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Sample records for adaptive response radio-protection

  1. A Review: Development of a Microdose Model for Analysis of Adaptive Response and Bystander Dose Response Behavior

    PubMed Central

    Leonard, Bobby E.

    2008-01-01

    Prior work has provided incremental phases to a microdosimetry modeling program to describe the dose response behavior of the radio-protective adaptive response effect. We have here consolidated these prior works (Leonard 2000, 2005, 2007a, 2007b, 2007c) to provide a composite, comprehensive Microdose Model that is also herein modified to include the bystander effect. The nomenclature for the model is also standardized for the benefit of the experimental cellular radio-biologist. It extends the prior work to explicitly encompass separately the analysis of experimental data that is 1.) only dose dependent and reflecting only adaptive response radio-protection, 2.) both dose and dose-rate dependent data and reflecting only adaptive response radio-protection for spontaneous and challenge dose damage, 3.) only dose dependent data and reflecting both bystander deleterious damage and adaptive response radio-protection (AR-BE model). The Appendix cites the various applications of the model. Here we have used the Microdose Model to analyze the, much more human risk significant, Elmore et al (2006) data for the dose and dose rate influence on the adaptive response radio-protective behavior of HeLa x Skin cells for naturally occurring, spontaneous chromosome damage from a Brachytherapy type 125I photon radiation source. We have also applied the AR-BE Microdose Model to the Chromosome inversion data of Hooker et al (2004) reflecting both low LET bystander and adaptive response effects. The micro-beam facility data of Miller et al (1999), Nagasawa and Little (1999) and Zhou et al (2003) is also examined. For the Zhou et al (2003) data, we use the AR-BE model to estimate the threshold for adaptive response reduction of the bystander effect. The mammogram and diagnostic X-ray induction of AR and protective BE are observed. We show that bystander damage is reduced in the similar manner as spontaneous and challenge dose damage as shown by the Azzam et al (1996) data. We cite

  2. 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.

  3. 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

  4. 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.

  5. Radio-protective role of antioxidant agents

    PubMed Central

    Shirazi, Alireza; Mihandoost, Ehsan; Mahdavi, Seied Rabie; Mohseni, Mehran

    2012-01-01

    Ionizing radiation interacts with biological systems to produce reactive oxygen species and reactive nitrogen species which attack various cellular components. Radio-protectors act as prophylactic agents to shield healthy cells and tissues from the harmful effects of radiation. Past research on synthetic radio-protectors has brought little success, primarily due to the various toxicity-related problems. Results of experimental research show that antioxidant nutrients, such as vitamin E and herbal products and melatonin, are protective against the damaging effects of radiation, with less toxicity and side effects. Therefore, we propose that in the future, antioxidant radio-protective agents may improve the therapeutic index in radiation oncology treatments. PMID:25992214

  6. 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

  7. 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.

  8. Adaptive Responses Limited by Intrinsic Noise.

    PubMed

    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.

  9. 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

  10. 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.

  11. Adaptive tracking of narrowband HF channel response

    NASA Astrophysics Data System (ADS)

    Arikan, F.; Arikan, O.

    2003-12-01

    Estimation of channel impulse response constitutes a first step in computation of scattering function, channel equalization, elimination of multipath, and optimum detection and identification of transmitted signals through the HF channel. Due to spatial and temporal variations, HF channel impulse response has to be estimated adaptively. Based on developed state-space and measurement models, an adaptive Kalman filter is proposed to track the HF channel variation in time. Robust methods of initialization and adaptively adjusting the noise covariance in the system dynamics are proposed. In simulated examples under good, moderate and poor ionospheric conditions, it is observed that the adaptive Kalman filter based channel estimator provides reliable channel estimates and can track the variation of the channel in time with high accuracy.

  12. Adaptive immune responses to Candida albicans infection

    PubMed Central

    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. PMID:25607781

  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. Individual differences in response conflict adaptations

    PubMed Central

    Keye, Doris; Wilhelm, Oliver; Oberauer, Klaus; Stürmer, Birgit

    2013-01-01

    Conflict-monitoring theory argues for a general cognitive mechanism that monitors for conflicts in information-processing. If that mechanism detects conflict, it engages cognitive control to resolve it. A slow-down in response to incongruent trials (conflict effect), and a modulation of the conflict effect by the congruence of the preceding trial (Gratton or context effect) have been taken as indicators of such a monitoring system. The present study (N = 157) investigated individual differences in the conflict and the context effect in a horizontal and a vertical Simon task, and their correlation with working memory capacity (WMC). Strength of conflict was varied by proportion of congruent trials. Coherent factors could be formed representing individual differences in speeded performance, conflict adaptation, and context adaptation. Conflict and context factors were not associated with each other. Contrary to theories assuming a close relation between working memory and cognitive control, WMC showed no relation with any factors representing adaptation to conflict. PMID:24385971

  15. Green light signaling and adaptive response.

    PubMed

    Zhang, Tingting; Folta, Kevin M

    2012-01-01

    To a plant, the sun's light is not exclusively energy for photosynthesis, it also provides information about time and prevailing conditions. The plant's surroundings may dampen or filter solar energies, presenting plants with different 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 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 and chloroplast gene expression. Recent evidence demonstrates a role for green light in sensing a shaded environment, independent from far-red shade responses.

  16. 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

  17. 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.

  18. Adaptive immune responses to Acanthamoeba cysts.

    PubMed

    McClellan, Kathy; Howard, Kevin; Mayhew, Elizabeth; Niederkorn, Jerry; Alizadeh, Hassan

    2002-09-01

    Acanthamoeba cysts are not eliminated from the corneas of human subjects or experimentally infected animals. The persistence of Acanthamoeba cysts in the cornea indicates that either the cysts escape immunological elimination or are not recognized by the host's immunological elements. The aim of this study was to determine the immunogenicity and antigenicity of the Acanthamoeba cyst. Mice were immunized intraperitoneally and serum anti-Acanthamoeba IgG was measured by ELISA. Lymphoproliferative assay and delayed type hypersensitivity (DTH) responses to Acanthamoeba castellanii cyst and trophozoite antigens were used to determine the cell mediated immune responses against Acanthamoeba cysts. A. castellanii cysts were both immunogenic and antigenic, producing anti-Acanthamoeba serum IgG, T lymphocyte proliferation, and delayed type hypersensitivity responses. These results indicate that Acanthamoeba cysts are recognized by the immune system. The persistence of the organism in the human cornea means that these adaptive immune responses fail to kill Acanthamoeba cysts.

  19. Adaptive immune cells temper initial innate responses

    PubMed Central

    Kim, Kwang Dong; Zhao, Jie; Auh, Sogyong; Yang, Xuanming; Du, Peishuang; Tang, Hong; Fu, Yang-Xin

    2008-01-01

    Toll-like receptors (TLRs) recognize conserved microbial structures called pathogen-associated molecular patterns. Signaling from TLRs leads to upregulation of co-stimulatory molecules for better priming of T cells and secretion of inflammatory cytokines by innate immune cells1–4. Lymphocytedeficient hosts often die of acute infection, presumably owing to their lack of an adaptive immune response to effectively clear pathogens. However, we show here that an unleashed innate immune response due to the absence of residential T cells can also be a direct cause of death. Viral infection or administration of poly(I:C), a ligand for TLR3, led to cytokine storm in T-cell- or lymphocyte-deficient mice in a fashion dependent on NK cells and tumor necrosis factor. We have further shown, through the depletion of CD4+ and CD8+ cells in wild-type mice and the transfer of T lymphocytes into Rag-1–deficient mice, respectively, that T cells are both necessary and sufficient to temper the early innate response. In addition to the effects of natural regulatory T cells, close contact of resting CD4+CD25−Foxp3− or CD8+ T cells with innate cells could also suppress the cytokine surge by various innate cells in an antigen-independent fashion. Therefore, adaptive immune cells have an unexpected role in tempering initial innate responses. PMID:17891146

  20. Adaptive immune cells temper initial innate responses.

    PubMed

    Kim, Kwang Dong; Zhao, Jie; Auh, Sogyong; Yang, Xuanming; Du, Peishuang; Tang, Hong; Fu, Yang-Xin

    2007-10-01

    Toll-like receptors (TLRs) recognize conserved microbial structures called pathogen-associated molecular patterns. Signaling from TLRs leads to upregulation of co-stimulatory molecules for better priming of T cells and secretion of inflammatory cytokines by innate immune cells. Lymphocyte-deficient hosts often die of acute infection, presumably owing to their lack of an adaptive immune response to effectively clear pathogens. However, we show here that an unleashed innate immune response due to the absence of residential T cells can also be a direct cause of death. Viral infection or administration of poly(I:C), a ligand for TLR3, led to cytokine storm in T-cell- or lymphocyte-deficient mice in a fashion dependent on NK cells and tumor necrosis factor. We have further shown, through the depletion of CD4+ and CD8+ cells in wild-type mice and the transfer of T lymphocytes into Rag-1-deficient mice, respectively, that T cells are both necessary and sufficient to temper the early innate response. In addition to the effects of natural regulatory T cells, close contact of resting CD4+CD25-Foxp3- or CD8+ T cells with innate cells could also suppress the cytokine surge by various innate cells in an antigen-independent fashion. Therefore, adaptive immune cells have an unexpected role in tempering initial innate responses.

  1. 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)

  2. The adaptive immune response in celiac disease.

    PubMed

    Qiao, Shuo-Wang; Iversen, Rasmus; Ráki, Melinda; Sollid, Ludvig M

    2012-07-01

    Compared to other human leukocyte antigen (HLA)-associated diseases such as type 1 diabetes, multiple sclerosis, and rheumatoid arthritis, fundamental aspects of the pathogenesis in celiac disease are relatively well understood. This is mostly because the causative antigen in celiac disease-cereal gluten proteins-is known and the culprit HLA molecules are well defined. This has facilitated the dissection of the disease-relevant CD4+ T cells interacting with the disease-associated HLA molecules. In addition, celiac disease has distinct antibody responses to gluten and the autoantigen transglutaminase 2, which give strong handles to understand all sides of the adaptive immune response leading to disease. Here we review recent developments in the understanding of the role of T cells, B cells, and antigen-presenting cells in the pathogenic immune response of this instructive disorder.

  3. 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…

  4. Local adaptation in transgenerational responses to predators

    PubMed Central

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

    2016-01-01

    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. Formation and Regulation of Adaptive Response in Nematode Caenorhabditis elegans

    PubMed Central

    Zhao, Y.-L.; Wang, D.-Y.

    2012-01-01

    All organisms respond to environmental stresses (e.g., heavy metal, heat, UV irradiation, hyperoxia, food limitation, etc.) with coordinated adjustments in order to deal with the consequences and/or injuries caused by the severe stress. The nematode Caenorhabditis elegans often exerts adaptive responses if preconditioned with low concentrations of agents or stressor. In C. elegans, three types of adaptive responses can be formed: hormesis, cross-adaptation, and dietary restriction. Several factors influence the formation of adaptive responses in nematodes, and some mechanisms can explain their response formation. In particular, antioxidation system, heat-shock proteins, metallothioneins, glutathione, signaling transduction, and metabolic signals may play important roles in regulating the formation of adaptive responses. In this paper, we summarize the published evidence demonstrating that several types of adaptive responses have converged in C. elegans and discussed some possible alternative theories explaining the adaptive response control. PMID:22997543

  6. Adaptive acidification tolerance response of Salmonella typhimurium.

    PubMed

    Foster, J W; Hall, H K

    1990-02-01

    Salmonella typhimurium can encounter a wide variety of environments during its life cycle. One component of the environment which will fluctuate widely is pH. In nature, S. typhimurium can experience and survive dramatic acid stresses that occur in diverse ecological niches ranging from pond water to phagolysosomes. However, in vitro the organism is very sensitive to acid. To provide an explanation for how this organism survives acid in natural environments, the adaptive ability of S. typhimurium to become acid tolerant was tested. Logarithmically grown cells (pH 7.6) shifted to mild acid (pH 5.8) for one doubling as an adaptive procedure were 100 to 1,000 times more resistant to subsequent strong acid challenge (pH 3.3) than were unadapted cells shifted directly from pH 7.6 to 3.3. This acidification tolerance response required protein synthesis and appears to be a specific defense mechanism for acid. No cross protection was noted for hydrogen peroxide, SOS, or heat shock. Two-dimensional polyacrylamide gel electrophoretic analysis of acid-regulated polypeptides revealed 18 proteins with altered expression, 6 of which were repressed while 12 were induced by mild acid shifts. An avirulent phoP mutant was 1,000-fold more sensitive to acid than its virulent phoP+ parent, suggesting a correlation between acid tolerance and virulence. The Mg2(+)-dependent proton-translocating ATPase was also found to play an important role in acid tolerance. Mutants (unc) lacking this activity were unable to mount an acid tolerance response and were extremely acid sensitive. In contrast to these acid-sensitive mutants, a constitutively acid-tolerant mutant (atr) was isolated from wild-type LT2 after prolonged acid exposure. This mutant overexpressed several acidification tolerance response polypeptides. The data presented reveal an important acidification defense modulon with broad significance toward survival in biologically hostile environments.

  7. 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.

  8. 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

  9. Adaptive responses to antibody based therapy.

    PubMed

    Rodems, Tamara S; Iida, Mari; Brand, Toni M; Pearson, Hannah E; Orbuch, Rachel A; Flanigan, Bailey G; Wheeler, Deric L

    2016-02-01

    Receptor tyrosine kinases (RTKs) represent a large class of protein kinases that span the cellular membrane. There are 58 human RTKs identified which are grouped into 20 distinct families based upon their ligand binding, sequence homology and structure. They are controlled by ligand binding which activates intrinsic tyrosine-kinase activity. This activity leads to the phosphorylation of distinct tyrosines on the cytoplasmic tail, leading to the activation of cell signaling cascades. These signaling cascades ultimately regulate cellular proliferation, apoptosis, migration, survival and homeostasis of the cell. The vast majority of RTKs have been directly tied to the etiology and progression of cancer. Thus, using antibodies to target RTKs as a cancer therapeutic strategy has been intensely pursued. Although antibodies against the epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) have shown promise in the clinical arena, the development of both intrinsic and acquired resistance to antibody-based therapies is now well appreciated. In this review we provide an overview of the RTK family, the biology of EGFR and HER2, as well as an in-depth review of the adaptive responses undertaken by cells in response to antibody based therapies directed against these receptors. A greater understanding of these mechanisms and their relevance in human models will lead to molecular insights in overcoming and circumventing resistance to antibody based therapy.

  10. Linear ubiquitination signals in adaptive immune responses.

    PubMed

    Ikeda, Fumiyo

    2015-07-01

    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-κB (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.

  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. The Knowledge of Radiation and the Attitude Towards Radio-Protection among Urology Residents in India

    PubMed Central

    2015-01-01

    Introduction Exposure to radiation is a hazard and precautions are necessary to limit it. This study was done to assess the knowledge of radiation and the attitude towards radio-protection among urology residents in India. Materials and Methods A questionnaire was administered to assess the knowledge and attitude of urology residents who came from all over the country to attend a clinical meeting at Apollo Gleneagles Hospital, Kolkata, India. Results All the respondents agreed to being exposed to radiation, with 78.2% using radiation in more than five cases a week. Only 65.2% always took some steps for radio-protection. Lead aprons and thyroid shields were the most common radiation protection devices used. None of the residents ever used lead gloves or protective eye glasses or dosimeters. An 82.6% felt that they did not have adequate knowledge, 85.4% of residents did not receive any formal classes regarding the risk of radiation, 21.7% either rarely or never moved out of the operating room when the radiation was being used, 42.4% did not know that the SI unit of the equivalent absorbed dose of radiation & 52.1% did not know about the amount of radiation delivered to an adult during a contrast enhanced CT scan of the abdomen. Conclusion Results of the present study reveal that the urology residents of India lack knowledge about the risks of radiation exposure. Majority of them did not take necessary precautions to limit their exposure to radiation. PMID:26816919

  13. [Mechanism of cytogenetic adaptive response induced by low dose radiation].

    PubMed

    Cai, L; Liu, S

    1990-11-01

    Cytogenetic observation on human lymphocytes indicated that pre-exposure of 10, 50 and 75 mGy X-rays could induced the adaptive response. Experimental results with different temperature treatment showed that the adaptive response induced by low dose radiation could be enhanced by 41 degrees C and 43 degrees C, but inhibited by 4 degrees C in addition the treatment by 41 degrees C for one hour could also cause the adaptive response as did low dose radiation. Results showed that adaptive response induced by low dose radiation (10 or 50 mGy X-rays) could be eliminated by the protein synthesis inhibitor, implying that the adaptive response is related with the metabolism of cells, especially with the production of certain protective proteins.

  14. Light-adaptation in the photophobic response by Stentor coeruleus.

    PubMed

    Hong, C B; Prusti, R K; Song, P S

    1987-03-01

    Effects of preillumination on photophobic response (light-adaptation) and recovery of the photophobic sensitivity in the dark (dark-adaptation) in Stentor coeruleus were examined. When the cells were preilluminated with white light of 7.80 W/m2 for 2 min, the fluence-rate response curve of photophobic response was shifted toward higher light intensities by half an order of magnitude compared to the one without preillumination. Preillumination with a higher light intensity resulted in a further shift of the fluence-rate response curve. An action spectrum for light-adaptation showed a primary peak at 610 nm and secondary peaks at 540 and 480 nm which are almost identical to the peaks observed in the photophobic action spectrum. The light-adapted cells showed a recovery of their photophobic sensing ability following dark treatment. Dark-adaptation resulted in total recovery of photophobic sensing ability in 8 minutes for the most cases examined.

  15. 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…

  16. Responsiveness-to-Intervention: A "Systems" Approach to Instructional Adaptation

    ERIC Educational Resources Information Center

    Fuchs, Douglas; Fuchs, Lynn S.

    2016-01-01

    Classroom research on adaptive teaching indicates few teachers modify instruction for at-risk students in a manner that benefits them. Responsiveness-To-Intervention, with its tiers of increasingly intensive instruction, represents an alternative approach to adaptive instruction that may prove more workable in today's schools.

  17. Impaired Adaptive Response to Mechanical Overloading in Dystrophic Skeletal Muscle

    PubMed Central

    Joanne, Pierre; Hourdé, Christophe; Ochala, Julien; Caudéran, Yvain; Medja, Fadia; Vignaud, Alban; Mouisel, Etienne; Hadj-Said, Wahiba; Arandel, Ludovic; Garcia, Luis; Goyenvalle, Aurélie; Mounier, Rémi; Zibroba, Daria; Sakamato, Kei; Butler-Browne, Gillian; Agbulut, Onnik; Ferry, Arnaud

    2012-01-01

    Dystrophin contributes to force transmission and has a protein-scaffolding role for a variety of signaling complexes in skeletal muscle. In the present study, we tested the hypothesis that the muscle adaptive response following mechanical overloading (ML) would be decreased in MDX dystrophic muscle lacking dystrophin. We found that the gains in muscle maximal force production and fatigue resistance in response to ML were both reduced in MDX mice as compared to healthy mice. MDX muscle also exhibited decreased cellular and molecular muscle remodeling (hypertrophy and promotion of slower/oxidative fiber type) in response to ML, and altered intracellular signalings involved in muscle growth and maintenance (mTOR, myostatin, follistatin, AMPKα1, REDD1, atrogin-1, Bnip3). Moreover, dystrophin rescue via exon skipping restored the adaptive response to ML. Therefore our results demonstrate that the adaptive response in response to ML is impaired in dystrophic MDX muscle, most likely because of the dystrophin crucial role. PMID:22511986

  18. 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.

  19. Oxidative stress, radiation-adaptive responses, and aging.

    PubMed

    Miura, Yuri

    2004-09-01

    Organisms living in an aerobic environment were forced to evolve effective cellular strategies to detoxify reactive oxygen species. Besides diverse antioxidant enzymes and compounds, DNA repair enzymes, and disassembly systems, which remove damaged proteins, regulation systems that control transcription, translation, and activation have also been developed. The adaptive responses, especially those to radiation, are defensive regulation mechanisms by which oxidative stress (conditioning irradiation) elicits a response against damage because of subsequent stress (challenging irradiation). Although many researchers have investigated these molecular mechanisms, they remain obscure because of their complex signaling pathways and the involvement of various proteins. This article reviews the factors concerned with radiation-adaptive response, the signaling pathways activated by conditioning irradiation, and the effects of aging on radiation-adaptive response. The proteomics approach is also introduced, which is a useful method for studying stress response in cells.

  20. 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

  1. Radio-protective effects of melatonin against irradiation-induced oxidative damage in rat peripheral blood.

    PubMed

    Shirazi, Alireza; Mihandoost, Ehsan; Mohseni, Mehran; Ghazi-Khansari, Mahmoud; Rabie Mahdavi, Seied

    2013-01-01

    During radiotherapy, ionizing irradiation interacts with biological systems to produce free radicals, which attacks various cellular components. The hematopoietic system is well-known to be radiosensitive and its damage may be life-threatening. Melatonin synergistically acts as an immunostimulator and antioxidant. In this study we used a total of 120 rats with 20 rats in each group. Group 1 did not receive melatonin or irradiation (Control group), Group 2 received only 10 mg/kg melatonin (Mel group), Group 3 exposed to dose of 2 Gy irradiation (2 Gy Rad group), Group 4 exposed to 8 Gy irradiation (8 Gy Rad group), Group 5 received 2 Gy irradiation plus 10 mg/kg melatonin (Mel +2 Gy Rad group) and Group 6 received 8 Gy irradiation plus 10 mg/kg melatonin (Mel+8 Gy Rad group). Following exposure to radiation, five rats from each group were sacrificed at 4, 24, 48 and 72 h. Exposure to different doses of irradiation resulted in a dose-dependent decline in the antioxidant enzymes activity and lymphocyte count (LC) and an increase in the nitric oxide (NO) levels of the serum. Pre-treatment with melatonin (10 mg/kg) ameliorates harmful effects of 2 and 8 Gy irradiation by increasing lymphocyte count(LC) as well as antioxidant enzymes activity and decreasing NO levels at all time-points. In conclusion 10 mg/kg melatonin is likely to be a threshold concentration for significant protection against lower dose of 2 Gy gamma irradiation compared to higher dose of 8 Gy. Therefore, it seems that radio-protective effects of melatonin are dose-dependent.

  2. 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.

  3. Mast cells in allergy: innate instructors of adaptive responses.

    PubMed

    Stelekati, Erietta; Orinska, Zane; Bulfone-Paus, Silvia

    2007-01-01

    The function of mast cells as effector cells in allergy has been extensively studied. However, increasing insight into mast cell physiology has revealed new mast cell functions and has introduced mast cells as key players in the regulation of innate as well as adaptive immunity. For example, mast cells have recently been found to express Toll-like receptors (TLRs), which enable them to participate in the innate immune response against pathogens. Furthermore, mast cells have been reported to interact with B cells, dendritic cells and T cells and thereby modulate the direction of an adaptive immune response. Finally, recent documentation that mast cells express functional MHC class II and costimulatory molecules and release immunologically active exosomes, has raised the possibility that mast cells also engage in (as yet) poorly understood antigen presentation functions. In this review, we explore the hypothesis that mast cells serve as central mediators between innate and adaptive immunity, rather as pure effector cells, during allergic innate responses.

  4. Readapting the adaptive immune response - therapeutic strategies for atherosclerosis.

    PubMed

    Sage, Andrew P; Mallat, Ziad

    2017-01-04

    Cardiovascular diseases remain a major global health issue, with the development of atherosclerosis as a major underlying cause. Our treatment of cardiovascular disease has improved greatly over the past three decades, but much remains to be done reduce disease burden. Current priorities include reducing atherosclerosis advancement to clinically significant stages and preventing plaque rupture or erosion. Inflammation and involvement of the adaptive immune system influences all these aspects and therefore is one focus for future therapeutic development. The atherosclerotic vascular wall is now recognized to be invaded from both sides (arterial lumen and adventitia), for better or worse, by the adaptive immune system. Atherosclerosis is also affected at several stages by adaptive immune responses, overall providing many opportunities to target these responses and to reduce disease progression. Protective influences that may be defective in diseased individuals include humoral responses to modified LDL and regulatory T cell responses. There are many strategies in development to boost these pathways in humans, including vaccine-based therapies. The effects of various existing adaptive immune targeting therapies, such as blocking critical co-stimulatory pathways or B cell depletion, on cardiovascular disease are beginning to emerge with important consequences for both autoimmune disease patients and the potential for wider use of such therapies. Entering the translation phase for adaptive immune targeting therapies is an exciting and promising prospect.

  5. Adaptive shaping of cortical response selectivity in the vibrissa pathway

    PubMed Central

    Zheng, He J. V.; Wang, Qi

    2015-01-01

    One embodiment of context-dependent sensory processing is bottom-up adaptation, where persistent stimuli decrease neuronal firing rate over hundreds of milliseconds. Adaptation is not, however, simply the fatigue of the sensory pathway, but shapes the information flow and selectivity to stimulus features. Adaptation enhances spatial discriminability (distinguishing stimulus location) while degrading detectability (reporting presence of the stimulus), for both the ideal observer of the cortex and awake, behaving animals. However, how the dynamics of the adaptation shape the cortical response and this detection and discrimination tradeoff is unknown, as is to what degree this phenomenon occurs on a continuum as opposed to a switching of processing modes. Using voltage-sensitive dye imaging in anesthetized rats to capture the temporal and spatial characteristics of the cortical response to tactile inputs, we showed that the suppression of the cortical response, in both magnitude and spatial spread, is continuously modulated by the increasing amount of energy in the adapting stimulus, which is nonuniquely determined by its frequency and velocity. Single-trial ideal observer analysis demonstrated a tradeoff between detectability and spatial discriminability up to a moderate amount of adaptation, which corresponds to the frequency range in natural whisking. This was accompanied by a decrease in both detectability and discriminability with high-energy adaptation, which indicates a more complex coupling between detection and discrimination than a simple switching of modes. Taken together, the results suggest that adaptation operates on a continuum and modulates the tradeoff between detectability and discriminability that has implications for information processing in ethological contexts. PMID:25787959

  6. 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.

  7. 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

  8. 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

  9. 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.

