination and survival responses to experimental fire-cues. We found that populations subjected to higher fire frequency had, in average, more rounded and pubescent seeds than populations from rarely burned areas. Populations with more rounded and pubescent seeds were more resistant to 80°C heat-shock and smoke treatments.There was correlated selection on seed traits: pubescent-rounded or glabrouscent-elongated seeds had the highest probability of germinating after heat-shock treatments. Seed pubescence and shape in H. aromaticum are heritable traits that modulate adaptive responses to fire. Our results provide new insights into the process of plant adaptation to fire and highlight the relevance of human-made fires as a strong evolutionary agent in the Anthropocene. PMID:27438267

  18. Adaptive thermoregulation in endotherms may alter responses to climate change.

    PubMed

    Boyles, Justin G; Seebacher, Frank; Smit, Ben; McKechnie, Andrew E

    2011-11-01

    Climate change is one of the major issues facing natural populations and thus a focus of recent research has been to predict the responses of organisms to these changes. Models are becoming more complex and now commonly include physiological traits of the organisms of interest. However, endothermic species have received less attention than have ectotherms in these mechanistic models. Further, it is not clear whether responses of endotherms to climate change are modified by variation in thermoregulatory characteristics associated with phenotypic plasticity and/or adaptation to past selective pressures. Here, we review the empirical data on thermal adaptation and acclimatization in endotherms and discuss how those factors may be important in models of responses to climate change. We begin with a discussion of why thermoregulation and thermal sensitivity at high body temperatures should be co-adapted. Importantly, we show that there is, in fact, considerable variation in the ability of endotherms to tolerate high body temperatures and/or high environmental temperatures, but a better understanding of this variation will likely be critical for predicting responses to future climatic scenarios. Next, we discuss why variation in thermoregulatory characteristics should be considered when modeling the effects of climate change on heterothermic endotherms. Finally, we review some biophysical and biochemical factors that will limit adaptation and acclimation in endotherms. We consider both long-term, directional climate change and short-term (but increasingly common) anomalies in climate such as extreme heat waves and we suggest areas of important future research relating to both our basic understanding of endothermic thermoregulation and the responses of endotherms to climate change.

  19. Adaptive response to cold temperatures in Vibrio vulnificus.

    PubMed

    Bryan, P J; Steffan, R J; DePaola, A; Foster, J W; Bej, A K

    1999-03-01

    The effectiveness of rapid chilling or freezing of oysters to reduce Vibrio vulnificus levels in shellfish may be compromised by product handling procedures that permit cold adaptation. When a V. vulnificus culture was shifted from 35 degrees C to 6 degrees C conditions, it underwent transition to a non-culturable state. Cells adapted to 15 degrees C prior to change to 6 degrees C condition, however, remain viable and culturable. In addition, cultures adapted to 15 degrees C were able to survive better upon freezing at -78 degrees C compared with cultures frozen directly from 35 degrees C. Inhibition of protein synthesis by addition of chloramphenicol in a V. vulnificus culture immediately prior to the exposure to the adaptive temperature eliminated inducible cold tolerance. These results suggest that cold-adaptive "protective" proteins may enhance survival and tolerance at cold temperatures. In addition, removal of iron from the growth medium by adding 2,2'-Dipyridyl prior to cold adaptation decreased the viability by approximately 2 logarithm levels. This suggests that iron plays an important role in adaptation at cold temperatures. Analysis of total cellular proteins on an SDS polyacrylamide gel electrophoresis, labeled with 35S-methionine during exposure at 15 degrees C, showed elevated expressions of a 6-kDa and a 40-kDa protein and decreased expression of an 80-kDa protein. These results suggest that, for V. vulnificus, survival and tolerance at cold temperatures could be due to the expression of cold-adaptive proteins other than previously documented major cold shock proteins such as CS7.4 and CsdA. In this study, for the first time we have shown that exposure to an intermediate cold temperature (15 degrees C) causes a cold adaptive response, helping this pathogen remain in culturable state when exposed to a much colder temperature (6 degrees C). This adaptive nature to cold temperatures could be important for shellfish industry efforts to reduce the risk of

  20. Membrane vesicle production by Chlamydia trachomatis as an adaptive response

    PubMed Central

    Frohlich, Kyla M.; Hua, Ziyu; Quayle, Alison J.; Wang, Jin; Lewis, Maria E.; Chou, Chau-wen; Luo, Miao; Buckner, Lyndsey R.; Shen, Li

    2014-01-01

    Bacteria have evolved specific adaptive responses to cope with changing environments. These adaptations include stress response phenotypes with dynamic modifications of the bacterial cell envelope and generation of membrane vesicles (MVs). The obligate intracellular bacterium, Chlamydia trachomatis, typically has a biphasic lifestyle, but can enter into an altered growth state typified by morphologically aberrant chlamydial forms, termed persistent growth forms, when induced by stress in vitro. How C. trachomatis can adapt to a persistent growth state in host epithelial cells in vivo is not well understood, but is an important question, since it extends the host-bacterial relationship in vitro and has thus been indicated as a survival mechanism in chronic chlamydial infections. Here, we review recent findings on the mechanistic aspects of bacterial adaptation to stress with a focus on how C. trachomatis remodels its envelope, produces MVs, and the potential important consequences of MV production with respect to host-pathogen interactions. Emerging data suggest that the generation of MVs may be an important mechanism for C. trachomatis intracellular survival of stress, and thus may aid in the establishment of a chronic infection in human genital epithelial cells. PMID:24959424

  1. Global relationships in fluctuation and response in adaptive evolution.

    PubMed

    Furusawa, Chikara; Kaneko, Kunihiko

    2015-08-01

    Cells change their internal state to adapt to environmental changes, and evolve in response to the new conditions. The phenotype changes first via adaptation in response to environmental changes, and then through mutational changes in the genomic sequence, followed by selection in evolution. Here, we analysed simulated adaptive evolution using a simple cell model consisting of thousands of intracellular components, and found that the changes in their concentrations by adaptation are proportional to those by evolution across all the components, where the proportion coefficient between the two agreed well with the change in the growth rate of a cell. Furthermore, we demonstrate that the phenotypic variance in concentrations of cellular components due to (non-genetic) noise and to genomic alternations is proportional across all components. This implies that the specific phenotypes that are highly evolvable were already given by non-genetic fluctuations. These global relationships in cellular states were also supported by phenomenological theory based on steady reproduction and transcriptome analysis of laboratory evolution in Escherichia coli. These findings demonstrate that a possible evolutionary change in phenotypic state is highly restricted. Our results provide a basis for the development of a quantitative theory of plasticity and robustness in phenotypic evolution.

  2. Global relationships in fluctuation and response in adaptive evolution

    PubMed Central

    Furusawa, Chikara; Kaneko, Kunihiko

    2015-01-01

    Cells change their internal state to adapt to environmental changes, and evolve in response to the new conditions. The phenotype changes first via adaptation in response to environmental changes, and then through mutational changes in the genomic sequence, followed by selection in evolution. Here, we analysed simulated adaptive evolution using a simple cell model consisting of thousands of intracellular components, and found that the changes in their concentrations by adaptation are proportional to those by evolution across all the components, where the proportion coefficient between the two agreed well with the change in the growth rate of a cell. Furthermore, we demonstrate that the phenotypic variance in concentrations of cellular components due to (non-genetic) noise and to genomic alternations is proportional across all components. This implies that the specific phenotypes that are highly evolvable were already given by non-genetic fluctuations. These global relationships in cellular states were also supported by phenomenological theory based on steady reproduction and transcriptome analysis of laboratory evolution in Escherichia coli. These findings demonstrate that a possible evolutionary change in phenotypic state is highly restricted. Our results provide a basis for the development of a quantitative theory of plasticity and robustness in phenotypic evolution. PMID:26202686

  3. Landowner response to wildfire risk: Adaptation, mitigation or doing nothing.

    PubMed

    Gan, Jianbang; Jarrett, Adam; Johnson Gaither, Cassandra

    2015-08-15

    Wildfire has brought about ecological, economic, and social consequences that engender human responses in many parts of the world. How to respond to wildfire risk is a common challenge across the globe particularly in areas where lands are controlled by many small private owners because effective wildfire prevention and protection require coordinated efforts of neighboring stakeholders. We explore (i) wildfire response strategies adopted by family forestland owners in the southern United States, one of the most important and productive forest regions in the world, through a landowner survey; and (ii) linkages between the responses of these landowners and their characteristics via multinomial logistic regression. We find that landowners used diverse strategies to respond to wildfire risk, with the most popular responses being "doing nothing" and combined adaptation and mitigation, followed by adaptation or mitigation alone. Landowners who had lost properties to wildfire, lived on their forestlands, had a forest management plan, and were better educated were more likely to proactively respond to wildfire risk. Our results indicate the possibility to enhance the effectiveness of collective action of wildfire risk response by private forestland owners and to coordinate wildfire response with forest conservation and certification efforts. These findings shed new light on engaging private landowners in wildfire management in the study region and beyond.

  4. Constraint to adaptive evolution in response to global warming.

    PubMed

    Etterson, J R; Shaw, R G

    2001-10-01

    We characterized the genetic architecture of three populations of a native North American prairie plant in field conditions that simulate the warmer and more arid climates predicted by global climate models. Despite genetic variance for traits under selection, among-trait genetic correlations that are antagonistic to the direction of selection limit adaptive evolution within these populations. Predicted rates of evolutionary response are much slower than the predicted rate of climate change.

  5. Evaluation of the Adaptive Immune Response to Respiratory Syncytial Virus.

    PubMed

    Knudson, Cory J; Weiss, Kayla A; Stoley, Megan E; Varga, Steven M

    2016-01-01

    Evaluation of the adaptive immune response is critical to the advancement of our basic knowledge and understanding of respiratory syncytial virus (RSV). The cellular composition in the lung following RSV infection is often evaluated using flow cytometry. However, a limitation of this approach has been the inability to readily distinguish cells that are within the lung parenchyma from cells that remain in the pulmonary blood vessels. Herein, we detail a procedure to evaluate the adaptive immune response via flow cytometric analysis that incorporates an in vivo intravascular staining technique. This technique allows for discrimination of immune cells in the lung tissue from cells that remain in the pulmonary vasculature following perfusion. Therefore at any given time point following an RSV infection, the leukocytic populations in the lung parenchyma can be quantified and phenotypically assessed with high resolution. While we focus on the T lymphocyte response in the lung, this technique can be readily adapted to examine various leukocytic cell types in the lung following RSV infection. PMID:27464699

  6. Adaptive response of pulmonary arterial smooth muscle to length change.

    PubMed

    Syyong, Harley; Cheung, Christine; Solomon, Dennis; Seow, Chun Y; Kuo, Kuo H

    2008-04-01

    Hypervasoconstriction is associated with pulmonary hypertension and dysfunction of the pulmonary arterial smooth muscle (PASM) is implicated. However, relatively little is known about the mechanical properties of PASM. Recent advances in our understanding of plastic adaptation in smooth muscle may shed light on the disease mechanism. In this study, we determined whether PASM is capable of adapting to length changes (especially shortening) and regain its contractile force. We examined the time course of length adaptation in PASM in response to step changes in length and to length oscillations mimicking the periodic stretches due to pulsatile arterial pressure. Rings from sheep pulmonary artery were mounted on myograph and stimulated using electrical field stimulation (12-16 s, 20 V, 60 Hz). The length-force relationship was determined at L(ref) to 0.6 L(ref), where L(ref) was a reference length close to the in situ length of PASM. The response to length oscillations was determined at L(ref), after the muscle was subjected to length oscillation of various amplitudes for 200 s at 1.5 Hz. Release (or stretch) of resting PASM from L(ref) to 0.6 (and vice versa) was followed by a significant force recovery (73 and 63%, respectively), characteristic of length adaptation. All recoveries of force followed a monoexponential time course. Length oscillations with amplitudes ranging from 5 to 20% L(ref) caused no significant change in force generation in subsequent contractions. It is concluded that, like many smooth muscles, PASM possesses substantial capability to adapt to changes in length. Under pathological conditions, this could contribute to hypervasoconstriction in pulmonary hypertension. PMID:18218913

  7. Universal response-adaptation relation in bacterial chemotaxis.

    PubMed

    Krembel, Anna K; Neumann, Silke; Sourjik, Victor

    2015-01-01

    The bacterial strategy of chemotaxis relies on temporal comparisons of chemical concentrations, where the probability of maintaining the current direction of swimming is modulated by changes in stimulation experienced during the recent past. A short-term memory required for such comparisons is provided by the adaptation system, which operates through the activity-dependent methylation of chemotaxis receptors. Previous theoretical studies have suggested that efficient navigation in gradients requires a well-defined adaptation rate, because the memory time scale needs to match the duration of straight runs made by bacteria. Here we demonstrate that the chemotaxis pathway of Escherichia coli does indeed exhibit a universal relation between the response magnitude and adaptation time which does not depend on the type of chemical ligand. Our results suggest that this alignment of adaptation rates for different ligands is achieved through cooperative interactions among chemoreceptors rather than through fine-tuning of methylation rates for individual receptors. This observation illustrates a yet-unrecognized function of receptor clustering in bacterial chemotaxis.

  8. Stress and adaptation responses to repeated acute acceleration.

    NASA Technical Reports Server (NTRS)

    Burton, R. R.; Smith, A. H.

    1972-01-01

    Study in which groups of adult male chickens (single-comb white leghorn) were exposed daily to acceleration (centrifugation) of 2 or 3 G for 10 min, 1, 4, 8, 12, 16, and 24 hr (continuously), or 0 time (controls). After approximately five months of this intermittent treatment (training), the birds were exposed to continuous accelerations of the same G force (intensity). The degree of stress and adaptation of each bird was determined by survival and relative lymphocyte count criteria. Intermittent training exposures of 2 G developed levels of adaptation in birds directly proportional to the duration of their daily exposure. Intermittent training periods at 3 G, however, produced a physiological deterioration in birds receiving daily exposures of 8 hr or more. Adaptive benefits were found only in the 1- and 4-hr-daily intermittent 3-G exposure groups. Exposure to 3 G produced an immediate stress response as indicated by a low relative lymphocyte count which returned to control (preexposed) values prior to the next daily acceleration period in the 10-min, 1-hr, and 4-hr groups. This daily recovery period from stress appeared to be necessary for adaptation as opposed to deterioration for the more severe environmental (3 G) alteration.

  9. A weak adaptive response to alkylation damage in Salmonella typhimurium.

    PubMed Central

    Vaughan, P; Sedgwick, B

    1991-01-01

    An efficient adaptive response to alkylation damage was observed in several enterobacterial species, including Klebsiella aerogenes, Shigella sonnei, Shigella boydii, Escherichia alkalescens, Escherichia hermanii, and Escherichia fergusonii. Increased O6-methylguanine-DNA and methylphosphotriester-DNA methyltransferase activities correlated with the induction of a 39-kDa protein recognized by monoclonal antibodies raised against the Escherichia coli Ada protein. Induced methyltransferase activities were similarly observed in Aerobacter aerogenes and Citrobacter intermedius, although no antigenically cross-reacting material was present. Weak induction of a 39-kDa protein immunologically related to the E. coli Ada protein occurred in Salmonella typhimurium. This protein encoded by the cloned S. typhimurium ada gene was shown to be an active methyltransferase which repaired O6-methylguanine and methylphosphotriesters in DNA as efficiently as did the E. coli Ada protein. However, the mehtyltransferase activity of the weakly induced 39-kDa protein in S. typhimurium was not detected, apparently because it was self-methylated and thus inactivated during the adaptive N-methyl-N-nitro-N-nitrosoguanidine pretreatment. In contrast, the E. coli ada gene on a low-copy-number plasmid was efficiently induced in S. typhimurium, and high methyltransferase activities were observed. We concluded that the inefficient induction of the adaptive response in S. typhimurium results from weak transcriptional activation of its ada gene by the self-methylated protein. Images PMID:2050626

  10. Stress Response and Perinatal Reprogramming: Unraveling (Mal)adaptive Strategies

    PubMed Central

    Musazzi, Laura; Marrocco, Jordan

    2016-01-01

    Environmental stressors induce coping strategies in the majority of individuals. The stress response, involving the activation of the hypothalamic-pituitary-adrenocortical axis and the consequent release of corticosteroid hormones, is indeed aimed at promoting metabolic, functional, and behavioral adaptations. However, behavioral stress is also associated with fast and long-lasting neurochemical, structural, and behavioral changes, leading to long-term remodeling of glutamate transmission, and increased susceptibility to neuropsychiatric disorders. Of note, early-life events, both in utero and during the early postnatal life, trigger reprogramming of the stress response, which is often associated with loss of stress resilience and ensuing neurobehavioral (mal)adaptations. Indeed, adverse experiences in early life are known to induce long-term stress-related neuropsychiatric disorders in vulnerable individuals. Here, we discuss recent findings about stress remodeling of excitatory neurotransmission and brain morphology in animal models of behavioral stress. These changes are likely driven by epigenetic factors that lie at the core of the stress-response reprogramming in individuals with a history of perinatal stress. We propose that reprogramming mechanisms may underlie the reorganization of excitatory neurotransmission in the short- and long-term response to stressful stimuli. PMID:27057367

  11. Adaptive Responses to Prochloraz Exposure That Alter Dose-Response and Time-Course Behaviors

    EPA Science Inventory

    Dose response and time-course (DRTC) are, along with exposure, the major determinants of health risk. Adaptive changes within exposed organisms in response to environmental stress are common, and alter DRTC behaviors to minimize the effects caused by stressors. In this project, ...

  12. Response and adaptation of bone cells to simulated microgravity

    NASA Astrophysics Data System (ADS)

    Hu, Lifang; Li, Runzhi; Su, Peihong; Arfat, Yasir; Zhang, Ge; Shang, Peng; Qian, Airong

    2014-11-01

    Bone loss induced by microgravity during space flight is one of the most deleterious factors on astronaut's health and is mainly attributed to an unbalance in the process of bone remodeling. Studies from the space microgravity have demonstrated that the disruption of bone remodeling is associated with the changes of four main functional bone cells, including osteoblast, osteoclast, osteocyte, and mesenchymal stem cells. For the limited availability, expensive costs and confined experiment conditions for conducting space microgravity studies, the mechanism of bone cells response and adaptation to microgravity is still unclear. Therefore, some ground-based simulated microgravity methods have been developed to investigate the bioeffects of microgravity and the mechanisms. Here, based on our studies and others, we review how bone cells (osteoblasts, osteoclasts, osteocytes and mesenchymal stem cells) respond and adapt to simulated microgravity.

  13. Exercise-induced stress response as an adaptive tolerance strategy.

    PubMed Central

    Sonneborn, J S; Barbee, S A

    1998-01-01

    Interaction between the quality of the environment and the health of the exposed population determines the survival response of living organisms. The phenomenon of induced tolerance by exposure to threshold levels of stressors to stimulate natural defense mechanisms has potential therapeutic value. The paucity of information on predictability of individual response and information on the operative fundamental mechanisms limit applicability of the adaptive tolerance strategy. A potential biomarker of the stress response includes members of the stress-inducible ubiquitin gene family. Transcript sizes detected with Northern blot analysis identify different classes of ubiquitin gene family members and the intensity of the radioactive signal allows abundance determinations. Using moderate exercise as the stressor, significant increase (p < 0.028) in abundance of inducible polyubiquitin genes was found in human blood. Both the potential of exercise as a model system of a natural stress inducer and polyubiquitin as a biomarker of stress were established in these studies. Images Figure 1 Figure 2 PMID:9539026

  14. Plant adaptation to low atmospheric pressures: potential molecular responses

    NASA Technical Reports Server (NTRS)

    Ferl, Robert J.; Schuerger, Andrew C.; Paul, Anna-Lisa; Gurley, William B.; Corey, Kenneth; Bucklin, Ray

    2002-01-01

    There is an increasing realization that it may be impossible to attain Earth normal atmospheric pressures in orbital, lunar, or Martian greenhouses, simply because the construction materials do not exist to meet the extraordinary constraints imposed by balancing high engineering requirements against high lift costs. This equation essentially dictates that NASA have in place the capability to grow plants at reduced atmospheric pressure. Yet current understanding of plant growth at low pressures is limited to just a few experiments and relatively rudimentary assessments of plant vigor and growth. The tools now exist, however, to make rapid progress toward understanding the fundamental nature of plant responses and adaptations to low pressures, and to develop strategies for mitigating detrimental effects by engineering the growth conditions or by engineering the plants themselves. The genomes of rice and the model plant Arabidopsis thaliana have recently been sequenced in their entirety, and public sector and commercial DNA chips are becoming available such that thousands of genes can be assayed at once. A fundamental understanding of plant responses and adaptation to low pressures can now be approached and translated into procedures and engineering considerations to enhance plant growth at low atmospheric pressures. In anticipation of such studies, we present here the background arguments supporting these contentions, as well as informed speculation about the kinds of molecular physiological responses that might be expected of plants in low-pressure environments.

  15. Plant adaptation to low atmospheric pressures: potential molecular responses.

    PubMed

    Ferl, Robert J; Schuerger, Andrew C; Paul, Anna-Lisa; Gurley, William B; Corey, Kenneth; Bucklin, Ray

    2002-01-01

    There is an increasing realization that it may be impossible to attain Earth normal atmospheric pressures in orbital, lunar, or Martian greenhouses, simply because the construction materials do not exist to meet the extraordinary constraints imposed by balancing high engineering requirements against high lift costs. This equation essentially dictates that NASA have in place the capability to grow plants at reduced atmospheric pressure. Yet current understanding of plant growth at low pressures is limited to just a few experiments and relatively rudimentary assessments of plant vigor and growth. The tools now exist, however, to make rapid progress toward understanding the fundamental nature of plant responses and adaptations to low pressures, and to develop strategies for mitigating detrimental effects by engineering the growth conditions or by engineering the plants themselves. The genomes of rice and the model plant Arabidopsis thaliana have recently been sequenced in their entirety, and public sector and commercial DNA chips are becoming available such that thousands of genes can be assayed at once. A fundamental understanding of plant responses and adaptation to low pressures can now be approached and translated into procedures and engineering considerations to enhance plant growth at low atmospheric pressures. In anticipation of such studies, we present here the background arguments supporting these contentions, as well as informed speculation about the kinds of molecular physiological responses that might be expected of plants in low-pressure environments. PMID:11987308

  16. Epithelium: At the interface of innate and adaptive immune responses

    PubMed Central

    Schleimer, Robert P.; Kato, Atsushi; Kern, Robert; Kuperman, Douglas; Avila, Pedro C.

    2009-01-01

    Several diseases of the airways have a strong component of allergic inflammation in their cause, including allergic rhinitis, asthma, polypoid chronic rhinosinusitis, eosinophilic bronchitis, and others. Although the roles played by antigens and pathogens vary, these diseases have in common a pathology that includes marked activation of epithelial cells in the upper airways, the lower airways, or both. Substantial new evidence indicates an important role of epithelial cells as both mediators and regulators of innate immune responses and adaptive immune responses, as well as the transition from innate immunity to adaptive immunity. The purpose of this review is to discuss recent studies that bear on the molecular and cellular mechanisms by which epithelial cells help to shape the responses of dendritic cells, T cells, and B cells and inflammatory cell recruitment in the context of human disease. Evidence will be discussed that suggests that secreted products of epithelial cells and molecules expressed on their cell surfaces can profoundly influence both immunity and inflammation in the airways. PMID:17949801

  17. Aeroelastic Response of the Adaptive Compliant Trailing Edge Transtition Section

    NASA Technical Reports Server (NTRS)

    Herrera, Claudia Y.; Spivey, Natalie D.; Lung, Shun-fat

    2016-01-01

    The Adaptive Compliant Trailing Edge demonstrator was a joint task under the Environmentally Responsible Aviation Project in partnership with the Air Force Research Laboratory and FlexSys, Inc. (Ann Arbor, Michigan), chartered by the National Aeronautics and Space Administration to develop advanced technologies that enable environmentally friendly aircraft, such as continuous mold-line technologies. The Adaptive Compliant Trailing Edge demonstrator encompassed replacing the Fowler flaps on the SubsoniC Aircraft Testbed, a Gulfstream III (Gulfstream Aerospace, Savannah, Georgia) aircraft, with control surfaces developed by FlexSys, Inc., a pair of uniquely-designed, unconventional flaps to be used as lifting surfaces during flight-testing to substantiate their structural effectiveness. The unconventional flaps consisted of a main flap section and two transition sections, inboard and outboard, which demonstrated the continuous mold-line technology. Unique characteristics of the transition sections provided a challenge to the airworthiness assessment for this part of the structure. A series of build-up tests and analyses were conducted to ensure the data required to support the airworthiness assessment were acquired and applied accurately. The transition sections were analyzed both as individual components and as part of the flight-test article assembly. Instrumentation was installed in the transition sections based on the analysis to best capture the in-flight aeroelastic response. Flight-testing was conducted and flight data were acquired to validate the analyses. This paper documents the details of the aeroelastic assessment and in-flight response of the transition sections of the unconventional Adaptive Compliant Trailing Edge flaps.

  18. Glassy Dynamics in the Adaptive Immune Response Prevents Autoimmune Disease

    NASA Astrophysics Data System (ADS)

    Sun, Jun; Earl, David J.; Deem, Michael W.

    2005-09-01

    The immune system normally protects the human host against death by infection. However, when an immune response is mistakenly directed at self-antigens, autoimmune disease can occur. We describe a model of protein evolution to simulate the dynamics of the adaptive immune response to antigens. Computer simulations of the dynamics of antibody evolution show that different evolutionary mechanisms, namely, gene segment swapping and point mutation, lead to different evolved antibody binding affinities. Although a combination of gene segment swapping and point mutation can yield a greater affinity to a specific antigen than point mutation alone, the antibodies so evolved are highly cross reactive and would cause autoimmune disease, and this is not the chosen dynamics of the immune system. We suggest that in the immune system’s search for antibodies, a balance has evolved between binding affinity and specificity.

  19. Innate and adaptive immune responses in neurodegeneration and repair.

    PubMed

    Amor, Sandra; Woodroofe, M Nicola

    2014-03-01

    Emerging evidence suggests important roles of the innate and adaptive immune responses in the central nervous system (CNS) in neurodegenerative diseases. In this special review issue, five leading researchers discuss the evidence for the beneficial as well as the detrimental impact of the immune system in the CNS in disorders including Alzheimer's disease, multiple sclerosis and CNS injury. Several common pathological mechanisms emerge indicating that these pathways could provide important targets for manipulating the immune reposes in neurodegenerative disorders. The articles highlight the role of the traditional resident immune cell of the CNS - the microglia - as well as the role of other glia astrocytes and oligodendrocytes in immune responses and their interplay with other immune cells including, mast cells, T cells and B cells. Future research should lead to new discoveries which highlight targets for therapeutic interventions which may be applicable to a range of neurodegenerative diseases.

  20. Radio-Adaptive Response to Environmental Exposures at Chernobyl

    PubMed Central

    Rodgers, Brenda E.; Holmes, Kristen M.

    2008-01-01

    The genetic consequences resulting from environmental exposure to ionizing radiation have a significant impact on both radiation regulatory policies and the comprehension of the human health risks associated with radiation exposure. The primary objectives of the study were to assess 1) genotoxicity of exposure to radiation as a function of absorbed dose and dose rate, and 2) induction of a radio-adaptive response following a priming dose at varying dose rates. Results demonstrated that sub-acute environmental exposures of 10cGy gamma radiation resulted in indistinguishable levels of chromosomal damage as compared to controls. A radio-adaptive response was observed in all experimental groups, exposed to a subsequent acute challenge dose of 1.5 Gy, demonstrating that low dose rates of low energy transfer (LET) radiation are effective in reducing genetic damage from a subsequent acute low-LET radiation exposure. Furthermore, the data presented herein demonstrate a potential beneficial effect of sub-chronic exposure to low levels of low-LET radiation in an environmental setting and do not support the Linear No Threshold (LNT) hypothesis. PMID:18648577

  1. Innate and Adaptive Immune Response to Fungal Products and Allergens.

    PubMed

    Williams, P Brock; Barnes, Charles S; Portnoy, Jay M

    2016-01-01

    Exposure to fungi and their products is practically ubiquitous, yet most of this is of little consequence to most healthy individuals. This is because there are a number of elaborate mechanisms to deal with these exposures. Most of these mechanisms are designed to recognize and neutralize such exposures. However, in understanding these mechanisms it has become clear that many of them overlap with our ability to respond to disruptions in tissue function caused by trauma or deterioration. These responses involve the innate and adaptive immune systems usually through the activation of nuclear factor kappa B and the production of cytokines that are considered inflammatory accompanied by other factors that can moderate these reactivities. Depending on different genetic backgrounds and the extent of activation of these mechanisms, various pathologies with resulting symptoms can ensue. Complicating this is the fact that these mechanisms can bias toward type 2 innate and adaptive immune responses. Thus, to understand what we refer to as allergens from fungal sources, we must first understand how they influence these innate mechanisms. In doing so it has become clear that many of the proteins that are described as fungal allergens are essentially homologues of our own proteins that signal or cause tissue disruptions.

  2. Autophagy suppresses host adaptive immune responses toward Borrelia burgdorferi.

    PubMed

    Buffen, Kathrin; Oosting, Marije; Li, Yang; Kanneganti, Thirumala-Devi; Netea, Mihai G; Joosten, Leo A B

    2016-09-01

    We have previously demonstrated that inhibition of autophagy increased the Borrelia burgdorferi induced innate cytokine production in vitro, but little is known regarding the effect of autophagy on in vivo models of Borrelia infection. Here, we showed that ATG7-deficient mice that were intra-articular injected with Borrelia spirochetes displayed increased joint swelling, cell influx, and enhanced interleukin-1β and interleukin-6 production by inflamed synovial tissue. Because both interleukin-1β and interleukin-6 are linked to the development of adaptive immune responses, we examine the function of autophagy on Borrelia induced adaptive immunity. Human peripheral blood mononuclear cells treated with autophagy inhibitors showed an increase in interleukin-17, interleukin-22, and interferon-γ production in response to exposure to Borrelia burgdorferi. Increased IL-17 production was dependent on IL-1β release but, interestingly, not on interleukin-23 production. In addition, cytokine quantitative trait loci in ATG9B modulate the Borrelia induced interleukin-17 production. Because high levels of IL-17 have been found in patients with confirmed, severe, chronic borreliosis, we propose that the modulation of autophagy may be a potential target for anti-inflammatory therapy in patients with persistent Lyme disease. PMID:27101991

  3. [Adaptive immune response and associated trigger factors in atopic dermatitis].

    PubMed

    Heratizadeh, A; Werfel, T; Rösner, L M

    2015-02-01

    Due to a broad variety of extrinsic trigger factors, patients with atopic dermatitis (AD) are characterized by complex response mechanisms of the adaptive immune system. Notably, skin colonization with Staphylococcus aureus seems to be of particular interest since not only exotoxins, but also other proteins of S. aureus can induce specific humoral and cellular immune responses which partially also correlate with the severity of AD. In a subgroup of AD patients Malassezia species induce specific IgE- and T cell-responses which has been demonstrated by atopy patch tests. Moreover, Mala s 13 is characterized by high cross-reactivity to the human corresponding protein (thioredoxin). Induction of a potential autoallergy due to molecular mimicry seems therefore to be relevant for Malassezia-sensitized AD patients. In addition, sensitization mechanisms to autoallergens aside from cross-reactivity are under current investigation. Regarding inhalant allergens, research projects are in progress with the aim to elucidate allergen-specific immune response mechanisms in more depth. For grass-pollen allergens a flare-up of AD following controlled exposure has been observed while for house dust mite-allergens a polarization towards Th2 and Th2/Th17 T cell phenotypes can be observed. These and further findings might finally contribute to the development of specific and effective treatments for aeroallergen-sensitized AD patients. PMID:25532900

  4. Response of pulmonary rapidly adapting receptors during lung inflation.

    PubMed

    Pack, A I; DeLaney, R G

    1983-09-01

    Studies were conducted to establish the factors that determine the response of canine pulmonary rapidly adapting receptors (RAR) during lung inflation. Inflations of the lung were performed at several constant rates during which the activity of individual RAR was counted. At each rate of inflation tested multiple identical tests were performed. The volume of each test inflation was controlled. Data obtained in all tests at each flow rate were averaged to give the mean response of the receptor at that rate of inflation. These studies indicate the major response characteristics of RAR during lung inflation in conditions of relatively constant lung mechanics. First, at a constant rate of inflation, the activity of RAR augments increasingly as the lung is expanded. Second, their activity is influenced markedly by the rate of inflation. However, this sensitivity is nonlinear. Specifically, at low rates of inflation increases in flow rate produce more marked augmentation of RAR firing than do identical increases in flow at higher rates of inflation. The major difference between receptors is in their threshold; however, this too is a function of flow rate. With increasing flow rate the threshold, whether measured as the inflation volume or transpulmonary pressure at which receptors begin to fire, declines. The response of receptors, however, with thresholds over the entire range show the major features discussed above. The present results provide quantitative information which are necessary to begin to eludicate the transduction properties of this receptor type.

  5. Development and Standardization of the Diagnostic Adaptive Behavior Scale: Application of Item Response Theory to the Assessment of Adaptive Behavior

    ERIC Educational Resources Information Center

    Tassé, Marc J.; Schalock, Robert L.; Thissen, David; Balboni, Giulia; Bersani, Henry, Jr.; Borthwick-Duffy, Sharon A.; Spreat, Scott; Widaman, Keith F.; Zhang, Dalun; Navas, Patricia

    2016-01-01

    The Diagnostic Adaptive Behavior Scale (DABS) was developed using item response theory (IRT) methods and was constructed to provide the most precise and valid adaptive behavior information at or near the cutoff point of making a decision regarding a diagnosis of intellectual disability. The DABS initial item pool consisted of 260 items. Using IRT…

  6. Biological stress response terminology: Integrating the concepts of adaptive response and preconditioning stress within a hormetic dose-response framework.

    PubMed

    Calabrese, Edward J; Bachmann, Kenneth A; Bailer, A John; Bolger, P Michael; Borak, Jonathan; Cai, Lu; Cedergreen, Nina; Cherian, M George; Chiueh, Chuang C; Clarkson, Thomas W; Cook, Ralph R; Diamond, David M; Doolittle, David J; Dorato, Michael A; Duke, Stephen O; Feinendegen, Ludwig; Gardner, Donald E; Hart, Ronald W; Hastings, Kenneth L; Hayes, A Wallace; Hoffmann, George R; Ives, John A; Jaworowski, Zbigniew; Johnson, Thomas E; Jonas, Wayne B; Kaminski, Norbert E; Keller, John G; Klaunig, James E; Knudsen, Thomas B; Kozumbo, Walter J; Lettieri, Teresa; Liu, Shu-Zheng; Maisseu, Andre; Maynard, Kenneth I; Masoro, Edward J; McClellan, Roger O; Mehendale, Harihara M; Mothersill, Carmel; Newlin, David B; Nigg, Herbert N; Oehme, Frederick W; Phalen, Robert F; Philbert, Martin A; Rattan, Suresh I S; Riviere, Jim E; Rodricks, Joseph; Sapolsky, Robert M; Scott, Bobby R; Seymour, Colin; Sinclair, David A; Smith-Sonneborn, Joan; Snow, Elizabeth T; Spear, Linda; Stevenson, Donald E; Thomas, Yolene; Tubiana, Maurice; Williams, Gary M; Mattson, Mark P

    2007-07-01

    Many biological subdisciplines that regularly assess dose-response relationships have identified an evolutionarily conserved process in which a low dose of a stressful stimulus activates an adaptive response that increases the resistance of the cell or organism to a moderate to severe level of stress. Due to a lack of frequent interaction among scientists in these many areas, there has emerged a broad range of terms that describe such dose-response relationships. This situation has become problematic because the different terms describe a family of similar biological responses (e.g., adaptive response, preconditioning, hormesis), adversely affecting interdisciplinary communication, and possibly even obscuring generalizable features and central biological concepts. With support from scientists in a broad range of disciplines, this article offers a set of recommendations we believe can achieve greater conceptual harmony in dose-response terminology, as well as better understanding and communication across the broad spectrum of biological disciplines.

  7. Offspring's hydromineral adaptive responses to maternal undernutrition during lactation.

    PubMed

    Nuñez, P; Arguelles, J; Perillan, C

    2015-12-01

    Early development, throughout gestation and lactation, represents a period of extreme vulnerability during which susceptibility to later metabolic and cardiovascular injuries increases. Maternal diet is a major determinant of the foetal and newborn developmental environment; maternal undernutrition may result in adaptive responses leading to structural and molecular alterations in various organs and tissues, such as the brain and kidney. New nephron anlages appear in the renal cortex up to postnatal day 4 and the last anlages to be formed develop into functional nephrons by postnatal day 10 in rodents. We used a model of undernutrition in rat dams that were food-restricted during the first half of the lactation period in order to study the long-term effects of maternal diet on renal development, behaviour and neural hydromineral control mechanisms. The study showed that after 40% food restriction in maternal dietary intake, the dipsogenic responses for both water and salt intake were not altered; Fos expression in brain areas investigated involved in hydromineral homeostasis control was always higher in the offspring in response to isoproterenol. This was accompanied by normal plasma osmolality changes and typical renal histology. These results suggest that the mechanisms for the control of hydromineral balance were unaffected in the offspring of these 40% food-restricted mothers. Undernutrition of the pups may not be as drastic as suggested by dams' restriction. PMID:26234469

  8. Proteasome function shapes innate and adaptive immune responses.

    PubMed

    Kammerl, Ilona E; Meiners, Silke

    2016-08-01

    The proteasome system degrades more than 80% of intracellular proteins into small peptides. Accordingly, the proteasome is involved in many essential cellular functions, such as protein quality control, transcription, immune responses, cell signaling, and apoptosis. Moreover, degradation products are loaded onto major histocompatibility class I molecules to communicate the intracellular protein composition to the immune system. The standard 20S proteasome core complex contains three distinct catalytic active sites that are exchanged upon stimulation with inflammatory cytokines to form the so-called immunoproteasome. Immunoproteasomes are constitutively expressed in immune cells and have different proteolytic activities compared with standard proteasomes. They are rapidly induced in parenchymal cells upon intracellular pathogen infection and are crucial for priming effective CD8(+) T-cell-mediated immune responses against infected cells. Beyond shaping these adaptive immune reactions, immunoproteasomes also regulate the function of immune cells by degradation of inflammatory and immune mediators. Accordingly, they emerge as novel regulators of innate immune responses. The recently unraveled impairment of immunoproteasome function by environmental challenges and by genetic variations of immunoproteasome genes might represent a currently underestimated risk factor for the development and progression of lung diseases. In particular, immunoproteasome dysfunction will dampen resolution of infections, thereby promoting exacerbations, may foster autoimmunity in chronic lung diseases, and possibly contributes to immune evasion of tumor cells. Novel pharmacological tools, such as site-specific inhibitors of the immunoproteasome, as well as activity-based probes, however, hold promises as innovative therapeutic drugs for respiratory diseases and biomarker profiling, respectively. PMID:27343191

  9. Proteasome function shapes innate and adaptive immune responses.

    PubMed

    Kammerl, Ilona E; Meiners, Silke

    2016-08-01

    The proteasome system degrades more than 80% of intracellular proteins into small peptides. Accordingly, the proteasome is involved in many essential cellular functions, such as protein quality control, transcription, immune responses, cell signaling, and apoptosis. Moreover, degradation products are loaded onto major histocompatibility class I molecules to communicate the intracellular protein composition to the immune system. The standard 20S proteasome core complex contains three distinct catalytic active sites that are exchanged upon stimulation with inflammatory cytokines to form the so-called immunoproteasome. Immunoproteasomes are constitutively expressed in immune cells and have different proteolytic activities compared with standard proteasomes. They are rapidly induced in parenchymal cells upon intracellular pathogen infection and are crucial for priming effective CD8(+) T-cell-mediated immune responses against infected cells. Beyond shaping these adaptive immune reactions, immunoproteasomes also regulate the function of immune cells by degradation of inflammatory and immune mediators. Accordingly, they emerge as novel regulators of innate immune responses. The recently unraveled impairment of immunoproteasome function by environmental challenges and by genetic variations of immunoproteasome genes might represent a currently underestimated risk factor for the development and progression of lung diseases. In particular, immunoproteasome dysfunction will dampen resolution of infections, thereby promoting exacerbations, may foster autoimmunity in chronic lung diseases, and possibly contributes to immune evasion of tumor cells. Novel pharmacological tools, such as site-specific inhibitors of the immunoproteasome, as well as activity-based probes, however, hold promises as innovative therapeutic drugs for respiratory diseases and biomarker profiling, respectively.

  10. Growth responses and adaptations of Fraxinus pennsylvanica seedlings to flooding

    SciTech Connect

    Sena Gomes, A.R.; Kozlowski, T.T.

    1980-01-01

    Flooding induced several physiological and morphological changes in Fraxinus pennsylvanica seedlings, with stomatal closure among the earliest responses. Subsequent changes included: reduction in dry weight increment of roots, stems, and leaves; formation of hypertrophied lenticles and production of adventitious roots on submerged portions of the stem above the soil line; leaf necrosis; and leaf abscission. After 15 days of stomatal closure as a results of flooding, stomata began to reopen progressively until stomata aperture was similar in flooded and unflooded plants. Adventitious roots began to form at about the time stomatal reopening began. As more adventitious roots formed, elongated, and branched, the stomata opened further. The formation of adventitious roots was in important adaptation for flooding tolerance as shown by the high efficiency of adventitious roots in absorption of water and in high correlation between the production of adventitious roots and stomatal reopening. 6 figures, 2 tables.

  11. Plant Heat Adaptation: priming in response to heat stress

    PubMed Central

    Bäurle, Isabel

    2016-01-01

    Abiotic stress is a major threat to crop yield stability. Plants can be primed by heat stress, which enables them to subsequently survive temperatures that are lethal to a plant in the naïve state. This is a rapid response that has been known for many years and that is highly conserved across kingdoms. Interestingly, recent studies in Arabidopsis and rice show that this thermo-priming lasts for several days at normal growth temperatures and that it is an active process that is genetically separable from the priming itself. This is referred to as maintenance of acquired thermotolerance or heat stress memory. Such a memory conceivably has adaptive advantages under natural conditions, where heat stress often is chronic or recurring. In this review, I will focus on recent advances in the mechanistic understanding of heat stress memory. PMID:27134736

  12. Glassy Dynamics in the Adaptive Immune Response Prevents Autoimmune Disease

    NASA Astrophysics Data System (ADS)

    Sun, Jun; Deem, Michael

    2006-03-01

    The immune system normally protects the human host against death by infection. However, when an immune response is mistakenly directed at self antigens, autoimmune disease can occur. We describe a model of protein evolution to simulate the dynamics of the adaptive immune response to antigens. Computer simulations of the dynamics of antibody evolution show that different evolutionary mechanisms, namely gene segment swapping and point mutation, lead to different evolved antibody binding affinities. Although a combination of gene segment swapping and point mutation can yield a greater affinity to a specific antigen than point mutation alone, the antibodies so evolved are highly cross-reactive and would cause autoimmune disease, and this is not the chosen dynamics of the immune system. We suggest that in the immune system a balance has evolved between binding affinity and specificity in the mechanism for searching the amino acid sequence space of antibodies. Our model predicts that chronic infection may lead to autoimmune disease as well due to cross-reactivity and suggests a broad distribution for the time of onset of autoimmune disease due to chronic exposure. The slow search of antibody sequence space by point mutation leads to the broad of distribution times.

  13. Control of the Adaptive Immune Response by Tumor Vasculature

    PubMed Central

    Mauge, Laetitia; Terme, Magali; Tartour, Eric; Helley, Dominique

    2014-01-01

    The endothelium is nowadays described as an entire organ that regulates various processes: vascular tone, coagulation, inflammation, and immune cell trafficking, depending on the vascular site and its specific microenvironment as well as on endothelial cell-intrinsic mechanisms like epigenetic changes. In this review, we will focus on the control of the adaptive immune response by the tumor vasculature. In physiological conditions, the endothelium acts as a barrier regulating cell trafficking by specific expression of adhesion molecules enabling adhesion of immune cells on the vessel, and subsequent extravasation. This process is also dependent on chemokine and integrin expression, and on the type of junctions defining the permeability of the endothelium. Endothelial cells can also regulate immune cell activation. In fact, the endothelial layer can constitute immunological synapses due to its close interactions with immune cells, and the delivery of co-stimulatory or co-inhibitory signals. In tumor conditions, the vasculature is characterized by an abnormal vessel structure and permeability, and by a specific phenotype of endothelial cells. All these abnormalities lead to a modulation of intra-tumoral immune responses and contribute to the development of intra-tumoral immunosuppression, which is a major mechanism for promoting the development, progression, and treatment resistance of tumors. The in-depth analysis of these various abnormalities will help defining novel targets for the development of anti-tumoral treatments. Furthermore, eventual changes of the endothelial cell phenotype identified by plasma biomarkers could secondarily be selected to monitor treatment efficacy. PMID:24734218

  14. Physiologically responsive, mechanically adaptive polymer optical fibers for optogenetics.

    PubMed

    Jorfi, Mehdi; Voirin, Guy; Foster, E Johan; Weder, Christoph

    2014-05-15

    The capability to deliver light to specific locations within the brain using optogenetic tools has opened up new possibilities in the field of neural interfacing. In this context, optical fibers are commonly inserted into the brain to activate or mute neurons using photosensitive proteins. While chronic optogenetic stimulation studies are just beginning to emerge, knowledge gathered in connection with electrophysiological implants suggests that the mechanical mismatch of conventional optical fibers and the cortical tissue may be a significant contributor to neuroinflammatory response. Here, we present the design and fabrication of physiologically responsive, mechanically adaptive optical fibers made of poly(vinyl alcohol) (PVA) that may mitigate this problem. Produced by a one-step wet-spinning process, the fibers display a tensile storage modulus E' of ∼7000  MPa in the dry state at 25°C and can thus readily be inserted into cortical tissue. Exposure to water causes a drastic reduction of E' to ∼35  MPa on account of modest swelling with the water. The optical properties at 470 and 590 were comparable with losses of 0.7±0.04  dB/cm at 470 nm and 0.6±0.1  dB/cm at 590 nm in the dry state and 1.1±0.1  dB/cm at 470 nm and 0.9±0.3  dB/cm at 590 nm in the wet state. The dry end of a partially switched fiber with a length of 10 cm was coupled with a light-emitting diode with an output of 10.1 mW to deliver light with a power density of >500  mW/cm2 from the wet end, which is more than sufficient to stimulate neurons in vivo. Thus, even without a low-refractive index cladding, the physiologically responsive, mechanically adaptive optical fibers presented here appear to be a very useful new tool for future optogenetic studies.

  15. Extratropical Transitions in Atlantic Canada: Impacts and Adaptive Responses

    NASA Astrophysics Data System (ADS)

    Masson, Athena; Catto, Norm

    2013-04-01

    . Storm surge damage occurred along the north shore of the Bonavista Peninsula. Similar effects, differing only in the size of the affected areas, have resulted from several extratropical transitions which have impacted Atlantic Canada since July 1989. Extratropical transition "Leslie" impacted Newfoundland on 10-11 September 2012. Although the area affected was comparable to "Igor", wind velocities and rainfall totals were less, fortunately limiting damage. Preparation, advance warning to the population, proaction, and response efforts all showed significant improvement, however, indicating that the experience gained from coping with "Igor" had been successfully applied in adaptation to "Leslie". Extratropical transitions pose a significantly different set of challenges for adaptation in comparison to purely tropical hurricanes, and responses and adaptation strategies should be tailored to address these specific events. Calculating the frequency, magnitude and intensity of potential shifts is important for accurate forecasting and public awareness, safety management, preparedness, and adaptation. Available data indicate an increase in extratropical frequency and severity in Atlantic Canada since 1991, but there are difficulties in establishing the extent and nature of transition for previous storm events. A cautionary policy would assume no significant changes in extratropical transition frequency for Atlantic Canada, but would also acknowledge that large events remain probable.

  16. Airway goblet cells: responsive and adaptable front-line defenders.

    PubMed

    Rogers, D F

    1994-09-01

    development of a hypersecretory epithelium include excessive discharge of mucus and increased expression of airway mucin messenger ribonucleic acid (mRNA). Cessation of chronic airway stress rapidly reverses the increased number of goblet cells. Irritant-induced increases in number of goblet cells can be inhibited by a variety of drugs with anti-inflammatory and mucoregulatory properties, and the reversal to normal numbers after cessation of the irritation is speeded by these drugs. The ability of goblet cells to be progenitors of ciliated cells, to rapidly produce vast quantities of mucus in response to acute airway insult, and to change in number according to variations in chronic insult indicates that these cells are vitally important responsive and adaptable front-line defenders of the airways. PMID:7995400

  17. Distributed adaptive diagnosis of sensor faults using structural response data

    NASA Astrophysics Data System (ADS)

    Dragos, Kosmas; Smarsly, Kay

    2016-10-01

    The reliability and consistency of wireless structural health monitoring (SHM) systems can be compromised by sensor faults, leading to miscalibrations, corrupted data, or even data loss. Several research approaches towards fault diagnosis, referred to as ‘analytical redundancy’, have been proposed that analyze the correlations between different sensor outputs. In wireless SHM, most analytical redundancy approaches require centralized data storage on a server for data analysis, while other approaches exploit the on-board computing capabilities of wireless sensor nodes, analyzing the raw sensor data directly on board. However, using raw sensor data poses an operational constraint due to the limited power resources of wireless sensor nodes. In this paper, a new distributed autonomous approach towards sensor fault diagnosis based on processed structural response data is presented. The inherent correlations among Fourier amplitudes of acceleration response data, at peaks corresponding to the eigenfrequencies of the structure, are used for diagnosis of abnormal sensor outputs at a given structural condition. Representing an entirely data-driven analytical redundancy approach that does not require any a priori knowledge of the monitored structure or of the SHM system, artificial neural networks (ANN) are embedded into the sensor nodes enabling cooperative fault diagnosis in a fully decentralized manner. The distributed analytical redundancy approach is implemented into a wireless SHM system and validated in laboratory experiments, demonstrating the ability of wireless sensor nodes to self-diagnose sensor faults accurately and efficiently with minimal data traffic. Besides enabling distributed autonomous fault diagnosis, the embedded ANNs are able to adapt to the actual condition of the structure, thus ensuring accurate and efficient fault diagnosis even in case of structural changes.

  18. Cardiac adaptations of bullfrog tadpoles in response to chytrid infection.

    PubMed

    Salla, Raquel Fernanda; Gamero, Fernando Urban; Ribeiro, Larissa Rodrigues; Rizzi, Gisele Miglioranza; Medico, Samuel Espinosa Dal; Rissoli, Rafael Zanelli; Vieira, Conrado Augusto; Silva-Zacarin, Elaine Cristina Mathias; Leite, Domingos Silva; Abdalla, Fábio Camargo; Toledo, Luis Felipe; Costa, Monica Jones

    2015-08-01

    The chytrid fungus Batrachochytrium dendrobatidis (Bd) can result in heart failure in Bd-susceptible species. Since Bd infection generally does not cause mortality in North American bullfrogs, the aim of this work was to verify whether this species presents any cardiac adaptation that could improve the tolerance to the fungus. Thus, we analyzed tadpoles' activity level, relative ventricular mass, ventricle morphology, in loco heart frequency, and in vitro cardiac function. The results indicate that infected animals present an increase in both ventricular relative mass and in myofibrils' incidence, which accompanied the increase in myocytes' diameter. Such morphological alterations enabled an increase in the in vitro twitch force that, in vivo, would result in elevation of the cardiac stroke volume. This response requires much less energy expenditure than an elevation in heart frequency, but still enables the heart to pump a higher volume of blood per minute (i.e., an increase in cardiac output). As a consequence, the energy saved in the regulation of the cardiac function of Bd-infected tadpoles can be employed in other homeostatic adjustments to avoid the lethal effect of the fungus. Whether other species present this ability, and to what extent, remains uncertain, but such possible interspecific variability might explain different mortality rates among different species of Bd-infected amphibians. PMID:26055358

  19. Adaptive Response of T and B Cells in Atherosclerosis.

    PubMed

    Ketelhuth, Daniel F J; Hansson, Göran K

    2016-02-19

    Atherosclerosis is a chronic inflammatory disease that is initiated by the retention and accumulation of cholesterol-containing lipoproteins, particularly low-density lipoprotein, in the artery wall. In the arterial intima, lipoprotein components that are generated through oxidative, lipolytic, and proteolytic activities lead to the formation of several danger-associated molecular patterns, which can activate innate immune cells as well as vascular cells. Moreover, self- and non-self-antigens, such as apolipoprotein B-100 and heat shock proteins, can contribute to vascular inflammation by triggering the response of T and B cells locally. This process can influence the initiation, progression, and stability of plaques. Substantial clinical and experimental data support that the modulation of adaptive immune system may be used for treating and preventing atherosclerosis. This may lead to the development of more selective and less harmful interventions, while keeping host defense mechanisms against infections and tumors intact. Approaches such as vaccination might become a realistic option for cardiovascular disease, especially if they can elicit regulatory T and B cells and the secretion of atheroprotective antibodies. Nevertheless, difficulties in translating certain experimental data into new clinical therapies remain a challenge. In this review, we discuss important studies on the function of T- and B-cell immunity in atherosclerosis and their manipulation to develop novel therapeutic strategies against cardiovascular disease.

  20. Mitochondrial role in adaptive response to stress conditions in preeclampsia

    PubMed Central

    Vishnyakova, Polina A.; Volodina, Maria A.; Tarasova, Nadezhda V.; Marey, Maria V.; Tsvirkun, Daria V.; Vavina, Olga V.; Khodzhaeva, Zulfiya S.; Kan, Natalya E.; Menon, Ramkumar; Vysokikh, Mikhail Yu.; Sukhikh, Gennady T.

    2016-01-01

    Preeclampsia (PE) is a pregnancy-specific syndrome, characterized in general by hypertension with proteinuria or other systemic disturbances. PE is the major cause of maternal and fetal morbidity and mortality worldwide. However, the etiology of PE still remains unclear. Our study involved 38 patients: 14 with uncomplicated pregnancy; 13 with early-onset PE (eoPE); and 11 with late-onset PE (loPE). We characterized the immunophenotype of cells isolated from the placenta and all biopsy samples were stained positive for Cytokeratin 7, SOX2, Nestin, Vimentin, and CD44. We obtained a significant increase in OPA1 mRNA and protein expression in the eoPE placentas. Moreover, TFAM expression was down-regulated in comparison to the control (p < 0.01). Mitochondrial DNA copy number in eoPE placentas was significantly higher than in samples from normal pregnancies. We observed an increase of maximum coupled state 3 respiration rate in mitochondria isolated from the placenta in the presence of complex I substrates in the eoPE group and an increase of P/O ratio, citrate synthase activity and decrease of Ca2+-induced depolarization rate in both PE groups. Our results suggest an essential role of mitochondrial activity changes in an adaptive response to the development of PE. PMID:27573305

  1. Distributed reinforcement learning for adaptive and robust network intrusion response

    NASA Astrophysics Data System (ADS)

    Malialis, Kleanthis; Devlin, Sam; Kudenko, Daniel

    2015-07-01

    Distributed denial of service (DDoS) attacks constitute a rapidly evolving threat in the current Internet. Multiagent Router Throttling is a novel approach to defend against DDoS attacks where multiple reinforcement learning agents are installed on a set of routers and learn to rate-limit or throttle traffic towards a victim server. The focus of this paper is on online learning and scalability. We propose an approach that incorporates task decomposition, team rewards and a form of reward shaping called difference rewards. One of the novel characteristics of the proposed system is that it provides a decentralised coordinated response to the DDoS problem, thus being resilient to DDoS attacks themselves. The proposed system learns remarkably fast, thus being suitable for online learning. Furthermore, its scalability is successfully demonstrated in experiments involving 1000 learning agents. We compare our approach against a baseline and a popular state-of-the-art throttling technique from the network security literature and show that the proposed approach is more effective, adaptive to sophisticated attack rate dynamics and robust to agent failures.

  2. Cardiac adaptations of bullfrog tadpoles in response to chytrid infection.

    PubMed

    Salla, Raquel Fernanda; Gamero, Fernando Urban; Ribeiro, Larissa Rodrigues; Rizzi, Gisele Miglioranza; Medico, Samuel Espinosa Dal; Rissoli, Rafael Zanelli; Vieira, Conrado Augusto; Silva-Zacarin, Elaine Cristina Mathias; Leite, Domingos Silva; Abdalla, Fábio Camargo; Toledo, Luis Felipe; Costa, Monica Jones

    2015-08-01

    The chytrid fungus Batrachochytrium dendrobatidis (Bd) can result in heart failure in Bd-susceptible species. Since Bd infection generally does not cause mortality in North American bullfrogs, the aim of this work was to verify whether this species presents any cardiac adaptation that could improve the tolerance to the fungus. Thus, we analyzed tadpoles' activity level, relative ventricular mass, ventricle morphology, in loco heart frequency, and in vitro cardiac function. The results indicate that infected animals present an increase in both ventricular relative mass and in myofibrils' incidence, which accompanied the increase in myocytes' diameter. Such morphological alterations enabled an increase in the in vitro twitch force that, in vivo, would result in elevation of the cardiac stroke volume. This response requires much less energy expenditure than an elevation in heart frequency, but still enables the heart to pump a higher volume of blood per minute (i.e., an increase in cardiac output). As a consequence, the energy saved in the regulation of the cardiac function of Bd-infected tadpoles can be employed in other homeostatic adjustments to avoid the lethal effect of the fungus. Whether other species present this ability, and to what extent, remains uncertain, but such possible interspecific variability might explain different mortality rates among different species of Bd-infected amphibians.

  3. Mitochondrial role in adaptive response to stress conditions in preeclampsia.

    PubMed

    Vishnyakova, Polina A; Volodina, Maria A; Tarasova, Nadezhda V; Marey, Maria V; Tsvirkun, Daria V; Vavina, Olga V; Khodzhaeva, Zulfiya S; Kan, Natalya E; Menon, Ramkumar; Vysokikh, Mikhail Yu; Sukhikh, Gennady T

    2016-01-01

    Preeclampsia (PE) is a pregnancy-specific syndrome, characterized in general by hypertension with proteinuria or other systemic disturbances. PE is the major cause of maternal and fetal morbidity and mortality worldwide. However, the etiology of PE still remains unclear. Our study involved 38 patients: 14 with uncomplicated pregnancy; 13 with early-onset PE (eoPE); and 11 with late-onset PE (loPE). We characterized the immunophenotype of cells isolated from the placenta and all biopsy samples were stained positive for Cytokeratin 7, SOX2, Nestin, Vimentin, and CD44. We obtained a significant increase in OPA1 mRNA and protein expression in the eoPE placentas. Moreover, TFAM expression was down-regulated in comparison to the control (p < 0.01). Mitochondrial DNA copy number in eoPE placentas was significantly higher than in samples from normal pregnancies. We observed an increase of maximum coupled state 3 respiration rate in mitochondria isolated from the placenta in the presence of complex I substrates in the eoPE group and an increase of P/O ratio, citrate synthase activity and decrease of Ca(2+)-induced depolarization rate in both PE groups. Our results suggest an essential role of mitochondrial activity changes in an adaptive response to the development of PE. PMID:27573305

  4. Evolutionary responses of innate Immunity to adaptive immunity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Innate immunity is present in all metazoans, whereas the evolutionarily more novel adaptive immunity is limited to jawed fishes and their descendants (gnathostomes). We observe that the organisms that possess adaptive immunity lack diversity in their innate pattern recognition receptors (PRRs), rais...

  5. Human Adaptation Genetic Response Suites: Toward New Interventions and Countermeasures for Spaceflight

    NASA Technical Reports Server (NTRS)

    Sundaresan, A.; Pellis, N. R.

    2005-01-01

    Genetic response suites in human lymphocytes in response to microgravity are important to identify and further study in order to augment human physiological adaptation to novel environments. Emerging technologies, such as DNA micro array profiling, have the potential to identify novel genes that are involved in mediating adaptation to these environments. These genes may prove to be therapeutically valuable as new targets for countermeasures, or as predictive biomarkers of response to these new environments. Human lymphocytes cultured in lg and microgravity analog culture were analyzed for their differential gene expression response. Different groups of genes related to the immune response, cardiovascular system and stress response were then analyzed. Analysis of cells from multiple donors reveals a small shared set that are likely to be essential to adaptation. These three groups focus on human adaptation to new environments. The shared set contains genes related to T cell activation, immune response and stress response to analog microgravity.

  6. Tactile response adaptation to whisker stimulation in the lemniscal somatosensory pathway of rats.

    PubMed

    Martin-Cortecero, Jesus; Nuñez, Angel

    2014-12-01

    Response adaptation is associated with attenuation of neural responses as the result of different mechanisms. However, the main function of adaptation may be to enhance the flow of relevant information transmission in sensory pathways. To study tactile response adaptation in the somatosensory pathway, unit recordings were performed in the principal trigeminal nucleus, ventro postero-medial thalamic nucleus and barrel cortex by means of tungsten microelectrodes in urethane anesthetized rats. Tactile stimuli consisted in 20 ms duration whisker deflections at different frequencies (0.5-10 Hz). Presumably pyramidal cortical neurons showed response adaptation at frequencies >2 Hz while putative inhibitory cortical neurons did not show response adaptation at 0.5, 5 or 10 Hz. Inhibitory activity was increased by muscimol application into the cortex (8mM, 0.1 µl); in this condition cortical adaptation was not affected, suggesting that adaptation was not due to an increase of inhibitory mechanisms. Adaptation was also observed in subcortical structures although the response attenuation was lesser than in the barrel cortex. Adaptation remained in subcortical structures after reversible cortical inactivation by cooling the barrel cortex. Acetylcholine application (10 μM; 0.1 μl) into the barrel cortex reduced response adaptation through the activation of muscarinic receptors because the effect was blocked by intraperitoneal injection of atropine (1mg/kg), suggesting that adaptation may change according to the cortical Ach level. Results indicate that response adaptation increases along the somatosensory pathway probably to alter the sensitivity of neurons in order to encode sensory stimuli more efficiently and to enhance the detectability of rare stimuli.

  7. Radio-protective effect of cinnamic acid, a phenolic phytochemical, on genomic instability induced by X-rays in human blood lymphocytes in vitro.

    PubMed

    Cinkilic, Nilufer; Tüzün, Ece; Çetintaş, Sibel Kahraman; Vatan, Özgür; Yılmaz, Dilek; Çavaş, Tolga; Tunç, Sema; Özkan, Lütfi; Bilaloğlu, Rahmi

    2014-08-01

    The present study was designed to determine the protective activity of cinnamic acid against induction by X-rays of genomic instability in normal human blood lymphocytes. This radio-protective activity was assessed by use of the cytokinesis-block micronucleus test and the alkaline comet assay, with human blood lymphocytes isolated from two healthy donors. A Siemens Mevatron MD2 (Siemens AG, USA, 1994) linear accelerator was used for the irradiation with 1 or 2 Gy. Treatment of the lymphocytes with cinnamic acid prior to irradiation reduced the number of micronuclei when compared with that in control samples. Treatment with cinnamic acid without irradiation did not increase the number of micronuclei and did not show a cytostatic effect in the lymphocytes. The results of the alkaline comet assay revealed that cinnamic acid reduces the DNA damage induced by X-rays, showing a significant radio-protective effect. Cinnamic acid decreased the frequency of irradiation-induced micronuclei by 16-55% and reduced DNA breakage by 17-50%, as determined by the alkaline comet assay. Cinnamic acid may thus act as a radio-protective compound, and future studies may focus on elucidating the mechanism by which cinnamic acid offers radioprotection.

  8. No Evidence for a Low Linear Energy Transfer Adaptive Response in Irradiated RKO Cells

    SciTech Connect

    Sowa, Marianne B.; Goetz, Wilfried; Baulch, Janet E.; Lewis, Adam J.; Morgan, William F.

    2011-01-06

    It has become increasingly evident from reports in the literature that there are many confounding factors that are capable of modulating radiation induced non-targeted responses such as the bystander effect and the adaptive response. In this paper we examine recent data that suggest that the observation of non-targeted responses may not be universally observable for differing radiation qualities. We have conducted a study of the adaptive response following low LET exposures for human colon carcinoma cells and failed to observe adaption for the endpoints of clonogenic survival or micronucleus formation.

  9. Adaptive Control of Response Preparedness in Task Switching

    ERIC Educational Resources Information Center

    Steinhauser, Marco; Hubner, Ronald; Druey, Michel

    2009-01-01

    When rapidly switching between two tasks, bivalent stimuli can accidentally trigger the previously executed and therefore still activated response. Recently, it has been suggested that behavioral response-repetition effects reflect response inhibition that reduces the risk of such erroneous response repetitions. The present study investigated…

  10. Epigenetic inhibition of adaptive bypass responses to lapatinib by targeting BET Bromodomains.

    PubMed

    Stuhlmiller, Timothy J; Miller, Samantha M; Johnson, Gary L

    2016-01-01

    The characterization of kinases as oncogenic drivers has led to more than 30 FDA-approved targeted kinase inhibitors for cancer treatment. Unfortunately, these therapeutics fail to have clinical durability because of adaptive responses from the kinome and transcriptome that bypass inhibition of the targeted pathway. In our recent work, we describe a method to prevent these adaptive responses at an epigenetic level, generating a durable response to kinase inhibition. PMID:27308566

  11. Adaptive immune response of Vγ2Vδ2 T cells: a new paradigm

    PubMed Central

    Chen, Zheng W.; Letvin, Norman L.

    2010-01-01

    The role of γδ T cells in adaptive immunity remains uncertain. Recent studies have demonstrated that a unique subset of γδ T cells in primates can mount adaptive immune responses during mycobacterial infections. This Review discusses notable similarities and differences in adaptive immune responses between non-peptide-specific γδ T cells and peptide-specific αβ T cells, and discusses both the molecular basis for γδ T-cell responses and potential functions of these enigmatic cells. PMID:12697454

  12. Energy Sector Adaptation in Response to Water Scarcity

    NASA Astrophysics Data System (ADS)

    Johnson, N. A.; Fricko, O.; Parkinson, S.; Riahi, K.

    2015-12-01

    Global energy systems models have largely ignored the impacts of water scarcity on the energy sector and the related implications for climate change mitigation. However, significant water is required in the production of energy, including for thermoelectric power plant cooling, hydropower generation, irrigation for bioenergy, and the extraction and refining of liquid fuels. With a changing climate and expectations of increasing competition for water from the agricultural and municipal sectors, it is unclear whether sufficient water will be available where needed to support water-intensive energy technologies in the future. Thus, it is important that water use and water constraints are incorporated into energy systems models to better understand energy sector adaptation to water scarcity. The global energy systems model, MESSAGE, has recently been updated to quantify the water consumption and withdrawal requirements of the energy sector and now includes several cooling technologies for addressing water scarcity. This study introduces water constraints into the model to examine whether and how the energy sector can adapt to water scarcity over the next century. In addition, the implications for climate mitigation are evaluated under a scenario in which warming is limited to 2˚C over the pre-industrial level. Given the difficulty of introducing meaningful water constraints into global models, we use a simplistic approach and evaluate a series of scenarios in which the water available to the energy sector is systematically reduced. This approach allows for the evaluation of energy sector adaptations under various levels of water scarcity and can provide insight into how water scarcity, whether from climate change or competing demands, may impact the energy sector in different world regions. This study will provide insight into the following questions: How does the energy sector adapt to water scarcity in different regions? What are the costs associated with adaptation

  13. Clinal adaptation and adaptive plasticity in Artemisia californica: implications for the response of a foundation species to predicted climate change.