  10. Replicated evolution of integrated plastic responses during early adaptive divergence.

    PubMed

    Parsons, Kevin J; Robinson, Beren W

    2006-04-01

    Colonization of a novel environment is expected to result in adaptive divergence from the ancestral population when selection favors a new phenotypic optimum. Local adaptation in the new environment occurs through the accumulation and integration of character states that positively affect fitness. The role played by plastic traits in adaptation to a novel environment has generally been ignored, except for variable environments. We propose that if conditions in a relatively stable but novel environment induce phenotypically plastic responses in many traits, and if genetic variation exists in the form of those responses, then selection may initially favor the accumulation and integration of functionally useful plastic responses. Early divergence between ancestral and colonist forms will then occur with respect to their plastic responses across the gradient bounded by ancestral and novel environmental conditions. To test this, we compared the magnitude, integration, and pattern of plastic character responses in external body form induced by shallow versus open water conditions between two sunfish ecomorphs that coexist in four postglacial lakes. The novel sunfish ecomorph is present in the deeper open water habitat, whereas the ancestral ecomorph inhabits the shallow waters along the lake margin. Plastic responses by open water ecomorphs were more correlated than those of their local shallow water ecomorph in two of the populations, whereas equal levels of correlated plastic character responses occurred between ecomorphs in the other two populations. Small but persistent differences occurred between ecomorph pairs in the pattern of their character responses, suggesting a recent divergence. Open water ecomorphs shared some similarities in the covariance among plastic responses to rearing environment. Replication in the form of correlated plastic responses among populations of open water ecomorphs suggests that plastic character states may evolve under selection

  11. 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.

  12. 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

  13. 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…

  14. Bayesian optimal response-adaptive design for binary responses using stopping rule.

    PubMed

    Komaki, Fumiyasu; Biswas, Atanu

    2016-05-02

    Response-adaptive designs are used in phase III clinical trials to allocate a larger number of patients to the better treatment arm. Optimal designs are explored in the recent years in the context of response-adaptive designs, in the frequentist view point only. In the present paper, we propose some response-adaptive designs for two treatments based on Bayesian prediction for phase III clinical trials. Some properties are studied and numerically compared with some existing competitors. A real data set is used to illustrate the applicability of the proposed methodology where we redesign the experiment using parameters derived from the data set.

  15. The Dose Window for Radiation-Induced Protective Adaptive Responses

    PubMed Central

    Mitchel, Ronald E. J.

    2009-01-01

    Adaptive responses to low doses of low LET radiation occur in all organisms thus far examined, from single cell lower eukaryotes to mammals. These responses reduce the deleterious consequences of DNA damaging events, including radiation-induced or spontaneous cancer and non-cancer diseases in mice. The adaptive response in mammalian cells and mammals operates within a certain window that can be defined by upper and lower dose thresholds, typically between about 1 and 100 mGy for a single low dose rate exposure. However, these thresholds for protection are not a fixed function of total dose, but also vary with dose rate, additional radiation or non-radiation stressors, tissue type and p53 functional status. Exposures above the upper threshold are generally detrimental, while exposures below the lower threshold may or may not increase either cancer or non-cancer disease risk. PMID:20585438

  16. The Influence of Innate and Adaptive Immune Responses on Atherosclerosis

    PubMed Central

    Witztum, Joseph L.; Lichtman, Andrew H.

    2014-01-01

    Both the chronic development of atherosclerotic lesions and the acute changes in lesion phenotype that lead to clinical cardiovascular events are significantly influenced by the innate and adaptive immune responses to lipoprotein deposition and oxidation in the arterial wall. The rapid pace of discovery of mechanisms of immunologic recognition, effector functions, and regulation has significantly influenced the study of atherosclerosis, and our new knowledge is beginning to affect how we treat this ubiquitous disease. In this review, we discuss recent advances in our understanding of how innate and adaptive immunity contribute to atherosclerosis, as well as therapeutic opportunities that arise from this knowledge. PMID:23937439

  17. Immune and stress responses in oysters with insights on adaptation.

    PubMed

    Guo, Ximing; He, Yan; Zhang, Linlin; Lelong, Christophe; Jouaux, Aude

    2015-09-01

    Oysters are representative bivalve molluscs that are widely distributed in world oceans. As successful colonizers of estuaries and intertidal zones, oysters are remarkably resilient against harsh environmental conditions including wide fluctuations in temperature and salinity as well as prolonged air exposure. Oysters have no adaptive immunity but can thrive in microbe-rich estuaries as filter-feeders. These unique adaptations make oysters interesting models to study the evolution of host-defense systems. Recent advances in genomic studies including sequencing of the oyster genome have provided insights into oyster's immune and stress responses underlying their amazing resilience. Studies show that the oyster genomes are highly polymorphic and complex, which may be key to their resilience. The oyster genome has a large gene repertoire that is enriched for immune and stress response genes. Thousands of genes are involved in oyster's immune and stress responses, through complex interactions, with many gene families expanded showing high sequence, structural and functional diversity. The high diversity of immune receptors and effectors may provide oysters with enhanced specificity in immune recognition and response to cope with diverse pathogens in the absence of adaptive immunity. Some members of expanded immune gene families have diverged to function at different temperatures and salinities or assumed new roles in abiotic stress response. Most canonical innate immunity pathways are conserved in oysters and supported by a large number of diverse and often novel genes. The great diversity in immune and stress response genes exhibited by expanded gene families as well as high sequence and structural polymorphisms may be central to oyster's adaptation to highly stressful and widely changing environments.

  18. Interferon regulatory factor 3 in adaptive immune responses.

    PubMed

    Ysebrant de Lendonck, Laure; Martinet, Valerie; Goriely, Stanislas

    2014-10-01

    Interferon regulatory factor (IRF) 3 plays a key role in innate responses against viruses. Indeed, activation of this transcription factor triggers the expression of type I interferons and downstream interferon-stimulated genes in infected cells. Recent evidences indicate that this pathway also modulates adaptive immune responses. This review focuses on the different mechanisms that are implicated in this process. We discuss the role of IRF3 within antigen-presenting cells and T lymphocytes in the polarization of the cellular immune response and its implication in the pathogenesis of immune disorders.

  19. 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...

  20. 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.

  1. The adaptive response of jaw muscles to varying functional demands.

    PubMed

    Grünheid, Thorsten; Langenbach, Geerling E J; Korfage, Joannes A M; Zentner, Andrej; van Eijden, Theo M G J

    2009-12-01

    Jaw muscles are versatile entities that are able to adapt their anatomical characteristics, such as size, cross-sectional area, and fibre properties, to altered functional demands. The dynamic nature of muscle fibres allows them to change their phenotype to optimize the required contractile function while minimizing energy use. Changes in these anatomical parameters are associated with changes in neuromuscular activity as the pattern of muscle activation by the central nervous system plays an important role in the modulation of muscle properties. This review summarizes the adaptive response of jaw muscles to various stimuli or perturbations in the orofacial system and addresses general changes in muscles as they adapt, specific adaptive changes in jaw muscles under various physiologic and pathologic conditions, and their adaptive response to non-surgical and surgical therapeutic interventions. Although the jaw muscles are used concertedly in the masticatory system, their adaptive changes are not always uniform and vary with the nature, intensity, and duration of the stimulus. In general, stretch, increases neuromuscular activity, and resistance training result in hypertrophy, elicits increases in mitochondrial content and cross-sectional area of the fibres, and may change the fibre-type composition of the muscle towards a larger percentage of slow-type fibres. In contrast, changes in the opposite direction occur when neuromuscular activity is reduced, the muscle is immobilized in a shortened position, or paralysed. The broad range of stimuli that affect the properties of jaw muscles might help explain the large variability in the anatomical and physiological characteristics found among individuals, muscles, and muscle portions.

  2. 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.

  3. 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.

  4. 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

  5. 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

  6. 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

  7. Higher Plants in Space: Microgravity Perception, Response, and Adaptation

    NASA Astrophysics Data System (ADS)

    Zheng, Hui Qiong; Han, Fei; Le, Jie

    2015-11-01

    Microgravity is a major abiotic stress in space. Its effects on plants may depend on the duration of exposure. We focused on two different phases of microgravity responses in space. When higher plants are exposed to short-term (seconds to hours) microgravity, such as on board parabolic flights and sounding rockets, their cells usually exhibit abiotic stress responses. For example, Ca 2+-, lipid-, and pH-signaling are rapidly enhanced, then the production of reactive oxygen species and other radicals increase dramatically along with changes in metabolism and auxin signaling. Under long-term (days to months) microgravity exposure, plants acclimatize to the stress by changing their metabolism and oxidative response and by enhancing other tropic responses. We conclude by suggesting that a systematic analysis of regulatory networks at the molecular level of higher plants is needed to understand the molecular signals in the distinct phases of the microgravity response and adaptation.

  8. Adaptation.

    PubMed

    Broom, Donald M

    2006-01-01

    welfare can be very good when it is occurring. Other adaptation is difficult and may involve lower or higher level emergency physiological responses or abnormal behaviour, often with bad feelings such as pain or fear. In that case, welfare is poor or very poor even if complete adaptation eventually occurs and there is no long-term threat to the life of the individual. In some circumstances, adaptation may be unsuccessful, the individual is not able to cope, stress occurs and welfare is ultimately very poor.

  9. 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.

  10. Adaptive Responses to Tissue Injury: Role of Heme Oxygenase-1

    PubMed Central

    Agarwal, Anupam; Bolisetty, Subhashini

    2013-01-01

    Tissue injury may result as a consequence of a physical, chemical, or biological insult. Such injury recruits an adaptive response to restore homeostasis and protect against further injury. One of the most prompt protective and adaptive responses by all tissues is the robust activation of the highly inducible, anti-inflammatory, anti-oxidant, and anti-apoptotic protein, heme oxygenase-1 (HO-1). HO-1, a microsomal enzyme, catalyzes the breakdown of pro-oxidant heme, which is released from heme proteins to equimolar quantities of iron, carbon monoxide, and biliverdin. Biliverdin is converted to bilirubin by biliverdin reductase. The beneficial effects of HO-1 expression are not merely due to heme degradation but are also attributed to the cytoprotective properties of the byproducts of the reaction. Manipulation of this enzymatic system in a myriad of disease models has provided substantial evidence to support its role as a cytoprotective enzyme and is therefore an emerging therapeutic molecule. PMID:23874015

  11. Biological Bases for Radiation Adaptive Responses in the Lung

    SciTech Connect

    Scott, Bobby R.; Lin, Yong; Wilder, Julie; Belinsky, Steven

    2015-03-01

    Our main research objective was to determine the biological bases for low-dose, radiation-induced adaptive responses in the lung and use the knowledge gained to produce an improved risk model for radiation-induced lung cancer that accounts for activated natural protection, genetic influences, and the role of epigenetic regulation (epiregulation). Currently, low-dose radiation risk assessment is based on the linear-no-threshold hypothesis which now is known to be unsupported by a large volume of data.

  12. Adaptive immune response during hepatitis C virus infection.

    PubMed

    Larrubia, Juan Ramón; Moreno-Cubero, Elia; Lokhande, Megha Uttam; García-Garzón, Silvia; Lázaro, Alicia; Miquel, Joaquín; Perna, Cristian; Sanz-de-Villalobos, Eduardo

    2014-04-07

    Hepatitis C virus (HCV) infection affects about 170 million people worldwide and it is a major cause of liver cirrhosis and hepatocellular carcinoma. HCV is a hepatotropic non-cytopathic virus able to persist in a great percentage of infected hosts due to its ability to escape from the immune control. Liver damage and disease progression during HCV infection are driven by both viral and host factors. Specifically, adaptive immune response carries out an essential task in controlling non-cytopathic viruses because of its ability to recognize infected cells and to destroy them by cytopathic mechanisms and to eliminate the virus by non-cytolytic machinery. HCV is able to impair this response by several means such as developing escape mutations in neutralizing antibodies and in T cell receptor viral epitope recognition sites and inducing HCV-specific cytotoxic T cell anergy and deletion. To impair HCV-specific T cell reactivity, HCV affects effector T cell regulation by modulating T helper and Treg response and by impairing the balance between positive and negative co-stimulatory molecules and between pro- and anti-apoptotic proteins. In this review, the role of adaptive immune response in controlling HCV infection and the HCV mechanisms to evade this response are reviewed.

  13. 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.

  14. 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.

  15. Bayesian response-adaptive designs for basket trials.

    PubMed

    Ventz, Steffen; Barry, William T; Parmigiani, Giovanni; Trippa, Lorenzo

    2017-02-17

    We develop a general class of response-adaptive Bayesian designs using hierarchical models, and provide open source software to implement them. Our work is motivated by recent master protocols in oncology, where several treatments are investigated simultaneously in one or multiple disease types, and treatment efficacy is expected to vary across biomarker-defined subpopulations. Adaptive trials such as I-SPY-2 (Barker et al., 2009) and BATTLE (Zhou et al., 2008) are special cases within our framework. We discuss the application of our adaptive scheme to two distinct research goals. The first is to identify a biomarker subpopulation for which a therapy shows evidence of treatment efficacy, and to exclude other subpopulations for which such evidence does not exist. This leads to a subpopulation-finding design. The second is to identify, within biomarker-defined subpopulations, a set of cancer types for which an experimental therapy is superior to the standard-of-care. This goal leads to a subpopulation-stratified design. Using simulations constructed to faithfully represent ongoing cancer sequencing projects, we quantify the potential gains of our proposed designs relative to conventional non-adaptive designs.

  16. 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, ...

  17. Nutritional strategies to modulate the adaptive response to endurance training.

    PubMed

    Hawley, John A

    2013-01-01

    In recent years, advances in molecular biology have allowed scientists to elucidate how endurance exercise training stimulates skeletal muscle remodeling (i.e. promotes mitochondrial biogenesis). A growing field of interest directly arising from our understanding of the molecular bases of training adaptation is how nutrient availability can alter the regulation of many contraction-induced events in muscle in response to endurance exercise. Acutely manipulating substrate availability can exert profound effects on muscle energy stores and patterns of fuel metabolism during exercise, as well as many processes activating gene expression and cell signaling. Accordingly, such interventions when repeated over weeks and months have the potential to modulate numerous adaptive processes in skeletal muscle that ultimately drive the phenotype-specific characteristics observed in highly trained athletes. In this review, the molecular and cellular events that occur in skeletal muscle during and after endurance exercise are discussed and evidence provided to demonstrate that nutrient availability plays an important role in modulating many of the adaptive responses to training. Emphasis is on human studies that have determined the regulatory role of muscle glycogen availability on cell metabolism, endurance training capacity and performance.

  18. 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

  19. Imbalanced adaptive responses associated with microsatellite instability in cholangiocarcinoma

    PubMed Central

    Loilome, Watcharin; Kadsanit, Sasithorn; Muisook, Kanha; Yongvanit, Puangrat; Namwat, Nisana; Techasen, Anchalee; Puapairoj, Anucha; Khuntikeo, Narong; Phonjit, Pichai

    2017-01-01

    The adaptive response of the genome protection mechanism occurs in cells when exposed to genotoxic stress due to the overproduction of free radicals via inflammation and infection. In such circumstances, cells attempt to maintain health via several genome protection mechanisms. However, evidence is increasing that this adaptive response may have deleterious effect; a reduction of antioxidant enzymes and/or imbalance in the DNA repair system generates microsatellite instability (MSI), which has procarcinogenic implications. Therefore, the present study hypothesized that MSI caused by imbalanced responses of antioxidant enzymes and/or DNA repair enzymes as a result of oxidative/nitrative stress arising from the inflammatory response is involved in liver fluke-associated cholangiocarcinogenesis. The present study investigated this hypothesis by identifying the expression patterns of antioxidant enzymes, including superoxide dismutase 2 (SOD2) and catalase (CAT), and DNA repair enzymes, including alkyladenine DNA glycosylase (AAG), apurinic endonuclease (APE) and DNA polymerase β (DNA pol β). In addition, the activities of the antioxidant enzymes, SOD2 and CAT, were examined in human cholangiocarcinoma (CCA) tissues using immunohistochemical staining. MSI was also analyzed in human CCA tissues. The resulting data demonstrated that the expression levels of the SOD2 and CAT enzymes decreased. The activities of SOD2 and CAT decreased significantly in the CCA tissues, compared with the hepatic tissue of cadaveric donors. In the DNA repairing enzymes, it was found that the expression levels of AAG and DNA pol β enzymes increased, whereas the expression of APE decreased. In addition, it was found that MSI-high was present in 69% of patients, whereas MSI-low was present in 31% of patients, with no patients classified as having microsatellite stability. In the patients, a MSI-high was correlated with poor prognosis, indicated by a shorter survival rate. These results

  20. 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.

  1. Adaptive Patterns of Stress Responsivity: A Preliminary Investigation

    PubMed Central

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

    2014-01-01

    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 taxonomy of the ACM via finite mixture modeling. Moreover, the 4 patterns of responsivity showed the predicted associations with family stress levels but no association with measures of ecological stress. Our hypotheses concerning sex differences in responsivity were only partly confirmed. This preliminary study provides initial support for the key predictions of the ACM and highlights some of the methodological challenges that will need to be considered in future research on this topic. PMID:22148947

  2. The adaptive response in radiobiology: evolving insights and implications.

    PubMed Central

    Wolff, S

    1998-01-01

    The first of the regularly reproducible experiments to show that very low doses of ionizing radiation, like very low doses of chemical agents, could induce mechanisms whereby cells become better fit to cope with subsequent exposures to high doses were carried out on the induction of chromosome aberrations in cultures of human lymphocytes. If cells that had been exposed to a very low dose (1 cGy) of X rays were subsequently exposed to a relatively high dose (1 Gy), approximately half as many chromosome breaks were induced. Subsequent experiments showed that this adaptive response to low doses requires a certain minimal dose before it becomes active; occurs only within a relatively small window of dose; is dose-rate dependent; and depends on the genetic constitution of the people or animals exposed, with some being unresponsive. It was further shown that the response to the low-dose preexposure was not instantaneous but took approximately 4 to 6 hr to become fully active, and could be prevented if during this period protein synthesis was inhibited, i.e., a necessary protein (enzyme) was being induced. In fact, subsequent experiments with two-dimensional gel electrophoresis showed new proteins in cells irradiated with 1 to 2 cGy. The adaptation induced by low doses of radiation was therefore attributed to the induction of a novel efficient chromosome break repair mechanism that if active at the time of challenge with high doses would lead to less residual damage. This hypothesis was strengthened by a series of experiments in which it was found that inhibitors of poly(ADP-ribose)polymerase, an enzyme implicated in DNA strand break rejoining, could prevent the adaptive response. Although the phenomenon is well established in cellular systems, it is still problematical as to whether or not it will have any utility in establishing risks of ionizing radiation to humans. Newer experiments have now been carried out on the mechanisms underlying the effect and whether or not

  3. 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.

  4. 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.

  5. 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.

  6. Protein phosphorylation and regulation of adaptive responses in bacteria.

    PubMed Central

    Stock, J B; Ninfa, A J; Stock, A M

    1989-01-01

    Bacteria continuously adapt to changes in their environment. Responses are largely controlled by signal transduction systems that contain two central enzymatic components, a protein kinase that uses adenosine triphosphate to phosphorylate itself at a histidine residue and a response regulator that accepts phosphoryl groups from the kinase. This conserved phosphotransfer chemistry is found in a wide range of bacterial species and operates in diverse systems to provide different regulatory outputs. The histidine kinases are frequently membrane receptor proteins that respond to environmental signals and phosphorylate response regulators that control transcription. Four specific regulatory systems are discussed in detail: chemotaxis in response to attractant and repellent stimuli (Che), regulation of gene expression in response to nitrogen deprivation (Ntr), control of the expression of enzymes and transport systems that assimilate phosphorus (Pho), and regulation of outer membrane porin expression in response to osmolarity and other culture conditions (Omp). Several additional systems are also examined, including systems that control complex developmental processes such as sporulation and fruiting-body formation, systems required for virulent infections of plant or animal host tissues, and systems that regulate transport and metabolism. Finally, an attempt is made to understand how cross-talk between parallel phosphotransfer pathways can provide a global regulatory curcuitry. PMID:2556636

  7. Biological and Theoretical Studies of Adaptive Networks: The Conditioned Response.

    DTIC Science & Technology

    1992-06-30

    Eichenbaum , H. and Butter, C.M., The role of frontalcortex-reticular interactions in performance and extinction of Recordings of multiple-unit activity in...such a way that they are appropriate to the ’task demands’ imposed by training parameters (Levey and Martin , 1968). The main evidence for this adaptive...8217 Science 237, 1445-1452. 12. Levey, A. B. and Martin , I. (1968) ’Shape of the conditioned eyelid response,’ Psychological Review 75, 398-408. 13. Millenson

  8. Deciphering the Adaptive Immune Response to Ovarian Cancer

    DTIC Science & Technology

    2014-10-01

    Weinstein JN, Collisson EA, Mills GB, Shaw KR, Ozenberger BA, Ellrott K, Shmulevich I, Sander C, Stuart JM. The Cancer Genome Atlas Pan-Cancer analysis...Holt, Ph.D., John Webb Ph.D., Peter Watson, M.D. Title of Project: Deciphering the Adaptive Immune Response to Ovarian Cancer INTRODUCTION...Cherniack AD, Akbani R, Liu Y, Shen H, Robertson AG, Pashtan I, Shen R, Benz CC, Yau C, Laird PW, Ding L, Zhang W, Mills GB, Kucherlapati R, Mardis ER

  9. 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.

  10. 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.

  11. Glycerol stress in Saccharomyces cerevisiae: Cellular responses and evolved adaptations.

    PubMed

    Mattenberger, Florian; Sabater-Muñoz, Beatriz; Hallsworth, John E; Fares, Mario A

    2017-03-01

    Glycerol synthesis is key to central metabolism and stress biology in Saccharomyces cerevisiae, yet the cellular adjustments needed to respond and adapt to glycerol stress are little understood. Here, we determined impacts of acute and chronic exposures to glycerol stress in S. cerevisiae. Glycerol stress can result from an increase of glycerol concentration in the medium due to the S. cerevisiae fermenting activity or other metabolic activities. Acute glycerol-stress led to a 50% decline in growth rate and altered transcription of more than 40% of genes. The increased genetic diversity in S. cerevisiae population, which had evolved in the standard nutrient medium for hundreds of generations, led to an increase in growth rate and altered transcriptome when such population was transferred to stressful media containing a high concentration of glycerol; 0.41 M (0.990 water activity). Evolution of S. cerevisiae populations during a 10-day period in the glycerol-containing medium led to transcriptome changes and readjustments to improve control of glycerol flux across the membrane, regulation of cell cycle, and more robust stress response; and a remarkable increase of growth rate under glycerol stress. Most of the observed regulatory changes arose in duplicated genes. These findings elucidate the physiological mechanisms, which underlie glycerol-stress response, and longer-term adaptations, in S. cerevisiae; they also have implications for enigmatic aspects of the ecology of this otherwise well-characterized yeast.

  12. 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.

  13. Autophagy is an adaptive response in desmin-related cardiomyopathy

    PubMed Central

    Tannous, Paul; Zhu, Hongxin; Johnstone, Janet L.; Shelton, John M.; Rajasekaran, Namakkal S.; Benjamin, Ivor J.; Nguyen, Lan; Gerard, Robert D.; Levine, Beth; Rothermel, Beverly A.; Hill, Joseph A.

    2008-01-01

    A missense mutation in the αB-crystallin (CryAB) gene triggers a severe form of desmin-related cardiomyopathy (DRCM) characterized by accumulation of misfolded proteins. We hypothesized that autophagy increases in response to protein aggregates and that this autophagic activity is adaptive. Mutant CryAB (CryABR120G) triggered a >2-fold increase in cardiomyocyte autophagic activity, and blunting autophagy increased the rate of aggregate accumulation and the abundance of insoluble CryABR120G-associated aggregates. Cardiomyocyte-restricted overexpression of CryABR120G in mice induced intracellular aggregate accumulation and systolic heart failure by 12 months. As early as 2 months (well before the earliest declines in cardiac function), we detected robust autophagic activity. To test the functional significance of autophagic activation, we crossed CryABR120G mice with animals harboring heterozygous inactivation of beclin 1, a gene required for autophagy. Blunting autophagy in vivo dramatically hastened heart failure progression with a 3-fold increase in interstitial fibrosis, greater accumulation of polyubiquitinated proteins, larger and more extensive intracellular aggregates, accelerated ventricular dysfunction, and early mortality. This study reports activation of autophagy in DRCM. Further, our findings point to autophagy as an adaptive response in this proteotoxic form of heart disease. PMID:18621691

  14. Chlamydia trachomatis: Protective Adaptive Responses and Prospects for a Vaccine.

    PubMed

    Poston, Taylor B; Darville, Toni

    2016-04-01

    Chlamydia trachomatis is the most common cause of sexually transmitted bacterial infection globally. These infections translate to a significant public health burden, particularly women's healthcare costs due to serious disease sequelae such as pelvic inflammatory disease (PID), tubal factor infertility, chronic pelvic pain, and ectopic pregnancy. There is no evidence that natural immunity can provide complete, long-term protection necessary to prevent chronic pathology, making human vaccine development critical. Vaccine design will require careful consideration of protective versus pathological host-response mechanisms in concert with elucidation of optimal antigens and adjuvants. Evidence suggests that a Th1 response, facilitated by IFN-γ-producing CD4 T cells, will be instrumental in generating long-term, sterilizing immunity. Although the role of antibodies is not completely understood, they have exhibited a protective effect by enhancing chlamydial clearance. Future work will require investigation of broadly neutralizing antibodies and antibody-augmented cellular immunity to successfully design a vaccine that potently elicits both arms of the immune response. Sterilizing immunity is the ultimate goal. However, vaccine-induced partial immunity that prevents upper genital tract infection and inflammation would be cost-effective compared to current screening and treatment strategies. In this chapter, we examine evidence from animal and human studies demonstrating protective adaptive immune responses to Chlamydia and discuss future challenges and prospects for vaccine development.

  15. Autophagy orchestrates adaptive responses to targeted therapy in endometrial cancer.

    PubMed

    Eritja, Núria; Chen, Bo-Juen; Rodríguez-Barrueco, Ruth; Santacana, Maria; Gatius, Sònia; Vidal, August; Martí, Maria Dolores; Ponce, Jordi; Bergadà, Laura; Yeramian, Andree; Encinas, Mario; Ribera, Joan; Reventós, Jaume; Boyd, Jeff; Villanueva, Alberto; Matias-Guiu, Xavier; Dolcet, Xavier; Llobet-Navàs, David

    2017-01-05

    Targeted therapies in endometrial cancer (EC) using kinase inhibitors rarely result in complete tumor remission and are frequently challenged by the appearance of refractory cell clones, eventually resulting in disease relapse. Dissecting adaptive mechanisms is of vital importance to circumvent clinical drug resistance and improve the efficacy of targeted agents in EC. Sorafenib is an FDA-approved multitarget tyrosine and serine/threonine kinase inhibitor currently used to treat hepatocellular carcinoma, advanced renal carcinoma and radioactive iodine-resistant thyroid carcinoma. Unfortunately, sorafenib showed very modest effects in a multi-institutional phase II trial in advanced uterine carcinoma patients. Here, by leveraging RNA-sequencing data from the Cancer Cell Line Encyclopedia and cell survival studies from compound-based high-throughput screenings we have identified the lysosomal pathway as a potential compartment involved in the resistance to sorafenib. By performing additional functional biology studies we have demonstrated that this resistance could be related to macroautophagy/autophagy. Specifically, our results indicate that sorafenib triggers a mechanistic MAPK/JNK-dependent early protective autophagic response in EC cells, providing an adaptive response to therapeutic stress. By generating in vivo subcutaneous EC cell line tumors, lung metastatic assays and primary EC orthoxenografts experiments, we demonstrate that targeting autophagy enhances sorafenib cytotoxicity and suppresses tumor growth and pulmonary metastasis progression. In conclusion, sorafenib induces the activation of a protective autophagic response in EC cells. These results provide insights into the unopposed resistance of advanced EC to sorafenib and highlight a new strategy for therapeutic intervention in recurrent EC.

  16. PD-1 blockade induces responses by inhibiting adaptive immune resistance

    PubMed Central

    Tumeh, Paul C.; Harview, Christina L.; Yearley, Jennifer H.; Shintaku, I. Peter; Taylor, Emma J. M.; Robert, Lidia; Chmielowski, Bartosz; Spasic, Marko; Henry, Gina; Ciobanu, Voicu; West, Alisha N.; Carmona, Manuel; Kivork, Christine; Seja, Elizabeth; Cherry, Grace; Gutierrez, Antonio; Grogan, Tristan R.; Mateus, Christine; Tomasic, Gorana; Glaspy, John A.; Emerson, Ryan O.; Robins, Harlan; Pierce, Robert H.; Elashoff, David A.; Robert, Caroline; Ribas, Antoni

    2014-01-01

    Therapies that target the programmed death-1 (PD-1) receptor have shown unprecedented rates of durable clinical responses in patients with various cancer types.1–5 One mechanism by which cancer tissues limit the host immune response is via upregulation of PD-1 ligand (PD-L1) and its ligation to PD-1 on antigen-specific CD8 T-cells (termed adaptive immune resistance).6,7 Here we show that pre-existing CD8 T-cells distinctly located at the invasive tumour margin are associated with expression of the PD-1/PD-L1 immune inhibitory axis and may predict response to therapy. We analyzed samples from 46 patients with metastatic melanoma obtained before and during anti-PD1 therapy (pembrolizumab) using quantitative immunohistochemistry, quantitative multiplex immunofluorescence, and next generation sequencing for T-cell receptors (TCR). In serially sampled tumours, responding patients showed proliferation of intratumoural CD8+ T-cells that directly correlated with radiographic reduction in tumour size. Pre-treatment samples obtained from responding patients showed higher numbers of CD8, PD1, and PD-L1 expressing cells at the invasive tumour margin and inside tumours, with close proximity between PD-1 and PD-L1, and a more clonal TCR repertoire. Using multivariate analysis, we established a predictive model based on CD8 expression at the invasive margin and validated the model in an independent cohort of 15 patients. Our findings indicate that tumour regression following therapeutic PD-1 blockade requires pre-existing CD8+ T cells that are negatively regulated by PD-1/PD-L1 mediated adaptive immune resistance. PMID:25428505

  17. Autophagy orchestrates adaptive responses to targeted therapy in endometrial cancer

    PubMed Central

    Eritja, Núria; Chen, Bo-Juen; Rodríguez-Barrueco, Ruth; Santacana, Maria; Gatius, Sònia; Vidal, August; Martí, Maria Dolores; Ponce, Jordi; Bergadà, Laura; Yeramian, Andree; Encinas, Mario; Ribera, Joan; Reventós, Jaume; Boyd, Jeff; Villanueva, Alberto; Matias-Guiu, Xavier; Dolcet, Xavier

    2017-01-01

    ABSTRACT Targeted therapies in endometrial cancer (EC) using kinase inhibitors rarely result in complete tumor remission and are frequently challenged by the appearance of refractory cell clones, eventually resulting in disease relapse. Dissecting adaptive mechanisms is of vital importance to circumvent clinical drug resistance and improve the efficacy of targeted agents in EC. Sorafenib is an FDA-approved multitarget tyrosine and serine/threonine kinase inhibitor currently used to treat hepatocellular carcinoma, advanced renal carcinoma and radioactive iodine-resistant thyroid carcinoma. Unfortunately, sorafenib showed very modest effects in a multi-institutional phase II trial in advanced uterine carcinoma patients. Here, by leveraging RNA-sequencing data from the Cancer Cell Line Encyclopedia and cell survival studies from compound-based high-throughput screenings we have identified the lysosomal pathway as a potential compartment involved in the resistance to sorafenib. By performing additional functional biology studies we have demonstrated that this resistance could be related to macroautophagy/autophagy. Specifically, our results indicate that sorafenib triggers a mechanistic MAPK/JNK-dependent early protective autophagic response in EC cells, providing an adaptive response to therapeutic stress. By generating in vivo subcutaneous EC cell line tumors, lung metastatic assays and primary EC orthoxenografts experiments, we demonstrate that targeting autophagy enhances sorafenib cytotoxicity and suppresses tumor growth and pulmonary metastasis progression. In conclusion, sorafenib induces the activation of a protective autophagic response in EC cells. These results provide insights into the unopposed resistance of advanced EC to sorafenib and highlight a new strategy for therapeutic intervention in recurrent EC. PMID:28055301

  18. Innate and adaptive immune responses against Staphylococcus aureus skin infections.

    PubMed

    Krishna, Sheila; Miller, Lloyd S

    2012-03-01

    Staphylococcus aureus is an important human pathogen that is responsible for the vast majority of bacterial skin and soft tissue infections in humans. S. aureus can also become more invasive and cause life-threatening infections such as bacteremia, pneumonia, abscesses of various organs, meningitis, osteomyelitis, endocarditis, and sepsis. These infections represent a major public health threat due to the enormous numbers of these infections and the widespread emergence of methicillin-resistant S. aureus (MRSA) strains. MSRA is endemic in hospitals worldwide and is rapidly spreading throughout the normal human population in the community. The increasing frequency of MRSA infections has complicated treatment as these strains are more virulent and are increasingly becoming resistant to multiple different classes of antibiotics. The important role of the immune response against S. aureus infections cannot be overemphasized as humans with certain genetic and acquired immunodeficiency disorders are at an increased risk for infection. Understanding the cutaneous immune responses against S. aureus is essential as most of these infections occur or originate from a site of infection or colonization of the skin and mucosa. This review will summarize the innate immune responses against S. aureus skin infections, including antimicrobial peptides that have direct antimicrobial activity against S. aureus as well as pattern recognition receptors and proinflammatory cytokines that promote neutrophil abscess formation in the skin, which is required for bacterial clearance. Finally, we will discuss the recent discoveries involving IL-17-mediated responses, which provide a key link between cutaneous innate and adaptive immune responses against S. aureus skin infections.

  19. 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.

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

    SciTech Connect

    Calabrese, Edward J. . E-mail: edwardc@schoolph.umass.edu; 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.

    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.

  1. 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…

  2. 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.

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

    PubMed

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

    2016-03-01

    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 modeling and a nationally representative standardization sample, the item set was reduced to 75 items that provide the most precise adaptive behavior information at the cutoff area determining the presence or not of significant adaptive behavior deficits across conceptual, social, and practical skills. The standardization of the DABS is described and discussed.

  4. 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.

  5. 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.

  6. Adaptation or Malignant Transformation: The Two Faces of Epigenetically Mediated Response to Stress

    PubMed Central

    Zoldoš, Vlatka

    2013-01-01

    Adaptive response to stress is a fundamental property of living systems. At the cellular level, many different types of stress elicit an essentially limited repertoire of adaptive responses. Epigenetic changes are the main mechanism for medium- to long-term adaptation to accumulated (intense, long-term, or repeated) stress. We propose the adaptive deregulation of the epigenome in response to stress (ADERS) hypothesis which assumes that the unspecific adaptive stress response grows stronger with the increasing stress level, epigenetically activating response gene clusters while progressively deregulating other cellular processes. The balance between the unspecific adaptive response and the general epigenetic deregulation is critical because a strong response can lead to pathology, particularly to malignant transformation. The main idea of our hypothesis is the continuum traversed by a cell subjected to accumulated stress, which lies between an unspecific adaptive response and pathological deregulation—the two extremes sharing the same underlying cause, which is a manifestation of a unified epigenetically mediated adaptive response to stress. The evolutionary potential of epigenetic regulation in multigenerational adaptation is speculatively discussed in the light of neo-Lamarckism. Finally, an approach to testing the proposed hypothesis is presented, relying on either the publicly available datasets or on conducting new experiments. PMID:24187667

  7. Adaptation or malignant transformation: the two faces of epigenetically mediated response to stress.

    PubMed

    Vojta, Aleksandar; Zoldoš, Vlatka

    2013-01-01

    Adaptive response to stress is a fundamental property of living systems. At the cellular level, many different types of stress elicit an essentially limited repertoire of adaptive responses. Epigenetic changes are the main mechanism for medium- to long-term adaptation to accumulated (intense, long-term, or repeated) stress. We propose the adaptive deregulation of the epigenome in response to stress (ADERS) hypothesis which assumes that the unspecific adaptive stress response grows stronger with the increasing stress level, epigenetically activating response gene clusters while progressively deregulating other cellular processes. The balance between the unspecific adaptive response and the general epigenetic deregulation is critical because a strong response can lead to pathology, particularly to malignant transformation. The main idea of our hypothesis is the continuum traversed by a cell subjected to accumulated stress, which lies between an unspecific adaptive response and pathological deregulation--the two extremes sharing the same underlying cause, which is a manifestation of a unified epigenetically mediated adaptive response to stress. The evolutionary potential of epigenetic regulation in multigenerational adaptation is speculatively discussed in the light of neo-Lamarckism. Finally, an approach to testing the proposed hypothesis is presented, relying on either the publicly available datasets or on conducting new experiments.

  8. 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.

  9. Adaptation responses in C4 photosynthesis of maize under salinity.

    PubMed

    Omoto, Eiji; Taniguchi, Mitsutaka; Miyake, Hiroshi

    2012-03-15

    The effect of salinity on C(4) photosynthesis was examined in leaves of maize, a NADP-malic enzyme (NADP-ME) type C(4) species. Potted plants with the fourth leaf blade fully developed were treated with 3% NaCl solution for 5d. Under salt treatment, the activities of pyruvate orthophosphate dikinase (PPDK), phosphoenolpyruvate carboxylase (PEPCase), NADP-dependent malate dehydrogenase (NADP-MDH) and NAD-dependent malate dehydrogenase (NAD-MDH), which are derived mainly from mesophyll cells, increased, whereas those of NADP-ME and ribulose-1,5-bisphosphate carboxylase, which are derived mainly from bundle sheath cells (BSCs), decreased. Immunocytochemical studies by electron microscopy revealed that PPDK protein increased, while the content of ribulose-1,5-bisphosphate carboxylase/oxygenase protein decreased under salinity. In salt-treated plants, the photosynthetic metabolites malate, pyruvate and starch decreased by 40, 89 and 81%, respectively. Gas-exchange analysis revealed that the net photosynthetic rate, the transpiration rate, stomatal conductance (g(s)) and the intercellular CO(2) concentration decreased strongly in salt-treated plants. The carbon isotope ratio (δ(13)C) in these plants was significantly lower than that in control. These findings suggest that the decrease in photosynthetic metabolites under salinity was induced by a reduction in gas-exchange. Moreover, in addition to the decrease in g(s), the decrease in enzyme activities in BSCs was responsible for the decline of C(4) photosynthesis. The increase of PPDK, PEPCase, NADP-MDH, and NAD-MDH activities and the decrease of NADP-ME activity are interpreted as adaptation responses to salinity.

  10. REM Sleep Rebound as an Adaptive Response to Stressful Situations

    PubMed Central

    Suchecki, Deborah; Tiba, Paula Ayako; Machado, Ricardo Borges

    2011-01-01

    Stress and sleep are related to each other in a bidirectional way. If on one hand poor or inadequate sleep exacerbates emotional, behavioral, and stress-related responses, on the other hand acute stress induces sleep rebound, most likely as a way to cope with the adverse stimuli. Chronic, as opposed to acute, stress impairs sleep and has been claimed to be one of the triggering factors of emotional-related sleep disorders, such as insomnia, depressive- and anxiety-disorders. These outcomes are dependent on individual psychobiological characteristics, conferring even more complexity to the stress-sleep relationship. Its neurobiology has only recently begun to be explored, through animal models, which are also valuable for the development of potential therapeutic agents and preventive actions. This review seeks to present data on the effects of stress on sleep and the different approaches used to study this relationship as well as possible neurobiological underpinnings and mechanisms involved. The results of numerous studies in humans and animals indicate that increased sleep, especially the rapid eye movement phase, following a stressful situation is an important adaptive behavior for recovery. However, this endogenous advantage appears to be impaired in human beings and rodent strains that exhibit high levels of anxiety and anxiety-like behavior. PMID:22485105

  11. 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.

  12. Epigenetic memory for stress response and adaptation in plants.

    PubMed

    Kinoshita, Tetsu; Seki, Motoaki

    2014-11-01

    In contrast to the majority of animal species, plants are sessile organisms and are, therefore, constantly challenged by environmental perturbations. Over the past few decades, our knowledge of how plants perceive environmental stimuli has increased considerably, e.g. the mechanisms for transducing environmental stress stimuli into cellular signaling cascades and gene transcription networks. In addition, it has recently been shown that plants can remember past environmental events and can use these memories to aid responses when these events recur. In this mini review, we focus on recent progress in determination of the epigenetic mechanisms used by plants under various environmental stresses. Epigenetic mechanisms are now known to play a vital role in the control of gene expression through small RNAs, histone modifications and DNA methylation. These are inherited through mitotic cell divisions and, in some cases, can be transmitted to the next generation. They therefore offer a possible mechanism for stress memories in plants. Recent studies have yielded evidence indicating that epigenetic mechanisms are indeed essential for stress memories and adaptation in plants.

  13. 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

  14. 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.

  15. 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.

  16. 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...

  17. Human adaptation genetic response suites: Toward new interventions and countermeasures for spaceflight

    NASA Astrophysics Data System (ADS)

    Sundaresan, A.; Pellis, N. R.

    2005-08-01

    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 1g 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.

  18. 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.

  19. Bioenergetic adaptation in response to autophagy regulators during rotenone exposure

    PubMed Central

    Giordano, Samantha; Dodson, Matthew; Ravi, Saranya; Redmann, Matthew; Ouyang, Xiaosen; Usmar, Victor M Darley; Zhang, Jianhua

    2015-01-01

    Parkinson’s disease (PD) is the second most common neurodegenerative disorder with both mitochondrial dysfunction and insufficient autophagy playing a key role in its pathogenesis. Among the risk factors, exposure to the environmental neurotoxin rotenone increases the probability of developing PD. We previously reported that in differentiated SH-SY5Y cells, rotenone-induced cell death is directly related to inhibition of mitochondrial function. How rotenone at nM concentrations inhibits mitochondrial function, and whether it can engage the autophagy pathway necessary to remove damaged proteins and organelles, is unknown. We tested the hypothesis that autophagy plays a protective role against rotenone toxicity in primary neurons. We found that rotenone (10–100 nM) immediately inhibited cellular bioenergetics. Concentrations that decreased mitochondrial function at 2 hr, caused cell death at 24 hr with an LD50 of 10 nM. Overall autophagic flux was decreased by 10 nM rotenone at both 2 and 24 hr, but surprisingly mitophagy, or autophagy of the mitochondria, was increased at 24 hr, suggesting that a mitochondrial-specific lysosomal degradation pathway may be activated. Upregulation of autophagy by rapamycin protected against cell death while inhibition of autophagy by 3-methyladenine (3-MA) exacerbated cell death. Interestingly, while 3-MA exacerbated the rotenone-dependent effects on bioenergetics, rapamycin did not prevent rotenone-induced mitochondrial dysfunction, but caused reprogramming of mitochondrial substrate usage associated with both complex I and complex II activities. Taken together, these data demonstrate that autophagy can play a protective role in primary neuron survival in response to rotenone; moreover, surviving neurons exhibit bioenergetic adaptations to this metabolic stressor. PMID:25081478

  20. 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.

  1. Adaptive response to hydrogen peroxide in yeast: induction, time course, and relationship to dose-response models.

    PubMed

    Hoffmann, George R; Moczula, Andrew V; Laterza, Amanda M; Macneil, Lindsey K; Tartaglione, Jason P

    2013-07-01

    The assay for trp5 gene conversion and ilv1-92 reversion in Saccharomyces cerevisiae strain D7 was used to characterize the induction of an adaptive response by hydrogen peroxide (H(2)O(2)). Effects of a small priming dose on the genotoxic effects of a larger challenge dose were measured in exponential cultures and in early stationary phase. An adaptive response, indicated by smaller convertant and revertant frequencies after the priming dose, occurred at lower priming and challenge doses in young, well-aerated cultures. Closely spaced priming doses from 0.000975 to 2 mM, followed by a 1 mM challenge, showed that the induction of the adaptive response is biphasic. In exponential cultures it was maximal with a priming dose of 0.125-0.25 mM. Very small priming doses were insufficient to induce the adaptive response, whereas higher doses contributed to damage. A significant adaptive response was detected when the challenge dose was administered 10-20 min after the priming exposure. It was fully expressed within 45 min, and the yeast began to return to the nonadapted state after 4-6 hr. Because of the similarity of the biphasic induction to hormetic curves and the proposal that adaptive responses are a manifestation of hormesis, we evaluated whether the low doses of H(2)O(2) that induce the adaptive response show a clear hormetic response without a subsequent challenge dose. Hormesis was not evident, but there was an apparent threshold for genotoxicity at or slightly below 0.125 mM. The results are discussed with respect to linear, threshold, and hormesis dose-response models.

  2. The effect of prism adaptation on the response AC/A ratio.

    PubMed

    Rainey, B B

    2000-05-01

    Vergence adaptation, also known as prism adaptation, is a phenomenon in which a patient's heterophoria changes after prolonged viewing through prism. The effect of prism adaptation on the accommodation-convergence relationship, quantified by the AC/A ratio, is not known. Previous studies of AC/A ratio stability and alterability have used only stimulus AC/A ratio calculations, or have measured accommodative responses to only one or two stimuli. The ideal study of AC/A ratio stability and alterability would measure accommodative responses to several accommodative stimuli, and use these along with vergence responses to calculate response AC/A ratios, rather than stimulus AC/A ratios. In addition, the gradient method should be used to avoid any effect of proximal vergence resulting from changes in target distance. This paper describes a project which investigated the effect of vergence (prism) adaptation on the gradient response AC/A ratio, using accommodative responses measured for five different accommodative stimuli. The response AC/A ratio did not significantly change following a period of adaptation to base-in prism for six of the eight subjects in this study. In addition, the response AC/A ratio did not significantly change following a period of adaptation to base-out prism for six of the eight subjects.

  3. 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

  4. 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…

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

    NASA Astrophysics Data System (ADS)

    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.

  6. 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

  7. 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…

  8. Molecular characterization of an adaptive response to alkylating agents in the opportunistic pathogen Aspergillus fumigatus

    PubMed Central

    O’Hanlon, Karen A.; Margison, Geoffrey P.; Hatch, Amy; Fitzpatrick, David A.; Owens, Rebecca A.; Doyle, Sean; Jones, Gary W.

    2012-01-01

    An adaptive response to alkylating agents based upon the conformational change of a methylphosphotriester (MPT) DNA repair protein to a transcriptional activator has been demonstrated in a number of bacterial species, but this mechanism appears largely absent from eukaryotes. Here, we demonstrate that the human pathogen Aspergillus fumigatus elicits an adaptive response to sub-lethal doses of the mono-functional alkylating agent N-methyl-N′-nitro-N-nitrosoguanidine (MNNG). We have identified genes that encode MPT and O6-alkylguanine DNA alkyltransferase (AGT) DNA repair proteins; deletions of either of these genes abolish the adaptive response and sensitize the organism to MNNG. In vitro DNA repair assays confirm the ability of MPT and AGT to repair methylphosphotriester and O6-methylguanine lesions respectively. In eukaryotes, the MPT protein is confined to a select group of fungal species, some of which are major mammalian and plant pathogens. The evolutionary origin of the adaptive response is bacterial and rooted within the Firmicutes phylum. Inter-kingdom horizontal gene transfer between Firmicutes and Ascomycete ancestors introduced the adaptive response into the Fungal kingdom. Our data constitute the first detailed characterization of the molecular mechanism of the adaptive response in a lower eukaryote and has applications for development of novel fungal therapeutics targeting this DNA repair system. PMID:22669901

  9. 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.

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

    PubMed

    Biondi, R; Capodicasa, E; Tassi, C; Mezzasoma, 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-beta-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 hypokinetic 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.

  11. 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.

  12. 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.

  13. Converging concepts: adaptive response, preconditioning, and the Yerkes-Dodson Law are manifestations of hormesis.

    PubMed

    Calabrese, Edward J

    2008-01-01

    The adaptive response in toxicology and environmental mutagenesis, preconditioning in biomedicine and the Yerkes-Dodson Law in psychology have dominating research themes with widespread and significant scientific and societal implications. This paper suggests that these apparently independent biological dose-response phenomena are manifestations of the common and more general biphasic dose-response relationship concept called hormesis. These three types of dose-response, as well as the hormesis concept, may represent the same general type of adaptation, which were discovered independently in different biological disciplines, amongst which there has been little communication. This intellectual isolation, due principally to progressively greater disciplinary specialization, resulted in the evolution of different terminologies for dose-response phenomena with strikingly similar quantitative features. This lack of recognition of converging dose-response concepts across disciplines has important implications since it limits the recognition of a common and basic biological concept while minimizing collaborations by investigators in related areas. The paper concludes that the broadly recognized biological adaptive responses, as described by the concepts of adaptive response, preconditioning and the Yerkes-Dodson Law, are special cases of the more general hormesis dose-response concept.

  14. 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.

  15. Adaptive response of human melanoma cells to methylglyoxal injury.

    PubMed

    Amicarelli, F; Bucciarelli, T; Poma, A; Aimola, P; Di Ilio, C; Ragnelli, A M; Miranda, M

    1998-03-01

    The effects of methylglyoxal on the growth of a line of human melanoma cells are investigated. Methylglyoxal inhibits cell growth in a dose-dependent manner and causes an increase in glyceraldehyde 3-phosphate dehydrogenase, and glyoxalase 1 and glyoxalase 2 specific activities. The cellular response to increasing concentrations of methylglyoxal in the culture medium is also studied by measuring L-lactate production, reduced-oxidized glutathione levels and apoptotic cell death. Methylglyoxal seems to promote a change of cell population phenotypic repertoire toward a more monomorphic phenotype. In conclusion, methylglyoxal seems to induce an enzymatic cellular response that lowers methylglyoxal levels and selects the most resistant cells.

  16. Response-Adaptive Decision-Theoretic Trial Design: Operating Characteristics and Ethics

    PubMed Central

    Lipsky, Ari M.; Lewis, Roger J.

    2013-01-01

    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 type 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 which 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 type I and II error rates largely negates the benefit of including competing needs in favor of the goal of parameter estimation. PMID:23558674

  17. Variability in the adaptive acid tolerance response phenotype of Salmonella enterica strains.

    PubMed

    Lianou, Alexandra; Nychas, George-John E; Koutsoumanis, Konstantinos P

    2017-04-01

    The objective of this study was the assessment of the stationary-phase, low-pH-inducible acid tolerance response (ATR) of different Salmonella enterica strains. For this purpose, 30 strains of the pathogen were grown in tryptone soy broth in the absence (non-adapted cultures) and presence (1% w/v; acid-adapted cultures) of glucose, and then subjected to 4-h acid challenge trials at pH 3.0. Surviving populations of each strain were determined at 1-h intervals, and the Weibull model was fitted to the derived microbiological data. Extensive variability in the acid stress responses of the tested S. enterica strains was observed, with the total population reductions (log CFU/ml) attained in 4 h of acid challenge ranging from 0.9 to 5.5 and from 0.6 to 7.0 for the non-adapted and acid-adapted cultures, respectively. As demonstrated by the model scale parameter δ and shape parameter p, the effect of acid adaptation on the inactivation curves was strain-specific. Although acid adaptation resulted in enhanced acid survival for the majority of the tested strains, there were strains exhibiting similar or decreased acid resistance compared to their non-adapted counterparts. Moreover, acid adaptation appeared to decrease the strain variability of δ whereas increasing the strain variability of p: the coefficient of variation of δ among the tested strains was 97.2 and 54.9% for the non-adapted and acid-adapted cultures, respectively, while the corresponding values for p were 12.7 and 48.1%. The data of the present study, which is the first one to systematically evaluate the adaptive ATR of multiple S. enterica strains, clearly demonstrate that this phenotype (attempted to be induced by growing the pathogen in the presence of glucose) is strain-dependent.

  18. 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

  19. Innate and Adaptive Immune Response to Apoptotic Cells

    PubMed Central

    Peng, YuFeng; Martin, David A; Kenkel, Justin; Zhang, Kang; Ogden, Carol Anne; Elkon, Keith B.

    2007-01-01

    The immune system is constantly exposed to dying cells, most of which arise during central tolerance and from effete circulating immune cells. Under homeostatic conditions, phagocytes (predominantly macrophages and dendritic cells) belonging to the innate immune system, rapidly ingest cells and their debris. Apoptotic cell removal requires recognition of altered self on the apoptotic membrane, a process which is facilitated by natural antibodies and serum opsonins. Recognition, may be site and context specific. Uptake and ingestion of apoptotic cells promotes an immunosuppressive environment that avoids inflammatory responses to self antigens. However, it does not preclude a T cell response and it is likely that constant exposure to self antigen, particularly by immature dendritic cells, leads to T cell tolerance. Tolerance occurs by several different mechanisms including anergy and deletion (for CD8+ T cells) and induction of T regulatory cells (for CD4+ T cells). Failed apoptotic cell clearance promotes immune responses to self antigens, especially when the cellular contents are leaked from the cell (necrosis). Inflammatory responses may be induced by nucleic acid stimulation of toll like receptors and other immune sensors, specific intracellular proteins and non protein (uric acid) stimulation of inflammasomes. PMID:17888627

  20. Analysis of differential immune responses induced by innate and adaptive immunity following transplantation

    PubMed Central

    He, Hongzhen; Stone, James R; Perkins, David L

    2003-01-01

    The roles of innate and adaptive immunity in allograft rejection remain incompletely understood. Previous studies analysing lymphocyte deficient or syngeneic graft recipients have identified subsets of inflammatory chemokines and cytokines induced by antigen independent mechanisms. In the current study, we analysed a panel of 60 inflammatory parameters including serum cytokines, intragraft chemokines and cytokines, receptors, and cellular markers. Our results confirmed the up-regulation of a subset of markers by innate mechanisms and also identified a subset of parameters up-regulated only in the context of an adaptive response. Thus, we successfully differentiated markers of the innate and adaptive phases of rejection. Current paradigms emphasize that innate signals can promote a subsequent adaptive response. Interestingly, in our studies, expression of the markers induced by innate mechanisms was markedly amplified in the allogeneic, but not syngeneic or lymphocyte deficient, recipients. These results suggest that inflammatory mediators can have functional overlap between the innate and adaptive responses, and that the adaptive component of the rejection process amplifies the innate response by positive feedback regulation. PMID:12757613

  1. 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…

  2. 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...