    PubMed

    Pratt, Jessica D; Mooney, Kailen A

    2013-08-01

    Local adaptation and plasticity pose significant obstacles to predicting plant responses to future climates. Although local adaptation and plasticity in plant functional traits have been documented for many species, less is known about population-level variation in plasticity and whether such variation is driven by adaptation to environmental variation. We examined clinal variation in traits and performance - and plastic responses to environmental change - for the shrub Artemisia californica along a 700 km gradient characterized (from south to north) by a fourfold increase in precipitation and a 61% decrease in interannual precipitation variation. Plants cloned from five populations along this gradient were grown for 3 years in treatments approximating the precipitation regimes of the north and south range margins. Most traits varying among populations did so clinally; northern populations (vs. southern) had higher water-use efficiencies and lower growth rates, C : N ratios and terpene concentrations. Notably, there was variation in plasticity for plant performance that was strongly correlated with source site interannual precipitation variability. The high-precipitation treatment (vs. low) increased growth and flower production more for plants from southern populations (181% and 279%, respectively) than northern populations (47% and 20%, respectively). Overall, precipitation variability at population source sites predicted 86% and 99% of variation in plasticity in growth and flowering, respectively. These striking, clinal patterns in plant traits and plasticity are indicative of adaptation to both the mean and variability of environmental conditions. Furthermore, our analysis of long-term coastal climate data in turn indicates an increase in interannual precipitation variation consistent with most global change models and, unexpectedly, this increased variation is especially pronounced at historically stable, northern sites. Our findings demonstrate the

  14. Clinal adaptation and adaptive plasticity in Artemisia californica: implications for the response of a foundation species to predicted climate change.

    PubMed

    Pratt, Jessica D; Mooney, Kailen A

    2013-08-01

    Local adaptation and plasticity pose significant obstacles to predicting plant responses to future climates. Although local adaptation and plasticity in plant functional traits have been documented for many species, less is known about population-level variation in plasticity and whether such variation is driven by adaptation to environmental variation. We examined clinal variation in traits and performance - and plastic responses to environmental change - for the shrub Artemisia californica along a 700 km gradient characterized (from south to north) by a fourfold increase in precipitation and a 61% decrease in interannual precipitation variation. Plants cloned from five populations along this gradient were grown for 3 years in treatments approximating the precipitation regimes of the north and south range margins. Most traits varying among populations did so clinally; northern populations (vs. southern) had higher water-use efficiencies and lower growth rates, C : N ratios and terpene concentrations. Notably, there was variation in plasticity for plant performance that was strongly correlated with source site interannual precipitation variability. The high-precipitation treatment (vs. low) increased growth and flower production more for plants from southern populations (181% and 279%, respectively) than northern populations (47% and 20%, respectively). Overall, precipitation variability at population source sites predicted 86% and 99% of variation in plasticity in growth and flowering, respectively. These striking, clinal patterns in plant traits and plasticity are indicative of adaptation to both the mean and variability of environmental conditions. Furthermore, our analysis of long-term coastal climate data in turn indicates an increase in interannual precipitation variation consistent with most global change models and, unexpectedly, this increased variation is especially pronounced at historically stable, northern sites. Our findings demonstrate the

  15. Light adaptation and the luminance-response function of the cone electroretinogram.

    PubMed

    Peachey, N S; Alexander, K R; Derlacki, D J; Fishman, G A

    1992-01-01

    Cone electroretinograms are typically isolated by presenting stimulus flashes against rod-desensitizing adapting fields. To investigate the manner in which adapting-field luminance affects cone electroretinogram response properties, we measured cone electroretinogram luminance-response functions of two normal subjects, with stimuli presented against adapting fields that ranged in luminance from -1.2 to 2.1 log cd/m2. A flicker rate of 31.1 Hz was used to isolate cone electroretinograms under all adaptation conditions. A hyperbolic equation of the form (R/Rmax) = Ln/(Ln + Kn) was fitted to each luminance-response function by a least-squares criterion. As adapting field luminance increased, the best-fit values of the variables K and n increased, which is in general agreement with results of electrophysiologic studies of light adaptation in retinal neurons. However, Rmax values also increased with adapting field luminance. The change in all three of these variables with adapting field luminance must be considered in the interpretation of cone electroretinogram luminance-response functions from patients with retinal disorders.

  16. Adaptability: Conceptual and Empirical Perspectives on Responses to Change, Novelty and Uncertainty

    ERIC Educational Resources Information Center

    Martin, Andrew J.; Nejad, Harry; Colmar, Susan; Liem, Gregory Arief D.

    2012-01-01

    Adaptability is proposed as individuals' capacity to constructively regulate psycho-behavioral functions in response to new, changing, and/or uncertain circumstances, conditions and situations. The present investigation explored the internal and external validity of an hypothesised adaptability scale. The sample comprised 2,731 high school…

  17. The effect of repeated mild cold water immersions on the adaptation of the vasomotor responses.

    PubMed

    Wakabayashi, Hitoshi; Wijayanto, Titis; Kuroki, Hideto; Lee, Joo-Young; Tochihara, Yutaka

    2012-07-01

    There are several types of cold adaptation based on the alteration of thermoregulatory response. It has been thought that the temperature of repeated cold exposures during the adaptation period is one of the factors affecting the type of cold adaptation developed. This study tested the hypothesis that repeated mild cold immersions would induce an insulative cold adaptation but would not alter the metabolic response. Seven healthy male participants were immersed to their xiphoid process level repeatedly in 26°C water for 60 min, 3 days every week, for 4 weeks. During the first and last exposure of this cold acclimation period, the participants underwent body immersion tests measuring their thermoregulatory responses to cold. Separately, they conducted finger immersion into 5°C water for 30 min to assess their cold-induced vasodilation (CIVD) response before and after cold acclimation. During the immersion to xiphoid process, participants showed significantly lower mean skin temperature and skin blood flow in the forearm post-acclimation, while no adaptation was observed in the metabolic response. Additionally, blunted CIVD responses were observed after cold acclimation. From these results, it was considered that the participants showed an insulative-type of cold acclimation after the repeated mild cold immersions. The major finding of this study was the acceptance of the hypothesis that repeated mild cold immersion was sufficient to induce insulative cold adaptation but did not alter the metabolic response. It is suggested that the adaptation in the thermoregulatory response is specific to the response which is repeatedly stimulated during the adaptation process.

  18. Cooperative adaptive responses in gene regulatory networks with many degrees of freedom.

    PubMed

    Inoue, Masayo; Kaneko, Kunihiko

    2013-04-01

    Cells generally adapt to environmental changes by first exhibiting an immediate response and then gradually returning to their original state to achieve homeostasis. Although simple network motifs consisting of a few genes have been shown to exhibit such adaptive dynamics, they do not reflect the complexity of real cells, where the expression of a large number of genes activates or represses other genes, permitting adaptive behaviors. Here, we investigated the responses of gene regulatory networks containing many genes that have undergone numerical evolution to achieve high fitness due to the adaptive response of only a single target gene; this single target gene responds to changes in external inputs and later returns to basal levels. Despite setting a single target, most genes showed adaptive responses after evolution. Such adaptive dynamics were not due to common motifs within a few genes; even without such motifs, almost all genes showed adaptation, albeit sometimes partial adaptation, in the sense that expression levels did not always return to original levels. The genes split into two groups: genes in the first group exhibited an initial increase in expression and then returned to basal levels, while genes in the second group exhibited the opposite changes in expression. From this model, genes in the first group received positive input from other genes within the first group, but negative input from genes in the second group, and vice versa. Thus, the adaptation dynamics of genes from both groups were consolidated. This cooperative adaptive behavior was commonly observed if the number of genes involved was larger than the order of ten. These results have implications in the collective responses of gene expression networks in microarray measurements of yeast Saccharomyces cerevisiae and the significance to the biological homeostasis of systems with many components.

  19. The Stress Response Systems: Universality and Adaptive Individual Differences

    ERIC Educational Resources Information Center

    Ellis, Bruce J.; Jackson, Jenee James; Boyce, W. Thomas

    2006-01-01

    Biological reactivity to psychological stressors comprises a complex, integrated system of central neural and peripheral neuroendocrine responses designed to prepare the organism for challenge or threat. Developmental experience plays a role, along with heritable variation, in calibrating the response dynamics of this system. This calibration…

  20. Inherited adaptation of genome-rewired cells in response to a challenging environment

    PubMed Central

    David, Lior; Stolovicki, Elad; Haziz, Efrat; Braun, Erez

    2010-01-01

    Despite their evolutionary significance, little is known about the adaptation dynamics of genomically rewired cells in evolution. We have confronted yeast cells carrying a rewired regulatory circuit with a severe and unforeseen challenge. The essential HIS3 gene from the histidine biosynthesis pathway was placed under the exclusive regulation of the galactose utilization system. Glucose containing medium strongly represses the GAL genes including HIS3 and these rewired cells are required to operate this essential gene. We show here that although there were no adapted cells prior to the encounter with glucose, a large fraction of cells adapted to grow in this medium and this adaptation was stably inherited. The adaptation relied on individual cells that switched into an adapted state and, thus, the adaptation was due to a response of many individual cells to the change in environment and not due to selection of rare advantageous phenotypes. The adaptation of numerous individual cells by heritable phenotypic switching in response to a challenge extends the common evolutionary framework and attests to the adaptive potential of regulatory circuits. PMID:20811567

  1. Length adaptation of smooth muscle contractile filaments in response to sustained activation.

    PubMed

    Stålhand, Jonas; Holzapfel, Gerhard A

    2016-05-21

    Airway and bladder smooth muscles are known to undergo length adaptation under sustained contraction. This adaptation process entails a remodelling of the intracellular actin and myosin filaments which shifts the peak of the active force-length curve towards the current length. Smooth muscles are therefore able to generate the maximum force over a wide range of lengths. In contrast, length adaptation of vascular smooth muscle has attracted very little attention and only a handful of studies have been reported. Although their results are conflicting on the existence of a length adaptation process in vascular smooth muscle, it seems that, at least, peripheral arteries and arterioles undergo such adaptation. This is of interest since peripheral vessels are responsible for pressure regulation, and a length adaptation will affect the function of the cardiovascular system. It has, e.g., been suggested that the inward remodelling of resistance vessels associated with hypertension disorders may be related to smooth muscle adaptation. In this study we develop a continuum mechanical model for vascular smooth muscle length adaptation by assuming that the muscle cells remodel the actomyosin network such that the peak of the active stress-stretch curve is shifted towards the operating point. The model is specialised to hamster cheek pouch arterioles and the simulated response to stepwise length changes under contraction. The results show that the model is able to recover the salient features of length adaptation reported in the literature.

  2. Cardiovascular and organ responses and adaptation responses to hypogravity in an experimental animal model.

    NASA Astrophysics Data System (ADS)

    Biondi, R.; Capodicasa, E.; Tassi, C.; Mezzasomal, L.; Benedetti, C.; Valiani, M.; Marconi, P.; Rossi, R.

    1995-10-01

    The head-down suspension (i.e antiorthostatic hypokinesia) rat is used to simulate weightlessness. However, little is known about cardiovascular and organ adaptation responses which, over a long time, can become pathologically significant. The purpose of this study was therefore to evaluate regional changes in the hematology parameters, Endotheline-1 (ET-1) concentration and urinary excretion of N-acetyl-β-D-glucosaminidase (EC 3.2.1.30) (NAG) in an experimental antiorthostatic rat model. The data indicate significant variations in the plasma ET-1 level in time, in the superior and inferior cava vessel blood of animals maintained for 10 days in hypogravity with respect to controls. These changes do not seem to be due to hemoconcentration. The increase in urinary NAG was observed during the first 24h of experiment, indicating renal stress, probably due to adverse blood flow variations within the organ. We conclude that the plasma ET-1 level changes could be responsible, overall for the blood flow variations in the kidney and renal stress could be the consequence of extended antiorthostatic hypokinesia. The ET-1 behaviour and urinary NAG excretion in rats exposed to antiorthostatic hypokjnetic hydynamia offer possibilities for understanding if these changes might be reversible or when they become pathological. This could give some relevant information about the effects of prolonged hypogravity during the space voyage.

  3. Influence of stimulus and oral adaptation temperature on gustatory responses in central taste-sensitive neurons.

    PubMed

    Li, Jinrong; Lemon, Christian H

    2015-04-01

    The temperature of taste stimuli can modulate gustatory processing. Perceptual data indicate that the adapted temperature of oral epithelia also influences gustation, although little is known about the neural basis of this effect. Here, we electrophysiologically recorded orosensory responses (spikes) to 25°C (cool) and 35°C (warm) solutions of sucrose (0.1 and 0.3 M), NaCl (0.004, 0.1, and 0.3 M), and water from taste-sensitive neurons in the nucleus of the solitary tract in mice under varied thermal adaptation of oral epithelia. Conditions included presentation of taste stimuli isothermal to adaptation temperatures of 25°C (constant cooling) and 35°C (constant warming), delivery of 25°C stimuli following 35°C adaptation (relative cooling), and presentation of 35°C stimuli following 25°C adaptation (relative warming). Responses to sucrose in sucrose-oriented cells (n = 15) were enhanced under the constant and relative warming conditions compared with constant cooling, where contiguous cooling across adaptation and stimulus periods induced the lowest and longest latency responses to sucrose. Yet compared with constant warming, cooling sucrose following warm adaptation (relative cooling) only marginally reduced activity to 0.1 M sucrose and did not alter responses to 0.3 M sucrose. Thus, warmth adaptation counteracted the attenuation in sucrose activity associated with stimulus cooling. Analysis of sodium-oriented (n = 25) neurons revealed adaptation to cool water, and cooling taste solutions enhanced unit firing to 0.004 M (perithreshold) NaCl, whereas warmth adaptation and stimulus warming could facilitate activity to 0.3 M NaCl. The concentration dependence of this thermal effect may reflect a dual effect of temperature on the sodium reception mechanism that drives sodium-oriented cells.

  4. Influence of stimulus and oral adaptation temperature on gustatory responses in central taste-sensitive neurons.

    PubMed

    Li, Jinrong; Lemon, Christian H

    2015-04-01

    The temperature of taste stimuli can modulate gustatory processing. Perceptual data indicate that the adapted temperature of oral epithelia also influences gustation, although little is known about the neural basis of this effect. Here, we electrophysiologically recorded orosensory responses (spikes) to 25°C (cool) and 35°C (warm) solutions of sucrose (0.1 and 0.3 M), NaCl (0.004, 0.1, and 0.3 M), and water from taste-sensitive neurons in the nucleus of the solitary tract in mice under varied thermal adaptation of oral epithelia. Conditions included presentation of taste stimuli isothermal to adaptation temperatures of 25°C (constant cooling) and 35°C (constant warming), delivery of 25°C stimuli following 35°C adaptation (relative cooling), and presentation of 35°C stimuli following 25°C adaptation (relative warming). Responses to sucrose in sucrose-oriented cells (n = 15) were enhanced under the constant and relative warming conditions compared with constant cooling, where contiguous cooling across adaptation and stimulus periods induced the lowest and longest latency responses to sucrose. Yet compared with constant warming, cooling sucrose following warm adaptation (relative cooling) only marginally reduced activity to 0.1 M sucrose and did not alter responses to 0.3 M sucrose. Thus, warmth adaptation counteracted the attenuation in sucrose activity associated with stimulus cooling. Analysis of sodium-oriented (n = 25) neurons revealed adaptation to cool water, and cooling taste solutions enhanced unit firing to 0.004 M (perithreshold) NaCl, whereas warmth adaptation and stimulus warming could facilitate activity to 0.3 M NaCl. The concentration dependence of this thermal effect may reflect a dual effect of temperature on the sodium reception mechanism that drives sodium-oriented cells. PMID:25673737

  5. Response and adaptation of Beagle dogs to hypergravity

    NASA Technical Reports Server (NTRS)

    Oyama, J.

    1975-01-01

    Eight male Beagle dogs, five months old, were centrifuged continuously for three months at progressively increasing loads. Heart rate and deep body temperature were monitored continuously by implant biotelemetry. Initially, centrifuged dogs showed transient decreases in heart rate and body temperature along with changes in their diurnal rhythm patterns. Compared with normal gravity controls, exposed dogs showed a slower growth rate and a reduced amount of body fat. Blood protein, total lipids, cholesterol, calcium, packed cell volume, red blood cell count, and hemoglobin were also decreased significantly. Absolute weights of the leg bones of centrifuged dogs were significantly greater than controls. Photon absorptiometry revealed significant density increases in selective regions of the femur and humerus of centrifuged dogs. In spite of the various changes noted, results from this and other studies affirm the view that dogs can tolerate and adapt to sustained loads as high as 2.5 g without serious impairment of their body structure and function.

  6. Exercise training - Blood pressure responses in subjects adapted to microgravity

    NASA Technical Reports Server (NTRS)

    Convertino, Victor A.

    1991-01-01

    Conventional endurance exercise training that involves daily workouts of 1-2 hr duration during exposure to microgravity has not proven completely effective in ameliorating postexposure orthostatic hypotension. Single bouts of intense exercise have been shown to increase plasma volume and baroreflex sensitivity in ambulatory subjects through 24 hr postexercise and to reverse decrements in maximal oxygen uptake and syncopal episodes following exposure to simulated microgravity. These physiological adaptations to acute intense exercise were opposite to those observed following exposure to microgravity. These results suggest that the 'exercise training' stimulus used to prevent orthostatic hypotension induced by microgravity may be specific and should be redefined to include single bouts of maximal exercise which may provide an acute effective countermeasure against postflight hypotension.

  7. Physiology and relevance of human adaptive thermogenesis response.

    PubMed

    Celi, Francesco S; Le, Trang N; Ni, Bin

    2015-05-01

    In homoeothermic organisms, the preservation of core temperature represents a primal function, and its costs in terms of energy expenditure can be considerable. In modern humans, the endogenous thermoregulation mechanisms have been replaced by clothing and environmental control, and the maintenance of thermoneutrality has been successfully achieved by manipulation of the micro- and macroenvironment. The rediscovery of the presence and activity of brown adipose tissue in adult humans has renewed the interest on adaptive thermogenesis (AT) as a means to facilitate weight loss and improve carbohydrate metabolism. The aim of this review is to describe the recent advancements in the study of this function, and to assess the potential and limitations of exploiting AT for environmental/behavioral, and pharmacological interventions. PMID:25869212

  8. Adapt

    NASA Astrophysics Data System (ADS)

    Bargatze, L. F.

    2015-12-01

    Active Data Archive Product Tracking (ADAPT) is a collection of software routines that permits one to generate XML metadata files to describe and register data products in support of the NASA Heliophysics Virtual Observatory VxO effort. ADAPT is also a philosophy. The ADAPT concept is to use any and all available metadata associated with scientific data to produce XML metadata descriptions in a consistent, uniform, and organized fashion to provide blanket access to the full complement of data stored on a targeted data server. In this poster, we present an application of ADAPT to describe all of the data products that are stored by using the Common Data File (CDF) format served out by the CDAWEB and SPDF data servers hosted at the NASA Goddard Space Flight Center. These data servers are the primary repositories for NASA Heliophysics data. For this purpose, the ADAPT routines have been used to generate data resource descriptions by using an XML schema named Space Physics Archive, Search, and Extract (SPASE). SPASE is the designated standard for documenting Heliophysics data products, as adopted by the Heliophysics Data and Model Consortium. The set of SPASE XML resource descriptions produced by ADAPT includes high-level descriptions of numerical data products, display data products, or catalogs and also includes low-level "Granule" descriptions. A SPASE Granule is effectively a universal access metadata resource; a Granule associates an individual data file (e.g. a CDF file) with a "parent" high-level data resource description, assigns a resource identifier to the file, and lists the corresponding assess URL(s). The CDAWEB and SPDF file systems were queried to provide the input required by the ADAPT software to create an initial set of SPASE metadata resource descriptions. Then, the CDAWEB and SPDF data repositories were queried subsequently on a nightly basis and the CDF file lists were checked for any changes such as the occurrence of new, modified, or deleted

  9. Adaptation response of Arabidopsis thaliana to random positioning

    NASA Astrophysics Data System (ADS)

    Kittang, A.-I.; Winge, P.; van Loon, J. J. W. A.; Bones, A. M.; Iversen, T.-H.

    2013-10-01

    Arabidopsis thaliana seedlings were exposed on a Random Positioning Machine (RPM) under light conditions for 16 h and the samples were analysed using microarray techniques as part of a preparation for a space experiment on the International Space Station (ISS). The results demonstrated a moderate to low regulation of 55 genes (<0.2% of the analysed genes). Genes encoding proteins associated with the chaperone system (e.g. heat shock proteins, HSPs) and enzymes in the flavonoid biosynthesis were induced. Most of the repressed genes were associated with light and sugar responses. Significant up-regulation of selected HSP genes was found by quantitative Real-Time PCR in 1 week old plants after the RPM exposure both in light and darkness. Higher quantity of DPBA (diphenylboric acid 2-amino-ethyl ester) staining was observed in the whole root and in the root elongation zone of the seedlings exposed on the RPM by use of fluorescent microscopy, indicating higher flavonoid content. The regulated genes and an increase of flavonoids are related to several stresses, but increased occurrence of HSPs and flavonoids are also representative for normal growth (e.g. gravitropism). The response could be a direct stress response or an integrated response of the two signal pathways of light and gravity resulting in an overall light response.

  10. Response-adaptive decision-theoretic trial design: operating characteristics and ethics.

    PubMed

    Lipsky, Ari M; Lewis, Roger J

    2013-09-20

    Adaptive randomization is used in clinical trials to increase statistical efficiency. In addition, some clinicians and researchers believe that using adaptive randomization leads necessarily to more ethical treatment of subjects in a trial. We develop Bayesian, decision-theoretic, clinical trial designs with response-adaptive randomization and a primary goal of estimating treatment effect and then contrast these designs with designs that also include in their loss function a cost for poor subject outcome. When the loss function did not incorporate a cost for poor subject outcome, the gains in efficiency from response-adaptive randomization were accompanied by ethically concerning subject allocations. Conversely, including a cost for poor subject outcome demonstrated a more acceptable balance between the competing needs in the trial. A subsequent, parallel set of trials designed to control explicitly types I and II error rates showed that much of the improvement achieved through modification of the loss function was essentially negated. Therefore, gains in efficiency from the use of a decision-theoretic, response-adaptive design using adaptive randomization may only be assumed to apply to those goals that are explicitly included in the loss function. Trial goals, including ethical ones, which do not appear in the loss function, are ignored and may even be compromised; it is thus inappropriate to assume that all adaptive trials are necessarily more ethical. Controlling types I and II error rates largely negates the benefit of including competing needs in favor of the goal of parameter estimation.

  11. Adaptation of high-gamma responses in human auditory association cortex

    PubMed Central

    Eliades, Steven J.; Crone, Nathan E.; Anderson, William S.; Ramadoss, Deepti; Lenz, Frederick A.

    2014-01-01

    This study investigates adaptation of high-frequency cortical responses [>60 Hz; high-gamma (HG)] to simple and complex sounds in human nonprimary auditory cortex. We used intracranial electrocorticographic recordings to measure event-related changes in HG power as a function of stimulus probability. Tone and speech stimuli were presented in a series of traditional oddball and control paradigms. We hypothesized that HG power attenuates with stimulus repetition over multiple concurrent time scales in auditory association cortex. Time-frequency analyses were performed to identify auditory-responsive sites. Single-trial analyses and quantitative modeling were then used to measure trial-to-trial changes in HG power for high (frequent), low (infrequent), and equal (control) stimulus probabilities. Results show strong reduction of HG responses to frequently repeated tones and speech, with no differences in responses to infrequent and equal-probability stimuli. Adaptation of the HG frequent response, and not stimulus-acoustic differences or deviance-detection enhancement effects, accounted for the differential responses observed for frequent and infrequent sounds. Adaptation of HG responses showed a rapid onset (less than two trials) with slower adaptation between consecutive, repeated trials (2–10 s) and across trials in a stimulus block (∼7 min). The auditory-evoked N100 response also showed repetition-related adaptation, consistent with previous human scalp and animal single-unit recordings. These findings indicate that HG responses are highly sensitive to the regularities of simple and complex auditory events and show adaptation on multiple concurrent time scales in human auditory association cortex. PMID:25122702

  12. Design of artificial genetic regulatory networks with multiple delayed adaptive responses*

    NASA Astrophysics Data System (ADS)

    Kaluza, Pablo; Inoue, Masayo

    2016-06-01

    Genetic regulatory networks with adaptive responses are widely studied in biology. Usually, models consisting only of a few nodes have been considered. They present one input receptor for activation and one output node where the adaptive response is computed. In this work, we design genetic regulatory networks with many receptors and many output nodes able to produce delayed adaptive responses. This design is performed by using an evolutionary algorithm of mutations and selections that minimizes an error function defined by the adaptive response in signal shapes. We present several examples of network constructions with a predefined required set of adaptive delayed responses. We show that an output node can have different kinds of responses as a function of the activated receptor. Additionally, complex network structures are presented since processing nodes can be involved in several input-output pathways. Supplementary material in the form of one nets file available from the Journal web page at http://dx.doi.org/10.1140/epjb/e2016-70172-9

  13. The innate and adaptive immune response to avian influenza virus infections and vaccines

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Protective immunity against viruses is mediated by the early innate immune responses and later on by the adaptive immune responses. The early innate immunity is designed to contain and limit virus replication in the host, primarily through cytokine and interferon production. Most all cells are cap...

  14. Roles and Responsibilities of Adapted Physical Education Teachers in an Urban School District

    ERIC Educational Resources Information Center

    Akuffo, Patrick B.; Hodge, Samuel R.

    2008-01-01

    The purpose of this study is to examine the roles and responsibilities of itinerant adapted physical education (APE) teachers at urban public schools. A second purpose is to determine how they execute their roles and responsibilities. Participants include six women with experience as itinerant APE teachers from the same urban school district. The…

  15. Adaptive response studies may help choose astronauts for long-term space travel

    NASA Astrophysics Data System (ADS)

    Mortazavi, S.

    Long-term manned exploratory missions are planned for the next decades. Exposure to high-energy neutrons, protons and high charge and energy particles during a deep space mission, requires proper radiation protection planning against the detrimental effects of space radiation. It has been estimated that exposure to unpredictable extremely large solar particle events would kill the astronauts without massive shielding in interplanetary space. Recent findings concerning the induction of adaptive response by neutrons or high levels of external and internal exposures including radon in human cells have opened a new horizon for possible implications of adaptive response in radiation protection and especially in protection against detrimental effects of high levels of radiation during a long-term space journey. Significant adaptive response has been demonstrated in humans after exposure to high levels of natural radiation. It has been shown that in some individuals who fail to show an adaptive response, extraordinary synergism was observed. Interestingly, it was observed that even when the frequency of chromosome aberrations in cells exposed to adapting dose alone or challenge dose alone, were not different than those of other study participants, a severe synergism observed in the cells exposed to challenge dose after an adapting dose. Based on the results obtained in this experiment, due to possible interactions between a chronic low dose and an acute high dose, a common G2 radiosensitivity assay cannot predict radiation risk during a long-term space mission. It can be suggested that the magnitude of adaptive response in lymphocyte samples of potential crew for a deep space mission should be assessed in ground based laboratory studies. Selected space crew who show a high magnitude of adaptive response in ground experiments, will be exposed to adapting higher than normal background radiation doses during mission and they will be considerably more resistant to high doses

  16. Chemical Tools To Monitor and Manipulate Adaptive Immune Responses.

    PubMed

    Doran, Todd M; Sarkar, Mohosin; Kodadek, Thomas

    2016-05-18

    Methods to monitor and manipulate the immune system are of enormous clinical interest. For example, the development of vaccines represents one of the earliest and greatest accomplishments of the biomedical research enterprise. More recently, drugs capable of "reawakening" the immune system to cancer have generated enormous excitement. But, much remains to be done. All drugs available today that manipulate the immune system cannot distinguish between "good" and "bad" immune responses and thus drive general and systemic immune suppression or activation. Indeed, with the notable exception of vaccines, our ability to monitor and manipulate antigen-specific immune responses is in its infancy. Achieving this finer level of control would be highly desirable. For example, it might allow the pharmacological editing of pathogenic immune responses without restricting the ability of the immune system to defend against infection. On the diagnostic side, a method to comprehensively monitor the circulating, antigen-specific antibody population could provide a treasure trove of clinically useful biomarkers, since many diseases expose the immune system to characteristic molecules that are deemed foreign and elicit the production of antibodies against them. This Perspective will discuss the state-of-the-art of this area with a focus on what we consider seminal opportunities for the chemistry community to contribute to this important field.

  17. Dark adaptation and the acuity/luminance response in senile macular degeneration (SMD).

    PubMed

    Brown, B; Kitchin, J L

    1983-08-01

    Patients with senile macular degeneration (SMD) often complain of problems with adaptation and have best acuity under a restricted range of lighting conditions. We investigated dark adaptation and acuity over a wide range of luminances in eight SMD patients and six age-matched controls. Some patients showed evidence of altered dark adaptation, with a much longer time required to reach asymptotic sensitivity levels than shown by normals; others had difficulty with spatial resolution at different light levels. There was good correlation between symptoms and test findings; all but one patient who reported difficulties with adaptation demonstrated either retarded adaptation, aberrant acuity/luminance response, or both. These data provide evidence that the processes which adjust the sensitivity of the retina and the spatial summation properties of the retina are disrupted in SMD.

  18. Gender differences in farmers' responses to climate change adaptation in Yongqiao District, China.

    PubMed

    Jin, Jianjun; Wang, Xiaomin; Gao, Yiwei

    2015-12-15

    This study examines the gender differences in farmers' responses to climate change adaption in Yongqiao District, China. A random sampling technique was used to select 220 household heads, while descriptive statistics and binary logit models were used to analyze the data obtained from the households. We determine that male and female respondents are not significantly different in their knowledge and perceptions of climate change, but there is a gender difference in adopting climate change adaptation measures. Male-headed households are more likely to adopt new technology for water conservation and to increase investment in irrigation infrastructure. The research also indicates that the adaptation decisions of male and female heads are influenced by different sets of factors. The findings of this research help to elucidate the determinants of climate change adaptation decisions for male and female-headed households and the strategic interventions necessary for effective adaptation.

  19. Prism adaptation magnitude has differential influences on perceptual versus manual responses.

    PubMed

    Striemer, Christopher L; Russell, Karyn; Nath, Priya

    2016-10-01

    Previous research has indicated that rightward prism adaptation can reduce symptoms of spatial neglect following right brain damage. In addition, leftward prism adaptation can create "neglect-like" patterns of performance in healthy adults on tasks that measure attention and spatial biases. Although a great deal of research has focused on which behaviors are influenced by prism adaptation, very few studies have focused directly on how the magnitude of visual shift induced by prisms might be related to the observed aftereffects, or the effects of prisms on measures of attentional and spatial biases. In the current study, we examined these questions by having groups of healthy adult participants complete manual line bisection and landmark tasks prior to and following adaptation to either 8.5° (15 diopter; n = 22) or 17° (30 diopter; n = 25) leftward shifting prisms. Our results demonstrated a significantly larger rightward shift in straight-ahead pointing (a measure of prism aftereffect) following adaptation to 17°, compared to 8.5° leftward shifting prisms. In addition, only 17° leftward shifting prisms resulted in a significant rightward shift in line bisection following adaptation. However, there was a significant change in performance on the landmark task pre- versus post-adaptation in both the 8.5° and 17° leftward shifting prism groups. Interestingly, correlation analyses indicated that changes in straight-ahead pointing pre- versus post-adaptation were positively correlated with changes in performance on the manual line bisection task, but not the landmark task. These data suggest that larger magnitudes of prism adaptation seem to have a greater influence on tasks that require a response with the adapted hand (i.e., line bisection), compared to tasks that only require a perceptual judgment (i.e., the landmark task). In addition, these data provide further evidence that the effects of prisms on manual and perceptual responses are not related to one

  20. Prism adaptation magnitude has differential influences on perceptual versus manual responses.

    PubMed

    Striemer, Christopher L; Russell, Karyn; Nath, Priya

    2016-10-01

    Previous research has indicated that rightward prism adaptation can reduce symptoms of spatial neglect following right brain damage. In addition, leftward prism adaptation can create "neglect-like" patterns of performance in healthy adults on tasks that measure attention and spatial biases. Although a great deal of research has focused on which behaviors are influenced by prism adaptation, very few studies have focused directly on how the magnitude of visual shift induced by prisms might be related to the observed aftereffects, or the effects of prisms on measures of attentional and spatial biases. In the current study, we examined these questions by having groups of healthy adult participants complete manual line bisection and landmark tasks prior to and following adaptation to either 8.5° (15 diopter; n = 22) or 17° (30 diopter; n = 25) leftward shifting prisms. Our results demonstrated a significantly larger rightward shift in straight-ahead pointing (a measure of prism aftereffect) following adaptation to 17°, compared to 8.5° leftward shifting prisms. In addition, only 17° leftward shifting prisms resulted in a significant rightward shift in line bisection following adaptation. However, there was a significant change in performance on the landmark task pre- versus post-adaptation in both the 8.5° and 17° leftward shifting prism groups. Interestingly, correlation analyses indicated that changes in straight-ahead pointing pre- versus post-adaptation were positively correlated with changes in performance on the manual line bisection task, but not the landmark task. These data suggest that larger magnitudes of prism adaptation seem to have a greater influence on tasks that require a response with the adapted hand (i.e., line bisection), compared to tasks that only require a perceptual judgment (i.e., the landmark task). In addition, these data provide further evidence that the effects of prisms on manual and perceptual responses are not related to one

  1. Adaptive responses to feeding in Burmese pythons: pay before pumping.

    PubMed

    Secor, S M; Diamond, J

    1995-06-01

    Burmese pythons normally consume large meals after long intervals. We measured gut contents, O2 consumption rates, small intestinal brush-border uptake rates of amino acids and glucose, organ masses and blood chemistry in pythons during the 30 days following ingestion of meals equivalent to 25% of their body mass. Within 1-3 days after ingestion, O2 consumption rates, intestinal nutrient uptake rates and uptake capacities peaked at 17, 6-26 and 11-24 times fasting levels, respectively. Small intestinal mass doubled, and other organs also increased in mass. Changes in blood chemistry included a 78% decline in PO2 and a large 'alkaline tide' associated with gastric acid section (i.e. a rise in blood pH and HCO3- concentrations and a fall in Cl- concentration). All of these values returned to fasting levels by the time of defecation at 8-14 days. The response of O2 consumption (referred to as specific dynamic action, SDA) is the largest, and the upregulation of intestinal nutrient transporters the second largest, response reported for any vertebrate upon feeding. The SDA is a large as the factorial rise in O2 consumption measured in mammalian sprinters and is sustained for much longer. The extra energy expended for digestion is equivalent to 32% of the meal's energy yield, with much of it being measured before the prey energy was absorbed. PMID:7782719

  2. Quantifying rates of evolutionary adaptation in response to ocean acidification.

    PubMed

    Sunday, Jennifer M; Crim, Ryan N; Harley, Christopher D G; Hart, Michael W

    2011-01-01

    The global acidification of the earth's oceans is predicted to impact biodiversity via physiological effects impacting growth, survival, reproduction, and immunology, leading to changes in species abundances and global distributions. However, the degree to which these changes will play out critically depends on the evolutionary rate at which populations will respond to natural selection imposed by ocean acidification, which remains largely unquantified. Here we measure the potential for an evolutionary response to ocean acidification in larval development rate in two coastal invertebrates using a full-factorial breeding design. We show that the sea urchin species Strongylocentrotus franciscanus has vastly greater levels of phenotypic and genetic variation for larval size in future CO(2) conditions compared to the mussel species Mytilus trossulus. Using these measures we demonstrate that S. franciscanus may have faster evolutionary responses within 50 years of the onset of predicted year-2100 CO(2) conditions despite having lower population turnover rates. Our comparisons suggest that information on genetic variation, phenotypic variation, and key demographic parameters, may lend valuable insight into relative evolutionary potentials across a large number of species.

  3. Is the Adaptive Response an Efficient Protection Against the Detrimental Effects of Space Radiation

    NASA Astrophysics Data System (ADS)

    Mortazavi, S. M. Javad; Cameron, J. R.; Niroomand-rad, A.

    2003-07-01

    exposure to high-energy neutrons, protons and HZE particles during a deep space mission, needs an efficient protection against the detrimental effects of space radiation. Recent findings concerning the induction of adaptive response by neutrons and high cumulative doses of gamma radiation in human cells have opened a new horizon for possible implications of adaptive response in radiation protection and esp ecially in protection against detrimental effects of high levels of radiation during a long-term space journey. We demonstrated significant adaptive response in humans after exposure to high levels of natural radiation. Individuals whose cumulative radiation doses were up to 950 mSv, showed a significant adaptive response after exposure to 1.5 Gy gamma radiation. These doses are much lower than those received by astronauts during a sixmonth space mission. Screening the adaptive response of candidates for long-term space missions will help scientists identify individuals who not only show low radiation susceptibility but also demonstrate a high magnitude of radioadaptive response. In selected individuals, chronic exposure to elevated levels of space radiation during a long-term mission can considerably decrease their radiation susceptibility and protect them against the unpredictable exposure to relatively high radiation levels due to solar activity. Keywords: Space radiation, adaptive response, chromosome aberrations. Introduction In recent decades, humans successfully experienced relatively long time space missions. No doubt, in the near future deep space journeys as long as a few years will be inevitable. Despite current advances, there are still some great problems that limit the duration of such long-term space missions. Radiation risk due to exposure to high levels of cosmic rays and the effects of microgravity are clearly the most important problems that need to be solved before a long-term

  4. Rapid evolution in response to introduced predators II: the contribution of adaptive plasticity

    PubMed Central

    Latta, Leigh C; Bakelar, Jeremy W; Knapp, Roland A; Pfrender, Michael E

    2007-01-01

    Background Introductions of non-native species can significantly alter the selective environment for populations of native species, which can respond through phenotypic plasticity or genetic adaptation. We examined phenotypic and genetic responses of Daphnia populations to recent introductions of non-native fish to assess the relative roles of phenotypic plasticity versus genetic change in causing the observed patterns. The Daphnia community in alpine lakes throughout the Sierra Nevada of California (USA) is ideally suited for investigation of rapid adaptive evolution because there are multiple lakes with and without introduced fish predators. We conducted common-garden experiments involving presence or absence of chemical cues produced by fish and measured morphological and life-history traits in Daphnia melanica populations collected from lakes with contrasting fish stocking histories. The experiment allowed us to assess the degree of population differentiation due to fish predation and examine the contribution of adaptive plasticity in the response to predator introduction. Results Our results show reductions in egg number and body size of D. melanica in response to introduced fish. These phenotypic changes have a genetic basis but are partly due to a direct response to chemical cues from fish via adaptive phenotypic plasticity. Body size showed the largest phenotypic change, on the order of nine phenotypic standard deviations, with approximately 11% of the change explained by adaptive plasticity. Both evolutionary and plastic changes in body size and egg number occurred but no changes in the timing of reproduction were observed. Conclusion Native Daphnia populations exposed to chemical cues produced by salmonid fish predators display adaptive plasticity for body size and fecundity. The magnitude of adaptive plasticity was insufficient to explain the total phenotypic change, so the realized change in phenotypic means in populations exposed to introduced fish may

  5. Polyreactive antibodies in adaptive immune responses to viruses.

    PubMed

    Mouquet, Hugo; Nussenzweig, Michel C

    2012-05-01

    B cells express immunoglobulins on their surface where they serve as antigen receptors. When secreted as antibodies, the same molecules are key elements of the humoral immune response against pathogens such as viruses. Although most antibodies are restricted to binding a specific antigen, some are polyreactive and have the ability to bind to several different ligands, usually with low affinity. Highly polyreactive antibodies are removed from the repertoire during B-cell development by physiologic tolerance mechanisms including deletion and receptor editing. However, a low level of antibody polyreactivity is tolerated and can confer additional binding properties to pathogen-specific antibodies. For example, high-affinity human antibodies to HIV are frequently polyreactive. Here we review the evidence suggesting that in the case of some pathogens like HIV, polyreactivity may confer a selective advantage to pathogen-specific antibodies.

  6. Adaptive liquid microlenses activated by stimuli-responsive hydrogels

    NASA Astrophysics Data System (ADS)

    Dong, Liang; Agarwal, Abhishek K.; Beebe, David J.; Jiang, Hongrui

    2006-08-01

    Despite its compactness, the human eye can easily focus on different distances by adjusting the shape of its lens with the help of ciliary muscles. In contrast, traditional man-made optical systems achieve focusing by physical displacement of the lenses used. But in recent years, advances in miniaturization technology have led to optical systems that no longer require complicated mechanical systems to tune and adjust optical performance. These systems have found wide use in photonics, displays and biomedical systems. They are either based on arrays of microlenses with fixed focal lengths, or use external control to adjust the microlens focal length. An intriguing example is the tunable liquid lens, where electrowetting or external pressure manipulates the shape of a liquid droplet and thereby adjusts its optical properties. Here we demonstrate a liquid lens system that allows for autonomous focusing. The central component is a stimuli-responsive hydrogel integrated into a microfluidic system and serving as the container for a liquid droplet, with the hydrogel simultaneously sensing the presence of stimuli and actuating adjustments to the shape-and hence focal length-of the droplet. By working at the micrometre scale where ionic diffusion and surface tension scale favourably, we can use pinned liquid-liquid interfaces to obtain stable devices and realize response times of ten to a few tens of seconds. The microlenses, which can have a focal length ranging from -∞ to +∞ (divergent and convergent), are also readily integrated into arrays that may find use in applications such as sensing, medical diagnostics and lab-on-a-chip technologies.

  7. Effects of local adaptation and interspecific competition on species' responses to climate change.

    PubMed

    Bocedi, Greta; Atkins, Katherine E; Liao, Jishan; Henry, Roslyn C; Travis, Justin M J; Hellmann, Jessica J

    2013-09-01

    Local adaptation and species interactions have been shown to affect geographic ranges; therefore, we need models of climate impact that include both factors. To identify possible dynamics of species when including these factors, we ran simulations of two competing species using an individual-based, coupled map-lattice model using a linear climatic gradient that varies across latitude and is warmed over time. Reproductive success is governed by an individual's adaptation to local climate as well as its location relative to global constraints. In exploratory experiments varying the strength of adaptation and competition, competition reduces genetic diversity and slows range change, although the two species can coexist in the absence of climate change and shift in the absence of competitors. We also found that one species can drive the other to extinction, sometimes long after climate change ends. Weak selection on local adaptation and poor dispersal ability also caused surfing of cooler-adapted phenotypes from the expanding margin backwards, causing loss of warmer-adapted phenotypes. Finally, geographic ranges can become disjointed, losing centrally-adapted genotypes. These initial results suggest that the interplay between local adaptation and interspecific competition can significantly influence species' responses to climate change, in a way that demands future research.

  8. Response normalization and blur adaptation: Data and multi-scale model

    PubMed Central

    Elliott, Sarah L.; Georgeson, Mark A.; Webster, Michael A.

    2011-01-01

    Adapting to blurred or sharpened images alters perceived blur of a focused image (M. A. Webster, M. A. Georgeson, & S. M. Webster, 2002). We asked whether blur adaptation results in (a) renormalization of perceived focus or (b) a repulsion aftereffect. Images were checkerboards or 2-D Gaussian noise, whose amplitude spectra had (log–log) slopes from −2 (strongly blurred) to 0 (strongly sharpened). Observers adjusted the spectral slope of a comparison image to match different test slopes after adaptation to blurred or sharpened images. Results did not show repulsion effects but were consistent with some renormalization. Test blur levels at and near a blurred or sharpened adaptation level were matched by more focused slopes (closer to 1/f) but with little or no change in appearance after adaptation to focused (1/f) images. A model of contrast adaptation and blur coding by multiple-scale spatial filters predicts these blur aftereffects and those of Webster et al. (2002). A key proposal is that observers are pre-adapted to natural spectra, and blurred or sharpened spectra induce changes in the state of adaptation. The model illustrates how norms might be encoded and recalibrated in the visual system even when they are represented only implicitly by the distribution of responses across multiple channels. PMID:21307174

  9. Concluding remarks: nutritional strategies to support the adaptive response to prolonged exercise training.

    PubMed

    van Loon, Luc J C; Tipton, Kevin D

    2013-01-01

    Nutrition plays a key role in allowing the numerous training hours to be translated into useful adaptive responses of various tissues in the individual athlete. Research over the last decade has shown many examples of the impact of dietary interventions to modulate the skeletal muscle adaptive response to prolonged exercise training. Proper nutritional coaching should be applied throughout both training and competition, each with their specific requirements regarding nutrient provision. Such dietary support will improve exercise training efficiency and, as such, further increase performance capacity. Here, we provide an overview on the properties of various nutritional interventions that may be useful to support the adaptive response to exercise training and competition and, as such, to augment exercise training efficiency.

  10. Plasticity and genetic adaptation mediate amphibian and reptile responses to climate change

    PubMed Central

    Urban, Mark C; Richardson, Jonathan L; Freidenfelds, Nicole A

    2014-01-01

    Phenotypic plasticity and genetic adaptation are predicted to mitigate some of the negative biotic consequences of climate change. Here, we evaluate evidence for plastic and evolutionary responses to climate variation in amphibians and reptiles via a literature review and meta-analysis. We included studies that either document phenotypic changes through time or space. Plasticity had a clear and ubiquitous role in promoting phenotypic changes in response to climate variation. For adaptive evolution, we found no direct evidence for evolution of amphibians or reptiles in response to climate change over time. However, we found many studies that documented adaptive responses to climate along spatial gradients. Plasticity provided a mixture of adaptive and maladaptive responses to climate change, highlighting that plasticity frequently, but not always, could ameliorate climate change. Based on our review, we advocate for more experiments that survey genetic changes through time in response to climate change. Overall, plastic and genetic variation in amphibians and reptiles could buffer some of the formidable threats from climate change, but large uncertainties remain owing to limited data. PMID:24454550

  11. Plasticity and genetic adaptation mediate amphibian and reptile responses to climate change.

    PubMed

    Urban, Mark C; Richardson, Jonathan L; Freidenfelds, Nicole A

    2014-01-01

    Phenotypic plasticity and genetic adaptation are predicted to mitigate some of the negative biotic consequences of climate change. Here, we evaluate evidence for plastic and evolutionary responses to climate variation in amphibians and reptiles via a literature review and meta-analysis. We included studies that either document phenotypic changes through time or space. Plasticity had a clear and ubiquitous role in promoting phenotypic changes in response to climate variation. For adaptive evolution, we found no direct evidence for evolution of amphibians or reptiles in response to climate change over time. However, we found many studies that documented adaptive responses to climate along spatial gradients. Plasticity provided a mixture of adaptive and maladaptive responses to climate change, highlighting that plasticity frequently, but not always, could ameliorate climate change. Based on our review, we advocate for more experiments that survey genetic changes through time in response to climate change. Overall, plastic and genetic variation in amphibians and reptiles could buffer some of the formidable threats from climate change, but large uncertainties remain owing to limited data.

  12. Global transcriptional, physiological and metabolite analyses of Desulfovibrio vulgaris Hildenborough responses to salt adaptation

    SciTech Connect

    He, Z.; Zhou, A.; Baidoo, E.; He, Q.; Joachimiak, M. P.; Benke, P.; Phan, R.; Mukhopadhyay, A.; Hemme, C.L.; Huang, K.; Alm, E.J.; Fields, M.W.; Wall, J.; Stahl, D.; Hazen, T.C.; Keasling, J.D.; Arkin, A.P.; Zhou, J.

    2009-12-01

    The response of Desulfovibrio vulgaris Hildenborough to salt adaptation (long-term NaCl exposure) was examined by physiological, global transcriptional, and metabolite analyses. The growth of D. vulgaris was inhibited by high levels of NaCl, and the growth inhibition could be relieved by the addition of exogenous amino acids (e.g., glutamate, alanine, tryptophan) or yeast extract. Salt adaptation induced the expression of genes involved in amino acid biosynthesis and transport, electron transfer, hydrogen oxidation, and general stress responses (e.g., heat shock proteins, phage shock proteins, and oxidative stress response proteins). Genes involved in carbon metabolism, cell motility, and phage structures were repressed. Comparison of transcriptomic profiles of D. vulgaris responses to salt adaptation with those of salt shock (short-term NaCl exposure) showed some similarity as well as a significant difference. Metabolite assays showed that glutamate and alanine were accumulated under salt adaptation, suggesting that they may be used as osmoprotectants in D. vulgaris. A conceptual model is proposed to link the observed results to currently available knowledge for further understanding the mechanisms of D. vulgaris adaptation to elevated NaCl.

  13. Immune adjuvants in early life: targeting the innate immune system to overcome impaired adaptive response.

    PubMed

    de Brito, Cyro Alves; Goldoni, Adriana Letícia; Sato, Maria Notomi

    2009-09-01

    The neonatal phase is a transitory period characterized by an absence of memory cells, favoring a slow adaptive response prone to tolerance effects and the development of Th2-type responses. However, when appropriately stimulated, neonates may achieve an immune response comparable with adult counterparts. One strategy to stimulate the immunological response of neonates or children in early infancy has been to explore natural or synthetic ligands of cell receptors to stimulate innate immunity. The use of adjuvants for activating different cell receptors may be the key to enhancing neonatal adaptive immunity. This review highlights recent advances in the emerging field of molecular adjuvants of innate immune response and their implications for the development of immunotherapies, with particular focus on the neonatal period.

  14. Evolution of taxis responses in virtual bacteria: non-adaptive dynamics.

    PubMed

    Goldstein, Richard A; Soyer, Orkun S

    2008-05-23

    Bacteria are able to sense and respond to a variety of external stimuli, with responses that vary from stimuli to stimuli and from species to species. The best-understood is chemotaxis in the model organism Escherichia coli, where the dynamics and the structure of the underlying pathway are well characterised. It is not clear, however, how well this detailed knowledge applies to mechanisms mediating responses to other stimuli or to pathways in other species. Furthermore, there is increasing experimental evidence that bacteria integrate responses from different stimuli to generate a coherent taxis response. We currently lack a full understanding of the different pathway structures and dynamics and how this integration is achieved. In order to explore different pathway structures and dynamics that can underlie taxis responses in bacteria, we perform a computational simulation of the evolution of taxis. This approach starts with a population of virtual bacteria that move in a virtual environment based on the dynamics of the simple biochemical pathways they harbour. As mutations lead to changes in pathway structure and dynamics, bacteria better able to localise with favourable conditions gain a selective advantage. We find that a certain dynamics evolves consistently under different model assumptions and environments. These dynamics, which we call non-adaptive dynamics, directly couple tumbling probability of the cell to increasing stimuli. Dynamics that are adaptive under a wide range of conditions, as seen in the chemotaxis pathway of E. coli, do not evolve in these evolutionary simulations. However, we find that stimulus scarcity and fluctuations during evolution results in complex pathway dynamics that result both in adaptive and non-adaptive dynamics depending on basal stimuli levels. Further analyses of evolved pathway structures show that effective taxis dynamics can be mediated with as few as two components. The non-adaptive dynamics mediating taxis responses

  15. Ionotropic glutamate receptors mediate OFF responses in light-adapted ON bipolar cells

    PubMed Central

    Pang, Ji-Jie; Gao, Fan; Wu, Samuel M.

    2013-01-01

    Previous studies have suggested that photoreceptor synaptic inputs to depolarizing bipolar cells (DBCs or ON bipolar cells) are mediated by mGluR6 receptors and those to hyperpolarizing bipolar cells (HBCs or OFF bipolar cells) are mediated by AMPA/kainate receptors. Here we show that in addition to mGluR6 receptors which mediate the sign-inverting, depolarizing light responses, subpopulations of cone-dominated and rod/cone mixed DBCs use GluR4 AMPA receptors to generate a transient sign-preserving OFF response under light adapted conditions. These AMPA receptors are located at the basal junctions postsynaptic to rods and they are silent under dark-adapted conditions, as tonic glutamate release in darkness desensitizes these receptors. Light adaptation enhances rod-cone coupling and thus allows cone photocurrents with an abrupt OFF depolarization to enter the rods. The abrupt rod depolarization triggers glutamate activation of unoccupied AMPA receptors, resulting in a transient OFF response in DBCs. It has been widely accepted that the DNQX-sensitive, OFF transient responses in retinal amacrine cells and ganglion cells are mediated exclusively by HBCs. Our results suggests that this view needs revision as AMPA receptors in subpopulations of DBCs are likely to significantly contribute to the DNQX-sensitive OFF transient responses in light-adapted third- and higher-order visual neurons. PMID:22842089

  16. Adaptive responses reveal contemporary and future ecotypes in a desert shrub

    USGS Publications Warehouse

    Richardson, Bryce A.; Kitchen, Stanley G.; Pendleton, Rosemary L.; Pendleton, Burton K.; Germino, Matthew J.; Rehfeldt, Gerald E.; Meyer, Susan E.

    2014-01-01

    Interacting threats to ecosystem function, including climate change, wildfire, and invasive species necessitate native plant restoration in desert ecosystems. However, native plant restoration efforts often remain unguided by ecological genetic information. Given that many ecosystems are in flux from climate change, restoration plans need to account for both contemporary and future climates when choosing seed sources. In this study we analyze vegetative responses, including mortality, growth, and carbon isotope ratios in two blackbrush (Coleogyne ramosissima) common gardens that included 26 populations from a range-wide collection. This shrub occupies ecotones between the warm and cold deserts of Mojave and Colorado Plateau ecoregions in western North America. The variation observed in the vegetative responses of blackbrush populations was principally explained by grouping populations by ecoregions and by regression with site-specific climate variables. Aridity weighted by winter minimum temperatures best explained vegetative responses; Colorado Plateau sites were usually colder and drier than Mojave sites. The relationship between climate and vegetative response was mapped within the boundaries of the species–climate space projected for the contemporary climate and for the decade surrounding 2060. The mapped ecological genetic pattern showed that genetic variation could be classified into cool-adapted and warm-adapted ecotypes, with populations often separated by steep clines. These transitions are predicted to occur in both the Mojave Desert and Colorado Plateau ecoregions. While under contemporary conditions the warm-adapted ecotype occupies the majority of climate space, climate projections predict that the cool-adapted ecotype could prevail as the dominant ecotype as the climate space of blackbrush expands into higher elevations and latitudes. This study provides the framework for delineating climate change-responsive seed transfer guidelines, which are

  17. Modeling light adaptation in circadian clock: prediction of the response that stabilizes entrainment.

    PubMed

    Tsumoto, Kunichika; Kurosawa, Gen; Yoshinaga, Tetsuya; Aihara, Kazuyuki

    2011-01-01

    Periods of biological clocks are close to but often different from the rotation period of the earth. Thus, the clocks of organisms must be adjusted to synchronize with day-night cycles. The primary signal that adjusts the clocks is light. In Neurospora, light transiently up-regulates the expression of specific clock genes. This molecular response to light is called light adaptation. Does light adaptation occur in other organisms? Using published experimental data, we first estimated the time course of the up-regulation rate of gene expression by light. Intriguingly, the estimated up-regulation rate was transient during light period in mice as well as Neurospora. Next, we constructed a computational model to consider how light adaptation had an effect on the entrainment of circadian oscillation to 24-h light-dark cycles. We found that cellular oscillations are more likely to be destabilized without light adaption especially when light intensity is very high. From the present results, we predict that the instability of circadian oscillations under 24-h light-dark cycles can be experimentally observed if light adaptation is altered. We conclude that the functional consequence of light adaptation is to increase the adjustability to 24-h light-dark cycles and then adapt to fluctuating environments in nature.

  18. Population variability in biological adaptive responses to DNA damage and the shapes of carcinogen dose-response curves

    SciTech Connect

    Conolly, Rory B. . E-mail: Conolly.Rory@epa.gov; Gaylor, David W.; Lutz, Werner K.

    2005-09-01

    Carcinogen dose-response curves for both ionizing radiation and chemicals are typically assumed to be linear at environmentally relevant doses. This assumption is used to ensure protection of the public health in the absence of relevant dose-response data. A theoretical justification for the assumption has been provided by the argument that low dose linearity is expected when an exogenous agent adds to an ongoing endogenous process. Here, we use computational modeling to evaluate (1) how two biological adaptive processes, induction of DNA repair and cell cycle checkpoint control, may affect the shapes of dose-response curves for DNA-damaging carcinogens and (2) how the resulting dose-response behaviors may vary within a population. Each model incorporating an adaptive process was capable of generating not only monotonic dose-responses but also nonmonotonic (J-shaped) and threshold responses. Monte Carlo analysis suggested that all these dose-response behaviors could coexist within a population, as the spectrum of qualitative differences arose from quantitative changes in parameter values. While this analysis is largely theoretical, it suggests that (a) accurate prediction of the qualitative form of the dose-response requires a quantitative understanding of the mechanism (b) significant uncertainty is associated with human health risk prediction in the absence of such quantitative understanding and (c) a stronger experimental and regulatory focus on biological mechanisms and interindividual variability would allow flexibility in regulatory treatment of environmental carcinogens without compromising human health.

  19. Natural variation in abiotic stress responsive gene expression and local adaptation to climate in Arabidopsis thaliana.

    PubMed

    Lasky, Jesse R; Des Marais, David L; Lowry, David B; Povolotskaya, Inna; McKay, John K; Richards, James H; Keitt, Timothy H; Juenger, Thomas E

    2014-09-01

    Gene expression varies widely in natural populations, yet the proximate and ultimate causes of this variation are poorly known. Understanding how variation in gene expression affects abiotic stress tolerance, fitness, and adaptation is central to the field of evolutionary genetics. We tested the hypothesis that genes with natural genetic variation in their expression responses to abiotic stress are likely to be involved in local adaptation to climate in Arabidopsis thaliana. Specifically, we compared genes with consistent expression responses to environmental stress (expression stress responsive, "eSR") to genes with genetically variable responses to abiotic stress (expression genotype-by-environment interaction, "eGEI"). We found that on average genes that exhibited eGEI in response to drought or cold had greater polymorphism in promoter regions and stronger associations with climate than those of eSR genes or genomic controls. We also found that transcription factor binding sites known to respond to environmental stressors, especially abscisic acid responsive elements, showed significantly higher polymorphism in drought eGEI genes in comparison to eSR genes. By contrast, eSR genes tended to exhibit relatively greater pairwise haplotype sharing, lower promoter diversity, and fewer nonsynonymous polymorphisms, suggesting purifying selection or selective sweeps. Our results indicate that cis-regulatory evolution and genetic variation in stress responsive gene expression may be important mechanisms of local adaptation to climatic selective gradients.

  20. Natural Variation in Abiotic Stress Responsive Gene Expression and Local Adaptation to Climate in Arabidopsis thaliana

    PubMed Central

    Lasky, Jesse R.; Des Marais, David L.; Lowry, David B.; Povolotskaya, Inna; McKay, John K.; Richards, James H.; Keitt, Timothy H.; Juenger, Thomas E.

    2014-01-01

    Gene expression varies widely in natural populations, yet the proximate and ultimate causes of this variation are poorly known. Understanding how variation in gene expression affects abiotic stress tolerance, fitness, and adaptation is central to the field of evolutionary genetics. We tested the hypothesis that genes with natural genetic variation in their expression responses to abiotic stress are likely to be involved in local adaptation to climate in Arabidopsis thaliana. Specifically, we compared genes with consistent expression responses to environmental stress (expression stress responsive, “eSR”) to genes with genetically variable responses to abiotic stress (expression genotype-by-environment interaction, “eGEI”). We found that on average genes that exhibited eGEI in response to drought or cold had greater polymorphism in promoter regions and stronger associations with climate than those of eSR genes or genomic controls. We also found that transcription factor binding sites known to respond to environmental stressors, especially abscisic acid responsive elements, showed significantly higher polymorphism in drought eGEI genes in comparison to eSR genes. By contrast, eSR genes tended to exhibit relatively greater pairwise haplotype sharing, lower promoter diversity, and fewer nonsynonymous polymorphisms, suggesting purifying selection or selective sweeps. Our results indicate that cis-regulatory evolution and genetic variation in stress responsive gene expression may be important mechanisms of local adaptation to climatic selective gradients. PMID:24850899

  1. Real-time molecular monitoring of chemical environment in obligate anaerobes during oxygen adaptive response

    PubMed Central

    Holman, Hoi-Ying N.; Wozei, Eleanor; Lin, Zhang; Comolli, Luis R.; Ball, David A.; Borglin, Sharon; Fields, Matthew W.; Hazen, Terry C.; Downing, Kenneth H.

    2009-01-01

    Determining the transient chemical properties of the intracellular environment can elucidate the paths through which a biological system adapts to changes in its environment, for example, the mechanisms that enable some obligate anaerobic bacteria to survive a sudden exposure to oxygen. Here we used high-resolution Fourier transform infrared (FTIR) spectromicroscopy to continuously follow cellular chemistry within living obligate anaerobes by monitoring hydrogen bond structures in their cellular water. We observed a sequence of well orchestrated molecular events that correspond to changes in cellular processes in those cells that survive, but only accumulation of radicals in those that do not. We thereby can interpret the adaptive response in terms of transient intracellular chemistry and link it to oxygen stress and survival. This ability to monitor chemical changes at the molecular level can yield important insights into a wide range of adaptive responses. PMID:19541631

  2. Real-Time Molecular Monitoring of Chemical Environment in ObligateAnaerobes during Oxygen Adaptive Response

    SciTech Connect

    Holman, Hoi-Ying N.; Wozei, Eleanor; Lin, Zhang; Comolli, Luis R.; Ball, David. A.; Borglin, Sharon; Fields, Matthew W.; Hazen, Terry C.; Downing, Kenneth H.

    2009-02-25

    Determining the transient chemical properties of the intracellular environment canelucidate the paths through which a biological system adapts to changes in its environment, for example, the mechanisms which enable some obligate anaerobic bacteria to survive a sudden exposure to oxygen. Here we used high-resolution Fourier Transform Infrared (FTIR) spectromicroscopy to continuously follow cellular chemistry within living obligate anaerobes by monitoring hydrogen bonding in their cellular water. We observed a sequence of wellorchestrated molecular events that correspond to changes in cellular processes in those cells that survive, but only accumulation of radicals in those that do not. We thereby can interpret the adaptive response in terms of transient intracellular chemistry and link it to oxygen stress and survival. This ability to monitor chemical changes at the molecular level can yield important insights into a wide range of adaptive responses.

  3. Integrating human responses to climate change into conservation vulnerability assessments and adaptation planning.

    PubMed

    Maxwell, Sean L; Venter, Oscar; Jones, Kendall R; Watson, James E M

    2015-10-01

    The impact of climate change on biodiversity is now evident, with the direct impacts of changing temperature and rainfall patterns and increases in the magnitude and frequency of extreme events on species distribution, populations, and overall ecosystem function being increasingly publicized. Changes in the climate system are also affecting human communities, and a range of human responses across terrestrial and marine realms have been witnessed, including altered agricultural activities, shifting fishing efforts, and human migration. Failing to account for the human responses to climate change is likely to compromise climate-smart conservation efforts. Here, we use a well-established conservation planning framework to show how integrating human responses to climate change into both species- and site-based vulnerability assessments and adaptation plans is possible. By explicitly taking into account human responses, conservation practitioners will improve their evaluation of species and ecosystem vulnerability, and will be better able to deliver win-wins for human- and biodiversity-focused climate adaptation.

  4. Adaptive Response, Evidence of Cross-Resistance and Its Potential Clinical Use

    PubMed Central

    Milisav, Irina; Poljsak, Borut; Šuput, Dušan

    2012-01-01

    Organisms and their cells are constantly exposed to environmental fluctuations. Among them are stressors, which can induce macromolecular damage that exceeds a set threshold, independent of the underlying cause. Stress responses are mechanisms used by organisms to adapt to and overcome stress stimuli. Different stressors or different intensities of stress trigger different cellular responses, namely induce cell repair mechanisms, induce cell responses that result in temporary adaptation to some stressors, induce autophagy or trigger cell death. Studies have reported life-prolonging effects of a wide variety of so-called stressors, such as oxidants, heat shock, some phytochemicals, ischemia, exercise and dietary energy restriction, hypergravity, etc. These stress responses, which result in enhanced defense and repair and even cross-resistance against multiple stressors, may have clinical use and will be discussed, while the emphasis will be on the effects/cross-effects of oxidants. PMID:23109822

  5. HCV Causes Chronic Endoplasmic Reticulum Stress Leading to Adaptation and Interference with the Unfolded Protein Response

    PubMed Central

    Merquiol, Emmanuelle; Uzi, Dotan; Mueller, Tobias; Goldenberg, Daniel; Nahmias, Yaakov; Xavier, Ramnik J.

    2011-01-01

    Background The endoplasmic reticulum (ER) is the cellular site for protein folding. ER stress occurs when protein folding capacity is exceeded. This stress induces a cyto-protective signaling cascades termed the unfolded protein response (UPR) aimed at restoring homeostasis. While acute ER stress is lethal, chronic sub-lethal ER stress causes cells to adapt by attenuation of UPR activation. Hepatitis C virus (HCV), a major human pathogen, was shown to cause ER stress, however it is unclear whether HCV induces chronic ER stress, and if so whether adaptation mechanisms are initiated. We wanted to characterize the kinetics of HCV-induced ER stress during infection and assess adaptation mechanisms and their significance. Methods and Findings The HuH7.5.1 cellular system and HCV-transgenic (HCV-Tg) mice were used to characterize HCV-induced ER stress/UPR pathway activation and adaptation. HCV induced a wave of acute ER stress peaking 2–5 days post-infection, which rapidly subsided thereafter. UPR pathways were activated including IRE1 and EIF2α phosphorylation, ATF6 cleavage and XBP-1 splicing. Downstream target genes including GADD34, ERdj4, p58ipk, ATF3 and ATF4 were upregulated. CHOP, a UPR regulated protein was activated and translocated to the nucleus. Remarkably, UPR activity did not return to baseline but remained elevated for up to 14 days post infection suggesting that chronic ER stress is induced. At this time, cells adapted to ER stress and were less responsive to further drug-induced ER stress. Similar results were obtained in HCV-Tg mice. Suppression of HCV by Interferon-α 2a treatment, restored UPR responsiveness to ER stress tolerant cells. Conclusions Our study shows, for the first time, that HCV induces adaptation to chronic ER stress which was reversed upon viral suppression. These finding represent a novel viral mechanism to manipulate cellular response pathways. PMID:21949742

  6. Adaptive response studies may help choose astronauts for long-term space travel

    NASA Astrophysics Data System (ADS)

    Mortazavi, S. M. Javad; Cameron, J. R.; Niroomand-rad, A.

    Long-term manned exploratory missions are planned for the future. Exposure to high-energy neutrons, protons and high charge and energy particles during a deep space mission, needs protection against the detrimental effects of space radiation. It has been suggested that exposure to unpredictable extremely large solar particle events would kill the astronauts without massive shielding. To reduce this risk to astronauts and to minimize the need for shielding, astronauts with highest significant adaptive responses should be chosen. It has been demonstrated that some humans living in very high natural radiation areas have acquired high adaptive responses to external radiation. Therefore, we suggest that for a deep space mission the adaptive response of all potential crew members be measured and only those with high adaptive response be chosen. We also proclaim that chronic exposure to elevated levels of radiation can considerably decrease radiation susceptibility and better protect astronauts against the unpredictable exposure to sudden and dramatic increase in flux due to solar flares and coronal mass ejections.