  3. 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

  4. Adaptive dose finding based on t-statistic for dose-response trials.

    PubMed

    Ivanova, Anastasia; Bolognese, James A; Perevozskaya, Inna

    2008-05-10

    The goals of phase II dose-response studies are to prove that the treatment is effective and to choose the dose for further development. Randomized designs with equal allocation to either a high dose and placebo or to each of several doses and placebo are typically used. However, in trials where response is observed relatively quickly, adaptive designs might offer an advantage over equal allocation. We propose an adaptive design for dose-response trials that concentrates the allocation of subjects in one or more areas of interest, for example, near a minimum clinically important effect level, or near some maximal effect level, and also allows for the possibility to stop the trial early if needed. The proposed adaptive design yields higher power to detect a dose-response relationship, higher power in comparison with placebo, and selects the correct dose more frequently compared with a corresponding randomized design with equal allocation to doses.

  5. gammadelta T cells link innate and adaptive immune responses.

    PubMed

    Holtmeier, Wolfgang; Kabelitz, Dieter

    2005-01-01

    While most T cells use a CD3-associated alpha/beta T cell receptor as antigen recognition structure, a second population of T cells expresses the alternative gamma/delta T cell receptor. gamma/delta T cells are a minor population in the peripheral blood but constitute a major population among intestinal intraepithelial lymphocytes. Most gamma/delta T cells recognize ligands which are fundamentally different from the short peptides that are seen by alpha/beta T cells in the context of MHC class I or class II molecules. Thus, human Vdelta2 T cells recognize small bacterial phosphoantigens, alkylamines and synthetic aminobisphosphonates, whereas Vdelta1 T cells recognize stress-inducible MHC-related molecules MICA/B as well as several other ligands. At the functional level, gamma/delta T cells rapidly produce a variety of cytokines and usually exert potent cytotoxic activity, also towards many tumor cells. In this article, we discuss the role of gamma/delta T cells as a bridge between the innate and the adaptive immune system, based on the interpretation that gamma/delta T cells use their T cell receptor as a pattern recognition receptor. Our increasing understanding of the ligand recognition and activation mechanisms of gamma/delta T cells also opens new perspectives for the development of gamma/delta T cell-based immunotherapies.

  6. 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

  7. Adaptive Control Responses to Behavioral Perturbation Based Upon the Insect

    DTIC Science & Technology

    2006-11-01

    autonomous robot Soc Neuroci Abstr CD ROM 31: :176.110 Harley CM, Predina JD, Ritzmann RE (2006) Responses to incomplete sensory information in cockroach...climbing behavior. Soc Neuroci Abstr CD ROM 32:449.412 Hess D, Buschges A (1999) Role of proprioceptive signals from an insect femur-tibia joint in...Altered joint reflexes in the cockroach may lead to 17 directional changes in leg extension. Soc Neuroci Abstr CD ROM 32:449.411 Pollack AJ

  8. 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.

  9. 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.

  10. Global transcriptional, physiological, and metabolite analyses of the responses of Desulfovibrio vulgaris hildenborough to salt adaptation.

    PubMed

    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

    2010-03-01

    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.

  11. The adaptive evolution of plasticity: phytochrome-mediated shade avoidance responses.

    PubMed

    Schmitt, Johanna; Stinchcombe, John R; Heschel, M Shane; Huber, Heidrun

    2003-07-01

    Many plants display a characteristic suite of developmental "shade avoidance" responses, such as stem elongation and accelerated reproduction, to the low ratio of red to far-red wavelengths (R:FR) reflected or transmitted from green vegetation. This R:FR cue of crowding and vegetation shade is perceived by the phytochrome family of photoreceptors. Phytochrome-mediated responses provide an ideal system for investigating the adaptive evolution of phenotypic plasticity in natural environments. The molecular and developmental mechanisms underlying shade avoidance responses are well studied, and testable ecological hypotheses exist for their adaptive significance. Experimental manipulation of phenotypes demonstrates that shade avoidance responses may be adaptive, resulting in phenotypes with high relative fitness in the environments that induce those phenotypes. The adaptive value of shade avoidance depends upon the competitive environment, resource availability, and the reliability of the R:FR cue for predicting the selective environment experienced by an induced phenotype. Comparative studies and a reciprocal transplant experiment with Impatiens capensis provide evidence of adaptive divergence in shade avoidance responses between woodland and clearing habitats, which may result from population differences in the frequency of selection on shade avoidance traits, as well as differences in the reliability of the R:FR cue. Recent rapid progress in elucidating phytochrome signaling pathways in the genetic model Arabidopsis thaliana and other species now provides the opportunity for studying how selection on shade avoidance traits in natural environments acts upon the molecular mechanisms underlying natural phenotypic variation.

  12. Understanding the adaptive response in vertebrates: the phenomenon of ease and ease response during post-stress acclimation.

    PubMed

    Subhash Peter, M C

    2013-01-15

    Vertebrates have evolved mechanisms to perceive stressors that arise either from their body or from the environment. Consequently, a state of stress and stress response occur in fish which is characterized by a disturbed physiological homeostasis. The pattern of stress response becomes complex as a result of neuroendocrine involvement and shows varied magnitudes in fishes depending on the nature and the severity of stressors. The integrated and compensatory physiological modifications in fishes during their early phase of adaptive response favor them to accommodate the imposed stressor through the process of stress acclimation. In contrast, with the direction of neuroendocrine signals, a phase of recovery often called post-stress acclimation occurs if the animal gets away from the stressor exposure. During this late phase of adaptive response, physiological modifications operate in favor of the animal that reduces the magnitude of stress response and finally to a phase of normality as animals possess the urge to correct its disrupted homeostasis. The phenomenon of ease and its response thus reduces the allostatic load, resets the homeostatic state through physiologic processes and corrects the stress-induced homeostatic disturbance with the aid of neuroendocrine signals. Ample evidences are now available to support this novel concept of ease and ease response where mitigation of the intensity of stress response occurs physiologically. Treatment of fish with melatonin or serotonin precursor tryptophan can modify the magnitude of stress response as evident in the pattern of tested physiological indices. In addition to cortisol, thyroid hormone as a major stress modifier hormone is involved in the regulation of ease response in fish probably due to the mechanisms involving inter-hormonal interference. Understanding the mechanisms of adaptive responses in vertebrates thus warranties more studies on the physiology of ease and its response.

  13. Quantifying Rates of Evolutionary Adaptation in Response to Ocean Acidification

    PubMed Central

    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 CO2 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 CO2 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. PMID:21857962

  14. 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.

  15. 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.

  16. Adaptive response in animals exposed to non-ionizing radiofrequency fields: some underlying mechanisms.

    PubMed

    Cao, Yi; Tong, Jian

    2014-04-22

    During the last few years, our research group has been investigating the phenomenon of adaptive response in animals exposed to non-ionizing radiofrequency fields. The results from several separate studies indicated a significant increase in survival, decreases in genetic damage as well as oxidative damage and, alterations in several cellular processes in mice pre-exposed to radiofrequency fields and subsequently subjected to sub-lethal or lethal doses of γ-radiation or injected with bleomycin, a radiomimetic chemical mutagen. These observations indicated the induction of adaptive response providing the animals the ability to resist subsequent damage. Similar studies conducted by independent researchers in mice and rats have supported our observation on increased survival. In this paper, we have presented a brief review of all of our own and other independent investigations on radiofrequency fields-induced adaptive response and some underlying mechanisms discussed.

  17. 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.

  18. Innate and adaptive antifungal immune responses: partners on an equal footing.

    PubMed

    Hamad, Mawieh

    2012-05-01

    Adaptive immunity has long been regarded as the major player in protection against most fungal infections. Mounting evidence suggest however, that both innate and adaptive responses intricately collaborate to produce effective antifungal protection. Dendritic cells (DCs) play an important role in initiating and orchestrating antifungal immunity; neutrophils, macrophages and other phagocytes also participate in recognising and eliminating fungal pathogens. Adaptive immunity provides a wide range of effector and regulatory responses against fungal infections. Th1 responses protect against most forms of mycoses but they associate with significant inflammation and limited pathogen persistence. By contrast, Th2 responses enhance persistence of and tolerance to fungal infections thus permitting the generation of long-lasting immunological memory. Although the role of Th17 cytokines in fungal immunity is not fully understood, they can enhance proinflammatory or anti-inflammatory responses or play a regulatory role in fungal immunity all depending on the pathogen, site/phase of infection and host immunostatus. T regulatory cells balance the activities of various Th cell subsets thereby permitting inflammation and protection on the one hand and allowing for tolerance and memory on the other. Here, recent developments in fungal immunity research are reviewed as means of tracing the emergence of a refined paradigm where innate and adaptive responses are viewed in the same light.

  19. Ebola Virus Altered Innate and Adaptive Immune Response Signalling Pathways: Implications for Novel Therapeutic Approaches.

    PubMed

    Kumar, Anoop

    2016-01-01

    Ebola virus (EBOV) arise attention for their impressive lethality by the poor immune response and high inflammatory reaction in the patients. It causes a severe hemorrhagic fever with case fatality rates of up to 90%. The mechanism underlying this lethal outcome is poorly understood. In 2014, a major outbreak of Ebola virus spread amongst several African countries, including Leone, Sierra, and Guinea. Although infections only occur frequently in Central Africa, but the virus has the potential to spread globally. Presently, there is no vaccine or treatment is available to counteract Ebola virus infections due to poor understanding of its interaction with the immune system. Accumulating evidence indicates that the virus actively alters both innate and adaptive immune responses and triggers harmful inflammatory responses. In the literature, some reports have shown that alteration of immune signaling pathways could be due to the ability of EBOV to interfere with dendritic cells (DCs), which link innate and adaptive immune responses. On the other hand, some reports have demonstrated that EBOV, VP35 proteins act as interferon antagonists. So, how the Ebola virus altered the innate and adaptive immune response signaling pathways is still an open question for the researcher to be explored. Thus, in this review, I try to summarize the mechanisms of the alteration of innate and adaptive immune response signaling pathways by Ebola virus which will be helpful for designing effective drugs or vaccines against this lethal infection. Further, potential targets, current treatment and novel therapeutic approaches have also been discussed.

  20. 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.

  1. 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

  2. Increased anterior cingulate cortex response precedes behavioural adaptation in anorexia nervosa

    PubMed Central

    Geisler, Daniel; Ritschel, Franziska; King, Joseph A.; Bernardoni, Fabio; Seidel, Maria; Boehm, Ilka; Runge, Franziska; Goschke, Thomas; Roessner, Veit; Smolka, Michael N.; Ehrlich, Stefan

    2017-01-01

    Patients with anorexia nervosa (AN) are characterised by increased self-control, cognitive rigidity and impairments in set-shifting, but the underlying neural mechanisms are poorly understood. Here we used functional magnetic resonance imaging (fMRI) to elucidate the neural correlates of behavioural adaptation to changes in reward contingencies in young acutely ill AN patients. Thirty-six adolescent/young adult, non-chronic female AN patients and 36 age-matched healthy females completed a well-established probabilistic reversal learning task during fMRI. We analysed hemodynamic responses in empirically-defined regions of interest during positive feedback and negative feedback not followed/followed by behavioural adaptation and conducted functional connectivity analyses. Although overall task performance was comparable between groups, AN showed increased shifting after receiving negative feedback (lose-shift behaviour) and altered dorsal anterior cingulate cortex (dACC) responses as a function of feedback. Specifically, patients had increased dACC responses (which correlated with perfectionism) and task-related coupling with amygdala preceding behavioural adaption. Given the generally preserved task performance in young AN, elevated dACC responses specifically during behavioural adaption is suggestive of increased monitoring for the need to adjust performance strategies. Higher dACC-amygdala coupling and increased adaptation after negative feedback underlines this interpretation and could be related to intolerance of uncertainty which has been suggested for AN. PMID:28198813

  3. Increased anterior cingulate cortex response precedes behavioural adaptation in anorexia nervosa.

    PubMed

    Geisler, Daniel; Ritschel, Franziska; King, Joseph A; Bernardoni, Fabio; Seidel, Maria; Boehm, Ilka; Runge, Franziska; Goschke, Thomas; Roessner, Veit; Smolka, Michael N; Ehrlich, Stefan

    2017-02-13

    Patients with anorexia nervosa (AN) are characterised by increased self-control, cognitive rigidity and impairments in set-shifting, but the underlying neural mechanisms are poorly understood. Here we used functional magnetic resonance imaging (fMRI) to elucidate the neural correlates of behavioural adaptation to changes in reward contingencies in young acutely ill AN patients. Thirty-six adolescent/young adult, non-chronic female AN patients and 36 age-matched healthy females completed a well-established probabilistic reversal learning task during fMRI. We analysed hemodynamic responses in empirically-defined regions of interest during positive feedback and negative feedback not followed/followed by behavioural adaptation and conducted functional connectivity analyses. Although overall task performance was comparable between groups, AN showed increased shifting after receiving negative feedback (lose-shift behaviour) and altered dorsal anterior cingulate cortex (dACC) responses as a function of feedback. Specifically, patients had increased dACC responses (which correlated with perfectionism) and task-related coupling with amygdala preceding behavioural adaption. Given the generally preserved task performance in young AN, elevated dACC responses specifically during behavioural adaption is suggestive of increased monitoring for the need to adjust performance strategies. Higher dACC-amygdala coupling and increased adaptation after negative feedback underlines this interpretation and could be related to intolerance of uncertainty which has been suggested for AN.

  4. 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.

  5. 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.

  6. 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

  7. 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

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

    PubMed

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

    2014-03-01

    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 dines. 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 needed

  9. 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

  10. 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.

  11. Modeling Light Adaptation in Circadian Clock: Prediction of the Response That Stabilizes Entrainment

    PubMed Central

    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. PMID:21698191

  12. Adaptive response of single and binary Pseudomonas aeruginosa and Escherichia coli biofilms to benzalkonium chloride.

    PubMed

    Machado, Idalina; Lopes, Susana Patrícia; Sousa, Ana Margarida; Pereira, Maria Olívia

    2012-02-01

    The main goal of this work was to examine whether the continuous exposure of single and binary P. aeruginosa and E. coli biofilms to sub-lethal benzalkonium chloride (BC) doses can induce adaptive response of bacteria. Biofilms were formed during 24 h and then put continuously in contact with BC for more 5 days. The six-day-old adapted biofilms were then submitted to BC challenge, characterized and inspected by SEM. Both single and binary adapted biofilms have clearly more biomass, polysaccharides and proteins and less activity even though the number of cells was identical. After BC treatment, adapted biofilms maintained their mass and activity. SEM examination revealed that those adapted biofilms had a slimier and denser matrix that became thicker after BC treatment. Continuous exposure of bacteria to antimicrobials can lead to development of biofilms encompassing more virulent and tolerant bacteria. This adaptive resistance can be the result of a phenotypic adaptation, a genetic acquired resistance or both. Instead of eradicating biofilms and kill microorganisms, the use of a disinfectant can, favour biofilm formation and tolerance. This must be a genuine concern as it can happen in clinical environments, where the use of antimicrobials is unavoidable.

  13. Multiple species of Bacillus subtilis DNA alkyltransferase involved in the adaptive response to simple alkylating agents

    SciTech Connect

    Morohoshi, F.; Munakata, N.

    1987-02-01

    Three molecular species of methyl-accepting proteins exist in Bacillus subtilis cells, which collect methyl groups from methylated DNA. A 20-kilodalton (kDa) protein was constitutively present in the cells of the ada/sup +/ (proficient in adaptive response) strain as well as in those of six ada (deficient in adaptive response) mutant strains and was assigned to the O/sup 6/-methylguanine:DNA methyltransferase. Another species of O/sup 6/-methylguanine:DNA methyltransferase, which had a molecular size of 22 kDa, emerged after adaptive treatment of the ada/sup +/ but not any of the ada mutant cells. A 27-kDa methyl-accepting protein, which preferred methylated poly(dT) to methylated calf thymus DNA as a substrate, was assigned to the methylphosphotriester:DNA methyltransferase. It was produced, after adaptive treatment, in the cells of ada/sup +/, ada-3, ada-4, and ada-6 strains but not in the cells of ada-1, ada-2, or ada-5 strains. These results support and extend the authors proposition that ada mutants can be classified into two groups; one (the ada-4 group) is defective only in the inducible synthesis of O/sup 6/-methylguanine:DNA methyltransferase (22-kDa protein), and the other (the ada-1 group) is deficient in the adaptive response in toto.

  14. 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.

  15. 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.

  16. Cold shock response and adaptation at near-freezing temperature in microorganisms.

    PubMed

    Inouye, Masayori; Phadtare, Sangita

    2004-06-09

    Microorganisms that naturally encounter sharp temperature shifts must develop strategies for responding and adapting to these shifts. Escherichia coli, which are adapted to living at both warm temperatures inside animals and cooler ambient temperatures, respond to low temperatures (10 degrees to 15 degrees C) by adjusting membrane lipid composition and increasing the production of proteins that act as "RNA chaperones" required for transcription and translation and proteins that facilitate ribosomal assembly. In contrast, yeast, which are adapted to cooler temperatures, show a relatively minor cold shock response after temperature shifts from 30 degrees to 10 degrees C but respond with a dramatic increase in the synthesis of trehalose and a heat shock protein when exposed to freezing or near-freezing temperatures. This emphasizes the fact that different groups of microorganisms exhibit distinct types of cold shock responses.

  17. 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.

  18. Stability of adaptive cruise control systems taking account of vehicle response time and delay

    NASA Astrophysics Data System (ADS)

    Davis, L. C.

    2012-08-01

    The region of string stability of a platoon of adaptive cruise control vehicles, taking into account the delay and response of the vehicle powertrain, is found. An upper bound on the explicit delay time as a function the first-order powertrain response time constant is determined. The system is characterized by a headway time constant, a sensitivity parameter, relative (to the vehicle immediately in front) velocity control, and delayed-velocity feedback or acceleration feedback.

  19. The Host Immune Response to Streptococcus pneumoniae: Bridging Innate and Adaptive Immunity

    DTIC Science & Technology

    2006-07-06

    caused by penicillin -resistant Streptococcus pneumoniae in rabbits. Antimicrob. Agents Chemother. 46: 1760- 1765. Takeuchi, O., Hoshino, K., and...2006 2. REPORT TYPE 3. DATES COVERED 00-00-2006 to 00-00-2006 4. TITLE AND SUBTITLE The host immune response to Streptococcus pneumoniae ...host immune response to Streptococcus pneumoniae : bridging innate and adaptive immunity Katherine Shi-Hui Lee Thesis directed by: Clifford M

  20. 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 ...

  1. 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...

  2. Operational Characteristics of Adaptive Testing Procedures Using the Graded Response Model.

    ERIC Educational Resources Information Center

    Dodd, Barbara G.; And Others

    1989-01-01

    General guidelines are developed to assist practitioners in devising operational computerized adaptive testing systems based on the graded response model. The effects of the following major variables were examined: item pool size; stepsize used along the trait continuum until maximum likelihood estimation could be calculated; and stopping rule…

  3. Item Response Theory and Computerized Adaptive Testing Conference Proceedings (Wayzata, Minnesota, July 27-30, 1982).

    ERIC Educational Resources Information Center

    Weiss, David J., Ed.

    This report contains the Proceedings of the 1982 Item Response Theory and Computerized Adaptive Testing Conference. The papers and their discussions are organized into eight sessions: (1) "Developments in Latent Trait Theory," with papers by Fumiko Samejima and Michael V. Levine; (2) "Parameter Estimation," with papers by…

  4. {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.

  5. 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 ...

  6. Microswitch Clusters Promote Adaptive Responses and Reduce Finger Mouthing in a Boy with Multiple Disabilities

    ERIC Educational Resources Information Center

    Lancioni, Giulio E.; O'reilly, Mark F.; Singh, Nirbhay N.; Sigafoos, Jeff; Oliva, Doretta; Baccani, Simona; Groeneweg, Jop

    2006-01-01

    The authors assessed new microswitch clusters (i.e., combinations of two microswitches) and contingent stimulation to increase adaptive responses (i.e., foot and head movements) and reduce aberrant behavior (i.e., finger mouthing) in a boy with multiple disabilities. Initially, intervention was directed at increasing the frequency of each adaptive…

  7. 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...

  8. 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…

  9. 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.

  10. 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…

  11. 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.

  12. Adaptive plasticity and epigenetic variation in response to warming in an Alpine plant

    PubMed Central

    Nicotra, Adrienne B; Segal, Deborah L; Hoyle, Gemma L; Schrey, Aaron W; Verhoeven, Koen J F; Richards, Christina L

    2015-01-01

    Environmentally induced phenotypic plasticity may be a critical component of response to changing environments. We examined local differentiation and adaptive phenotypic plasticity in response to elevated temperature in half-sib lines collected across an elevation gradient for the alpine herb, Wahlenbergia ceracea. Using Amplified Fragment Length Polymorphism (AFLP), we found low but significant genetic differentiation between low- and high-elevation seedlings, and seedlings originating from low elevations grew faster and showed stronger temperature responses (more plasticity) than those from medium and high elevations. Furthermore, plasticity was more often adaptive for plants of low-elevation origin and maladaptive for plants of high elevation. With methylation sensitive-AFLP (MS-AFLP), we revealed an increase in epigenetic variation in response to temperature in low-elevation seedlings. Although we did not find significant direct correlations between MS-AFLP loci and phenotypes, our results demonstrate that adaptive plasticity in temperature response to warming varies over fine spatial scales and suggest the involvement of epigenetic mechanisms in this response. PMID:25691987

  13. Secretome analysis revealed adaptive and non-adaptive responses of the Staphylococcus carnosus femB mutant.

    PubMed

    Nega, Mulugeta; Dube, Linda; Kull, Melanie; Ziebandt, Anne-Kathrin; Ebner, Patrick; Albrecht, Dirk; Krismer, Bernhard; Rosenstein, Ralf; Hecker, Michael; Götz, Friedrich

    2015-04-01

    FemABX peptidyl transferases are involved in non-ribosomal pentaglycine interpeptide bridge biosynthesis. Here, we characterized the phenotype of a Staphylococcus carnosus femB deletion mutant, which was affected in growth and showed pleiotropic effects such as enhanced methicillin sensitivity, lysostaphin resistance, cell clustering, and decreased peptidoglycan cross-linking. However, comparative secretome analysis revealed a most striking difference in the massive secretion or release of proteins into the culture supernatant in the femB mutant than the wild type. The secreted proteins can be categorized into typical cytosolic proteins and various murein hydrolases. As the transcription of the murein hydrolase genes was up-regulated in the mutant, they most likely represent an adaption response to the life threatening mutation. Even though the transcription of the cytosolic protein genes was unaltered, their high abundance in the supernatant of the mutant is most likely due to membrane leakage triggered by the weakened murein sacculus and enhanced autolysins.

  14. Light adaptation increases response latency of alpha ganglion cells via a threshold-like nonlinearity.

    PubMed

    Chang, L; He, S

    2014-01-03

    Adaptation is an important process of sensory systems to adjust sensitivity to ensure the appropriate information encoding. Sensitivity and kinetics of retinal ganglion cell (RGC) responses have been studied extensively using a brief flash superimposed on different but steady backgrounds. However, it is still unclear if light adaptation exerts any effect on more complex response properties, such as response nonlinearity. In this study, we found that the latency of spike responses to a repeated flashing spot stimulation increased by 30 ms in the mouse ON α RGCs (An ON-type RGC is excited when a spot is turned on in the center of its receptive field). A single dimming event preceding the test flash on a steady adapting background could also produce similar effect in increasing latency of light responses. A simple computational model with a linear transformation of the light stimulus and a threshold-like nonlinearity could account for the experimental data. Moreover, the strength of the measured nonlinearity and the response latency were affected by the duration of light adaptation. The possible biological processes underlying this nonlinearity were explored. Voltage clamp recording revealed the presence of the increase in latency and threshold-like nonlinearity in the excitatory input of RGCs. However, no comparable nonlinearity was observed in the light responses of the ON cone bipolar cells. We further excluded GABAergic and glycinergic inhibition, N-methyl-D-aspartate receptor rectification and voltage-gated Na(+) channels as potential sources of this nonlinearity by pharmacological experiments. Our results indicate the bipolar cell terminals as the potential site of nonlinearity. Computational modeling constrained by experimental data supports that conclusion and suggests the voltage-sensitive Ca(++) channels and Ca(++)-dependent vesicle release in the bipolar cell terminals as mechanistic basis.

  15. 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.

  16. 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

  17. Genome-wide transcriptional responses to a lipid hydroperoxide: adaptation occurs without induction of oxidant defenses.

    PubMed

    Alic, Nazif; Felder, Thomas; Temple, Mark D; Gloeckner, Christian; Higgins, Vincent J; Briza, Peter; Dawes, Ian W

    2004-07-01

    Free radicals can initiate the oxidation of polyunsaturated fatty acids in cells through the process of lipid peroxidation. The genome-wide transcriptional changes in Saccharomyces cerevisiae after treatment with the toxic lipid peroxidation product linoleic acid hydroperoxide (LoaOOH) were identified. High-dose treatment led to a switch in transcription from biosynthetic to protective functions. This response encompassed a set of genes stimulated predominantly by LoaOOH, and not by other oxidants or heat shock, which contained components of the pleiotropic drug resistance system. The dose dependence of the transcriptional response revealed that large and widespread changes occur only in response to higher doses. Pretreatment of cells with sublethal doses of LoaOOH induces resistance to an otherwise lethal dose through the process of adaptation. Adaptive doses elicited a more subtle transcriptional response affecting metabolic functions, including an increase in the capacity for detoxification and downregulation of the rate of protein synthesis. Surprisingly, the cellular response to adaptive doses did not include induction of oxidative-stress defense enzymes nor of transcripts involved in general cellular defense systems.