  7. Adaptive response studies may help choose astronauts for long-term space travel.

    PubMed

    Mortazavi, S M; Cameron, J R; Niroomand-rad, A

    2003-01-01

    Long-term manned exploratory missions are planned for the future. Exposure to high-energy neutrons, protons and high charge and energy particles during a deep space mission, needs protection against the detrimental effects of space radiation. It has been suggested that exposure to unpredictable extremely large solar particle events would kill the astronauts without massive shielding. To reduce this risk to astronauts and to minimize the need for shielding, astronauts with highest significant adaptive responses should be chosen. It has been demonstrated that some humans living in very high natural radiation areas have acquired high adaptive responses to external radiation. Therefore, we suggest that for a deep space mission the adaptive response of all potential crew members be measured and only those with high adaptive response be chosen. We also proclaim that chronic exposure to elevated levels of radiation can considerably decrease radiation susceptibility and better protect astronauts against the unpredictable exposure to sudden and dramatic increase in flux due to solar flares and coronal mass ejections.

  8. Adapting a Multigenre-Response Model for College Readers of American Literature

    ERIC Educational Resources Information Center

    Hsu, Jeng-yih Tim

    2006-01-01

    As an English teacher who has been teaching nearly 10 years in a college of southern Taiwan, the presenter reports his successful experience on a course, titled "Selected Readings from American Literature." In this try-out study, the presenter adapts a multigenre-response model via which he encourages Taiwan college students to bravely write down…

  9. Firestar-"D": Computerized Adaptive Testing Simulation Program for Dichotomous Item Response Theory Models

    ERIC Educational Resources Information Center

    Choi, Seung W.; Podrabsky, Tracy; McKinney, Natalie

    2012-01-01

    Computerized adaptive testing (CAT) enables efficient and flexible measurement of latent constructs. The majority of educational and cognitive measurement constructs are based on dichotomous item response theory (IRT) models. An integral part of developing various components of a CAT system is conducting simulations using both known and empirical…

  10. Item Pocket Method to Allow Response Review and Change in Computerized Adaptive Testing

    ERIC Educational Resources Information Center

    Han, Kyung T.

    2013-01-01

    Most computerized adaptive testing (CAT) programs do not allow test takers to review and change their responses because it could seriously deteriorate the efficiency of measurement and make tests vulnerable to manipulative test-taking strategies. Several modified testing methods have been developed that provide restricted review options while…

  11. {sub p}53-Dependent Adaptive Responses in Human Cells Exposed to Space Radiations

    SciTech Connect

    Takahashi, Akihisa; Su Xiaoming; Suzuki, Hiromi; Omori, Katsunori; Seki, Masaya; Hashizume, Toko; Shimazu, Toru; Ishioka, Noriaki; Iwasaki, Toshiyasu; Ohnishi, Takeo

    2010-11-15

    Purpose: It has been reported that priming irradiation or conditioning irradiation with a low dose of X-rays in the range of 0.02-0.1 Gy induces a p53-dependent adaptive response in mammalian cells. The aim of the present study was to clarify the effect of space radiations on the adaptive response. Methods and Materials: Two human lymphoblastoid cell lines were used; one cell line bears a wild-type p53 (wtp53) gene, and another cell line bears a mutated p53 (mp53) gene. The cells were frozen during transportation on the space shuttle and while in orbit in the International Space Station freezer for 133 days between November 15, 2008 and March 29, 2009. After the frozen samples were returned to Earth, the cells were cultured for 6 h and then exposed to a challenging X-ray-irradiation (2 Gy). Cellular sensitivity, apoptosis, and chromosome aberrations were scored using dye-exclusion assays, Hoechst33342 staining assays, and chromosomal banding techniques, respectively. Results: In cells exposed to space radiations, adaptive responses such as the induction of radioresistance and the depression of radiation-induced apoptosis and chromosome aberrations were observed in wtp53 cells but not in mp53 cells. Conclusion: These results have confirmed the hypothesis that p53-dependent adaptive responses are apparently induced by space radiations within a specific range of low doses. The cells exhibited this effect owing to space radiations exposure, even though the doses in space were very low.

  12. Innate and adaptive immune responses to in utero infection with bovine viral diarrhea virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Infection of pregnant cows with noncytopathic (ncp) BVDV induces rapid innate and adaptive immune responses resulting in clearance of the virus in less than 3 weeks. Seven to 14 days after inoculation of the cow, ncpBVDV crosses the placenta and induces a fetal viremia. Establishment of persistent ...

  13. Determining adaptive and adverse oxidative stress responses in human bronical epithelial cells exposed to zinc

    EPA Science Inventory

    Determining adaptive and adverse oxidative stress responses in human bronchial epithelial cells exposed to zincJenna M. Currier1,2, Wan-Yun Cheng1, Rory Conolly1, Brian N. Chorley1Zinc is a ubiquitous contaminant of ambient air that presents an oxidant challenge to the human lung...

  14. Starvation stress during larval development reveals predictive adaptive response in adult worker honey bees (Apis mellifera)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A variety of organisms exhibit developmental plasticity that results in differences in adult morphology, physiology or behavior. This variation in the phenotype, called “Predictive Adaptive Response (PAR),” gives a selective advantage in an adult's environment if the adult experiences environments s...

  15. Adaptive response studies may help choose astronauts for long-term space travel.

    PubMed

    Mortazavi, S M; Cameron, J R; Niroomand-rad, A

    2003-01-01

    Long-term manned exploratory missions are planned for the future. Exposure to high-energy neutrons, protons and high charge and energy particles during a deep space mission, needs protection against the detrimental effects of space radiation. It has been suggested that exposure to unpredictable extremely large solar particle events would kill the astronauts without massive shielding. To reduce this risk to astronauts and to minimize the need for shielding, astronauts with highest significant adaptive responses should be chosen. It has been demonstrated that some humans living in very high natural radiation areas have acquired high adaptive responses to external radiation. Therefore, we suggest that for a deep space mission the adaptive response of all potential crew members be measured and only those with high adaptive response be chosen. We also proclaim that chronic exposure to elevated levels of radiation can considerably decrease radiation susceptibility and better protect astronauts against the unpredictable exposure to sudden and dramatic increase in flux due to solar flares and coronal mass ejections. PMID:12971409

  16. Rhetorical Dissent as an Adaptive Response to Classroom Problems: A Test of Protection Motivation Theory

    ERIC Educational Resources Information Center

    Bolkan, San; Goodboy, Alan K.

    2016-01-01

    Protection motivation theory (PMT) explains people's adaptive behavior in response to personal threats. In this study, PMT was used to predict rhetorical dissent episodes related to 210 student reports of perceived classroom problems. In line with theoretical predictions, a moderated moderation analysis revealed that students were likely to voice…

  17. BYSTANDER EFFECTS GENOMIC INSTABILITY, ADAPTIVE RESPONSE AND CANCER RISK ASSESSMENT FOR RADIAION AND CHEMICAL EXPOSURES

    EPA Science Inventory

    BYSTANDER EFFECTS, GENOMIC INSTABILITY, ADAPTIVE RESPONSE AND CANCER RISK ASSESSMENT FOR RADIATION AND CHEMICAL EXPOSURES

    R. Julian Preston
    Environmental Carcinogenesis Division, U.S. Environmental Protection Agency, Research Triangle Park, N.C. 27711, USA

    There ...

  18. RNA regulators of host immunity and pathogen adaptive responses in the oral cavity

    PubMed Central

    Kreth, Jens; Liu, Nan; Chen, Zhiyun; Merritt, Justin

    2015-01-01

    The recent explosion of RNA-seq studies has resulted in a newfound appreciation for the importance of riboregulatory RNAs in the posttranscriptional control of eukaryotic and prokaryotic genetic networks. The current review will explore the role of trans-riboregulatory RNAs in various adaptive responses of host and pathogen in the oral cavity. PMID:25790757

  19. A Comparison of the Partial Credit and Graded Response Models in Computerized Adaptive Testing.

    ERIC Educational Resources Information Center

    De Ayala, R. J.; And Others

    Computerized adaptive testing procedures (CATPs) based on the graded response method (GRM) of F. Samejima (1969) and the partial credit model (PCM) of G. Masters (1982) were developed and compared. Both programs used maximum likelihood estimation of ability, and item selection was conducted on the basis of information. Two simulated data sets, one…

  20. Computerized Adaptive Testing Using a Class of High-Order Item Response Theory Models

    ERIC Educational Resources Information Center

    Huang, Hung-Yu; Chen, Po-Hsi; Wang, Wen-Chung

    2012-01-01

    In the human sciences, a common assumption is that latent traits have a hierarchical structure. Higher order item response theory models have been developed to account for this hierarchy. In this study, computerized adaptive testing (CAT) algorithms based on these kinds of models were implemented, and their performance under a variety of…

  1. De novo cholesterol synthesis at the crossroads of adaptive response to extracellular stress through SREBP.

    PubMed

    Robichon, Céline; Dugail, Isabelle

    2007-02-01

    Cell sterol supply is subjected to tight negative feedback regulation through the SREBP pathway. Upon cholesterol depletion, SREBP transcription factors become activated by cleavage of a membrane bound precursor form, which stimulates the expression of the genes encoding proteins of the cholesterol synthesis pathway. In this paper, we discuss two situations of extracellular stress (hypoxia and heat shock) in which the cholesterol synthesis pathway and SREBPs are directly impacted to generate an adaptive response to cell damage. On one hand, the lack of oxygen in fission yeast Saccharomyces pombe induces a drop in cholesterol synthesis which in turn activates SREBP-mediated transcription. The presence of genes involved in the anaerobic growth program among SREBP target genes in fission yeast, indicates that SREBP behaves as an oxygen sensor, required for adaptive growth in low oxygen. On the other hand, upon heat shock in mammalian cells, SREBP-responsive heat shock proteins have been characterized, which were able to upregulate sterol synthesis by targeting the activity of HMG-CoA reductase, the rate limiting enzyme in this pathway. Although not yet proven, high rates of sterol synthesis can be viewed as an adaptive response to correct structural membrane damage and bilayer fluidification induced by thermal stress. Together these situations illustrate how the highly regulated SREBP pathway for the control of sterol synthesis can be used to achieve cell adaptive responses to extracellular stresses.

  2. Bystander effects, genomic instability, adaptive response, and cancer risk assessment for radiation and chemical exposures

    SciTech Connect

    Preston, R. Julian . E-mail: preston.julian@epa.gov

    2005-09-01

    There is an increased interest in utilizing mechanistic data in support of the cancer risk assessment process for ionizing radiation and environmental chemical exposures. In this regard, the use of biologically based dose-response models is particularly advocated. The aim is to provide an enhanced basis for describing the nature of the dose-response curve for induced tumors at low levels of exposure. Cellular responses that might influence the nature of the dose-response curve at low exposures are understandably receiving attention. These responses (bystander effects, genomic instability, and adaptive responses) have been studied most extensively for radiation exposures. The former two could result in an enhancement of the tumor response at low doses and the latter could lead to a reduced response compared to that predicted by a linear extrapolation from high dose responses. Bystander responses, whereby cells other than those directly traversed by radiation tracks are damaged, can alter the concept of target cell population per unit dose. Similarly, induced genomic instability can alter the concept of total response to an exposure. There appears to be a role for oxidative damage and cellular signaling in the etiology of these cellular responses. The adaptive response appears to be inducible at very low doses of radiation or of some chemicals and reduces the cellular response to a larger challenge dose. It is currently unclear how these cellular toxic responses might be involved in tumor formation, if indeed they are. In addition, it is not known how widespread they are as regards inducing agents. Thus, their impact on low dose cancer risk remains to be established.

  3. The adaptive immune response does not influence hantavirus disease or persistence in the Syrian hamster.

    PubMed

    Prescott, Joseph; Safronetz, David; Haddock, Elaine; Robertson, Shelly; Scott, Dana; Feldmann, Heinz

    2013-10-01

    Pathogenic New World hantaviruses cause severe disease in humans characterized by a vascular leak syndrome, leading to pulmonary oedema and respiratory distress with case fatality rates approaching 40%. Hantaviruses infect microvascular endothelial cells without conspicuous cytopathic effects, indicating that destruction of the endothelium is not a mechanism of disease. In humans, high levels of inflammatory cytokines are present in the lungs of patients that succumb to infection. This, along with other observations, suggests that disease has an immunopathogenic component. Currently the only animal model available to study hantavirus disease is the Syrian hamster, where infection with Andes virus (ANDV), the primary agent of disease in South America, results in disease that closely mimics that seen in humans. Conversely, inoculation of hamsters with a passaged Sin Nombre virus (SNV), the virus responsible for most cases of disease in North America, results in persistent infection with high levels of viral replication. We found that ANDV elicited a stronger innate immune response, whereas SNV elicited a more robust adaptive response in the lung. Additionally, ANDV infection resulted in significant changes in the blood lymphocyte populations. To determine whether the adaptive immune response influences infection outcome, we depleted hamsters of CD4(+) and CD8(+) T cells before infection with hantaviruses. Depletion resulted in inhibition of virus-specific antibody responses, although the pathogenesis and replication of these viruses were unaltered. These data show that neither hantavirus replication, nor pathogenesis caused by these viruses, is influenced by the adaptive immune response in the Syrian hamster.

  4. Context-Specific Adaptation of Gravity-Dependent Vestibular Reflex Responses (NSBRI Neurovestibular Project 1)

    NASA Technical Reports Server (NTRS)

    Shelhamer, Mark; Goldberg, Jefim; Minor, Lloyd B.; Paloski, William H.; Young, Laurence R.; Zee, David S.

    1999-01-01

    Impairment of gaze and head stabilization reflexes can lead to disorientation and reduced performance in sensorimotor tasks such as piloting of spacecraft. Transitions between different gravitoinertial force (gif) environments - as during different phases of space flight - provide an extreme test of the adaptive capabilities of these mechanisms. We wish to determine to what extent the sensorimotor skills acquired in one gravity environment will transfer to others, and to what extent gravity serves as a context cue for inhibiting such transfer. We use the general approach of adapting a response (saccades, vestibuloocular reflex: VOR, or vestibulocollic reflex: VCR) to a particular change in gain or phase in one gif condition, adapting to a different gain or phase in a second gif condition, and then seeing if gif itself - the context cue - can recall the previously-learned adapted responses. Previous evidence indicates that unless there is specific training to induce context-specificity, reflex adaptation is sequential rather than simultaneous. Various experiments in this project investigate the behavioral properties, neurophysiological basis, and anatomical substrate of context-specific learning, using otolith (gravity) signals as a context cue. In the following, we outline the methods for all experiments in this project, and provide details and results on selected experiments.

  5. Smooth muscle overexpression of IGF-I induces a novel adaptive response to small bowel resection.

    PubMed

    Knott, Andrew W; Juno, Russell J; Jarboe, Marcus D; Profitt, Sherri A; Erwin, Christopher R; Smith, Eric P; Fagin, James A; Warner, Brad W

    2004-09-01

    Prior studies of intestinal adaptation after massive small bowel resection (SBR) have focused on growth factors and their effects on amplification of the gut mucosa. Because adaptive changes have also been described in intestinal smooth muscle, we sought to determine the effect of targeted smooth muscle growth factor overexpression on resection-induced intestinal adaptation. Male transgenic mice with smooth muscle cell overexpression of insulin-like growth factor I (IGF-I) by virtue of an alpha-smooth muscle actin promoter were obtained. SMP8 IGF-I transgenic (IGF-I TG) and nontransgenic (NT) littermates underwent 50% proximal SBR or sham operation and were then killed after 3 or 28 days. NT mice showed the expected alterations in mucosal adaptive parameters after SBR, such as increased wet weight and villus height. The IGF-I TG mice had inherently taller villi, which did not increase significantly after SBR. In addition, IGF-I TG mice had a 50% postresection persistent increase in remnant intestinal length, which was associated with an early decline and later increase in relative mucosal surface area. These results indicate that growth factor overexpression within the muscularis layer of the bowel wall induces significant postresection adaptive intestinal lengthening and a unique mucosal response. IGF-I signaling within the muscle wall may play an important role in the pathogenesis of resection-induced adaptation.

  6. Degree of adaptive response in urban tolerant birds shows influence of habitat-of-origin

    PubMed Central

    2014-01-01

    Urban exploiters and adapters are often coalesced under a term of convenience as ‘urban tolerant’. This useful but simplistic characterisation masks a more nuanced interplay between and within assemblages of birds that are more or less well adapted to a range of urban habitats. I test the hypotheses that objectively-defined urban exploiter and suburban adapter assemblages within the broad urban tolerant grouping in Melbourne vary in their responses within the larger group to predictor variables, and that the most explanatory predictor variables vary between the two assemblages. A paired, partitioned analysis of exploiter and adapter preferences for points along the urban–rural gradient was undertaken to decompose the overall trend into diagnosable parts for each assemblage. In a similar way to that in which time since establishment has been found to be related to high urban densities of some bird species and biogeographic origin predictive of urban adaptation extent, habitat origins of members of bird assemblages influence the degree to which they become urban tolerant. Bird species that objectively classify as urban tolerant will further classify as either exploiters or adapters according to the degree of openness of their habitats-of-origin. PMID:24688881

  7. Physiological and proteomic analysis of Lactobacillus casei in response to acid adaptation.

    PubMed

    Wu, Chongde; He, Guiqiang; Zhang, Juan

    2014-10-01

    The aim of this study was to investigate the acid tolerance response (ATR) in Lactobacillus casei by a combined physiological and proteomic analysis. To optimize the ATR induction, cells were acid adapted for 1 h at different pHs, and then acid challenged at pH 3.5. The result showed that acid adaptation improved acid tolerance, and the highest survival was observed in cells adapted at pH 4.5 for 1 h. Analysis of the physiological data showed that the acid-adapted cells exhibited higher intracellular pH (pHi), intracellular NH4 (+) content, and lower inner permeability compared with the cells without adaptation. Proteomic analysis was performed upon acid adaptation to different pHs (pH 6.5 vs. pH 4.5) using two-dimensional electrophoresis. A total of 24 proteins that exhibited at least 1.5-fold differential expression were identified. Four proteins (Pgk, LacD, Hpr, and Galm) involved in carbohydrate catabolism and five classic stress response proteins (GroEL, GrpE, Dnak, Hspl, and LCAZH_2811) were up-regulated after acid adaptation at pH 4.5 for 1 h. Validation of the proteomic data was performed by quantitative RT-PCR, and transcriptional regulation of all selected genes showed a positive correlation with the proteomic patterns of the identified proteins. Results presented in this study may be useful for further elucidating the acid tolerance mechanisms and may help in formulating new strategies to improve the industrial performance of this species during acid stress. PMID:25062817

  8. A cascade reaction network mimicking the basic functional steps of adaptive immune response

    NASA Astrophysics Data System (ADS)

    Han, Da; Wu, Cuichen; You, Mingxu; Zhang, Tao; Wan, Shuo; Chen, Tao; Qiu, Liping; Zheng, Zheng; Liang, Hao; Tan, Weihong

    2015-10-01

    Biological systems use complex ‘information-processing cores’ composed of molecular networks to coordinate their external environment and internal states. An example of this is the acquired, or adaptive, immune system (AIS), which is composed of both humoral and cell-mediated components. Here we report the step-by-step construction of a prototype mimic of the AIS that we call an adaptive immune response simulator (AIRS). DNA and enzymes are used as simple artificial analogues of the components of the AIS to create a system that responds to specific molecular stimuli in vitro. We show that this network of reactions can function in a manner that is superficially similar to the most basic responses of the vertebrate AIS, including reaction sequences that mimic both humoral and cellular responses. As such, AIRS provides guidelines for the design and engineering of artificial reaction networks and molecular devices.

  9. Adaptive all the way down: building responsive materials from hierarchies of chemomechanical feedback.

    PubMed

    Grinthal, Alison; Aizenberg, Joanna

    2013-09-01

    A living organism is a bundle of dynamic, integrated adaptive processes: not only does it continuously respond to constant changes in temperature, sunlight, nutrients, and other features of its environment, but it does so by coordinating hierarchies of feedback among cells, tissues, organs, and networks all continuously adapting to each other. At the root of it all is one of the most fundamental adaptive processes: the constant tug of war between chemistry and mechanics that interweaves chemical signals with endless reconfigurations of macromolecules, fibers, meshworks, and membranes. In this tutorial we explore how such chemomechanical feedback - as an inherently dynamic, iterative process connecting size and time scales - can and has been similarly evoked in synthetic materials to produce a fascinating diversity of complex multiscale responsive behaviors. We discuss how chemical kinetics and architecture can be designed to generate stimulus-induced 3D spatiotemporal waves and topographic patterns within a single bulk material, and how feedback between interior dynamics and surface-wide instabilities can further generate higher order buckling and wrinkling patterns. Building on these phenomena, we show how yet higher levels of feedback and spatiotemporal complexity can be programmed into hybrid materials, and how these mechanisms allow hybrid materials to be further integrated into multicompartmental systems capable of hierarchical chemo-mechano-chemical feedback responses. These responses no doubt represent only a small sample of the chemomechanical feedback behaviors waiting to be discovered in synthetic materials, and enable us to envision nearly limitless possibilities for designing multiresponsive, multifunctional, self-adapting materials and systems.

  10. Thermotolerant yeasts selected by adaptive evolution express heat stress response at 30 °C

    PubMed Central

    Caspeta, Luis; Chen, Yun; Nielsen, Jens

    2016-01-01

    Exposure to long-term environmental changes across >100s of generations results in adapted phenotypes, but little is known about how metabolic and transcriptional responses are optimized in these processes. Here, we show that thermotolerant yeast strains selected by adaptive laboratory evolution to grow at increased temperature, activated a constitutive heat stress response when grown at the optimal ancestral temperature, and that this is associated with a reduced growth rate. This preventive response was perfected by additional transcriptional changes activated when the cultivation temperature is increased. Remarkably, the sum of global transcriptional changes activated in the thermotolerant strains when transferred from the optimal to the high temperature, corresponded, in magnitude and direction, to the global changes observed in the ancestral strain exposed to the same transition. This demonstrates robustness of the yeast transcriptional program when exposed to heat, and that the thermotolerant strains streamlined their path to rapidly and optimally reach post-stress transcriptional and metabolic levels. Thus, long-term adaptation to heat improved yeasts ability to rapidly adapt to increased temperatures, but this also causes a trade-off in the growth rate at the optimal ancestral temperature. PMID:27229477

  11. Context-Specific Adaptation of Gravity-Dependent Vestibular Reflex Responses

    NASA Technical Reports Server (NTRS)

    Shelhamer, Mark J.

    1999-01-01

    Stabilization of the eyes and head during body movements is important for maintaining balance and keeping the images of objects stationary on our retinas. Impairment of this ability can lead to disorientation and reduced performance in sensorimotor tasks such as piloting of spacecraft. In the absence of a normal earth gravity field, the dynamics of head stabilization, and the interpretation of vestibular signals that sense gravity and linear acceleration, are subject to change. Transitions between different gravitoinertial force environments - as during different phases of space flight - provide an extreme test of the adaptive mechanisms that maintain these reflexive abilities. It is vitally important to determine human adaptive capabilities in such a circumstance, so that we can know to what extent the sensorimotor skills acquired in one gravity environment will transfer to others. Our work lays the foundation for understanding these capabilities, and for determining how we can aid the processes of adaptation and readaptation. An integrated set of experiments addresses this issue. We use the general approach of adapting some type of reflexive eye movement (saccades, the angular vestibulo-ocular reflex (AVOR), the linear vestibulo-ocular reflex (LVOR)), or the vestibulo-collic reflex (VCR), to a particular change in gain or phase in one condition of gravitoiner-tial force, and adapting to a different gain or phase (or asking for no change) in a second gravitoinertial force condition, and then seeing if the gravitoinertial force itself - the context cue - can recall the previously learned adapted responses. The majority of the experiments in the laboratory use the direction of vertical gaze or the direction of gravity (head tilt) as the context cue. This allows us to study context-specificity in a ground-based setting. One set of experiments, to be performed in parabolic flight, specifically uses the magnitude of gravitoinertial force as a context cue. This is a

  12. The Response of the Root Apex in Plant Adaptation to Iron Heterogeneity in Soil

    PubMed Central

    Li, Guangjie; Kronzucker, Herbert J.; Shi, Weiming

    2016-01-01

    Iron (Fe) is an essential micronutrient for plant growth and development, and is frequently limiting. By contrast, over-accumulation of Fe in plant tissues leads to toxicity. In soils, the distribution of Fe is highly heterogeneous. To cope with this heterogeneity, plant roots engage an array of adaptive responses to adjust their morphology and physiology. In this article, we review root morphological and physiological changes in response to low- and high-Fe conditions and highlight differences between these responses. We especially focus on the role of the root apex in dealing with the stresses resulting from Fe shortage and excess. PMID:27047521

  13. Evasion of Influenza A Viruses from Innate and Adaptive Immune Responses

    PubMed Central

    van de Sandt, Carolien E.; Kreijtz, Joost H. C. M.; Rimmelzwaan, Guus F.

    2012-01-01

    The influenza A virus is one of the leading causes of respiratory tract infections in humans. Upon infection with an influenza A virus, both innate and adaptive immune responses are induced. Here we discuss various strategies used by influenza A viruses to evade innate immune responses and recognition by components of the humoral and cellular immune response, which consequently may result in reduced clearing of the virus and virus-infected cells. Finally, we discuss how the current knowledge about immune evasion can be used to improve influenza A vaccination strategies. PMID:23170167

  14. Adaptive response of vascular endothelial cells to an acute increase in shear stress frequency

    PubMed Central

    Zhang, Ji

    2013-01-01

    Local shear stress sensed by arterial endothelial cells is occasionally altered by changes in global hemodynamic parameters, e.g., heart rate and blood flow rate, as a result of normal physiological events, such as exercise. In a recently study (41), we demonstrated that during the adaptive response to increased shear magnitude, porcine endothelial cells exhibited an unique phenotype featuring a transient increase in permeability and the upregulation of a set of anti-inflammatory and antioxidative genes. In the present study, we characterize the adaptive response of these cells to an increase in shear frequency, another important hemodynamic parameter with implications in atherogenesis. Endothelial cells were preconditioned by a basal-level sinusoidal shear stress of 15 ± 15 dyn/cm2 at 1 Hz, and the frequency was then elevated to 2 Hz. Endothelial permeability increased slowly after the frequency step-up, but the increase was relatively small. Using microarrays, we identified 37 genes that are sensitive to the frequency step-up. The acute increase in shear frequency upregulates a set of cell-cycle regulation and angiogenesis-related genes. The overall adaptive response to the increased frequency is distinctly different from that to a magnitude step-up. However, consistent with the previous study, our data support the notion that endothelial function during an adaptive response is different than that of fully adapted endothelial cells. Our studies may also provide insights into the beneficial effects of exercise on vascular health: transient increases in frequency may facilitate endothelial repair, whereas similar increases in shear magnitude may keep excessive inflammation and oxidative stress at bay. PMID:23851277

  15. Multiscale biomechanical responses of adapted bone-periodontal ligament-tooth fibrous joints.

    PubMed

    Jang, Andrew T; Merkle, Arno P; Fahey, Kevin P; Gansky, Stuart A; Ho, Sunita P

    2015-12-01

    Reduced functional loads cause adaptations in organs. In this study, temporal adaptations of bone-ligament-tooth fibrous joints to reduced functional loads were mapped using a holistic approach. Systematic studies were performed to evaluate organ-level and tissue-level adaptations in specimens harvested periodically from rats (N=60) given powder food for 6 months over 8,12,16,20, and 24 weeks. Bone-periodontal ligament (PDL)-tooth fibrous joint adaptation was evaluated by comparing changes in joint stiffness with changes in functional space between the tooth and alveolar bony socket. Adaptations in tissues included mapping changes in the PDL and bone architecture as observed from collagen birefringence, bone hardness and volume fraction in rats fed soft foods (soft diet, SD) compared to those fed hard pellets as a routine diet (hard diet, HD). In situ biomechanical testing on harvested fibrous joints revealed increased stiffness in SD groups (SD:239-605 N/mm) (p<0.05) at 8 and 12 weeks. Increased joint stiffness in early development phase was due to decreased functional space (at 8 weeks change in functional space was -33 μm, at 12 weeks change in functional space was -30 μm) and shifts in tissue quality as highlighted by birefringence, architecture and hardness. These physical changes were not observed in joints that were well into function, that is, in rodents older than 12 weeks of age. Significant adaptations in older groups were highlighted by shifts in bone growth (bone volume fraction 24 weeks: Δ-0.06) and bone hardness (8 weeks: Δ-0.04 GPa, 16 weeks: Δ-0.07 GPa, 24 weeks: Δ-0.06 GPa). The response rate (N/s) of joints to mechanical loads decreased in SD groups. Results from the study showed that joint adaptation depended on age. The initial form-related adaptation (observed change in functional space) can challenge strain-adaptive nature of tissues to meet functional demands with increasing age into adulthood. The coupled effect between functional

  16. Progression of Cellular Adaptations in Medial Prefrontal and Orbitofrontal Cortex in Response to Repeated Amphetamine

    PubMed Central

    Homayoun, Houman; Moghaddam, Bita

    2010-01-01

    Recent theories on addiction implicate adaptive changes in prefrontal cortex (PFC) neurons in reinforcing and psychotomimetic properties of psychostimulants, yet little is known about how neuronal responses to these drugs change over time. Here we describe electrophysiological evidence for a progressive and sustained change in the response of PFC neurons to amphetamine during repeated exposure. In spontaneously behaving rats and in rats engaged in an instrumental responding task, we followed the activity of medial PFC (mPFC) and orbitofrontal cortex (OFC) neurons during daily exposure to amphetamine and after a post-withdrawal challenge. Repeated amphetamine increased the number of responsive neurons and the magnitude of responses and modified spontaneous burst patterns. These changes were apparent after a few exposures to amphetamine, were amplified after withdrawal, and were region specific in that repeated amphetamine increasingly produced inhibitory responses in mPFC and excitatory responses in OFC. In behaviorally engaged animals, the gradual enhancement in mPFC inhibition and OFC overactivation correlated with a progressive impairment of instrumental responding. Furthermore, these changes were evident predominately in neurons that displayed phasic responses during task-related events. These rapid-onset and sustained cellular adaptations suggest that even limited exposure to psychostimulants may reduce the influence of mPFC neurons on behavior while at the same time exaggerating information encoded by OFC neurons. PMID:16885216

  17. Robust projective lag synchronization in drive-response dynamical networks via adaptive control

    NASA Astrophysics Data System (ADS)

    Al-mahbashi, G.; Noorani, M. S. Md; Bakar, S. A.; Al-sawalha, M. M.

    2016-02-01

    This paper investigates the problem of projective lag synchronization behavior in drive-response dynamical networks (DRDNs) with identical and non-identical nodes. An adaptive control method is designed to achieve projective lag synchronization with fully unknown parameters and unknown bounded disturbances. These parameters were estimated by adaptive laws obtained by Lyapunov stability theory. Furthermore, sufficient conditions for synchronization are derived analytically using the Lyapunov stability theory and adaptive control. In addition, the unknown bounded disturbances are also overcome by the proposed control. Finally, analytical results show that the states of the dynamical network with non-delayed coupling can be asymptotically synchronized onto a desired scaling factor under the designed controller. Simulation results show the effectiveness of the proposed method.

  18. Increased rate of response of the pituitary-adrenal system in rats adapted to chronic stress

    NASA Technical Reports Server (NTRS)

    Sakellaris, P. C.; Vernikos-Danellis, J.

    1975-01-01

    The response and adaptation of the pituitary-adrenal system to chronic stresses was investigated. These included individual caging, confinement, and exposure to cold for varying periods of time. Studies were carried out demonstrating that during the period of adaptation when plasma corticosterone concentrations returned toward their prestress level despite continued exposure to the stressor, the animals responded to additional stimuli of ether for 1 min, a saline injection, or release from confinement with a faster increase (within 2.5 min) in plasma corticosterone than controls (10 min). It is concluded that during adaptation to a chronic stress the pituitary-adrenal system is not inhibited by the circulating steroid level but is actually hypersensitive to additional stimuli.

  19. Enhanced Sleep Is an Evolutionarily Adaptive Response to Starvation Stress in Drosophila.

    PubMed

    Slocumb, Melissa E; Regalado, Josue M; Yoshizawa, Masato; Neely, Greg G; Masek, Pavel; Gibbs, Allen G; Keene, Alex C

    2015-01-01

    Animals maximize fitness by modulating sleep and foraging strategies in response to changes in nutrient availability. Wild populations of the fruit fly, Drosophila melanogaster, display highly variable levels of starvation and desiccation resistance that differ in accordance with geographic location, nutrient availability, and evolutionary history. Further, flies potently modulate sleep in response to changes in food availability, and selection for starvation resistance enhances sleep, revealing strong genetic relationships between sleep and nutrient availability. To determine the genetic and evolutionary relationship between sleep and nutrient deprivation, we assessed sleep in flies selected for desiccation or starvation resistance. While starvation resistant flies have higher levels of triglycerides, desiccation resistant flies have enhanced glycogen stores, indicative of distinct physiological adaptations to food or water scarcity. Strikingly, selection for starvation resistance, but not desiccation resistance, leads to increased sleep, indicating that enhanced sleep is not a generalized consequence of higher energy stores. Thermotolerance is not altered in starvation or desiccation resistant flies, providing further evidence for context-specific adaptation to environmental stressors. F2 hybrid flies were generated by crossing starvation selected flies with desiccation selected flies, and the relationship between nutrient deprivation and sleep was examined. Hybrids exhibit a positive correlation between starvation resistance and sleep, while no interaction was detected between desiccation resistance and sleep, revealing that prolonged sleep provides an adaptive response to starvation stress. Therefore, these findings demonstrate context-specific evolution of enhanced sleep in response to chronic food deprivation, and provide a model for understanding the evolutionary relationship between sleep and nutrient availability.

  20. Quantifying the Early Immune Response and Adaptive Immune Response Kinetics in Mice Infected with Influenza A Virus ▿

    PubMed Central

    Miao, Hongyu; Hollenbaugh, Joseph A.; Zand, Martin S.; Holden-Wiltse, Jeanne; Mosmann, Tim R.; Perelson, Alan S.; Wu, Hulin; Topham, David J.

    2010-01-01

    Seasonal and pandemic influenza A virus (IAV) continues to be a public health threat. However, we lack a detailed and quantitative understanding of the immune response kinetics to IAV infection and which biological parameters most strongly influence infection outcomes. To address these issues, we use modeling approaches combined with experimental data to quantitatively investigate the innate and adaptive immune responses to primary IAV infection. Mathematical models were developed to describe the dynamic interactions between target (epithelial) cells, influenza virus, cytotoxic T lymphocytes (CTLs), and virus-specific IgG and IgM. IAV and immune kinetic parameters were estimated by fitting models to a large data set obtained from primary H3N2 IAV infection of 340 mice. Prior to a detectable virus-specific immune response (before day 5), the estimated half-life of infected epithelial cells is ∼1.2 days, and the half-life of free infectious IAV is ∼4 h. During the adaptive immune response (after day 5), the average half-life of infected epithelial cells is ∼0.5 days, and the average half-life of free infectious virus is ∼1.8 min. During the adaptive phase, model fitting confirms that CD8+ CTLs are crucial for limiting infected cells, while virus-specific IgM regulates free IAV levels. This may imply that CD4 T cells and class-switched IgG antibodies are more relevant for generating IAV-specific memory and preventing future infection via a more rapid secondary immune response. Also, simulation studies were performed to understand the relative contributions of biological parameters to IAV clearance. This study provides a basis to better understand and predict influenza virus immunity. PMID:20410284

  1. The human milk oligosaccharide 2'-fucosyllactose augments the adaptive response to extensive intestinal.

    PubMed

    Mezoff, Ethan A; Hawkins, Jennifer A; Ollberding, Nicholas J; Karns, Rebekah; Morrow, Ardythe L; Helmrath, Michael A

    2016-03-15

    Intestinal resection resulting in short bowel syndrome (SBS) carries a heavy burden of long-term morbidity, mortality, and cost of care, which can be attenuated with strategies that improve intestinal adaptation. SBS infants fed human milk, compared with formula, have more rapid intestinal adaptation. We tested the hypothesis that the major noncaloric human milk oligosaccharide 2'-fucosyllactose (2'-FL) contributes to the adaptive response after intestinal resection. Using a previously described murine model of intestinal adaptation, we demonstrated increased weight gain from 21 to 56 days (P < 0.001) and crypt depth at 56 days (P < 0.0095) with 2'-FL supplementation after ileocecal resection. Furthermore, 2'-FL increased small bowel luminal content microbial alpha diversity following resection (P < 0.005) and stimulated a bloom in organisms of the genus Parabacteroides (log2-fold = 4.1, P = 0.035). Finally, transcriptional analysis of the intestine revealed enriched ontologies and pathways related to antimicrobial peptides, metabolism, and energy processing. We conclude that 2'-FL supplementation following ileocecal resection increases weight gain, energy availability through microbial community modulation, and histological changes consistent with improved adaptation.

  2. Adaptive Governance, Uncertainty, and Risk: Policy Framing and Responses to Climate Change, Drought, and Flood.

    PubMed

    Hurlbert, Margot; Gupta, Joyeeta

    2016-02-01

    As climate change impacts result in more extreme events (such as droughts and floods), the need to understand which policies facilitate effective climate change adaptation becomes crucial. Hence, this article answers the question: How do governments and policymakers frame policy in relation to climate change, droughts, and floods and what governance structures facilitate adaptation? This research interrogates and analyzes through content analysis, supplemented by semi-structured qualitative interviews, the policy response to climate change, drought, and flood in relation to agricultural producers in four case studies in river basins in Chile, Argentina, and Canada. First, an epistemological explanation of risk and uncertainty underscores a brief literature review of adaptive governance, followed by policy framing in relation to risk and uncertainty, and an analytical model is developed. Pertinent findings of the four cases are recounted, followed by a comparative analysis. In conclusion, recommendations are made to improve policies and expand adaptive governance to better account for uncertainty and risk. This article is innovative in that it proposes an expanded model of adaptive governance in relation to "risk" that can help bridge the barrier of uncertainty in science and policy.

  3. Adaptive Governance, Uncertainty, and Risk: Policy Framing and Responses to Climate Change, Drought, and Flood.

    PubMed

    Hurlbert, Margot; Gupta, Joyeeta

    2016-02-01

    As climate change impacts result in more extreme events (such as droughts and floods), the need to understand which policies facilitate effective climate change adaptation becomes crucial. Hence, this article answers the question: How do governments and policymakers frame policy in relation to climate change, droughts, and floods and what governance structures facilitate adaptation? This research interrogates and analyzes through content analysis, supplemented by semi-structured qualitative interviews, the policy response to climate change, drought, and flood in relation to agricultural producers in four case studies in river basins in Chile, Argentina, and Canada. First, an epistemological explanation of risk and uncertainty underscores a brief literature review of adaptive governance, followed by policy framing in relation to risk and uncertainty, and an analytical model is developed. Pertinent findings of the four cases are recounted, followed by a comparative analysis. In conclusion, recommendations are made to improve policies and expand adaptive governance to better account for uncertainty and risk. This article is innovative in that it proposes an expanded model of adaptive governance in relation to "risk" that can help bridge the barrier of uncertainty in science and policy. PMID:26630544

  4. Non-climatic thermal adaptation: implications for species' responses to climate warming.

    PubMed

    Marshall, David J; McQuaid, Christopher D; Williams, Gray A

    2010-10-23

    There is considerable interest in understanding how ectothermic animals may physiologically and behaviourally buffer the effects of climate warming. Much less consideration is being given to how organisms might adapt to non-climatic heat sources in ways that could confound predictions for responses of species and communities to climate warming. Although adaptation to non-climatic heat sources (solar and geothermal) seems likely in some marine species, climate warming predictions for marine ectotherms are largely based on adaptation to climatically relevant heat sources (air or surface sea water temperature). Here, we show that non-climatic solar heating underlies thermal resistance adaptation in a rocky-eulittoral-fringe snail. Comparisons of the maximum temperatures of the air, the snail's body and the rock substratum with solar irradiance and physiological performance show that the highest body temperature is primarily controlled by solar heating and re-radiation, and that the snail's upper lethal temperature exceeds the highest climatically relevant regional air temperature by approximately 22°C. Non-climatic thermal adaptation probably features widely among marine and terrestrial ectotherms and because it could enable species to tolerate climatic rises in air temperature, it deserves more consideration in general and for inclusion into climate warming models.

  5. The stringent response regulates adaptation to darkness in the cyanobacterium Synechococcus elongatus.

    PubMed

    Hood, Rachel D; Higgins, Sean A; Flamholz, Avi; Nichols, Robert J; Savage, David F

    2016-08-16

    The cyanobacterium Synechococcus elongatus relies upon photosynthesis to drive metabolism and growth. During darkness, Synechococcus stops growing, derives energy from its glycogen stores, and greatly decreases rates of macromolecular synthesis via unknown mechanisms. Here, we show that the stringent response, a stress response pathway whose genes are conserved across bacteria and plant plastids, contributes to this dark adaptation. Levels of the stringent response alarmone guanosine 3'-diphosphate 5'-diphosphate (ppGpp) rise after a shift from light to dark, indicating that darkness triggers the same response in cyanobacteria as starvation in heterotrophic bacteria. High levels of ppGpp are sufficient to stop growth and dramatically alter many aspects of cellular physiology, including levels of photosynthetic pigments and polyphosphate, DNA content, and the rate of translation. Cells unable to synthesize ppGpp display pronounced growth defects after exposure to darkness. The stringent response regulates expression of a number of genes in Synechococcus, including ribosomal hibernation promoting factor (hpf), which causes ribosomes to dimerize in the dark and may contribute to decreased translation. Although the metabolism of Synechococcus differentiates it from other model bacterial systems, the logic of the stringent response remains remarkably conserved, while at the same time having adapted to the unique stresses of the photosynthetic lifestyle. PMID:27486247

  6. Mitochondrial SIRT3 Mediates Adaptive Responses of Neurons to Exercise and Metabolic and Excitatory Challenges.

    PubMed

    Cheng, Aiwu; Yang, Ying; Zhou, Ye; Maharana, Chinmoyee; Lu, Daoyuan; Peng, Wei; Liu, Yong; Wan, Ruiqian; Marosi, Krisztina; Misiak, Magdalena; Bohr, Vilhelm A; Mattson, Mark P

    2016-01-12

    The impact of mitochondrial protein acetylation status on neuronal function and vulnerability to neurological disorders is unknown. Here we show that the mitochondrial protein deacetylase SIRT3 mediates adaptive responses of neurons to bioenergetic, oxidative, and excitatory stress. Cortical neurons lacking SIRT3 exhibit heightened sensitivity to glutamate-induced calcium overload and excitotoxicity and oxidative and mitochondrial stress; AAV-mediated Sirt3 gene delivery restores neuronal stress resistance. In models relevant to Huntington's disease and epilepsy, Sirt3(-/-) mice exhibit increased vulnerability of striatal and hippocampal neurons, respectively. SIRT3 deficiency results in hyperacetylation of several mitochondrial proteins, including superoxide dismutase 2 and cyclophilin D. Running wheel exercise increases the expression of Sirt3 in hippocampal neurons, which is mediated by excitatory glutamatergic neurotransmission and is essential for mitochondrial protein acetylation homeostasis and the neuroprotective effects of running. Our findings suggest that SIRT3 plays pivotal roles in adaptive responses of neurons to physiological challenges and resistance to degeneration. PMID:26698917

  7. Phenotypic plasticity and adaptive evolution contribute to advancing flowering phenology in response to climate change.

    PubMed

    Anderson, Jill T; Inouye, David W; McKinney, Amy M; Colautti, Robert I; Mitchell-Olds, Tom

    2012-09-22

    Anthropogenic climate change has already altered the timing of major life-history transitions, such as the initiation of reproduction. Both phenotypic plasticity and adaptive evolution can underlie rapid phenological shifts in response to climate change, but their relative contributions are poorly understood. Here, we combine a continuous 38 year field survey with quantitative genetic field experiments to assess adaptation in the context of climate change. We focused on Boechera stricta (Brassicaeae), a mustard native to the US Rocky Mountains. Flowering phenology advanced significantly from 1973 to 2011, and was strongly associated with warmer temperatures and earlier snowmelt dates. Strong directional selection favoured earlier flowering in contemporary environments (2010-2011). Climate change could drive this directional selection, and promote even earlier flowering as temperatures continue to increase. Our quantitative genetic analyses predict a response to selection of 0.2 to 0.5 days acceleration in flowering per generation, which could account for more than 20 per cent of the phenological change observed in the long-term dataset. However, the strength of directional selection and the predicted evolutionary response are likely much greater now than even 30 years ago because of rapidly changing climatic conditions. We predict that adaptation will likely be necessary for long-term in situ persistence in the context of climate change.

  8. Phenotypic plasticity and adaptive evolution contribute to advancing flowering phenology in response to climate change.

    PubMed

    Anderson, Jill T; Inouye, David W; McKinney, Amy M; Colautti, Robert I; Mitchell-Olds, Tom

    2012-09-22

    Anthropogenic climate change has already altered the timing of major life-history transitions, such as the initiation of reproduction. Both phenotypic plasticity and adaptive evolution can underlie rapid phenological shifts in response to climate change, but their relative contributions are poorly understood. Here, we combine a continuous 38 year field survey with quantitative genetic field experiments to assess adaptation in the context of climate change. We focused on Boechera stricta (Brassicaeae), a mustard native to the US Rocky Mountains. Flowering phenology advanced significantly from 1973 to 2011, and was strongly associated with warmer temperatures and earlier snowmelt dates. Strong directional selection favoured earlier flowering in contemporary environments (2010-2011). Climate change could drive this directional selection, and promote even earlier flowering as temperatures continue to increase. Our quantitative genetic analyses predict a response to selection of 0.2 to 0.5 days acceleration in flowering per generation, which could account for more than 20 per cent of the phenological change observed in the long-term dataset. However, the strength of directional selection and the predicted evolutionary response are likely much greater now than even 30 years ago because of rapidly changing climatic conditions. We predict that adaptation will likely be necessary for long-term in situ persistence in the context of climate change. PMID:22787021

  9. Thermo-sensitive response based on the membrane fluidity adaptation in Paramecium multimicronucleatum.

    PubMed

    Toyoda, Taichi; Hiramatsu, Yoshinori; Sasaki, Toshiaki; Nakaoka, Yasuo

    2009-09-01

    Relationships between the thermo-sensitive response and membrane lipid fluidity were studied using a ciliated protozoan, Paramecium multimicronucleatum. Paramecium elicits a transient membrane depolarization in response to a cooling stimulus (temperature drop). The depolarization amplitude was largest when the cooling stimulus was started from the culture temperature, whilst when cooling started at a temperature more than 5 degrees C higher or lower than the culture temperature, only a small depolarization was induced. Therefore, the cooling-induced response was dependent on the culture temperature and its sensitivity to the cooling stimulus was highest at the culture temperature. Membrane fluidity measurements of living cells using the fluorescent dye 6-lauroyl-2-dimethylaminonaphthalene (laurdan) showed that the fluidity measured at the culture temperature was almost constant irrespective of the temperature at which the cells had been cultured and adapted, which is consistent with homeoviscous adaptation. The constant fluidity at the culture temperature quickly decreased within a few seconds of application of the cooling stimulus, and the decreased fluidity gradually readapted to a constant level at the decreased temperature within 1 h. When the constant fluidity at culture temperature was modified by the addition of procaine or benzyl alcohol, the cooling-induced depolarization was completely abolished. These results suggest the possibility that the adaptation of fluidity to a constant level and its quick decrease below the constant level activate cooling-sensitive channels to elicit the transient depolarization.

  10. Biological Response of Positron Emission Tomography Scan Exposure and Adaptive Response in Humans

    PubMed Central

    Schnarr, Kara; Carter, Timothy F.; Gillis, Daniel; Webber, Colin; Dayes, Ian; Dolling, Joanna A.; Gulenchyn, Karen; Boreham, Douglas R.

    2015-01-01

    The biological effects of exposure to radioactive fluorodeoxyglucose (18F-FDG) were investigated in the lymphocytes of patients undergoing positron emission tomography (PET) procedures. Low-dose, radiation-induced cellular responses were measured using 3 different end points: (1) apoptosis; (2) chromosome aberrations; and (3) γH2AX foci formation. The results showed no significant change in lymphocyte apoptosis, or chromosome aberrations, as a result of in vivo 18F-FDG exposure, and there was no evidence the PET scan modified the apoptotic response of lymphocytes to a subsequent 2 Gy in vitro challenge irradiation. However, lymphocytes sampled from patients following a PET scan showed an average of 22.86% fewer chromosome breaks and 39.16% fewer dicentrics after a subsequent 2 Gy in vitro challenge irradiation. The effect of 18F-FDG exposure on phosphorylation of histone H2AX (γH2AX) in lymphocytes of patients showed a varied response between individuals. The relationship between γH2AX foci formation and increasing activity of 18F-FDG was not directly proportional to dose. This variation is most likely attributed to differences in the factors that combine to constitute an individual’s radiation response. In summary, the results of this study indicate18F-FDG PET scans may not be detrimental but can elicit variable responses between individuals and can modify cellular response to subsequent radiation exposures. PMID:26740810

  11. Homeland security and virtual reality: building a Strategic Adaptive Response System (STARS).

    PubMed

    Swift, Christopher; Rosen, Joseph M; Boezer, Gordon; Lanier, Jaron; Henderson, Joseph V; Liu, Alan; Merrell, Ronald C; Nguyen, Sinh; Demas, Alex; Grigg, Elliot B; McKnight, Matthew F; Chang, Janelle; Koop, C Everett

    2005-01-01

    The advent of the Global War on Terrorism (GWOT) underscored the need to improve the U.S. disaster response paradigm. Existing systems involve numerous agencies spread across disparate functional and geographic jurisdictions. The current architecture remains vulnerable to sophisticated terrorist strikes. To address these vulnerabilities, we must continuously adapt and improve our Homeland Security architecture. Virtual Reality (VR) technologies will help model those changes and integrate technologies. This paper provides a broad overview of the strategic threats, together with a detailed examination of how specific VR technologies could be used to ensure successful disaster responses. PMID:15718795

  12. Adapting human postural reflexes following localized cerebrovascular lesion: analysis of bilateral long latency responses.

    PubMed

    Di Fabio, R P; Badke, M B; Duncan, P W

    1986-01-22

    The symmetry and adaptability of long latency stretch responses was studied in a group of 4 adult hemiplegics and 5 normals of similar age. Subjects stood on a moveable platform which directly rotated the ankles unexpectedly during a series of horizontal anterioposterior (AP) translations. When the platform was rotated toes-up, long latency discharge of gastrocnemius and hamstring muscles enhanced loss of balance by pulling the body backwards. Toes-down platform rotation elicited a reflex response from tibialis anterior and quadriceps which inappropriately pulled the body forward. Attenuation of these long latency responses was necessary to minimize functional destabilization. Normal and stroke subjects demonstrated appropriate suppression of long latency responses, but the magnitude of attenuation was not uniform in hemiplegics. Adaptation was decreased in the proximal synergists compared to normal. Latency of muscle activation in the paretic limb was prolonged, and a preference for initial non-paretic limb activation was evident. Both lower extremities in hemiplegics showed a disruption of timing between distal and proximal synergists. These results suggest that stroke victims retain or recover the ability to modulate stretch reflex activity for balance. Temporal and spatial response asymmetries surface as critical factors underlying disequilibrium associated with localized cerebrovascular lesion. PMID:3942897

  13. Sex-related adaptive responses to interaction of drought and salinity in Populus yunnanensis.

    PubMed

    Chen, Lianghua; Zhang, Sheng; Zhao, Hongxia; Korpelainen, Helena; Li, Chunyang

    2010-10-01

    We used Populus yunnanensis Dode., a native dioecious species in southwestern China, as a model species to study morphological, physiological, biochemical and ultrastructural responses to drought, salinity and their combination. Females exhibited more growth inhibition, gas exchange rate depression and reactive oxygen species (ROS) accumulation; higher lipid peroxide levels, lower osmotic adjustment capacity and ascorbate-glutathione cycle enzyme activities; and more damage to cell organelles than did males under drought, salinity and especially under their combination. In addition, we found sex-specific responses in total chlorophyll content (TC), carotenoid concentration and carbon isotope composition under different osmotic stresses. Our results indicated that: (1) females are more sensitive and suffer from greater negative effects than do males under drought, salinity and especially under their combination; (2) sexual differences in adaptive responses to drought, salinity and their combination are context dependent; and (3) sex-specific reactions under a combination of stresses are distinct from single-stress responses. Thus, these results provide evidence for adaptive differentiation between sexes in responses to osmotic stresses and in the sensitivity to environmental change.

  14. A NAP-Family Histone Chaperone Functions in Abiotic Stress Response and Adaptation1[OPEN

    PubMed Central

    Pareek, Ashwani; Singla-Pareek, Sneh Lata

    2016-01-01

    Modulation of gene expression is one of the most significant molecular mechanisms of abiotic stress response in plants. Via altering DNA accessibility, histone chaperones affect the transcriptional competence of genomic loci. However, in contrast to other factors affecting chromatin dynamics, the role of plant histone chaperones in abiotic stress response and adaptation remains elusive. Here, we studied the physiological function of a stress-responsive putative rice (Oryza sativa) histone chaperone of the NAP superfamily: OsNAPL6. We show that OsNAPL6 is a nuclear-localized H3/H4 histone chaperone capable of assembling a nucleosome-like structure. Utilizing overexpression and knockdown approaches, we found a positive correlation between OsNAPL6 expression levels and adaptation to multiple abiotic stresses. Results of comparative transcriptome profiling and promoter-recruitment studies indicate that OsNAPL6 functions during stress response via modulation of expression of various genes involved in diverse functions. For instance, we show that OsNAPL6 is recruited to OsRad51 promoter, activating its expression and leading to more efficient DNA repair and abrogation of programmed cell death under salinity and genotoxic stress conditions. These results suggest that the histone chaperone OsNAPL6 may serve a regulatory role in abiotic stress physiology possibly via modulating nucleosome dynamics at various stress-associated genomic loci. Taken together, our findings establish a hitherto unknown link between histone chaperones and abiotic stress response in plants. PMID:27342307

  15. Bioanalytical evidence that chemicals in tattoo ink can induce adaptive stress responses.

    PubMed

    Neale, Peta A; Stalter, Daniel; Tang, Janet Y M; Escher, Beate I

    2015-10-15

    Tattooing is becoming increasingly popular, particularly amongst young people. However, tattoo inks contain a complex mixture of chemical impurities that may pose a long-term risk for human health. As a first step towards the risk assessment of these complex mixtures we propose to assess the toxicological hazard potential of tattoo ink chemicals with cell-based bioassays. Targeted modes of toxic action and cellular endpoints included cytotoxicity, genotoxicity and adaptive stress response pathways. The studied tattoo inks, which were extracted with hexane as a proxy for the bioavailable fraction, caused effects in all bioassays, with the red and yellow tattoo inks having the greatest response, particularly inducing genotoxicity and oxidative stress response endpoints. Chemical analysis revealed the presence of polycyclic aromatic hydrocarbons in the tested black tattoo ink at concentrations twice the recommended level. The detected polycyclic aromatic hydrocarbons only explained 0.06% of the oxidative stress response of the black tattoo ink, thus the majority of the effect was caused by unidentified components. The study indicates that currently available tattoo inks contain components that induce adaptive stress response pathways, but to evaluate the risk to human health further work is required to understand the toxicokinetics of tattoo ink chemicals in the body.

  16. Controlled Aeroelastic Response and Airfoil Shaping Using Adaptive Materials and Integrated Systems

    NASA Technical Reports Server (NTRS)

    Pinkerton, Jennifer L.; McGowan, Anna-Maria R.; Moses, Robert W.; Scott, Robert C.; Heeg, Jennifer

    1996-01-01

    This paper presents an overview of several activities of the Aeroelasticity Branch at the NASA Langley Research Center in the area of applying adaptive materials and integrated systems for controlling both aircraft aeroelastic response and airfoil shape. The experimental results of four programs are discussed: the Piezoelectric Aeroelastic Response Tailoring Investigation (PARTI); the Adaptive Neural Control of Aeroelastic Response (ANCAR) program; the Actively Controlled Response of Buffet Affected Tails (ACROBAT) program; and the Airfoil THUNDER Testing to Ascertain Characteristics (ATTACH) project. The PARTI program demonstrated active flutter control and significant rcductions in aeroelastic response at dynamic pressures below flutter using piezoelectric actuators. The ANCAR program seeks to demonstrate the effectiveness of using neural networks to schedule flutter suppression control laws. Th,e ACROBAT program studied the effectiveness of a number of candidate actuators, including a rudder and piezoelectric actuators, to alleviate vertical tail buffeting. In the ATTACH project, the feasibility of using Thin-Layer Composite-Uimorph Piezoelectric Driver and Sensor (THUNDER) wafers to control airfoil aerodynamic characteristics was investigated. Plans for future applications are also discussed.

  17. Controlled aeroelastic response and airfoil shaping using adaptive materials and integrated systems

    NASA Astrophysics Data System (ADS)

    Pinkerton, Jennifer L.; McGowan, Anna-Maria R.; Moses, Robert W.; Scott, Robert C.; Heeg, Jennifer

    1996-05-01

    This paper presents an overview of several activities of the Aeroelasticity Branch at the NASA Langley Research Center in the area of applying adaptive materials and integrated systems for controlling both aircraft aeroelastic response and airfoil shape. The experimental results of four programs are discussed: the Piezoelectric Aeroelastic Response Tailoring Investigation (PARTI); the adaptive neural control of aeroelastic response (ANCAR) program; the actively controlled response of buffet affected tails (ACROBAT) program; and the Airfoil THUNDER Testing to ascertain charcteristics (ATTACH) project. The PARTI program demonstrated active flutter control and significant reductions in aeroelastic response at dynamic pressures below flutter using piezoelectric actuators. The ANCAR program seeks to demonstrate the effectiveness of using neural networks to schedule flutter suppression control laws. The ACROBAT program studied the effectiveness of a number of candidate actuators, including a rudder and piezoelectric actuators, to alleviate vertical tail buffeting. In the ATTACH project, the feasibility of using thin-layer composite-unimorph piezoelectric driver and sensor (THUNDER) wafers to control airfoil aerodynamic characteristics was investigated. Plans for future applications are also discussed.

  18. Adaptation response surfaces from an ensemble of wheat projections under climate change in Europe

    NASA Astrophysics Data System (ADS)

    Ruiz-Ramos, Margarita; Ferrise, Roberto

    2016-04-01

    The uncertainty about climate change (CC) complicates impact adaptation and risk management evaluation at the regional level. Approaches for managing this uncertainty and for simulating and communicating climate change impacts and adaptation opportunities are required. Here we apply an ensemble of crop models for adapting rainfed winter wheat at Lleida (NE Spain), constructing adaptation response surfaces (ARS). Our methodology has been adapted from Pirttioja et al. (2015). Impact response surfaces (IRS) are plotted surfaces showing the response of an impact variable (here crop yield Y) to changes in two explanatory variables (here precipitation P and temperature T). By analyzing adaptation variables such as changes in crop yield (ΔY) when an adaptation option is simulated, these can be interpreted as the adaptation response to potential changes of P and T, i.e. ARS. To build these ARS, we explore the sensitivity of an ensemble of wheat models to changes in T and P. Baseline (1981-2010) T and P were modified using a delta change approach with changes in the seasonal patterns. Three levels of CO2 (representing future conditions until 2050) and two actual soil profiles are considered. Crop models were calibrated with field data from Abeledo et al. (2008) and Cartelle et al. (2006). Most promising adaptation options to be analyzed by the ARS approach are identified in a pilot stage with the models DSSAT4.5 and SiriusQuality v.2, subsequently simulating the selected adaptation combinations by the whole ensemble of 11 crop models. The adaptation options identified from pilot stage were: a cultivar with no vernalisation requirements, shortening or extending a 10 % the crop cycle of the standard cultivar, sowing 15 days earlier and 30 days later than the standard date, supplementary irrigation with 40 mm at flowering and full irrigation. These options and those of the standard cultivar and management resulted in 54 combinations and 450.000 runs per crop model. Our

  19. Adaptation response surfaces from an ensemble of wheat projections under climate change in Europe

    NASA Astrophysics Data System (ADS)

    Ruiz-Ramos, Margarita; Ferrise, Roberto

    2016-04-01

    The uncertainty about climate change (CC) complicates impact adaptation and risk management evaluation at the regional level. Approaches for managing this uncertainty and for simulating and communicating climate change impacts and adaptation opportunities are required. Here we apply an ensemble of crop models for adapting rainfed winter wheat at Lleida (NE Spain), constructing adaptation response surfaces (ARS). Our methodology has been adapted from Pirttioja et al. (2015). Impact response surfaces (IRS) are plotted surfaces showing the response of an impact variable (here crop yield Y) to changes in two explanatory variables (here precipitation P and temperature T). By analyzing adaptation variables such as changes in crop yield (ΔY) when an adaptation option is simulated, these can be interpreted as the adaptation response to potential changes of P and T, i.e. ARS. To build these ARS, we explore the sensitivity of an ensemble of wheat models to changes in T and P. Baseline (1981-2010) T and P were modified using a delta change approach with changes in the seasonal patterns. Three levels of CO2 (representing future conditions until 2050) and two actual soil profiles are considered. Crop models were calibrated with field data from Abeledo et al. (2008) and Cartelle et al. (2006). Most promising adaptation options to be analyzed by the ARS approach are identified in a pilot stage with the models DSSAT4.5 and SiriusQuality v.2, subsequently simulating the selected adaptation combinations by the whole ensemble of 11 crop models. The adaptation options identified from pilot stage were: a cultivar with no vernalisation requirements, shortening or extending a 10 % the crop cycle of the standard cultivar, sowing 15 days earlier and 30 days later than the standard date, supplementary irrigation with 40 mm at flowering and full irrigation. These options and those of the standard cultivar and management resulted in 54 combinations and 450.000 runs per crop model. Our

  20. Hepatitis C virus evasion of adaptive immune responses: a model for viral persistence.

    PubMed

    Burke, Kelly P; Cox, Andrea L

    2010-07-01

    Hepatitis C virus (HCV) infects over 170 million people worldwide and is a leading cause of cirrhosis and hepatocellular carcinoma. Approximately 20% [corrected] of those acutely infected clear the infection, whereas the remaining 80% [corrected] progress to chronic infection. Hepatitis C thus provides a model in which successful and unsuccessful responses can be compared to better understand the human response to viral infection. Our laboratory studies the strategies by which HCV evades the adaptive immune response. This review describes the impact of viral mutation on T cell recognition, the role of cell surface inhibitory receptors in recognition of HCV, and the development of antibodies that neutralize HCV infection. Understanding what constitutes an effective immune response in the control of HCV may enable the development of prophylactic and therapeutic vaccines for HCV and other chronic viral infections.

  1. Radiation-induced bystander effect and adaptive response in mammalian cells

    NASA Technical Reports Server (NTRS)

    Zhou, H.; Randers-Pehrson, G.; Waldren, C. A.; Hei, T. K.

    2004-01-01

    Two conflicting phenomena, bystander effect and adaptive response, are important in determining the biological responses at low doses of radiation and have the potential to impact the shape of the dose-response relationship. Using the Columbia University charged-particle microbeam and the highly sensitive AL cell mutagenic assay, we show here that non-irradiated cells acquire mutagenesis through direct contact with cells whose nuclei have been traversed with a single alpha particle each. Pretreatment of cells with a low dose of X-rays four hours before alpha particle irradiation significantly decreased this bystander mutagenic response. Results from the present study address some of the fundamental issues regarding both the actual target and radiation dose effect and can contribute to our current understanding in radiation risk assessment. c2004 COSPAR. Published by Elsevier Ltd. All rights reserved.

  2. Radiation-induced bystander effect and adaptive response in mammalian cells.

    PubMed

    Zhou, H; Randers-Pehrson, G; Waldren, C A; Hei, T K

    2004-01-01

    Two conflicting phenomena, bystander effect and adaptive response, are important in determining the biological responses at low doses of radiation and have the potential to impact the shape of the dose-response relationship. Using the Columbia University charged-particle microbeam and the highly sensitive AL cell mutagenic assay, we show here that non-irradiated cells acquire mutagenesis through direct contact with cells whose nuclei have been traversed with a single alpha particle each. Pretreatment of cells with a low dose of X-rays four hours before alpha particle irradiation significantly decreased this bystander mutagenic response. Results from the present study address some of the fundamental issues regarding both the actual target and radiation dose effect and can contribute to our current understanding in radiation risk assessment. PMID:15881649

  3. Transcription Factor ADS-4 Regulates Adaptive Responses and Resistance to Antifungal Azole Stress

    PubMed Central

    Wang, Kangji; Zhang, Zhenying; Chen, Xi; Sun, Xianyun

    2015-01-01

    Azoles are commonly used as antifungal drugs or pesticides to control fungal infections in medicine and agriculture. Fungi adapt to azole stress by rapidly activating the transcription of a number of genes, and transcriptional increases in some azole-responsive genes can elevate azole resistance. The regulatory mechanisms that control transcriptional responses to azole stress in filamentous fungi are not well understood. This study identified a bZIP transcription factor, ADS-4 (antifungal drug sensitive-4), as a new regulator of adaptive responses and resistance to antifungal azoles. Transcription of ads-4 in Neurospora crassa cells increased when they were subjected to ketoconazole treatment, whereas the deletion of ads-4 resulted in hypersensitivity to ketoconazole and fluconazole. In contrast, the overexpression of ads-4 increased resistance to fluconazole and ketoconazole in N. crassa. Transcriptome sequencing (RNA-seq) analysis, followed by quantitative reverse transcription (qRT)-PCR confirmation, showed that ADS-4 positively regulated the transcriptional responses of at least six genes to ketoconazole stress in N. crassa. The gene products of four ADS-4-regulated genes are known contributors to azole resistance, including the major efflux pump CDR4 (Pdr5p ortholog), an ABC multidrug transporter (NcAbcB), sterol C-22 desaturase (ERG5), and a lipid transporter (NcRTA2) that is involved in calcineurin-mediated azole resistance. Deletion of the ads-4-homologous gene Afads-4 in Aspergillus fumigatus caused hypersensitivity to itraconazole and ketoconazole, which suggested that ADS-4 is a functionally conserved regulator of adaptive responses to azoles. This study provides important information on a new azole resistance factor that could be targeted by a new range of antifungal pesticides and drugs. PMID:26100701

  4. Renal cortex taurine content regulates renal adaptive response to altered dietary intake of sulfur amino acids.

    PubMed Central

    Chesney, R W; Gusowski, N; Dabbagh, S

    1985-01-01

    Rats fed a reduced sulfur amino acid diet (LTD) or a high-taurine diet (HTD) demonstrate a renal adaptive response. The LTD results in hypotaurinuria and enhanced brush border membrane vesicle (BBMV) accumulation of taurine. The HTD causes hypertaurinuria and reduced BBMV uptake. This adaptation may relate to changes in plasma or renal cortex taurine concentration. Rats were fed a normal-taurine diet (NTD), LTD, or HTD for 14 d or they underwent: (a) 3% beta-alanine for the last 8 d of each diet; (b) 3 d of fasting; or (c) a combination of 3% beta-alanine added for 8 d and 3 d of fasting. Each maneuver lowered the cortex taurine concentration, but did not significantly lower plasma taurine values compared with controls. Increased BBMV taurine uptake occurred after each manipulation. Feeding 3% glycine did not alter the plasma, renal cortex, or urinary taurine concentrations, or BBMV uptake of taurine. Feeding 3% methionine raised plasma and urinary taurine excretion but renal tissue taurine was unchanged, as was initial BBMV uptake. Hence, nonsulfur-containing alpha-amino acids did not change beta-amino acid transport. The increase in BBMV uptake correlates with the decline in renal cortex and plasma taurine content. However, since 3% methionine changed plasma taurine without altering BBMV uptake, it is more likely that the change in BBMV uptake and the adaptive response expressed at the brush border surface relate to changes in renal cortex taurine concentrations. Finally, despite changes in urine and renal cortex taurine content, brain taurine values were unchanged, which suggests that this renal adaptive response maintains stable taurine concentrations where taurine serves as a neuromodulator. PMID:3935668

  5. Improving the response of accelerometers for automotive applications by using LMS adaptive filters: Part II.

    PubMed

    Hernandez, Wilmar; de Vicente, Jesús; Sergiyenko, Oleg Y; Fernández, Eduardo

    2010-01-01

    In this paper, the fast least-mean-squares (LMS) algorithm was used to both eliminate noise corrupting the important information coming from a piezoresisitive accelerometer for automotive applications, and improve the convergence rate of the filtering process based on the conventional LMS algorithm. The response of the accelerometer under test was corrupted by process and measurement noise, and the signal processing stage was carried out by using both conventional filtering, which was already shown in a previous paper, and optimal adaptive filtering. The adaptive filtering process relied on the LMS adaptive filtering family, which has shown to have very good convergence and robustness properties, and here a comparative analysis between the results of the application of the conventional LMS algorithm and the fast LMS algorithm to solve a real-life filtering problem was carried out. In short, in this paper the piezoresistive accelerometer was tested for a multi-frequency acceleration excitation. Due to the kind of test conducted in this paper, the use of conventional filtering was discarded and the choice of one adaptive filter over the other was based on the signal-to-noise ratio improvement and the convergence rate. PMID:22315579

  6. Improving the Response of Accelerometers for Automotive Applications by Using LMS Adaptive Filters: Part II

    PubMed Central

    Hernandez, Wilmar; de Vicente, Jesús; Sergiyenko, Oleg Y.; Fernández, Eduardo

    2010-01-01

    In this paper, the fast least-mean-squares (LMS) algorithm was used to both eliminate noise corrupting the important information coming from a piezoresisitive accelerometer for automotive applications, and improve the convergence rate of the filtering process based on the conventional LMS algorithm. The response of the accelerometer under test was corrupted by process and measurement noise, and the signal processing stage was carried out by using both conventional filtering, which was already shown in a previous paper, and optimal adaptive filtering. The adaptive filtering process relied on the LMS adaptive filtering family, which has shown to have very good convergence and robustness properties, and here a comparative analysis between the results of the application of the conventional LMS algorithm and the fast LMS algorithm to solve a real-life filtering problem was carried out. In short, in this paper the piezoresistive accelerometer was tested for a multi-frequency acceleration excitation. Due to the kind of test conducted in this paper, the use of conventional filtering was discarded and the choice of one adaptive filter over the other was based on the signal-to-noise ratio improvement and the convergence rate. PMID:22315579

  7. Radiation-Induced Bystander Effects: Evidence for an Adaptive Response to Low Dose Exposures?

    PubMed Central

    Mothersill, Carmel; Seymour, Colin

    2006-01-01

    This paper reviews our current knowledge of the mechanisms underlying the induction of bystander effects by low dose, low-LET ionizing radiation and discusses how they may be related to observed adaptive responses or other protective effects of low dose exposures. Bystander effects appear to be the result of a generalized stress response in tissues or cells. The signals may be produced by all exposed cells, but the response appears to require a quorum in order to be expressed. The major response involving low LET radiation exposure discussed in the existing literature is a death response. This has many characteristics of apoptosis but is p53 independent. While a death response might appear to be adverse, the position is argued in this paper that it is in fact protective and removes damaged cells from the population. Since many cell populations carry damaged cells without being exposed to radiation, so called “background damage”, it is possible that low doses exposures cause removal of cells damaged by agents other than the test dose of radiation. This mechanism would lead to the production of “U-shaped” dose response curves. In this scenario, the level of “adaptive” or beneficial response will be related to the background damage carried by the cell population. This model may be important when attempting to predict the consequences of mixed exposures involving radiation and other environmental stressors. PMID:18648593

  8. Gene expression in closely related species mirrors local adaptation: consequences for responses to a warming world.

    PubMed

    O'Neil, Shawn T; Dzurisin, Jason D K; Williams, Caroline M; Lobo, Neil F; Higgins, Jessica K; Deines, Jillian M; Carmichael, Rory D; Zeng, Erliang; Tan, John C; Wu, Grace C; Emrich, Scott J; Hellmann, Jessica J

    2014-06-01

    Local adaptation of populations could preclude or slow range expansions in response to changing climate, particularly when dispersal is limited. To investigate the differential responses of populations to changing climatic conditions, we exposed poleward peripheral and central populations of two Lepidoptera to reciprocal, common-garden climatic conditions and compared their whole-transcriptome expression. We found evidence of simple population differentiation in both species, and in the species with previously identified population structure and phenotypic local adaptation, we found several hundred genes that responded in a synchronized and localized fashion. These genes were primarily involved in energy metabolism and oxidative stress, and expression levels were most divergent between populations in the same environment in which we previously detected divergence for metabolism. We found no localized genes in the species with less population structure and for which no local adaptation was previously detected. These results challenge the assumption that species are functionally similar across their ranges and poleward peripheral populations are preadapted to warmer conditions. Rather, some taxa deserve population-level consideration when predicting the effects of climate change because they respond in genetically based, distinctive ways to changing conditions.

  9. Inactivation of Semicircular Canals Causes Adaptive Increases in Otolith-driven Tilt Responses

    NASA Technical Reports Server (NTRS)

    Angelaki, Dora E.; Newlands, Shawn D.; Dickman, J. David

    2002-01-01

    Growing experimental and theoretical evidence suggests a functional synergy in the processing of otolith and semicircular canal signals for the generation of the vestibulo-ocular reflexes (VORs). In this study we have further tested this functional interaction by quantifying the adaptive changes in the otolith-ocular system during both rotational and translational movements after surgical inactivation of the semicircular canals. For 0.1- 0.5 Hz (stimuli for which there is no recovery of responses from the plugged canals), pitch and roll VOR gains recovered during earth- horizontal (but not earth-vertical) axis rotations. Corresponding changes were also observed in eye movements elicited by translational motion (0.1 - 5 Hz). Specifically, torsional eye movements increased during lateral motion, whereas vertical eye movements increased during fore-aft motion. The findings indicate that otolith signals can be adapted according to compromised strategy that leads to improved gaze stabilization during motion. Because canal-plugged animals permanently lose the ability to discriminate gravitoinertial accelerations, adapted animals can use the presence of gravity through otolith-driven tilt responses to assist gaze stabilization during earth-horizontal axis rotations.

  10. Effects of Adrenergic Blockade on Postpartum Adaptive Responses Induced by Labor Contractions

    NASA Technical Reports Server (NTRS)

    Ronca, April E.; Mills, N. A.; Lam, K. P.; Hayes, L. E.; Bowley, Susan M. (Technical Monitor)

    2000-01-01

    Prenatal exposure to labor contractions augments the expression of postnatal adaptive responses in newborn rats. Near-term rat fetuses exposed prenatally to simulated labor contractions and delivered by cesarean section breath and attach to nipples at greater frequencies than non-stimulated fetuses. Plasma NE (norepinephrine) and EPI (epinephrine) was significantly elevated in newborn rats exposed to vaginal birth or simulated labor contractions (compressions) with cesarean delivery as compared to non-compressed fetuses. In the present study, we investigated adrenergic mechanisms underlying labor-induced postnatal adaptive responses. Following spinal transection of late pregnant rat dams, fetuses were administered neurogenic or non-neurogenic adrenergic blockade: 1) bretylium (10 mg/kg sc) to prevent sympathetic neuronal release, 2) hexamethonium (30 mg/kg) to produce ganglionic blockade, 3) phenoxybenzanune (10mg/kg sc), an a- adrenergic receptor antagonist, 4) ICI-118551, 10 mg/kg sc), a b receptor antagonist, or 5) vehicle alone. Fetuses were either compressed (C) or non-compressed (NC) prior to cesarean delivery. a- and b- adrenergic antagonists reduced respiration and nipple attachment rates while sympathetic and vehicle alone did not. These results provide additional support for the hypothesis that adaptive neonatal effects of labor contractions are mediated by adrenal and extra-adrenal catecholamines.

  11. Responses to temperature and hypoxia as interacting stressors in fish: implications for adaptation to environmental change.

    PubMed

    McBryan, T L; Anttila, K; Healy, T M; Schulte, P M

    2013-10-01

    Anthropogenic environmental change is exposing animals to changes in a complex array of interacting stressors and is already having important effects on the distribution and abundance of species. However, despite extensive examination of the effects of stressors in isolation, knowledge of the effects of stressors in combination is limited. This lack of information makes predicting the responses of organisms to anthropogenic environmental change challenging. Here, we focus on the effects of temperature and hypoxia as interacting stressors in fishes. A review of the available evidence suggests that temperature and hypoxia act synergistically such that small shifts in one stressor could result in large effects on organismal performance when a fish is exposed to the 2 stressors in combination. Although these stressors pose substantial challenges for fish, there also is substantial intraspecific variation in tolerance to these stressors that could act as the raw material for the evolution of improved tolerance. However, the potential for adaptive change is, in part, dependent on the nature of the correlations among traits associated with tolerance. For example, negative genetic correlations (or trade-offs) between tolerances to temperature and hypoxia could limit the potential for adaptation to the combined stressors, while positive genetic correlations might be of benefit. The limited data currently available suggest that tolerances to hypoxia and to high-temperature may be positively correlated in some species of fish, suggesting the possibility for adaptive evolution in these traits in response to anthropogenic environmental change.

  12. Scientists in a Changed Institutional Environment: Subjective Adaptation and Social Responsibility Norms in Russia

    SciTech Connect

    Gerber, T P; Ball, D Y

    2008-06-05

    How do scientists react when the institutional setting in which they conduct their work changes radically? How do long-standing norms regarding the social responsibility of scientists fare? What factors influence whether scientists embrace or reject the new institutions and norms? We examine these questions using data from a unique survey of 602 scientists in Russia, whose science system experienced a sustained crisis and sweeping changes in science institutions following the collapse of the Soviet Union. We develop measures of how respondents view financing based on grants and other institutional changes in the Russian science system, as well as measures of two norms regarding scientists social responsibility. We find that the majority of scientists have adapted, in the sense that they hold positive views of the new institutions, but a diversity of orientations remains. Social responsibility norms are common among Russian scientists, but far from universal. The main correlates of adaptation are age and current success at negotiating the new institutions, though prospective success, work context, and ethnicity have some of the hypothesized associations. As for social responsibility norms, the main source of variation is age: younger scientists are more likely to embrace individualistic rather than socially-oriented norms.

  13. Mechanical Strain Causes Adaptive Change in Bronchial Fibroblasts Enhancing Profibrotic and Inflammatory Responses

    PubMed Central

    Manuyakorn, Wiparat; Smart, David E.; Noto, Antonio; Bucchieri, Fabio; Haitchi, Hans Michael; Holgate, Stephen T.; Howarth, Peter H.; Davies, Donna E.

    2016-01-01

    Asthma is characterized by periodic episodes of bronchoconstriction and reversible airway obstruction; these symptoms are attributable to a number of factors including increased mass and reactivity of bronchial smooth muscle and extracellular matrix (ECM) in asthmatic airways. Literature has suggested changes in cell responses and signaling can be elicited via modulation of mechanical stress acting upon them, potentially affecting the microenvironment of the cell. In this study, we hypothesized that mechanical strain directly affects the (myo)fibroblast phenotype in asthma. Therefore, we characterized responses of bronchial fibroblasts, from 6 normal and 11 asthmatic non-smoking volunteers, exposed to cyclical mechanical strain using flexible silastic membranes. Samples were analyzed for proteoglycans, α-smooth muscle actin (αSMA), collagens I and III, matrix metalloproteinase (MMP) 2 & 9 and interleukin-8 (IL-8) by qRT-PCR, Western blot, zymography and ELISA. Mechanical strain caused a decrease in αSMA mRNA but no change in either αSMA protein or proteoglycan expression. In contrast the inflammatory mediator IL-8, MMPs and interstitial collagens were increased at both the transcriptional and protein level. The results demonstrate an adaptive response of bronchial fibroblasts to mechanical strain, irrespective of donor. The adaptation involves cytoskeletal rearrangement, matrix remodelling and inflammatory cytokine release. These results suggest that mechanical strain could contribute to disease progression in asthma by promoting inflammation and remodelling responses. PMID:27101406

  14. RARtool: A MATLAB Software Package for Designing Response-Adaptive Randomized Clinical Trials with Time-to-Event Outcomes

    PubMed Central

    Ryeznik, Yevgen; Sverdlov, Oleksandr; Wong, Weng Kee

    2016-01-01

    Response-adaptive randomization designs are becoming increasingly popular in clinical trial practice. In this paper, we present RARtool, a user interface software developed in MATLAB for designing response-adaptive randomized comparative clinical trials with censored time-to-event outcomes. The RARtool software can compute different types of optimal treatment allocation designs, and it can simulate response-adaptive randomization procedures targeting selected optimal allocations. Through simulations, an investigator can assess design characteristics under a variety of experimental scenarios and select the best procedure for practical implementation. We illustrate the utility of our RARtool software by redesigning a survival trial from the literature. PMID:26997924

  15. Regulation of dopamine system responsivity and its adaptive and pathological response to stress

    PubMed Central

    Belujon, Pauline; Grace, Anthony A.

    2015-01-01

    Although, historically, the norepinephrine system has attracted the majority of attention in the study of the stress response, the dopamine system has also been consistently implicated. It has long been established that stress plays a crucial role in the pathogenesis of psychiatric disorders. However, the neurobiological mechanisms that mediate the stress response and its effect in psychiatric diseases are not well understood. The dopamine system can play distinct roles in stress and psychiatric disorders. It is hypothesized that, even though the dopamine (DA) system forms the basis for a number of psychiatric disorders, the pathology is likely to originate in the afferent structures that are inducing dysregulation of the DA system. This review explores the current knowledge of afferent modulation of the stress/DA circuitry, and presents recent data focusing on the effect of stress on the DA system and its relevance to psychiatric disorders. PMID:25788601

  16. Molecular Adaptation Mechanisms Employed by Ethanologenic Bacteria in Response to Lignocellulose-derived Inhibitory Compounds

    PubMed Central

    Ibraheem, Omodele; Ndimba, Bongani K.

    2013-01-01

    Current international interest in finding alternative sources of energy to the diminishing supplies of fossil fuels has encouraged research efforts in improving biofuel production technologies. In countries which lack sufficient food, the use of sustainable lignocellulosic feedstocks, for the production of bioethanol, is an attractive option. In the pre-treatment of lignocellulosic feedstocks for ethanol production, various chemicals and/or enzymatic processes are employed. These methods generally result in a range of fermentable sugars, which are subjected to microbial fermentation and distillation to produce bioethanol. However, these methods also produce compounds that are inhibitory to the microbial fermentation process. These compounds include products of sugar dehydration and lignin depolymerisation, such as organic acids, derivatised furaldehydes and phenolic acids. These compounds are known to have a severe negative impact on the ethanologenic microorganisms involved in the fermentation process by compromising the integrity of their cell membranes, inhibiting essential enzymes and negatively interact with their DNA/RNA. It is therefore important to understand the molecular mechanisms of these inhibitions, and the mechanisms by which these microorganisms show increased adaptation to such inhibitors. Presented here is a concise overview of the molecular adaptation mechanisms of ethanologenic bacteria in response to lignocellulose-derived inhibitory compounds. These include general stress response and tolerance mechanisms, which are typically those that maintain intracellular pH homeostasis and cell membrane integrity, activation/regulation of global stress responses and inhibitor substrate-specific degradation pathways. We anticipate that understanding these adaptation responses will be essential in the design of 'intelligent' metabolic engineering strategies for the generation of hyper-tolerant fermentation bacteria strains. PMID:23847442

  17. Molecular adaptation mechanisms employed by ethanologenic bacteria in response to lignocellulose-derived inhibitory compounds.

    PubMed

    Ibraheem, Omodele; Ndimba, Bongani K

    2013-01-01

    Current international interest in finding alternative sources of energy to the diminishing supplies of fossil fuels has encouraged research efforts in improving biofuel production technologies. In countries which lack sufficient food, the use of sustainable lignocellulosic feedstocks, for the production of bioethanol, is an attractive option. In the pre-treatment of lignocellulosic feedstocks for ethanol production, various chemicals and/or enzymatic processes are employed. These methods generally result in a range of fermentable sugars, which are subjected to microbial fermentation and distillation to produce bioethanol. However, these methods also produce compounds that are inhibitory to the microbial fermentation process. These compounds include products of sugar dehydration and lignin depolymerisation, such as organic acids, derivatised furaldehydes and phenolic acids. These compounds are known to have a severe negative impact on the ethanologenic microorganisms involved in the fermentation process by compromising the integrity of their cell membranes, inhibiting essential enzymes and negatively interact with their DNA/RNA. It is therefore important to understand the molecular mechanisms of these inhibitions, and the mechanisms by which these microorganisms show increased adaptation to such inhibitors. Presented here is a concise overview of the molecular adaptation mechanisms of ethanologenic bacteria in response to lignocellulose-derived inhibitory compounds. These include general stress response and tolerance mechanisms, which are typically those that maintain intracellular pH homeostasis and cell membrane integrity, activation/regulation of global stress responses and inhibitor substrate-specific degradation pathways. We anticipate that understanding these adaptation responses will be essential in the design of 'intelligent' metabolic engineering strategies for the generation of hyper-tolerant fermentation bacteria strains. PMID:23847442

  18. Adaptive antioxidant response of manganese-superoxide dismutase following repetitive UVA irradiation.

    PubMed

    Poswig, A; Wenk, J; Brenneisen, P; Wlaschek, M; Hommel, C; Quel, G; Faisst, K; Dissemond, J; Briviba, K; Krieg, T; Scharffetter-Kochanek, K

    1999-01-01

    In response to the attack of reactive oxygen species, the skin has developed a complex antioxidant defense system including among others the manganese-superoxide dismutase (MnSOD). MnSOD dismutates the superoxide anion (O2*-) derived from the reduction of molecular oxygen to hydrogen peroxide (H2O2), which is detoxified by glutathione peroxidase to water and molecular oxygen. We have addressed the question whether MnSOD is inducible upon UVA irradiation and whether repetitive UV exposure, as practiced for the light-hardening during phototherapy of various photodermatoses, can even enhance the adaptive antioxidant response. Single exposure of four different strains of fibroblasts to UVA irradiation resulted in a dose- and time-dependent increase in specific MnSOD mRNA levels. Interestingly, repetitive UVA exposure at days 1, 2, and 3 at a dose rate of 200 kJ per m2 resulted in a 5-fold induction of specific MnSOD mRNA levels following the third UVA exposure. Similar results were obtained for MnSOD activity. This adaptive response in terms of upregulation of the antioxidant enzyme MnSOD correlates with the protection against high UV doses, if cells were preexposed to sublethal UV doses. Importantly, MnSOD substantially differed between the tested individuals in both mRNA and activity levels. Taken together, we here provide evidence for the increasing induction of MnSOD upon repetitive UVA irradiation that may contribute to the effective adaptive UVA response of the skin during light hardening in phototherapy. Interindividual differences in the inducibility of MnSOD might account for differences in the susceptibility to develop photodermatologic disorders related to photosensitivity, photoaging, and skin cancer. The molecular basis for interindividual differences in the inducibility of antioxidant enzymes remains to be elucidated. PMID:9886257

  19. Adaptive Human CDKAL1 Variants Underlie Hormonal Response Variations at the Enteroinsular Axis

    PubMed Central

    Chang, Chia Lin; Cai, James J.; Huang, Shang Yu; Cheng, Po Jen; Chueh, Ho Yen; Hsu, Sheau Yu Teddy

    2014-01-01

    Recent analyses have identified positively selected loci that explain differences in immune responses, body forms, and adaptations to extreme climates, but variants that describe adaptations in energy-balance regulation remain underexplored. To identify variants that confer adaptations in energy-balance regulation, we explored the evolutionary history and functional associations of candidate variants in 207 genes. We screened single nucleotide polymorphisms in genes that had been associated with energy-balance regulation for unusual genetic patterns in human populations, followed by studying associations among selected variants and serum levels of GIP, insulin, and C-peptide in pregnant women after an oral glucose tolerance test. Our analysis indicated that 5′ variants in CDKAL1, CYB5R4, GAD2, and PPARG are marked with statistically significant signals of gene–environment interactions. Importantly, studies of serum hormone levels showed that variants in CDKAL1 are associated with glucose-induced GIP and insulin responses (p<0.05). On the other hand, a GAD2 variant exhibited a significant association with glucose-induced C-peptide response. In addition, simulation analysis indicated that a type 2 diabetes risk variant in CDKAL1 (rs7754840) was selected in East Asians ∼6,900 years ago. Taken together, these data indicated that variants in CDKAL1 and GAD2 were targets of prior environmental selection. Because the selection of the CDKAL1 variant overlapped with the selection of a cluster of GIP variants in the same population ∼11,800 to 2,000 years ago, we speculate that these regulatory genes at the human enteroinsular axis could be highly responsive to environmental selection in recent human history. PMID:25222615

  20. HLA alleles associated with the adaptive immune response to smallpox vaccine: a replication study.

    PubMed

    Ovsyannikova, Inna G; Pankratz, V Shane; Salk, Hannah M; Kennedy, Richard B; Poland, Gregory A

    2014-09-01

    We previously reported HLA allelic associations with vaccinia virus (VACV)-induced adaptive immune responses in a cohort of healthy individuals (n = 1,071 subjects) after a single dose of the licensed smallpox (Dryvax) vaccine. This study demonstrated that specific HLA alleles were significantly associated with VACV-induced neutralizing antibody (NA) titers (HLA-B*13:02, *38:02, *44:03, *48:01, and HLA-DQB1*03:02, *06:04) and cytokine (HLA-DRB1*01:03, *03:01, *10:01, *13:01, *15:01) immune responses. We undertook an independent study of 1,053 healthy individuals and examined associations between HLA alleles and measures of adaptive immunity after a single dose of Dryvax-derived ACAM2000 vaccine to evaluate previously discovered HLA allelic associations from the Dryvax study and determine if these associations are replicated with ACAM2000. Females had significantly higher NA titers than male subjects in both study cohorts [median ID50 discovery cohort 159 (93, 256) vs. 125 (75, 186), p < 0.001; replication cohort 144 (82, 204) vs. 110 (61, 189), p = 0.024]. The association between the DQB1*03:02 allele (median ID50 discovery cohort 152, p = 0.015; replication cohort 134, p = 0.010) and higher NA titers was replicated. Two HLA associations of comparable magnitudes were consistently found between DRB1*04:03 and DRB1*08:01 alleles and IFN-γ ELISPOT responses. The association between the DRB1*15:01 allele with IFN-γ secretion was also replicated (median pg/mL discovery cohort 182, p = 0.052; replication cohort 203, p = 0.014). Our results suggest that smallpox vaccine-induced adaptive immune responses are significantly influenced by HLA gene polymorphisms. These data provide information for functional studies and design of novel candidate smallpox vaccines.

  1. Epigenetic regulation of adaptive responses of forest tree species to the environment

    PubMed Central

    Bräutigam, Katharina; Vining, Kelly J; Lafon-Placette, Clément; Fossdal, Carl G; Mirouze, Marie; Marcos, José Gutiérrez; Fluch, Silvia; Fraga, Mario Fernández; Guevara, M Ángeles; Abarca, Dolores; Johnsen, Øystein; Maury, Stéphane; Strauss, Steven H; Campbell, Malcolm M; Rohde, Antje; Díaz-Sala, Carmen; Cervera, María-Teresa

    2013-01-01

    Epigenetic variation is likely to contribute to the phenotypic plasticity and adaptative capacity of plant species, and may be especially important for long-lived organisms with complex life cycles, including forest trees. Diverse environmental stresses and hybridization/polyploidization events can create reversible heritable epigenetic marks that can be transmitted to subsequent generations as a form of molecular “memory”. Epigenetic changes might also contribute to the ability of plants to colonize or persist in variable environments. In this review, we provide an overview of recent data on epigenetic mechanisms involved in developmental processes and responses to environmental cues in plant, with a focus on forest tree species. We consider the possible role of forest tree epigenetics as a new source of adaptive traits in plant breeding, biotechnology, and ecosystem conservation under rapid climate change. PMID:23467802

  2. The Inhibitor of Apoptosis (IAPs) in Adaptive Response to Cellular Stress.

    PubMed

    Marivin, Arthur; Berthelet, Jean; Plenchette, Stéphanie; Dubrez, Laurence

    2012-10-10

    Cells are constantly exposed to endogenous and exogenous cellular injuries. They cope with stressful stimuli by adapting their metabolism and activating various "guardian molecules." These pro-survival factors protect essential cell constituents, prevent cell death, and possibly repair cellular damages. The Inhibitor of Apoptosis (IAPs) proteins display both anti-apoptotic and pro-survival properties and their expression can be induced by a variety of cellular stress such as hypoxia, endoplasmic reticular stress and DNA damage. Thus, IAPs can confer tolerance to cellular stress. This review presents the anti-apoptotic and survival functions of IAPs and their role in the adaptive response to cellular stress. The involvement of IAPs in human physiology and diseases in connection with a breakdown of cellular homeostasis will be discussed.

  3. Adapting the Helpful Responses Questionnaire to assess communication skills involved in delivering contingency management: Preliminary psychometrics

    PubMed Central

    Hartzler, Bryan

    2015-01-01

    A paper/pencil instrument, adapted from Miller and colleagues’ (1991) Helpful Responses Questionnaire (HRQ), was developed to assess clinician skill with core communicative aspects involved in delivering contingency management (CM). The instrument presents a single vignette consisting of six points of client dialogue to which respondents write ‘what they would say next.’ In the context of an implementation/effectiveness hybrid trial, 19 staff clinicians at an opiate treatment program completed serial training outcome assessments before, following, and three months after CM training. Assessments included this adaptation of the HRQ, a multiple-choice CM knowledge test, and a recorded standardized patient encounter scored for CM skillfulness. Study results reveal promising psychometric properties for the instrument, including strong scoring reliability, internal consistency, concurrent and predictive validity, test-retest reliability and sensitivity to training effects. These preliminary findings suggest the instrument is a viable, practical method to assess clinician skill in communicative aspects of CM delivery. PMID:25770870

  4. Why Does Exercise “Trigger” Adaptive Protective Responses in the Heart?

    PubMed Central

    Alleman, Rick J.; Stewart, Luke M.; Tsang, Alvin M.

    2015-01-01

    Numerous epidemiological studies suggest that individuals who exercise have decreased cardiac morbidity and mortality. Pre-clinical studies in animal models also find clear cardioprotective phenotypes in animals that exercise, specifically characterized by lower myocardial infarction and arrhythmia. Despite the clear benefits, the underlying cellular and molecular mechanisms that are responsible for exercise preconditioning are not fully understood. In particular, the adaptive signaling events that occur during exercise to “trigger” cardioprotection represent emerging paradigms. In this review, we discuss recent studies that have identified several different factors that appear to initiate exercise preconditioning. We summarize the evidence for and against specific cellular factors in triggering exercise adaptations and identify areas for future study. PMID:26674259

  5. The Inhibitor of Apoptosis (IAPs) in Adaptive Response to Cellular Stress

    PubMed Central

    Marivin, Arthur; Berthelet, Jean; Plenchette, Stéphanie; Dubrez, Laurence

    2012-01-01

    Cells are constantly exposed to endogenous and exogenous cellular injuries. They cope with stressful stimuli by adapting their metabolism and activating various “guardian molecules.” These pro-survival factors protect essential cell constituents, prevent cell death, and possibly repair cellular damages. The Inhibitor of Apoptosis (IAPs) proteins display both anti-apoptotic and pro-survival properties and their expression can be induced by a variety of cellular stress such as hypoxia, endoplasmic reticular stress and DNA damage. Thus, IAPs can confer tolerance to cellular stress. This review presents the anti-apoptotic and survival functions of IAPs and their role in the adaptive response to cellular stress. The involvement of IAPs in human physiology and diseases in connection with a breakdown of cellular homeostasis will be discussed. PMID:24710527

  6. Regulation of the Adaptive Immune Response by the IκB Family Protein Bcl-3

    PubMed Central

    Herrington, Felicity D.; Nibbs, Robert J. B.

    2016-01-01

    Bcl-3 is a member of the IκB family of proteins and an important regulator of Nuclear Factor (NF)-κB activity. The ability of Bcl-3 to bind and regulate specific NF-κB dimers has been studied in great depth, but its physiological roles in vivo are still not fully understood. It is, however, becoming clear that Bcl-3 is essential for the proper development, survival and activity of adaptive immune cells. Bcl-3 dysregulation can be observed in a number of autoimmune pathologies, and Bcl3-deficient animals are more susceptible to bacterial and parasitic infection. This review will describe our current understanding of the roles played by Bcl-3 in the development and regulation of the adaptive immune response, including lymphoid organogenesis, immune tolerance, lymphocyte function and dendritic cell biology. PMID:27023613

  7. Request for Information Response for the Flight Validation of Adaptive Control to Prevent Loss-of-Control Events. Overview of RFI Responses

    NASA Technical Reports Server (NTRS)

    Bosworth, John T.

    2009-01-01

    Adaptive control should be integrated with a baseline controller and only used when necessary (5 responses). Implementation as an emergency system. Immediately re-stabilize and return to controlled flight. Forced perturbation (excitation) for fine-tuning system a) Check margins; b) Develop requirements for amplitude of excitation. Adaptive system can improve performance by eating into margin constraints imposed on the non-adaptive system. Nonlinear effects due to multi-string voting.

  8. Risk factors that may modify the innate and adaptive immune responses in periodontal diseases.

    PubMed

    Knight, Ellie T; Liu, Jenny; Seymour, Gregory J; Faggion, Clovis M; Cullinan, Mary P

    2016-06-01

    Plaque-induced periodontal diseases occur in response to the accumulation of dental plaque. Disease manifestation and progression is determined by the nature of the immune response to the bacterial complexes in plaque. In general, predisposing factors for these periodontal diseases can be defined as those factors which retain or hinder the removal of plaque and, depending upon the nature of the immune response to this plaque, the disease will either remain stable and not progress or it may progress and result in chronic periodontitis. In contrast, modifying factors can be defined as those factors that alter the nature or course of the inflammatory lesion. These factors do not cause the disease but rather modify the chronic inflammatory response, which, in turn, is determined by the nature of the innate and adaptive immune responses and the local cytokine and inflammatory mediator networks. Chronic inflammation is characterized by vascular, cellular and repair responses within the tissues. This paper will focus on how common modifying factors, such as smoking, stress, hormonal changes, diabetes, metabolic syndrome and HIV/AIDS, influence each of these responses, together with treatment implications. As treatment planning in periodontics requires an understanding of the etiology and pathogenesis of the disease, it is important for all modifying factors to be taken into account. For some of these, such as smoking, stress and diabetic control, supportive health behavior advice within the dental setting should be an integral component for overall patient management. PMID:27045429

  9. Evidence of local adaptation in the demographic response of American ginseng to interannual temperature variation.

    PubMed

    Souther, Sara; McGraw, James B

    2011-10-01

    Bioclimatic envelope models of species' responses to climate change are used to predict how species will respond to increasing temperatures. These models are frequently based on the assumption that the northern and southern boundaries of a species' range define its thermal niche. However, this assumption may be violated if populations are adapted to local temperature regimes and have evolved population-specific thermal optima. Considering the prevalence of local adaptation, the assumption of a species-wide thermal optimum may be violated for many species. We used spatially and temporally extensive demographic data for American ginseng (Panax quinquefolius L.) to examine range-wide variation in response of population growth rate (λ) to climatic factors. Our results suggest adaptation to local temperature, but not precipitation. For each population, λ was maximized when annual temperatures were similar to site-specific, long-term mean temperatures. Populations from disparate climatic zones responded differently to temperature variation, and there was a linear relation between population-level thermal optima and the 30-year mean temperature at each site. For species that are locally adapted to temperature, bioclimatic envelope models may underestimate the extent to which increasing temperatures will decrease population growth rate. Because any directional change from long-term mean temperatures will decrease population growth rates, all populations throughout a species' range will be adversely affected by temperature increase, not just populations at southern and low-elevation boundaries. Additionally, when a species' local thermal niche is narrower than its range-wide thermal niche, a smaller temperature increase than would be predicted by bioclimatic envelope approaches may be sufficient to decrease population growth.

  10. Adaptation to large-magnitude treadmill-based perturbations: improvements in reactive balance response

    PubMed Central

    Patel, Prakruti; Bhatt, Tanvi

    2015-01-01

    We aimed to examine the trial-to-trial changes in the reactive balance response to large magnitude slip-like treadmill perturbations in stance and whether the acquired adaptive changes could be appropriately scaled to a higher intensity perturbation. Seventeen young adults experienced 15 slips for training on level I intensity. Pre- and post-training slips were delivered at a higher intensity (20% > level I). Pre- and post-slip onset stability (at liftoff and touchdown of stepping limb) was measured as the shortest distance of the center of mass (COM) position (XCOM/BOS) and velocity (ẊCOM/BOS) relative to base of support (BOS) from a predicted threshold for backward loss of balance. The number of steps to recover balance, compensatory step length and peak trunk angle were recorded. The post-slip onset stability (at liftoff and touchdown) significantly increased across the trials with no change in preslip stability. Improvement in stability at touchdown positively correlated with an anterior shift in XCOM/BOS but not with ẊCOM/BOS. Consequently, the number of steps required to recover balance declined. The adaptive change in XCOM/BOS resulted from an increase in compensatory step length and reduced trunk extension. Individuals also improved post-slip onset stability on a higher intensity perturbation post-training compared with the pre-training trial. The results support that the CNS adapts to fixed intensity slip-like perturbations primarily by improving the reactive stability via modulation in compensatory step length and trunk extension. Furthermore, based on prior experience from the training phase, the acquired adaptive response can be successfully calibrated to a higher intensity perturbation. PMID:25649245

  11. Responses of leaf traits to climatic gradients: adaptive variation versus compositional shifts

    NASA Astrophysics Data System (ADS)

    Meng, T.-T.; Wang, H.; Harrison, S. P.; Prentice, I. C.; Ni, J.; Wang, G.

    2015-09-01

    Dynamic global vegetation models (DGVMs) typically rely on plant functional types (PFTs), which are assigned distinct environmental tolerances and replace one another progressively along environmental gradients. Fixed values of traits are assigned to each PFT; modelled trait variation along gradients is thus driven by PFT replacement. But empirical studies have revealed "universal" scaling relationships (quantitative trait variations with climate that are similar within and between species, PFTs and communities); and continuous, adaptive trait variation has been proposed to replace PFTs as the basis for next-generation DGVMs. Here we analyse quantitative leaf-trait variation on long temperature and moisture gradients in China with a view to understanding the relative importance of PFT replacement vs. continuous adaptive variation within PFTs. Leaf area (LA), specific leaf area (SLA), leaf dry matter content (LDMC) and nitrogen content of dry matter were measured on all species at 80 sites ranging from temperate to tropical climates and from dense forests to deserts. Chlorophyll fluorescence traits and carbon, phosphorus and potassium contents were measured at 47 sites. Generalized linear models were used to relate log-transformed trait values to growing-season temperature and moisture indices, with or without PFT identity as a predictor, and to test for differences in trait responses among PFTs. Continuous trait variation was found to be ubiquitous. Responses to moisture availability were generally similar within and between PFTs, but biophysical traits (LA, SLA and LDMC) of forbs and grasses responded differently from woody plants. SLA and LDMC responses to temperature were dominated by the prevalence of evergreen PFTs with thick, dense leaves at the warm end of the gradient. Nutrient (N, P and K) responses to climate gradients were generally similar within all PFTs. Area-based nutrients generally declined with moisture; Narea and Karea declined with temperature

  12. Influence of resveratrol release on the tissue response to mechanically adaptive cortical implants.

    PubMed

    Nguyen, Jessica K; Jorfi, Mehdi; Buchanan, Kelly L; Park, Daniel J; Foster, E Johan; Tyler, Dustin J; Rowan, Stuart J; Weder, Christoph; Capadona, Jeffrey R

    2016-01-01

    The stability and longevity of recordings obtained from intracortical microelectrodes continues to remain an area of concern for neural interfacing applications. The limited longevity of microelectrode performance has been associated with the integrity of the blood brain barrier (BBB) and the neuroinflammatory response to the microelectrode. Here, we report the investigation of an additive approach that targets both mechanical and chemical factors believed to contribute to chronic BBB instability and the neuroinflammatory response associated with implanted intracortical microelectrodes. The implants investigated were based on a mechanically adaptive, compliant nanocomposite (NC), which reduces the tissue response and tissue strain. This material was doped with various concentrations of the antioxidant resveratrol with the objective of local and rapid delivery. In vitro analysis of resveratrol release, antioxidant activity, and cytotoxicity suggested that a resveratrol content of 0.01% was optimal for in vivo assessment. Thus, probes made from the neat NC reference and probes containing resveratrol (NC Res) were implanted into the cortical tissue of rats for up to sixteen weeks. Histochemical analysis suggested that at three days post-implantation, neither materials nor therapeutic approaches (independently or in combination) could alter the initial wound healing response. However, at two weeks post-implantation, the NC Res implant showed a reduction in activated microglia/macrophages and improvement in neuron density at the tissue-implant interface when compared to the neat NC reference. However, sixteen weeks post-implantation, when the antioxidant was exhausted, NC Res and the neat NC reference exhibited similar tissue responses. The data show that NC Res provides short-term, short-lived benefits due to the antioxidant release, and a long-term reduction in neuroinflammation on account of is mechanical adaptive, compliant nature. Together, these results

  13. Influence of resveratrol release on the tissue response to mechanically adaptive cortical implants.

    PubMed

    Nguyen, Jessica K; Jorfi, Mehdi; Buchanan, Kelly L; Park, Daniel J; Foster, E Johan; Tyler, Dustin J; Rowan, Stuart J; Weder, Christoph; Capadona, Jeffrey R

    2016-01-01

    The stability and longevity of recordings obtained from intracortical microelectrodes continues to remain an area of concern for neural interfacing applications. The limited longevity of microelectrode performance has been associated with the integrity of the blood brain barrier (BBB) and the neuroinflammatory response to the microelectrode. Here, we report the investigation of an additive approach that targets both mechanical and chemical factors believed to contribute to chronic BBB instability and the neuroinflammatory response associated with implanted intracortical microelectrodes. The implants investigated were based on a mechanically adaptive, compliant nanocomposite (NC), which reduces the tissue response and tissue strain. This material was doped with various concentrations of the antioxidant resveratrol with the objective of local and rapid delivery. In vitro analysis of resveratrol release, antioxidant activity, and cytotoxicity suggested that a resveratrol content of 0.01% was optimal for in vivo assessment. Thus, probes made from the neat NC reference and probes containing resveratrol (NC Res) were implanted into the cortical tissue of rats for up to sixteen weeks. Histochemical analysis suggested that at three days post-implantation, neither materials nor therapeutic approaches (independently or in combination) could alter the initial wound healing response. However, at two weeks post-implantation, the NC Res implant showed a reduction in activated microglia/macrophages and improvement in neuron density at the tissue-implant interface when compared to the neat NC reference. However, sixteen weeks post-implantation, when the antioxidant was exhausted, NC Res and the neat NC reference exhibited similar tissue responses. The data show that NC Res provides short-term, short-lived benefits due to the antioxidant release, and a long-term reduction in neuroinflammation on account of is mechanical adaptive, compliant nature. Together, these results

  14. Exploring the Relevance of the Personal and Social Responsibility Model in Adapted Physical Activity: A Collective Case Study

    ERIC Educational Resources Information Center

    Wright, Paul M.; White, Katherine; Gaebler-Spira, Deborah

    2004-01-01

    The purpose of this study was to examine the application of the Personal and Social Responsibility Model (PSRM) in an adapted physical activity program. Although the PSRM was developed for use with underserved youth, scholars in the field of adapted physical activity have noted its potential relevance for children with disabilities. Using a…

  15. Application of Low Dose Radiation Adaptive Response to Control Aging-Related Disease

    SciTech Connect

    Doss, Mohan

    2013-11-01

    Oxidative damage has been implicated in the pathogenesis of most aging-related diseases including neurodegenerative diseases. Antioxidant supplementation has been found to be ineffective in reducing such diseases, but increased endogenous production of antioxidants from the adaptive response due to physical and cognitive exercises (which increase oxidative metabolism and oxidative stress) has been effective in reducing some of the diseases. Low dose radiation (LDR), which increases oxidative stress and results in adaptive response of increased antioxidants, may provide an alternative method of controlling the aging-related diseases. We have studied the effect of LDR on the induction of adaptive response in rat brains and the effectiveness of the LDR in reducing the oxidative damage caused by subsequent high dose radiation. We have also investigated the effect of LDR on apomorphine-induced rotations in the 6-hydroxydopamine (6-OHDA) unilaterally-lesioned rat model of Parkinson?s disease (PD). LDR was observed to initiate an adaptive response in the brain, and reduce the oxidative damage from subsequent high dose radiation exposure, confirming the effectiveness of LDR adaptive response in reducing the oxidative damage from the free radicals due to high dose radiation. LDR resulted in a slight improvement in Tyrosine hydroxylase expression on the lesioned side of substantia nigra (indicative of its protective effect on the dopaminergic neurons), and reduced the behavioral symptoms in the 6-OHDA rat model of PD. Translation of this concept to humans, if found to be applicable, may be a possible approach for controlling the progression of PD and other neurodegenerative diseases. Since any translation of the concept to humans would be hindered by the currently prevalent carcinogenic concerns regarding LDR based on the linear no-threshold (LNT) model, we have also studied the justifications for the use of the LNT model. One of the shortcomings of the LNT model is that it

  16. Improving the response of accelerometers for automotive applications by using LMS adaptive filters.

    PubMed

    Hernandez, Wilmar; de Vicente, Jesús; Sergiyenko, Oleg; Fernández, Eduardo

    2010-01-01

    In this paper, the least-mean-squares (LMS) algorithm was used to eliminate noise corrupting the important information coming from a piezoresisitive accelerometer for automotive applications. This kind of accelerometer is designed to be easily mounted in hard to reach places on vehicles under test, and they usually feature ranges from 50 to 2,000 g (where is the gravitational acceleration, 9.81 m/s(2)) and frequency responses to 3,000 Hz or higher, with DC response, durable cables, reliable performance and relatively low cost. However, here we show that the response of the sensor under test had a lot of noise and we carried out the signal processing stage by using both conventional and optimal adaptive filtering. Usually, designers have to build their specific analog and digital signal processing circuits, and this fact increases considerably the cost of the entire sensor system and the results are not always satisfactory, because the relevant signal is sometimes buried in a broad-band noise background where the unwanted information and the relevant signal sometimes share a very similar frequency band. Thus, in order to deal with this problem, here we used the LMS adaptive filtering algorithm and compare it with others based on the kind of filters that are typically used for automotive applications. The experimental results are satisfactory. PMID:22315542

  17. Once Upon a Time: The Adaptive Immune Response in Atherosclerosis—a Fairy Tale No More

    PubMed Central

    Le Borgne, Marie; Caligiuri, Giuseppina; Nicoletti, Antonino

    2015-01-01

    Extensive research has been carried out to decipher the function of the adaptive immune response in atherosclerosis, with the expectation that it will pave the road for the design of immunomodulatory therapies that will prevent or reverse the progression of the disease. All this work has led to the concept that some T- and B-cell subsets are proatherogenic, whereas others are atheroprotective. In addition to the immune response occurring in the spleen and lymph nodes, it has been shown that lymphoid neo-genesis takes place in the adventitia of atherosclerotic vessels, leading to the formation of tertiary lymphoid organs where an adaptive immune response can be mounted. Whereas the mechanisms orchestrating the formation of these organs are becoming better understood, their impact on atherosclerosis progression remains unclear. Several potential therapeutic strategies against atherosclerosis, such as protective vaccination against atherosclerosis antigens or inhibiting the activation of proatherogenic B cells, have been proposed based on our improving knowledge of the role of the immune system in atherosclerosis. These strategies have shown success in preclinical studies, giving hope that they will lead to clinical applications. PMID:26605642

  18. Evolutionary Influences of Plastic Behavioral Responses Upon Environmental Challenges in an Adaptive Radiation.

    PubMed

    Foster, Susan A; Wund, Matthew A; Baker, John A

    2015-09-01

    At the end of the 19th century, the suggestion was made by several scientists, including J. M. Baldwin, that behavioral responses to environmental change could both rescue populations from extinction (Baldwin Effect) and influence the course of subsequent evolution. Here we provide the historical and theoretical background for this argument and offer evidence of the importance of these ideas for understanding how animals (and other organisms that exhibit behavior) will respond to the rapid environmental changes caused by human activity. We offer examples from long-term research on the evolution of behavioral and other phenotypes in the adaptive radiation of the threespine stickleback fish (Gasterosteus aculeatus), a radiation in which it is possible to infer ancestral patterns of behavioral plasticity relative to the post-glacial freshwater radiation in northwestern North America, and to use patterns of parallelism and contemporary evolution to understand adaptive causes of responses to environmental modification. Our work offers insights into the complexity of cognitive responses to environmental change, and into the importance of examining multiple aspects of the phenotype simultaneously, if we are to understand how behavioral shifts contribute to the persistence of populations and to subsequent evolution. We conclude by discussing the origins of apparent novelties induced by environmental shifts, and the importance of accounting for geographic variation within species if we are to accurately anticipate the effects of anthropogenic environmental modification on the persistence and evolution of animals. PMID:26163679

  19. Adaptive responses and invasion: the role of plasticity and evolution in snail shell morphology

    PubMed Central

    Kistner, Erica J; Dybdahl, Mark F

    2013-01-01

    Invasive species often exhibit either evolved or plastic adaptations in response to spatially varying environmental conditions. We investigated whether evolved or plastic adaptation was driving variation in shell morphology among invasive populations of the New Zealand mud snail (Potamopyrgus antipodarum) in the western United States. We found that invasive populations exhibit considerable shell shape variation and inhabit a variety of flow velocity habitats. We investigated the importance of evolution and plasticity by examining variation in shell morphological traits 1) between the parental and F1 generations for each population and 2) among populations of the first lab generation (F1) in a common garden, full-sib design using Canonical Variate Analyses (CVA). We compared the F1 generation to the parental lineages and found significant differences in overall shell shape indicating a plastic response. However, when examining differences among the F1 populations, we found that they maintained among-population shell shape differences, indicating a genetic response. The F1 generation exhibited a smaller shell morph more suited to the low-flow common garden environment within a single generation. Our results suggest that phenotypic plasticity in conjunction with evolution may be driving variation in shell morphology of this widespread invasive snail. PMID:23467920

  20. Improving the response of accelerometers for automotive applications by using LMS adaptive filters.

    PubMed

    Hernandez, Wilmar; de Vicente, Jesús; Sergiyenko, Oleg; Fernández, Eduardo

    2010-01-01

    In this paper, the least-mean-squares (LMS) algorithm was used to eliminate noise corrupting the important information coming from a piezoresisitive accelerometer for automotive applications. This kind of accelerometer is designed to be easily mounted in hard to reach places on vehicles under test, and they usually feature ranges from 50 to 2,000 g (where is the gravitational acceleration, 9.81 m/s(2)) and frequency responses to 3,000 Hz or higher, with DC response, durable cables, reliable performance and relatively low cost. However, here we show that the response of the sensor under test had a lot of noise and we carried out the signal processing stage by using both conventional and optimal adaptive filtering. Usually, designers have to build their specific analog and digital signal processing circuits, and this fact increases considerably the cost of the entire sensor system and the results are not always satisfactory, because the relevant signal is sometimes buried in a broad-band noise background where the unwanted information and the relevant signal sometimes share a very similar frequency band. Thus, in order to deal with this problem, here we used the LMS adaptive filtering algorithm and compare it with others based on the kind of filters that are typically used for automotive applications. The experimental results are satisfactory.

  1. Acute Anabolic Response and Muscular Adaptation After Hypertrophy-Style and Strength-Style Resistance Exercise.

    PubMed

    Gonzalez, Adam M

    2016-10-01

    Gonzalez, AM. Acute anabolic response and muscular adaptation after hypertrophy-style and strength-style resistance exercise. J Strength Cond Res 30(10): 2959-2964, 2016-Resistance training paradigms are often divided into protocols designed to promote an increase in either hypertrophy or strength. Hypertrophy-style protocols (HYPs) typically involve greater volume (3-6 sets; 8-12 repetitions), moderate intensities (<85% 1 repetition maximum [1RM]), and short rest intervals (30-90 seconds), whereas strength-style protocols (STRs) typically involve higher intensities (≥85% 1RM), low volumes (2-6 sets; ≤6 repetitions), and longer rest intervals (3-5 minutes). However, the literature supporting such classifications is surprisingly sparse in trained individuals, and the distinct classifications of such protocols may be an oversimplification. Thus, the purpose of this review was to examine the acute anabolic responses and training-induced muscular adaptations after HYP and STR styles of resistance exercise in trained individuals. Despite the classification of training paradigms, HYP and STR resistance training routines appear to elicit similar magnitudes of muscle growth, although STR routines appear to be more conducive to increasing strength in resistance-trained individuals. Current evidence suggests that the classification of HYP and STR is an oversimplification, and practitioners are advised to look beyond the classification of resistance exercise protocols when aiming to elicit specific physiological responses.

  2. Evolutionary Influences of Plastic Behavioral Responses Upon Environmental Challenges in an Adaptive Radiation.

    PubMed

    Foster, Susan A; Wund, Matthew A; Baker, John A

    2015-09-01

    At the end of the 19th century, the suggestion was made by several scientists, including J. M. Baldwin, that behavioral responses to environmental change could both rescue populations from extinction (Baldwin Effect) and influence the course of subsequent evolution. Here we provide the historical and theoretical background for this argument and offer evidence of the importance of these ideas for understanding how animals (and other organisms that exhibit behavior) will respond to the rapid environmental changes caused by human activity. We offer examples from long-term research on the evolution of behavioral and other phenotypes in the adaptive radiation of the threespine stickleback fish (Gasterosteus aculeatus), a radiation in which it is possible to infer ancestral patterns of behavioral plasticity relative to the post-glacial freshwater radiation in northwestern North America, and to use patterns of parallelism and contemporary evolution to understand adaptive causes of responses to environmental modification. Our work offers insights into the complexity of cognitive responses to environmental change, and into the importance of examining multiple aspects of the phenotype simultaneously, if we are to understand how behavioral shifts contribute to the persistence of populations and to subsequent evolution. We conclude by discussing the origins of apparent novelties induced by environmental shifts, and the importance of accounting for geographic variation within species if we are to accurately anticipate the effects of anthropogenic environmental modification on the persistence and evolution of animals.

  3. GH3-mediated auxin homeostasis links growth regulation with stress adaptation response in Arabidopsis.

    PubMed

    Park, Jung-Eun; Park, Ju-Young; Kim, Youn-Sung; Staswick, Paul E; Jeon, Jin; Yun, Ju; Kim, Sun-Young; Kim, Jungmook; Lee, Yong-Hwan; Park, Chung-Mo

    2007-03-30

    Plants constantly monitor environmental fluctuations to optimize their growth and metabolism. One example is adaptive growth occurring in response to biotic and abiotic stresses. Here, we demonstrate that GH3-mediated auxin homeostasis is an essential constituent of the complex network of auxin actions that regulates stress adaptation responses in Arabidopsis. Endogenous auxin pool is regulated, at least in part, through negative feedback by a group of auxin-inducible GH3 genes encoding auxin-conjugating enzymes. An Arabidopsis mutant, wes1-D, in which a GH3 gene WES1 is activated by nearby insertion of the (35)S enhancer, exhibited auxin-deficient traits, including reduced growth and altered leaf shape. Interestingly, WES1 is also induced by various stress conditions as well as by salicylic acid and abscisic acid. Accordingly, wes1-D was resistant to both biotic and abiotic stresses, and stress-responsive genes, such as pathogenesis-related genes and CBF genes, were upregulated in this mutant. In contrast, a T-DNA insertional mutant showed reduced stress resistance. We therefore propose that GH3-mediated growth suppression directs reallocation of metabolic resources to resistance establishment and represents the fitness costs of induced resistance.

  4. Vitamin E supplementation modifies adaptive responses to training in rat skeletal muscle.

    PubMed

    Venditti, P; Napolitano, G; Barone, D; Di Meo, S

    2014-10-01

    Aim of the present study was to test, by vitamin E treatment, the hypothesis that muscle adaptive responses to training are mediated by free radicals produced during the single exercise sessions. Therefore, we determined aerobic capacity of tissue homogenates and mitochondrial fractions, tissue content of mitochondrial proteins and expression of factors (PGC-1, NRF-1, and NRF-2) involved in mitochondrial biogenesis. Moreover, we determined the oxidative damage extent, antioxidant enzyme activities, and glutathione content in both tissue preparations, mitochondrial ROS production rate. Finally we tested mitochondrial ROS production rate and muscle susceptibility to oxidative stress. The metabolic adaptations to training, consisting in increased muscle oxidative capacity coupled with the proliferation of a mitochondrial population with decreased oxidative capacity, were generally prevented by antioxidant supplementation. Accordingly, the expression of the factors involved in mitochondrial biogenesis, which were increased by training, was restored to the control level by the antioxidant treatment. Even the training-induced increase in antioxidant enzyme activities, glutathione level and tissue capacity to oppose to an oxidative attach were prevented by vitamin E treatment. Our results support the idea that the stimulus for training-induced adaptive responses derives from the increased production, during the training sessions, of reactive oxygen species that stimulates the expression of PGC-1, which is involved in mitochondrial biogenesis and antioxidant enzymes expression. On the other hand, the observation that changes induced by training in some parameters are only attenuated by vitamin E treatment suggests that other signaling pathways, which are activated during exercise and impinge on PGC-1, can modify the response to the antioxidant integration.

  5. Climate Change and Infectious Disease Risk in Western Europe: A Survey of Dutch Expert Opinion on Adaptation Responses and Actors.

    PubMed

    Akin, Su-Mia; Martens, Pim; Huynen, Maud M T E

    2015-08-18

    There is growing evidence of climate change affecting infectious disease risk in Western Europe. The call for effective adaptation to this challenge becomes increasingly stronger. This paper presents the results of a survey exploring Dutch expert perspectives on adaptation responses to climate change impacts on infectious disease risk in Western Europe. Additionally, the survey explores the expert sample's prioritization of mitigation and adaptation, and expert views on the willingness and capacity of relevant actors to respond to climate change. An integrated view on the causation of infectious disease risk is employed, including multiple (climatic and non-climatic) factors. The results show that the experts consider some adaptation responses as relatively more cost-effective, like fostering interagency and community partnerships, or beneficial to health, such as outbreak investigation and response. Expert opinions converge and diverge for different adaptation responses. Regarding the prioritization of mitigation and adaptation responses expert perspectives converge towards a 50/50 budgetary allocation. The experts consider the national government/health authority as the most capable actor to respond to climate change-induced infectious disease risk. Divergence and consensus among expert opinions can influence adaptation policy processes. Further research is necessary to uncover prevailing expert perspectives and their roots, and compare these.

  6. Characterizing early molecular biomarkers of zinc-induced adaptive and adverseoxidative stress responses in human bronchial epithelial cells

    EPA Science Inventory

    Determining mechanism-based biomarkers that distinguish adaptive and adverse cellular processes is critical to understanding the health effects of environmental exposures. Here, we examined cellular responses of the tracheobronchial airway to zinc (Zn) exposure. A pharmacokinetic...

  7. Role of Cell Cycle Regulation and MLH1, A Key DNA Mismatch Repair Protein, In Adaptive Survival Responses. Final Report

    SciTech Connect

    David A. Boothman

    1999-08-11

    Due to several interesting findings on both adaptive survival responses (ASRs) and DNA mismatch repair (MMR), this grant was separated into two discrete Specific Aim sets (each with their own discrete hypotheses). The described experiments were simultaneously performed.

  8. Evasion of Innate and Adaptive Immune Responses by Influenza A Virus

    PubMed Central

    Schmolke, Mirco; García-Sastre, Adolfo

    2010-01-01

    Summary Host organisms have developed sophisticated antiviral responses in order to defeat emerging influenza A viruses (IAV). At the same time IAV have evolved immune evasion strategies. The immune system of mammals provides several lines of defense to neutralize invading pathogens or limit their replication. Here, we summarize the mammalian innate and adaptive immune mechanisms involved in host defense against viral infection and review strategies by which IAV avoid, circumvent or subvert these mechanisms. We highlight well-characterized, as well as recently described features of this intriguing virus-host molecular battle. PMID:20482552

  9. The acid adaptive tolerance response in Campylobacter jejuni induces a global response, as suggested by proteomics and microarrays

    PubMed Central

    Varsaki, Athanasia; Murphy, Caroline; Barczynska, Alicja; Jordan, Kieran; Carroll, Cyril

    2015-01-01

    Campylobacter jejuni CI 120 is a natural isolate obtained during poultry processing and has the ability to induce an acid tolerance response (ATR) to acid + aerobic conditions in early stationary phase. Other strains tested they did not induce an ATR or they induced it in exponential phase. Campylobacter spp. do not contain the genes that encode the global stationary phase stress response mechanism. Therefore, the aim of this study was to identify genes that are involved in the C. jejuni CI 120 early stationary phase ATR, as it seems to be expressing a novel mechanism of stress tolerance. Two-dimensional gel electrophoresis was used to examine the expression profile of cytosolic proteins during the C. jejuni CI 120 adaptation to acid + aerobic stress and microarrays to determine the genes that participate in the ATR. The results indicate induction of a global response that activated a number of stress responses, including several genes encoding surface components and genes involved with iron uptake. The findings of this study provide new insights into stress tolerance of C. jejuni, contribute to a better knowledge of the physiology of this bacterium and highlight the diversity among different strains. PMID:26221965

  10. Immune adaptive response induced by Bicotylophora trachinoti (Monogenea: Diclidophoridae) infestation in pompano Trachinotus marginatus (Perciformes: Carangidae).

    PubMed

    Chaves, I S; Luvizzotto-Santos, R; Sampaio, L A N; Bianchini, A; Martínez, P E

    2006-09-01

    Fish have developed protective strategies against monogeneans through immunological responses. In this study, immune adaptive response to parasites was analysed in the pompano Trachinotus marginatus infested by Bicotylophora trachinoti. Hosts were pre-treated with formalin and after 10 days assigned to one of the following experimental treatments: (1) fish infested with remaining eggs of B. trachinoti; (2) fish infested with remaining eggs of B. trachinoti and experimentally re-infested by exposure to T. marginatus heavily infested with B. trachinoti. Samples were collected at 0, 15, and 30 days. Gills were dissected to check the presence of B. trachinoti. Blood was collected for haematological and biochemical assays. Spleen and head-kidney were dissected for phagocytosis assay. The spleen-somatic index was also calculated. Re-infested fish showed a faster and higher parasite infestation than infested ones. The parasite mean abundance at 15 days was 24.86+/-13.32 and 11.67+/-8.57 for re-infested and infested fish, respectively. In both groups, hosts showed an immune adaptive response to parasite infestation that was marked by an increased number of leukocytes. Also, phagocytosis (%) in spleen and head-kidney cells was stimulated after parasite infestation (92.50+/-3.73 and 66.00+/-9.54, respectively), becoming later depressed (77.39+/-6.69 and 53.23+/-9.14, respectively). These results support the hypothesis that monogenean infestation induces a biphasic response of the non-specific defence mechanisms in the pompano T. marginatus. This response is marked by an initial stimulation followed by a later depression of the non-specific defence mechanisms.

  11. Adaptive response of bacteria: Multiple hurdles, cross-tolerance and tools to illustrate underlying mechanisms

    NASA Astrophysics Data System (ADS)

    Paramythiotis, Spyridon; Skandamis, Panagiotis N.

    2015-01-01

    A basic principle in the bacterial resistance against lethal stresses is that exposure of microbial cells to a sublethal hurdle (e.g., pH 5.0, 3% NaCl, or 48°C) may induce resistance to lethal level of the same or different stress. The latter is called "cross-tolerance" and the bacteria experiencing such situations are termed "stress-hardened". The majority of scientific reports on the adaptive responses of bacteria to stresses have recently addressed the need to elucidate the underlying mechanisms controlling bacterial stress response. This in turn, will assist in the efficient application of the multiple hurdle approach, e.g., by selecting specific sanitizers, combining stress treatments or antimicrobials, especially in mild processing, against specific cellular targets, eliminating the possibility of the development of stress adapted cells. Common scientific approaches for studying the link between phenotype (e.g., inactivation, survival, or growth) and physiology is the assessment of global transcriptional changes (up- or down-regulation) or those of certain genes, as well as of proteins involved in certain metabolic pathways, occurring during exposure to stress. This may also be performed in parallel to comparative evaluation of the phenotypic response of wild and mutant strains. The post-genomics research on foodborne pathogens has extended our knowledge beyond their phenotypic behavior and may offer mechanistic insights in the following: (i) the top-down approach (induction), which is the search of the underlying mechanisms (low level) responsible for a specific phenotype based on "-omic" studies; and (ii) the bottom-up approach (deduction), which starts from intracellular level and forms a mechanistic (functional) basis for the cellular response. All these may eventually enable the development of mechanistic microbial models and efficient strategies for controlling survival and growth of pathogens in foods.

  12. Plant natriuretic peptides induce proteins diagnostic for an adaptive response to stress

    PubMed Central

    Turek, Ilona; Marondedze, Claudius; Wheeler, Janet I.; Gehring, Chris; Irving, Helen R.

    2014-01-01

    In plants, structural and physiological evidence has suggested the presence of biologically active natriuretic peptides (PNPs). PNPs are secreted into the apoplast, are systemically mobile and elicit a range of responses signaling via cGMP. The PNP-dependent responses include tissue specific modifications of cation transport and changes in stomatal conductance and the photosynthetic rate. PNP also has a critical role in host defense responses. Surprisingly, PNP-homologs are produced by several plant pathogens during host colonization suppressing host defense responses. Here we show that a synthetic peptide representing the biologically active fragment of the Arabidopsis thaliana PNP (AtPNP-A) induces the production of reactive oxygen species in suspension-cultured A. thaliana (Col-0) cells. To identify proteins whose expression changes in an AtPNP-A dependent manner, we undertook a quantitative proteomic approach, employing tandem mass tag (TMT) labeling, to reveal temporal responses of suspension-cultured cells to 1 nM and 10 pM PNP at two different time-points post-treatment. Both concentrations yield a distinct differential proteome signature. Since only the higher (1 nM) concentration induces a ROS response, we conclude that the proteome response at the lower concentration reflects a ROS independent response. Furthermore, treatment with 1 nM PNP results in an over-representation of the gene ontology (GO) terms “oxidation-reduction process,” “translation” and “response to salt stress” and this is consistent with a role of AtPNP-A in the adaptation to environmental stress conditions. PMID:25505478

  13. A response adaptive randomization platform trial for efficient evaluation of Ebola virus treatments: A model for pandemic response.

    PubMed

    Berry, Scott M; Petzold, Elizabeth A; Dull, Peter; Thielman, Nathan M; Cunningham, Coleen K; Corey, G Ralph; McClain, Micah T; Hoover, David L; Russell, James; Griffiss, J McLeod; Woods, Christopher W

    2016-02-01

    The outbreak of Ebola virus disease in West Africa is the largest ever recorded. Numerous treatment alternatives for Ebola have been considered, including widely available repurposed drugs, but initiation of enrollment into clinical trials has been limited. The proposed trial is an adaptive platform design. Multiple agents and combinations will be investigated simultaneously. Additionally, new agents may enter the trial as they become available, and failing agents may be removed. In order to accommodate the many possible agents and combinations, a critical feature of this design is the use of response adaptive randomization to assign treatment regimens. As the trial progresses, the randomization ratio evolves to favor the arms that are performing better, making the design also suitable for all-cause pandemic preparedness planning. The study was approved by US and Sierra Leone ethics committees, and reviewed by the US Food and Drug Administration. Additionally, data management, drug supply lines, and local sites were prepared. However, in response to the declining epidemic seen in February 2015, the trial was not initiated. Sierra Leone remains ready to rapidly activate the protocol as an emergency response trial in the event of a resurgence of Ebola. (ClinicalTrials.gov Identifier: NCT02380625.) In summary, we have designed a single controlled trial capable of efficiently identifying highly effective or failing regimens among a rapidly evolving list of proposed therapeutic alternatives for Ebola virus disease and to treat the patients within the trial effectively based on accruing data. Provision of these regimens, if found safe and effective, would have a major impact on future epidemics by providing effective treatment options. PMID:26768569

  14. A response adaptive randomization platform trial for efficient evaluation of Ebola virus treatments: A model for pandemic response.

    PubMed

    Berry, Scott M; Petzold, Elizabeth A; Dull, Peter; Thielman, Nathan M; Cunningham, Coleen K; Corey, G Ralph; McClain, Micah T; Hoover, David L; Russell, James; Griffiss, J McLeod; Woods, Christopher W

    2016-02-01

    The outbreak of Ebola virus disease in West Africa is the largest ever recorded. Numerous treatment alternatives for Ebola have been considered, including widely available repurposed drugs, but initiation of enrollment into clinical trials has been limited. The proposed trial is an adaptive platform design. Multiple agents and combinations will be investigated simultaneously. Additionally, new agents may enter the trial as they become available, and failing agents may be removed. In order to accommodate the many possible agents and combinations, a critical feature of this design is the use of response adaptive randomization to assign treatment regimens. As the trial progresses, the randomization ratio evolves to favor the arms that are performing better, making the design also suitable for all-cause pandemic preparedness planning. The study was approved by US and Sierra Leone ethics committees, and reviewed by the US Food and Drug Administration. Additionally, data management, drug supply lines, and local sites were prepared. However, in response to the declining epidemic seen in February 2015, the trial was not initiated. Sierra Leone remains ready to rapidly activate the protocol as an emergency response trial in the event of a resurgence of Ebola. (ClinicalTrials.gov Identifier: NCT02380625.) In summary, we have designed a single controlled trial capable of efficiently identifying highly effective or failing regimens among a rapidly evolving list of proposed therapeutic alternatives for Ebola virus disease and to treat the patients within the trial effectively based on accruing data. Provision of these regimens, if found safe and effective, would have a major impact on future epidemics by providing effective treatment options.