  18. Receptor for advanced glycation end products (RAGE) regulates sepsis but not the adaptive immune response

    PubMed Central

    Liliensiek, Birgit; Weigand, Markus A.; Bierhaus, Angelika; Nicklas, Werner; Kasper, Michael; Hofer, Stefan; Plachky, Jens; Gröne, Herman-Josef; Kurschus, Florian C.; Schmidt, Ann Marie; Yan, Shi Du; Martin, Eike; Schleicher, Erwin; Stern, David M.; Hämmerling, Günter J.; Nawroth, Peter P.; Arnold, Bernd

    2004-01-01

    While the initiation of the adaptive and innate immune response is well understood, less is known about cellular mechanisms propagating inflammation. The receptor for advanced glycation end products (RAGE), a transmembrane receptor of the immunoglobulin superfamily, leads to perpetuated cell activation. Using novel animal models with defective or tissue-specific RAGE expression, we show that in these animal models RAGE does not play a role in the adaptive immune response. However, deletion of RAGE provides protection from the lethal effects of septic shock caused by cecal ligation and puncture. Such protection is reversed by reconstitution of RAGE in endothelial and hematopoietic cells. These results indicate that the innate immune response is controlled by pattern-recognition receptors not only at the initiating steps but also at the phase of perpetuation. PMID:15173891

  19. An adaptive two-stage dose-response design method for establishing Proof of Concept

    PubMed Central

    Franchetti, Yoko; Anderson, Stewart J.; Sampson, Allan R.

    2013-01-01

    We propose an adaptive two-stage dose-response design where a pre-specified adaptation rule is used to add and/or drop treatment arms between the stages. We extend the multiple comparison procedures-modeling (MCP-Mod) approach into a two-stage design. In each stage, we use the same set of candidate dose-response models and test for a dose-response relationship or proof of concept (PoC) via model-associated statistics. The stage-wise test results are then combined to establish ‘global’ PoC using a conditional error function. Our simulation studies showed good and more robust power in our design method compared to conventional and fixed designs. PMID:23957520

  20. 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.

  1. Adaptive urn designs for estimating several percentiles of a dose--response curve.

    PubMed

    Mugno, Raymond; Zhus, Wei; Rosenberger, William F

    2004-07-15

    Dose--response experiments are crucial in biomedical studies. There are usually multiple objectives in such experiments and among the goals is the estimation of several percentiles on the dose--response curve. Here we present the first non-parametric adaptive design approach to estimate several percentiles simultaneously via generalized Pólya urns. Theoretical properties of these designs are investigated and their performance is gaged by the locally compound optimal designs. As an example, we re-investigated a psychophysical experiment where one of the goals was to estimate the three quartiles. We show that these multiple-objective adaptive designs are more efficient than the original single-objective adaptive design targeting the median only. We also show that urn designs which target the optimal designs are slightly more efficient than those which target the desired percentiles directly. Guidelines are given as to when to use which type of design. Overall we are pleased with the efficiency results and hope compound adaptive designs proposed in this work or their variants may prove to be a viable non-parametric alternative in multiple-objective dose--response studies.

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

    PubMed

    Grinthal, Alison; Aizenberg, Joanna

    2013-09-07

    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.

  3. 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

  4. Adaptive changes in prey vulnerability shape the response of predator populations to mortality.

    PubMed

    Abrams, Peter A

    2009-11-21

    Simple models are used to explore how adaptive changes in prey vulnerability alter the population response of their predator to increased mortality. If the mortality is an imposed harvest, the change in prey vulnerability also influences the relationship between harvest effort and yield of the predator. The models assume that different prey phenotypes share a single resource, but have different vulnerabilities to the predator. Decreased vulnerability is assumed to decrease resource consumption rate. Adaptive change may occur by phenotypic changes in the traits of a single species or by shifts in the abundances of a pair of coexisting species or morphs. The response of the predator population is influenced by the shape of the predator's functional response, the shape of resource density dependence, and the shape of the tradeoff between vulnerability and food intake in the prey. Given a linear predator functional response, adaptive prey defense tends to produce a decelerating decline in predator population size with increased mortality. Prey defense may also greatly increase the range of mortality rates that allow predator persistence. If the predator has a type-2 response with a significant handling time, adaptive prey defense may have a greater variety of effects on the predator's response to mortality, sometimes producing alternative attractors, population cycles, or increased mean predator density. Situations in which there is disruptive selection on prey defense often imply a bimodal change in yield as a function of harvesting effort, with a minimum at intermediate effort. These results argue against using single-species models of density dependent growth to manage predatory species, and illustrate the importance of incorporating anti-predator behavior into models in applied population ecology.

  5. 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

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

    PubMed

    Zhang, Ji; Friedman, Morton H

    2013-09-15

    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/cm(2) 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.

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

    PubMed Central

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

    2015-01-01

    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 given powder food for 6 months (N = 60 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 8wks change in functional space was −33 µm, at 12wks 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 24wks: Δ-0.06) and bone hardness (8wks: Δ−0.04 GPa, 16 wks: Δ−0.07 GPa, 24wks: 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 space in

  8. Water Demands with Two Adaptation Responses to Climate Change in a Mexican Irrigation District

    NASA Astrophysics Data System (ADS)

    Ojeda, W.; Iñiguez-Covarrubias, M.; Rojano, A.

    2012-12-01

    It is well documented that climate change is inevitable and that farmers need to adapt to changes in projected climate. Changes in water demands for a Mexican irrigation district were assessed using an irrigation scheduling model. The impact of two adaptations actions on water demands were estimated and compared with a baseline scenario. Wet and dry cropping plans were selected from the last 15 water years with actual climatology (1961-1990) taken as reference and three A1B climate change projection periods P1, P2 and P3 (2011-2040, 2041-2070, and 2071-2098). Projected precipitation and air temperature (medium, maximum and minimum) data were obtained through weighted averages of the best CGCM projections for Mexico, available at the IPCC data distribution center, using the Reliability Ensemble Averaging method (REA). Two adaptation farmers' responses were analyzed: use of longer season varieties and reduction of planting dates toward colder season as warming intensifies in the future. An annual accumulated ETo value of 1554 mm was estimated for the base period P0. Cumulative and Daily irrigations demands were generated for each agricultural season using the four climate projection series and considering adaptations actions. Figure 1 integrates in a unique net flow curve for the Fall-Winter season under selected adaptations actions. The simulation results indicated that for mid century (Period P2), the use of longer-season cultivars (AV) will have more pronounced effect in daily net flow based than the reduction of planting season (APS) as climate change intensifies during present century. Without adaptation (WA), the increase in temperature will shorten the growing season of all annual crops, generating a peak shift with respect to reference case (WA-P0). Combined adoptions of adaptation actions (AP+V) can generate higher, peak and cumulative, crop water requirements than actual values as Figure 1 shows. There are clear trends that without adaptations, water

  9. 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

  10. 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.

  11. Principles of exercise physiology: responses to acute exercise and long-term adaptations to training.

    PubMed

    Rivera-Brown, Anita M; Frontera, Walter R

    2012-11-01

    Physical activity and fitness are associated with a lower prevalence of chronic diseases, such as heart disease, cancer, high blood pressure, and diabetes. This review discusses the body's response to an acute bout of exercise and long-term physiological adaptations to exercise training with an emphasis on endurance exercise. An overview is provided of skeletal muscle actions, muscle fiber types, and the major metabolic pathways involved in energy production. The importance of adequate fluid intake during exercise sessions to prevent impairments induced by dehydration on endurance exercise, muscular power, and strength is discussed. Physiological adaptations that result from regular exercise training such as increases in cardiorespiratory capacity and strength are mentioned. The review emphasizes the cardiovascular and metabolic adaptations that lead to improvements in maximal oxygen capacity.

  12. 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.

  13. 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.

  14. 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.

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

    PubMed Central

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

    2010-01-01

    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. PMID:20375046

  16. The human milk oligosaccharide 2′-fucosyllactose augments the adaptive response to extensive intestinal

    PubMed Central

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

    2015-01-01

    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. PMID:26702137

  17. Radio-adaptive Response in Myocardial Perfusion Imaging Induced by Technetium-99m

    PubMed Central

    Shirazi, Mohammad Mehdi; Shabestani-Monfared, Ali; Shahidi, Maryam; Amiri, Mehrangiz; Abedi, Seyed Mohammad; Borzoueisileh, Sajad; Gorji, Kourosh Ebrahim Nejad

    2017-01-01

    Purpose of the Study: Low dose radiation will induce adaptation and following exposure to an adaptive dose, the cells are more resistance to following challenging doses. This phenomenon is known as radio-adaptive response. The aim of this study was to investigate the percentage of apoptotic cells in the peripheral blood samples of the patients which undergo myocardial perfusion imaging (MPI) with technetium-99m (Tc-99m) before thallium scan to assess the induction of radio-adaptive response. Materials and Methods: In this study, 97 samples from 74 patients, referred to nuclear medicine center of Mazandaran Heart Hospital for MPI, which had no history of diagnostic, therapeutic, occupational, and radioactive exposures during past 2 years, were provided. The participants were classified into four groups including control, patients which were scanned solely with technetium, the patients which examined by thallium and the last group were the patients that examined by technetium followed by thallium. Then 2 ml Peripheral blood samples were obtained, and after 24 h incubating, the samples were studied by neutral comet assay. Statistical analysis was carried out using Student's t-test along with one-way analysis of variance. Results: The mean percentage of apoptotic cells in the exposed groups were higher than the control. Furthermore, among exposed groups, the apoptotic cells in thallium group were more than others and this index was significantly lower in the group which was undergone technetium administration before thallium scan. Conclusions: These findings suggest that exposure to Tc-99m could induce a radio-adaptive response against the exposure of thallium-201. PMID:28242975

  18. Dendritic Cells in Innate and Adaptive Immune Responses against Influenza Virus

    PubMed Central

    Summerfield, Artur; McCullough, Kenneth C.

    2009-01-01

    Dendritic cells (DC) are major players in both innate and adaptive immune responses against influenza virus. These immune responses, as well as the important interface between the innate and adaptive systems, are orchestrated by specialized subsets of DC, including conventional steady-state DC, migratory DC and plasmacytoid DC. The characteristics and efficacy of the responses are dependent on the relative activity of these DC subsets, rendering DC crucial for the development of both naïve and memory immune responses. However, due to their critical role, DC also contribute to the immunopathological processes observed during acute influenza, such as that caused by the pathogenic H5N1 viruses. Therein, the role of different DC subsets in the induction of interferon type I, pro-inflammatory cytokine and chemokine responses is important for the outcome of interaction between the virus and host immune defences. The present review will present current knowledge on this area, relating to the importance of DC activity for the induction of efficacious humoral and cell-mediated immune responses. This will include the main viral elements associated with the triggering or inhibition of DC activation. Finally, the current knowledge on understanding how differences in various vaccines influence the manner of immune defence induction will be presented. PMID:21994580

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

    PubMed Central

    Hood, Rachel D.; Higgins, Sean A.; Flamholz, Avi; Nichols, Robert J.

    2016-01-01

    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

  20. Resident memory CD8 T cells trigger protective innate and adaptive immune responses

    PubMed Central

    Schenkel, Jason M.; Fraser, Kathryn A.; Beura, Lalit K.; Pauken, Kristen E.; Vezys, Vaiva; Masopust, David

    2015-01-01

    The pathogen recognition theory dictates that upon viral infection, the innate immune system first detects microbial products, and then responds by providing instructions to adaptive CD8 T cells. Here, we show in mice that resident memory CD8 T cells (TRM), non-recirculating cells located at common sites of infection, can achieve near sterilizing immunity against viral infections by reversing this flow of information. Upon antigen re-sensitization within the mouse female reproductive mucosae, CD8+ TRM secrete cytokines that trigger rapid adaptive and innate immune responses including local humoral responses, maturation of local dendritic cells, and activation of natural killer cells. This provided near sterilizing immunity against an antigenically unrelated viral infection. Thus, CD8+ TRM rapidly trigger an antiviral state by amplifying receptor-derived signals from previously encountered pathogens. PMID:25170049

  1. Subverting the adaptive immune resistance mechanism to improve clinical responses to immune checkpoint blockade therapy

    PubMed Central

    Kim, Young J

    2015-01-01

    The correlation between tumor-infiltrating lymphocyte (TIL)-expression of programmed cell death ligand 1 (PD-L1) and clinical responsiveness to the PD-1 blocking antibody nivolumab implicates adaptive immune evasion mechanisms in cancer. We review our findings that tumor cell PD-L1 expression is induced by interferon γ (IFNγ) producing TILs. We provide a mechanistic rationale for combining IFNγ+ T helper type 1 (Th1)-inducing cancer vaccines with PD-1 immune checkpoint blockade. PMID:25964860

  2. Radio protective effect of black mulberry extract on radiation-induced damage in bone marrow cells and liver in the rat

    NASA Astrophysics Data System (ADS)

    Ghasemnezhad Targhi, Reza; Homayoun, Mansour; Mansouri, Somaieh; Soukhtanloo, Mohammad; Soleymanifard, Shokouhozaman; Seghatoleslam, Masoumeh

    2017-01-01

    Ionizing radiation by producing free radicals induces tissue oxidative stress and has clastogenic and cytotoxic effects. The radio protective effect of black mulberry extract (BME) has been investigated on liver tissue and bone marrow cells in the rat. Intraperitoneal (ip) administration of 200 mg/kg BME three days before and three days after 3 Gy and 6 Gy gamma irradiation significantly reduced the frequencies of micro nucleated polychromatic erythrocytes (MnPCEs) and micro nucleated norm chromatic erythrocyte (MnNCEs) and increased PCE/PCE+NCE ratio in rat bone marrow compared to the non-treated irradiated groups. Moreover, this concentration of BME extract decreased the level of malondialdehyde (MDA) and superoxide dismutase (SOD), as well as enhanced the total thiol content and catalase activity in rat's liver compared to the non-treated irradiated groups. It seems that BME extract with antioxidant activity reduced the genotoxicity and cytotoxicity induced by gamma irradiation in bone marrow cells and liver in the rat.

  3. Adaptive responses of the maternal hypothalamic-pituitary-adrenal axis during pregnancy and lactation.

    PubMed

    Brunton, P J; Russell, J A; Douglas, A J

    2008-06-01

    Over the past 40 years, it has been recognised that the maternal hypothalamic-pituitary-adrenal (HPA) axis undergoes adaptations through pregnancy and lactation that might contribute to avoidance of adverse effects of stress on the mother and offspring. The extent of the global adaptations in the HPA axis has been revealed and the underlying mechanisms investigated within the last 20 years. Both basal, including the circadian rhythm, and stress-induced adrenocorticotrophic hormone and glucocorticoid secretory patterns are altered. Throughout most of pregnancy, and in lactation, these changes predominantly reflect reduced drive by the corticotropin-releasing factor (CRF) neurones in the parvocellular paraventricular nucleus (pPVN). An accompanying profound attenuation of HPA axis responses to a wide variety of psychological and physical stressors emerges after mid-pregnancy and persists until the end of lactation. Central to this suppression of stress responsiveness is reduced activation of the pPVN CRF neurones. This is consequent on the reduced effectiveness of the stimulation of brainstem afferents to these CRF neurones (for physical stressors) and of altered processing by limbic structures (for emotional stressors). The mechanism of reduced CRF neurone responses to physical stressors in pregnancy is the suppression of noradrenaline release in the PVN by an up-regulated endogenous opioid mechanism, which is induced by neuroactive steroid produced from progesterone. By contrast, in lactation suckling the young provides a neural stimulus that dampens the HPA axis circadian rhythm and reduces stress responses. Reduced noradrenergic input activity is involved in reduced stress responses in lactation, although central prolactin action also appears important. Such adaptations limit the adverse effects of excess glucocorticoid exposure on the foetus(es) and facilitate appropriate metabolic and immune responses.

  4. Pre-Sleep Protein Ingestion to Improve the Skeletal Muscle Adaptive Response to Exercise Training.

    PubMed

    Trommelen, Jorn; van Loon, Luc J C

    2016-11-28

    Protein ingestion following resistance-type exercise stimulates muscle protein synthesis rates, and enhances the skeletal muscle adaptive response to prolonged resistance-type exercise training. As the adaptive response to a single bout of resistance exercise extends well beyond the first couple of hours of post-exercise recovery, recent studies have begun to investigate the impact of the timing and distribution of protein ingestion during more prolonged recovery periods. Recent work has shown that overnight muscle protein synthesis rates are restricted by the level of amino acid availability. Protein ingested prior to sleep is effectively digested and absorbed, and thereby stimulates muscle protein synthesis rates during overnight recovery. When applied during a prolonged period of resistance-type exercise training, protein supplementation prior to sleep can further augment gains in muscle mass and strength. Recent studies investigating the impact of pre-sleep protein ingestion suggest that at least 40 g of protein is required to display a robust increase in muscle protein synthesis rates throughout overnight sleep. Furthermore, prior exercise allows more of the pre-sleep protein-derived amino acids to be utilized for de novo muscle protein synthesis during sleep. In short, pre-sleep protein ingestion represents an effective dietary strategy to improve overnight muscle protein synthesis, thereby improving the skeletal muscle adaptive response to exercise training.

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

    PubMed Central

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

    2012-01-01

    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

  6. Climatic variability in combination with eutrophication drives adaptive responses in the gills of Lake Victoria cichlids.

    PubMed

    van Rijssel, Jacco C; Hecky, Robert E; Kishe-Machumu, Mary A; Meijer, Saskia E; Pols, Johan; van Tienderen, Kaj M; Ververs, Jan D; Wanink, Jan H; Witte, Frans

    2016-12-01

    Textbook examples of adaptive radiation often show rapid morphological changes in response to environmental perturbations. East Africa's Lake Victoria, famous for its stunning adaptive radiation of cichlids, has suffered from human-induced eutrophication over the past decades. This cultural eutrophication is thought to be partly responsible for the dramatically reduced cichlid biodiversity, but climatic variability in itself might also have contributed to the eutrophication which resulted in low oxygen levels and decreased water transparency. To determine how recent environmental changes have influenced the lake and its cichlids over the past 50 years, we gathered environmental and meteorological variables and compared these with gill surface area of four cichlid species. We found that during the period of severe eutrophication and temperature increase (1980s), reduced wind speeds coincided with a reduction in oxygen levels and a decrease in both water temperature and transparency. The gill surface area in three out of the four cichlid species increased during this period which is consistent with adaptive change in response to increased hypoxia. During the 2000s, wind speeds, oxygen levels, water transparency and water temperature increased again, while cichlid gill surface area decreased. Our results imply that climatic changes and especially wind speed and direction might play a crucial role in tropical lake dynamics. The changes in Lake Victoria's water quality coincide with fluctuations in cichlid gill surface area, suggesting that these fish can respond rapidly to environmental perturbations, but also that climatic variability, together with continued eutrophication, might be detrimental to the lake's cichlid biodiversity.

  7. Pre-Sleep Protein Ingestion to Improve the Skeletal Muscle Adaptive Response to Exercise Training

    PubMed Central

    Trommelen, Jorn; van Loon, Luc J. C.

    2016-01-01

    Protein ingestion following resistance-type exercise stimulates muscle protein synthesis rates, and enhances the skeletal muscle adaptive response to prolonged resistance-type exercise training. As the adaptive response to a single bout of resistance exercise extends well beyond the first couple of hours of post-exercise recovery, recent studies have begun to investigate the impact of the timing and distribution of protein ingestion during more prolonged recovery periods. Recent work has shown that overnight muscle protein synthesis rates are restricted by the level of amino acid availability. Protein ingested prior to sleep is effectively digested and absorbed, and thereby stimulates muscle protein synthesis rates during overnight recovery. When applied during a prolonged period of resistance-type exercise training, protein supplementation prior to sleep can further augment gains in muscle mass and strength. Recent studies investigating the impact of pre-sleep protein ingestion suggest that at least 40 g of protein is required to display a robust increase in muscle protein synthesis rates throughout overnight sleep. Furthermore, prior exercise allows more of the pre-sleep protein-derived amino acids to be utilized for de novo muscle protein synthesis during sleep. In short, pre-sleep protein ingestion represents an effective dietary strategy to improve overnight muscle protein synthesis, thereby improving the skeletal muscle adaptive response to exercise training. PMID:27916799

  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.

  9. Targeting the TLR9-MyD88 pathway in the regulation of adaptive immune responses

    PubMed Central

    Huang, Xiaopei; Yang, Yiping

    2010-01-01

    IMPORTANCE OF THE FIELD Toll-like receptors (TLRs) are innate immune receptors critical in the innate immune defense against invading pathogens. Recent advances also reveal a crucial role for TLRs in shaping adaptive immune responses, conferring a potential therapeutic value to their modulation in the treatment of diseases. AREAS COVERED IN THIS REVIEW The aim of this review is to discuss TLR9, the TLR9-MyD88 signaling pathway and its role in regulation of adaptive immune responses, as well as potential therapeutic implications by targeting this pathway. WHAT THE READER WILL GAIN This review shows that the TLR9-MyD88 signaling pathway plays a critical role in promoting adaptive immune responses and that modulation of this pathway may have enormous therapeutic potential in enhancing vaccine potency, controlling autoimmunity, as well as improving the outcome of viral vector-mediated gene therapy. TAKE HOME MESSAGE Although TLR9 agonists have been used as adjuvants for enhancing vaccine potency, further exploitation of the TLR9-MyD88 pathway and its dynamic interaction with the immune system in vivo is needed to provide more effective therapeutic inventions in the design of vaccines for infectious diseases, allergies and cancer, in the control of autoimmunity, as well as in the improvement of viral vector-mediated gene therapy. PMID:20560798

  10. Anomalous signed passive fathometer impulse response when using adaptive beam forming (L).

    PubMed

    Harrison, Chris H

    2009-06-01

    The impulse response of the seabed can be extracted from sea surface ambient noise by cross-correlating the time series from an upward and a downward steered beam. When the steering for each beam is standard minimum variance adaptive beam forming it has been found that the impulse response for significant echoes appears to have the same amplitude but opposite sign. A mathematical explanation is offered for this strange phenomenon. Crucial contributing factors are that the cross-spectral density matrix for the vertical array typically consists of the sum of a Toeplitz matrix and a much weaker Hankel matrix and that it is ill-conditioned.

  11. 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

  12. 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.

  13. 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.

  14. 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.

  15. Functional phase response curves: a method for understanding synchronization of adapting neurons.

    PubMed

    Cui, Jianxia; Canavier, Carmen C; Butera, Robert J

    2009-07-01

    Phase response curves (PRCs) for a single neuron are often used to predict the synchrony of mutually coupled neurons. Previous theoretical work on pulse-coupled oscillators used single-pulse perturbations. We propose an alternate method in which functional PRCs (fPRCs) are generated using a train of pulses applied at a fixed delay after each spike, with the PRC measured when the phasic relationship between the stimulus and the subsequent spike in the neuron has converged. The essential information is the dependence of the recovery time from pulse onset until the next spike as a function of the delay between the previous spike and the onset of the applied pulse. Experimental fPRCs in Aplysia pacemaker neurons were different from single-pulse PRCs, principally due to adaptation. In the biological neuron, convergence to the fully adapted recovery interval was slower at some phases than that at others because the change in the effective intrinsic period due to adaptation changes the effective phase resetting in a way that opposes and slows the effects of adaptation. The fPRCs for two isolated adapting model neurons were used to predict the existence and stability of 1:1 phase-locked network activity when the two neurons were coupled. A stability criterion was derived by linearizing a coupled map based on the fPRC and the existence and stability criteria were successfully tested in two-simulated-neuron networks with reciprocal inhibition or excitation. The fPRC is the first PRC-based tool that can account for adaptation in analyzing networks of neural oscillators.

  16. Functional Phase Response Curves: A Method for Understanding Synchronization of Adapting Neurons

    PubMed Central

    Cui, Jianxia; Canavier, Carmen C.; Butera, Robert J.

    2009-01-01

    Phase response curves (PRCs) for a single neuron are often used to predict the synchrony of mutually coupled neurons. Previous theoretical work on pulse-coupled oscillators used single-pulse perturbations. We propose an alternate method in which functional PRCs (fPRCs) are generated using a train of pulses applied at a fixed delay after each spike, with the PRC measured when the phasic relationship between the stimulus and the subsequent spike in the neuron has converged. The essential information is the dependence of the recovery time from pulse onset until the next spike as a function of the delay between the previous spike and the onset of the applied pulse. Experimental fPRCs in Aplysia pacemaker neurons were different from single-pulse PRCs, principally due to adaptation. In the biological neuron, convergence to the fully adapted recovery interval was slower at some phases than that at others because the change in the effective intrinsic period due to adaptation changes the effective phase resetting in a way that opposes and slows the effects of adaptation. The fPRCs for two isolated adapting model neurons were used to predict the existence and stability of 1:1 phase-locked network activity when the two neurons were coupled. A stability criterion was derived by linearizing a coupled map based on the fPRC and the existence and stability criteria were successfully tested in two-simulated-neuron networks with reciprocal inhibition or excitation. The fPRC is the first PRC-based tool that can account for adaptation in analyzing networks of neural oscillators. PMID:19420126

  17. 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

  18. 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.

  19. Innate and adaptive immunologic functions of complement in the host response to Listeria monocytogenes infection

    PubMed Central

    Calame, Daniel G.; Mueller-Ortiz, Stacey L.; Wetsel, Rick A.