  15. Cystic fibrosis–adapted Pseudomonas aeruginosa quorum sensing lasR mutants cause hyperinflammatory responses

    PubMed Central

    LaFayette, Shantelle L.; Houle, Daniel; Beaudoin, Trevor; Wojewodka, Gabriella; Radzioch, Danuta; Hoffman, Lucas R.; Burns, Jane L.; Dandekar, Ajai A.; Smalley, Nicole E.; Chandler, Josephine R.; Zlosnik, James E.; Speert, David P.; Bernier, Joanie; Matouk, Elias; Brochiero, Emmanuelle; Rousseau, Simon; Nguyen, Dao

    2015-01-01

    Cystic fibrosis lung disease is characterized by chronic airway infections with the opportunistic pathogen Pseudomonas aeruginosa and severe neutrophilic pulmonary inflammation. P. aeruginosa undergoes extensive genetic adaptation to the cystic fibrosis (CF) lung environment, and adaptive mutations in the quorum sensing regulator gene lasR commonly arise. We sought to define how mutations in lasR alter host-pathogen relationships. We demonstrate that lasR mutants induce exaggerated host inflammatory responses in respiratory epithelial cells, with increased accumulation of proinflammatory cytokines and neutrophil recruitment due to the loss of bacterial protease–dependent cytokine degradation. In subacute pulmonary infections, lasR mutant–infected mice show greater neutrophilic inflammation and immunopathology compared with wild-type infections. Finally, we observed that CF patients infected with lasR mutants have increased plasma interleukin-8 (IL-8), a marker of inflammation. These findings suggest that bacterial adaptive changes may worsen pulmonary inflammation and directly contribute to the pathogenesis and progression of chronic lung disease in CF patients. PMID:26457326

  16. Response of buoyant plumes to transient discharges investigated using an adaptive solver

    NASA Astrophysics Data System (ADS)

    O'Callaghan, J.; Rickard, G.; Popinet, S.; Stevens, C.

    2010-11-01

    The behavior of buoyant plumes driven by variable momentum inputs were examined using an adaptive Navier-Stokes solver (Gerris). Boundary conditions were representative of an idealized stratified, coastal environment. Salinity ranged from 5 to 30 in the top 5 m of the water column to replicate the strong vertical gradients experienced in fjord environments. Two-dimensional simulations examined the response of the buoyant plume driven by zero, steady, and variable momentum fluxes. The behavior was quantified in terms of the characteristic features of a buoyant plume, the thickness of the nose (or head of gravity current), and the trailing tail. Both the nose and tail of the plume were substantially thicker for the variable momentum run, whereas elongation and thinning of the plume was evident for the steady and zero momentum inputs. Furthermore, an order of magnitude difference in available potential energy was found for the variable momentum run. Validation of the Boussinesq approximation initially utilized the classic lock-exchange experiment with excellent agreement to previous numerical and theoretical experiments. Frontal speeds of the gravity current converged toward the theoretical value of Benjamin (1968). The adaptive mesh permitted lock-exchange simulations at Reynolds number (Re) of ˜10,500 and are some of the highest Re runs to date. Moreover, improved computational efficiency was achieved using the adaptive solver with simulations completed in 20% of the time they took on a static, high-resolution grid.

  17. Pregnancy Adaptive Programming of Capacitative Entry Responses Alters NO Output in Vascular Endothelium: New Insights Into eNOS Regulation through Adaptive Cell Signaling

    PubMed Central

    Boeldt, DS; Yi, FX; Bird, IM

    2014-01-01

    In pregnancy, vascular nitric oxide (NO) production is increased in the systemic and more so in the uterine vasculature, so supporting maximal perfusion of the uterus. This high level of functionality is matched in the umbilical vein, and in corresponding disease states such as preeclampsia, reduced vascular responses are seen in both uterine artery and umbilical vein. In any endothelial cell, NO actually produced by endothelial nitric oxide synthase (eNOS) is determined by the maximum capacity of the cell (eNOS expression levels), eNOS phosphorylation state, and the intracellular [Ca2+]i concentration in response to circulating hormones or physical forces. Herein we discuss how pregnancy specific reprogramming of NO output is determined as much by pregnancy adaptation of [Ca2+]i signaling responses as it is by eNOS expression and phosphorylation. By examining changes in [Ca2+]i signaling responses from HHVE, UAEC, and HUVEC in (where appropriate) nonpregnant, normal pregnant, and pathological pregnant (preeclamptic) state, it is clear that pregnancy adaptation of NO output occurs at the level of sustained phase ‘capacitative entry’ [Ca2+]i response, and the adapted response is lacking in preeclamptic pregnancies. Further, gap junction function is an essential permissive regulator of the capacitative response and impairment of NO output results from any inhibitor of gap junction function, or capacitative entry using TRPC channels. Identifying these [Ca2+]i signaling mechanisms underlying normal pregnancy adaptation of NO output not only provides novel targets for future treatment of diseases of pregnancy, but may also apply to other common forms of hypertension. PMID:21555345

  18. Governmental responses and smallholders' adaptations to climatic variability in southeastern Mexico

    NASA Astrophysics Data System (ADS)

    Mardero Jimenez, Silvia Sofia; Schmook, Birgit; Christman, Zachary; Radel, Claudia

    2016-04-01

    Maize agriculture comprises a third of the area under cultivation in Mexico (75 million hectares), with only a quarter of this crop irrigated artificially. With the great dependence of the country's dominant crop on natural rainfall, there is potential for major losses in maize production due to climatic events, such as irregular rainfalls, droughts, and hurricanes. In 2012, droughts alone caused losses of 16 billion Mexican pesos nationwide in the agricultural sector. Over the last decades, political and economic pressures in the agrarian sector have further stressed Mexican smallholder farmers, as they have to respond to a combination of economic and climatic factors. This interdisciplinary study first documents local climate changes and then explores smallholder farmers' adaptations and governmental policy responses to the variable and changing precipitation and temperature patterns across southeastern Mexico. To assess local climate changes, we analyzed precipitation and temperature data from the land-based weather station network of CONAGUA for the 1973-2012 period. Precipitation anomalies were estimated to evaluate the annual and seasonal stability, deficit, or surplus; and linear regressions used to evaluate precipitation and temperature trends. Climatic analysis demonstrated, 1) a considerable increase in temperature across the study area; 2) a decline in precipitation across a sub-section; 3) increased drought frequency; and 4) an increase in negative anomalies in recent years. We then combine findings from our previous research (Mardero et al. 2014 and Mardero et al. 2015), based on interviews with 150 swidden maize smallholders in 10 communities, to new data from in-depth interviews with managers of local and regional agricultural associations and with members of governmental institutions in charge of climate policy implementation (n=19). The new data allow us to explore governmental responses to climatic variability in the agricultural sector in direct

  19. Priority of repetitive adaptation to mismatch response following undiscriminable auditory stimulation: a magnetoencephalographic study.

    PubMed

    Hoshiyama, Minoru; Okamoto, Hidehiko; Kakigi, Ryusuke

    2007-02-01

    We analysed two different neural mechanisms related to the unconscious processing of auditory stimulation, neural adaptation and mismatch negativity (MMN), using magnetoencephalography in healthy non-musicians. Four kinds of conditioning stimulus (CS): white noise, a 675-Hz pure tone, and complex tones with six (CT6) and seven components (CT7), were used for analysing neural adaptation. The seven spectral components of CT7 were spaced by 1/7 octaves between 500 and 906 Hz on the logarithmic scale. The CT6 components contained the same spectral components as CT7, except for the center frequency, 675 kHz. Subjects could not distinguish CT6 from CT7 in a discrimination test. A test stimulus (TS), a 675-Hz tone, was presented after CS, and the effects of the presence of the same 675-Hz frequency in the CS on the magnetoencephalographic response elicited by TS was evaluated. The P2m component following CT7 was significantly smaller in current strength than that following CT6. The equivalent current dipole for P2m was located approximately 10 mm anterior to the preceding N1m. This result indicated that neural adaptation was taking place in the anterior part of the auditory cortex, even if the sound difference was subthreshold. By contrast, the magnetic counterpart of the MMN was not recorded when CT6 and CT7 were used as standard and deviant stimuli, respectively, being consistent with the discrimination test. In conclusion, neural adaptation is considered to be more sensitive than our consciousness or the MMN, or is caused by an independent mechanism.

  20. Physiological responses to food deprivation in the house sparrow, a species not adapted to prolonged fasting.

    PubMed

    Khalilieh, Anton; McCue, Marshall D; Pinshow, Berry

    2012-09-01

    Many wild birds fast during reproduction, molting, migration, or because of limited food availability. Species that are adapted to fasting sequentially oxidize endogenous fuels in three discrete phases. We hypothesized that species not adapted to long fasts have truncated, but otherwise similar, phases of fasting, sequential changes in fuel oxidization, and similar changes in blood metabolites to fasting-adapted species. We tested salient predictions in house sparrows (Passer domesticus biblicus), a subspecies that is unable to tolerate more than ~32 h of fasting. Our main hypothesis was that fasting sparrows sequentially oxidize substrates in the order carbohydrates, lipids, and protein. We dosed 24 house sparrows with [(13)C]glucose, palmitic acid, or glycine and measured (13)CO(2) in their breath while they fasted for 24 h. To ascertain whether blood metabolite levels reflect fasting-induced changes in metabolic fuels, we also measured glucose, triacylglycerides, and β-hydroxybutyrate in the birds' blood. The results of both breath (13)CO(2) and plasma metabolite analyses did not support our hypothesis; i.e., that sparrows have the same metabolic responses characteristic of fasting-adapted species, but on a shorter time scale. Contrary to our main prediction, we found that recently assimilated (13)C-tracers were oxidized continuously in different patterns with no definite peaks corresponding to the three phases of fasting and also that changes in plasma metabolite levels accurately tracked the changes found by breath analysis. Notably, the rate of recently assimilated [(13)C]glycine oxidization was significantly higher (P < 0.001) than that of the other metabolic tracers at all postdosing intervals. We conclude that the inability of house sparrows to fast for longer than 32 h is likely related to their inability to accrue large lipid stores, separately oxidize different fuels, and/or spare protein during fasting.

  1. Osmotic pressure-adaptive responses in the eye tissues of rainbow smelt (Osmerus mordax)

    PubMed Central

    Armstrong, Elizabeth; Paradis, Hélène; Haines, Lacey; Desjardins, Mariève; Short, Connie E.; Clow, Kathy A.; Driedzic, William R.

    2011-01-01

    Purpose The rainbow smelt (Osmerus mordax), is a teleost fish, which avoids freezing by becoming virtually isosmotic with seawater. The effects that such massive changes in osmolarity have on both its visual system and its highly evolved and specialized circulation are not known. New knowledge about the osmotic adaptation of the rainbow smelt eye is highly relevant to the adaptation and survival of this species and to its ability to feed as a visual predator in the face of environmental pressures. Moreover, the molecular physiologic response of the smelt to osmotic stress might provide valuable insights into understanding and managing mammalian pathological hyperosmolarity conditions, such as diabetes. We undertook the present study to provide an initial assessment of gene expression in ocular vasculature during osmotic adaptation in rainbow smelt. Methods Immunohistochemistry with species cross reactive antibodies was used to assess blood vessel protein expression in paraffin sections. Western blotting was used to further verify antibody specificity for orthologs of mammalian blood vessel proteins in rainbow smelt. Thermal hysteresis and the analysis of glycerol concentrations in vitreous fluid were used to assess the physiologic adaptive properties of cold stressed eyes. Results Glycerol levels and osmotic pressure were significantly increased in the vitreal fluid of smelt maintained at <0.5 °C versus those maintained at 8–10 °C. Compared to the 8–10 °C adapted specimens, the rete mirabile blood vessels and connecting regions of the endothelial linings of the choroidal vessels of the <0.5 °C adapted specimens showed a higher expression level of Tubedown (Tbdn) protein, a marker of the endothelial transcellular permeability pathway. Expression of the zonula occludens protein ZO-1, a marker of the endothelial paracellular permeability pathway showed a reciprocal expression pattern and was downregulated in rete mirabile blood vessels and connecting

  2. Molecular mechanisms of Saccharomyces cerevisiae stress adaptation and programmed cell death in response to acetic acid

    PubMed Central

    Giannattasio, Sergio; Guaragnella, Nicoletta; Ždralević, Maša; Marra, Ersilia

    2013-01-01

    Beyond its classical biotechnological applications such as food and beverage production or as a cell factory, the yeast Saccharomyces cerevisiae is a valuable model organism to study fundamental mechanisms of cell response to stressful environmental changes. Acetic acid is a physiological product of yeast fermentation and it is a well-known food preservative due to its antimicrobial action. Acetic acid has recently been shown to cause yeast cell death and aging. Here we shall focus on the molecular mechanisms of S. cerevisiae stress adaptation and programmed cell death in response to acetic acid. We shall elaborate on the intracellular signaling pathways involved in the cross-talk of pro-survival and pro-death pathways underlying the importance of understanding fundamental aspects of yeast cell homeostasis to improve the performance of a given yeast strain in biotechnological applications. PMID:23430312

  3. Molecular mechanisms of Saccharomyces cerevisiae stress adaptation and programmed cell death in response to acetic acid.

    PubMed

    Giannattasio, Sergio; Guaragnella, Nicoletta; Zdralević, Maša; Marra, Ersilia

    2013-01-01

    Beyond its classical biotechnological applications such as food and beverage production or as a cell factory, the yeast Saccharomyces cerevisiae is a valuable model organism to study fundamental mechanisms of cell response to stressful environmental changes. Acetic acid is a physiological product of yeast fermentation and it is a well-known food preservative due to its antimicrobial action. Acetic acid has recently been shown to cause yeast cell death and aging. Here we shall focus on the molecular mechanisms of S. cerevisiae stress adaptation and programmed cell death in response to acetic acid. We shall elaborate on the intracellular signaling pathways involved in the cross-talk of pro-survival and pro-death pathways underlying the importance of understanding fundamental aspects of yeast cell homeostasis to improve the performance of a given yeast strain in biotechnological applications. PMID:23430312

  4. Regulating adaptive immune responses using small molecule modulators of aminopeptidases that process antigenic peptides.

    PubMed

    Stratikos, Efstratios

    2014-12-01

    Antigenic peptide processing by intracellular aminopeptidases has emerged recently as an important pathway that regulates adaptive immune responses. Pathogens and cancer can manipulate the activity of key enzymes of this pathway to promote immune evasion. Furthermore, the activity of these enzymes is naturally variable due to polymorphic variation, contributing to predisposition to disease, most notably autoimmunity. Here, we review recent findings that suggest that the pharmacological regulation of the activity of these aminopeptidases constitutes a valid approach for regulating human immune responses. We furthermore review the state of the art in chemical tools for inhibiting these enzymes and how these tools can be useful for the development of innovative therapeutic approaches for a variety of diseases including cancer, viral infections and autoimmunity.

  5. The interplay between the microbiome and the adaptive immune response in cancer development

    PubMed Central

    Russo, Edda; Taddei, Antonio; Ringressi, Maria Novella; Ricci, Federica; Amedei, Amedeo

    2016-01-01

    The data from different studies suggest a bacterial role in cancer genesis/progression, often modulating the local immune response. This is particularly so at the mucosal level where the bacterial presence is strong and the immune system is highly reactive. The epithelial surfaces of the body, such as the skin and mucosa, are colonized by a vast number of microorganisms, which represent the so-called normal microbiome. Normally the microbiome does not cause a proinflammatory response because the immune system has developed different strategies for the tolerance of commensal bacteria, but when these mechanisms are impaired or new pathogenic bacteria are introduced into this balanced system, the immune system reacts to the microbiome and can trigger tumor growth in the intestine. In this review, we discuss the potential role of the bacterial microbiome in carcinogenesis, focusing on the direct and indirect immune adaptive mechanisms, that the bacteria can modulate in different ways. PMID:27366226

  6. The role of seasonal flowering responses in adaptation of grasses to temperate climates

    PubMed Central

    Fjellheim, Siri; Boden, Scott; Trevaskis, Ben

    2014-01-01

    Grasses of the subfamily Pooideae, including important cereal crops and pasture grasses, are widespread in temperate zones. Seasonal regulation of developmental transitions coordinates the life cycles of Pooideae with the passing seasons so that flowering and seed production coincide with favorable conditions in spring. This review examines the molecular pathways that control the seasonal flowering responses of Pooideae and how variation in the activity of genes controlling these pathways can adapt cereals or grasses to different climates and geographical regions. The possible evolutionary origins of the seasonal flowering responses of the Pooideae are discussed and key questions for future research highlighted. These include the need to develop a better understanding of the molecular basis for seasonal flowering in perennial Pooideae and in temperate grasses outside the core Pooideae group. PMID:25221560

  7. Cyclone preparedness and response: an analysis of lessons identified using an adapted military planning framework.

    PubMed

    Tatham, Peter; Oloruntoba, Richard; Spens, Karen

    2012-01-01

    The United Kingdom uses the Defence Lines of Development (DLOD) framework to analyse and understand the key components and costs of a military capability. Rooted in the Resource Based View (RBV) of a firm, an adapted DLOD approach is employed to explore, analyse and discuss the preparedness, planning and response strategies of two markedly different countries (Australia and Bangladesh) when faced with a major cyclone event of a comparable size. Given the numerous similarities in the challenges facing military forces in a complex emergency and humanitarian agencies in a natural disaster, the paper demonstrates the applicability of the DLOD framework as an analysis and planning tool in the cyclone preparedness planning and response phases, and more broadly within the disaster management area. In addition, the paper highlights the benefit to disaster managers, policymakers and researchers of exploiting comparative cross-learning opportunities from disaster events, drawn from different sectors and countries.

  8. Suppression of the GLUT4 adaptive response to exercise in fructose-fed rats

    PubMed Central

    Goyaram, Veeraj; Kohn, Tertius A.

    2013-01-01

    Exercise-induced increase in skeletal muscle GLUT4 expression is associated with hyperacetylation of histone H3 within a 350-bp DNA region surrounding the myocyte enhancer factor 2 (MEF2) element on the Glut4 promoter and increased binding of MEF2A. Previous studies have hypothesized that the increase in MEF2A binding is a result of improved accessibility of this DNA segment. Here, we investigated the impact of fructose consumption on exercise-induced GLUT4 adaptive response and directly measured the accessibility of the above segment to nucleases. Male Wistar rats (n = 30) were fed standard chow or chow + 10% fructose or maltodextrin drinks ad libitum for 13 days. In the last 6 days five animals per group performed 3 × 17-min bouts of intermittent swimming daily and five remained untrained. Triceps muscles were harvested and used to measure 1) GLUT4, pAMPK, and HDAC5 contents by Western blot, 2) accessibility of the DNA segment from intact nuclei using nuclease accessibility assays, 3) acetylation level of histone H3 and bound MEF2A by ChIP assays, and 4) glycogen content. Swim training increased GLUT4 content by ∼66% (P < 0.05) but fructose and maltodextrin feeding suppressed the adaptation. Accessibility of the DNA region to MNase and DNase I was significantly increased by swimming (∼2.75- and 5.75-fold, respectively) but was also suppressed in trained rats that consumed fructose or maltodextrin. Histone H3 acetylation and MEF2A binding paralleled the accessibility pattern. These findings indicate that both fructose and maltodextrin modulate the GLUT4 adaptive response to exercise by mechanisms involving chromatin remodeling at the Glut4 promoter. PMID:24326422

  9. The evolving role of response-adapted PET imaging in Hodgkin lymphoma

    PubMed Central

    Coyle, Michael; Kostakoglu, Lale; Evens, Andrew M.

    2016-01-01

    18F-fluorodeoxyglucose positron emission tomography with (FDG-PET) has a well-established role in the pre- and post-treatment staging of Hodgkin lymphoma (HL), however its use as a predictive therapeutic tool via responded-adapted therapy continues to evolve. There have been a multitude of retrospective and noncontrolled clinical studies showing that early (or interim) FDG-PET is highly prognostic in HL, particularly in the advanced-stage setting. Response-adapted treatment approaches in HL are attempting to diminish toxicity for low-risk patients by minimizing therapy, and conversely, intensify treatment for high-risk patients. Results from phase III noninferiority studies in early-stage HL with negative interim FDG-PET that randomized patients to chemotherapy alone versus combined modality therapy showed a continued small improvement in progression-free survival for patients who did not receive radiation. Preliminary reports of data escalating therapy for positive interim FDG-PET in early-stage HL and for de-escalation of therapy [i.e. bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine and prednisone (BEACOPP)] for negative interim FDG-PET in advanced stage HL (i.e. deletion of bleomycin) have demonstrated improved outcomes. Maturation of these studies and continued follow up of all response-adapted studies are needed. Altogether, the treatment of HL remains an individualized clinical management choice for physicians and patients. Continued refinement and optimization of FDG-PET is needed, including within the context of targeted therapeutic agents. In addition, a number of new and novel techniques of functional imaging, including metabolic tumor volume and tumor proliferation, are being explored in order to enhance staging, characterization, prognostication and ultimately patient outcome. PMID:27054026

  10. Specificity of the Human Frequency Following Response for Carrier and Modulation Frequency Assessed Using Adaptation.

    PubMed

    Gockel, Hedwig E; Krugliak, Alexandra; Plack, Christopher J; Carlyon, Robert P

    2015-12-01

    The frequency following response (FFR) is a scalp-recorded measure of phase-locked brainstem activity to stimulus-related periodicities. Three experiments investigated the specificity of the FFR for carrier and modulation frequency using adaptation. FFR waveforms evoked by alternating-polarity stimuli were averaged for each polarity and added, to enhance envelope, or subtracted, to enhance temporal fine structure information. The first experiment investigated peristimulus adaptation of the FFR for pure and complex tones as a function of stimulus frequency and fundamental frequency (F0). It showed more adaptation of the FFR in response to sounds with higher frequencies or F0s than to sounds with lower frequency or F0s. The second experiment investigated tuning to modulation rate in the FFR. The FFR to a complex tone with a modulation rate of 213 Hz was not reduced more by an adaptor that had the same modulation rate than by an adaptor with a different modulation rate (90 or 504 Hz), thus providing no evidence that the FFR originates mainly from neurons that respond selectively to the modulation rate of the stimulus. The third experiment investigated tuning to audio frequency in the FFR using pure tones. An adaptor that had the same frequency as the target (213 or 504 Hz) did not generally reduce the FFR to the target more than an adaptor that differed in frequency (by 1.24 octaves). Thus, there was no evidence that the FFR originated mainly from neurons tuned to the frequency of the target. Instead, the results are consistent with the suggestion that the FFR for low-frequency pure tones at medium to high levels mainly originates from neurons tuned to higher frequencies. Implications for the use and interpretation of the FFR are discussed. PMID:26162415

  11. Optimization of biguanide derivatives as selective antitumor agents blocking adaptive stress responses in the tumor microenvironment.

    PubMed

    Narise, Kosuke; Okuda, Kensuke; Enomoto, Yukihiro; Hirayama, Tasuku; Nagasawa, Hideko

    2014-01-01

    Adaptive cellular responses resulting from multiple microenvironmental stresses, such as hypoxia and nutrient deprivation, are potential novel drug targets for cancer treatment. Accordingly, we focused on developing anticancer agents targeting the tumor microenvironment (TME). In this study, to search for selective antitumor agents blocking adaptive responses in the TME, thirteen new compounds, designed and synthesized on the basis of the arylmethylbiguanide scaffold of phenformin, were used in structure activity relationship studies of inhibition of hypoxia inducible factor (HIF)-1 and unfolded protein response (UPR) activation and of selective cytotoxicity under glucose-deprived stress conditions, using HT29 cells. We conducted luciferase reporter assays using stable cell lines expressing either an HIF-1-responsive reporter gene or a glucose-regulated protein 78 promoter-reporter gene, which were induced by hypoxia and glucose deprivation stress, respectively, to screen for TME-targeting antitumor drugs. The guanidine analog (compound 2), obtained by bioisosteric replacement of the biguanide group, had activities comparable with those of phenformin (compound 1). Introduction of various substituents on the phenyl ring significantly affected the activities. In particular, the o-methylphenyl analog compound 7 and the o-chlorophenyl analog compound 12 showed considerably more potent inhibitory effects on HIF-1 and UPR activation than did phenformin, and excellent selective cytotoxicity under glucose deprivation. These compounds, therefore, represent an improvement over phenformin. They also suppressed HIF-1- and UPR-related protein expression and secretion of vascular endothelial growth factor-A. Moreover, these compounds exhibited significant antiangiogenic effects in the chick chorioallantoic membrane assay. Our structural development studies of biguanide derivatives provided promising candidates for a novel anticancer agent targeting the TME for selective cancer

  12. Transcriptomic Analysis Reveals Adaptive Responses of an Enterobacteriaceae Strain LSJC7 to Arsenic Exposure.

    PubMed

    Zhang, Yingjiao; Chen, Songcan; Hao, Xiuli; Su, Jian-Qiang; Xue, Ximei; Yan, Yu; Zhu, Yong-Guan; Ye, Jun

    2016-01-01

    Arsenic (As) resistance determinant ars operon is present in many bacteria and has been demonstrated to enhance As(V) resistance of bacteria. However, whole molecular mechanism adaptations of bacteria in response to As(V) stress remain largely unknown. In this study, transcriptional profiles of Enterobacteriaceae strain LSJC7 responding to As(V) stress were analyzed using RNA-seq and qRT-PCR. As expected, genes involved in As(V) uptake were down-regulated, those involved in As(V) reduction and As(III) efflux were up-regulated, which avoided cellular As accumulation. Reactive oxygen species and nitric oxide (NO) were induced, which caused cellular damages including DNA, protein, and Fe-S cluster damage in LSJC7. The expression of specific genes encoding transcriptional regulators, such as nsrR and soxRS were also induced. NsrR and SoxRS modulated many critical metabolic activities in As(V) stressed LSJC7 cells, including reactive species scavenging and repairing damaged DNA, proteins, and Fe-S clusters. Therefore, besides As uptake, reduction, and efflux; oxidative stress defense and damage repair were the main cellular adaptive responses of LSJC7 to As(V) stress. PMID:27199962

  13. Ultramarathon is an outstanding model for the study of adaptive responses to extreme load and stress

    PubMed Central

    2012-01-01

    Ultramarathons comprise any sporting event involving running longer than the traditional marathon length of 42.195 km (26.2 miles). Studies on ultramarathon participants can investigate the acute consequences of ultra-endurance exercise on inflammation and cardiovascular or renal consequences, as well as endocrine/energetic aspects, and examine the tissue recovery process over several days of extreme physical load. In a study published in BMC Medicine, Schütz et al. followed 44 ultramarathon runners over 4,487 km from South Italy to North Cape, Norway (the Trans Europe Foot Race 2009) and recorded daily sets of data from magnetic resonance imaging, psychometric, body composition and biological measurements. The findings will allow us to better understand the timecourse of degeneration/regeneration of some lower leg tissues such as knee joint cartilage, to differentiate running-induced from age-induced pathologies (for example, retropatelar arthritis) and finally to assess the interindividual susceptibility to injuries. Moreover, it will also provide new information about the complex interplay between cerebral adaptations/alterations and hormonal influences resulting from endurance exercise and provide data on the dose-response relationship between exercise and brain structure/function. Overall, this study represents a unique attempt to investigate the limits of the adaptive response of human bodies. Please see related article: http://www.biomedcentral.com/1741-7015/10/78 PMID:22812424

  14. Enhanced response inhibition during intensive meditation training predicts improvements in self-reported adaptive socioemotional functioning.

    PubMed

    Sahdra, Baljinder K; MacLean, Katherine A; Ferrer, Emilio; Shaver, Phillip R; Rosenberg, Erika L; Jacobs, Tonya L; Zanesco, Anthony P; King, Brandon G; Aichele, Stephen R; Bridwell, David A; Mangun, George R; Lavy, Shiri; Wallace, B Alan; Saron, Clifford D

    2011-04-01

    We examined the impact of training-induced improvements in self-regulation, operationalized in terms of response inhibition, on longitudinal changes in self-reported adaptive socioemotional functioning. Data were collected from participants undergoing 3 months of intensive meditation training in an isolated retreat setting (Retreat 1) and a wait-list control group that later underwent identical training (Retreat 2). A 32-min response inhibition task (RIT) was designed to assess sustained self-regulatory control. Adaptive functioning (AF) was operationalized as a single latent factor underlying self-report measures of anxious and avoidant attachment, mindfulness, ego resilience, empathy, the five major personality traits (extroversion, agreeableness, conscientiousness, neuroticism, and openness to experience), difficulties in emotion regulation, depression, anxiety, and psychological well-being. Participants in Retreat 1 improved in RIT performance and AF over time whereas the controls did not. The control participants later also improved on both dimensions during their own retreat (Retreat 2). These improved levels of RIT performance and AF were sustained in follow-up assessments conducted approximately 5 months after the training. Longitudinal dynamic models with combined data from both retreats showed that improvement in RIT performance during training influenced the change in AF over time, which is consistent with a key claim in the Buddhist literature that enhanced capacity for self-regulation is an important precursor of changes in emotional well-being. PMID:21500899

  15. Adaptive responses to cool climate promotes persistence of a non-native lizard.

    PubMed

    While, Geoffrey M; Williamson, Joseph; Prescott, Graham; Horváthová, Terézia; Fresnillo, Belén; Beeton, Nicholas J; Halliwell, Ben; Michaelides, Sozos; Uller, Tobias

    2015-03-22

    Successful establishment and range expansion of non-native species often require rapid accommodation of novel environments. Here, we use common-garden experiments to demonstrate parallel adaptive evolutionary response to a cool climate in populations of wall lizards (Podarcis muralis) introduced from southern Europe into England. Low soil temperatures in the introduced range delay hatching, which generates directional selection for a shorter incubation period. Non-native lizards from two separate lineages have responded to this selection by retaining their embryos for longer before oviposition--hence reducing the time needed to complete embryogenesis in the nest--and by an increased developmental rate at low temperatures. This divergence mirrors local adaptation across latitudes and altitudes within widely distributed species and suggests that evolutionary responses to climate can be very rapid. When extrapolated to soil temperatures encountered in nests within the introduced range, embryo retention and faster developmental rate result in one to several weeks earlier emergence compared with the ancestral state. We show that this difference translates into substantial survival benefits for offspring. This should promote short- and long-term persistence of non-native populations, and ultimately enable expansion into areas that would be unattainable with incubation duration representative of the native range. PMID:25694617

  16. Design of a Virtual Reality Based Adaptive Response Technology for Children With Autism

    PubMed Central

    Lahiri, Uttama; Bekele, Esubalew; Dohrmann, Elizabeth; Warren, Zachary; Sarkar, Nilanjan

    2013-01-01

    Children with autism spectrum disorder (ASD) demonstrate potent impairments in social communication skills including atypical viewing patterns during social interactions. Recently, several assistive technologies, particularly virtual reality (VR), have been investigated to address specific social deficits in this population. Some studies have coupled eye-gaze monitoring mechanisms to design intervention strategies. However, presently available systems are designed to primarily chain learning via aspects of one’s performance only which affords restricted range of individualization. The presented work seeks to bridge this gap by developing a novel VR-based interactive system with Gaze-sensitive adaptive response technology that can seamlessly integrate VR-based tasks with eye-tracking techniques to intelligently facilitate engagement in tasks relevant to advancing social communication skills. Specifically, such a system is capable of objectively identifying and quantifying one’s engagement level by measuring real-time viewing patterns, subtle changes in eye physiological responses, as well as performance metrics in order to adaptively respond in an individualized manner to foster improved social communication skills among the participants. The developed system was tested through a usability study with eight adolescents with ASD. The results indicate the potential of the system to promote improved social task performance along with socially-appropriate mechanisms during VR-based social conversation tasks. PMID:23033333

  17. chr genes from adaptive replicons are responsible for chromate resistance by Burkholderia xenovorans LB400.

    PubMed

    Reyes-Gallegos, Rosa I; Ramírez-Díaz, Martha I; Cervantes, Carlos

    2016-03-01

    The chromate ion transporter (CHR) superfamily includes proteins that confer chromate resistance by extruding toxic chromate ions from cytoplasm. Burkholderia xenovorans strain LB400 encodes six CHR homologues in its multireplicon genome and has been reported as highly chromate-resistant. The objective of this work was to analyze the involvement of chr redundant genes in chromate resistance by LB400. It was found that B. xenovorans plant rhizosphere strains lacking the megaplasmid are chromate-sensitive, suggesting that the chr gene present in this replicon is responsible for the chromate-resistance phenotype of the LB400 strain. Transformation of a chromate-sensitive B. xenovorans strain with each of the six cloned LB400 chr genes showed that genes from 'adaptive replicons' (chrA1b and chr1NCb from chromosome 2 and chrA2 from the megaplasmid) conferred higher chromate resistance levels than chr genes from 'central' chromosome 1 (chrA1a, chrA6, and chr1NCa). An LB400 insertion mutant affected in the chrA2 gene displayed a chromate-sensitive phenotype, which was fully reverted by transferring the chrA2 wild-type gene, and partially reverted by chrA1b or chr1NCb genes. These data indicate that chr genes from adaptive replicons, mainly chrA2 from the megaplasmid, are responsible for the B. xenovorans LB400 chromate-resistance phenotype.

  18. Transcriptomic Analysis Reveals Adaptive Responses of an Enterobacteriaceae Strain LSJC7 to Arsenic Exposure.

    PubMed

    Zhang, Yingjiao; Chen, Songcan; Hao, Xiuli; Su, Jian-Qiang; Xue, Ximei; Yan, Yu; Zhu, Yong-Guan; Ye, Jun

    2016-01-01

    Arsenic (As) resistance determinant ars operon is present in many bacteria and has been demonstrated to enhance As(V) resistance of bacteria. However, whole molecular mechanism adaptations of bacteria in response to As(V) stress remain largely unknown. In this study, transcriptional profiles of Enterobacteriaceae strain LSJC7 responding to As(V) stress were analyzed using RNA-seq and qRT-PCR. As expected, genes involved in As(V) uptake were down-regulated, those involved in As(V) reduction and As(III) efflux were up-regulated, which avoided cellular As accumulation. Reactive oxygen species and nitric oxide (NO) were induced, which caused cellular damages including DNA, protein, and Fe-S cluster damage in LSJC7. The expression of specific genes encoding transcriptional regulators, such as nsrR and soxRS were also induced. NsrR and SoxRS modulated many critical metabolic activities in As(V) stressed LSJC7 cells, including reactive species scavenging and repairing damaged DNA, proteins, and Fe-S clusters. Therefore, besides As uptake, reduction, and efflux; oxidative stress defense and damage repair were the main cellular adaptive responses of LSJC7 to As(V) stress.

  19. Adaptive responses to cool climate promotes persistence of a non-native lizard.

    PubMed

    While, Geoffrey M; Williamson, Joseph; Prescott, Graham; Horváthová, Terézia; Fresnillo, Belén; Beeton, Nicholas J; Halliwell, Ben; Michaelides, Sozos; Uller, Tobias

    2015-03-22

    Successful establishment and range expansion of non-native species often require rapid accommodation of novel environments. Here, we use common-garden experiments to demonstrate parallel adaptive evolutionary response to a cool climate in populations of wall lizards (Podarcis muralis) introduced from southern Europe into England. Low soil temperatures in the introduced range delay hatching, which generates directional selection for a shorter incubation period. Non-native lizards from two separate lineages have responded to this selection by retaining their embryos for longer before oviposition--hence reducing the time needed to complete embryogenesis in the nest--and by an increased developmental rate at low temperatures. This divergence mirrors local adaptation across latitudes and altitudes within widely distributed species and suggests that evolutionary responses to climate can be very rapid. When extrapolated to soil temperatures encountered in nests within the introduced range, embryo retention and faster developmental rate result in one to several weeks earlier emergence compared with the ancestral state. We show that this difference translates into substantial survival benefits for offspring. This should promote short- and long-term persistence of non-native populations, and ultimately enable expansion into areas that would be unattainable with incubation duration representative of the native range.

  20. Adaptive responses to cool climate promotes persistence of a non-native lizard

    PubMed Central

    While, Geoffrey M.; Williamson, Joseph; Prescott, Graham; Horváthová, Terézia; Fresnillo, Belén; Beeton, Nicholas J.; Halliwell, Ben; Michaelides, Sozos; Uller, Tobias

    2015-01-01

    Successful establishment and range expansion of non-native species often require rapid accommodation of novel environments. Here, we use common-garden experiments to demonstrate parallel adaptive evolutionary response to a cool climate in populations of wall lizards (Podarcis muralis) introduced from southern Europe into England. Low soil temperatures in the introduced range delay hatching, which generates directional selection for a shorter incubation period. Non-native lizards from two separate lineages have responded to this selection by retaining their embryos for longer before oviposition—hence reducing the time needed to complete embryogenesis in the nest—and by an increased developmental rate at low temperatures. This divergence mirrors local adaptation across latitudes and altitudes within widely distributed species and suggests that evolutionary responses to climate can be very rapid. When extrapolated to soil temperatures encountered in nests within the introduced range, embryo retention and faster developmental rate result in one to several weeks earlier emergence compared with the ancestral state. We show that this difference translates into substantial survival benefits for offspring. This should promote short- and long-term persistence of non-native populations, and ultimately enable expansion into areas that would be unattainable with incubation duration representative of the native range. PMID:25694617

  1. Design of a virtual reality based adaptive response technology for children with autism.

    PubMed

    Lahiri, Uttama; Bekele, Esubalew; Dohrmann, Elizabeth; Warren, Zachary; Sarkar, Nilanjan

    2013-01-01

    Children with autism spectrum disorder (ASD) demonstrate potent impairments in social communication skills including atypical viewing patterns during social interactions. Recently, several assistive technologies, particularly virtual reality (VR), have been investigated to address specific social deficits in this population. Some studies have coupled eye-gaze monitoring mechanisms to design intervention strategies. However, presently available systems are designed to primarily chain learning via aspects of one's performance only which affords restricted range of individualization. The presented work seeks to bridge this gap by developing a novel VR-based interactive system with Gaze-sensitive adaptive response technology that can seamlessly integrate VR-based tasks with eye-tracking techniques to intelligently facilitate engagement in tasks relevant to advancing social communication skills. Specifically, such a system is capable of objectively identifying and quantifying one's engagement level by measuring real-time viewing patterns, subtle changes in eye physiological responses, as well as performance metrics in order to adaptively respond in an individualized manner to foster improved social communication skills among the participants. The developed system was tested through a usability study with eight adolescents with ASD. The results indicate the potential of the system to promote improved social task performance along with socially-appropriate mechanisms during VR-based social conversation tasks. PMID:23033333

  2. Transcriptomic Analysis Reveals Adaptive Responses of an Enterobacteriaceae Strain LSJC7 to Arsenic Exposure

    PubMed Central

    Zhang, Yingjiao; Chen, Songcan; Hao, Xiuli; Su, Jian-Qiang; Xue, Ximei; Yan, Yu; Zhu, Yong-Guan; Ye, Jun

    2016-01-01

    Arsenic (As) resistance determinant ars operon is present in many bacteria and has been demonstrated to enhance As(V) resistance of bacteria. However, whole molecular mechanism adaptations of bacteria in response to As(V) stress remain largely unknown. In this study, transcriptional profiles of Enterobacteriaceae strain LSJC7 responding to As(V) stress were analyzed using RNA-seq and qRT-PCR. As expected, genes involved in As(V) uptake were down-regulated, those involved in As(V) reduction and As(III) efflux were up-regulated, which avoided cellular As accumulation. Reactive oxygen species and nitric oxide (NO) were induced, which caused cellular damages including DNA, protein, and Fe–S cluster damage in LSJC7. The expression of specific genes encoding transcriptional regulators, such as nsrR and soxRS were also induced. NsrR and SoxRS modulated many critical metabolic activities in As(V) stressed LSJC7 cells, including reactive species scavenging and repairing damaged DNA, proteins, and Fe–S clusters. Therefore, besides As uptake, reduction, and efflux; oxidative stress defense and damage repair were the main cellular adaptive responses of LSJC7 to As(V) stress. PMID:27199962

  3. Whether Plant Responses to Microgravity are Adaptive in Full or in Part.

    NASA Astrophysics Data System (ADS)

    Kordyum, Elizabeth

    F1.1 Microgravity is well known to be an unusual factor for plant but plants grow and develop in space flight from seed-to-seed, as it has been perfectly shown in the experiments aboard shut-tle Columbia (STS-87) and ISS. Under the more or less optimal conditions for plant growing, namely temperature, humidity, CO2, light intensity and directivity, in the hardware, high-quality seeds germinate one hundred percent.. Cytological studies of plants developing in real and simulated microgravity made it possible to establish that the processes of mitosis, cytoki-nesis, and tissue differentiation of vegetative and generative organs are largely normal. The patterns of histogenesis and cell differentiation established for root caps in microgravity lead to the conclusion that the graviperceptive apparatus of the intact embryonic roots has formed but does not function in the absence of a gravitational vector. Normal space orientation of plant organs is provided by autotropism and phototropism. At the same time, under micro-gravity, essential reconstruction in the structural and functional organization of cell organelles and cytoskeleton, as well as changes in cell metabolism and homeostasis have been described. In addition, new interesting data concerning the influence of altered gravity on lipid peroxi-dation intensity, the level of reactive oxygen species, and antioxidant system activity, just like on the level of gene expression and synthesis of low-molecular and high-molecular heat shock proteins were recently obtained Available experimental data are discussed in the light of notions on adaptive syndrome in plants. The dynamics of the observable patterns demonstrate that adaptation occurs on the principle of self-regulating systems within the physiological response limits.. However, a delay in synthesis of storage nutrients and the lower level its accumulation in seeds in microgravty, as well as the formation of seeds with anomalous embryos in some cases made it

  4. Innate and adaptive immune responses in migrating spring-run adult chinook salmon, Oncorhynchus tshawytscha.

    PubMed

    Dolan, Brian P; Fisher, Kathleen M; Colvin, Michael E; Benda, Susan E; Peterson, James T; Kent, Michael L; Schreck, Carl B

    2016-01-01

    Adult Chinook salmon (Oncorhynchus tshawytscha) migrate from salt water to freshwater streams to spawn. Immune responses in migrating adult salmon are thought to diminish in the run up to spawning, though the exact mechanisms for diminished immune responses remain unknown. Here we examine both adaptive and innate immune responses as well as pathogen burdens in migrating adult Chinook salmon in the Upper Willamette River basin. Messenger RNA transcripts encoding antibody heavy chain molecules slightly diminish as a function of time, but are still present even after fish have successfully spawned. In contrast, the innate anti-bacterial effector proteins present in fish plasma rapidly decrease as spawning approaches. Fish also were examined for the presence and severity of eight different pathogens in different organs. While pathogen burden tended to increase during the migration, no specific pathogen signature was associated with diminished immune responses. Transcript levels of the immunosuppressive cytokines IL-10 and TGF beta were measured and did not change during the migration. These results suggest that loss of immune functions in adult migrating salmon are not due to pathogen infection or cytokine-mediated immune suppression, but is rather part of the life history of Chinook salmon likely induced by diminished energy reserves or hormonal changes which accompany spawning.

  5. Innate and adaptive immune responses in migrating spring-run adult chinook salmon, Oncorhynchus tshawytscha.

    PubMed

    Dolan, Brian P; Fisher, Kathleen M; Colvin, Michael E; Benda, Susan E; Peterson, James T; Kent, Michael L; Schreck, Carl B

    2016-01-01

    Adult Chinook salmon (Oncorhynchus tshawytscha) migrate from salt water to freshwater streams to spawn. Immune responses in migrating adult salmon are thought to diminish in the run up to spawning, though the exact mechanisms for diminished immune responses remain unknown. Here we examine both adaptive and innate immune responses as well as pathogen burdens in migrating adult Chinook salmon in the Upper Willamette River basin. Messenger RNA transcripts encoding antibody heavy chain molecules slightly diminish as a function of time, but are still present even after fish have successfully spawned. In contrast, the innate anti-bacterial effector proteins present in fish plasma rapidly decrease as spawning approaches. Fish also were examined for the presence and severity of eight different pathogens in different organs. While pathogen burden tended to increase during the migration, no specific pathogen signature was associated with diminished immune responses. Transcript levels of the immunosuppressive cytokines IL-10 and TGF beta were measured and did not change during the migration. These results suggest that loss of immune functions in adult migrating salmon are not due to pathogen infection or cytokine-mediated immune suppression, but is rather part of the life history of Chinook salmon likely induced by diminished energy reserves or hormonal changes which accompany spawning. PMID:26581919

  6. Innate and adaptive immune responses in migrating spring-run adult chinook salmon, Oncorhynchus tshawytscha

    USGS Publications Warehouse

    Dolan, Brian P.; Fisher, Kathleen M.; Colvin, Michael E.; Benda, Susan E.; Peterson, James T.; Kent, Michael L.; Schreck, Carl B.

    2016-01-01

    Adult Chinook salmon (Oncorhynchus tshawytscha) migrate from salt water to freshwater streams to spawn. Immune responses in migrating adult salmon are thought to diminish in the run up to spawning, though the exact mechanisms for diminished immune responses remain unknown. Here we examine both adaptive and innate immune responses as well as pathogen burdens in migrating adult Chinook salmon in the Upper Willamette River basin. Messenger RNA transcripts encoding antibody heavy chain molecules slightly diminish as a function of time, but are still present even after fish have successfully spawned. In contrast, the innate anti-bacterial effector proteins present in fish plasma rapidly decrease as spawning approaches. Fish also were examined for the presence and severity of eight different pathogens in different organs. While pathogen burden tended to increase during the migration, no specific pathogen signature was associated with diminished immune responses. Transcript levels of the immunosuppressive cytokines IL-10 and TGF beta were measured and did not change during the migration. These results suggest that loss of immune functions in adult migrating salmon are not due to pathogen infection or cytokine-mediated immune suppression, but is rather part of the life history of Chinook salmon likely induced by diminished energy reserves or hormonal changes which accompany spawning.

  7. Cortical response to psycho-physiological changes in auto-adaptive robot assisted gait training.

    PubMed

    Jelinek, Herbert F; August, Katherine G; Imam, Md Hasan; Khandoker, Ahsan H; Koenig, Alexander; Riener, Robert

    2011-01-01

    Robot-assisted treadmill training improves motor function and walking ability in neurologically impaired patients. However, despite attention having been shown to play a role in training success, psychological responsiveness to task difficulty and motivational levels at task onset have not been measured. Seven healthy subjects participated in a robot-assist treadmill training task. Subjects engaged in a virtual task with varying difficulty levels that was shown to induce a feeling of being bored, excited and over-stressed. The participants' mental engagement was measured using the ECG-based heart rate variability in real time, during gait training as a proxy for EEG and psychological test batteries. Heart rate variability (HRV), which has been shown to reflect cortical engagement for both cognitive and physical tasks, was measured using nonlinear measures obtained from the Poincaré plot. We show that the cortical response to the task measured with HRV varies in relation to the level of mental engagement in response to the difficulty level of the virtual task. From these results we propose that nonlinear measures quantify cortical response / motivational level to robot-assist motor learning tasks and that the adaptation to the task is dependent on the level of motivation.

  8. Smart plants, smart models? On adaptive responses in vegetation-soil systems

    NASA Astrophysics Data System (ADS)

    van der Ploeg, Martine; Teuling, Ryan; van Dam, Nicole; de Rooij, Gerrit

    2015-04-01

    Hydrological models that will be able to cope with future precipitation and evapotranspiration regimes need a solid base describing the essence of the processes involved [1]. The essence of emerging patterns at large scales often originates from micro-behaviour in the soil-vegetation-atmosphere system. A complicating factor in capturing this behaviour is the constant interaction between vegetation and geology in which water plays a key role. The resilience of the coupled vegetation-soil system critically depends on its sensitivity to environmental changes. To assess root water uptake by plants in a changing soil environment, a direct indication of the amount of energy required by plants to take up water can be obtained by measuring the soil water potential in the vicinity of roots with polymer tensiometers [2]. In a lysimeter experiment with various levels of imposed water stress the polymer tensiometer data suggest maize roots regulate their root water uptake on the derivative of the soil water retention curve, rather than the amount of moisture alone. As a result of environmental changes vegetation may wither and die, or these changes may instead trigger gene adaptation. Constant exposure to environmental stresses, biotic or abiotic, influences plant physiology, gene adaptations, and flexibility in gene adaptation [3-7]. To investigate a possible relation between plant genotype, the plant stress hormone abscisic acid (ABA) and the soil water potential, a proof of principle experiment was set up with Solanum Dulcamare plants. The results showed a significant difference in ABA response between genotypes from a dry and a wet environment, and this response was also reflected in the root water uptake. Adaptive responses may have consequences for the way species are currently being treated in models (single plant to global scale). In particular, model parameters that control root water uptake and plant transpiration are generally assumed to be a property of the plant

  9. Temperature responses of photosynthesis and respiration in Populus balsamifera L.: acclimation versus adaptation.

    PubMed

    Silim, Salim N; Ryan, Natalie; Kubien, David S

    2010-04-01

    To examine the role of acclimation versus adaptation on the temperature responses of CO(2) assimilation, we measured dark respiration (R(n)) and the CO(2) response of net photosynthesis (A) in Populus balsamifera collected from warm and cool habitats and grown at warm and cool temperatures. R(n) and the rate of photosynthetic electron transport (J) are significantly higher in plants grown at 19 versus 27 degrees C; R(n) is not affected by the native thermal habitat. By contrast, both the maximum capacity of rubisco (V(cmax)) and A are relatively insensitive to growth temperature, but both parameters are slightly higher in plants from cool habitats. A is limited by rubisco capacity from 17-37 degrees C regardless of growth temperature, and there is little evidence for an electron-transport limitation. Stomatal conductance (g(s)) is higher in warm-grown plants, but declines with increasing measurement temperature from 17 to 37 degrees C, regardless of growth temperature. The mesophyll conductance (g(m)) is relatively temperature insensitive below 25 degrees C, but g(m) declines at 37 degrees C in cool-grown plants. Plants acclimated to cool temperatures have increased R(n)/A, but this response does not differ between warm- and cool-adapted populations. Primary carbon metabolism clearly acclimates to growth temperature in P. balsamifera, but the ecotypic differences in A suggest that global warming scenarios might affect populations at the northern and southern edges of the boreal forest in different ways.

  10. Systems Analysis of Adaptive Responses to MAP Kinase Pathway Blockade in BRAF Mutant Melanoma

    PubMed Central

    Capaldo, Brian J.; Roller, Devin; Axelrod, Mark J.; Koeppel, Alex F.; Petricoin, Emanuel F.; Slingluff, Craig L.; Weber, Michael J.; Mackey, Aaron J.; Gioeli, Daniel; Bekiranov, Stefan

    2015-01-01

    Fifty percent of cutaneous melanomas are driven by activated BRAFV600E, but tumors treated with RAF inhibitors, even when they respond dramatically, rapidly adapt and develop resistance. Thus, there is a pressing need to identify the major mechanisms of intrinsic and adaptive resistance and develop drug combinations that target these resistance mechanisms. In a combinatorial drug screen on a panel of 12 treatment-naïve BRAFV600E mutant melanoma cell lines of varying levels of resistance to mitogen-activated protein kinase (MAPK) pathway inhibition, we identified the combination of PLX4720, a targeted inhibitor of mutated BRaf, and lapatinib, an inhibitor of the ErbB family of receptor tyrosine kinases, as synergistically cytotoxic in the subset of cell lines that displayed the most resistance to PLX4720. To identify potential mechanisms of resistance to PLX4720 treatment and synergy with lapatinib treatment, we performed a multi-platform functional genomics analysis to profile the genome as well as the transcriptional and proteomic responses of these cell lines to treatment with PLX4720. We found modest levels of resistance correlated with the zygosity of the BRAF V600E allele and receptor tyrosine kinase (RTK) mutational status. Layered over base-line resistance was substantial upregulation of many ErbB pathway genes in response to BRaf inhibition, thus generating the vulnerability to combination with lapatinib. The transcriptional responses of ErbB pathway genes are associated with a number of transcription factors, including ETS2 and its associated cofactors that represent a convergent regulatory mechanism conferring synergistic drug susceptibility in the context of diverse mutational landscapes. PMID:26405815

  11. Genome and low-iron response of an oceanic diatom adapted to chronic iron limitation

    PubMed Central

    2012-01-01

    Background Biogeochemical elemental cycling is driven by primary production of biomass via phototrophic phytoplankton growth, with 40% of marine productivity being assigned to diatoms. Phytoplankton growth is widely limited by the availability of iron, an essential component of the photosynthetic apparatus. The oceanic diatom Thalassiosira oceanica shows a remarkable tolerance to low-iron conditions and was chosen as a model for deciphering the cellular response upon shortage of this essential micronutrient. Results The combined efforts in genomics, transcriptomics and proteomics reveal an unexpected metabolic flexibility in response to iron availability for T. oceanica CCMP1005. The complex response comprises cellular retrenchment as well as remodeling of bioenergetic pathways, where the abundance of iron-rich photosynthetic proteins is lowered, whereas iron-rich mitochondrial proteins are preserved. As a consequence of iron deprivation, the photosynthetic machinery undergoes a remodeling to adjust the light energy utilization with the overall decrease in photosynthetic electron transfer complexes. Conclusions Beneficial adaptations to low-iron environments include strategies to lower the cellular iron requirements and to enhance iron uptake. A novel contribution enhancing iron economy of phototrophic growth is observed with the iron-regulated substitution of three metal-containing fructose-bisphosphate aldolases involved in metabolic conversion of carbohydrates for enzymes that do not contain metals. Further, our data identify candidate components of a high-affinity iron-uptake system, with several of the involved genes and domains originating from duplication events. A high genomic plasticity, as seen from the fraction of genes acquired through horizontal gene transfer, provides the platform for these complex adaptations to a low-iron world. PMID:22835381

  12. LDRD final report on adaptive-responsive nanostructures for sensing applications.

    SciTech Connect

    Shelnutt, John Allen; van Swol, Frank B.; Wang, Zhongchun; Medforth, Craig J.

    2005-11-01

    Functional organic nanostructures such as well-formed tubes or fibers that can easily be fabricated into electronic and photonic devices are needed in many applications. Especially desirable from a national security standpoint are nanostructures that have enhanced sensitivity for the detection of chemicals and biological (CB) agents and other environmental stimuli. We recently discovered the first class of highly responsive and adaptive porphyrin-based nanostructures that may satisfy these requirements. These novel porphyrin nanostructures, which are formed by ionic self-assembly of two oppositely charged porphyrins, may function as conductors, semiconductors, or photoconductors, and they have additional properties that make them suitable for device fabrication (e.g., as ultrasensitive colorimetric CB microsensors). Preliminary studies with porphyrin nanotubes have shown that these nanostructures have novel optical and electronic properties, including strong resonant light scattering, quenched fluorescence, and electrical conductivity. In addition, they are photochemically active and capable of light-harvesting and photosynthesis; they may also have nonlinear optical properties. Remarkably, the nanotubes and potentially other porphyrin nanostructure are mechanically responsive and adaptive (e.g., the rigidity of the micrometers-long nanotubes is altered by light, ultrasound, or chemicals) and they self-heal upon removal the environmental stimulus. Given the tremendous degree of structural variation possible in the porphyrin subunits, additional types of nanostructures and greater control over their morphology can be anticipated. Molecular modification also provides a means of controlling their electronic, photonic, and other functional properties. In this work, we have greatly broadened the range of ionic porphyrin nanostructures that can be made, and determined the optical and responsivity properties of the nanotubes and other porphyrin nanostructures. We have

  13. Induction of a Radio-Adaptive Response by Low-dose Gamma Irradiation in Mouse Cardiomyocytes

    NASA Technical Reports Server (NTRS)

    Westby, Christian M.; Seawright, John W.; Wu, Honglu

    2011-01-01

    One of the most significant occupational hazards to an astronaut is the frequent exposure to radiation. Commonly associated with increased risk for cancer related morbidity and mortality, radiation is also known to increase the risk for cardiovascular related disorders including: pericarditis, hypertension, and heart failure. It is believed that these radiation-induced disorders are a result of abnormal tissue remodeling. It is unknown whether radiation exposure promotes remodeling through fibrotic changes alone or in combination with programmed cell death. Furthermore, it is not known whether it is possible to mitigate the hazardous effects of radiation exposure. As such, we assessed the expression and mechanisms of radiation-induced tissue remodeling and potential radio-adaptive responses of p53-mediated apoptosis and fibrosis pathways along with markers for oxidative stress and inflammation in mice myocardium. 7 week old, male, C57Bl/6 mice were exposed to 6Gy (H) or 5cGy followed 24hr later with 6Gy (LH) 137Cs gamma radiation. Mice were sacrificed and their hearts extirpated 4, 24, or 72hr after final irradiation. Real Time - Polymerase Chain Reaction was used to evaluate target genes. Apoptotic genes Bad and Bax, pro-cell survival genes Bcl2 and Bcl2l2, fibrosis gene Vegfa, and oxidative stress genes Sod2 and GPx4 showed a reduced fold regulation change (Bad,-6.18; Bax,-6.94; Bcl2,-5.09; Bcl2l2,-4.03; Vegfa, -11.84; Sod2,-5.97; GPx4*,-28.72; * = Bonferroni adjusted p-value < or = 0.003) 4hr after H, but not after 4hr LH compared to control. Other p53-mediated apoptosis genes Casp3, Casp9, Trp53, and Myc exhibited down-regulation but did not achieve a notable level of significance 4hr after H. 24hr after H, genetic down-regulation was no longer present compared to 24hr control. These data suggest a general reduction in genetic expression 4hrs after a high dose of gamma radiation. However, pre-exposure to 5cGy gamma radiation appears to facilitate a radio-adaptive

  14. Enteral supplementation with ornithine alpha ketoglutarate improves the early adaptive response to resection.

    PubMed Central

    Czernichow, B; Nsi-Emvo, E; Galluser, M; Gossé, F; Raul, F

    1997-01-01

    BACKGROUND: Polyamine synthesis or uptake, or both, might be an important event that initiates the adaptive hyperplasia seen in the intestinal remnant after partial small bowel resection. AIM: The ability of an enteral diet supplemented with the ornithine salt: ornithine alpha ketoglutarate (OKG), a precursor for polyamine synthesis, to modulate the adaptive response of the remnant ileum after jejunectomy was evaluated. METHODS: Adult Wistar rats underwent a resection of the proximal 50% of the small intestine. Controls underwent a single transection. The rats were fed intragastrically with a nutritive mixture supplemented either with casein hydrolysate or with OKG (1 g/kg). The isoenergetic and isonitrogeneous diets was given continuously for seven days. RESULTS: Villus and crypt hyperplasia was observed in the remnant ileum compared with transfected controls. OKG supplementation started after resection a further increase in villus height. After resection, OKG supplementation increased significantly the putrescine content and the amount of ornithine decarboxylase mRNA. A twofold to threefold increase of sucrase activity was measured in the resected animals compared with the transected rats. In contrast, the amount of sucrase mRNA was significantly lower in the ileum of the resected rats and OKG supplementation initiated a further drop in the amount of sucrase mRNA without pronounced changes in enzyme activity. CONCLUSIONS: The adaptive hypertrophy seen after resection can be accelerated by supplementing the diet with ornithine (OKG) a precursor of polyamine synthesis. In the remnant ileum, the reduced amount of sucrase mRNA, despite the increased level of sucrase activity, suggests a post-translational control of sucrase expression. PMID:9155578

  15. Effects of extracellular calcium and of light adaptation on the response to dim light in honey bee drone photoreceptors.

    PubMed

    Raggenbass, M

    1983-11-01

    Light responses in honey bee drone photoreceptors were recorded with intracellular micro-electrodes in superfused slices of retina. The effects of changes in extracellular calcium on the size and the shape of the response to dim light were studied and compared with the effects of light adaptation. Dim light stimuli were used so that the amplitude of the response was linearly related to the number of the photons absorbed, the effects of voltage-dependent mechanisms were negligible and no detectable light adaptation was produced by the stimulus. Lowering the extracellular calcium concentration increased the amplitude and the duration of the response. Raising the extracellular calcium concentration produced the opposite effects. Changing the extracellular calcium concentration modified the response without altering either the linearity of the intensity--response relation or the resting membrane potential in the dark. Light adaptation decreased the amplitude and the duration of the response in a manner that could be quantitatively simulated, in the same photoreceptors, by an increase in the extracellular calcium concentration. Changing the extracellular calcium concentration, or light-adapting the preparation, modified the response without altering its early depolarizing phase. Lowering external calcium either did not affect, or slightly increased, the maximum rate of the light-induced depolarization; raising external calcium, or light-adapting the preparation, either did not affect, or slightly decreased, the maximum rate of the light-induced depolarization. The experimental data can be quantitatively described by a mathematical model with the basic assumption that calcium acts in the process of light adaptation by decreasing the mean open time of the light-activated channels.

  16. Effects of extracellular calcium and of light adaptation on the response to dim light in honey bee drone photoreceptors.

    PubMed Central

    Raggenbass, M

    1983-01-01

    Light responses in honey bee drone photoreceptors were recorded with intracellular micro-electrodes in superfused slices of retina. The effects of changes in extracellular calcium on the size and the shape of the response to dim light were studied and compared with the effects of light adaptation. Dim light stimuli were used so that the amplitude of the response was linearly related to the number of the photons absorbed, the effects of voltage-dependent mechanisms were negligible and no detectable light adaptation was produced by the stimulus. Lowering the extracellular calcium concentration increased the amplitude and the duration of the response. Raising the extracellular calcium concentration produced the opposite effects. Changing the extracellular calcium concentration modified the response without altering either the linearity of the intensity--response relation or the resting membrane potential in the dark. Light adaptation decreased the amplitude and the duration of the response in a manner that could be quantitatively simulated, in the same photoreceptors, by an increase in the extracellular calcium concentration. Changing the extracellular calcium concentration, or light-adapting the preparation, modified the response without altering its early depolarizing phase. Lowering external calcium either did not affect, or slightly increased, the maximum rate of the light-induced depolarization; raising external calcium, or light-adapting the preparation, either did not affect, or slightly decreased, the maximum rate of the light-induced depolarization. The experimental data can be quantitatively described by a mathematical model with the basic assumption that calcium acts in the process of light adaptation by decreasing the mean open time of the light-activated channels. PMID:6655592

  17. Electricity for groundwater use: constraints and opportunities for adaptive response to climate change

    NASA Astrophysics Data System (ADS)

    Scott, Christopher A.

    2013-09-01

    Globally, groundwater use is intensifying to meet demands for irrigation, urban supply, industrialization, and, in some instances, electrical power generation. In response to hydroclimatic variability, surface water is being substituted with groundwater, which must be viewed as a strategic resource for climate adaptation. In this sense, the supply of electricity for pumping is an adaptation policy tool. Additionally, planning for climate-change mitigation must consider CO2 emissions resulting from pumping. This paper examines the influence of electricity supply and pricing on groundwater irrigation and resulting emissions, with specific reference to Mexico—a climate-water-energy ‘perfect storm’. Night-time power supply at tariffs below the already-subsidized rates for agricultural groundwater use has caused Mexican farmers to increase pumping, reversing important water and electricity conservation gains achieved. Indiscriminate groundwater pumping, including for virtual water exports of agricultural produce, threatens the long-term sustainability of aquifers, non-agricultural water uses, and stream-aquifer interactions that sustain riparian ecosystems. Emissions resulting from agricultural groundwater pumping in Mexico are estimated to be 3.6% of total national emissions and are equivalent to emissions from transporting the same agricultural produce to market. The paper concludes with an assessment of energy, water, and climate trends coupled with policy futures to address these challenges.

  18. Administration of DNA Encoding the Interleukin-27 Gene Augments Antitumour Responses through Non-adaptive Immunity.

    PubMed

    Li, Q; Sato, A; Shimozato, O; Shingyoji, M; Tada, Y; Tatsumi, K; Shimada, H; Hiroshima, K; Tagawa, M

    2015-10-01

    DNA-mediated immunization of a tumour antigen is a possible immunotherapy for cancer, and interleukin (IL)-27 has diverse functions in adaptive immunity. In this study, we examined whether IL-27 DNA administration enhanced antitumour effects in mice vaccinated with DNA encoding a putative tumour antigen, β-galactosidase (β-gal). An intramuscular injection of cardiotoxin before DNA administration facilitated the exogenous gene expression. In mice received β-gal and IL-27 DNA, growth of β-gal-positive P815 tumours was retarded and survival of the mice was prolonged. Development of β-gal-positive Colon 26 tumours was suppressed by vaccination of β-gal DNA and further inhibited by additional IL-27 DNA administration or IL-12 family cytokines. Nevertheless, a population of β-gal-specific CD8(+) T cells did not increase, and production of anti-β-gal antibody was not enhanced by IL-27 DNA administration. Spleen cells from mice bearing IL-27-expressing Colon 26 tumours showed greater YAC-1-targeted cytotoxicity although CD3(-)/DX5(+) natural killer (NK) cell numbers remained unchanged. Recombinant IL-27 enhanced YAC-1-targeted cytotoxicity of IL-2-primed splenic NK cells and augmented a phosphorylation of signal transducer and activator of transcription 3 and an expression of perforin. These data collectively indicate that IL-27 DNA administration activates NK cells and augments vaccination effects of DNA encoding a tumour antigen through non-adaptive immune responses. PMID:26095954

  19. Metainflammation in Diabetic Coronary Artery Disease: Emerging Role of Innate and Adaptive Immune Responses

    PubMed Central

    Madhumitha, Haridoss

    2016-01-01

    Globally, noncommunicable chronic diseases such as Type-2 Diabetes Mellitus (T2DM) and Coronary Artery Disease (CAD) are posing a major threat to the world. T2DM is known to potentiate CAD which had led to the coining of a new clinical entity named diabetic CAD (DM-CAD), leading to excessive morbidity and mortality. The synergistic interaction between these two comorbidities is through sterile inflammation which is now being addressed as metabolic inflammation or metainflammation, which plays a pivotal role during both early and late stages of T2DM and also serves as a link between T2DM and CAD. This review summarises the current concepts on the role played by both innate and adaptive immune responses in setting up metainflammation in DM-CAD. More specifically, the role played by innate pattern recognition receptors (PRRs) like Toll-like receptors (TLRs), NOD1-like receptors (NLRs), Rig-1-like receptors (RLRs), and C-type lectin like receptors (CLRs) and metabolic endotoxemia in fuelling metainflammation in DM-CAD would be discussed. Further, the role played by adaptive immune cells (Th1, Th2, Th17, and Th9 cells) in fuelling metainflammation in DM-CAD will also be discussed.