    2017-01-01

    Listeria monocytogenes is a leading cause of foodborne-illness associated mortality that has attracted considerable attention in recent years due to several significant outbreaks. It has also served as a model organism for the study of intracellular pathogens. For these reasons the host response to L. monocytogenes has long been the subject of investigation. A potent innate and adaptive immune response is required for containment and clearance of L. monocytogenes. However, some elements of this response, such as type 1 interferons, can be detrimental to the host. Recent studies have revealed novel functions for the complement system, an ancient arm of innate immunity, in this process. Here we review the role of complement in the host response to L. monocytogenes. PMID:27476791

  20. PET-CT for staging and early response: results from the Response-Adapted Therapy in Advanced Hodgkin Lymphoma study.

    PubMed

    Barrington, Sally F; Kirkwood, Amy A; Franceschetto, Antonella; Fulham, Michael J; Roberts, Thomas H; Almquist, Helén; Brun, Eva; Hjorthaug, Karin; Viney, Zaid N; Pike, Lucy C; Federico, Massimo; Luminari, Stefano; Radford, John; Trotman, Judith; Fosså, Alexander; Berkahn, Leanne; Molin, Daniel; D'Amore, Francesco; Sinclair, Donald A; Smith, Paul; O'Doherty, Michael J; Stevens, Lindsey; Johnson, Peter W

    2016-03-24

    International guidelines recommend that positron emission tomography-computed tomography (PET-CT) should replace CT in Hodgkin lymphoma (HL). The aims of this study were to compare PET-CT with CT for staging and measure agreement between expert and local readers, using a 5-point scale (Deauville criteria), to adapt treatment in a clinical trial: Response-Adapted Therapy in Advanced Hodgkin Lymphoma (RATHL). Patients were staged using clinical assessment, CT, and bone marrow biopsy (RATHL stage). PET-CT was performed at baseline (PET0) and after 2 chemotherapy cycles (PET2) in a response-adapted design. PET-CT was reported centrally by experts at 5 national core laboratories. Local readers optionally scored PET2 scans. The RATHL and PET-CT stages were compared. Agreement among experts and between expert and local readers was measured. RATHL and PET0 stage were concordant in 938 (80%) patients. PET-CT upstaged 159 (14%) and downstaged 74 (6%) patients. Upstaging by extranodal disease in bone marrow (92), lung (11), or multiple sites (12) on PET-CT accounted for most discrepancies. Follow-up of discrepant findings confirmed the PET characterization of lesions in the vast majority. Five patients were upstaged by marrow biopsy and 7 by contrast-enhanced CT in the bowel and/or liver or spleen. PET2 agreement among experts (140 scans) with a κ (95% confidence interval) of 0.84 (0.76-0.91) was very good and between experts and local readers (300 scans) at 0.77 (0.68-0.86) was good. These results confirm PET-CT as the modern standard for staging HL and that response assessment using Deauville criteria is robust, enabling translation of RATHL results into clinical practice.

  1. Dark Adaptation at High Altitude: An Unexpected Pupillary Response to Chronic Hypoxia in Andean Highlanders.

    PubMed

    Healy, Katherine; Labrique, Alain B; Miranda, J Jaime; Gilman, Robert H; Danz, David; Davila-Roman, Victor G; Huicho, Luis; León-Velarde, Fabiola; Checkley, William

    2016-09-01

    Healy, Katherine, Alain B. Labrique, J. Jaime Miranda, Robert H. Gilman, David Danz, Victor G. Davila-Roman, Luis Huicho, Fabiola León-Velarde, and William Checkley. Dark adaptation at high altitude: an unexpected pupillary response to chronic hypoxia in Andean highlanders. High Alt Med Biol. 17:208-213, 2016.-Chronic mountain sickness is a maladaptive response to high altitude (>2500 m above sea level) and is characterized by excessive erythrocytosis and hypoxemia resulting from long-term hypobaric hypoxia. There is no known early predictor of chronic mountain sickness and the diagnosis is based on the presence of excessive erythrocytosis and clinical features. Impaired dark adaptation, or an inability to visually adjust from high- to low-light settings, occurs in response to mild hypoxia and may serve as an early predictor of hypoxemia and chronic mountain sickness. We aimed to evaluate the association between pupillary response assessed by dark adaptometry and daytime hypoxemia in resident Andean highlanders aged ≥35 years living in Puno, Peru. Oxyhemoglobin saturation (SpO2) was recorded using a handheld pulse oximeter. Dark adaptation was quantitatively assessed as the magnitude of pupillary contraction to light stimuli of varying intensities (-2.9 to 0.1 log-cd/m(2)) using a portable dark adaptometer. Individual- and stimulus-specific multilevel analyses were conducted using mixed-effect models to elicit the relationship between SpO2 and pupillary responsiveness. Among 93 participants, mean age was 54.9 ± 11.0 years, 48% were male, 44% were night blind, and mean SpO2 was 89.3% ± 3.4%. The magnitude of pupillary contraction was greater with lower SpO2 (p < 0.01), and this dose relationship remained significant in multiple variable analyses (p = 0.047). Pupillary responsiveness to light stimuli under dark-adapted conditions was exaggerated with hypoxemia and may serve as an early predictor of chronic mountain sickness. This unexpected

  2. Adaptive responses of cardiac function to fetal postural change as gestational age increases

    PubMed Central

    Kim, Woo Jin; Choi, Hye Jin; Yang, Sun Young; Koo, Boo Hae; Ahn, Ki Hoon; Hong, Soon Cheol; Oh, Min-Jeong; Kim, Hai-Joong

    2016-01-01

    Objective The cardiovascular system maintains homeostasis through a series of adaptive responses to physiological requirements. However, little is known about the adaptation of fetal cardiac function to gravity, according to gestational age. In the present study, we aimed to evaluate the adaptive responses of cardiac function to postural changes, using Tei index measurements. Methods Fetal echocardiography and Doppler examination were performed on 114 women with vertex singleton pregnancies at 19 to 40 weeks' gestation. Participants were placed in an upright seated position, and the Tei index for fetal left ventricular cardiac function was measured. The women were then moved into a supine position and the Tei index was re-measured. Results The mean Tei index when measured in an upright seated position was significantly lower than that measured in a supine positioning for all fetuses (0.528±0.103 vs. 0.555±0.106, P=0.014, respectively). This difference was also noted in fetuses with a gestational age of 28–40 weeks (0.539±0.107 vs. 0.574±0.102, P=0.011, respectively). However, there was no difference in the Tei index between an upright seated and a supine position among fetuses with a gestational age of <28 weeks (0.505±0.091 vs. 0.516±0.103, P=0.571, respectively). Conclusion Postural changes from an upright seated to a supine position result in an increased Tei index after a gestational age of 28 weeks. This appears to reflect maturation in the adaptive responses of the fetal cardiovascular system to postural changes. PMID:27896244

  3. 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.

  4. [Quasi-adaptive response to alkylating agents in Escherichia coli and Ada-protein functions].

    PubMed

    Vasil'eva, S V; Moshkovskaia, E Iu; Terekhov, A S; Mikoian, V D; Vanin, A F

    2008-01-01

    In 2005 we have described in exponentially growing E. coli cells a new fundamental genetic phenomenon,--quasi-adaptive response to alkylating compounds (quasi-Ada). Phenotypic expression of quasi-Ada is similar to the true Ada response. However, in contrast to the letter, it develops in the course of pretreatment of the cells by a sublethal dose of nonalkylating agent, an NO-containing dinitrosyl iron complex with glutathione (DNICglu). To reveal the mechanisms of quasi-adaptation and its association with the function of the Ada regulatory protein, here we used a unique property of dual gene expression regulation of aidB1 gene, a part of the Ada-regulon, namely its relative independence from Ada protein in anaerobic conditions. Based on the results of aidB1 gene expression analysis an EPR spectra of E. coli MV2176 cells (aidB1::lacZ) in aerobic and anaerobic conditions after the corresponding treatments, we conclude that the function and the spatial structure of meAda and [(Cys-)2Fe+(NO+)2]Ada are identical and thus the nitrosylated protein represents a regulator of the Ada regulon gene expression during quasi-adaptation development.

  5. 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.

  6. Studies on the response of ewes to live chlamydiae adapted to chicken embryos or tissue culture.

    PubMed Central

    Becerra, V M; Ata, F A; Storz, J

    1976-01-01

    Ewes infected before gestation with chicken embryo or tissue culture adapted chlamydial strain B-577 were challenge inoculated with the homologous strain at four to 18 weeks of gestation. The ewes responsed with group specific complement fixing antibody titers of 1:8 to 1:256 by the second week after initial infection. A secondary antibody response in the surviving challenge inoculated ewes occurred at the time of lambing and reached titers of 1:32 to 1:256 by the second week after parturition. Group specific complement fixing antibodies did not appear to play a significant role in resistance to chlamydial infection. Ewes infected with the chicken embryo adapted strain B-577 excreted chlamydiae in their feces 60 days after inoculation. However, chlamydiae were not recovered from feces of ewes infected with the tissue culture adapted strain B-577. Placentas of ewes challenge inoculated by the intravenous route were consistently infected. Chlamydiae were recovered from placentas, some fetuses and lambs. In two instances when challenge inoculation was given by the intramuscular route, infection was detected only by the direct fluorescent antibody method. PMID:1000377

  7. 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.

  8. 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.

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

    PubMed

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

    2015-08-01

    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.

  10. Recent Visual Experience Shapes Visual Processing in Rats through Stimulus-Specific Adaptation and Response Enhancement.

    PubMed

    Vinken, Kasper; Vogels, Rufin; Op de Beeck, Hans

    2017-03-20

    From an ecological point of view, it is generally suggested that the main goal of vision in rats and mice is navigation and (aerial) predator evasion [1-3]. The latter requires fast and accurate detection of a change in the visual environment. An outstanding question is whether there are mechanisms in the rodent visual system that would support and facilitate visual change detection. An experimental protocol frequently used to investigate change detection in humans is the oddball paradigm, in which a rare, unexpected stimulus is presented in a train of stimulus repetitions [4]. A popular "predictive coding" theory of cortical responses states that neural responses should decrease for expected sensory input and increase for unexpected input [5, 6]. Despite evidence for response suppression and enhancement in noninvasive scalp recordings in humans with this paradigm [7, 8], it has proven challenging to observe both phenomena in invasive action potential recordings in other animals [9-11]. During a visual oddball experiment, we recorded multi-unit spiking activity in rat primary visual cortex (V1) and latero-intermediate area (LI), which is a higher area of the rodent ventral visual stream. In rat V1, there was only evidence for response suppression related to stimulus-specific adaptation, and not for response enhancement. However, higher up in area LI, spiking activity showed clear surprise-based response enhancement in addition to stimulus-specific adaptation. These results show that neural responses along the rat ventral visual stream become increasingly sensitive to changes in the visual environment, suggesting a system specialized in the detection of unexpected events.

  11. 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.

  12. 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

  13. 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.

  14. 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

  15. 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

  16. 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

  17. Imaging of non-Hodgkin lymphomas: diagnosis and response-adapted strategies.

    PubMed

    El-Galaly, Tarec Christoffer; Hutchings, Martin

    2015-01-01

    Optimal lymphoma management requires accurate pretreatment staging and reliable assessment of response, both during and after therapy. Positron emission tomography with computerized tomography (PET/CT) combines functional and anatomical imaging and provides the most sensitive and accurate methods for lymphoma imaging. New guidelines for lymphoma imaging and recently revised criteria for lymphoma staging and response assessment recommend PET/CT staging, treatment monitoring, and response evaluation in all FDG-avid lymphomas, while CT remains the method of choice for non-FDG-avid histologies. Since interim PET imaging has high prognostic value in lymphoma, a number of trials investigate PET-based, response-adapted therapy for non-Hodgkin lymphomas (NHL). PET response is the main determinant of response according to the new response criteria, but PET/CT has little or no role in routine surveillance imaging, the value which is itself questionable. This review presents from a clinical point of view the evidence for the use of imaging and primarily PET/CT in NHL before, during, and after therapy. The reader is given an overview of the current PET-based interventional NHL trials and an insight into possible future developments in the field, including new PET tracers.

  18. Adaptations in endocannabinoid signaling in response to repeated homotypic stress: a novel mechanism for stress habituation.

    PubMed

    Patel, Sachin; Hillard, Cecilia J

    2008-06-01

    Daily life stressors are a major environmental factor contributing to precipitation and exacerbation of mental illness. Animal models using repeated homotypic stress induce anxious and depressive phenotypes and are used to study the pathophysiology of affective disorders. Here we discuss data demonstrating that repeated homotypic stress produces temporally and anatomically distinct changes in endocannabinoid signaling components within stress-responsive brain regions. We also present evidence describing the neural and behavioral correlates of these adaptations in endocannabinoid signaling. These data support a role for endocannabinoid signaling in the central nervous system response to chronic, homotypic stress, and specifically in the process of stress-response habituation. The clinical implications of these findings for the pathophysiology and treatment of affective disorders are discussed.

  19. Adaptive antioxidant response protects dermal fibroblasts from UVA-induced phototoxicity.

    PubMed

    Meewes, C; Brenneisen, P; Wenk, J; Kuhr, L; Ma, W; Alikoski, J; Poswig, A; Krieg, T; Scharffetter-Kochanek, K

    2001-02-01

    In response to the attack of reactive oxygen species (ROS) produced upon UV irradiation, the skin has developed a complex antioxidant defense system. Here we report that, in addition to the previously published induction of manganese superoxide dismutase (MnSOD) activity, single and, to a higher extent, repetitive low-dose UVA irradiation also leads to a substantial upregulation of glutathione peroxidase (GPx) activity. This concomitant adaptive response of two antioxidant enzymes acting in the same detoxification pathway coincided with the protection from high-UVA-dose-induced cytotoxicity conferred by low-dose UVA preirradiation. Whereas an interval of 24 h did not, an interval of 12 h did lead to the induction of MnSOD activity and, under selenium-supplemented conditions, of GPx activity as well, conferring definite cellular protection from UVA-induced phototoxicity. Moreover, under selenium-deficient conditions, which abrogate the UVA-mediated induction of GPx activity, adaptive protection against the cytotoxic effects of high UVA doses was significantly lower compared with selenium supplementation. Isolated 4.6-fold overexpression of MnSOD activity in stably transfected fibroblasts led to specific resistance from UVA-mediated phototoxicity under selenium-deficient conditions. Collectively, these data indicate that the concomitant induction of MnSOD and GPx activity is related to the optimal adaptive protection from photooxidative damage. This adaptive antioxidant protection clearly depends on the irradiation interval and a sufficient selenium concentration, findings that may have important implications for the improvement of photoprotective and phototherapeutic strategies in medicine.

  20. 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

  1. 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…

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

    PubMed Central

    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.

    2015-01-01

    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

  3. Ontogeny of Adaptive Antibody Response to a Model Antigen in Captive Altricial Zebra Finches

    PubMed Central

    Killpack, Tess L.; Karasov, William H.

    2012-01-01

    Based on studies from the poultry literature, all birds are hypothesized to require at least 4 weeks to develop circulating mature B-cell lineages that express functionally different immunoglobulin specificities. However, many altricial passerines fledge at adult size less than four weeks after the start of embryonic development, and therefore may experience a period of susceptibility during the nestling and post-fledging periods. We present the first study, to our knowledge, to detail the age-related changes in adaptive antibody response in an altricial passerine. Using repeated vaccinations with non-infectious keyhole limpet hemocyanin (KLH) antigen, we studied the ontogeny of specific adaptive immune response in altricial zebra finches Taeniopygia guttata. Nestling zebra finches were first injected at 7 days (7d), 14 days (14d), or 21 days post-hatch (21d) with KLH-adjuvant emulsions, and boosted 7 days later. Adults were vaccinated in the same manner. Induced KLH-specific IgY antibodies were measured using ELISA. Comparisons within age groups revealed no significant increase in KLH-specific antibody levels between vaccination and boost in 7d birds, yet significant increases between vaccination and boost were observed in 14d, 21d, and adult groups. There was no significant difference among age groups in KLH antibody response to priming vaccination, yet KLH antibody response post-boost significantly increased with age among groups. Post-boost antibody response in all nestling age groups was significantly lower than in adults, indicating that mature adult secondary antibody response level was not achieved in zebra finches prior to fledging (21 days post-hatch in zebra finches). Findings from this study contribute fundamental knowledge to the fields of developmental immunology and ecological immunology and strengthen the utility of zebra finches as a model organism for future studies of immune ontogeny. PMID:23056621

  4. Adaptation of Perceptual Responses to Low-Load Blood Flow Restriction Training.

    PubMed

    Martín-Hernández, Juan; Ruiz-Aguado, Jorge; Herrero, Azael J; Loenneke, Jeremy P; Aagaard, Per; Cristi-Montero, Carlos; Menéndez, Héctor; Marín, Pedro J

    2017-03-01

    Martín-Hernández, J, Ruiz-Aguado, J, Herrero, AJ, Loenneke, JP, Aagaard, P, Cristi-Montero, C, Menéndez, H, and Marín, PJ. Adaptation of perceptual responses to low-load blood flow restriction training. J Strength Cond Res 31(3): 765-772, 2017-The purpose of this study was to determine the adaptive response of ratings of perceived exertion (RPE) and pain over 6 consecutive training sessions. Thirty subjects were assigned to either a blood flow restriction training (BFRT) group or a high-intensity resistance training (HIT) group. Blood flow-restricted training group performed 4 sets (30 + 15 + 15 + 15, respectively) of unilateral leg extension at an intensity of 20% one repetition maximum (1RM) while a restrictive cuff was applied to the most proximal part of the leg. The HIT group performed 3 sets of 8 repetitions with 85% 1RM. Ratings of perceived exertion and pain were assessed immediately after each exercise set along the 6 training sessions and were then averaged to obtain the overall RPE and pain per session. Statistical analyses showed significant main effects for group (p ≤ 0.05) and time (p < 0.001). Ratings of perceived exertion values dropped from session 1 to session 6 in both BFRT (8.12 ± 1.3 to 5.7 ± 1.1, p < 0.001) and HIT (8.5 ± 1.2 to 6.40 ± 1.2, p < 0.001). Similar results were observed regarding pain ratings (BFRT: 8.12 ± 1.3 to 5.90 ± 1.55, p < 0.001; HIT: 6.22 ± 1.7 to 5.14 ± 1.42, p < 0.01). Our results indicate that RPE was higher after HIT, whereas differences did not reach significance regarding pain. These perceptual responses were attenuated over time, and the time course of this adaptive response was similar between BFRT and HIT. In summary, BFRT induces a marked perceptual response to training, comparable with that observed with HIT. However, this response becomes attenuated with continuous practice, leading to moderate values of RPE and pain. Perceptual responses may not limit the application of BFRT to highly motivated

  5. Intellectual Achievement Responsibility Scale: Child's Work Copy and Examiner's Copy for Use with Third Grade. [Stanford Research Institute Adaptation].

    ERIC Educational Resources Information Center

    Stanford Research Inst., Menlo Park, CA.

    This test was adapted from the Intellectual Achievement Responsibility Scale by V.C. Crandall, Walter Katkovsky, and Vaughan C. Crandall. It is a scale for assessing children's beliefs that they, rather than external forces, are responsible for their intellectual academic successes and failures. Previous data indicates that self responsibility is…

  6. 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

  7. Adaptive Response Against Spontaneous Neoplastic Transformation In Vitro Induced by Ionizing Radiation

    SciTech Connect

    J. Leslie Redpath, Ph.D.

    2003-11-10

    The goal of this project was to establish a dose response curve for radiation-induced neoplastic transformation of HeLa x skin fibroblast human hybrid cells in vitro under experimental conditions were an adaptive response, if it were induced, would have an opportunity to be expressed. During the first two years of the grant an exhaustive series of experiments were performed and the resulting data were reported at the 2000 Annual Meeting of the Radiation Research Society and then Subsequently published. The data showed that an adaptive response against spontaneous neoplastic transformation was seen up to doses of 10cGy of Cs-137 gamma rays. At dose of 30, 50 and 100 cGy the transformation frequencies were above background. This indicated that for this system, under the specific experimental conditions used, there was a threshold of somewhere between 10 and 30 cGy. The results also indicated some unexpected, though very interesting, correlations with relative risk estimates made from human epidemiologic studies.

  8. Simulation study for evaluating the performance of response-adaptive randomization.

    PubMed

    Du, Yining; Wang, Xuan; Jack Lee, J

    2015-01-01

    A response-adaptive randomization (RAR) design refers to the method in which the probability of treatment assignment changes according to how well the treatments are performing in the trial. Holding the promise of treating more patients with the better treatments, RARs have been successfully implemented in clinical trials. We compared equal randomization (ER) with three RARs: Bayesian adaptive randomization, sequential maximum likelihood, and sequential posterior mean. We fixed the total number of patients, considered as patient horizon, but varied the number of patients in the trial. Among the designs, we compared the proportion of patients assigned to the superior arm, overall response rate, statistical power, and total patients enrolled in the trial with and without adding an efficacy early stopping rule. Without early stopping, ER is preferred when the number of patients beyond the trial is much larger than the number of patients in the trial. RAR is favored for large treatment difference or when the number of patients beyond the trial is small. With early stopping, the difference between these two types of designs was reduced. By carefully choosing the design parameters, both RAR and ER methods can achieve the desirable statistical properties. Within three RAR methods, we recommend SPM considering the larger proportion in the better arm and higher overall response rate than BAR and similar power and trial size with ER. The ultimate choice of RAR or ER methods depends on the investigator's preference, the trade-off between group ethics and individual ethics, and logistic considerations in the trial conduct, etc.

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

    PubMed Central

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

    2015-01-01

    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

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

    PubMed

    Kistner, Erica J; Dybdahl, Mark F

    2013-02-01

    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.

  11. 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.

  12. Osmyb4 expression improves adaptive responses to drought and cold stress in transgenic apples.

    PubMed

    Pasquali, Gemma; Biricolti, Stefano; Locatelli, Franca; Baldoni, Elena; Mattana, Monica

    2008-10-01

    Constitutive expression of the rice cold-inducible Osmyb4 gene in transgenic Arabidopsis (Arabidopsis thaliana) plants improves adaptive responses to cold and drought stress, most likely due to the constitutive activation of several stress-inducible pathways and to the accumulation of several compatible solutes (e.g., glucose, fructose, sucrose, proline, glycine betaine and some aromatic compounds). Although the Osmyb4 gene seems able to activate stress responsive pathways in different species, we previously reported that its specific effect on stress tolerance depends on the transformed species. In the present work, we report the effects of the Osmyb4 expression for improving the stress response in apple (Malus pumila Mill.) plants. Namely, we found that the ectopic expression of the Myb4 transcription factor improved physiological and biochemical adaptation to cold and drought stress and modified metabolite accumulation. Based on these results it may be of interest to use Osmyb4 as a tool for improving the productivity of woody perennials under environmental stress conditions.

  13. 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.

  14. 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

  15. Proteomic insights into adaptive responses of Saccharomyces cerevisiae to the repeated vacuum fermentation.

    PubMed

    Cheng, Jing-Sheng; Zhou, Xiao; Ding, Ming-Zhu; Yuan, Ying-Jin

    2009-07-01

    The responses and adaptation mechanisms of the industrial Saccharomyces cerevisiae to vacuum fermentation were explored using proteomic approach. After qualitative and quantitative analyses, a total of 106 spots corresponding to 68 different proteins were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The differentially expressed proteins were involved in amino acid and carbohydrate metabolisms, various signal pathways (Ras/MAPK, Ras-cyclic adenosine monophosphate, and HOG pathway), and heat shock and oxidative responses. Among them, alternations in levels of 17 proteins associated with carbohydrate metabolisms, in particular, the upregulations of proteins involved in glycolysis, trehalose biosynthesis, and the pentose phosphate pathway, suggested vacuum-induced redistribution of the metabolic fluxes. The upregulation of 17 heat stress and oxidative response proteins indicated that multifactors contributed to oxidative stresses by affecting cell redox homeostasis. Taken together with upregulation in 14-3-3 proteins levels, 22 proteins were detected in multispots, respectively, indicating that vacuum might have promoted posttranslational modifications of some proteins in S. cerevisiae. Further investigation revealed that the elevations of the differentially expressed proteins were mainly derived from vacuum stress rather than the absence of oxygen. These findings provide new molecular mechanisms for understanding of adaptation and tolerance of yeast to vacuum fermentation.

  16. Congruency sequence effects and previous response times: conflict adaptation or temporal learning?

    PubMed

    Schmidt, James R; Weissman, Daniel H

    2016-07-01

    In the present study, we followed up on a recent report of two experiments in which the congruency sequence effect-the reduction of the congruency effect after incongruent relative to congruent trials in Stroop-like tasks-was observed without feature repetition or contingency learning confounds. Specifically, we further scrutinized these data to determine the plausibility of a temporal learning account as an alternative to the popular conflict adaptation account. To this end, we employed a linear mixed effects model to investigate the role of previous response time in producing the congruency sequence effect, because previous response time is thought to influence temporal learning. Interestingly, slower previous response times were associated with a reduced current-trial congruency effect, but only when the previous trial was congruent. An adapted version of the parallel episodic processing (PEP) model was able to fit these data if it was additionally assumed that attention "wanders" during different parts of the experiment (e.g., due to fatigue or other factors). Consistent with this assumption, the magnitude of the congruency effect was correlated across small blocks of trials. These findings demonstrate that a temporal learning mechanism provides a plausible account of the congruency sequence effect.

  17. 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.

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

    PubMed Central

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

    2015-01-01

    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. PMID:26295247

  19. 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...

  20. 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.

  1. Computational Model of the Hypothalamic-pituitary-gonadal Axis to Predict Biochemical Adaptive Response to Endocrine Disrupting Fungicide Prochloraz

    EPA Science Inventory

    There is increasing evidence that exposure to endocrine disrupting chemicals can induce adverse effects on reproduction and development in both humans and wildlife. Recent studies report adaptive changes within exposed organisms in response to endocrine disrupting chemicals, and ...

  2. 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

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

    PubMed

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

    2015-11-01

    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.

  4. Adaptation of Medicago truncatula to nitrogen limitation is modulated via local and systemic nodule developmental responses.

    PubMed

    Jeudy, Christian; Ruffel, Sandrine; Freixes, Sandra; Tillard, Pascal; Santoni, Anne Lise; Morel, Sylvain; Journet, Etienne-Pascal; Duc, Gérard; Gojon, Alain; Lepetit, Marc; Salon, Christophe

    2010-02-01

    Adaptation of Medicago truncatula to local nitrogen (N) limitation was investigated to provide new insights into local and systemic N signaling. The split-root technique allowed a characterization of the local and systemic responses of NO(3)(-) or N(2)-fed plants to localized N limitation. (15)N and (13)C labeling were used to monitor plant nutrition. Plants expressing pMtENOD11-GUS and the sunn-2 hypernodulating mutant were used to unravel mechanisms involved in these responses. Unlike NO(3)(-)-fed plants, N(2)-fixing plants lacked the ability to compensate rapidly for a localized N limitation by up-regulating the N(2)-fixation activity of roots supplied elsewhere with N. However they displayed a long-term response via a growth stimulation of pre-existing nodules, and the generation of new nodules, likely through a decreased abortion rate of early nodulation events. Both these responses involve systemic signaling. The latter response is abolished in the sunn mutant, but the mutation does not prevent the first response. Local but also systemic regulatory mechanisms related to plant N status regulate de novo nodule development in Mt, and SUNN is required for this systemic regulation. By contrast, the stimulation of nodule growth triggered by systemic N signaling does not involve SUNN, indicating SUNN-independent signaling.

  5. Adaptive stress response pathways induced by environmental mixtures of bioaccumulative chemicals in dugongs.

    PubMed

    Jin, Ling; Gaus, Caroline; Escher, Beate I

    2015-06-02

    To address the poorly understood mixture effects of chemicals in the marine mammal dugong, we coupled equilibrium-based passive sampling in blubber to a range of in vitro bioassays for screening mixtures of bioaccumulative chemicals. The modes of action included early effect indicators along important toxicity pathways, such as induction of xenobiotic metabolism, and some integrative indicators downstream of the molecular initiating event, such as adaptive stress responses. Activation of aryl hydrocarbon receptor (AhR) and Nrf2-mediated oxidative stress response were found to be the most prominent effects, while the p53-mediated DNA damage response and NF-κB-mediated response to inflammation were not significantly affected. Although polychlorinated dibenzo-p-dioxins (PCDDs) quantified in the samples accounted for the majority of AhR-mediated activity, PCDDs explained less than 5% of the total oxidative stress response, despite their known ability to activate this pathway. Altered oxidative stress response was observed with both individual chemicals and blubber extracts subject to metabolic activation by rat liver S9 fraction. Metabolic activation resulted in both enhanced and reduced toxicity, suggesting the relevance and utility of incorporating metabolic enzymes into in vitro bioassays. Our approach provides a first insight into the burden of toxicologically relevant bioaccumulative chemical mixtures in dugongs and can be applied to lipid tissue of other wildlife species.

  6. The trapezius muscle uniquely lacks adaptive process in response to a repeated moderate cognitive stressor.

    PubMed

    Willmann, Magali; Bolmont, Benoît

    2012-01-06

    The aim of this study was to examine the adaptive process of muscular responses in healthy subjects over two repeated exposures to the same moderate cognitive stressor. The electromyographic (EMG) activity of the flexor pollicis brevis, biceps brachii, triceps brachii, trapezius, gastrocnemius and soleus muscles was recorded in 35 males during video-recorded Stroop color-word interference tests. The results showed lower EMG activity in all muscles during the second exposure to the stressful task, but not in the trapezius muscle. These findings could help to the understanding of the role of stressful situations in the development of musculoskeletal disorders.

  7. Evasion of innate and adaptive immune responses by influenza A virus.

    PubMed

    Schmolke, Mirco; García-Sastre, Adolfo

    2010-07-01

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

  8. 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.

  9. In Vitro Cytotoxicity and Adaptive Stress Responses to Selected Haloacetic Acid and Halobenzoquinone Water Disinfection Byproducts.

    PubMed

    Procházka, Erik; Escher, Beate I; Plewa, Michael J; Leusch, Frederic D L

    2015-10-19

    The process of disinfecting drinking water inadvertently leads to the formation of numerous disinfection byproducts (DBPs). Some of these are mutagenic, genotoxic, teratogenic, and cytotoxic, as well as potentially carcinogenic both in vivo and in vitro. We investigated the in vitro biological activity of five DBPs: three monohaloacetic acids (monoHAAs) [chloroacetic acid (CAA), bromoacetic acid (BAA), and iodoacetic acid (IAA)] and two novel halobenzoquinones (HBQs) [2,6-dichloro-p-benzoquinone (DCBQ) and 2,6-dibromo-p-benzoquinone]. We focused particularly on cytotoxicity and induction of two adaptive stress response pathways: the oxidative stress responsive Nrf2/ARE and DNA-damage responsive p53 pathways. All five DBPs were cytotoxic to the Caco-2 cell line after a 4 h exposure, and all DBPs induced both of the adaptive stress response pathways, Nrf2/ARE and p53, in the micromolar range, as measured by two β-lactamase-based reporter gene assays. The decreasing order of potency for all three endpoints for the five DBPs was IAA ∼ BAA > DCBQ ∼ DBBQ > CAA. Induction of oxidative stress was previously proposed to be the molecular initiating event (MIE) for both classes of DBPs. However, comparing the levels of activation of the two pathways uncovered that the Nrf2/ARE pathway was the more sensitive endpoint for HAAs, whereas the p53 pathway was more sensitive in the case of HBQs. Therefore, the DNA damage-responsive p53 pathway may be an important piece of information to fill in a gap in the adverse outcome pathway framework for the assessment of HBQs. Finally, we cautiously compared the potential risk of the two novel HBQs using a benchmarking approach to that of the well-studied CAA, which suggested that their relative risk may be lower than that of BAA and IAA.

  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. Evidence of fast serotonin transmission in frog slowly adapting type 1 responses.

    PubMed

    Press, Daniel; Mutlu, Sevinç; Güçlü, Burak

    2010-01-01

    The Merkel cell-neurite (MCN) complex generates slowly adapting type 1 (SA1) response when mechanically stimulated. Both serotonin (5-HT) and glutamate have been implicated in the generation of normal SA1 responses, but previous studies have been inconclusive as to what their roles are or how synaptic transmission occurs. In this study, excised dorsal skin patches from common water frogs (Rana ridibunda) were stimulated by von Frey hairs during perfusion in a tissue bath, and single-unit spike activity was recorded from SA1 fibres. Serotonin had no significant effect on the SA1 response at low (10 µM) concentration, significantly increased activity in a force-independent manner at 100 µM, but decreased activity with reduced responsiveness to force at 1 mM. Glutamate showed no effect on the responsiveness to force at 100 µM. MDL 72222 (100 µM), an ionotropic 5-HT3 receptor antagonist, completely abolished the responsiveness to force, suggesting that serotonin is released from Merkel cells as a result of mechanical stimulation, and activated 5-HT3 receptors on the neurite. The metabotropic 5-HT2 receptor antagonist, ketanserin, greatly reduced the SA1 fibre's responsiveness to force, as did the non-specific glutamate receptor antagonist, kynurenic acid. This supports a role for serotonin and glutamate as neuromodulators in the MCN complex, possibly by activation and/or inhibition of signalling cascades in the Merkel cell associated with vesicle release. Additionally, it was observed that SA1 responses contained a force-independent component, similar to a dynamic response observed during mechanical vibrations.

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

    PubMed

    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

    2015-07-01

    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.

  14. Durable antitumor responses to CD47 blockade require adaptive immune stimulation

    PubMed Central

    Sockolosky, Jonathan T.; Dougan, Michael; Ingram, Jessica R.; Ho, Chia Chi M.; Kauke, Monique J.; Almo, Steven C.; Ploegh, Hidde L.; Garcia, K. Christopher

    2016-01-01

    Therapeutic antitumor antibodies treat cancer by mobilizing both innate and adaptive immunity. CD47 is an antiphagocytic ligand exploited by tumor cells to blunt antibody effector functions by transmitting an inhibitory signal through its receptor signal regulatory protein alpha (SIRPα). Interference with the CD47–SIRPα interaction synergizes with tumor-specific monoclonal antibodies to eliminate human tumor xenografts by enhancing macrophage-mediated antibody-dependent cellular phagocytosis (ADCP), but synergy between CD47 blockade and ADCP has yet to be demonstrated in immunocompetent hosts. Here, we show that CD47 blockade alone or in combination with a tumor-specific antibody fails to generate antitumor immunity against syngeneic B16F10 tumors in mice. Durable tumor immunity required programmed death-ligand 1 (PD-L1) blockade in combination with an antitumor antibody, with incorporation of CD47 antagonism substantially improving response rates. Our results highlight an underappreciated contribution of the adaptive immune system to anti-CD47 adjuvant therapy and suggest that targeting both innate and adaptive immune checkpoints can potentiate the vaccinal effect of antitumor antibody therapy. PMID:27091975

  15. Transcriptomic Analysis of Laribacter hongkongensis Reveals Adaptive Response Coupled with Temperature

    PubMed Central

    Kong, Hoi-Kuan; Law, Hon-Wai; Liu, Xuan; Law, Carmen O. K.; Pan, Qing; Gao, Lin; Xiong, Lifeng; Lau, Susanna K. P.; Woo, Patrick C. Y.; Lau, Terrence chi kong

    2017-01-01

    Bacterial adaptation to different hosts requires transcriptomic alteration in response to the environmental conditions. Laribacter hongkongensis is a gram-negative, facultative anaerobic, urease-positive bacillus caused infections in liver cirrhosis patients and community-acquired gastroenteritis. It was also found in intestine from commonly consumed freshwater fishes and drinking water reservoirs. Since L. hongkongensis could survive as either fish or human pathogens, their survival mechanisms in two different habitats should be temperature-regulated and highly complex. Therefore, we performed transcriptomic analysis of L. hongkongensis at body temperatures of fish and human in order to elucidate the versatile adaptation mechanisms coupled with the temperatures. We identified numerous novel temperature-induced pathways involved in host pathogenesis, in addition to the shift of metabolic equilibriums and overexpression of stress-related proteins. Moreover, these pathways form a network that can be activated at a particular temperature, and change the physiology of the bacteria to adapt to the environments. In summary, the dynamic of transcriptomes in L. hongkongensis provides versatile strategies for the bacterial survival at different habitats and this alteration prepares the bacterium for the challenge of host immunity. PMID:28085929

  16. Somatic-evoked brain responses as indicators of adaptation to nitrogen narcosis.

    PubMed

    Langley, T D; Hamilton, R W

    1975-02-01

    Two 2-week experimental pressure chamber exposures to nitrogen-oxygen breathing mixtures afforded an opportunity to study adaptation to nitrogen narcosis. Somatic-evoked brain responses induced by electrical stimulation of the median nerve in the wrist were processed on-line with a signal averager. The N1P2 interval was seen generally to be reduced in amplitude as a result of exposure to increased nitrogen partial pressure. Compressions with air were made from sea level and saturation to 200, 250 and 300 ft of sea water (fsw) equivalent (61, 76, and 91m). The decrement was found to be less, for equivalent exposures, in subjects who had been saturated at the pressure of 90 and 120 fsw (27 and 36 m); we interpret this as evidence of a nonspecific "adaptation." Less adaptation was seen from 30 and 60 fsw (9 and 18 m). These results are consistent with performance tests on the same exposures, and with subjective impressions. Saturation with 3 0r 4 atm of nitrogen may permit somewhat deeper diving without serious narcosis, than is possible from sea level.

  17. Durable antitumor responses to CD47 blockade require adaptive immune stimulation.

    PubMed

    Sockolosky, Jonathan T; Dougan, Michael; Ingram, Jessica R; Ho, Chia Chi M; Kauke, Monique J; Almo, Steven C; Ploegh, Hidde L; Garcia, K Christopher

    2016-05-10

    Therapeutic antitumor antibodies treat cancer by mobilizing both innate and adaptive immunity. CD47 is an antiphagocytic ligand exploited by tumor cells to blunt antibody effector functions by transmitting an inhibitory signal through its receptor signal regulatory protein alpha (SIRPα). Interference with the CD47-SIRPα interaction synergizes with tumor-specific monoclonal antibodies to eliminate human tumor xenografts by enhancing macrophage-mediated antibody-dependent cellular phagocytosis (ADCP), but synergy between CD47 blockade and ADCP has yet to be demonstrated in immunocompetent hosts. Here, we show that CD47 blockade alone or in combination with a tumor-specific antibody fails to generate antitumor immunity against syngeneic B16F10 tumors in mice. Durable tumor immunity required programmed death-ligand 1 (PD-L1) blockade in combination with an antitumor antibody, with incorporation of CD47 antagonism substantially improving response rates. Our results highlight an underappreciated contribution of the adaptive immune system to anti-CD47 adjuvant therapy and suggest that targeting both innate and adaptive immune checkpoints can potentiate the vaccinal effect of antitumor antibody therapy.

  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. 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.

  20. Studies of adaptive response and mutation induction in MCF-10A cells following exposure to chronic or acute ionizing radiation.

    PubMed

    Manesh, Sara Shakeri; Sangsuwan, Traimate; Wojcik, Andrzej; Haghdoost, Siamak

    2015-10-01

    A phenomenon in which exposure to a low adapting dose of radiation makes cells more resistant to the effects of a subsequent high dose exposure is termed radio-adaptive response. Adaptive response could hypothetically reduce the risk of late adverse effects of chronic or acute radiation exposures in humans. Understanding the underlying mechanisms of such responses is of relevance for radiation protection as well as for the clinical applications of radiation in medicine. However, due to the variability of responses depending on the model system and radiation condition, there is a need to further study under what conditions adaptive response can be induced. In this study, we analyzed if there is a dose rate dependence for the adapting dose, assuming that the adapting dose induces DNA response/repair pathways that are dose rate dependent. MCF-10A cells were exposed to a 50mGy adapting dose administered acutely (0.40Gy/min) or chronically (1.4mGy/h or 4.1mGy/h) and then irradiated by high acute challenging doses. The endpoints of study include clonogenic cell survival and mutation frequency at X-linked hprt locus. In another series of experiment, cells were exposed to 100mGy and 1Gy at different dose rates (acutely and chronically) and then the mutation frequencies were studied. Adaptive response was absent at the level of clonogenic survival. The mutation frequencies were significantly decreased in the cells pre-exposed to 50mGy at 1.4mGy/h followed by 1Gy acute exposure as challenging dose. Importantly, at single dose exposures (1 Gy or 100mGy), no differences at the level of mutation were found comparing different dose rates.

  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. Prostate Cancer Patients Treated with Androgen Deprivation Therapy Develop Persistent Changes in Adaptive Immune Responses

    PubMed Central

    Morse, Matthew D.; McNeel, Douglas G.

    2010-01-01

    Prostate cancer is a significant cause of morbidity and mortality among men worldwide. The cornerstone treatment for metastatic prostate cancer is androgen deprivation, which has known effects on prostate tissue apoptosis and thymic regrowth. These findings, plus interest in developing immune-based treatments for prostate cancer, lead us to question whether androgen deprivation causes changes in the adaptive immune responses of prostate cancer patients, and if the timing of changes has implications for the sequencing of immunotherapies in combination with androgen deprivation. Peripheral blood mononuclear cells (PBMC) were obtained from patients prior to beginning androgen deprivation therapy (ADT) and at several time points thereafter. These cells were analyzed for the frequency of specific lymphocyte populations, and their response to stimulation. The development of prostate antigen-specific immune responses was assessed using SEREX. Patients developed expansion of the naïve T cell compartment persisting over the course of androgen deprivation, together with an increase in effector cell response to stimulation, and the generation of prostate tissue-associated IgG antibody responses, implying a potential benefit to the use of ADT in combination with prostate cancer-directed immunotherapies. The optimal timing and sequence of androgen deprivation with immune-based therapies awaits future experimental evaluation. PMID:20153396

  3. Adaptive innate immunity? Responsive-mode prophylaxis in the mealworm beetle, Tenebrio molitor.

    PubMed Central

    Moret, Yannick; Siva-Jothy, Michael T

    2003-01-01

    A primary infection by a parasite may indicate a higher risk of being reinfected in the near future (since infection may indicate that enemies are becoming more abundant). Acquired immunity does not exist in invertebrates despite the fact that they also face increased risks of reinfection following primary exposure. However, when subjected to immune insult, insects can produce immune responses that persist for long enough to provide prophylaxis. Because these immune responses are costly, persistence must be maintained through a selective advantage. We tested for the possibility that these long-lasting immune responses provided increased resistance to later infections by experimentally mimicking a primary immune insult (pre-challenge) in larvae of the mealworm beetle, Tenebrio molitor, with lipopolysaccharides (LPS) prior to early or late exposure to spores of the entomopathogenic fungus Metarhizium anisopliae. We found that pre-challenged larvae produced a long-lasting antimicrobial response, which provided a survival benefit when the larvae were exposed to fungal infection. These results suggest that the observed response is functionally "adaptive". PMID:14667338

  4. Mouse retinal adaptive response to proton irradiation: Correlation with DNA repair and photoreceptor cell death

    NASA Astrophysics Data System (ADS)

    Tronov, V. A.; Vinogradova, Yu. V.; Poplinskaya, V. A.; Nekrasova, E. I.; Ostrovsky, M. A.

    2015-01-01

    Emerging body of data indicate protecting effect of low level of stress (preconditioning) on retina. Our previous study revealed non-linear dose-response relationship for cytotoxicity of both ionizing radiation and N-methyl-N-nitrosourea (MNU) on mouse retina. Moreover, non cytotoxic dose of MNU increased tolerance of retina to following challenge dose of MNU. This result displays protection of retina through mechanism of recovery. In present study we used the mouse model for MNU-induced retinal degeneration to evaluate adaptive response of retina to proton irradiation and implication in it of glial Muller cells. The data showed that the recovery of retina after genotoxic agents has been associated with increased efficacy of DNA damage repair and lowered death of retinal photoreceptor cells.

  5. Neuroticism and responsiveness to error feedback: adaptive self-regulation versus affective reactivity.

    PubMed

    Robinson, Michael D; Moeller, Sara K; Fetterman, Adam K

    2010-10-01

    Responsiveness to negative feedback has been seen as functional by those who emphasize the value of reflecting on such feedback in self-regulating problematic behaviors. On the other hand, the very same responsiveness has been viewed as dysfunctional by its link to punishment sensitivity and reactivity. The present 4 studies, involving 203 undergraduate participants, sought to reconcile such discrepant views in the context of the trait of neuroticism. In cognitive tasks, individuals were given error feedback when they made mistakes. It was found that greater tendencies to slow down following error feedback were associated with higher levels of accuracy at low levels of neuroticism but lower levels of accuracy at high levels of neuroticism. Individual differences in neuroticism thus appear crucial in understanding whether behavioral alterations following negative feedback reflect proactive versus reactive mechanisms and processes. Implications for understanding the processing basis of neuroticism and adaptive self-regulation are discussed.

  6. 5-Lipoxygenase deficiency impairs innate and adaptive immune responses during fungal infection.

    PubMed

    Secatto, Adriana; Rodrigues, Lilian Cataldi; Serezani, Carlos Henrique; Ramos, Simone Gusmão; Dias-Baruffi, Marcelo; Faccioli, Lúcia Helena; Medeiros, Alexandra I

    2012-01-01

    5-Lipoxygenase-derived products have been implicated in both the inhibition and promotion of chronic infection. Here, we sought to investigate the roles of endogenous 5-lipoxygenase products and exogenous leukotrienes during Histoplasma capsulatum infection in vivo and in vitro. 5-LO deficiency led to increased lung CFU, decreased nitric oxide production and a deficient primary immune response during active fungal infection. Moreover, H. capsulatum-infected 5-LO(-/-) mice showed an intense influx of neutrophils and an impaired ability to generate and recruit effector T cells to the lung. The fungal susceptibility of 5-LO(-/-) mice correlated with a lower rate of macrophage ingestion of IgG-H. capsulatum relative to WT macrophages. Conversely, exogenous LTB4 and LTC4 restored macrophage phagocytosis in 5-LO deficient mice. Our results demonstrate that leukotrienes are required to control chronic fungal infection by amplifying both the innate and adaptive immune response during histoplasmosis.

  7. Living in an adaptive world: Genomic dissection of the genus Homo and its immune response.

    PubMed

    Quach, Hélène; Quintana-Murci, Lluis

    2017-04-03

    More than a decade after the sequencing of the human genome, a deluge of genome-wide population data are generating a portrait of human genetic diversity at an unprecedented level of resolution. Genomic studies have provided new insight into the demographic and adaptive history of our species, Homo sapiens, including its interbreeding with other hominins, such as Neanderthals, and the ways in which natural selection, in its various guises, has shaped genome diversity. These studies, combined with functional genomic approaches, such as the mapping of expression quantitative trait loci, have helped to identify genes, functions, and mechanisms of prime importance for host survival and involved in phenotypic variation and differences in disease risk. This review summarizes new findings in this rapidly developing field, focusing on the human immune response. We discuss the importance of defining the genetic and evolutionary determinants driving immune response variation, and highlight the added value of population genomic approaches in settings relevant to immunity and infection.

  8. 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.

  9. 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

  10. 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

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

    PubMed

    Goyaram, Veeraj; Kohn, Tertius A; Ojuka, Edward O

    2014-02-01

    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.

  12. Chronic joint disease caused by persistent Chikungunya virus infection is controlled by the adaptive immune response.

    PubMed

    Hawman, David W; Stoermer, Kristina A; Montgomery, Stephanie A; Pal, Pankaj; Oko, Lauren; Diamond, Michael S; Morrison, Thomas E

    2013-12-01

    Chikungunya virus (CHIKV) is a reemerging mosquito-borne pathogen that causes incapacitating disease in humans characterized by intense joint pain that can persist for weeks, months, or even years. Although there is some evidence of persistent CHIKV infection in humans suffering from chronic rheumatologic disease symptoms, little is known about chronic disease pathogenesis, and no specific therapies exist for acute or chronic CHIKV disease. To investigate mechanisms of chronic CHIKV-induced disease, we utilized a mouse model and defined the duration of CHIKV infection in tissues and the associated histopathological changes. Although CHIKV RNA was readily detectable in a variety of tissues very early after infection, CHIKV RNA persisted specifically in joint-associated tissues for at least 16 weeks. Inoculation of Rag1(-/-) mice, which lack T and B cells, resulted in higher viral levels in a variety of tissues, suggesting that adaptive immunity controls the tissue specificity and persistence of CHIKV infection. The presence of CHIKV RNA in tissues of wild-type and Rag1(-/-) mice was associated with histopathological evidence of synovitis, arthritis, and tendonitis; thus, CHIKV-induced persistent arthritis is not mediated primarily by adaptive immune responses. Finally, we show that prophylactic administration of CHIKV-specific monoclonal antibodies prevented the establishment of CHIKV persistence, whereas therapeutic administration had tissue-specific efficacy. These findings suggest that chronic musculoskeletal tissue pathology is caused by persistent CHIKV infection and controlled by adaptive immune responses. Our results have significant implications for the development of strategies to mitigate the disease burden associated with CHIKV infection in humans.

  13. Impaired calcium calmodulin kinase signaling and muscle adaptation response in the absence of calpain 3.

    PubMed

    Kramerova, I; Kudryashova, E; Ermolova, N; Saenz, A; Jaka, O; López de Munain, A; Spencer, M J

    2012-07-15

    Mutations in the non-lysosomal, cysteine protease calpain 3 (CAPN3) result in the disease limb girdle muscular dystrophy type 2A (LGMD2A). CAPN3 is localized to several subcellular compartments, including triads, where it plays a structural, rather than a proteolytic, role. In the absence of CAPN3, several triad components are reduced, including the major Ca(2+) release channel, ryanodine receptor (RyR). Furthermore, Ca(2+) release upon excitation is impaired in the absence of CAPN3. In the present study, we show that Ca-calmodulin protein kinase II (CaMKII) signaling is compromised in CAPN3 knockout (C3KO) mice. The CaMK pathway has been previously implicated in promoting the slow skeletal muscle phenotype. As expected, the decrease in CaMKII signaling that was observed in the absence of CAPN3 is associated with a reduction in the slow versus fast muscle fiber phenotype. We show that muscles of WT mice subjected to exercise training activate the CaMKII signaling pathway and increase expression of the slow form of myosin; however, muscles of C3KO mice do not exhibit these adaptive changes to exercise. These data strongly suggest that skeletal muscle's adaptive response to functional demand is compromised in the absence of CAPN3. In agreement with our mouse studies, RyR levels were also decreased in biopsies from LGMD2A patients. Moreover, we observed a preferential pathological involvement of slow fibers in LGMD2A biopsies. Thus, impaired CaMKII signaling and, as a result, a weakened muscle adaptation response identify a novel mechanism that may underlie LGMD2A and suggest a pharmacological target that should be explored for therapy.

  14. 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

  15. Dispositional Mindfulness Predicts Adaptive Affective Responses to Health Messages and Increased Exercise Motivation.

    PubMed

    Kang, Yoona; O'Donnell, Matthew Brook; Strecher, Victor J; Falk, Emily B

    2017-04-01

    Feelings can shape how people respond to persuasive messages. In health communication, adaptive affective responses to potentially threating messages constitute one key to intervention success. The current study tested dispositional mindfulness, characterized by awareness of the present moment, as a predictor of adaptive affective responses to potentially threatening health messages and desirable subsequent health outcomes. Both general and discrete negative affective states (i.e., shame) were examined in relation to mindfulness and intervention success. Individuals (n=67) who reported less than 195 weekly minutes of exercise were recruited. At baseline, participants' dispositional mindfulness and exercise outcomes were assessed, including self-reported exercise motivation and physical activity. A week later, all participants were presented with potentially threatening and self-relevant health messages encouraging physical activity and discouraging sedentary lifestyle, and their subsequent affective response and exercise motivation were assessed. Approximately one month later, changes in exercise motivation and physical activity were assessed again. In addition, participants' level of daily physical activity was monitored by a wrist worn accelerometer throughout the entire duration of the study. Higher dispositional mindfulness predicted greater increases in exercise motivation one month after the intervention. Importantly, this effect was fully mediated by lower negative affect and shame specifically, in response to potentially threatening health messages among highly mindful individuals. Baseline mindfulness was also associated with increased self-reported vigorous activity, but not with daily physical activity as assessed by accelerometers. These findings suggest potential benefits of considering mindfulness as an active individual difference variable in theories of affective processing and health communication.

  16. Adaptive radiation of photosynthetic physiology in the Hawaiian lobeliads: dynamic photosynthetic responses.

    PubMed

    Montgomery, Rebecca A; Givnish, Thomas J

    2008-03-01

    Hawaiian lobeliads have radiated into habitats from open alpine bogs to densely shaded rainforest interiors, and show corresponding adaptations in steady-state photosynthetic light responses and associated leaf traits. Shaded environments are not uniformly dark, however, but punctuated by sunflecks that carry most of the photosynthetically active light that strikes plants. We asked whether lobeliads have diversified in their dynamic photosynthetic light responses and how dynamic responses influence daily leaf carbon gain. We quantified gas exchange and dynamic light regimes under field conditions for ten species representing each major Hawaiian sublineage. Species in shadier habitats experienced shorter and less numerous sunflecks: average sunfleck length varied from 1.4 +/- 1.7 min for Cyanea floribunda in shaded forest understories to 31.2 +/- 2.1 min for Trematolobelia kauaiensis on open ridges. As expected, the rate of photosynthetic induction increased significantly toward shadier sites, with assimilation after 60 s rising from ca. 30% of fully induced rates in species from open environments to 60% in those from densely shaded habitats. Uninduced light use efficiency-actual photosynthesis versus that expected under steady-state conditions-increased from 10 to 70% across the same gradient. In silico transplants-modeling daily carbon gain using one species' photosynthetic light response in its own and other species' dynamic light regimes-demonstrated the potential adaptive nature of species differences: understory Cyanea pilosa in its light regimes outperformed gap-dwelling Clermontia parviflora, while Clermontia in its light regimes outperformed Cyanea. The apparent crossover in daily photosynthesis occurred at about the same photon flux density where dominance shifts from Cyanea to Clermontia in the field. Our results further support our hypothesis that the lobeliads have diversified physiologically across light environments in Hawaiian ecosystems and that

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

    PubMed Central

    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

  18. Metabotropic glutamate receptor antagonists selectively enhance responses of slowly adapting type I mechanoreceptors.