  20. Metainflammation in Diabetic Coronary Artery Disease: Emerging Role of Innate and Adaptive Immune Responses

    PubMed Central

    Madhumitha, Haridoss

    2016-01-01

    Globally, noncommunicable chronic diseases such as Type-2 Diabetes Mellitus (T2DM) and Coronary Artery Disease (CAD) are posing a major threat to the world. T2DM is known to potentiate CAD which had led to the coining of a new clinical entity named diabetic CAD (DM-CAD), leading to excessive morbidity and mortality. The synergistic interaction between these two comorbidities is through sterile inflammation which is now being addressed as metabolic inflammation or metainflammation, which plays a pivotal role during both early and late stages of T2DM and also serves as a link between T2DM and CAD. This review summarises the current concepts on the role played by both innate and adaptive immune responses in setting up metainflammation in DM-CAD. More specifically, the role played by innate pattern recognition receptors (PRRs) like Toll-like receptors (TLRs), NOD1-like receptors (NLRs), Rig-1-like receptors (RLRs), and C-type lectin like receptors (CLRs) and metabolic endotoxemia in fuelling metainflammation in DM-CAD would be discussed. Further, the role played by adaptive immune cells (Th1, Th2, Th17, and Th9 cells) in fuelling metainflammation in DM-CAD will also be discussed. PMID:27610390

  1. FGF21 and the late adaptive response to starvation in humans.

    PubMed

    Fazeli, Pouneh K; Lun, Mingyue; Kim, Soo M; Bredella, Miriam A; Wright, Spenser; Zhang, Yang; Lee, Hang; Catana, Ciprian; Klibanski, Anne; Patwari, Parth; Steinhauser, Matthew L

    2015-11-03

    In mice, FGF21 is rapidly induced by fasting, mediates critical aspects of the adaptive starvation response, and displays a number of positive metabolic properties when administered pharmacologically. In humans, however, fasting does not consistently increase FGF21, suggesting a possible evolutionary divergence in FGF21 function. Moreover, many key aspects of FGF21 function in mice have been identified in the context of transgenic overexpression or administration of supraphysiologic doses, rather than in a physiologic setting. Here, we explored the dynamics and function of FGF21 in human volunteers during a 10-day fast. Unlike mice, which show an increase in circulating FGF21 after only 6 hours, human subjects did not have a notable surge in FGF21 until 7 to 10 days of fasting. Moreover, we determined that FGF21 induction was associated with decreased thermogenesis and adiponectin, an observation that directly contrasts with previous reports based on supraphysiologic dosing. Additionally, FGF21 levels increased after ketone induction, demonstrating that endogenous FGF21 does not drive starvation-mediated ketogenesis in humans. Instead, a longitudinal analysis of biologically relevant variables identified serum transaminases--markers of tissue breakdown--as predictors of FGF21. These data establish FGF21 as a fasting-induced hormone in humans and indicate that FGF21 contributes to the late stages of adaptive starvation, when it may regulate the utilization of fuel derived from tissue breakdown.

  2. Compensatory structural adaptive modifications of vagina in response to functional demand in goat.

    PubMed

    Hussin, Amer M; Zaid, Nazih W; Hussain, S O

    2014-01-01

    Vaginal biopsies and smears were collected from ten adult local healthy goats. Routine histological methods were carried out on vaginal biopsies and then stained with PAS stain. The smears were stained with Methylene blue. All samples were inspected under light microscope. The present study found that many constituents of the wall of the vagina, which have an important functional role, were absent; among these were the vaginal glands, goblet cells, muscularis mucosa, and lymphatic nodules. On the other hand, vagina showed special compensatory histological mechanisms, namely, the deep epithelial folds, the well-developed germinated stratum basale, the apparent basement membrane, and the profuse defensive cells, such as neutrophils, macrophages, lymphocytes, plasma cells, and mast cells. The general stains of this study could not recognize dendritic cells although they play an important functional role. Moreover, the herein study declared also that the vaginal smears showing many adaptive cellular mechanisms among these were, the keratinization, the process of sheet formation that lines the vaginal lumen, the process of metachromasia which is related to the cellular activity in protein synthesis, keratin, and finally the presence of endogenous microorganisms. It was concluded that all the above cellular compensatory adaptive mechanisms may compensate the lacking vaginal constituents and act to raise the immune response of the vagina.

  3. Membrane transporters mediating root signalling and adaptive responses to oxygen deprivation and soil flooding.

    PubMed

    Shabala, Sergey; Shabala, Lana; Barcelo, Juan; Poschenrieder, Charlotte

    2014-10-01

    This review provides a comprehensive assessment of a previously unexplored topic: elucidating the role that plasma- and organelle-based membrane transporters play in plant-adaptive responses to flooding. We show that energy availability and metabolic shifts under hypoxia and anoxia are critical in regulating membrane-transport activity. We illustrate the high tissue and time dependence of this regulation, reveal the molecular identity of transporters involved and discuss the modes of their regulation. We show that both reduced oxygen availability and accumulation of transition metals in flooded roots result in a reduction in the cytosolic K(+) pool, ultimately determining the cell's fate and transition to programmed cell death (PCD). This process can be strongly affected by hypoxia-induced changes in the amino acid pool profile and, specifically, ϒ-amino butyric acid (GABA) accumulation. It is suggested that GABA plays an important regulatory role, allowing plants to proceed with H2 O2 signalling to activate a cascade of genes that mediate plant adaptation to flooding while at the same time, preventing the cell from entering a 'suicide program'. We conclude that progress in crop breeding for flooding tolerance can only be achieved by pyramiding the numerous physiological traits that confer efficient energy maintenance, cytosolic ion homeostasis, and reactive oxygen species (ROS) control and detoxification.

  4. Metainflammation in Diabetic Coronary Artery Disease: Emerging Role of Innate and Adaptive Immune Responses.

    PubMed

    Aravindhan, Vivekanandhan; Madhumitha, Haridoss

    2016-01-01

    Globally, noncommunicable chronic diseases such as Type-2 Diabetes Mellitus (T2DM) and Coronary Artery Disease (CAD) are posing a major threat to the world. T2DM is known to potentiate CAD which had led to the coining of a new clinical entity named diabetic CAD (DM-CAD), leading to excessive morbidity and mortality. The synergistic interaction between these two comorbidities is through sterile inflammation which is now being addressed as metabolic inflammation or metainflammation, which plays a pivotal role during both early and late stages of T2DM and also serves as a link between T2DM and CAD. This review summarises the current concepts on the role played by both innate and adaptive immune responses in setting up metainflammation in DM-CAD. More specifically, the role played by innate pattern recognition receptors (PRRs) like Toll-like receptors (TLRs), NOD1-like receptors (NLRs), Rig-1-like receptors (RLRs), and C-type lectin like receptors (CLRs) and metabolic endotoxemia in fuelling metainflammation in DM-CAD would be discussed. Further, the role played by adaptive immune cells (Th1, Th2, Th17, and Th9 cells) in fuelling metainflammation in DM-CAD will also be discussed. PMID:27610390

  5. FGF21 and the late adaptive response to starvation in humans

    PubMed Central

    Fazeli, Pouneh K.; Lun, Mingyue; Kim, Soo M.; Bredella, Miriam A.; Wright, Spenser; Zhang, Yang; Lee, Hang; Catana, Ciprian; Klibanski, Anne; Patwari, Parth; Steinhauser, Matthew L.

    2015-01-01

    In mice, FGF21 is rapidly induced by fasting, mediates critical aspects of the adaptive starvation response, and displays a number of positive metabolic properties when administered pharmacologically. In humans, however, fasting does not consistently increase FGF21, suggesting a possible evolutionary divergence in FGF21 function. Moreover, many key aspects of FGF21 function in mice have been identified in the context of transgenic overexpression or administration of supraphysiologic doses, rather than in a physiologic setting. Here, we explored the dynamics and function of FGF21 in human volunteers during a 10-day fast. Unlike mice, which show an increase in circulating FGF21 after only 6 hours, human subjects did not have a notable surge in FGF21 until 7 to 10 days of fasting. Moreover, we determined that FGF21 induction was associated with decreased thermogenesis and adiponectin, an observation that directly contrasts with previous reports based on supraphysiologic dosing. Additionally, FGF21 levels increased after ketone induction, demonstrating that endogenous FGF21 does not drive starvation-mediated ketogenesis in humans. Instead, a longitudinal analysis of biologically relevant variables identified serum transaminases — markers of tissue breakdown — as predictors of FGF21. These data establish FGF21 as a fasting-induced hormone in humans and indicate that FGF21 contributes to the late stages of adaptive starvation, when it may regulate the utilization of fuel derived from tissue breakdown. PMID:26529252

  6. Membrane transporters mediating root signalling and adaptive responses to oxygen deprivation and soil flooding.

    PubMed

    Shabala, Sergey; Shabala, Lana; Barcelo, Juan; Poschenrieder, Charlotte

    2014-10-01

    This review provides a comprehensive assessment of a previously unexplored topic: elucidating the role that plasma- and organelle-based membrane transporters play in plant-adaptive responses to flooding. We show that energy availability and metabolic shifts under hypoxia and anoxia are critical in regulating membrane-transport activity. We illustrate the high tissue and time dependence of this regulation, reveal the molecular identity of transporters involved and discuss the modes of their regulation. We show that both reduced oxygen availability and accumulation of transition metals in flooded roots result in a reduction in the cytosolic K(+) pool, ultimately determining the cell's fate and transition to programmed cell death (PCD). This process can be strongly affected by hypoxia-induced changes in the amino acid pool profile and, specifically, ϒ-amino butyric acid (GABA) accumulation. It is suggested that GABA plays an important regulatory role, allowing plants to proceed with H2 O2 signalling to activate a cascade of genes that mediate plant adaptation to flooding while at the same time, preventing the cell from entering a 'suicide program'. We conclude that progress in crop breeding for flooding tolerance can only be achieved by pyramiding the numerous physiological traits that confer efficient energy maintenance, cytosolic ion homeostasis, and reactive oxygen species (ROS) control and detoxification. PMID:24689809

  7. A novel AKT1 mutant amplifies an adaptive melanoma response to BRAF inhibition

    PubMed Central

    Shi, Hubing; Hong, Aayoung; Kong, Xiangju; Koya, Richard C.; Song, Chunying; Moriceau, Gatien; Hugo, Willy; Yu, Clarissa C.; Ng, Charles; Chodon, Thinle; Scolyer, Richard A.; Kefford, Richard F.; Ribas, Antoni; Long, Georgina V.; Lo, Roger S.

    2013-01-01

    BRAF inhibitor (BRAFi) therapy leads to remarkable anti-melanoma responses, but the initial tumor shrinkage is commonly incomplete, providing a nidus for subsequent disease progression. Adaptive signaling may underlie early BRAFi resistance and influence the selection pattern for genetic variants causing late, acquired resistance. We show here that BRAFi (or BRAFi+MEKi) therapy in patients frequently led to rebound p-AKT levels in their melanomas early on treatment. In cell lines, BRAFi treatment led to rebound levels of RTKs (including PDGFRβ), PIP3, pleckstrin homology domain (PHD) recruitment, and p-AKT. PTEN expression limited this BRAFi-elicited PI3K-AKT signaling, which could be rescued by introduction of a mutant AKT1 (Q79K) kown to confer acquired BRAFi resistance. Functionally, AKT1 Q79K conferred BRAFi resistance via amplifying BRAFi-elicited PI3K-AKT signaling. Additionally, MAPK pathway inhibition enhanced clonogenic growth dependency on PI3K or AKT. Thus, adaptive or genetic upregulation of AKT critically participates in melanoma survival during BRAFi therapy. PMID:24265152

  8. The biology of developmental plasticity and the Predictive Adaptive Response hypothesis

    PubMed Central

    Bateson, Patrick; Gluckman, Peter; Hanson, Mark

    2014-01-01

    Many forms of developmental plasticity have been observed and these are usually beneficial to the organism. The Predictive Adaptive Response (PAR) hypothesis refers to a form of developmental plasticity in which cues received in early life influence the development of a phenotype that is normally adapted to the environmental conditions of later life. When the predicted and actual environments differ, the mismatch between the individual's phenotype and the conditions in which it finds itself can have adverse consequences for Darwinian fitness and, later, for health. Numerous examples exist of the long-term effects of cues indicating a threatening environment affecting the subsequent phenotype of the individual organism. Other examples consist of the long-term effects of variations in environment within a normal range, particularly in the individual's nutritional environment. In mammals the cues to developing offspring are often provided by the mother's plane of nutrition, her body composition or stress levels. This hypothetical effect in humans is thought to be important by some scientists and controversial by others. In resolving the conflict, distinctions should be drawn between PARs induced by normative variations in the developmental environment and the ill effects on development of extremes in environment such as a very poor or very rich nutritional environment. Tests to distinguish between different developmental processes impacting on adult characteristics are proposed. Many of the mechanisms underlying developmental plasticity involve molecular epigenetic processes, and their elucidation in the context of PARs and more widely has implications for the revision of classical evolutionary theory. PMID:24882817

  9. Public health and climate change adaptation at the federal level: one agency's response to Executive Order 13514.

    PubMed

    Hess, Jeremy J; Schramm, Paul J; Luber, George

    2014-03-01

    Climate change will likely have adverse human health effects that require federal agency involvement in adaptation activities. In 2009, President Obama issued Executive Order 13514, Federal Leadership in Environmental, Energy, and Economic Performance. The order required federal agencies to develop and implement climate change adaptation plans. The Centers for Disease Control and Prevention (CDC), as part of a larger Department of Health and Human Services response to climate change, is developing such plans. We provide background on Executive Orders, outline tenets of climate change adaptation, discuss public health adaptation planning at both the Department of Health and Human Services and the CDC, and outline possible future CDC efforts. We also consider how these activities may be better integrated with other adaptation activities that manage emerging health threats posed by climate change.

  10. Public Health and Climate Change Adaptation at the Federal Level: One Agency’s Response to Executive Order 13514

    PubMed Central

    Schramm, Paul J.; Luber, George

    2014-01-01

    Climate change will likely have adverse human health effects that require federal agency involvement in adaptation activities. In 2009, President Obama issued Executive Order 13514, Federal Leadership in Environmental, Energy, and Economic Performance. The order required federal agencies to develop and implement climate change adaptation plans. The Centers for Disease Control and Prevention (CDC), as part of a larger Department of Health and Human Services response to climate change, is developing such plans. We provide background on Executive Orders, outline tenets of climate change adaptation, discuss public health adaptation planning at both the Department of Health and Human Services and the CDC, and outline possible future CDC efforts. We also consider how these activities may be better integrated with other adaptation activities that manage emerging health threats posed by climate change. PMID:24432931

  11. Adaptive Physiological Response to Perceived Scarcity as a Mechanism of Sensory Modulation of Life Span

    PubMed Central

    Waterson, Michael J.; Chan, Tammy P.

    2015-01-01

    Chemosensation is a potent modulator of organismal physiology and longevity. In Drosophila, loss of recognition of diverse tastants has significant and bidirectional life-span effects. Recently published results revealed that when flies were unable to taste water, they increased its internal generation, which may have subsequently altered life span. To determine whether similar adaptive responses occur in other contexts, we explored the impact of sensory deficiency of other metabolically important molecules. Trehalose is a major circulating carbohydrate in the fly that is recognized by the gustatory receptor Gr5a. Gr5a mutant flies are short lived, and we found that they specifically increased whole-body and circulating levels of trehalose, but not other carbohydrates, likely through upregulation of de novo synthesis. dILP2 transcript levels were increased in Gr5a mutants, a possible response intended to reduce hypertrehalosemia, and likely a contributing factor to their reduced life span. Together, these data suggest that compensatory physiological responses to perceived environmental scarcity, which are designed to alleviate the ostensive shortage, may be a common outcome of sensory manipulation. We suggest that future investigations into the mechanisms underlying sensory modulation of aging may benefit by focusing on direct or indirect consequences of physiological changes that are designed to correct perceived disparity with the environment. PMID:25878032

  12. Evidence of bacterioplankton community adaptation in response to long-term mariculture disturbance

    PubMed Central

    Xiong, Jinbo; Chen, Heping; Hu, Changju; Ye, Xiansen; Kong, Dingjiang; Zhang, Demin

    2015-01-01

    Understanding the underlying mechanisms that shape the temporal dynamics of a microbial community has important implications for predicting the trajectory of an ecosystem’s response to anthropogenic disturbances. Here, we evaluated the seasonal dynamics of bacterioplankton community composition (BCC) following more than three decades of mariculture disturbance in Xiangshan Bay. Clear seasonal succession and site (fish farm and control site) separation of the BCC were observed, which were primarily shaped by temperature, dissolved oxygen and sampling time. However, the sensitive bacterial families consistently changed in relative abundance in response to mariculture disturbance, regardless of the season. Temporal changes in the BCC followed the time-decay for similarity relationship at both sites. Notably, mariculture disturbance significantly (P < 0.001) flattened the temporal turnover but intensified bacterial species-to-species interactions. The decrease in bacterial temporal turnover under long-term mariculture disturbance was coupled with a consistent increase in the percentage of deterministic processes that constrained bacterial assembly based on a null model analysis. The results demonstrate that the BCC is sensitive to mariculture disturbance; however, a bacterioplankton community could adapt to a long-term disturbance via attenuating temporal turnover and intensifying species-species interactions. These findings expand our current understanding of microbial assembly in response to long-term anthropogenic disturbances. PMID:26471739

  13. Learning theories reveal loss of pancreatic electrical connectivity in diabetes as an adaptive response.

    PubMed

    Goel, Pranay; Mehta, Anita

    2013-01-01

    Cells of almost all solid tissues are connected with gap junctions which permit the direct transfer of ions and small molecules, integral to regulating coordinated function in the tissue. The pancreatic islets of Langerhans are responsible for secreting the hormone insulin in response to glucose stimulation. Gap junctions are the only electrical contacts between the beta-cells in the tissue of these excitable islets. It is generally believed that they are responsible for synchrony of the membrane voltage oscillations among beta-cells, and thereby pulsatility of insulin secretion. Most attempts to understand connectivity in islets are often interpreted, bottom-up, in terms of measurements of gap junctional conductance. This does not, however, explain systematic changes, such as a diminished junctional conductance in type 2 diabetes. We attempt to address this deficit via the model presented here, which is a learning theory of gap junctional adaptation derived with analogy to neural systems. Here, gap junctions are modelled as bonds in a beta-cell network, that are altered according to homeostatic rules of plasticity. Our analysis reveals that it is nearly impossible to view gap junctions as homogeneous across a tissue. A modified view that accommodates heterogeneity of junction strengths in the islet can explain why, for example, a loss of gap junction conductance in diabetes is necessary for an increase in plasma insulin levels following hyperglycemia.

  14. Adaptive allocation of decisionmaking responsibility between human and computer in multitask situations

    NASA Technical Reports Server (NTRS)

    Chu, Y.-Y.; Rouse, W. B.

    1979-01-01

    As human and computer come to have overlapping decisionmaking abilities, a dynamic or adaptive allocation of responsibilities may be the best mode of human-computer interaction. It is suggested that the computer serve as a backup decisionmaker, accepting responsibility when human workload becomes excessive and relinquishing responsibility when workload becomes acceptable. A queueing theory formulation of multitask decisionmaking is used and a threshold policy for turning the computer on/off is proposed. This policy minimizes event-waiting cost subject to human workload constraints. An experiment was conducted with a balanced design of several subject runs within a computer-aided multitask flight management situation with different task demand levels. It was found that computer aiding enhanced subsystem performance as well as subjective ratings. The queueing model appears to be an adequate representation of the multitask decisionmaking situation, and to be capable of predicting system performance in terms of average waiting time and server occupancy. Server occupancy was further found to correlate highly with the subjective effort ratings.

  15. Adaptive Physiological Response to Perceived Scarcity as a Mechanism of Sensory Modulation of Life Span.

    PubMed

    Waterson, Michael J; Chan, Tammy P; Pletcher, Scott D

    2015-09-01

    Chemosensation is a potent modulator of organismal physiology and longevity. In Drosophila, loss of recognition of diverse tastants has significant and bidirectional life-span effects. Recently published results revealed that when flies were unable to taste water, they increased its internal generation, which may have subsequently altered life span. To determine whether similar adaptive responses occur in other contexts, we explored the impact of sensory deficiency of other metabolically important molecules. Trehalose is a major circulating carbohydrate in the fly that is recognized by the gustatory receptor Gr5a. Gr5a mutant flies are short lived, and we found that they specifically increased whole-body and circulating levels of trehalose, but not other carbohydrates, likely through upregulation of de novo synthesis. dILP2 transcript levels were increased in Gr5a mutants, a possible response intended to reduce hypertrehalosemia, and likely a contributing factor to their reduced life span. Together, these data suggest that compensatory physiological responses to perceived environmental scarcity, which are designed to alleviate the ostensive shortage, may be a common outcome of sensory manipulation. We suggest that future investigations into the mechanisms underlying sensory modulation of aging may benefit by focusing on direct or indirect consequences of physiological changes that are designed to correct perceived disparity with the environment. PMID:25878032

  16. Control of Dichotomic Innate and Adaptive Immune Responses by Artery Tertiary Lymphoid Organs in Atherosclerosis

    PubMed Central

    Weih, Falk; Gräbner, Rolf; Hu, Desheng; Beer, Michael; Habenicht, Andreas J. R.

    2012-01-01

    Tertiary lymphoid organs (TLOs) emerge in tissues in response to non-resolving inflammation such as chronic infection, graft rejection, and autoimmune disease. We identified artery TLOs (ATLOs) in the adventitia adjacent to atherosclerotic plaques of aged hyperlipidemic ApoE−/− mice. ATLOs are structured into T cell areas harboring conventional dendritic cells and monocyte-derived DCs; B cell follicles containing follicular dendritic cells within activated germinal centers; and peripheral niches of plasma cells. ATLOs also show extensive neoangiogenesis, aberrant lymphangiogenesis, and high endothelial venule (HEV) neogenesis. Newly formed conduit networks connect the external lamina of the artery with HEVs in T cell areas. ATLOs recruit and generate lymphocyte subsets with opposing activities including activated CD4+ and CD8+ effector T cells, natural and induced CD4+ T regulatory (nTregs; iTregs) cells as well as B-1 and B-2 cells at different stages of differentiation. These data indicate that ATLOs organize dichotomic innate and adaptive immune responses in atherosclerosis. In this review we discuss the novel concept that dichotomic immune responses toward atherosclerosis-specific antigens are carried out by ATLOs in the adventitia of the arterial wall and that malfunction of the tolerogenic arm of ATLO immunity triggers transition from silent autoimmune reactivity to clinically overt disease. PMID:22783198

  17. Adaptive response and tolerance to weak acids in Saccharomyces cerevisiae: a genome-wide view.

    PubMed

    Mira, Nuno P; Teixeira, Miguel Cacho; Sá-Correia, Isabel

    2010-10-01

    Weak acids are widely used as food preservatives (e.g., acetic, propionic, benzoic, and sorbic acids), herbicides (e.g., 2,4-dichlorophenoxyacetic acid), and as antimalarial (e.g., artesunic and artemisinic acids), anticancer (e.g., artesunic acid), and immunosuppressive (e.g., mycophenolic acid) drugs, among other possible applications. The understanding of the mechanisms underlying the adaptive response and resistance to these weak acids is a prerequisite to develop more effective strategies to control spoilage yeasts, and the emergence of resistant weeds, drug resistant parasites or cancer cells. Furthermore, the identification of toxicity mechanisms and resistance determinants to weak acid-based pharmaceuticals increases current knowledge on their cytotoxic effects and may lead to the identification of new drug targets. This review integrates current knowledge on the mechanisms of toxicity and tolerance to weak acid stress obtained in the model eukaryote Saccharomyces cerevisiae using genome-wide approaches and more detailed gene-by-gene analysis. The major features of the yeast response to weak acids in general, and the more specific responses and resistance mechanisms towards a specific weak acid or a group of weak acids, depending on the chemical nature of the side chain R group (R-COOH), are highlighted. The involvement of several transcriptional regulatory networks in the genomic response to different weak acids is discussed, focusing on the regulatory pathways controlled by the transcription factors Msn2p/Msn4p, War1p, Haa1p, Rim101p, and Pdr1p/Pdr3p, which are known to orchestrate weak acid stress response in yeast. The extrapolation of the knowledge gathered in yeast to other eukaryotes is also attempted.

  18. Melanopsin-Derived Visual Responses under Light Adapted Conditions in the Mouse dLGN

    PubMed Central

    Davis, Katherine E.; Eleftheriou, Cyril G.; Allen, Annette E.; Procyk, Christopher A.; Lucas, Robert J.

    2015-01-01

    A direct projection from melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs) reaches the primary visual thalamus (dorsal lateral geniculate nucleus; dLGN). The significance of this melanopsin input to the visual system is only recently being investigated. One unresolved question is the degree to which neurons in the dLGN could use melanopsin to track dynamic changes in light intensity under light adapted conditions. Here we set out to address this question. We were able to present full field steps visible only to melanopsin by switching between rod-isoluminant ‘yellow’ and ‘blue’ lights in a mouse lacking cone function (Cnga3-/-). In the retina these stimuli elicited melanopsin-like responses from a subset of ganglion cells. When presented to anaesthetised mice, we found that ~25-30% of visually responsive neurones in the contralateral dLGN responded to these melanopsin-isolating steps with small increases in firing rate. Such responses could be elicited even with fairly modest increases in effective irradiance (32% Michelson contrast for melanopsin). These melanopsin-driven responses were apparent at bright backgrounds (corresponding to twilight-daylight conditions), but their threshold irradiance was strongly dependent upon prior light exposure when stimuli were superimposed on a spectrally neutral ramping background light. While both onset and offset latencies were long for melanopsin-derived responses compared to those evoked by rods, there was great variability in these parameters with some cells responding to melanopsin steps in <1 s. These data indicate that a subset of dLGN units can employ melanopsin signals to detect modest changes in irradiance under photopic conditions. PMID:25822371

  19. The innate and adaptive immune response induced by alveolar macrophages exposed to ambient particulate matter

    SciTech Connect

    Miyata, Ryohei; Eeden, Stephan F. van

    2011-12-15

    Emerging epidemiological evidence suggests that exposure to particulate matter (PM) air pollution increases the risk of cardiovascular events but the exact mechanism by which PM has adverse effects is still unclear. Alveolar macrophages (AM) play a major role in clearing and processing inhaled PM. This comprehensive review of research findings on immunological interactions between AM and PM provides potential pathophysiological pathways that interconnect PM exposure with adverse cardiovascular effects. Coarse particles (10 {mu}m or less, PM{sub 10}) induce innate immune responses via endotoxin-toll-like receptor (TLR) 4 pathway while fine (2.5 {mu}m or less, PM{sub 2.5}) and ultrafine particles (0.1 {mu}m or less, UFP) induce via reactive oxygen species generation by transition metals and/or polyaromatic hydrocarbons. The innate immune responses are characterized by activation of transcription factors [nuclear factor (NF)-{kappa}B and activator protein-1] and the downstream proinflammatory cytokine [interleukin (IL)-1{beta}, IL-6, and tumor necrosis factor-{alpha}] production. In addition to the conventional opsonin-dependent phagocytosis by AM, PM can also be endocytosed by an opsonin-independent pathway via scavenger receptors. Activation of scavenger receptors negatively regulates the TLR4-NF-{kappa}B pathway. Internalized particles are subsequently subjected to adaptive immunity involving major histocompatibility complex class II (MHC II) expression, recruitment of costimulatory molecules, and the modulation of the T helper (Th) responses. AM show atypical antigen presenting cell maturation in which phagocytic activity decreases while both MHC II and costimulatory molecules remain unaltered. PM drives AM towards a Th1 profile but secondary responses in a Th1- or Th-2 up-regulated milieu drive the response in favor of a Th2 profile.

  20. Innate and adaptive immune responses against picornaviruses and their counteractions: An overview

    PubMed Central

    Dotzauer, Andreas; Kraemer, Leena

    2012-01-01

    Picornaviruses, small positive-stranded RNA viruses, cause a wide range of diseases which is based on their differential tissue and cell type tropisms. This diversity is reflected by the immune responses, both innate and adaptive, induced after infection, and the subsequent interactions of the viruses with the immune system. The defense mechanisms of the host and the countermeasures of the virus significantly contribute to the pathogenesis of the infections. Important human pathogens are poliovirus, coxsackievirus, human rhinovirus and hepatitis A virus. These viruses are the best-studied members of the family, and in this review we want to present the major aspects of the reciprocal effects between the immune system and these viruses. PMID:24175214

  1. Subjectivity: A Case of Biological Individuation and an Adaptive Response to Informational Overflow.

    PubMed

    Jonkisz, Jakub

    2016-01-01

    The article presents a perspective on the scientific explanation of the subjectivity of conscious experience. It proposes plausible answers for two empirically valid questions: the 'how' question concerning the developmental mechanisms of subjectivity, and the 'why' question concerning its function. Biological individuation, which is acquired in several different stages, serves as a provisional description of how subjective perspectives may have evolved. To the extent that an individuated informational space seems the most efficient way for a given organism to select biologically valuable information, subjectivity is deemed to constitute an adaptive response to informational overflow. One of the possible consequences of this view is that subjectivity might be (at least functionally) dissociated from consciousness, insofar as the former primarily facilitates selection, the latter action. PMID:27555835

  2. Stress Responses, Adaptation, and Virulence of Bacterial Pathogens During Host Gastrointestinal Colonization.

    PubMed

    Flint, Annika; Butcher, James; Stintzi, Alain

    2016-04-01

    Invading pathogens are exposed to a multitude of harmful conditions imposed by the host gastrointestinal tract and immune system. Bacterial defenses against these physical and chemical stresses are pivotal for successful host colonization and pathogenesis. Enteric pathogens, which are encountered due to the ingestion of or contact with contaminated foods or materials, are highly successful at surviving harsh conditions to colonize and cause the onset of host illness and disease. Pathogens such as Campylobacter, Helicobacter, Salmonella, Listeria, and virulent strains of Escherichia have evolved elaborate defense mechanisms to adapt to the diverse range of stresses present along the gastrointestinal tract. Furthermore, these pathogens contain a multitude of defenses to help survive and escape from immune cells such as neutrophils and macrophages. This chapter focuses on characterized bacterial defenses against pH, osmotic, oxidative, and nitrosative stresses with emphasis on both the direct and indirect mechanisms that contribute to the survival of each respective stress response. PMID:27227312

  3. Innate and adaptive immune responses against picornaviruses and their counteractions: An overview.

    PubMed

    Dotzauer, Andreas; Kraemer, Leena

    2012-06-12

    Picornaviruses, small positive-stranded RNA viruses, cause a wide range of diseases which is based on their differential tissue and cell type tropisms. This diversity is reflected by the immune responses, both innate and adaptive, induced after infection, and the subsequent interactions of the viruses with the immune system. The defense mechanisms of the host and the countermeasures of the virus significantly contribute to the pathogenesis of the infections. Important human pathogens are poliovirus, coxsackievirus, human rhinovirus and hepatitis A virus. These viruses are the best-studied members of the family, and in this review we want to present the major aspects of the reciprocal effects between the immune system and these viruses.

  4. The adaptive response of lichens to mercury exposure involves changes in the photosynthetic machinery.

    PubMed

    Nicolardi, Valentina; Cai, Giampiero; Parrotta, Luigi; Puglia, Michele; Bianchi, Laura; Bini, Luca; Gaggi, Carlo

    2012-01-01

    Lichens are an excellent model to study the bioaccumulation of heavy metals but limited information is available on the molecular mechanisms occurring during bioaccumulation. We investigated the changes of the lichen proteome during exposure to constant concentrations of mercury. We found that most of changes involves proteins of the photosynthetic pathway, such as the chloroplastic photosystem I reaction center subunit II, the oxygen-evolving protein and the chloroplastic ATP synthase β-subunit. This suggests that photosynthesis is a target of the toxic effects of mercury. These findings are also supported by changes in the content of photosynthetic pigments (chlorophyll a and b, and β-carotene). Alterations to the photosynthetic machinery also reflect on the structure of thylakoid membranes of algal cells. Response of lichens to mercury also involves stress-related proteins (such as Hsp70) but not cytoskeletal proteins. Results suggest that lichens adapt to mercury exposure by changing the metabolic production of energy.

  5. Subjectivity: A Case of Biological Individuation and an Adaptive Response to Informational Overflow

    PubMed Central

    Jonkisz, Jakub

    2016-01-01

    The article presents a perspective on the scientific explanation of the subjectivity of conscious experience. It proposes plausible answers for two empirically valid questions: the ‘how’ question concerning the developmental mechanisms of subjectivity, and the ‘why’ question concerning its function. Biological individuation, which is acquired in several different stages, serves as a provisional description of how subjective perspectives may have evolved. To the extent that an individuated informational space seems the most efficient way for a given organism to select biologically valuable information, subjectivity is deemed to constitute an adaptive response to informational overflow. One of the possible consequences of this view is that subjectivity might be (at least functionally) dissociated from consciousness, insofar as the former primarily facilitates selection, the latter action. PMID:27555835

  6. Stress Responses, Adaptation, and Virulence of Bacterial Pathogens During Host Gastrointestinal Colonization.

    PubMed

    Flint, Annika; Butcher, James; Stintzi, Alain

    2016-04-01

    Invading pathogens are exposed to a multitude of harmful conditions imposed by the host gastrointestinal tract and immune system. Bacterial defenses against these physical and chemical stresses are pivotal for successful host colonization and pathogenesis. Enteric pathogens, which are encountered due to the ingestion of or contact with contaminated foods or materials, are highly successful at surviving harsh conditions to colonize and cause the onset of host illness and disease. Pathogens such as Campylobacter, Helicobacter, Salmonella, Listeria, and virulent strains of Escherichia have evolved elaborate defense mechanisms to adapt to the diverse range of stresses present along the gastrointestinal tract. Furthermore, these pathogens contain a multitude of defenses to help survive and escape from immune cells such as neutrophils and macrophages. This chapter focuses on characterized bacterial defenses against pH, osmotic, oxidative, and nitrosative stresses with emphasis on both the direct and indirect mechanisms that contribute to the survival of each respective stress response.

  7. Insertion of Retrotransposons at Chromosome Ends: Adaptive Response to Chromosome Maintenance

    PubMed Central

    Servant, Geraldine; Deininger, Prescott L.

    2016-01-01

    The telomerase complex is a specialized reverse transcriptase (RT) that inserts tandem DNA arrays at the linear chromosome ends and contributes to the protection of the genetic information in eukaryotic genomes. Telomerases are phylogenetically related to retrotransposons, encoding also the RT activity required for the amplification of their sequences throughout the genome. Intriguingly the telomerase gene is lost from the Drosophila genome and tandem retrotransposons replace telomeric sequences at the chromosome extremities. This observation suggests the versatility of RT activity in counteracting the chromosome shortening associated with genome replication and that retrotransposons can provide this activity in case of a dysfunctional telomerase. In this review paper, we describe the major classes of retroelements present in eukaryotic genomes in order to point out the differences and similarities with the telomerase complex. In a second part, we discuss the insertion of retroelements at the ends of chromosomes as an adaptive response for dysfunctional telomeres. PMID:26779254

  8. Single-cell responses to face adaptation in the human medial temporal lobe.

    PubMed

    Quian Quiroga, Rodrigo; Kraskov, Alexander; Mormann, Florian; Fried, Itzhak; Koch, Christof

    2014-10-22

    We used a face adaptation paradigm to bias the perception of ambiguous images of faces and study how single neurons in the human medial temporal lobe (MTL) respond to the same images eliciting different percepts. The ambiguous images were morphs between the faces of two familiar individuals, chosen because at least one MTL neuron responded selectively to one but not to the other face. We found that the firing of MTL neurons closely followed the subjects' perceptual decisions--i.e., recognizing one person or the other. In most cases, the response to the ambiguous images was similar to the one obtained when showing the pictures without morphing. Altogether, these results show that many neurons in the medial temporal lobe signal the subjects' perceptual decisions rather than the visual features of the stimulus.

  9. DNA microarray analyses of the long-term adaptive response of Escherichia coli to acetate and propionate.

    PubMed

    Polen, T; Rittmann, D; Wendisch, V F; Sahm, H

    2003-03-01

    In its natural environment, Escherichia coli is exposed to short-chain fatty acids, such as acetic acid or propionic acid, which can be utilized as carbon sources but which inhibit growth at higher concentrations. DNA microarray experiments revealed expression changes during exponential growth on complex medium due to the presence of sodium acetate or sodium propionate at a neutral external pH. The adaptive responses to acetate and propionate were similar and involved genes in three categories. First, the RNA levels for chemotaxis and flagellum genes increased. Accordingly, the expression of chromosomal fliC'-'lacZ and flhDC'-'lacZ fusions and swimming motility increased after adaptation to acetate or propionate. Second, the expression of many genes that are involved in the uptake and utilization of carbon sources decreased, indicating some kind of catabolite repression by acetate and propionate. Third, the expression of some genes of the general stress response increased, but the increases were more pronounced after short-term exposure for this response than for the adaptive response. Adaptation to propionate but not to acetate involved increased expression of threonine and isoleucine biosynthetic genes. The gene expression changes after adaptation to acetate or propionate were not caused solely by uncoupling or osmotic effects but represented specific characteristics of the long-term response of E. coli to either compound. PMID:12620868

  10. Global Transcriptional, Physiological, and Metabolite Analyses of the Responses of Desulfovibrio vulgaris Hildenborough to Salt Adaptation ▿ †

    PubMed Central

    He, Zhili; Zhou, Aifen; Baidoo, Edward; He, Qiang; Joachimiak, Marcin P.; Benke, Peter; Phan, Richard; Mukhopadhyay, Aindrila; Hemme, Christopher L.; Huang, Katherine; Alm, Eric J.; Fields, Matthew W.; Wall, Judy; Stahl, David; Hazen, Terry C.; Keasling, Jay D.; Arkin, Adam P.; Zhou, Jizhong

    2010-01-01

    The response of Desulfovibrio vulgaris Hildenborough to salt adaptation (long-term NaCl exposure) was examined by performing physiological, global transcriptional, and metabolite analyses. Salt adaptation was reflected by increased expression of genes involved in amino acid biosynthesis and transport, electron transfer, hydrogen oxidation, and general stress responses (e.g., heat shock proteins, phage shock proteins, and oxidative stress response proteins). The expression of genes involved in carbon metabolism, cell growth, and phage structures was decreased. Transcriptome profiles of D. vulgaris responses to salt adaptation were compared with transcriptome profiles of D. vulgaris responses to salt shock (short-term NaCl exposure). Metabolite assays showed that glutamate and alanine accumulated under salt adaptation conditions, suggesting that these amino acids may be used as osmoprotectants in D. vulgaris. Addition of amino acids (glutamate, alanine, and tryptophan) or yeast extract to the growth medium relieved salt-related growth inhibition. A conceptual model that links the observed results to currently available knowledge is proposed to increase our understanding of the mechanisms of D. vulgaris adaptation to elevated NaCl levels. PMID:20038696

  11. Misregulation of an adaptive metabolic response contributes to the age-related disruption of lipid homeostasis in Drosophila.

    PubMed

    Karpac, Jason; Biteau, Benoit; Jasper, Heinrich

    2013-09-26

    Loss of metabolic homeostasis is a hallmark of aging and is commonly characterized by the deregulation of adaptive signaling interactions that coordinate energy metabolism with dietary changes. The mechanisms driving age-related changes in these adaptive responses remain unclear. Here, we characterize the deregulation of an adaptive metabolic response and the development of metabolic dysfunction in the aging intestine of Drosophila. We find that activation of the insulin-responsive transcription factor Foxo in intestinal enterocytes is required to inhibit the expression of evolutionarily conserved lipases as part of a metabolic response to dietary changes. This adaptive mechanism becomes chronically activated in the aging intestine, mediated by changes in Jun-N-terminal kinase (JNK) signaling. Age-related chronic JNK/Foxo activation in enterocytes is deleterious, leading to sustained repression of intestinal lipase expression and the disruption of lipid homeostasis. Changes in the regulation of Foxo-mediated adaptive responses thus contribute to the age-associated breakdown of metabolic homeostasis.

  12. The Adaptive Significance of Natural Genetic Variation in the DNA Damage Response of Drosophila melanogaster

    PubMed Central

    Svetec, Nicolas; Cridland, Julie M.; Zhao, Li; Begun, David J.

    2016-01-01

    Despite decades of work, our understanding of the distribution of fitness effects of segregating genetic variants in natural populations remains largely incomplete. One form of selection that can maintain genetic variation is spatially varying selection, such as that leading to latitudinal clines. While the introduction of population genomic approaches to understanding spatially varying selection has generated much excitement, little successful effort has been devoted to moving beyond genome scans for selection to experimental analysis of the relevant biology and the development of experimentally motivated hypotheses regarding the agents of selection; it remains an interesting question as to whether the vast majority of population genomic work will lead to satisfying biological insights. Here, motivated by population genomic results, we investigate how spatially varying selection in the genetic model system, Drosophila melanogaster, has led to genetic differences between populations in several components of the DNA damage response. UVB incidence, which is negatively correlated with latitude, is an important agent of DNA damage. We show that sensitivity of early embryos to UVB exposure is strongly correlated with latitude such that low latitude populations show much lower sensitivity to UVB. We then show that lines with lower embryo UVB sensitivity also exhibit increased capacity for repair of damaged sperm DNA by the oocyte. A comparison of the early embryo transcriptome in high and low latitude embryos provides evidence that one mechanism of adaptive DNA repair differences between populations is the greater abundance of DNA repair transcripts in the eggs of low latitude females. Finally, we use population genomic comparisons of high and low latitude samples to reveal evidence that multiple components of the DNA damage response and both coding and non-coding variation likely contribute to adaptive differences in DNA repair between populations. PMID:26950216

  13. The Adaptive Significance of Natural Genetic Variation in the DNA Damage Response of Drosophila melanogaster.

    PubMed

    Svetec, Nicolas; Cridland, Julie M; Zhao, Li; Begun, David J

    2016-03-01

    Despite decades of work, our understanding of the distribution of fitness effects of segregating genetic variants in natural populations remains largely incomplete. One form of selection that can maintain genetic variation is spatially varying selection, such as that leading to latitudinal clines. While the introduction of population genomic approaches to understanding spatially varying selection has generated much excitement, little successful effort has been devoted to moving beyond genome scans for selection to experimental analysis of the relevant biology and the development of experimentally motivated hypotheses regarding the agents of selection; it remains an interesting question as to whether the vast majority of population genomic work will lead to satisfying biological insights. Here, motivated by population genomic results, we investigate how spatially varying selection in the genetic model system, Drosophila melanogaster, has led to genetic differences between populations in several components of the DNA damage response. UVB incidence, which is negatively correlated with latitude, is an important agent of DNA damage. We show that sensitivity of early embryos to UVB exposure is strongly correlated with latitude such that low latitude populations show much lower sensitivity to UVB. We then show that lines with lower embryo UVB sensitivity also exhibit increased capacity for repair of damaged sperm DNA by the oocyte. A comparison of the early embryo transcriptome in high and low latitude embryos provides evidence that one mechanism of adaptive DNA repair differences between populations is the greater abundance of DNA repair transcripts in the eggs of low latitude females. Finally, we use population genomic comparisons of high and low latitude samples to reveal evidence that multiple components of the DNA damage response and both coding and non-coding variation likely contribute to adaptive differences in DNA repair between populations. PMID:26950216

  14. The response of the heart to stress: a biological view of myocardial adaptation and failure.

    PubMed

    Alpert, N R; Mulieri, L A

    1987-01-01

    The response of the myocardium to persistent stress involves an increase in mass and a restructuring of the cellular and subcellular elements. The experiments described in this article are designed to test the hypothesis that the restructuring of the various systems (contractile, excitation-contraction coupling, recovery, etc.) that occurs in adaptive hypertrophy is a coordinated (matched) process. When the restructuring of the systems in response to stress occurs in an uncoordinated fashion, congestive heart failure results. In addition to controls, three heart models with normal pump performance are used (control, C; pressure overload, P; thyrotoxic, T; and pressure overload plus thyrotoxic, PT4) and one with inadequate pump performance (pressure overload plus thyrotoxic, PT2). In this analysis the contractile and excitation-contraction coupling systems are evaluated. The former is assessed by sensitive myothermal measurement of tension dependent heat (TDH) normalized for the isometric tension time integral (integral of Pdt). The latter is assessed from measurement of the time to peak isometric tension (TPT). The TDH/integral of Pdt (mu cal/g.cm.s) and TPT (ms) for the C, P, T, PT4, and PT2 hearts are 2.4, 1.8, 5.2, 5.1, and 0.1, mu cal/g.cm.s and 627, 816, 352, 484, and 465 ms, respectively. According to the coordination or matching hypothesis, if TDH/integral of Pdt is low, then TPT should be increased, or if TDH/integral of Pdt is high, then TPT should be decreased. Relative to control hearts, matched restructuring of the contractile and excitation-contraction coupling systems occurred for the P, T, and PT4 preparations. In these animals the hypertrophy has been adaptive and the pump performance is adequate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2485028

  15. Investigating the adaptive immune response in influenza and secondary bacterial pneumonia and nanoparticle based therapeutic delivery

    NASA Astrophysics Data System (ADS)

    Chakravarthy, Krishnan V.

    In early 2000, influenza and its associated complications were the 7 th leading cause of death in the United States[1-4]. As of today, this major health problem has become even more of a concern, with the possibility of a potentially devastating avian flu (H5N1) or swine flu pandemic (H1N1). According to the Centers for Disease Control (CDC), over 10 countries have reported transmission of influenza A (H5N1) virus to humans as of June 2006 [5]. In response to this growing concern, the United States pledged over $334 million dollars in international aid for battling influenza[1-4]. The major flu pandemic of the early 1900's provided the first evidence that secondary bacterial pneumonia (not primary viral pneumonia) was the major cause of death in both community and hospital-based settings. Secondary bacterial infections currently account for 35-40% mortality following a primary influenza viral infection [1, 6]. The first component of this work addresses the immunological mechanisms that predispose patients to secondary bacterial infections following a primary influenza viral infection. By assessing host immune responses through various immune-modulatory tools, such as use of volatile anesthetics (i.e. halothane) and Apilimod/STA-5326 (an IL-12/Il-23 transcription blocker), we provide experimental evidence that demonstrates that the overactive adaptive Th1 immune response is critical in mediating increased susceptibility to secondary bacterial infections. We also present data that shows that suppressing the adaptive Th1 immune response enhances innate immunity, specifically in alveolar macrophages, by favoring a pro anti-bacterial phenotype. The second component of this work addresses the use of nanotechnology to deliver therapeutic modalities that affect the primary viral and associated secondary bacterial infections post influenza. First, we used surface functionalized quantum dots for selective targeting of lung alveolar macrophages both in vitro and in vivo

  16. Innate and adaptive type 2 immune cell responses in genetically controlled resistance to intestinal helminth infection.

    PubMed

    Filbey, Kara J; Grainger, John R; Smith, Katherine A; Boon, Louis; van Rooijen, Nico; Harcus, Yvonne; Jenkins, Stephen; Hewitson, James P; Maizels, Rick M

    2014-01-01

    The nematode Heligmosomoides polygyrus is an excellent model for intestinal helminth parasitism. Infection in mice persists for varying lengths of time in different inbred strains, with CBA and C57BL/6 mice being fully susceptible, BALB/c partially so and SJL able to expel worms within 2-3 weeks of infection. We find that resistance correlates not only with the adaptive Th2 response, including IL-10 but with activation of innate lymphoid cell and macrophage populations. In addition, the titer and specificity range of the serum antibody response is maximal in resistant mice. In susceptible strains, Th2 responses were found to be counterbalanced by IFN-γ-producing CD4(+) and CD8(+) cells, but these are not solely responsible for susceptibility as mice deficient in either CD8(+) T cells or IFN-γ remain unable to expel the parasites. Foxp3(+) Treg numbers were comparable in all strains, but in the most resistant SJL strain, this population does not upregulate CD103 in infection, and in the lamina propria the frequency of Foxp3(+)CD103(+) T cells is significantly lower than in susceptible mice. The more resistant SJL and BALB/c mice develop macrophage-rich IL-4Rα-dependent Type 2 granulomas around intestinal sites of larval invasion, and expression of alternative activation markers Arginase-1, Ch3L3 (Ym1) and RELM-α within the intestine and the peritoneal lavage was also strongly correlated with helminth elimination in these strains. Clodronate depletion of phagocytic cells compromises resistance of BALB/c mice and slows expulsion in the SJL strain. Thus, Type 2 immunity involves IL-4Rα-dependent innate cells including but not limited to a phagocyte population, the latter likely involving the action of specific antibodies.

  17. Effect of antioxidant supplementation on the adaptive response of human skin fibroblasts to UV-induced oxidative stress.

    PubMed

    Jones, S A; McArdle, F; Jack, C I; Jackson, M J

    1999-01-01

    The effect of supplementation with substances having antioxidant properties on the adaptive responses of human skin fibroblasts to UV-induced oxidative stress was studied in vitro. UVR was found to induce a substantial oxidative stress in fibroblasts, resulting in an increased release of superoxide anions and an increase in lipid peroxidation (shown by an elevated malonaldehyde content). Sub-lethal doses of UVR were also found to induce adaptive responses in the fibroblast antioxidant defences, with a transient rise in catalase and superoxide dismutase activities followed by a slower, large increase in cellular glutathione content. Supplementation of the fibroblasts with the antioxidants, Trolox (a water soluble analogue of alpha-tocopherol), ascorbic acid or beta-carotene, had differential effects on these responses. Trolox supplementation reduced the UVR-induced cellular oxidative stress and adaptive response in a predictable concentration-dependent manner. This was in contrast to ascorbic acid which increased superoxide release from fibroblasts. At low doses, ascorbate supplements also reduced the magnitude of the adaptive increases in catalase and superoxide dismutase activities and increase in glutathione content. Beta-carotene had a similar effect to ascorbic acid, reducing the extent of the adaptations to UVR at lower doses while simultaneously increasing superoxide release and malonaldehyde content. These in vitro data indicate that only the vitamin E analogue suppressed UVR-induced oxidative stress in a predictable manner and suggest that common dietary antioxidants may not be equally effective in reducing the potential deleterious effects of UVR-induced oxidative stress in skin.

  18. Developing a Gene Biomarker at the Tipping Point of Adaptive and Adverse Responses in Human Bronchial Epithelial Cells.

    PubMed

    Currier, Jenna M; Cheng, Wan-Yun; Menendez, Daniel; Conolly, Rory; Chorley, Brian N

    2016-01-01

    Determining mechanism-based biomarkers that distinguish adaptive and adverse cellular processes is critical to understanding the health effects of environmental exposures. Shifting from in vivo, low-throughput toxicity studies to high-throughput screening (HTS) paradigms and risk assessment based on in vitro and in silico testing requires utilizing toxicity pathway information to distinguish adverse outcomes from recoverable adaptive events. Little work has focused on oxidative stresses in human airway for the purposes of predicting adverse responses. We hypothesize that early gene expression-mediated molecular changes could be used to delineate adaptive and adverse responses to environmentally-based perturbations. Here, we examined cellular responses of the tracheobronchial airway to zinc (Zn) exposure, a model oxidant. Airway derived BEAS-2B cells exposed to 2-10 μM Zn2+ elicited concentration- and time-dependent cytotoxicity. Normal, adaptive, and cytotoxic Zn2+ exposure conditions were determined with traditional apical endpoints, and differences in global gene expression around the tipping point of the responses were used to delineate underlying molecular mechanisms. Bioinformatic analyses of differentially expressed genes indicate early enrichment of stress signaling pathways, including those mediated by the transcription factors p53 and NRF2. After 4 h, 154 genes were differentially expressed (p < 0.01) between the adaptive and cytotoxic Zn2+ concentrations. Nearly 40% of the biomarker genes were related to the p53 signaling pathway with 30 genes identified as likely direct targets using a database of p53 ChIP-seq studies. Despite similar p53 activation profiles, these data revealed widespread dampening of p53 and NRF2-related genes as early as 4 h after exposure at higher, unrecoverable Zn2+ exposures. Thus, in our model early increased activation of stress response pathways indicated a recoverable adaptive event. Overall, this study highlights the

  19. Developing a Gene Biomarker at the Tipping Point of Adaptive and Adverse Responses in Human Bronchial Epithelial Cells

    PubMed Central

    Currier, Jenna M.; Cheng, Wan-Yun; Menendez, Daniel; Conolly, Rory; Chorley, Brian N.

    2016-01-01

    Determining mechanism-based biomarkers that distinguish adaptive and adverse cellular processes is critical to understanding the health effects of environmental exposures. Shifting from in vivo, low-throughput toxicity studies to high-throughput screening (HTS) paradigms and risk assessment based on in vitro and in silico testing requires utilizing toxicity pathway information to distinguish adverse outcomes from recoverable adaptive events. Little work has focused on oxidative stresses in human airway for the purposes of predicting adverse responses. We hypothesize that early gene expression-mediated molecular changes could be used to delineate adaptive and adverse responses to environmentally-based perturbations. Here, we examined cellular responses of the tracheobronchial airway to zinc (Zn) exposure, a model oxidant. Airway derived BEAS-2B cells exposed to 2–10 μM Zn2+ elicited concentration- and time-dependent cytotoxicity. Normal, adaptive, and cytotoxic Zn2+ exposure conditions were determined with traditional apical endpoints, and differences in global gene expression around the tipping point of the responses were used to delineate underlying molecular mechanisms. Bioinformatic analyses of differentially expressed genes indicate early enrichment of stress signaling pathways, including those mediated by the transcription factors p53 and NRF2. After 4 h, 154 genes were differentially expressed (p < 0.01) between the adaptive and cytotoxic Zn2+ concentrations. Nearly 40% of the biomarker genes were related to the p53 signaling pathway with 30 genes identified as likely direct targets using a database of p53 ChIP-seq studies. Despite similar p53 activation profiles, these data revealed widespread dampening of p53 and NRF2-related genes as early as 4 h after exposure at higher, unrecoverable Zn2+ exposures. Thus, in our model early increased activation of stress response pathways indicated a recoverable adaptive event. Overall, this study highlights the

  20. In Vivo Synthesis of Cyclic-di-GMP Using a Recombinant Adenovirus Preferentially Improves Adaptive Immune Responses against Extracellular Antigens.

    PubMed

    Alyaqoub, Fadel S; Aldhamen, Yasser A; Koestler, Benjamin J; Bruger, Eric L; Seregin, Sergey S; Pereira-Hicks, Cristiane; Godbehere, Sarah; Waters, Christopher M; Amalfitano, Andrea

    2016-02-15

    There is a compelling need for more effective vaccine adjuvants to augment induction of Ag-specific adaptive immune responses. Recent reports suggested the bacterial second messenger bis-(3'-5')-cyclic-dimeric-guanosine monophosphate (c-di-GMP) acts as an innate immune system modulator. We recently incorporated a Vibrio cholerae diguanylate cyclase into an adenovirus vaccine, fostering production of c-di-GMP as well as proinflammatory responses in mice. In this study, we recombined a more potent diguanylate cyclase gene, VCA0848, into a nonreplicating adenovirus serotype 5 (AdVCA0848) that produces elevated amounts of c-di-GMP when expressed in mammalian cells in vivo. This novel platform further improved induction of type I IFN-β and activation of innate and adaptive immune cells early after administration into mice as compared with control vectors. Coadministration of the extracellular protein OVA and the AdVCA0848 adjuvant significantly improved OVA-specific T cell responses as detected by IFN-γ and IL-2 ELISPOT, while also improving OVA-specific humoral B cell adaptive responses. In addition, we found that coadministration of AdVCA0848 with another adenovirus serotype 5 vector expressing the HIV-1-derived Gag Ag or the Clostridium difficile-derived toxin B resulted in significant inhibitory effects on the induction of Gag and toxin B-specific adaptive immune responses. As a proof of principle, these data confirm that in vivo synthesis of c-di-GMP stimulates strong innate immune responses that correlate with enhanced adaptive immune responses to concomitantly administered extracellular Ag, which can be used as an adjuvant to heighten effective immune responses for protein-based vaccine platforms against microbial infections and cancers. PMID:26792800

  1. In Vivo Synthesis of Cyclic-di-GMP Using a Recombinant Adenovirus Preferentially Improves Adaptive Immune Responses against Extracellular Antigens.

    PubMed

    Alyaqoub, Fadel S; Aldhamen, Yasser A; Koestler, Benjamin J; Bruger, Eric L; Seregin, Sergey S; Pereira-Hicks, Cristiane; Godbehere, Sarah; Waters, Christopher M; Amalfitano, Andrea

    2016-02-15

    There is a compelling need for more effective vaccine adjuvants to augment induction of Ag-specific adaptive immune responses. Recent reports suggested the bacterial second messenger bis-(3'-5')-cyclic-dimeric-guanosine monophosphate (c-di-GMP) acts as an innate immune system modulator. We recently incorporated a Vibrio cholerae diguanylate cyclase into an adenovirus vaccine, fostering production of c-di-GMP as well as proinflammatory responses in mice. In this study, we recombined a more potent diguanylate cyclase gene, VCA0848, into a nonreplicating adenovirus serotype 5 (AdVCA0848) that produces elevated amounts of c-di-GMP when expressed in mammalian cells in vivo. This novel platform further improved induction of type I IFN-β and activation of innate and adaptive immune cells early after administration into mice as compared with control vectors. Coadministration of the extracellular protein OVA and the AdVCA0848 adjuvant significantly improved OVA-specific T cell responses as detected by IFN-γ and IL-2 ELISPOT, while also improving OVA-specific humoral B cell adaptive responses. In addition, we found that coadministration of AdVCA0848 with another adenovirus serotype 5 vector expressing the HIV-1-derived Gag Ag or the Clostridium difficile-derived toxin B resulted in significant inhibitory effects on the induction of Gag and toxin B-specific adaptive immune responses. As a proof of principle, these data confirm that in vivo synthesis of c-di-GMP stimulates strong innate immune responses that correlate with enhanced adaptive immune responses to concomitantly administered extracellular Ag, which can be used as an adjuvant to heighten effective immune responses for protein-based vaccine platforms against microbial infections and cancers.

  2. Photosynthetic responses mediate the adaptation of two Lotus japonicus ecotypes to low temperature.

    PubMed

    Calzadilla, Pablo Ignacio; Signorelli, Santiago; Escaray, Francisco Jose; Menéndez, Ana Bernardina; Monza, Jorge; Ruiz, Oscar Adolfo; Maiale, Santiago Javier

    2016-09-01

    Lotus species are important forage legumes due to their high nutritional value and adaptability to marginal conditions. However, the dry matter production and regrowth rate of cultivable Lotus spp. is drastically reduced during colder seasons. In this work, we evaluated the chilling response of Lotus japonicus ecotypes MG-1 and MG-20. No significant increases were observed in reactive oxygen species and nitric oxide production or in lipid peroxidation, although a chilling-induced redox imbalance was suggested through NADPH/NADP(+) ratio alterations. Antioxidant enzyme catalase, ascorbate peroxidase, and superoxide dismutase activities were also measured. Superoxide dismutase, in particular the chloroplastic isoform, showed different activity for different ecotypes and treatments. Stress-induced photoinhibition also differentially influenced both ecotypes, with MG-1 more affected than MG-20. Data showed that the D2 PSII subunit was more affected than D1 after 1 d of low temperature exposure, although its protein levels recovered over the course of the experiment. Interestingly, D2 recovery was accompanied by improvements in photosynthetic parameters (Asat and Fv/Fm) and the NADPH/NADP(+) ratio. Our results suggest that the D2 protein is involved in the acclimation response of L. japonicus to low temperature. This may provide a deeper insight into the chilling tolerance mechanisms of the Lotus genus.

  3. Genomic Response to Selection for Predatory Behavior in a Mammalian Model of Adaptive Radiation.

    PubMed

    Konczal, Mateusz; Koteja, Paweł; Orlowska-Feuer, Patrycja; Radwan, Jacek; Sadowska, Edyta T; Babik, Wiesław

    2016-09-01

    If genetic architectures of various quantitative traits are similar, as studies on model organisms suggest, comparable selection pressures should produce similar molecular patterns for various traits. To test this prediction, we used a laboratory model of vertebrate adaptive radiation to investigate the genetic basis of the response to selection for predatory behavior and compare it with evolution of aerobic capacity reported in an earlier work. After 13 generations of selection, the proportion of bank voles (Myodes [=Clethrionomys] glareolus) showing predatory behavior was five times higher in selected lines than in controls. We analyzed the hippocampus and liver transcriptomes and found repeatable changes in allele frequencies and gene expression. Genes with the largest differences between predatory and control lines are associated with hunger, aggression, biological rhythms, and functioning of the nervous system. Evolution of predatory behavior could be meaningfully compared with evolution of high aerobic capacity, because the experiments and analyses were performed in the same methodological framework. The number of genes that changed expression was much smaller in predatory lines, and allele frequencies changed repeatably in predatory but not in aerobic lines. This suggests that more variants of smaller effects underlie variation in aerobic performance, whereas fewer variants of larger effects underlie variation in predatory behavior. Our results thus contradict the view that comparable selection pressures for different quantitative traits produce similar molecular patterns. Therefore, to gain knowledge about molecular-level response to selection for complex traits, we need to investigate not only multiple replicate populations but also multiple quantitative traits.

  4. Dietary methionine restriction in mice elicits an adaptive cardiovascular response to hyperhomocysteinemia.

    PubMed

    Ables, Gene P; Ouattara, Amadou; Hampton, Thomas G; Cooke, Diana; Perodin, Frantz; Augie, Ines; Orentreich, David S

    2015-03-06

    Dietary methionine restriction (MR) in rodents increased lifespan despite higher heart-to-body weight ratio (w/w) and hyperhomocysteinemia, which are symptoms associated with increased risk for cardiovascular disease. We investigated this paradoxical effect of MR on cardiac function using young, old, and apolipoprotein E-deficient (ApoE-KO) mice. Indeed, MR animals exhibited higher heart-to-body weight ratio (w/w) and hyperhomocysteinemia with a molecular pattern consistent with cardiac stress while maintaining the integrity of cardiac structure. Baseline cardiac function, which was measured by non-invasive electrocardiography (ECG), showed that young MR mice had prolonged QRS intervals compared with control-fed (CF) mice, whereas old and ApoE-KO mice showed similar results for both groups. Following β-adrenergic challenge, responses of MR mice were either similar or attenuated compared with CF mice. Cardiac contractility, which was measured by isolated heart retrograde perfusion, was similar in both groups of old mice. Finally, the MR diet induced secretion of cardioprotective hormones, adiponectin and fibroblast growth factor 21 (FGF21), in MR mice with concomitant alterations in cardiac metabolic molecular signatures. Our findings demonstrate that MR diet does not alter cardiac function in mice despite the presence of hyperhomocysteinemia because of the adaptive responses of increased adiponectin and FGF21 levels.

  5. "My worries are rational, climate change is not": habitual ecological worrying is an adaptive response.

    PubMed

    Verplanken, Bas; Roy, Deborah

    2013-01-01

    Qualifications such as "global warming hysteria" and "energy policy schizophrenia" put forward by some climate change skeptics, usually outside the academic arena, may suggest that people who seriously worry about the environment suffer from psychological imbalance. The present study aimed to refute this thesis. While habitual worrying in general is strongly associated with psychopathological symptoms, in a survey a near-zero correlation was found between habitual ecological worrying and pathological worry. Instead, habitual ecological worrying was associated with pro-environmental attitudes and behaviors, and with a personality structure characterized by imagination and an appreciation for new ideas. The study had sufficient statistical power and measures were valid and reliable. The results confirm that those who habitually worry about the ecology are not only lacking in any psychopathology, but demonstrate a constructive and adaptive response to a serious problem. In the public domain, these findings may contribute to a more rational and less emotional debate on climate change and to the prevention of stigmatization of people who are genuinely concerned about our habitat and are prepared to do something about it ("habitual worriers are not crazy"). In the academic arena this study may contribute to environmental psychology ("habitual worrying is part of a green identity"), as well as to the literature on worry and anxiety ("habitual worrying can be a constructive response"). PMID:24023958

  6. Genomic Response to Selection for Predatory Behavior in a Mammalian Model of Adaptive Radiation.

    PubMed

    Konczal, Mateusz; Koteja, Paweł; Orlowska-Feuer, Patrycja; Radwan, Jacek; Sadowska, Edyta T; Babik, Wiesław

    2016-09-01

    If genetic architectures of various quantitative traits are similar, as studies on model organisms suggest, comparable selection pressures should produce similar molecular patterns for various traits. To test this prediction, we used a laboratory model of vertebrate adaptive radiation to investigate the genetic basis of the response to selection for predatory behavior and compare it with evolution of aerobic capacity reported in an earlier work. After 13 generations of selection, the proportion of bank voles (Myodes [=Clethrionomys] glareolus) showing predatory behavior was five times higher in selected lines than in controls. We analyzed the hippocampus and liver transcriptomes and found repeatable changes in allele frequencies and gene expression. Genes with the largest differences between predatory and control lines are associated with hunger, aggression, biological rhythms, and functioning of the nervous system. Evolution of predatory behavior could be meaningfully compared with evolution of high aerobic capacity, because the experiments and analyses were performed in the same methodological framework. The number of genes that changed expression was much smaller in predatory lines, and allele frequencies changed repeatably in predatory but not in aerobic lines. This suggests that more variants of smaller effects underlie variation in aerobic performance, whereas fewer variants of larger effects underlie variation in predatory behavior. Our results thus contradict the view that comparable selection pressures for different quantitative traits produce similar molecular patterns. Therefore, to gain knowledge about molecular-level response to selection for complex traits, we need to investigate not only multiple replicate populations but also multiple quantitative traits. PMID:27401229

  7. Photosynthetic responses mediate the adaptation of two Lotus japonicus ecotypes to low temperature.

    PubMed

    Calzadilla, Pablo Ignacio; Signorelli, Santiago; Escaray, Francisco Jose; Menéndez, Ana Bernardina; Monza, Jorge; Ruiz, Oscar Adolfo; Maiale, Santiago Javier

    2016-09-01

    Lotus species are important forage legumes due to their high nutritional value and adaptability to marginal conditions. However, the dry matter production and regrowth rate of cultivable Lotus spp. is drastically reduced during colder seasons. In this work, we evaluated the chilling response of Lotus japonicus ecotypes MG-1 and MG-20. No significant increases were observed in reactive oxygen species and nitric oxide production or in lipid peroxidation, although a chilling-induced redox imbalance was suggested through NADPH/NADP(+) ratio alterations. Antioxidant enzyme catalase, ascorbate peroxidase, and superoxide dismutase activities were also measured. Superoxide dismutase, in particular the chloroplastic isoform, showed different activity for different ecotypes and treatments. Stress-induced photoinhibition also differentially influenced both ecotypes, with MG-1 more affected than MG-20. Data showed that the D2 PSII subunit was more affected than D1 after 1 d of low temperature exposure, although its protein levels recovered over the course of the experiment. Interestingly, D2 recovery was accompanied by improvements in photosynthetic parameters (Asat and Fv/Fm) and the NADPH/NADP(+) ratio. Our results suggest that the D2 protein is involved in the acclimation response of L. japonicus to low temperature. This may provide a deeper insight into the chilling tolerance mechanisms of the Lotus genus. PMID:27457984

  8. Adaptive peripheral immune response increases proliferation of neural precursor cells in the adult hippocampus.

    PubMed

    Wolf, Susanne A; Steiner, Barbara; Wengner, Antje; Lipp, Martin; Kammertoens, Thomas; Kempermann, Gerd

    2009-09-01

    To understand the link between peripheral immune activation and neuronal precursor biology, we investigated the effect of T-cell activation on adult hippocampal neurogenesis in female C57Bl/6 mice. A peripheral adaptive immune response triggered by adjuvant-induced rheumatoid arthritis (2 microg/microl methylated BSA) or staphylococcus enterotoxin B (EC(50) of 0.25 microg/ml per 20 g body weight) was associated with a transient increase in hippocampal precursor cell proliferation and neurogenesis as assessed by immunohistochemistry and confocal microscopy. Both treatments were paralleled by an increase in corticosterone levels in the hippocampus 1- to 2-fold over the physiological amount measured by quantitative radioimmunoassay. In contrast, intraperitoneal administration of the innate immune response activator lipopolysaccaride (EC(50) of 0.5 microg/ml per 20 g body weight) led to a chronic 5-fold increase of hippocampal glucocorticoid levels and a decrease of adult neurogenesis. In vitro exposure of murine neuronal progenitor cells to corticosterone triggered either cell death at high (1.5 nM) or proliferation at low (0.25 nM) concentrations. This effect could be blocked using a viral vector system expressing a transdomain of the glucocorticoid receptor. We suggest an evolutionary relevant communication route for the brain to respond to environmental stressors like inflammation mediated by glucocorticoid levels in the hippocampus.

  9. Dietary methionine restriction in mice elicits an adaptive cardiovascular response to hyperhomocysteinemia.

    PubMed

    Ables, Gene P; Ouattara, Amadou; Hampton, Thomas G; Cooke, Diana; Perodin, Frantz; Augie, Ines; Orentreich, David S

    2015-01-01

    Dietary methionine restriction (MR) in rodents increased lifespan despite higher heart-to-body weight ratio (w/w) and hyperhomocysteinemia, which are symptoms associated with increased risk for cardiovascular disease. We investigated this paradoxical effect of MR on cardiac function using young, old, and apolipoprotein E-deficient (ApoE-KO) mice. Indeed, MR animals exhibited higher heart-to-body weight ratio (w/w) and hyperhomocysteinemia with a molecular pattern consistent with cardiac stress while maintaining the integrity of cardiac structure. Baseline cardiac function, which was measured by non-invasive electrocardiography (ECG), showed that young MR mice had prolonged QRS intervals compared with control-fed (CF) mice, whereas old and ApoE-KO mice showed similar results for both groups. Following β-adrenergic challenge, responses of MR mice were either similar or attenuated compared with CF mice. Cardiac contractility, which was measured by isolated heart retrograde perfusion, was similar in both groups of old mice. Finally, the MR diet induced secretion of cardioprotective hormones, adiponectin and fibroblast growth factor 21 (FGF21), in MR mice with concomitant alterations in cardiac metabolic molecular signatures. Our findings demonstrate that MR diet does not alter cardiac function in mice despite the presence of hyperhomocysteinemia because of the adaptive responses of increased adiponectin and FGF21 levels. PMID:25744495

  10. Responses of the autonomic nervous system in altitude adapted and high altitude pulmonary oedema subjects

    NASA Astrophysics Data System (ADS)

    Mathew, Lazar; Purkayastha, S. S.; Jayashankar, A.; Radhakrishnan, U.; Sen Gupta, J.; Nayar, H. S.

    1985-06-01

    Studies were carried out to ascertain the role of sympatho-parasympathetic responses in the process of adaptation to altitude. The assessment of status of autonomic balance was carried out in a group of 20 young male subjects by recording their resting heart rate, blood pressure, oral temperature, mean skin temperature, extremity temperatures, pupillary diameter, cold pressor response, oxygen consumption, cardioacceleration during orthostasis and urinary excretion of catecholamines; in a thermoneutral laboratory. The same parameters were repeated on day 3 and at weekly intervals for a period of 3 weeks, after exposing them to 3,500 m; and also after return to sea level. At altitude, similar studies were carried out in a group of 10 acclimatized lowlanders, 10 high altitude natives and 6 patients who had recently recovered from high altitude pulmonary oedema. In another phase, similar studies were done in two groups of subjects, one representing 15 subjects who had stayed at altitude (3,500 4,000 m) without any ill effects and the other comprising of 10 subjects who had either suffered from high altitude pulmonary oedema (HAPO) or acute mountain sickness (AMS). The results revealed sympathetic overactivity on acute induction to altitude which showed gradual recovery on prolonged stay, the high altitude natives had preponderance to parasympathetic system. Sympathetic preponderance may not be an essential etiological factor for the causation of maladaptation syndromes.

  11. A review of adaptive mechanisms in cell responses towards oxidative stress caused by dental resin monomers.

    PubMed

    Krifka, Stephanie; Spagnuolo, Gianrico; Schmalz, Gottfried; Schweikl, Helmut

    2013-06-01

    Dental composite resins are biomaterials commonly used to aesthetically restore the structure and function of teeth impaired by caries, erosion, or fracture. Residual monomers released from resin restorations as a result of incomplete polymerization processes interact with living oral tissues. Monomers like triethylene glycol dimethacrylate (TEGDMA) or 2-hydroxylethyl methacrylate (HEMA) are cytotoxic via apoptosis, induce genotoxic effects, and delay the cell cycle. Monomers also influence the response of cells of the innate immune system, inhibit specific odontoblast cell functions, or delay the odontogenic differentiation and mineralization processes in pulp-derived cells including stem cells. These observations indicate that resin monomers act as environmental stressors which inevitably disturb regulatory cellular networks through interference with signal transduction pathways. We hypothesize that an understanding of the cellular mechanisms underlying these phenomena will provide a better estimation of the consequences associated with dental therapy using composite materials, and lead to innovative therapeutic strategies and improved materials being used at tissue interfaces within the oral cavity. Current findings strongly suggest that monomers enhance the formation of reactive oxygen species (ROS), which is most likely the cause of biological reactions activated by dental composites and resin monomers. The aim of the present review manuscript is to discuss adaptive cell responses to oxidative stress caused by monomers. The particular significance of a tightly controlled network of non-enzymatic as well as enzymatic antioxidants for the regulation of cellular redox homeostasis and antioxidant defense in monomer-exposed cells will be addressed. The expression of ROS-metabolizing antioxidant enzymes like superoxide dismutase (SOD1), glutathione peroxidase (GPx1/2), and catalase in cells exposed to monomers will be discussed with particular emphasis on the role

  12. A review of adaptive mechanisms in cell responses towards oxidative stress caused by dental resin monomers.

    PubMed

    Krifka, Stephanie; Spagnuolo, Gianrico; Schmalz, Gottfried; Schweikl, Helmut

    2013-06-01

    Dental composite resins are biomaterials commonly used to aesthetically restore the structure and function of teeth impaired by caries, erosion, or fracture. Residual monomers released from resin restorations as a result of incomplete polymerization processes interact with living oral tissues. Monomers like triethylene glycol dimethacrylate (TEGDMA) or 2-hydroxylethyl methacrylate (HEMA) are cytotoxic via apoptosis, induce genotoxic effects, and delay the cell cycle. Monomers also influence the response of cells of the innate immune system, inhibit specific odontoblast cell functions, or delay the odontogenic differentiation and mineralization processes in pulp-derived cells including stem cells. These observations indicate that resin monomers act as environmental stressors which inevitably disturb regulatory cellular networks through interference with signal transduction pathways. We hypothesize that an understanding of the cellular mechanisms underlying these phenomena will provide a better estimation of the consequences associated with dental therapy using composite materials, and lead to innovative therapeutic strategies and improved materials being used at tissue interfaces within the oral cavity. Current findings strongly suggest that monomers enhance the formation of reactive oxygen species (ROS), which is most likely the cause of biological reactions activated by dental composites and resin monomers. The aim of the present review manuscript is to discuss adaptive cell responses to oxidative stress caused by monomers. The particular significance of a tightly controlled network of non-enzymatic as well as enzymatic antioxidants for the regulation of cellular redox homeostasis and antioxidant defense in monomer-exposed cells will be addressed. The expression of ROS-metabolizing antioxidant enzymes like superoxide dismutase (SOD1), glutathione peroxidase (GPx1/2), and catalase in cells exposed to monomers will be discussed with particular emphasis on the role

  13. Adaptability: How Students' Responses to Uncertainty and Novelty Predict Their Academic and Non-Academic Outcomes

    ERIC Educational Resources Information Center

    Martin, Andrew J.; Nejad, Harry G.; Colmar, Susan; Liem, Gregory Arief D.

    2013-01-01

    Adaptability is defined as appropriate cognitive, behavioral, and/or affective adjustment in the face of uncertainty and novelty. Building on prior measurement work demonstrating the psychometric properties of an adaptability construct, the present study investigates dispositional predictors (personality, implicit theories) of adaptability, and…

  14. Tissue mechanics govern the rapidly adapting and symmetrical response to touch.

    PubMed

    Eastwood, Amy L; Sanzeni, Alessandro; Petzold, Bryan C; Park, Sung-Jin; Vergassola, Massimo; Pruitt, Beth L; Goodman, Miriam B

    2015-12-15

    Interactions with the physical world are deeply rooted in our sense of touch and depend on ensembles of somatosensory neurons that invade and innervate the skin. Somatosensory neurons convert the mechanical energy delivered in each touch into excitatory membrane currents carried by mechanoelectrical transduction (MeT) channels. Pacinian corpuscles in mammals and touch receptor neurons (TRNs) in Caenorhabditis elegans nematodes are embedded in distinctive specialized accessory structures, have low thresholds for activation, and adapt rapidly to the application and removal of mechanical loads. Recently, many of the protein partners that form native MeT channels in these and other somatosensory neurons have been identified. However, the biophysical mechanism of symmetric responses to the onset and offset of mechanical stimulation has eluded understanding for decades. Moreover, it is not known whether applied force or the resulting indentation activate MeT channels. Here, we introduce a system for simultaneously recording membrane current, applied force, and the resulting indentation in living C. elegans (Feedback-controlled Application of mechanical Loads Combined with in vivo Neurophysiology, FALCON) and use it, together with modeling, to study these questions. We show that current amplitude increases with indentation, not force, and that fast stimuli evoke larger currents than slower stimuli producing the same or smaller indentation. A model linking body indentation to MeT channel activation through an embedded viscoelastic element reproduces the experimental findings, predicts that the TRNs function as a band-pass mechanical filter, and provides a general mechanism for symmetrical and rapidly adapting MeT channel activation relevant to somatosensory neurons across phyla and submodalities.

  15. Different Responses to Heat Shock Stress Revealed Heteromorphic Adaptation Strategy of Pyropia haitanensis (Bangiales, Rhodophyta)

    PubMed Central

    Zhu, Zhujun; Yang, Rui; Qian, Feijian; Chen, Haimin; Yan, Xiaojun

    2014-01-01

    Pyropia has a unique heteromorphic life cycle with alternation stages between thallus and conchocelis, which lives at different water temperatures in different seasons. To better understand the different adaptation strategies for temperature stress, we tried to observe comparative biochemical changes of Pyropia haitanensis based on a short term heat shock model. The results showed that: (1) At normal temperature, free-living conchocelis contains significantly higher levels of H2O2, fatty acid-derived volatiles, the copy number of Phrboh and Phhsp70 genes,the activities of NADPH oxidase and floridoside than those in thallus. The released H2O2 and NADPH oxidase activity of conchocelis were more than 7 times higher than those of thallus. The copy number of Phrboh in conchocelis was 32 times that in thallus. (2) After experiencing heat shock at 35°C for 30 min, the H2O2 contents, the mRNA levels of Phrboh and Phhsp70, NADPH oxidase activity and the floridoside content in thallus were all significantly increased. The mRNA levels of Phrboh increased 5.78 times in 5 min, NADPH oxidase activity increased 8.45 times in 20 min. (3) Whereas, in conchocelis, the changes in fatty acids and their down-stream volatiles predominated, significantly increasing levels of saturated fatty acids and decreasing levels of polyunsaturated fatty acids occurred, and the 8-carbon volatiles were accumulated. However, the changes in H2O2 content and expression of oxidant-related genes and enzymatic activity were not obvious. Overall, these results indicate that conchocelis maintains a high level of active protective apparatus to endure its survival at high temperature, while thallus exhibit typical stress responses to heat shock. It is concluded that Pyropia haitanensis has evolved a delicate strategy for temperature adaptation for its heteromorphic life cycle. PMID:24709783

  16. Titin isoform switching is a major cardiac adaptive response in hibernating grizzly bears.

    PubMed

    Nelson, O Lynne; Robbins, Charles T; Wu, Yiming; Granzier, Henk

    2008-07-01

    The hibernation phenomenon captures biological as well as clinical interests to understand how organs adapt. Here we studied how hibernating grizzly bears (Ursus arctos horribilis) tolerate extremely low heart rates without developing cardiac chamber dilation. We evaluated cardiac filling function in unanesthetized grizzly bears by echocardiography during the active and hibernating period. Because both collagen and titin are involved in altering diastolic function, we investigated both in the myocardium of active and hibernating grizzly bears. Heart rates were reduced from 84 beats/min in active bears to 19 beats/min in hibernating bears. Diastolic volume, stroke volume, and left ventricular ejection fraction were not different. However, left ventricular muscle mass was significantly lower (300 +/- 12 compared with 402 +/- 14 g; P = 0.003) in the hibernating bears, and as a result the diastolic volume-to-left ventricular muscle mass ratio was significantly greater. Early ventricular filling deceleration times (106.4 +/- 14 compared with 143.2 +/- 20 ms; P = 0.002) were shorter during hibernation, suggesting increased ventricular stiffness. Restrictive pulmonary venous flow patterns supported this conclusion. Collagen type I and III comparisons did not reveal differences between the two groups of bears. In contrast, the expression of titin was altered by a significant upregulation of the stiffer N2B isoform at the expense of the more compliant N2BA isoform. The mean ratio of N2BA to N2B titin was 0.73 +/- 0.07 in the active bears and decreased to 0.42 +/- 0.03 (P = 0.006) in the hibernating bears. The upregulation of stiff N2B cardiac titin is a likely explanation for the increased ventricular stiffness that was revealed by echocardiography, and we propose that it plays a role in preventing chamber dilation in hibernating grizzly bears. Thus our work identified changes in the alternative splicing of cardiac titin as a major adaptive response in hibernating grizzly

  17. Titin isoform switching is a major cardiac adaptive response in hibernating grizzly bears.

    PubMed

    Nelson, O Lynne; Robbins, Charles T; Wu, Yiming; Granzier, Henk

    2008-07-01

    The hibernation phenomenon captures biological as well as clinical interests to understand how organs adapt. Here we studied how hibernating grizzly bears (Ursus arctos horribilis) tolerate extremely low heart rates without developing cardiac chamber dilation. We evaluated cardiac filling function in unanesthetized grizzly bears by echocardiography during the active and hibernating period. Because both collagen and titin are involved in altering diastolic function, we investigated both in the myocardium of active and hibernating grizzly bears. Heart rates were reduced from 84 beats/min in active bears to 19 beats/min in hibernating bears. Diastolic volume, stroke volume, and left ventricular ejection fraction were not different. However, left ventricular muscle mass was significantly lower (300 +/- 12 compared with 402 +/- 14 g; P = 0.003) in the hibernating bears, and as a result the diastolic volume-to-left ventricular muscle mass ratio was significantly greater. Early ventricular filling deceleration times (106.4 +/- 14 compared with 143.2 +/- 20 ms; P = 0.002) were shorter during hibernation, suggesting increased ventricular stiffness. Restrictive pulmonary venous flow patterns supported this conclusion. Collagen type I and III comparisons did not reveal differences between the two groups of bears. In contrast, the expression of titin was altered by a significant upregulation of the stiffer N2B isoform at the expense of the more compliant N2BA isoform. The mean ratio of N2BA to N2B titin was 0.73 +/- 0.07 in the active bears and decreased to 0.42 +/- 0.03 (P = 0.006) in the hibernating bears. The upregulation of stiff N2B cardiac titin is a likely explanation for the increased ventricular stiffness that was revealed by echocardiography, and we propose that it plays a role in preventing chamber dilation in hibernating grizzly bears. Thus our work identified changes in the alternative splicing of cardiac titin as a major adaptive response in hibernating grizzly

  18. Adaptive growth of tree root systems in response to wind action and site conditions.

    PubMed

    Nicoll, Bruce C.; Ray, Duncan

    1996-01-01

    Soil-root plate dimensions and structural root architecture were examined on 46-year-old Sitka spruce (Picea sitchensis (Bong.) Carr.) trees that had been mechanically uprooted. Rooting depth was restricted by a water table, and root system morphology had adapted to resist the wind movement associated with shallow rooting. The spread of the root system and the ratio of root mass to shoot mass (root/shoot ratio) were both negatively related to soil-root plate depth. Root systems had more structural root mass on the leeward side than the windward side of the tree relative to the prevailing wind direction. Cross sections of structural roots were obtained at distances of 0.5, 0.75, 1.0, and 1.25 m from the tree center. Buttressed parts of roots had greater lateral and vertical secondary thickening above rather than below the biological center. This uneven growth, which produced a shape similar in cross section to a T-beam, was greater on the leeward side of the tree, and was greatest at 0.5 m from the tree center of shallow rooted trees. Further from the tree, particularly on the windward side, many roots developed eccentric cross-sectional shapes comparable to I-beams, which would efficiently resist vertical flexing. Roots became more ovoid in shape with increasing distance from the tree, especially on deep rooted trees where lateral roots tapered rapidly to a small diameter. We conclude that these forms of adaptive growth in response to wind movement improve the rigidity of the soil-root plate and counteract the increasing vulnerability to windthrow as the tree grows.

  19. Tissue mechanics govern the rapidly adapting and symmetrical response to touch

    PubMed Central

    Eastwood, Amy L.; Sanzeni, Alessandro; Petzold, Bryan C.; Park, Sung-Jin; Vergassola, Massimo; Pruitt, Beth L.

    2015-01-01

    Interactions with the physical world are deeply rooted in our sense of touch and depend on ensembles of somatosensory neurons that invade and innervate the skin. Somatosensory neurons convert the mechanical energy delivered in each touch into excitatory membrane currents carried by mechanoelectrical transduction (MeT) channels. Pacinian corpuscles in mammals and touch receptor neurons (TRNs) in Caenorhabditis elegans nematodes are embedded in distinctive specialized accessory structures, have low thresholds for activation, and adapt rapidly to the application and removal of mechanical loads. Recently, many of the protein partners that form native MeT channels in these and other somatosensory neurons have been identified. However, the biophysical mechanism of symmetric responses to the onset and offset of mechanical stimulation has eluded understanding for decades. Moreover, it is not known whether applied force or the resulting indentation activate MeT channels. Here, we introduce a system for simultaneously recording membrane current, applied force, and the resulting indentation in living C. elegans (Feedback-controlled Application of mechanical Loads Combined with in vivo Neurophysiology, FALCON) and use it, together with modeling, to study these questions. We show that current amplitude increases with indentation, not force, and that fast stimuli evoke larger currents than slower stimuli producing the same or smaller indentation. A model linking body indentation to MeT channel activation through an embedded viscoelastic element reproduces the experimental findings, predicts that the TRNs function as a band-pass mechanical filter, and provides a general mechanism for symmetrical and rapidly adapting MeT channel activation relevant to somatosensory neurons across phyla and submodalities. PMID:26627717

  20. Hurricane Sandy: Caught in the eye of the storm and a city's adaptation response

    NASA Astrophysics Data System (ADS)

    Orton, P. M.; Horton, R. M.; Blumberg, A. F.; Rosenzweig, C.; Solecki, W.; Bader, D.

    2015-12-01

    The NOAA RISA program has funded the seven-institution Consortium for Climate Risk in the Urban Northeast (CCRUN) for the past five years to serve stakeholder needs in assessing and managing risks from climate variability and change. When Hurricane Sandy struck, we were in an ideal position, making flood forecasts and communicating NOAA forecasts to the public with dozens of media placements, translating the poorly understood flood forecasts into human dimensions. In 2013 and 2015, by request of New York City (NYC), we worked through the NYC Panel on Climate Change to deliver updated climate risk assessment reports, to be used in the post-Sandy rebuilding and resiliency efforts. These utilized innovative methodologies for probabilistic local and regional sea level change projections, and contrasted methods of dynamic versus (the more common) static flood mapping. We participated in a federal-academic partnership that developed a Sea Level Tool for Sandy Recovery that integrates CCRUN sea level rise projections with policy-relevant FEMA flood maps, and now several updated flood maps and coastal flood mapping tools (NOAA, FEMA, and USACE) incorporate our projections. For the adaptation response, we helped develop NYC's $20 billion flood adaptation plan, and we were on a winning team under the Housing and Urban Development Rebuild By Design (RBD) competition, a few of the many opportunities that arose with negligible additional funding and which CCRUN funds supported. Our work at times disrupted standard lines of thinking, but NYC showed an openness to altering course. In one case we showed that an NYC plan of wetland restoration in Jamaica Bay would provide no reduction in flooding unless deep-dredged channels circumventing them were shallowed or narrowed. In another, the lead author's RBD team challenged the notion at one location that levees were the solution to accelerating sea level rise, developing a plan to use ecological breakwaters and layered components of

  1. Adaptive responses of energy storage and fish life histories to climatic gradients.

    PubMed

    Giacomini, Henrique C; Shuter, Brian J

    2013-12-21

    Energy storage is a common adaptation of fish living in seasonal environments. For some species, the energy accumulated during the growing season, and stored primarily as lipids, is crucial to preventing starvation mortality over winter. Thus, in order to understand the adaptive responses of fish life history to climate, it is important to determine how energy should be allocated to storage and how it trades off with the other body components that contribute to fitness. In this paper, we extend previous life history theory to include an explicit representation of how the seasonal allocation of energy to storage acts as a constraint on fish growth. We show that a strategy that privileges allocation to structural mass in the first part of the growing season and switches to storage allocation later on, as observed empirically in several fish species, is the strategy that maximizes growth efficiency and hence is expected to be favored by natural selection. Stochastic simulations within this theoretical framework demonstrate that the relative performance of this switching strategy is robust to a wide range of fluctuations in growing season length, and to moderate short-term (i.e., daily) fluctuations in energy intake and/or expenditure within the growing season. We then integrate this switching strategy with a biphasic growth modeling framework to predict typical growth rates of walleye Sander vitreus, a cool water species, and lake trout Salvelinus namaycush, a cold water specialist, across a climatic gradient in North America. As predicted, growth rates increased linearly with the duration of the growing season. Regression line intercepts were negative, indicating that growth can only occur when growing season length exceeds a threshold necessary to produce storage for winter survival. The model also reveals important differences between species, showing that observed growth rates of lake trout are systematically higher than those of walleye in relatively colder lakes

  2. Adaptation of the Agrobacterium tumefaciens VirG response regulator to activate transcription in plants.

    PubMed

    Czarnecka-Verner, Eva; Salem, Tarek A; Gurley, William B

    2016-02-01

    The Agrobacterium tumefaciens VirG response regulator of the VirA/VirG two-component system was adapted to function in tobacco protoplasts. The subcellular localization of VirG and VirA proteins transiently expressed in onion cells was determined using GFP fusions. Preliminary studies using Gal4DBD-VP16 fusions with VirG and Escherichia coli UhpA, and NarL response regulators indicated compatibility of these bacterial proteins with the eukaryotic transcriptional apparatus. A strong transcriptional activator based on tandem activation domains from the Drosophila fushi tarazu and Herpes simplex VP16 was created. Selected configurations of the two-site Gal4-vir box GUS reporters were activated by chimeric effectors dependent on either the yeast Gal4 DNA-binding domain or that of VirG. Transcriptional induction of the GUS reporter was highest for the VirE19-element promoter with both constitutive and wild-type VirG-tandem activation domain effectors. Multiple VirE19 elements increased the reporter activity proportionately, indicating that the VirG DNA binding domain was functional in plants. The VirG constitutive-Q-VP16 effector was more active than the VirG wild-type. In both the constitutive and wild-type forms of VirG, Q-VP16 activated transcription of the GUS reporter best when located at the C-terminus, i.e. juxtaposed to the VirG DNA binding domain. These results demonstrate the possibility of using DNA binding domains from bacterial response regulators and their cognate binding elements in the engineering of plant gene expression. PMID:26646288

  3. Adaptation of the Agrobacterium tumefaciens VirG response regulator to activate transcription in plants.

    PubMed

    Czarnecka-Verner, Eva; Salem, Tarek A; Gurley, William B

    2016-02-01

    The Agrobacterium tumefaciens VirG response regulator of the VirA/VirG two-component system was adapted to function in tobacco protoplasts. The subcellular localization of VirG and VirA proteins transiently expressed in onion cells was determined using GFP fusions. Preliminary studies using Gal4DBD-VP16 fusions with VirG and Escherichia coli UhpA, and NarL response regulators indicated compatibility of these bacterial proteins with the eukaryotic transcriptional apparatus. A strong transcriptional activator based on tandem activation domains from the Drosophila fushi tarazu and Herpes simplex VP16 was created. Selected configurations of the two-site Gal4-vir box GUS reporters were activated by chimeric effectors dependent on either the yeast Gal4 DNA-binding domain or that of VirG. Transcriptional induction of the GUS reporter was highest for the VirE19-element promoter with both constitutive and wild-type VirG-tandem activation domain effectors. Multiple VirE19 elements increased the reporter activity proportionately, indicating that the VirG DNA binding domain was functional in plants. The VirG constitutive-Q-VP16 effector was more active than the VirG wild-type. In both the constitutive and wild-type forms of VirG, Q-VP16 activated transcription of the GUS reporter best when located at the C-terminus, i.e. juxtaposed to the VirG DNA binding domain. These results demonstrate the possibility of using DNA binding domains from bacterial response regulators and their cognate binding elements in the engineering of plant gene expression.

  4. ADAPTATION OF SUBJECTIVE RESPONSES TO ALCOHOL IS AFFECTED BY AN INTERACTION OF GABRA2 GENOTYPE AND RECENT DRINKING

    PubMed Central

    Kosobud, Ann E.K.; Wetherill, Leah; Plawecki, Martin H.; Kareken, David A.; Liang, Tiebing; Nurnberger, John L.; Windisch, Kyle; Xuei, Xiaoling; Edenberg, Howard J.; Foroud, Tatiana M.; O’Connor, Sean J.

    2015-01-01

    Background Subjective perceptions of alcohol intoxication are associated with altered risk for alcohol abuse and dependence. Acute adaptation of these perceptions may influence such risk, and may involve genes associated with pleasant perceptions or the relief of anxiety. This study assessed the effect of variation in the GABAA receptor genes GABRG1 and GABRA2 and recent drinking history on the acute adaptation of subjective responses to alcohol. Methods 132 non-dependent moderate to heavy drinkers, aged 21–27, participated in 2 single-blind, counterbalanced sessions, approximately one week apart. One session was an intravenous alcohol “clamp”, during which breath alcohol concentration was held steady at 60 mg/dL (60 mg%) for 3 hours, and the other an identical session using saline infusion. Subjective perceptions of intoxication, enjoyment, stimulation, relaxation, anxiety, tiredness and estimated number of drinks were acquired before (baseline), and during the first and final 45 minutes of the clamp. A placebo-adjusted index of the subject’s acute adaptation to alcohol was calculated for each of the 7 subjective measures, and used in a principal component analysis to create a single aggregate estimate for each subject’s adaptive response to alcohol. Analysis of covariance tested if GABRA2 and GABRG1 single nucleotide polymorphism (SNP) genotypes, gender, placebo session, family history of alcoholism, recent drinking history, and the genotype x recent drinking history interaction significantly predicted the adaptive response. Results Recent drinking history (p=0.01), and recent drinking history x genotype interaction (p=0.01) were significantly associated with acute adaptation of the subjective responses to alcohol for the GABRA2 SNP rs279858. Conclusion Higher recent drinking was found to be associated with reduced acute tolerance to positive, stimulating effects of alcohol in carriers of the rs279858 risk allele. We postulate that the GABRA2 effect on

  5. Inbreeding and adaptive plasticity: an experimental analysis on predator-induced responses in the water flea Daphnia

    PubMed Central

    Swillen, Ine; Vanoverbeke, Joost; De Meester, Luc

    2015-01-01

    Several studies have emphasized that inbreeding depression (ID) is enhanced under stressful conditions. Additionally, one might imagine a loss of adaptively plastic responses which may further contribute to a reduction in fitness under environmental stress. Here, we quantified ID in inbred families of the cyclical parthenogen Daphnia magna in the absence and presence of fish predation risk. We test whether predator stress affects the degree of ID and if inbred families have a reduced capacity to respond to predator stress by adaptive phenotypic plasticity. We obtained two inbred families through clonal selfing within clones isolated from a fish pond. After mild purging under standardized conditions, we compared life history traits and adaptive plasticity between inbred and outbred lineages (directly hatched from the natural dormant egg bank of the same pond). Initial purging of lineages under standardized conditions differed among inbred families and exceeded that in outbreds. The least purged inbred family exhibited strong ID for most life history traits. Predator-induced stress hardly affected the severity of ID, but the degree to which the capacity for adaptive phenotypic plasticity was retained varied strongly among the inbred families. The least purged family overall lacked the capacity for adaptive phenotypic plasticity, whereas the family that suffered only mild purging exhibited a potential for adaptive plasticity that was comparable to the outbred population. We thus found that inbred offspring may retain the capacity to respond to the presence of fish by adaptive phenotypic plasticity, but this strongly depends on the parental clone engaging in selfing. PMID:26257883

  6. Asymmetry Compensation by Nonlinear Adaptive Partial Response Equalizer for 31.3 GB Blu-ray Disk ROM

    NASA Astrophysics Data System (ADS)

    Kajiwara, Yoshiyuki; Higashino, Satoru; Yamagami, Tamotsu

    2005-05-01

    We investigated a nonlinear adaptive partial response equalizer for the asymmetry compensation of a 31.3 GB higher linear density Blu-ray disc read only memory (ROM) with a 16% asymmetry. A second-order adaptive Volterra filter approximately equalizes a nonlinear signal into a linear one. We reduced its calculation complexity to design a digital circuit in optimum hardware resources by the result of computer simulations. Then we designed an adaptive Volterra filter on an FPGA evaluation board for bit error rate measurements. Finally, we determined that an adaptive Volterra filter has a capability to obtain improved bit error rates by signal linearization in a conventional Viterbi detector for PR(1221).

  7. New concepts in immunity to Neisseria gonorrhoeae: innate responses and suppression of adaptive immunity favor the pathogen, not the host.

    PubMed

    Liu, Yingru; Feinen, Brandon; Russell, Michael W

    2011-01-01

    It is well-known that gonorrhea can be acquired repeatedly with no apparent development of protective immunity arising from previous episodes of infection. Symptomatic infection is characterized by a purulent exudate, but the host response mechanisms are poorly understood. While the remarkable antigenic variability displayed by Neisseria gonorrhoeae and its capacity to inhibit complement activation allow it to evade destruction by the host's immune defenses, we propose that it also has the capacity to avoid inducing specific immune responses. In a mouse model of vaginal gonococcal infection, N. gonorrhoeae elicits Th17-driven inflammatory-immune responses, which recruit innate defense mechanisms including an influx of neutrophils. Concomitantly, N. gonorrhoeae suppresses Th1- and Th2-dependent adaptive immunity, including specific antibody responses, through a mechanism involving TGF-β and regulatory T cells. Blockade of TGF-β alleviates the suppression of specific anti-gonococcal responses and allows Th1 and Th2 responses to emerge with the generation of immune memory and protective immunity. Genital tract tissues are naturally rich in TGF-β, which fosters an immunosuppressive environment that is important in reproduction. In exploiting this niche, N. gonorrhoeae exemplifies a well-adapted pathogen that proactively elicits from its host innate responses that it can survive and concomitantly suppresses adaptive immunity. Comprehension of these mechanisms of gonococcal pathogenesis should allow the development of novel approaches to therapy and facilitate the development of an effective vaccine. PMID:21833308

  8. Deep-sea pennatulaceans (sea pens) - recent discoveries, morphological adaptations, and responses to benthic oceanographic parameters

    NASA Astrophysics Data System (ADS)

    Williams, G. C.

    2015-12-01

    Pennatulaceans are sessile, benthic marine organisms that are bathymetrically wide-ranging, from the intertidal to approximately 6300 m in depth, and are conspicuous constituents of deep-sea environments. The vast majority of species are adapted for anchoring in soft sediments by the cylindrical peduncle - a muscular hydrostatic skeleton. However, in the past decade a few species ("Rockpens") have been discovered and described that can attach to hard substratum such as exposed rocky outcrops at depths between 669 and 1969 m, by a plunger-like adaptation of the base of the peduncle. Of the thirty-six known genera, eleven (or 30%) have been recorded from depths greater than 1000 m. The pennatulacean depth record holders are an unidentified species of Umbellula from 6260 m in the Peru-Chile Trench and a recently-discovered and described genus and species, Porcupinella profunda, from 5300 m the Porcupine Abyssal Plain of the northeastern Atlantic. A morphologically-differentiated type of polyp (acrozooid) have recently been discovered and described in two genera of shallow-water coral reef sea pens. Acrozooids apparently represent asexual buds and presumably can detach from the adult to start clonal colonies through asexual budding. Acrozooids are to be expected in deep-sea pennatulaceans, but so far have not been observed below 24 m in depth. Morphological responses at depths greater than 1000 m in deep-sea pennatulaceas include: fewer polyps, larger polyps, elongated stalks, and clustering of polyps along the rachis. Responses to deep-ocean physical parameters and anthropogenic changes that could affect the abundance and distribution of deep-sea pennatulaceans include changes in bottom current flow and food availability, changes in seawater temperature and pH, habitat destruction by fish trawling, and sunken refuse pollution. No evidence of the effects of ocean acidification or other effects of anthropogenic climate change in sea pens of the deep-sea has been

  9. Involvement of Escherichia coli DNA polymerase II in response to oxidative damage and adaptive mutation.

    PubMed Central

    Escarceller, M; Hicks, J; Gudmundsson, G; Trump, G; Touati, D; Lovett, S; Foster, P L; McEntee, K; Goodman, M F

    1994-01-01

    DNA polymerase II (Pol II) is regulated as part of the SOS response to DNA damage in Escherichia coli. We examined the participation of Pol II in the response to oxidative damage, adaptive mutation, and recombination. Cells lacking Pol II activity (polB delta 1 mutants) exhibited 5- to 10-fold-greater sensitivity to mode 1 killing by H2O2 compared with isogenic polB+ cells. Survival decreased by about 15-fold when polB mutants containing defective superoxide dismutase genes, sodA and sodB, were compared with polB+ sodA sodB mutants. Resistance to peroxide killing was restored following P1 transduction of polB cells to polB+ or by conjugation of polB cells with an F' plasmid carrying a copy of polB+. The rate at which Lac+ mutations arose in Lac- cells subjected to selection for lactose utilization, a phenomenon known as adaptive mutation, was increased threefold in polB backgrounds and returned to wild-type rates when polB cells were transduced to polB+. Following multiple passages of polB cells or prolonged starvation, a progressive loss of sensitivity to killing by peroxide was observed, suggesting that second-site suppressor mutations may be occurring with relatively high frequencies. The presence of suppressor mutations may account for the apparent lack of a mutant phenotype in earlier studies. A well-established polB strain, a dinA Mu d(Apr lac) fusion (GW1010), exhibited wild-type (Pol II+) sensitivity to killing by peroxide, consistent with the accumulation of second-site suppressor mutations. A high titer anti-Pol II polyclonal antibody was used to screen for the presence of Pol II in other bacteria and in the yeast Saccharomyces cerevisiae. Cross-reacting material was found in all gram-negative strains tested but was not detected in gram-positive strains or in S. cerevisiae. Induction of Pol II by nalidixic acid was observed in E. coli K-12, B, and C, in Shigella flexneri, and in Salmonella typhimurium. Images PMID:7928992

  10. Global Megacities Differing Adaptation Responses to Climate Change: an Analysis of Annual Spend of Ten Major cities on the adaptation economy

    NASA Astrophysics Data System (ADS)

    Maslin, M. A.; Georgeson, L.

    2015-12-01

    Urban areas are increasingly at risk from climate change with negative impacts predicted for human health, the economy and ecosystems. These risks require responses from cities, to improve the resilience of their infrastructure, economy and environment to climate change. Policymakers need to understand what is already being spent on adaptation so that they can make more effective and comprehensive adaptation plans. Through the measurement of spend in the newly defined 'Adaptation Economy' we analysis the current efforts of 10 global megacities in adapting to climate change. These cities were chosen based on their size, geographical location and their developmental status. The cities are London, Paris, New York, Mexico City, Sao Paulo, Beijing, Mumbai, Jakarta, Lagos and Addis Ababa. It is important to study a range of cities in different regions of the world, with different climates and at different states of socio-economic development. While in economic terms, disaster losses from weather, climate and geophysical events are greater in developed countries, fatalities and economic losses as a proportion of GDP are higher in developing countries. In all cities examined the Adaptation Economy is still a small part of the overall economy accounting for a maximum of 0.3% of the Cities total GDP (GDPc). The differences in total spend are significant between cities in developed and rapidly emerging countries, compared to those in developing countries with a spend ranging from £16 million to £1,500 million. Comparing key sub sectors, we demonstrate that there are distinctive adaptation profiles with developing cities having a higher relative spend on health, while developed cities have a higher spend on disaster preparedness, ICT and professional services. Comparing spend per capita and as a percentage of GDPc demonstrates even more clearly disparities between the cities in the study; developing country cities spend half as much as a proportion of GPCc in some cases, and

  11. Social Influences on Executive Functions Development in Children and Adolescents: Steps Toward a Social Neuroscience of Predictive Adaptive Responses.

    PubMed

    Dishion, Thomas J

    2016-01-01

    This commentary discusses the findings and implications of four empirical papers that establish a reciprocal, longitudinal link between the social environment and executive functions from childhood to adolescence. Two future directions are suggested by this work. The first is a call for measurement research to clarify the nomological network of various measurements of self-regulation and executive functions across a variety of methods and procedures. The second new direction is to broaden the analysis of executive function to include a wider array of predictive adaptive responses to various environmental conditions, including those where youth are chronically marginalized or otherwise stressed. Findings from these studies suggest that the executive functions within the brain guide adaptation in both deviant as well as competent responses to the social environment. Understanding various forms of adaptation will enhance the potential for prevention as well as avoid iatrogenic intervention strategies with misinformed targets. PMID:26729426

  12. Computer Adaptive Practice of Maths Ability Using a New Item Response Model for on the Fly Ability and Difficulty Estimation

    ERIC Educational Resources Information Center

    Klinkenberg, S.; Straatemeier, M.; van der Maas, H. L. J.

    2011-01-01

    In this paper we present a model for computerized adaptive practice and monitoring. This model is used in the Maths Garden, a web-based monitoring system, which includes a challenging web environment for children to practice arithmetic. Using a new item response model based on the Elo (1978) rating system and an explicit scoring rule, estimates of…

  13. Effectiveness of Item Response Theory (IRT) Proficiency Estimation Methods under Adaptive Multistage Testing. Research Report. ETS RR-15-11

    ERIC Educational Resources Information Center

    Kim, Sooyeon; Moses, Tim; Yoo, Hanwook Henry

    2015-01-01

    The purpose of this inquiry was to investigate the effectiveness of item response theory (IRT) proficiency estimators in terms of estimation bias and error under multistage testing (MST). We chose a 2-stage MST design in which 1 adaptation to the examinees' ability levels takes place. It includes 4 modules (1 at Stage 1, 3 at Stage 2) and 3 paths…

  14. A Reevaluation of the Role of the Unfolded Protein Response in Islet Dysfunction: Maladaptation or a Failure to Adapt?

    PubMed

    Herbert, Terence P; Laybutt, D Ross

    2016-06-01

    Endoplasmic reticulum (ER) stress caused by perturbations in ER homeostasis activates an adaptive response termed the unfolded protein response (UPR) whose function is to resolve ER stress. If unsuccessful, the UPR initiates a proapoptotic program to eliminate the malfunctioning cells from the organism. It is the activation of this proapoptotic UPR in pancreatic β-cells that has been implicated in the onset of type 2 diabetes and thus, in this context, is considered a maladaptive response. However, there is growing evidence that β-cell death in type 2 diabetes may not be caused by a maladaptive UPR but by the inhibition of the adaptive UPR. In this review, we discuss the evidence for a role of the UPR in β-cell dysfunction and death in the development of type 2 diabetes and ask the following question: Is β-cell dysfunction the result of a maladaptive UPR or a failure of the UPR to adequately adapt? The answer to this question is critically important in defining potential therapeutic strategies for the treatment and prevention of type 2 diabetes. In addition, we discuss the potential role of the adaptive UPR in staving off type 2 diabetes by enhancing β-cell mass and function in response to insulin resistance. PMID:27222391

  15. Adaptive Stress Response in Segmental Progeria Resembles Long-Lived Dwarfism and Calorie Restriction in Mice

    PubMed Central

    Holcomb, Valerie B; von Lindern, Marieke; Jong, Willeke M. C; Zeeuw, Chris I. De; Suh, Yousin; Hasty, Paul; Hoeijmakers, Jan H. J; van der Horst, Gijsbertus T. J; Mitchell, James R

    2006-01-01

    How congenital defects causing genome instability can result in the pleiotropic symptoms reminiscent of aging but in a segmental and accelerated fashion remains largely unknown. Most segmental progerias are associated with accelerated fibroblast senescence, suggesting that cellular senescence is a likely contributing mechanism. Contrary to expectations, neither accelerated senescence nor acute oxidative stress hypersensitivity was detected in primary fibroblast or erythroblast cultures from multiple progeroid mouse models for defects in the nucleotide excision DNA repair pathway, which share premature aging features including postnatal growth retardation, cerebellar ataxia, and death before weaning. Instead, we report a prominent phenotypic overlap with long-lived dwarfism and calorie restriction during postnatal development (2 wk of age), including reduced size, reduced body temperature, hypoglycemia, and perturbation of the growth hormone/insulin-like growth factor 1 neuroendocrine axis. These symptoms were also present at 2 wk of age in a novel progeroid nucleotide excision repair-deficient mouse model (XPDG602D/R722W/XPA−/−) that survived weaning with high penetrance. However, despite persistent cachectic dwarfism, blood glucose and serum insulin-like growth factor 1 levels returned to normal by 10 wk, with hypoglycemia reappearing near premature death at 5 mo of age. These data strongly suggest changes in energy metabolism as part of an adaptive response during the stressful period of postnatal growth. Interestingly, a similar perturbation of the postnatal growth axis was not detected in another progeroid mouse model, the double-strand DNA break repair deficient Ku80−/− mouse. Specific (but not all) types of genome instability may thus engage a conserved response to stress that evolved to cope with environmental pressures such as food shortage. PMID:17173483

  16. Asymmetric response properties of rapidly adapting mechanoreceptive fibers in the rat glabrous skin.

    PubMed

    Devecıoğlu, Ismaıl; Güçlü, Burak

    2013-01-01

    Previous histological and neurophysiological studies have shown that the innervation density of rapidly adapting (RA) mechanoreceptive fibers increases towards the fingertip. Since the psychophysical detection threshold depends on the contribution of several RA fibers, a high innervation density would imply lower thresholds. However, our previous human study showed that psychophysical detection thresholds for the Non-Pacinian I channel mediated by RA fibers do not improve towards the fingertip. By recording single-unit spike activity from rat RA fibers, here we tested the hypothesis that the responsiveness of RA fibers is asymmetric in the proximo-distal axis which may counterbalance the effects of innervation density. RA fibers (n = 32) innervating the digital glabrous skin of rat hind paw were stimulated with 40-Hz sinusoidal mechanical bursts at five different stimulus locations relative to the receptive field (RF) center (two distal, one RF center, two proximal). Different contactor sizes (area: 0.39, 1.63, 2.96 mm²) were used. Rate-intensity functions were constructed based on average firing rates, and the absolute spike threshold and the entrainment threshold were obtained for each RA fiber. Thresholds for proximal stimulus locations were found to be significantly higher than those for distal stimulus locations, which suggests that the mechanical stimulus is transmitted better towards the proximal direction. The effect of contactor size was not significant. Mechanical impedance of the rat digital glabrous skin was further measured and a lumped-parameter model was proposed to interpret the relationship between the asymmetric response properties of RA fibers and the mechanical properties of the skin.

  17. Turning inducible defenses on and off: adaptive responses of Daphnia to a gape-limited predator.

    PubMed

    Riessen, Howard P; Trevett-Smith, Julie B

    2009-12-01

    The use of inducible defenses is a common strategy to reduce predation while minimizing associated costs for prey. The most effective use of these defenses, however, may involve turning them on and off at different stages of ontogenetic development, with the timing dependent on prey body size and the nature of the predation environment. We develop a model based on the strike efficiency of a size-selective predator that examines the interaction between induced morphological defenses and prey body size, including the consequences of this interaction for the optimal development of the defenses during the prey's ontogeny. We then examine this model with respect to a model system of inducible defenses: neck spine induction in the water flea Daphnia in response to predatory larvae of the phantom midge Chaoborus. In accordance with predictions of the model, the body size and timing of neck spine acquisition during Daphnia development are related to the relative sizes of the Daphnia and Chaoborus species interacting in a pond or lake. The Daphnia species examined first acquire neck spines in either the first, second, or third juvenile instar, at body lengths that range from 0.58 to 0.83 mm. Neck spine formation is initiated at larger Daphnia body sizes when these prey are subject to predation by a larger Chaoborus species (C. trivittatus) and at smaller sizes when exposed only to a smaller predator (C. americanus). Induction of these morphological defenses in Daphnia occurs later in juvenile development in the smaller of the two species we examined (D. minnehaha) than in the larger (D. pulex). Delayed acquisition of neck spines also occurs when Daphnia are exposed to predation by larger Chaoborus. The close match between model predictions and the patterns observed in nature suggests that these patterns are adaptive developmental responses to different predator environments.

  18. Flavin-Induced Oligomerization in Escherichia coli Adaptive Response Protein AidB

    SciTech Connect

    Hamill, Michael J.; Jost, Marco; Wong, Cintyu; Elliott, Sean J.; Drennan, Catherine L.

    2011-11-21

    The process known as 'adaptive response' allows Escherichia coli to respond to small doses of DNA-methylating agents by upregulating the expression of four proteins. While the role of three of these proteins in mitigating DNA damage is well understood, the function of AidB is less clear. Although AidB is a flavoprotein, no catalytic role has been established for the bound cofactor. Here we investigate the possibility that flavin plays a structural role in the assembly of the AidB tetramer. We report the generation and biophysical characterization of deflavinated AidB and of an AidB mutant that has greatly reduced affinity for flavin adenine dinucleotide (FAD). Using fluorescence quenching and analytical ultracentrifugation, we find that apo AidB has a high affinity for FAD, as indicated by an apparent dissociation constant of 402.1 {+-} 35.1 nM, and that binding of substoichiometric amounts of FAD triggers a transition in the AidB oligomeric state. In particular, deflavinated AidB is dimeric, whereas the addition of FAD yields a tetramer. We further investigate the dimerization and tetramerization interfaces of AidB by determining a 2.8 {angstrom} resolution crystal structure in space group P3{sub 2} that contains three intact tetramers in the asymmetric unit. Taken together, our findings provide strong evidence that FAD plays a structural role in the formation of tetrameric AidB.

  19. Adaptive and Pathogenic Responses to Stress by Stem Cells during Development.

    PubMed

    Mansouri, Ladan; Xie, Yufen; Rappolee, Daniel A

    2012-01-01

    Cellular stress is the basis of a dose-dependent continuum of responses leading to adaptive health or pathogenesis. For all cells, stress leads to reduction in macromolecular synthesis by shared pathways and tissue and stress-specific homeostatic mechanisms. For stem cells during embryonic, fetal, and placental development, higher exposures of stress lead to decreased anabolism, macromolecular synthesis and cell proliferation. Coupled with diminished stem cell proliferation is a stress-induced differentiation which generates minimal necessary function by producing more differentiated product/cell. This compensatory differentiation is accompanied by a second strategy to insure organismal survival as multipotent and pluripotent stem cells differentiate into the lineages in their repertoire. During stressed differentiation, the first lineage in the repertoire is increased and later lineages are suppressed, thus prioritized differentiation occurs. Compensatory and prioritized differentiation is regulated by at least two types of stress enzymes. AMP-activated protein kinase (AMPK) which mediates loss of nuclear potency factors and stress-activated protein kinase (SAPK) that does not. SAPK mediates an increase in the first essential lineage and decreases in later lineages in placental stem cells. The clinical significance of compensatory and prioritized differentiation is that stem cell pools are depleted and imbalanced differentiation leads to gestational diseases and long term postnatal pathologies.

  20. Adaptive response and tolerance to sugar and salt stress in the food yeast Zygosaccharomyces rouxii.

    PubMed

    Dakal, Tikam Chand; Solieri, Lisa; Giudici, Paolo

    2014-08-18

    The osmotolerant and halotolerant food yeast Zygosaccharomyces rouxii is known for its ability to grow and survive in the face of stress caused by high concentrations of non-ionic (sugars and polyols) and ionic (mainly Na(+) cations) solutes. This ability determines the success of fermentation on high osmolarity food matrices and leads to spoilage of high sugar and high salt foods. The knowledge about the genes, the metabolic pathways, and the regulatory circuits shaping the Z. rouxii sugar and salt-tolerance, is a prerequisite to develop effective strategies for fermentation control, optimization of food starter culture, and prevention of food spoilage. This review summarizes recent insights on the mechanisms used by Z. rouxii and other osmo and halotolerant food yeasts to endure salts and sugars stresses. Using the information gathered from S. cerevisiae as guide, we highlight how these non-conventional yeasts integrate general and osmoticum-specific adaptive responses under sugar and salts stresses, including regulation of Na(+) and K(+)-fluxes across the plasma membrane, modulation of cell wall properties, compatible osmolyte production and accumulation, and stress signalling pathways. We suggest how an integrated and system-based knowledge on these mechanisms may impact food and biotechnological industries, by improving the yeast spoilage control in food, enhancing the yeast-based bioprocess yields, and engineering the osmotolerance in other organisms.

  1. Electrochemical Characterization of Escherichia coli Adaptive Response Protein AidB

    PubMed Central

    Hamill, Michael J.; Jost, Marco; Wong, Cintyu; Bene, Nicholas C.; Drennan, Catherine L.; Elliott, Sean J.

    2012-01-01

    When exposed to known DNA-damaging alkylating agents, Escherichia coli cells increase production of four DNA repair enzymes: Ada, AlkA, AlkB, and AidB. The role of three enzymes (Ada, AlkA, and AlkB) in repairing DNA lesions has been well characterized, while the function of AidB is poorly understood. AidB has a distinct cofactor that is potentially related to the elusive role of AidB in adaptive response: a redox active flavin adenine dinucleotide (FAD). In this study, we report the thermodynamic redox properties of the AidB flavin for the first time, both for free protein and in the presence of potential substrates. We find that the midpoint reduction potential of the AidB flavin is within a biologically relevant window for redox chemistry at −181 mV, that AidB significantly stabilizes the flavin semiquinone, and that small molecule binding perturbs the observed reduction potential. Our electrochemical results combined with structural analysis allow for fresh comparisons between AidB and the homologous acyl-coenzyme A dehydrogenase (ACAD) family of enzymes. AidB exhibits several discrepancies from ACADs that suggest a novel catalytic mechanism distinct from that of the ACAD family enzymes. PMID:23443126

  2. Cyclic variations in incubation conditions induce adaptive responses to later heat exposure in chickens: a review.

    PubMed

    Loyau, T; Bedrani, L; Berri, C; Métayer-Coustard, S; Praud, C; Coustham, V; Mignon-Grasteau, S; Duclos, M J; Tesseraud, S; Rideau, N; Hennequet-Antier, C; Everaert, N; Yahav, S; Collin, A

    2015-01-01

    Selection programs have enabled broiler chickens to gain muscle mass without similar enlargement of the cardiovascular and respiratory systems that are essential for thermoregulatory efficiency. Meat-type chickens cope with high ambient temperature by reducing feed intake and growth during chronic and moderate heat exposure. In case of acute heat exposure, a dramatic increase in morbidity and mortality can occur. In order to alleviate heat stress in the long term, research has recently focused on early thermal manipulation. Aimed at stimulation of long-term thermotolerance, the thermal manipulation of embryos is a method based on fine tuning of incubation conditions, taking into account the level and duration of increases in temperature and relative humidity during a critical period of embryogenesis. The consequences of thermal manipulation on the performance and meat quality of broiler chickens have been explored to ensure the potential application of this strategy. The physiological basis of the method is the induction of epigenetic and metabolic mechanisms that control body temperature in the long term. Early thermal manipulation can enhance poultry resistance to environmental changes without much effect on growth performance. This review presents the main strategies of early heat exposure and the physiological concepts on which these methods were based. The cellular mechanisms potentially underlying the adaptive response are discussed as well as the potential interest of thermal manipulation of embryos for poultry production.

  3. Neural Mechanisms Behind Identification of Leptokurtic Noise and Adaptive Behavioral Response.

    PubMed

    d'Acremont, Mathieu; Bossaerts, Peter

    2016-04-01

    Large-scale human interaction through, for example, financial markets causes ceaseless random changes in outcome variability, producing frequent and salient outliers that render the outcome distribution more peaked than the Gaussian distribution, and with longer tails. Here, we study how humans cope with this evolutionary novel leptokurtic noise, focusing on the neurobiological mechanisms that allow the brain, 1) to recognize the outliers as noise and 2) to regulate the control necessary for adaptive response. We used functional magnetic resonance imaging, while participants tracked a target whose movements were affected by leptokurtic noise. After initial overreaction and insufficient subsequent correction, participants improved performance significantly. Yet, persistently long reaction times pointed to continued need for vigilance and control. We ran a contrasting treatment where outliers reflected permanent moves of the target, as in traditional mean-shift paradigms. Importantly, outliers were equally frequent and salient. There, control was superior and reaction time was faster. We present a novel reinforcement learning model that fits observed choices better than the Bayes-optimal model. Only anterior insula discriminated between the 2 types of outliers. In both treatments, outliers initially activated an extensive bottom-up attention and belief network, followed by sustained engagement of the fronto-parietal control network.

  4. Emergency measures: Adaptive response to pathogen intrusion in the ant nest.

    PubMed

    Diez, Lise; Urbain, Laure; Lejeune, Philippe; Detrain, Claire

    2015-07-01

    Ants have developed prophylactic and hygienic behaviours in order to limit risks of pathogenic outbreaks inside their nest, which are often called social immunity. Here, we test whether ants can adapt the "social immune response" to the level of pathogenic risk in the colony. We challenged Myrmica rubra colonies with dead nestmates that had either died from being frozen or from infection by the fungus Metarhizium anisopliae. Ant survival was compromised by the presence of the fungus-bearing corpses: workers died faster with a significantly lower survival from the 4th day compared to workers challenged with freeze-killed corpses. When faced with fungus-bearing corpses, workers responded quickly by increasing hygienic behaviours: they spent more time cleaning the nest, moving the corpses, and self-grooming. Ants in fungus-threatened colonies also decreased contact rates with other workers, and moved corpses further in the corners of the nest than in colonies in contact with non-infected corpses. These results show that ant colonies are able to assess the risk level associated with the presence of corpses in the nest, and adjust their investment in terms of hygienic behaviour. PMID:25939763

  5. The role of astrocytes in the hypothalamic response and adaptation to metabolic signals.

    PubMed

    Chowen, Julie A; Argente-Arizón, Pilar; Freire-Regatillo, Alejandra; Frago, Laura M; Horvath, Tamas L; Argente, Jesús

    2016-09-01

    The hypothalamus is crucial in the regulation of homeostatic functions in mammals, with the disruption of hypothalamic circuits contributing to chronic conditions such as obesity, diabetes mellitus, hypertension, and infertility. Metabolic signals and hormonal inputs drive functional and morphological changes in the hypothalamus in attempt to maintain metabolic homeostasis. However, the dramatic increase in the incidence of obesity and its secondary complications, such as type 2 diabetes, have evidenced the need to better understand how this system functions and how it can go awry. Growing evidence points to a critical role of astrocytes in orchestrating the hypothalamic response to metabolic cues by participating in processes of synaptic transmission, synaptic plasticity and nutrient sensing. These glial cells express receptors for important metabolic signals, such as the anorexigenic hormone leptin, and determine the type and quantity of nutrients reaching their neighboring neurons. Understanding the mechanisms by which astrocytes participate in hypothalamic adaptations to changes in dietary and metabolic signals is fundamental for understanding the neuroendocrine control of metabolism and key in the search for adequate treatments of metabolic diseases.

  6. Mitochondrial fission is an acute and adaptive response in injured motor neurons

    PubMed Central

    Kiryu-Seo, Sumiko; Tamada, Hiromi; Kato, Yukina; Yasuda, Katsura; Ishihara, Naotada; Nomura, Masatoshi; Mihara, Katsuyoshi; Kiyama, Hiroshi

    2016-01-01

    Successful recovery from neuronal damage requires a huge energy supply, which is provided by mitochondria. However, the physiological relevance of mitochondrial dynamics in damaged neurons in vivo is poorly understood. To address this issue, we established unique bacterial artificial chromosome transgenic (BAC Tg) mice, which develop and function normally, but in which neuronal injury induces labelling of mitochondria with green fluorescent protein (GFP) and expression of cre recombinase. GFP-labelled mitochondria in BAC Tg mice appear shorter in regenerating motor axons soon after nerve injury compared with mitochondria in non-injured axons, suggesting the importance of increased mitochondrial fission during the early phase of nerve regeneration. Crossing the BAC Tg mice with mice carrying a floxed dynamin-related protein 1 gene (Drp1), which is necessary for mitochondrial fission, ablates mitochondrial fission specifically in injured neurons. Injury-induced Drp1-deficient motor neurons show elongated or abnormally gigantic mitochondria, which have impaired membrane potential and axonal transport velocity during the early phase after injury, and eventually promote neuronal death. Our in vivo data suggest that acute and prominent mitochondrial fission during the early stage after nerve injury is an adaptive response and is involved in the maintenance of mitochondrial and neuronal integrity to prevent neurodegeneration. PMID:27319806

  7. Neural Mechanisms Behind Identification of Leptokurtic Noise and Adaptive Behavioral Response

    PubMed Central

    d'Acremont, Mathieu; Bossaerts, Peter

    2016-01-01

    Large-scale human interaction through, for example, financial markets causes ceaseless random changes in outcome variability, producing frequent and salient outliers that render the outcome distribution more peaked than the Gaussian distribution, and with longer tails. Here, we study how humans cope with this evolutionary novel leptokurtic noise, focusing on the neurobiological mechanisms that allow the brain, 1) to recognize the outliers as noise and 2) to regulate the control necessary for adaptive response. We used functional magnetic resonance imaging, while participants tracked a target whose movements were affected by leptokurtic noise. After initial overreaction and insufficient subsequent correction, participants improved performance significantly. Yet, persistently long reaction times pointed to continued need for vigilance and control. We ran a contrasting treatment where outliers reflected permanent moves of the target, as in traditional mean-shift paradigms. Importantly, outliers were equally frequent and salient. There, control was superior and reaction time was faster. We present a novel reinforcement learning model that fits observed choices better than the Bayes-optimal model. Only anterior insula discriminated between the 2 types of outliers. In both treatments, outliers initially activated an extensive bottom-up attention and belief network, followed by sustained engagement of the fronto-parietal control network. PMID:26850528

  8. Temperature-responsive release of thyroxine and its environmental adaptation in Australians.

    PubMed

    Qi, Xiaoqiang; Chan, Wee Lee; Read, Randy J; Zhou, Aiwu; Carrell, Robin W

    2014-03-22

    The hormone thyroxine that regulates mammalian metabolism is carried and stored in the blood by thyroxine-binding globulin (TBG). We demonstrate here that the release of thyroxine from TBG occurs by a temperature-sensitive mechanism and show how this will provide a homoeostatic adjustment of the concentration of thyroxine to match metabolic needs, as with the hypothermia and torpor of small animals. In humans, a rise in temperature, as in infections, will trigger an accelerated release of thyroxine, resulting in a predictable 23% increase in the concentration of free thyroxine at 39°C. The in vivo relevance of this fever-response is affirmed in an environmental adaptation in aboriginal Australians. We show how two mutations incorporated in their TBG interact in a way that will halve the surge in thyroxine release, and hence the boost in metabolic rate that would otherwise occur as body temperatures exceed 37°C. The overall findings open insights into physiological changes that accompany variations in body temperature, as notably in fevers.

  9. An adaptive response of Enterobacter aerogenes to imipenem: regulation of porin balance in clinical isolates.

    PubMed

    Lavigne, Jean-Philippe; Sotto, Albert; Nicolas-Chanoine, Marie-Hélène; Bouziges, Nicole; Pagès, Jean-Marie; Davin-Regli, Anne

    2013-02-01

    Imipenem (IPM) is a carbapenem antibiotic frequently used in severe hospital infections. Several reports have mentioned the emergence of resistant isolates exhibiting membrane modifications. A study was conducted between September 2005 and August 2007 to survey infections due to Enterobacter aerogenes in patients hospitalised in a French university hospital. Resistant E. aerogenes clinical isolates obtained from patients treated with IPM and collected during the 3 months following initiation of treatment were phenotypically and molecularly characterised for β-lactamases, efflux pumps activity and outer membrane proteins. Among the 339 patients infected with E. aerogenes during the study period, 41 isolates (12.1%) were resistant to extended-spectrum cephalosporins and 17 patients (5.0%) were treated with IPM. The isolates from these 17 patients presented TEM-24 and basal efflux expression. Following IPM treatment, an IPM-intermediate-susceptible (IPM-I) isolate emerged in 11 patients and an IPM-resistant (IPM-R) isolate in 6 patients. A change in the porin balance (Omp35/Omp36) was observed in IPM-I isolates exhibiting ertapenem resistance. Finally, a porin deficiency (Omp35 and Omp36 absence) was detected in IPM-R isolates associated with efflux pump expression. This study indicates that the alteration in porin expression, including the shift of porin expression and lack of porins, contribute to the E. aerogenes adaptive response to IPM treatment.

  10. Functional responses and adaptation of mesophilic microbial communities to psychrophilic anaerobic digestion.

    PubMed

    Gunnigle, Eoin; Nielsen, Jeppe L; Fuszard, Matthew; Botting, Catherine H; Sheahan, Jerome; O'Flaherty, Vincent; Abram, Florence

    2015-12-01

    Psychrophilic (<20°C) anaerobic digestion (AD) represents an attractive alternative to mesophilic wastewater treatment. In order to investigate the AD microbiome response to temperature change, with particular emphasis on methanogenic archaea, duplicate laboratory-scale AD bioreactors were operated at 37°C followed by a temperature drop to 15°C. A volatile fatty acid-based wastewater (composed of propionic acid, butyric acid, acetic acid and ethanol) was used to provide substrates representing the later stages of AD. Community structure was monitored using 16S rRNA gene clone libraries, as well as DNA and cDNA-based DGGE analysis, while the abundance of relevant methanogens was followed using qPCR. In addition, metaproteomics, microautoradiography-fluorescence in situ hybridization, and methanogenic activity measurements were employed to investigate microbial activities and functions. Methanomicrobiales abundance increased at low temperature, which correlated with an increased contribution of CH4 production from hydrogenotrophic methanogenesis at 15°C. Methanosarcinales utilized acetate and H2/CO2 as CH4 precursors at both temperatures and a partial shift from acetoclastic to hydrogenotrophic methanogenesis was observed for this archaeal population at 15°C. An upregulation of protein expression was reported at low temperature as well as the detection of chaperones indicating that mesophilic communities experienced stress during long-term exposure to 15°C. Overall, changes in microbial community structure and function were found to underpin the adaptation of mesophilic sludge to psychrophilic AD.

  11. Functional responses and adaptation of mesophilic microbial communities to psychrophilic anaerobic digestion.

    PubMed

    Gunnigle, Eoin; Nielsen, Jeppe L; Fuszard, Matthew; Botting, Catherine H; Sheahan, Jerome; O'Flaherty, Vincent; Abram, Florence

    2015-12-01

    Psychrophilic (<20°C) anaerobic digestion (AD) represents an attractive alternative to mesophilic wastewater treatment. In order to investigate the AD microbiome response to temperature change, with particular emphasis on methanogenic archaea, duplicate laboratory-scale AD bioreactors were operated at 37°C followed by a temperature drop to 15°C. A volatile fatty acid-based wastewater (composed of propionic acid, butyric acid, acetic acid and ethanol) was used to provide substrates representing the later stages of AD. Community structure was monitored using 16S rRNA gene clone libraries, as well as DNA and cDNA-based DGGE analysis, while the abundance of relevant methanogens was followed using qPCR. In addition, metaproteomics, microautoradiography-fluorescence in situ hybridization, and methanogenic activity measurements were employed to investigate microbial activities and functions. Methanomicrobiales abundance increased at low temperature, which correlated with an increased contribution of CH4 production from hydrogenotrophic methanogenesis at 15°C. Methanosarcinales utilized acetate and H2/CO2 as CH4 precursors at both temperatures and a partial shift from acetoclastic to hydrogenotrophic methanogenesis was observed for this archaeal population at 15°C. An upregulation of protein expression was reported at low temperature as well as the detection of chaperones indicating that mesophilic communities experienced stress during long-term exposure to 15°C. Overall, changes in microbial community structure and function were found to underpin the adaptation of mesophilic sludge to psychrophilic AD. PMID:26507125

  12. Hippocampal adaptive response following extensive neuronal loss in an inducible transgenic mouse model.

    PubMed

    Myczek, Kristoffer; Yeung, Stephen T; Castello, Nicholas; Baglietto-Vargas, David; LaFerla, Frank M

    2014-01-01

    Neuronal loss is a common component of a variety of neurodegenerative disorders (including Alzheimer's, Parkinson's, and Huntington's disease) and brain traumas (stroke, epilepsy, and traumatic brain injury). One brain region that commonly exhibits neuronal loss in several neurodegenerative disorders is the hippocampus, an area of the brain critical for the formation and retrieval of memories. Long-lasting and sometimes unrecoverable deficits caused by neuronal loss present a unique challenge for clinicians and for researchers who attempt to model these traumas in animals. Can these deficits be recovered, and if so, is the brain capable of regeneration following neuronal loss? To address this significant question, we utilized the innovative CaM/Tet-DT(A) mouse model that selectively induces neuronal ablation. We found that we are able to inflict a consistent and significant lesion to the hippocampus, resulting in hippocampally-dependent behavioral deficits and a long-lasting upregulation in neurogenesis, suggesting that this process might be a critical part of hippocampal recovery. In addition, we provide novel evidence of angiogenic and vasculature changes following hippocampal neuronal loss in CaM/Tet-DTA mice. We posit that angiogenesis may be an important factor that promotes neurogenic upregulation following hippocampal neuronal loss, and both factors, angiogenesis and neurogenesis, can contribute to the adaptive response of the brain for behavioral recovery. PMID:25184527

  13. Adaptive and Pathogenic Responses to Stress by Stem Cells during Development

    PubMed Central

    Mansouri, Ladan; Xie, Yufen; Rappolee, Daniel A

    2012-01-01

    Cellular stress is the basis of a dose-dependent continuum of responses leading to adaptive health or pathogenesis. For all cells, stress leads to reduction in macromolecular synthesis by shared pathways and tissue and stress-specific homeostatic mechanisms. For stem cells during embryonic, fetal, and placental development, higher exposures of stress lead to decreased anabolism, macromolecular synthesis and cell proliferation. Coupled with diminished stem cell proliferation is a stress-induced differentiation which generates minimal necessary function by producing more differentiated product/cell. This compensatory differentiation is accompanied by a second strategy to insure organismal survival as multipotent and pluripotent stem cells differentiate into the lineages in their repertoire. During stressed differentiation, the first lineage in the repertoire is increased and later lineages are suppressed, thus prioritized differentiation occurs. Compensatory and prioritized differentiation is regulated by at least two types of stress enzymes. AMP-activated protein kinase (AMPK) which mediates loss of nuclear potency factors and stress-activated protein kinase (SAPK) that does not. SAPK mediates an increase in the first essential lineage and decreases in later lineages in placental stem cells. The clinical significance of compensatory and prioritized differentiation is that stem cell pools are depleted and imbalanced differentiation leads to gestational diseases and long term postnatal pathologies. PMID:24710551

  14. The Professional Context as a Predictor for Response Distortion in the Adaption-Innovation Inventory--An Investigation Using Mixture Distribution Item Response Theory Models

    ERIC Educational Resources Information Center

    Fischer, Sebastian; Freund, Philipp Alexander

    2014-01-01

    The Adaption-Innovation Inventory (AII), originally developed by Kirton (1976), is a widely used self-report instrument for measuring problem-solving styles at work. The present study investigates how scores on the AII are affected by different response styles. Data are collected from a combined sample (N = 738) of students, employees, and…

  15. Fast response and high sensitivity to microsaccades in a cascading-adaptation neural network with short-term synaptic depression

    NASA Astrophysics Data System (ADS)

    Yuan, Wu-Jie; Zhou, Jian-Fang; Zhou, Changsong

    2016-04-01

    Microsaccades are very small eye movements during fixation. Experimentally, they have been found to play an important role in visual information processing. However, neural responses induced by microsaccades are not yet well understood and are rarely studied theoretically. Here we propose a network model with a cascading adaptation including both retinal adaptation and short-term depression (STD) at thalamocortical synapses. In the neural network model, we compare the microsaccade-induced neural responses in the presence of STD and those without STD. It is found that the cascading with STD can give rise to faster and sharper responses to microsaccades. Moreover, STD can enhance response effectiveness and sensitivity to microsaccadic spatiotemporal changes, suggesting improved detection of small eye movements (or moving visual objects). We also explore the mechanism of the response properties in the model. Our studies strongly indicate that STD plays an important role in neural responses to microsaccades. Our model considers simultaneously retinal adaptation and STD at thalamocortical synapses in the study of microsaccade-induced neural activity, and may be useful for further investigation of the functional roles of microsaccades in visual information processing.

  16. Fast response and high sensitivity to microsaccades in a cascading-adaptation neural network with short-term synaptic depression.

    PubMed

    Yuan, Wu-Jie; Zhou, Jian-Fang; Zhou, Changsong

    2016-04-01

    Microsaccades are very small eye movements during fixation. Experimentally, they have been found to play an important role in visual information processing. However, neural responses induced by microsaccades are not yet well understood and are rarely studied theoretically. Here we propose a network model with a cascading adaptation including both retinal adaptation and short-term depression (STD) at thalamocortical synapses. In the neural network model, we compare the microsaccade-induced neural responses in the presence of STD and those without STD. It is found that the cascading with STD can give rise to faster and sharper responses to microsaccades. Moreover, STD can enhance response effectiveness and sensitivity to microsaccadic spatiotemporal changes, suggesting improved detection of small eye movements (or moving visual objects). We also explore the mechanism of the response properties in the model. Our studies strongly indicate that STD plays an important role in neural responses to microsaccades. Our model considers simultaneously retinal adaptation and STD at thalamocortical synapses in the study of microsaccade-induced neural activity, and may be useful for further investigation of the functional roles of microsaccades in visual information processing. PMID:27176307

  17. Bacterial economics: adaptation to stress conditions via stage-wise changes in the response mechanism.

    PubMed

    Baranyi, J; Metris, A; George, S M

    2015-02-01

    Common features of microbial adaptation are analysed with mathematical models and extended to stress conditions when the bacterial population declines before growing again. A parallel is drawn between bacterial and human communities in terms of non-mutation-based adaptation (acclimation) to stress. For a case study, the behaviour of Escherichia coli under osmotic stress, is detailed. It is suggested that stress modelling adaptation should be the focus of further developments in predictive food microbiology.

  18. A Comparison of the Adaptive Immune Response between Recovered Anthrax Patients and Individuals Receiving Three Different Anthrax Vaccines

    PubMed Central

    Laws, Thomas R.; Kuchuloria, Tinatin; Chitadze, Nazibriola; Little, Stephen F.; Webster, Wendy M.; Debes, Amanda K.; Saginadze, Salome; Tsertsvadze, Nikoloz; Chubinidze, Mariam; Rivard, Robert G.; Tsanava, Shota; Dyson, Edward H.; Simpson, Andrew J. H.; Hepburn, Matthew J.; Trapaidze, Nino

    2016-01-01

    Several different human vaccines are available to protect against anthrax. We compared the human adaptive immune responses generated by three different anthrax vaccines or by previous exposure to cutaneous anthrax. Adaptive immunity was measured by ELISPOT to count cells that produce interferon (IFN)-γ in response to restimulation ex vivo with the anthrax toxin components PA, LF and EF and by measuring circulating IgG specific to these antigens. Neutralising activity of antisera against anthrax toxin was also assayed. We found that the different exposures to anthrax antigens promoted varying immune responses. Cutaneous anthrax promoted strong IFN-γ responses to all three antigens and antibody responses to PA and LF. The American AVA and Russian LAAV vaccines induced antibody responses to PA only. The British AVP vaccine produced IFN-γ responses to EF and antibody responses to all three antigens. Anti-PA (in AVA and LAAV vaccinees) or anti-LF (in AVP vaccinees) antibody titres correlated with toxin neutralisation activities. Our study is the first to compare all three vaccines in humans and show the diversity of responses against anthrax antigens. PMID:27007118

  19. A Comparison of the Adaptive Immune Response between Recovered Anthrax Patients and Individuals Receiving Three Different Anthrax Vaccines.

    PubMed

    Laws, Thomas R; Kuchuloria, Tinatin; Chitadze, Nazibriola; Little, Stephen F; Webster, Wendy M; Debes, Amanda K; Saginadze, Salome; Tsertsvadze, Nikoloz; Chubinidze, Mariam; Rivard, Robert G; Tsanava, Shota; Dyson, Edward H; Simpson, Andrew J H; Hepburn, Matthew J; Trapaidze, Nino

    2016-01-01

    Several different human vaccines are available to protect against anthrax. We compared the human adaptive immune responses generated by three different anthrax vaccines or by previous exposure to cutaneous anthrax. Adaptive immunity was measured by ELISPOT to count cells that produce interferon (IFN)-γ in response to restimulation ex vivo with the anthrax toxin components PA, LF and EF and by measuring circulating IgG specific to these antigens. Neutralising activity of antisera against anthrax toxin was also assayed. We found that the different exposures to anthrax antigens promoted varying immune responses. Cutaneous anthrax promoted strong IFN-γ responses to all three antigens and antibody responses to PA and LF. The American AVA and Russian LAAV vaccines induced antibody responses to PA only. The British AVP vaccine produced IFN-γ responses to EF and antibody responses to all three antigens. Anti-PA (in AVA and LAAV vaccinees) or anti-LF (in AVP vaccinees) antibody titres correlated with toxin neutralisation activities. Our study is the first to compare all three vaccines in humans and show the diversity of responses against anthrax antigens. PMID:27007118

  20. A Comparison of the Adaptive Immune Response between Recovered Anthrax Patients and Individuals Receiving Three Different Anthrax Vaccines.

    PubMed

    Laws, Thomas R; Kuchuloria, Tinatin; Chitadze, Nazibriola; Little, Stephen F; Webster, Wendy M; Debes, Amanda K; Saginadze, Salome; Tsertsvadze, Nikoloz; Chubinidze, Mariam; Rivard, Robert G; Tsanava, Shota; Dyson, Edward H; Simpson, Andrew J H; Hepburn, Matthew J; Trapaidze, Nino

    2016-01-01

    Several different human vaccines are available to protect against anthrax. We compared the human adaptive immune responses generated by three different anthrax vaccines or by previous exposure to cutaneous anthrax. Adaptive immunity was measured by ELISPOT to count cells that produce interferon (IFN)-γ in response to restimulation ex vivo with the anthrax toxin components PA, LF and EF and by measuring circulating IgG specific to these antigens. Neutralising activity of antisera against anthrax toxin was also assayed. We found that the different exposures to anthrax antigens promoted varying immune responses. Cutaneous anthrax promoted strong IFN-γ responses to all three antigens and antibody responses to PA and LF. The American AVA and Russian LAAV vaccines induced antibody responses to PA only. The British AVP vaccine produced IFN-γ responses to EF and antibody responses to all three antigens. Anti-PA (in AVA and LAAV vaccinees) or anti-LF (in AVP vaccinees) antibody titres correlated with toxin neutralisation activities. Our study is the first to compare all three vaccines in humans and show the diversity of responses against anthrax antigens.

  1. Cytogenetic adaptive response with multiple small X-ray doses in mouse germ cells and its biological influence on the offspring of adapted males.

    PubMed

    Cai, L; Wang, P; Piao, X G

    1994-06-01

    Cytogenetic adaptive response of mouse germ cells was studied by exposing male mice to a sequence of 4 conditioning doses of 0.05 Gy each (D1) administered at 10-day intervals and subsequently to a single challenging dose of 1.5 Gy (D2). In concurrent experiments, male mice after treatment with D1 doses alone were mated to unirradiated females and the F1 males were given the D2 dose. Chromosomal aberrations in both spermatocytes and bone-marrow cells and UV-induced UDS in splenocytes of these mice were studied. Adapted mice (i.e., D1 + D2 exposures) responded with a significantly lower frequency of chromosomal aberrations than the non-adapted (D2 exposure only) controls. The relative reduction in frequencies was, however, similar to that observed in earlier work with a single conditioning dose of 0.05 Gy. The frequencies of chromosomal aberrations in spermatocytes and bone-marrow cells as well as the levels of UV-induced UDS in splenocytes of the F1 males in the group D1 to fathers + D2 to F1 males were the same as those in F1 males which received only the D2 exposure. PMID:7515464

  2. Horizontal vestibuloocular reflex evoked by high-acceleration rotations in the squirrel monkey. IV. Responses after spectacle-induced adaptation

    NASA Technical Reports Server (NTRS)

    Clendaniel, R. A.; Lasker, D. M.; Minor, L. B.; Shelhamer, M. J. (Principal Investigator)

    2001-01-01

    The horizontal angular vestibuloocular reflex (VOR) evoked by sinusoidal rotations from 0.5 to 15 Hz and acceleration steps up to 3,000 degrees /s(2) to 150 degrees /s was studied in six squirrel monkeys following adaptation with x2.2 magnifying and x0.45 minimizing spectacles. For sinusoidal rotations with peak velocities of 20 degrees /s, there were significant changes in gain at all frequencies; however, the greatest gain changes occurred at the lower frequencies. The frequency- and velocity-dependent gain enhancement seen in normal monkeys was accentuated following adaptation to magnifying spectacles and diminished with adaptation to minimizing spectacles. A differential increase in gain for the steps of acceleration was noted after adaptation to the magnifying spectacles. The gain during the acceleration portion, G(A), of a step of acceleration (3,000 degrees /s(2) to 150 degrees /s) increased from preadaptation values of 1.05 +/- 0.08 to 1.96 +/- 0.16, while the gain during the velocity plateau, G(V), only increased from 0.93 +/- 0.04 to 1.36 +/- 0.08. Polynomial fits to the trajectory of the response during the acceleration step revealed a greater increase in the cubic than the linear term following adaptation with the magnifying lenses. Following adaptation to the minimizing lenses, the value of G(A) decreased to 0.61 +/- 0.08, and the value of G(V) decreased to 0.59 +/- 0.09 for the 3,000 degrees /s(2) steps of acceleration. Polynomial fits to the trajectory of the response during the acceleration step revealed that there was a significantly greater reduction in the cubic term than in the linear term following adaptation with the minimizing lenses. These findings indicate that there is greater modification of the nonlinear as compared with the linear component of the VOR with spectacle-induced adaptation. In addition, the latency to the onset of the adapted response varied with the dynamics of the stimulus. The findings were modeled with a bilateral model

  3. Olive response to water availability: yield response functions, soil water content indicators and evaluation of adaptability to climate change

    NASA Astrophysics Data System (ADS)

    Riccardi, Maria; Alfieri, Silvia Maria; Basile, Angelo; Bonfante, Antonello; Menenti, Massimo; Monaco, Eugenia; De Lorenzi, Francesca

    2013-04-01

    Climate evolution, with the foreseen increase of temperature and frequency of drought events during the summer, could cause significant changes in the availability of water resources specially in the Mediterranean region. European countries need to encourage sustainable agriculture practices, reducing inputs, especially of water, and minimizing any negative impact on crop quantity and quality. Olive is an important crop in the Mediterranean region that has traditionally been cultivated with no irrigation and is known to attain acceptable production under dry farming. Therefore this crop will not compete for foreseen reduced water resources. However, a good quantitative knowledge must be available about effects of reduced precipitation and water availability on yield. Yield response functions, coupled with indicators of soil water availability, provide a quantitative description of the cultivar- specific behavior in relation to hydrological conditions. Yield response functions of 11 olive cultivars, typical of Mediterranean environment, were determined using experimental data (unpublished or reported in scientific literature). The yield was expressed as relative yield (Yr); the soil water availability was described by means of different indicators: relative soil water deficit (RSWD), relative evapotranspiration (RED) and transpiration deficit (RTD). Crops can respond nonlinearly to changes in their growing conditions and exhibit threshold responses, so for the yield functions of each olive cultivar both linear regression and threshold-slope models were considered to evaluate the best fit. The level of relative yield attained in rain-fed conditions was identified and defined as the acceptable yield level (Yrrainfed). The value of the indicator (RSWD, RED and RTD) corresponding to Yrrainfed was determined for each cultivar and indicated as the critical value of water availability. The error in the determination of the critical value was estimated. By means of a

  4. Immune response of mice to non-adapted avian influenza A virus.

    PubMed

    Stropkovská, A; Mikušková, T; Bobišová, Z; Košík, I; Mucha, V; Kostolanský, F; Varečková, E

    2015-12-01

    Human infections with avian influenza A viruses (IAVs) without or with clinical symptoms of disease were recently reported from several continents, mainly in high risk groups of people, who came into the contact with infected domestic birds or poultry. It was shown that avian IAVs are able to infect humans directly without previous adaptation, however, their ability to replicate and to cause a disease in this new host can differ. No spread of these avian IAVs among humans has been documented until now, except for one case described in Netherlands in the February of 2003 in people directly involved in handling IAV (H7N7)-infected poultry. The aim of our work was to examine whether a low pathogenic avian IAV can induce a virus-specific immune response of biological relevancy, in spite of its restricted replication in mammals. As a model we used a low pathogenic virus A/Duck/Czechoslovakia/1956 (H4N6) (A/Duck), which replicated well in MDCK cells and produced plaques on cell monolayers, but was unable to replicate productively in mouse lungs. We examined how the immune system of mice responds to the intranasal application of this non-adapted avian virus. Though we did not prove the infectious virus in lungs of mice following A/Duck application even after its multiple passaging in mice, we detected virus-specific vRNA till day 8 post infection. Moreover, we detected virus-specific mRNA and de novo synthesized viral nucleoprotein (NP) and membrane protein (M1) in lungs of mice on day 2 and 4 after exposure to A/Duck. Virus-specific antibodies in sera of these mice were detectable by ELISA already after a single intranasal dose of A/Duck virus. Not only antibodies specific to the surface glycoprotein hemagglutinin (HA) were induced, but also antibodies specific to the NP and M1 of IAV were detected by Western blot and their titers increased after the second exposure of mice to this virus. Importantly, antibodies neutralizing virus A/Duck were proved in mouse

  5. Immune response of mice to non-adapted avian influenza A virus.

    PubMed

    Stropkovská, A; Mikušková, T; Bobišová, Z; Košík, I; Mucha, V; Kostolanský, F; Varečková, E

    2015-12-01

    Human infections with avian influenza A viruses (IAVs) without or with clinical symptoms of disease were recently reported from several continents, mainly in high risk groups of people, who came into the contact with infected domestic birds or poultry. It was shown that avian IAVs are able to infect humans directly without previous adaptation, however, their ability to replicate and to cause a disease in this new host can differ. No spread of these avian IAVs among humans has been documented until now, except for one case described in Netherlands in the February of 2003 in people directly involved in handling IAV (H7N7)-infected poultry. The aim of our work was to examine whether a low pathogenic avian IAV can induce a virus-specific immune response of biological relevancy, in spite of its restricted replication in mammals. As a model we used a low pathogenic virus A/Duck/Czechoslovakia/1956 (H4N6) (A/Duck), which replicated well in MDCK cells and produced plaques on cell monolayers, but was unable to replicate productively in mouse lungs. We examined how the immune system of mice responds to the intranasal application of this non-adapted avian virus. Though we did not prove the infectious virus in lungs of mice following A/Duck application even after its multiple passaging in mice, we detected virus-specific vRNA till day 8 post infection. Moreover, we detected virus-specific mRNA and de novo synthesized viral nucleoprotein (NP) and membrane protein (M1) in lungs of mice on day 2 and 4 after exposure to A/Duck. Virus-specific antibodies in sera of these mice were detectable by ELISA already after a single intranasal dose of A/Duck virus. Not only antibodies specific to the surface glycoprotein hemagglutinin (HA) were induced, but also antibodies specific to the NP and M1 of IAV were detected by Western blot and their titers increased after the second exposure of mice to this virus. Importantly, antibodies neutralizing virus A/Duck were proved in mouse

  6. iTRAQ-based proteomic analysis of adaptive response in the regenerating limb of the Cynops orientalis newt.

    PubMed

    Geng, Xiao-Fang; Guo, Jian-Lin; Zang, Xia-Yan; Sun, Jing-Yan; Li, Peng-Fei; Zhang, Fu-Chun; Xu, Cun-Shuan

    2015-01-01

    The newt has the powerful capacity to regenerate lost limbs following amputation, and represents an excellent model organism to study regenerative processes. However, the molecular basis of the adaptive response in the regenerating limb of the Chinese fire-bellied newt Cynops orientalis immediately after amputation remains unclear. To better understand the adaptive response immediately after limb amputation at the protein level, we used isobaric tags for relative and absolute quantitation (iTRAQ) coupled with LC-MS/MS methods to analyze changes in the proteome of the regenerating newt limb that occurred 2 h and 8 h after amputation. We identified 152 proteins with more than 1.5-fold change in expression compared to control. GO annotation analysis classified these proteins into several categories such as signaling, Ca(2+) binding and translocation, transcription and translation, immune response, cell death, cytoskeleton, metabolism, etc. Further ingenuity pathway analysis (IPA) showed that several signaling pathways were significantly changed at 2 h and 8 h after amputation, including EIF2 signaling, acute phase response signaling, tight junction signaling and calcium signaling, suggesting these pathways may be closely related to the adaptive response immediately after limb amputation. This work provides novel insights into understanding the molecular processes related to newt limb regeneration immediately after amputation, and a basis for further study of regenerative medicine. PMID:26864489

  7. Arousal regulation and affective adaptation to human responsiveness by a robot that explores and learns a novel environment.

    PubMed

    Hiolle, Antoine; Lewis, Matthew; Cañamero, Lola

    2014-01-01

    In the context of our work in developmental robotics regarding robot-human caregiver interactions, in this paper we investigate how a "baby" robot that explores and learns novel environments can adapt its affective regulatory behavior of soliciting help from a "caregiver" to the preferences shown by the caregiver in terms of varying responsiveness. We build on two strands of previous work that assessed independently (a) the differences between two "idealized" robot profiles-a "needy" and an "independent" robot-in terms of their use of a caregiver as a means to regulate the "stress" (arousal) produced by the exploration and learning of a novel environment, and (b) the effects on the robot behaviors of two caregiving profiles varying in their responsiveness-"responsive" and "non-responsive"-to the regulatory requests of the robot. Going beyond previous work, in this paper we (a) assess the effects that the varying regulatory behavior of the two robot profiles has on the exploratory and learning patterns of the robots; (b) bring together the two strands previously investigated in isolation and take a step further by endowing the robot with the capability to adapt its regulatory behavior along the "needy" and "independent" axis as a function of the varying responsiveness of the caregiver; and (c) analyze the effects that the varying regulatory behavior has on the exploratory and learning patterns of the adaptive robot.

  8. Stress response in Pectobacterium atrosepticum SCRI1043 under starvation conditions: adaptive reactions at a low population density.

    PubMed

    Petrova, Olga; Gorshkov, Vladimir; Daminova, Amina; Ageeva, Marina; Moleleki, Lucy N; Gogolev, Yuri

    2014-01-01

    The adaptive reactions of plant pathogenic bacterium Pectobacterium atrosepticum SCRI1043 under starvation conditions were studied. The main emphasis was given to the peculiarities of stress responses depending on the bacterial population densities. When bacteria were subjected to starvation at high population densities (10(7)-10(9) CFU ml(-1)), their adaptive reactions conformed to the conventional conception of bacterial adaptation related to autolysis of part of the population, specific modification of cell ultrastructure, activation of expression of stress responsive genes and acquiring cross protection against other stress factors. In contrast, at low initial population densities (10(3)-10(5) CFU ml(-1)), as described in our recent work, the cell density increased due to multiple cell division despite the absence of exogenous growth substrate. Here we present data that demonstrate that such unconventional behavior is part of a stress response, which provides increased stress tolerance while retaining virulence. Cell morphology and gene expression in high- and low-cell-density starving Pba cultures were compared. Our investigation demonstrates the existence of alternative adaptive strategies enabling pathogenic bacteria to cope with a variety of stress factors, including starvation, especially necessary when residing outside of their host.

  9. On the Issue of Item Selection in Computerized Adaptive Testing with Response Times

    ERIC Educational Resources Information Center

    Veldkamp, Bernard P.

    2016-01-01

    Many standardized tests are now administered via computer rather than paper-and-pencil format. The computer-based delivery mode brings with it certain advantages. One advantage is the ability to adapt the difficulty level of the test to the ability level of the test taker in what has been termed computerized adaptive testing (CAT). A second…

  10. Addressing the limits to adaptation across four damage--response systems

    EPA Science Inventory

    Our ability to adapt to climate change is not boundless, and previous modeling shows that capacity limited adaptation will play a policy-significant role in future decisions about climate change. These limits are delineated by capacity thresholds, after which climate damages beg...

  11. Genomic, transcriptomic and phenomic variation reveals the complex adaptation to stress response of modern maize breeding

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Early maize adaptation to different agricultural environments was an important process associated with the creation of a stable food supply that allowed the evolution of human civilization in the Americas. To explore the mechanisms of maize adaptation, genomic, transcriptomic and phenomic data were ...

  12. Adaptive and nonadaptive responses to voluntary wheel running by mdx mice.

    PubMed

    Landisch, Rachel M; Kosir, Allison M; Nelson, Steven A; Baltgalvis, Kristen A; Lowe, Dawn A

    2008-10-01

    The purpose of this study was to determine the extent to which hindlimb muscles of mdx mice adapt to a voluntary endurance type of exercise. mdx and C57BL mice engaged in 8 weeks of wheel running or maintained normal cage activities. Beneficial adaptations that occurred in mdx mice included changes in muscle mass, fiber size, and fiber types based on myosin heavy chain (MHC) isoform expression. These adaptations occurred without increases in fiber central nuclei and embryonic MHC expression. An undesirable outcome, however, was that muscle mitochondrial enzyme activities did not improve with exercise in mdx mice as they did in C57BL mice. Cellular remodeling of dystrophic muscle following exercise has not been studied adequately. In this study we found that some, but not all, of the expected adaptations occurred in mdx mouse muscle. We must better understand these (non)adaptations in order to inform individuals with DMD about the benefits of exercise.

  13. Adaptive strategies in nocturnally migrating insects and songbirds: contrasting responses to wind.

    PubMed

    Chapman, Jason W; Nilsson, Cecilia; Lim, Ka S; Bäckman, Johan; Reynolds, Don R; Alerstam, Thomas

    2016-01-01

    Animals that use flight as their mode of transportation must cope with the fact that their migration and orientation performance is strongly affected by the flow of the medium they are moving in, that is by the winds. Different strategies can be used to mitigate the negative effects and benefit from the positive effects of a moving flow. The strategies an animal can use will be constrained by the relationship between the speed of the flow and the speed of the animal's own propulsion in relation to the surrounding air. Here we analyse entomological and ornithological radar data from north-western Europe to investigate how two different nocturnal migrant taxa, the noctuid moth Autographa gamma and songbirds, deal with wind by analysing variation in resulting flight directions in relation to the wind-dependent angle between the animal's heading and track direction. Our results, from fixed locations along the migratory journey, reveal different global strategies used by moths and songbirds during their migratory journeys. As expected, nocturnally migrating moths experienced a greater degree of wind drift than nocturnally migrating songbirds, but both groups were more affected by wind in autumn than in spring. The songbirds' strategies involve elements of both drift and compensation, providing some benefits from wind in combination with destination and time control. In contrast, moths expose themselves to a significantly higher degree of drift in order to obtain strong wind assistance, surpassing the songbirds in mean ground speed, at the cost of a comparatively lower spatiotemporal migratory precision. Moths and songbirds show contrasting but adaptive responses to migrating through a moving flow, which are fine-tuned to the respective flight capabilities of each group in relation to the wind currents they travel within.

  14. Using Rapid-Response Scenario-Building Methodology for Climate Change Adaptation Planning

    NASA Astrophysics Data System (ADS)

    Ludwig, K. A.; Stoepler, T. M.; Schuster, R.

    2015-12-01

    Rapid-response scenario-building methodology can be modified to develop scenarios for slow-onset disasters associated with climate change such as drought. Results of a collaboration between the Department of the Interior (DOI) Strategic Sciences Group (SSG) and the Southwest Colorado Social-Ecological Climate Resilience Project are presented in which SSG scenario-building methods were revised and applied to climate change adaptation planning in Colorado's Gunnison Basin, United States. The SSG provides the DOI with the capacity to rapidly assemble multidisciplinary teams of experts to develop scenarios of the potential environmental, social, and economic cascading consequences of environmental crises, and to analyze these chains to determine actionable intervention points. By design, the SSG responds to acute events of a relatively defined duration. As a capacity-building exercise, the SSG explored how its scenario-building methodology could be applied to outlining the cascading consequences of slow-onset events related to climate change. SSG staff facilitated two workshops to analyze the impacts of drought, wildfire, and insect outbreak in the sagebrush and spruce-fir ecosystems. Participants included local land managers, natural and social scientists, ranchers, and other stakeholders. Key findings were: 1) scenario framing must be adjusted to accommodate the multiple, synergistic components and longer time frames of slow-onset events; 2) the development of slow-onset event scenarios is likely influenced by participants having had more time to consider potential consequences, relative to acute events; 3) participants who are from the affected area may have a more vested interest in the outcome and/or may be able to directly implement interventions.

  15. Differential Molecular Responses of Rapeseed Cotyledons to Light and Dark Reveal Metabolic Adaptations toward Autotrophy Establishment

    PubMed Central

    He, Dongli; Damaris, Rebecca N.; Fu, Jinlei; Tu, Jinxing; Fu, Tingdong; Xi, Chen; Yi, Bin; Yang, Pingfang

    2016-01-01

    Photosynthesis competent autotrophy is established during the postgerminative stage of plant growth. Among the multiple factors, light plays a decisive role in the switch from heterotrophic to autotrophic growth. Under dark conditions, the rapeseed hypocotyl extends quickly with an apical hook, and the cotyledon is yellow and folded, and maintains high levels of the isocitrate lyase (ICL). By contrast, in the light, the hypocotyl extends slowly, the cotyledon unfolds and turns green, the ICL content changes in parallel with cotyledon greening. To reveal metabolic adaptations during the establishment of postgerminative autotrophy in rapeseed, we conducted comparative proteomic and metabolomic analyses of the cotyledons of seedlings grown under light versus dark conditions. Under both conditions, the increase in proteases, fatty acid β-oxidation and glyoxylate-cycle related proteins was accompanied by rapid degradation of the stored proteins and lipids with an accumulation of the amino acids. While light condition partially retarded these conversions. Light significantly induced the expression of chlorophyll-binding and photorespiration related proteins, resulting in an increase in reducing-sugars. However, the levels of some chlorophyllide conversion, Calvin-cycle and photorespiration related proteins also accumulated in dark grown cotyledons, implying that the transition from heterotrophy to autotrophy is programmed in the seed rather than induced by light. Various anti-stress systems, e.g., redox related proteins, salicylic acid, proline and chaperones, were employed to decrease oxidative stress, which was mainly derived from lipid oxidation or photorespiration, under both conditions. This study provides a comprehensive understanding of the differential molecular responses of rapeseed cotyledons to light and dark conditions, which will facilitate further study on the complex mechanism underlying the transition from heterotrophy to autotrophy. PMID:27471506

  16. Adaptive strategies in nocturnally migrating insects and songbirds: contrasting responses to wind.

    PubMed

    Chapman, Jason W; Nilsson, Cecilia; Lim, Ka S; Bäckman, Johan; Reynolds, Don R; Alerstam, Thomas

    2016-01-01

    Animals that use flight as their mode of transportation must cope with the fact that their migration and orientation performance is strongly affected by the flow of the medium they are moving in, that is by the winds. Different strategies can be used to mitigate the negative effects and benefit from the positive effects of a moving flow. The strategies an animal can use will be constrained by the relationship between the speed of the flow and the speed of the animal's own propulsion in relation to the surrounding air. Here we analyse entomological and ornithological radar data from north-western Europe to investigate how two different nocturnal migrant taxa, the noctuid moth Autographa gamma and songbirds, deal with wind by analysing variation in resulting flight directions in relation to the wind-dependent angle between the animal's heading and track direction. Our results, from fixed locations along the migratory journey, reveal different global strategies used by moths and songbirds during their migratory journeys. As expected, nocturnally migrating moths experienced a greater degree of wind drift than nocturnally migrating songbirds, but both groups were more affected by wind in autumn than in spring. The songbirds' strategies involve elements of both drift and compensation, providing some benefits from wind in combination with destination and time control. In contrast, moths expose themselves to a significantly higher degree of drift in order to obtain strong wind assistance, surpassing the songbirds in mean ground speed, at the cost of a comparatively lower spatiotemporal migratory precision. Moths and songbirds show contrasting but adaptive responses to migrating through a moving flow, which are fine-tuned to the respective flight capabilities of each group in relation to the wind currents they travel within. PMID:26147535

  17. Differential Molecular Responses of Rapeseed Cotyledons to Light and Dark Reveal Metabolic Adaptations toward Autotrophy Establishment.

    PubMed

    He, Dongli; Damaris, Rebecca N; Fu, Jinlei; Tu, Jinxing; Fu, Tingdong; Xi, Chen; Yi, Bin; Yang, Pingfang

    2016-01-01

    Photosynthesis competent autotrophy is established during the postgerminative stage of plant growth. Among the multiple factors, light plays a decisive role in the switch from heterotrophic to autotrophic growth. Under dark conditions, the rapeseed hypocotyl extends quickly with an apical hook, and the cotyledon is yellow and folded, and maintains high levels of the isocitrate lyase (ICL). By contrast, in the light, the hypocotyl extends slowly, the cotyledon unfolds and turns green, the ICL content changes in parallel with cotyledon greening. To reveal metabolic adaptations during the establishment of postgerminative autotrophy in rapeseed, we conducted comparative proteomic and metabolomic analyses of the cotyledons of seedlings grown under light versus dark conditions. Under both conditions, the increase in proteases, fatty acid β-oxidation and glyoxylate-cycle related proteins was accompanied by rapid degradation of the stored proteins and lipids with an accumulation of the amino acids. While light condition partially retarded these conversions. Light significantly induced the expression of chlorophyll-binding and photorespiration related proteins, resulting in an increase in reducing-sugars. However, the levels of some chlorophyllide conversion, Calvin-cycle and photorespiration related proteins also accumulated in dark grown cotyledons, implying that the transition from heterotrophy to autotrophy is programmed in the seed rather than induced by light. Various anti-stress systems, e.g., redox related proteins, salicylic acid, proline and chaperones, were employed to decrease oxidative stress, which was mainly derived from lipid oxidation or photorespiration, under both conditions. This study provides a comprehensive understanding of the differential molecular responses of rapeseed cotyledons to light and dark conditions, which will facilitate further study on the complex mechanism underlying the transition from heterotrophy to autotrophy. PMID:27471506

  18. Apnea stimulates the adaptive response to oxidative stress in elephant seal pups.

    PubMed

    Vázquez-Medina, José Pablo; Zenteno-Savín, Tania; Tift, Michael S; Forman, Henry Jay; Crocker, Daniel E; Ortiz, Rudy M

    2011-12-15

    Extended breath-hold (apnea) bouts are routine during diving and sleeping in seals. These apneas result in oxygen store depletion and blood flow redistribution towards obligatory oxygen-dependent tissues, exposing seals to critical levels of ischemia and hypoxemia. The subsequent reperfusion/reoxygenation has the potential to increase oxidant production and thus oxidative stress. The contributions of extended apnea to oxidative stress in adapted mammals are not well defined. To address the hypothesis that apnea in seals is not associated with increased oxidative damage, blood samples were collected from northern elephant seal pups (N=6) during eupnea, rest- and voluntary submersion-associated apneas, and post-apnea (recovery). Plasma 4-hydroxynonenal (HNE), 8-isoprostanes (8-isoPGF(2α)), nitrotyrosine (NT), protein carbonyls, xanthine and hypoxanthine (HX) levels, along with xanthine oxidase (XO) activity, were measured. Protein content of XO, superoxide dismutase 1 (Cu,ZnSOD), catalase and myoglobin (Mb), as well as the nuclear content of hypoxia inducible factor 1α (HIF-1α) and NF-E2-related factor 2 (Nrf2), were measured in muscle biopsies collected before and after the breath-hold trials. HNE, 8-iso PGF(2α), NT and protein carbonyl levels did not change among eupnea, apnea or recovery. XO activity and HX and xanthine concentrations were increased at the end of the apneas and during recovery. Muscle protein content of XO, CuZnSOD, catalase, Mb, HIF-1α and Nrf2 increased 25-70% after apnea. Results suggest that rather than inducing the damaging effects of hypoxemia and ischemia/reperfusion that have been reported in non-diving mammals, apnea in seals stimulates the oxidative stress and hypoxic hormetic responses, allowing these mammals to cope with the potentially detrimental effects associated with this condition.

  19. The Adaptive Response in p53 Cancer Prone Mice: Loss of heterozygosity and Genomic Instability

    SciTech Connect

    Josee, Lavoie; Dolling, Jo-Anna; Mitchel, Ron E.J.; Boreham, Douglas R.

    2004-09-28

    The Trp53 gene is clearly associated with increased cancer risk. This, coupled with the broad understanding of its mode of action at the molecular level, makes this gene a good candidate for investigating the relationship between genetic risk factors and spontaneous cancer occurring in a mouse model exposed to low dose radiation. We have shown that adaptive response to chronic low dose radiation could increase cancer latency, as well as overall lifespan. To better understand the molecular processes that influence cellular risk, modern tools in molecular biology were used to evaluate the loss of heterozigozity (LOH) at the Trp53 locus, and chromosomal instability in the cells from mice exposed to chronic low dose radiation. Female mice carrying a single defective copy of the Trp53 gene were irradiated with doses of gamma-radiation delivered at a low dose rate of about 0.7 mGy/hr. Groups of mice (5 irradiated and 5 unexposed) were exposed to 0.33 mGy per day for 15, 30, 45, 60, 67 and 75 weeks equaling total body doses of 2.4, 4.7, 7.2, 9.7, 10.9 and 12.1 cGy, respectively. The presence of a single defective copy of the Trp53 gene increases cancer risk in these mice. However, in vivo exposure to low dose radiation increased cancer latency. We hypothesized that: (1) These mice might have spontaneous chromosome instability, and (2) that this low dose adaptive exposure would reduce the chromosomal instability. This instability was investigated using spectral karyotyping (SKY). Bone marrow cells from 5 irradiated mice (doses of 10.9 and 12.1 cGy) and 5 control mice were collected for metaphase harvest. Briefly, the cells were incubated at 37 C for 4 hours in RPMI containing 25% heat-inactivated FBS and 0.1 mg/ml colcemid, and then given a hypotonic treatment of 0.075M KCl for 20 minutes at 37 C. An average of 100 metaphases per mouse were karyotyped. The Trp53 heterozygous mice do not show apparent structural chromosome instability. From both unexposed and irradiated

  20. A family of variable step-size affine projection adaptive filter algorithms using statistics of channel impulse response

    NASA Astrophysics Data System (ADS)

    Shams Esfand Abadi, Mohammad; AbbasZadeh Arani, Seyed Ali Asghar

    2011-12-01

    This paper extends the recently introduced variable step-size (VSS) approach to the family of adaptive filter algorithms. This method uses prior knowledge of the channel impulse response statistic. Accordingly, optimal step-size vector is obtained by minimizing the mean-square deviation (MSD). The presented algorithms are the VSS affine projection algorithm (VSS-APA), the VSS selective partial update NLMS (VSS-SPU-NLMS), the VSS-SPU-APA, and the VSS selective regressor APA (VSS-SR-APA). In VSS-SPU adaptive algorithms the filter coefficients are partially updated which reduce the computational complexity. In VSS-SR-APA, the optimal selection of input regressors is performed during the adaptation. The presented algorithms have good convergence speed, low steady state mean square error (MSE), and low computational complexity features. We demonstrate the good performance of the proposed algorithms through several simulations in system identification scenario.

  1. A Microswitch-Cluster Program to Foster Adaptive Responses and Head Control in Students with Multiple Disabilities: Replication and Validation Assessment

    ERIC Educational Resources Information Center

    Lancioni, Giulio E.; Singh, Nirbhay N.; O'Reilly, Mark F.; Sigafoos, Jeff; Oliva, Doretta; Gatti, Michela; Manfredi, Francesco; Megna, Gianfranco; La Martire, Maria L.; Tota, Alessia; Smaldone, Angela; Groeneweg, Jop

    2008-01-01

    A program relying on microswitch clusters (i.e., combinations of microswitches) and preferred stimuli was recently developed to foster adaptive responses and head control in persons with multiple disabilities. In the last version of this program, preferred stimuli (a) are scheduled for adaptive responses occurring in combination with head control…

  2. Fostering Adaptive Responses and Head Control in Students with Multiple Disabilities through a Microswitch-Based Program: Follow-Up Assessment and Program Revision

    ERIC Educational Resources Information Center

    Lancioni, Giulio E.; Singh, Nirbhay N.; O'Reilly, Mark F.; Sigafoos, Jeff; Didden, Robert; Oliva, Doretta; Severini, Laura

    2007-01-01

    A program was recently developed to promote adaptive responses and upright head position in students with multiple disabilities through the use of microswitch clusters (i.e., combinations of two microswitches). The five students exposed to the program showed a significant increase in adaptive responses performed with head upright. The first…

  3. Contribution of radiation-induced, nitric oxide-mediated bystander effect to radiation-induced adaptive response.

    NASA Astrophysics Data System (ADS)

    Matsumoto, H.; Ohnishi, T.

    There has been a recent upsurge of interest in radiation-induced adaptive response and bystander effect which are specific modes in stress response to low-dose low-dose rate radiation Recently we found that the accumulation of inducible nitric oxide NO synthase iNOS in wt p53 cells was induced by chronic irradiation with gamma rays followed by acute irradiation with X-rays but not by each one resulting in an increase in nitrite concentrations of medium It is suggested that the accumulation of iNOS may be due to the depression of acute irradiation-induced p53 functions by pre-chronic irradiation In addition we found that the radiosensitivity of wt p53 cells against acute irradiation with X-rays was reduced after chronic irradiation with gamma rays This reduction of radiosensitivity of wt p53 cells was nearly completely suppressed by the addition of NO scavenger carboxy-PTIO to the medium This reduction of radiosensitivity of wt p53 cells is just radiation-induced adaptive response suggesting that NO-mediated bystander effect may considerably contribute to adaptive response induced by radiation

  4. Introduction to the symposium: responses of organisms to climate change: a synthetic approach to the role of thermal adaptation.

    PubMed

    Sears, Michael W; Angilletta, Michael J

    2011-11-01

    On a global scale, changing climates are affecting ecological systems across multiple levels of biological organization. Moreover, climates are changing at rates unprecedented in recent geological history. Thus, one of the most pressing concerns of the modern era is to understand the biological responses to climate such that society can both adapt and implement measures that attempt to offset the negative impacts of a rapidly changing climate. One crucial question, to understand organismal responses to climate, is whether the ability of organisms to adapt can keep pace with quickly changing environments. To address this question, a syntheses of knowledge from a broad set of biological disciplines will be needed that integrates information from the fields of ecology, behavior, physiology, genetics, and evolution. This symposium assembled a diverse group of scientists from these subdisciplines to present their perspectives regarding the ability of organisms to adapt to changing climates. Specifically, the goals of this symposia were to (1) highlight what each discipline brings to a discussion of organismal responses to climate, (2) to initiate and foster a discussion to break barriers in the transfer of knowledge across disciplines, and (3) to synthesize an approach to address ongoing issues concerning biological responses to climate.

  5. Is Linear Displacement Information Or Angular Displacement Information Used During The Adaptation of Pointing Responses To An Optically Shifted Image?

    NASA Technical Reports Server (NTRS)

    Bautista, Abigail B.

    1994-01-01

    Twenty-four observers looked through a pair of 20 diopter wedge prisms and pointed to an image of a target which was displaced vertically from eye level by 6 cm at a distance of 30 cm. Observers pointed 40 times, using only their right hand, and received error-corrective feedback upon termination of each pointing response (terminal visual feedback). At three testing distances, 20, 30, and 40 cm, ten pre-exposure and ten post-exposure pointing responses were recorded for each hand as observers reached to a mirror-viewed target located at eye level. The difference between pre- and post-exposure pointing response (adaptive shift) was compared for both Exposed and Unexposed hands across all three testing distances. The data were assessed according to the results predicted by two alternative models for processing spatial-information: one using angular displacement information and another using linear displacement information. The angular model of spatial mapping best predicted the observer's pointing response for the Exposed hand. Although the angular adaptive shift did not change significantly as a function of distance (F(2,44) = 1.12, n.s.), the linear adaptive shift increased significantly over the three testing distances 02 44) = 4.90 p less than 0.01).

  6. Coordinate actions of innate immune responses oppose those of the adaptive immune system during Salmonella infection of mice.

    PubMed

    Hotson, Andrew N; Gopinath, Smita; Nicolau, Monica; Khasanova, Anna; Finck, Rachel; Monack, Denise; Nolan, Garry P

    2016-01-12

    The immune system enacts a coordinated response when faced with complex environmental and pathogenic perturbations. We used the heterogeneous responses of mice to persistent Salmonella infection to model system-wide coordination of the immune response to bacterial burden. We hypothesized that the variability in outcomes of bacterial growth and immune response across genetically identical mice could be used to identify immune elements that serve as integrators enabling co-regulation and interconnectedness of the innate and adaptive immune systems. Correlation analysis of immune response variation to Salmonella infection linked bacterial load with at least four discrete, interacting functional immune response "cassettes." One of these, the innate cassette, in the chronically infected mice included features of the innate immune system, systemic neutrophilia, and high serum concentrations of the proinflammatory cytokine interleukin-6. Compared with mice with a moderate bacterial load, mice with the highest bacterial burden exhibited high activity of this innate cassette, which was associated with a dampened activity of the adaptive T cell cassette-with fewer plasma cells and CD4(+) T helper 1 cells and increased numbers of regulatory T cells-and with a dampened activity of the cytokine signaling cassette. System-wide manipulation of neutrophil numbers revealed that neutrophils regulated signal transducer and activator of transcription (STAT) signaling in B cells during infection. Thus, a network-level approach demonstrated unappreciated interconnections that balanced innate and adaptive immune responses during the dynamic course of disease and identified signals associated with pathogen transmission status, as well as a regulatory role for neutrophils in cytokine signaling.

  7. Adaptation to Cold and Proteomic Responses of the Psychrotrophic Biopreservative Lactococcus piscium Strain CNCM I-4031▿

    PubMed Central

    Garnier, Matthieu; Matamoros, Sebastien; Chevret, Didier; Pilet, Marie-France; Leroi, Francoise; Tresse, Odile

    2010-01-01

    There is considerable interest in the use of psychrotrophic bacteria for food biopreservation and in the understanding of cold adaptation mechanisms. The psychrotrophic biopreservative Lactococcus piscium strain CNCM I-4031 was studied for its growth behavior and proteomic responses after cold shock and during cold acclimation. Growth kinetics highlighted the absence of growth latency after cold shock, suggesting a very high promptness in cold adaptation, a behavior that has never been described before for lactic acid bacteria (LAB). A comparative proteomic analysis was applied with two-dimensional gel electrophoresis (2-DE), and upregulated proteins were identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Both cold shock and cold acclimation triggered the upregulation of proteins involved in general and oxidative stress responses and fatty acid and energetic metabolism. However, 2-DE profiles and upregulated proteins were different under both conditions, suggesting a sequence of steps in cold adaptation. In addition, the major 7-kDa Csp protein was identified in the L. piscium CNCM I-4031 genome but was not cold regulated. The implication of the identified cold shock proteins and cold acclimation proteins in efficient cold adaptation, the possible regulation of a histidyl phosphocarrier protein, and the roles of a constitutive major 7-kDa Csp are discussed. PMID:20935127

  8. Plasticity in reproduction and growth among 52 range-wide populations of a Mediterranean conifer: adaptive responses to environmental stress.

    PubMed

    Santos-Del-Blanco, L; Bonser, S P; Valladares, F; Chambel, M R; Climent, J

    2013-09-01

    A plastic response towards enhanced reproduction is expected in stressful environments, but it is assumed to trade off against vegetative growth and efficiency in the use of available resources deployed in reproduction [reproductive efficiency (RE)]. Evidence supporting this expectation is scarce for plants, particularly for long-lived species. Forest trees such as Mediterranean pines provide ideal models to study the adaptive value of allocation to reproduction vs. vegetative growth given their among-population differentiation for adaptive traits and their remarkable capacity to cope with dry and low-fertility environments. We studied 52 range-wide Pinus halepensis populations planted into two environmentally contrasting sites during their initial reproductive stage. We investigated the effect of site, population and their interaction on vegetative growth, threshold size for female reproduction, reproductive-vegetative size relationships and RE. We quantified correlations among traits and environmental variables to identify allocation trade-offs and ecotypic trends. Genetic variation for plasticity was high for vegetative growth, whereas it was nonsignificant for reproduction. Size-corrected reproduction was enhanced in the more stressful site supporting the expectation for adverse conditions to elicit plastic responses in reproductive allometry. However, RE was unrelated with early reproductive investment. Our results followed theoretical predictions and support that phenotypic plasticity for reproduction is adaptive under stressful environments. Considering expectations of increased drought in the Mediterranean, we hypothesize that phenotypic plasticity together with natural selection on reproductive traits will play a relevant role in the future adaptation of forest tree species.

  9. Adaptation of visually evoked responses of relay cells in the dorsal lateral geniculate nucleus of the cat following prolonged exposure to drifting gratings.

    PubMed

    Shou, T; Li, X; Zhou, Y; Hu, B

    1996-01-01

    Adaptation of visual cortical cells' responses is observed following repeated presentation of grating stimuli. Grating adaptation is believed to exist only at the cortical level. The purpose of this study was to see if grating adaptation also occurs in the lateral geniculate nucleus. We studied the responses of 164 relay cells in layer A and A1 of the dorsal lateral geniculate nucleus (LGNd) to grating stimuli. Normal cats, as well as cats in which visual cortex was ablated, were studied. Adaptation was investigated using repeated presentation of gratings of different contrasts and orientations. The results showed the following: (1) Grating adaptation reduced the responses of 46% of the LGNd cells recorded. The responses normally decreased within 30 s and then stabilized. However, there was heterogeneity in the effects observed. About 38% of the cells studied were not affected by the adapting gratings. Some cells (16%) showed facilitation rather than habituation of their responses to test stimuli. (2) There was no significant difference between X and Y cells in their susceptibility to adaptation. This suggests that grating adaptation is a general property, independent of cell type. (3) The contrast-response curves of 57% of the LGNd cells studied shifted down after exposure to high-contrast adapting gratings. (4) Adapting gratings of the cells' preferred orientation decreased the orientation sensitivity of 56% of the orientation-sensitive cells. Adapting gratings at the nonpreferred orientation did not affect orientation sensitivity. (5) Prolonged grating adaptation also reduced the responses of 49% of the LGNd cells after inactivation of cortical inputs to the LGNd. PMID:8870219

  10. Genetic changes in flowering and morphology in response to adaptation to a high-latitude environment in Arabidopsis lyrata

    PubMed Central

    Quilot-Turion, Bénédicte; Leppälä, Johanna; Leinonen, Päivi H.; Waldmann, Patrik; Savolainen, Outi; Kuittinen, Helmi

    2013-01-01

    Background and Aims The adaptive plastic reactions of plant populations to changing climatic factors, such as winter temperatures and photoperiod, have changed during range shifts after the last glaciation. Timing of flowering is an adaptive trait regulated by environmental cues. Its genetics has been intensively studied in annual plants, but in perennials it is currently not well characterized. This study examined the genetic basis of differentiation in flowering time, morphology, and their plastic responses to vernalization in two locally adapted populations of the perennial Arabidopsis lyrata: (1) to determine whether the two populations differ in their vernalization responses for flowering phenology and morphology; and (2) to determine the genomic areas governing differentiation and vernalization responses. Methods Two A. lyrata populations, from central Europe and Scandinavia, were grown in growth-chamber conditions with and without cold treatment. A QTL analysis was performed to find genomic regions that interact with vernalization. Key Results The population from central Europe flowered more rapidly and invested more in inflorescence growth than the population from alpine Scandinavia, especially after vernalization. The alpine population had consistently a low number of inflorescences and few flowers, suggesting strong constraints due to a short growing season, but instead had longer leaves and higher leaf rosettes. QTL mapping in the F2 population revealed genomic regions governing differentiation in flowering time and morphology and, in some cases, the allelic effects from the two populations on a trait were influenced by vernalization (QTL × vernalization interactions). Conclusions The results indicate that many potentially adaptive genetic changes have occurred during colonization; the two populations have diverged in their plastic responses to vernalization in traits closely connected to fitness through changes in many genomic areas. PMID:23519836

  11. Spatial aggregation across ephemeral resource patches in insect communities: an adaptive response to natural enemies?

    PubMed

    Rohlfs, Marko; Hoffmeister, Thomas S

    2004-08-01

    Although an increase in competition is a common cost associated with intraspecific crowding, spatial aggregation across food-limited resource patches is a widespread phenomenon in many insect communities. Because intraspecific aggregation of competing insect larvae across, e.show $132#g. fruits, dung, mushrooms etc., is an important means by which many species can coexist (aggregation model of species coexistence), there is a strong need to explore the mechanisms that contribute to the maintenance of this kind of spatial resource exploitation. In the present study, by using Drosophila-parasitoid interactions as a model system, we tested the hypothesis whether intraspecific aggregation reflects an adaptive response to natural enemies. Most of the studies that have hitherto been carried out on Drosophila-parasitoid interactions used an almost two-dimensional artificial host environment, where host larvae could not escape from parasitoid attacks, and have demonstrated positive density-dependent parasitism risk. To test whether these studies captured the essence of such interactions, we used natural breeding substrates (decaying fruits). In a first step, we analysed the parasitism risk of Drosophila larvae on a three-dimensional substrate in natural fly communities in the field, and found that the risk of parasitism decreased with increasing host larval density (inverse density dependence). In a second step, we analysed the parasitism risk of Drosophila subobscura larvae on three breeding substrate types exposed to the larval parasitoids Asobara tabida and Leptopilina heterotoma. We found direct density-dependent parasitism on decaying sloes, inverse density dependence on plums, and a hump-shaped relationship between fly larval density and parasitism risk on crab apples. On crab apples and plums, fly larvae benefited from a density-dependent refuge against the parasitoids. While the proportion of larvae feeding within the fruit tissues increased with larval density

  12. Adhesin competence repressor (AdcR) from Streptococcus pyogenes controls adaptive responses to zinc limitation and contributes to virulence

    PubMed Central

    Sanson, Misu; Makthal, Nishanth; Flores, Anthony R.; Olsen, Randall J.; Musser, James M.; Kumaraswami, Muthiah

    2015-01-01

    Altering zinc bioavailability to bacterial pathogens is a key component of host innate immunity. Thus, the ability to sense and adapt to the alterations in zinc concentrations is critical for bacterial survival and pathogenesis. To understand the adaptive responses of group A Streptococcus (GAS) to zinc limitation and its regulation by AdcR, we characterized gene regulation by AdcR. AdcR regulates the expression of 70 genes involved in zinc acquisition and virulence. Zinc-bound AdcR interacts with operator sequences in the negatively regulated promoters and mediates differential regulation of target genes in response to zinc deficiency. Genes involved in zinc mobilization and conservation are derepressed during mild zinc deficiency, whereas the energy-dependent zinc importers are upregulated during severe zinc deficiency. Further, we demonstrated that transcription activation by AdcR occurs by direct binding to the promoter. However, the repression and activation by AdcR is mediated by its interactions with two distinct operator sequences. Finally, mutational analysis of the metal ligands of AdcR caused impaired DNA binding and attenuated virulence, indicating that zinc sensing by AdcR is critical for GAS pathogenesis. Together, we demonstrate that AdcR regulates GAS adaptive responses to zinc limitation and identify molecular components required for GAS survival during zinc deficiency. PMID:25510500

  13. Dark adaptation recovery of human rod bipolar cell response kinetics estimated from scotopic b-wave measurements.

    PubMed

    Cameron, A M; Miao, L; Ruseckaite, R; Pianta, M J; Lamb, T D

    2008-11-15

    We recorded ganzfeld scotopic ERGs to examine the responses of human rod bipolar cells in vivo, during dark adaptation recovery following bleaching exposures, as well as during adaptation to steady background lights. In order to be able to record responses at relatively early times in recovery, we utilized a 'criterion response amplitude' protocol in which the test flash strength was adjusted to elicit responses of nearly constant amplitude. In order to provide accurate and unbiased measures of response kinetics, we utilized a curve-fitting procedure to fit a smooth function to the measured responses in the vicinity of the peak, thereby extracting both the time-to-peak and the amplitude of the responses. Following bleaching exposures, the responses exhibited both desensitization and accelerated kinetics. During early post-bleach recovery, the flash sensitivity and time-to-peak varied according to a power-law expression (with an exponent of 6), as found in the presence of steady background light. This light-like phenomenon, however, appeared to be set against the backdrop of a second, more slowly recovering 'pure' desensitization, most clearly evident at late post-bleach times. The post-bleach 'equivalent background intensity' derived from measurements of flash sensitivity faded initially with an S2 slope of approximately 0.24 decades min(-1), and later as a gentle S3 tail. When calculated from kinetics, the results displayed only the S2 slope. While the recovery of rod bipolar cell response kinetics can be described accurately by a declining level of opsin in the rods, the sensitivity of these cells is reduced further than expected by this mechanism alone.

  14. Global Rsh-dependent transcription profile of Brucella suis during stringent response unravels adaptation to nutrient starvation and cross-talk with other stress responses

    PubMed Central

    2013-01-01

    Background In the intracellular pathogen Brucella spp., the activation of the stringent response, a global regulatory network providing rapid adaptation to growth-affecting stress conditions such as nutrient deficiency, is essential for replication in the host. A single, bi-functional enzyme Rsh catalyzes synthesis and hydrolysis of the alarmone (p)ppGpp, responsible for differential gene expression under stringent conditions. Results cDNA microarray analysis allowed characterization of the transcriptional profiles of the B. suis 1330 wild-type and Δrsh mutant in a minimal medium, partially mimicking the nutrient-poor intramacrophagic environment. A total of 379 genes (11.6% of the genome) were differentially expressed in a rsh-dependent manner, of which 198 were up-, and 181 were down-regulated. The pleiotropic character of the response was confirmed, as the genes encoded an important number of transcriptional regulators, cell envelope proteins, stress factors, transport systems, and energy metabolism proteins. Virulence genes such as narG and sodC, respectively encoding respiratory nitrate reductase and superoxide dismutase, were under the positive control of (p)ppGpp, as well as expression of the cbb3-type cytochrome c oxidase, essential for chronic murine infection. Methionine was the only amino acid whose biosynthesis was absolutely dependent on stringent response in B. suis. Conclusions The study illustrated the complexity of the processes involved in adaptation to nutrient starvation, and contributed to a better understanding of the correlation between stringent response and Brucella virulence. Most interestingly, it clearly indicated (p)ppGpp-dependent cross-talk between at least three stress responses playing a central role in Brucella adaptation to the host: nutrient, oxidative, and low-oxygen stress. PMID:23834488

  15. The adaptive response of bacterial food-borne pathogens in the environment, host and food: Implications for food safety.

    PubMed

    Alvarez-Ordóñez, Avelino; Broussolle, Véronique; Colin, Pierre; Nguyen-The, Christophe; Prieto, Miguel

    2015-11-20

    Bacteria are constantly faced to stress situations in their ecological niches, the food and the host gastrointestinal tract. The capacity to detect and respond to surrounding changes is crucial for bacterial pathogens to survive or grow in changing environments. To this purpose, cells have evolved various sophisticated networks designed to protect against stressors or repair damage caused by them. Challenges can occur during production of foods when subjected to processing, and after food ingestion when confronted with host defensive barriers. Some pathogenic bacteria have shown the capacity to develop stable resistance against extreme conditions within a defined genomic context and a limited number of generations. On the other hand, bacteria can also respond to adverse conditions in a transient manner, through the so-called stress tolerance responses. Bacterial stress tolerance responses include both structural and physiological modifications in the cell and are mediated by complex genetic regulatory machinery. Major aspects in the adaptive response are the sensing mechanisms, the characterization of cell defensive systems, such as the operation of regulatory proteins (e.g. RpoS), the induction of homeostatic and repair systems, the synthesis of shock response proteins, and the modifications of cell membranes, particularly in their fatty acid composition and physical properties. This article reviews certain strategies used by food-borne bacteria to respond to particular stresses (acid, cold stress, extreme pressure) in a permanent or transient manner and discusses the implications that such adaptive responses pose for food safety.

  16. The Footprint of Polygenic Adaptation on Stress-Responsive Cis-Regulatory Divergence in the Arabidopsis Genus.

    PubMed

    He, Fei; Arce, Agustin L; Schmitz, Gregor; Koornneef, Maarten; Novikova, Polina; Beyer, Andreas; de Meaux, Juliette

    2016-08-01

    Adaptation of a complex trait often requires the accumulation of many modifications to finely tune its underpinning molecular components to novel environmental requirements. The investigation of cis-acting regulatory modifications can be used to pinpoint molecular systems partaking in such complex adaptations. Here, we identify cis-acting modifications with the help of an interspecific crossing scheme designed to distinguish modifications derived in each of the two sister species, Arabidopsis halleri and A. lyrata Allele-specific expression levels were assessed in three environmental conditions chosen to reflect interspecific ecological differences: cold exposure, dehydration, and standard conditions. The functions described by Gene Ontology categories enriched in cis-acting mutations are markedly different in A. halleri and A. lyrata, suggesting that polygenic adaptation reshaped distinct polygenic molecular functions in the two species. In the A. halleri lineage, an excess of cis-acting changes affecting metal transport and homeostasis was observed, confirming that the well-known heavy metal tolerance of this species is the result of polygenic selection. In A. lyrata, we find a marked excess of cis-acting changes among genes showing a transcriptional response to cold stress in the outgroup species A. thaliana The adaptive relevance of these changes will have to be validated. We finally observed that polygenic molecular functions enriched in derived cis-acting changes are more constrained at the amino acid level. Using the distribution of cis-acting variation to tackle the polygenic basis of adaptation thus reveals the contribution of mutations of small effect to Darwinian adaptation. PMID:27189540

  17. Inhibition of glutathione synthesis eliminates the adaptive response of ascitic hepatoma 22 cells to nedaplatin that targets thioredoxin reductase

    SciTech Connect

    Wang, Yijun; Lu, Hongjuan; Wang, Dongxu; Li, Shengrong; Sun, Kang; Wan, Xiaochun; Taylor, Ethan Will; Zhang, Jinsong

    2012-12-15

    Thioredoxin reductase (TrxR) is a target for cancer therapy and the anticancer mechanism of cisplatin involves TrxR inhibition. We hypothesize that the anticancer drug nedaplatin (NDP), an analogue of cisplatin and a second-generation platinum complex, also targets TrxR. Furthermore, we investigate whether the therapeutic efficacy of NDP can be enhanced by simultaneous modulation of 1) TrxR, via NDP, and 2) glutathione (GSH), via the GSH synthesis inhibitor buthionine sulfoximine (BSO). Mice bearing ascitic hepatoma 22 (H22) cells were treated with NDP alone or NDP plus BSO. TrxR activity of H22 cells was inhibited by NDP in a dose-dependent manner. A high correlation between the inhibition of TrxR activity at 6 h and the inhibition of ascitic fluid volume at 72 h was established (r = 0.978, p < 0.01). As an adaptive response, the viable ascitic cancer cells after NDP treatment displayed an enlarged cell phenotype, assembled with several-fold more antioxidant enzymes and GSH-predominant non-protein free thiols. This adaptive response was largely eliminated when BSO was co-administered with NDP, leading to the decimation of the H22 cell population without enhancing renal toxicity, since at this dose, NDP did not inhibit renal TrxR activity. In conclusion, the pharmacological effect of NDP involves TrxR inhibition, and the adaptive response of NDP-treated ascitic H22 cells can be efficiently counteracted by BSO. Simultaneous modulation of TrxR and GSH on ascitic H22 cells using NDP plus BSO greatly enhances therapeutic efficacy as compared with the single modulation of TrxR using NDP alone. -- Highlights: ► Nedaplatin at a pharmacological dose inhibits TrxR in cancer cells but not in kidney. ► The nedaplatin-treated cancer cells exhibit adaptive response. ► Buthionine sulfoximine inhibits glutathione in both cancer cells and kidney. ► Buthionine sulfoximine counteracts the adaptive response to the nedaplatin treatment. ► Buthionine sulfoximine does not

  18. Klinefelter syndrome has increased brain responses to auditory stimuli and motor output, but not to visual stimuli or Stroop adaptation

    PubMed Central

    Wallentin, Mikkel; Skakkebæk, Anne; Bojesen, Anders; Fedder, Jens; Laurberg, Peter; Østergaard, John R.; Hertz, Jens Michael; Pedersen, Anders Degn; Gravholt, Claus Højbjerg

    2016-01-01

    Klinefelter syndrome (47, XXY) (KS) is a genetic syndrome characterized by the presence of an extra X chromosome and low level of testosterone, resulting in a number of neurocognitive abnormalities, yet little is known about brain function. This study investigated the fMRI-BOLD response from KS relative to a group of Controls to basic motor, perceptual, executive and adaptation tasks. Participants (N: KS = 49; Controls = 49) responded to whether the words “GREEN” or “RED” were displayed in green or red (incongruent versus congruent colors). One of the colors was presented three times as often as the other, making it possible to study both congruency and adaptation effects independently. Auditory stimuli saying “GREEN” or “RED” had the same distribution, making it possible to study effects of perceptual modality as well as Frequency effects across modalities. We found that KS had an increased response to motor output in primary motor cortex and an increased response to auditory stimuli in auditory cortices, but no difference in primary visual cortices. KS displayed a diminished response to written visual stimuli in secondary visual regions near the Visual Word Form Area, consistent with the widespread dyslexia in the group. No neural differences were found in inhibitory control (Stroop) or in adaptation to differences in stimulus frequencies. Across groups we found a strong positive correlation between age and BOLD response in the brain's motor network with no difference between groups. No effects of testosterone level or brain volume were found. In sum, the present findings suggest that auditory and motor systems in KS are selectively affected, perhaps as a compensatory strategy, and that this is not a systemic effect as it is not seen in the visual system. PMID:26958463

  19. Klinefelter syndrome has increased brain responses to auditory stimuli and motor output, but not to visual stimuli or Stroop adaptation.

    PubMed

    Wallentin, Mikkel; Skakkebæk, Anne; Bojesen, Anders; Fedder, Jens; Laurberg, Peter; Østergaard, John R; Hertz, Jens Michael; Pedersen, Anders Degn; Gravholt, Claus Højbjerg

    2016-01-01

    Klinefelter syndrome (47, XXY) (KS) is a genetic syndrome characterized by the presence of an extra X chromosome and low level of testosterone, resulting in a number of neurocognitive abnormalities, yet little is known about brain function. This study investigated the fMRI-BOLD response from KS relative to a group of Controls to basic motor, perceptual, executive and adaptation tasks. Participants (N: KS = 49; Controls = 49) responded to whether the words "GREEN" or "RED" were displayed in green or red (incongruent versus congruent colors). One of the colors was presented three times as often as the other, making it possible to study both congruency and adaptation effects independently. Auditory stimuli saying "GREEN" or "RED" had the same distribution, making it possible to study effects of perceptual modality as well as Frequency effects across modalities. We found that KS had an increased response to motor output in primary motor cortex and an increased response to auditory stimuli in auditory cortices, but no difference in primary visual cortices. KS displayed a diminished response to written visual stimuli in secondary visual regions near the Visual Word Form Area, consistent with the widespread dyslexia in the group. No neural differences were found in inhibitory control (Stroop) or in adaptation to differences in stimulus frequencies. Across groups we found a strong positive correlation between age and BOLD response in the brain's motor network with no difference between groups. No effects of testosterone level or brain volume were found. In sum, the present findings suggest that auditory and motor systems in KS are selectively affected, perhaps as a compensatory strategy, and that this is not a systemic effect as it is not seen in the visual system. PMID:26958463

  20. Klinefelter syndrome has increased brain responses to auditory stimuli and motor output, but not to visual stimuli or Stroop adaptation.

    PubMed

    Wallentin, Mikkel; Skakkebæk, Anne; Bojesen, Anders; Fedder, Jens; Laurberg, Peter; Østergaard, John R; Hertz, Jens Michael; Pedersen, Anders Degn; Gravholt, Claus Højbjerg

    2016-01-01

    Klinefelter syndrome (47, XXY) (KS) is a genetic syndrome characterized by the presence of an extra X chromosome and low level of testosterone, resulting in a number of neurocognitive abnormalities, yet little is known about brain function. This study investigated the fMRI-BOLD response from KS relative to a group of Controls to basic motor, perceptual, executive and adaptation tasks. Participants (N: KS = 49; Controls = 49) responded to whether the words "GREEN" or "RED" were displayed in green or red (incongruent versus congruent colors). One of the colors was presented three times as often as the other, making it possible to study both congruency and adaptation effects independently. Auditory stimuli saying "GREEN" or "RED" had the same distribution, making it possible to study effects of perceptual modality as well as Frequency effects across modalities. We found that KS had an increased response to motor output in primary motor cortex and an increased response to auditory stimuli in auditory cortices, but no difference in primary visual cortices. KS displayed a diminished response to written visual stimuli in secondary visual regions near the Visual Word Form Area, consistent with the widespread dyslexia in the group. No neural differences were found in inhibitory control (Stroop) or in adaptation to differences in stimulus frequencies. Across groups we found a strong positive correlation between age and BOLD response in the brain's motor network with no difference between groups. No effects of testosterone level or brain volume were found. In sum, the present findings suggest that auditory and motor systems in KS are selectively affected, perhaps as a compensatory strategy, and that this is not a systemic effect as it is not seen in the visual system.