    PubMed

    Cahusac, Peter M B; Senok, Solomon S

    2006-03-15

    There is evidence that glutamate may participate as a transmitter at the junction between Merkel cells and the nerve terminals of slowly adapting type I (St I) units. We recorded extracellularly from the deep vibrissal nerve of an isolated rat vibrissa preparation in vitro. Five second trapezoid stimulus ramp deflections of the hair shaft were used to evoke responses. We bath-applied two compounds, which we planned would interfere with glutamatergic transmission. (2S)-2-Amino-2-[(1S,2S)-2-carboxycycloprop-1-yl]-3-(xanth-9-yl) propanoic acid (LY341495) was used at concentrations up to 100 microM to block all known metabotropic glutamate (mGlu) receptors. The racemic mixture (RS)-4-carboxy-3-hydroxyphenylglycine ((RS)-4C3HPG) was used up to 100 microM to block ionotropic and Group I metabotropic glutamate receptors, and as an agonist at Group II mGlu receptors. Unexpectedly, both compounds had rapid onset excitatory effects on mechanically-evoked responses. (RS)-4C3HPG increased responses, with a mean 146% of control (P < 0.05) in a concentration-dependent manner. LY341495 increased responses, with a mean 128% of control (P < 0.05). With (RS)-4C3HPG in particular, it was noted that the static component (the firing during the last 1 s plateau) was preferentially enhanced relative to the dynamic component (firing during the first 0.5 s). Rapid recovery was seen after wash. Slowly adapting type II units, which have no junctional transmission, were completely unaffected by these compounds up to 200 microM. These results suggest that mGlu receptors play a role in Merkel cell-neurite complex mechanotransduction, although other explanations are considered.

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

    PubMed

    Millet, Grégoire P; Millet, Guillaume Y

    2012-07-19

    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.

  20. Rat mandibular distraction osteogenesis: latency, rate, and rhythm determine the adaptive response.

    PubMed

    Paccione, M F; Mehrara, B J; Warren, S M; Greenwald, J A; Spector, J A; Luchs, J S; Longaker, M T

    2001-03-01

    Distraction osteogenesis is a well-established technique of endogenous tissue engineering. The biomechanical factors thought to affect the quality of the distraction regenerate include the latency, rate, rhythm, and consolidation period. In an effort to understand the impact of these parameters on regenerate bone formation, this study was designed to decipher the most adaptive response in a rat model of mandibular distraction osteogenesis. Ninety-six adult Sprague-Dawley rats were divided into 16 subgroups (n = 6 per subgroup) based on variations in the distraction parameters (i.e., latency, rate, and rhythm). After a 28-day consolidation period, the mandibles were harvested, decalcified, and sectioned. A standardized histologic ranking system was used to evaluate the effect of each protocol on the adaptive response of the regenerate bone. In this study, we have demonstrated that the latency period dramatically affects the success of distraction osteogenesis. Furthermore, distraction rates up to 0.50 mm per day stimulated excellent regenerate bone formation, whereas greater distraction rates produced a fibrous union. Finally, higher frequency distraction (i.e., increased rhythm) appeared to accelerate regenerate bone formation. We believe that defining the critical parameters of this model will improve future analysis of gene expression during rat mandibular distraction osteogenesis and may facilitate the development of biologically based strategies designed to enhance regenerate bone formation.

  1. 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

  2. Adaptation responses of individuals to environmental changes in the ciliate Euplotes crassus

    NASA Astrophysics Data System (ADS)

    Kim, Se-Joo; Kim, Jin-Hyoung; Ju, Se-Jong

    2017-02-01

    Although the response unit of living organisms to environmental changes is at the individual level, most experiments on the adaptation responses of ciliates have been conducted in batches, comprising multiple-individuals, due to their microscopic size. However, here, we confirmed that individuals undergo different division cycles in monocultures of Euplotes crassus. They also exhibited transcript variations of 4.63-fold in SSU and of 22.78- fold in Hsp70. Additionally, in salt-stressed E. crassus individuals, SSU transcripts of individuals varied by 6.92-fold at 27 psu, 8.69- fold at 32 psu, and 2.51-fold at 37 psu. However, the maximum difference in Hsp70 was only 4.23-fold under all conditions. These results suggest there may be different biological rhythms even in siblings derived from the same parent. It can also be inferred that various environmental factors have different effects on different E. crassus individuals. Therefore, to elucidate relationships between organism adaptations and environmental changes, studies at the individual level should be conducted with multi-individual approaches.

  3. Adaptation responses of individuals to environmental changes in the ciliate Euplotes crassus

    NASA Astrophysics Data System (ADS)

    Kim, Se-Joo; Kim, Jin-Hyoung; Ju, Se-Jong

    2017-03-01

    Although the response unit of living organisms to environmental changes is at the individual level, most experiments on the adaptation responses of ciliates have been conducted in batches, comprising multiple-individuals, due to their microscopic size. However, here, we confirmed that individuals undergo different division cycles in monocultures of Euplotes crassus. They also exhibited transcript variations of 4.63-fold in SSU and of 22.78- fold in Hsp70. Additionally, in salt-stressed E. crassus individuals, SSU transcripts of individuals varied by 6.92-fold at 27 psu, 8.69- fold at 32 psu, and 2.51-fold at 37 psu. However, the maximum difference in Hsp70 was only 4.23-fold under all conditions. These results suggest there may be different biological rhythms even in siblings derived from the same parent. It can also be inferred that various environmental factors have different effects on different E. crassus individuals. Therefore, to elucidate relationships between organism adaptations and environmental changes, studies at the individual level should be conducted with multi-individual approaches.

  4. 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.

  5. Adaptations in horizontal head stabilization in response to altered vision and gaze during natural walking.

    PubMed

    Cromwell, Ronita L; Pidcoe, Peter E; Griffin, Lori A; Sotillo, Tanya; Ganninger, Daniel; Feagin, Montgomery

    2004-01-01

    The purpose of this study was to determine adaptations in head stability resulting from altered gaze control and vision during over-ground walking. Using over-ground walking permitted adaptations in walking velocity and cadence that are otherwise not possible during treadmill walking or walking-in-place. Gaze control and vision were manipulated by having 20 young adult subjects 1) walk naturally, 2) view a distant, earth-fixed target to enhance the vestibulo-ocular reflex (VOR), 3) view a head-fixed target to suppress the VOR, and 4) walk in darkness. Horizontal head and trunk angular velocities in space, walking velocity and cadence were measured. Root-mean-square head and trunk angular velocities were calculated and frequency analyses determined head-trunk movement patterns. Results demonstrated that when given the opportunity, subjects slowed down and decreased cadence in response to challenging tasks. Despite strongly reduced walking velocity and cadence, walking in darkness proved most challenging for head stabilization, indicating the importance of vision during this process. Viewing the earth-fixed target demonstrated the greatest head stability thereby, facilitating gaze stabilization. However, comparisons between the earth-fixed and head-fixed target conditions suggest a reciprocal relationship where gaze stability also facilitates head stability. This contribution of gaze stability to head stability is more important than vision alone as the head stabilization response was diminished during the VOR suppressed condition.

  6. 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

  7. 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.

  8. Differential Adaptive Response and Survival of Salmonella enterica Serovar Enteritidis Planktonic and Biofilm Cells Exposed to Benzalkonium Chloride▿

    PubMed Central

    Mangalappalli-Illathu, Anil K.; Vidović, Sinisa; Korber, Darren R.

    2008-01-01

    This study examined the adaptive response and survival of planktonic and biofilm phenotypes of Salmonella enterica serovar Enteritidis adapted to benzalkonium chloride (BC). Planktonic cells and biofilms were continuously exposed to 1 μg ml−1 of BC for 144 h. The proportion of BC-adapted biofilm cells able to survive a lethal BC treatment (30 μg ml−1) was significantly higher (4.6-fold) than that of BC-adapted planktonic cells. Similarly, there were 18.3-fold more survivors among the BC-adapted biofilm cells than among their nonadapted (i.e., without prior BC exposure) cell counterparts at the lethal BC concentration, and this value was significantly higher than the value for BC-adapted planktonic cells versus nonadapted cells (3.2-fold). A significantly higher (P < 0.05) proportion of surviving cells was noticed among BC-adapted biofilm cells relative to BC-adapted planktonic cells following a 10-min heat shock at 55°C. Fatty acid composition was significantly influenced by phenotype (planktonic cells or biofilm) and BC adaptation. Cell surface roughness of biofilm cells was also significantly greater (P < 0.05) than that of planktonic cells. Key proteins upregulated in BC-adapted planktonic and biofilm cells included CspA, TrxA, Tsf, YjgF, and a probable peroxidase, STY0440. Nine and 17 unique proteins were upregulated in BC-adapted planktonic and biofilm cells, respectively. These results suggest that enhanced biofilm-specific upregulation of 17 unique proteins, along with the increased expression of CspA, TrxA, Tsf, YjgF, and a probable peroxidase, phenotype-specific alterations in cell surface roughness, and a shift in fatty acid composition conferred enhanced survival to the BC-adapted biofilm cell population relative to their BC-adapted planktonic cell counterparts. PMID:18663028

  9. The Vibrio cholerae Cpx Envelope Stress Response Senses and Mediates Adaptation to Low Iron

    PubMed Central

    Acosta, Nicole; Pukatzki, Stefan

    2014-01-01

    The Cpx pathway, a two-component system that employs the sensor histidine kinase CpxA and the response regulator CpxR, regulates crucial envelope stress responses across bacterial species and affects antibiotic resistance. To characterize the CpxR regulon in Vibrio cholerae, the transcriptional profile of the pandemic V. cholerae El Tor C6706 strain was examined upon overexpression of cpxR. Our data show that the Cpx regulon of V. cholerae is enriched in genes encoding membrane-localized and transport proteins, including a large number of genes known or predicted to be iron regulated. Activation of the Cpx pathway further led to the expression of TolC, the major outer membrane pore, and of components of two RND efflux systems in V. cholerae. We show that iron chelation, toxic compounds, or deletion of specific RND efflux components leads to Cpx pathway activation. Furthermore, mutations that eliminate the Cpx response or members of its regulon result in growth phenotypes in the presence of these inducers that, together with Cpx pathway activation, are partially suppressed by iron. Cumulatively, our results suggest that a major function of the Cpx response in V. cholerae is to mediate adaptation to envelope perturbations caused by toxic compounds and the depletion of iron. PMID:25368298

  10. The influence of innate and adaptative immune responses on the differential clinical outcomes of leprosy.

    PubMed

    Fonseca, Adriana Barbosa de Lima; Simon, Marise do Vale; Cazzaniga, Rodrigo Anselmo; de Moura, Tatiana Rodrigues; de Almeida, Roque Pacheco; Duthie, Malcolm S; Reed, Steven G; de Jesus, Amelia Ribeiro

    2017-02-06

    Leprosy is a chronic infectious disease caused by Mycobacterium leprae. According to official reports from 121 countries across five WHO regions, there were 213 899 newly diagnosed cases in 2014. Although leprosy affects the skin and peripheral nerves, it can present across a spectrum of clinical and histopathological forms that are strongly influenced by the immune response of the infected individuals. These forms comprise the extremes of tuberculoid leprosy (TT), with a M. leprae-specific Th1, but also a Th17, response that limits M. leprae multiplication, through to lepromatous leprosy (LL), with M. leprae-specific Th2 and T regulatory responses that do not control M. leprae replication but rather allow bacterial dissemination. The interpolar borderline clinical forms present with similar, but less extreme, immune biases. Acute inflammatory episodes, known as leprosy reactions, are complications that may occur before, during or after treatment, and cause further neurological damages that can cause irreversible chronic disabilities. This review discusses the innate and adaptive immune responses, and their interactions, that are known to affect pathogenesis and influence the clinical outcome of leprosy.

  11. 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.

  12. 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

  13. 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

  14. 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

  15. Detrimental effects for colonocytes of an increased exposure to luminal hydrogen sulfide: The adaptive response.

    PubMed

    Beaumont, Martin; Andriamihaja, Mireille; Lan, Annaïg; Khodorova, Nadezda; Audebert, Marc; Blouin, Jean-Marc; Grauso, Marta; Lancha, Luciana; Benetti, Pierre-Henri; Benamouzig, Robert; Tomé, Daniel; Bouillaud, Frédéric; Davila, Anne-Marie; Blachier, François

    2016-04-01

    Protein fermentation by the gut microbiota releases in the large intestine lumen various amino-acid derived metabolites. Among them, hydrogen sulfide (H2S) in excess has been suspected to be detrimental for colonic epithelium energy metabolism and DNA integrity. The first objective of this study was to evaluate in rats the epithelial response to an increased exposure to H2S. Experiments from colonocyte incubation and intra-colonic instillation indicate that low millimolar concentrations of the sulfide donor NaHS reversibly inhibited colonocyte mitochondrial oxygen consumption and increased gene expression of hypoxia inducible factor 1α (Hif-1α) together with inflammation-related genes namely inducible nitric oxide synthase (iNos) and interleukin-6 (Il-6). Additionally, rat colonocyte H2S detoxification capacity was severely impaired in the presence of nitric oxide. Based on the γH2AX ICW technique, NaHS did not induce DNA damage in colonocytes. Since H2S is notably produced by the gut microbiota from sulfur containing amino acids, the second objective of the study was to investigate the effects of a high protein diet (HPD) on large intestine luminal sulfide content and on the expression of genes involved in H2S detoxification in colonocytes. We found that HPD markedly increased H2S content in the large intestine but the concomitant increase of the content mass maintained the luminal sulfide concentration. HPD also provoked an increase of sulfide quinone reductase (Sqr) gene expression in colonocytes, indicating an adaptive response to increased H2S bacterial production. In conclusion, low millimolar NaHS concentration severely affects colonocyte respiration in association with increased expression of genes associated with intestinal inflammation. Although HPD increases the sulfide content of the large intestine, the colonic adaptive responses to this modification limit the epithelial exposure to this deleterious bacterial metabolite.

  16. Adaptation of the inflammatory immune response across pregnancy and postpartum in Black and White women.

    PubMed

    Gillespie, Shannon L; Porter, Kyle; Christian, Lisa M

    2016-04-01

    Pregnancy is a period of considerable physiological adaption in neuroendocrine, cardiovascular, as well as immune function. Understanding of typical changes in inflammatory immune responses during healthy pregnancy is incomplete. In addition, despite considerable racial difference in adverse pregnancy outcomes, data are lacking on potential racial differences in such adaptation. This repeated measures prospective cohort study included 37 Black and 39 White women who provided blood samples during early, mid-, and late pregnancy and 8-10 weeks postpartum. Peripheral blood mononuclear cells were incubated with lipopolysaccharide (LPS) for 24h and supernatants assayed by electrochemiluminescence to quantify interleukin(IL)-6, tumor necrosis factor(TNF)-α, IL-1β, and IL-8 production. While no changes were observed in IL-8 production over time, significant increases in IL-6, TNF-α, and IL-1β production were observed from early to late pregnancy, with subsequent declines approaching early pregnancy values at postpartum (ps<0.05). Overall, inflammatory response patterns were highly similar among Black versus White women. However, Black women had greater TNF-α production during mid-pregnancy (p=0.002) and marginally lower IL-1β production at postpartum (p=0.054). These data show a clear trajectory of change in the inflammatory immune response across pregnancy and postpartum. In this cohort of generally healthy women, Black and White women exhibited minimal differences in LPS-stimulated cytokine production across the perinatal period. Future prospective studies in Black and White women with healthy versus adverse outcomes (e.g., preeclampsia, preterm birth) would inform our understanding of the potential role of immune dysregulation in pregnant women and in relation to racial disparities in perinatal health.

  17. 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

  18. The adaptive endoplasmic reticulum stress response to lipotoxicity in progressive human nonalcoholic fatty liver disease.

    PubMed

    Lake, April D; Novak, Petr; Hardwick, Rhiannon N; Flores-Keown, Brieanna; Zhao, Fei; Klimecki, Walter T; Cherrington, Nathan J

    2014-01-01

    Nonalcoholic fatty liver disease (NAFLD) may progress from simple steatosis to severe, nonalcoholic steatohepatitis (NASH) in 7%-14% of the U.S. population through a second "hit" in the form of increased oxidative stress and inflammation. Endoplasmic reticulum (ER) stress signaling and the unfolded protein response (UPR) are triggered when high levels of lipids and misfolded proteins alter ER homeostasis creating a lipotoxic environment within NAFLD livers. The objective of this study was to determine the coordinate regulation of ER stress-associated genes in the progressive stages of human NAFLD. Human liver samples categorized as normal, steatosis, NASH (Fatty), and NASH (Not Fatty) were analyzed by individual Affymetrix GeneChip Human 1.0 ST microarrays, immunoblots, and immunohistochemistry. A gene set enrichment analysis was performed on autophagy, apoptosis, lipogenesis, and ER stress/UPR gene categories. An enrichment of downregulated genes in the ER stress-associated lipogenesis and ER stress/UPR gene categories was observed in NASH. Conversely, an enrichment of upregulated ER stress-associated genes for autophagy and apoptosis gene categories was observed in NASH. Protein expression of the adaptive liver response protein STC2 and the transcription factor X-box binding protein 1 spliced (XBP-1s) were significantly elevated among NASH samples, whereas other downstream ER stress proteins including CHOP, ATF4, and phosphorylated JNK and eIF2α were not significantly changed in disease progression. Increased nuclear accumulation of total XBP-1 protein was observed in steatosis and NASH livers. The findings reveal the presence of a coordinated, adaptive transcriptional response to hepatic ER stress in human NAFLD.

  19. Adaptive and plastic responses of Quercus petraea populations to climate across Europe.

    PubMed

    Sáenz-Romero, Cuauhtémoc; Lamy, Jean-Baptiste; Ducousso, Alexis; Musch, Brigitte; Ehrenmann, François; Delzon, Sylvain; Cavers, Stephen; Chałupka, Władysław; Dağdaş, Said; Hansen, Jon Kehlet; Lee, Steve J; Liesebach, Mirko; Rau, Hans-Martin; Psomas, Achilleas; Schneck, Volker; Steiner, Wilfried; Zimmermann, Niklaus E; Kremer, Antoine

    2016-11-25

    How temperate forests will respond to climate change is uncertain; projections range from severe decline to increased growth. We conducted field tests of sessile oak (Quercus petraea), a widespread keystone European forest tree species, including more than 150 000 trees sourced from 116 geographically diverse populations. The tests were planted on 23 field sites in six European countries, in order to expose them to a wide range of climates, including sites reflecting future warmer and drier climates. By assessing tree height and survival, our objectives were twofold: (i) to identify the source of differential population responses to climate (genetic differentiation due to past divergent climatic selection vs. plastic responses to ongoing climate change) and (ii) to explore which climatic variables (temperature or precipitation) trigger the population responses. Tree growth and survival were modeled for contemporary climate and then projected using data from four regional climate models for years 2071-2100, using two greenhouse gas concentration trajectory scenarios each. Overall, results indicated a moderate response of tree height and survival to climate variation, with changes in dryness (either annual or during the growing season) explaining the major part of the response. While, on average, populations exhibited local adaptation, there was significant clinal population differentiation for height growth with winter temperature at the site of origin. The most moderate climate model (HIRHAM5-EC; rcp4.5) predicted minor decreases in height and survival, while the most extreme model (CCLM4-GEM2-ES; rcp8.5) predicted large decreases in survival and growth for southern and southeastern edge populations (Hungary and Turkey). Other nonmarginal populations with continental climates were predicted to be severely and negatively affected (Bercé, France), while populations at the contemporary northern limit (colder and humid maritime regions; Denmark and Norway) will

  20. 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

  1. Adaptive stress response of glutathione and uric acid metabolism in man following controlled exercise and diet.

    PubMed

    Svensson, M B; Ekblom, B; Cotgreave, I A; Norman, B; Sjöberg, B; Ekblom, O; Sjödin, B; Sjödin, A

    2002-09-01

    Ergometer cycling performance as well as acute exercise-induced changes in the metabolism of energy-intermediates and glutathione (GSH) were investigated in skeletal muscle (SM) of 15 healthy young male subjects (VO(2max) approximately 54.7 mL kg(-1) min(-1), age approximately 25 years), before and after 3 days of controlled 'ìoverload-training' in combination with either high (62% of energy intake) or low (26% of energy intake) dietary intake of carbohydrates. The intake of a carbohydrate-rich diet clearly reduced the depletion of SM glycogen following the short-term training period, paralleled with a positive effect on the endurance performance, but not on high-intensity work-performance. An 'delayed over-reaching effect', defined as impaired work-performance, was observed after 2.5 days of recovery from the short-term training period, irrespective of the carbohydrate content of the diet and basal glycogen level in SM. Taken together, the main and novel findings of present investigation are: (1) an acute decrease of reduced GSH content and altered thiol-redox homeostasis in SM induced by strenuous high-intensity exercise; (2) an adaptive elevation of basal GSH level following the short-term training period; (3) an adaptive decrease of basal GSH level following 2.5 days recovery from training; (4) evidence of a relationship between the SM fibre type, physical performance capacity and GSH turnover during acute bouts of exercise; and (5) no evident effect of the level of carbohydrate intake on metabolism of GSH or energy intermediates. Furthermore, the induction of acute oxidative stress in exercising human SM and the adaptive responses to training are suggested to provide a protective antioxidant phenotype to the exercising SM during periods with repeated intense intermittent training.

  2. The immune response in the CNS in Theiler's virus induced demyelinating disease switches from an early adaptive response to a chronic innate-like response.

    PubMed

    Gilli, Francesca; Li, Libin; Pachner, Andrew R

    2016-02-01

    Theiler's murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD) is an important model of the progressive disability caused by irreversible CNS tissue injury, and provides an example of how a CNS pathogen can cause inflammation, demyelination, and neuronal damage. We were interested in which molecules, especially inflammatory mediators, might be upregulated in the CNS throughout TMEV-IDD. We quantitated by a real-time RT-PCR multi-gene system the expression of a pathway-focused panel of genes at 30 and 165 days post infection, characterizing both the early inflammatory and the late neurodegenerative stages of TMEV-IDD. Also, we measured 32 cytokines/chemokines by multiplex Luminex analysis in CSF specimens from early and late TMEV-IDD as well as sham-treated mice. Results indicate that, in the later stage of TMEV-IDD, activation of the innate immune response is most prominent: TLRs, type I IFN response genes, and innate immunity-associated cytokines were highly expressed in late TMEV-IDD compared to sham (p ≤ 0.0001) and early TMEV-IDD (p < 0.05). Conversely, several molecular mediators of adaptive immune response were highly expressed in early TMEV-IDD (all p ≤ 0.001). Protein detection in the CSF was broadly concordant with mRNA abundance of the corresponding gene measured by real-time RT-PCR in the spinal cord, since several cytokines/chemokines were increased in the CSF of TMEV-IDD mice. Results show a clear shift from adaptive to innate immunity from early to late TMEV-IDD, indicating that adaptive and innate immune pathways are likely involved in the development and progression of the disease to different extents. CSF provides an optimal source of biomarkers of CNS neuroinflammation.

  3. 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

  4. 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.

  5. Reproductive and metabolic responses of desert adapted common spiny male mice (Acomys cahirinus) to vasopressin treatment.

    PubMed

    Bukovetzky, Elena; Fares, Fuad; Schwimmer, Hagit; Haim, Abraham

    2012-08-01

    Sufficient amounts of water and food are important cues for reproduction in an unpredictable environment. We previously demonstrated that increased osmolarity levels, or exogenous vasopressin (VP) treatment halt reproduction of desert adapted golden spiny mice Acomys russatus. In this research we studied gonad regulation by VP and food restriction (FR) in desert adapted common spiny mouse (A. cahirinus) males, kept under two different photoperiod regimes-short (SD-8L:16D) and long (LD-16L:8D) days. Mice were treated with VP, FR, and VP+FR for three weeks. Response was assessed from changes in relative testis mass, serum testosterone levels and mRNA receptor gene expression of VP, aldosterone and leptin in treated groups, compared with their controls. SD-acclimation increased testosterone levels, VP treatment decreased expression of aldosterone mRNA receptor in the testes of SD-acclimated males. FR under SD-conditions resulted in testosterone decrease and elevation of VP- receptor gene expression in testes. Aldosterone receptor mRNA expression was also detected in WAT. These results support the idea that water and food availability in the habitat may be used as signals for activating the reproductive system through direct effects of VP, aldosterone and leptin on the testes or through WAT by indirect effects.

  6. The biology of developmental plasticity and the Predictive Adaptive Response hypothesis.

    PubMed

    Bateson, Patrick; Gluckman, Peter; Hanson, Mark

    2014-06-01

    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.

  7. 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

  8. 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.

  9. Importance of catalase in the adaptive response to hydrogen peroxide: analysis of acatalasaemic Saccharomyces cerevisiae.

    PubMed Central

    Izawa, S; Inoue, Y; Kimura, A

    1996-01-01

    Controversy about the importance of catalase in the detoxification of H2O2 in human erythrocytes continues. It has been suggested that catalase has no role in the clearance of H2O2 in erythrocytes. In the present study we investigated the role of catalase in the defence mechanism against oxidative stress using Saccharomyces cerevisiae. S. cerevisiae has two catalases, catalase A and catalase T. We constructed a double mutant (acatalasaemic mutant) unable to produce either catalase A or catalase T, and compared it with wild-type and single-mutant cells. The acatalasaemic mutant cells showed a similar growth rate to wild-type cells under non-oxidative stress conditions, and showed a similar susceptibility to H2O2 stress in the exponential growth phase. The acatalasaemic mutant cells at stationary phase were, however, much more sensitive to H2O2 stress than wild-type and single-mutant cells. Moreover, the ability of acatalasaemic and single-mutant cells to show adaptation to 2 mM H2O2 was distinctly inferior to that of wild-type cells. These results suggest that catalase is not essential for yeast cells under normal conditions, but plays an important role in the acquisition of tolerance to oxidative stress in the adaptive response of these cells. PMID:8947468

  10. 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

  11. Induction of adaptive response in mice exposed to 900MHz radiofrequency fields: application of micronucleus assay.

    PubMed

    Jiang, Bingcheng; Zong, Chunyan; Zhao, Hua; Ji, Yongxin; Tong, Jian; Cao, Yi

    2013-03-18

    Adult male ICR mice were pre-exposed to non-ionizing radiofrequency fields (RF), 900MHz at 120μW/cm(2) power density for 4h/day for 7 days (adaptation dose, AD) and then subjected to an acute whole body dose of 3Gy γ-radiation (challenge dose, CD). The classical micronucleus (MN) assay was used to determine the extent of genotoxicity in immature erythrocytes in peripheral blood and bone marrow. The data obtained in mice exposed to AD+CD were compared with those exposed to CD alone. The results indicated that in both tissues, the MN indices were similar in un-exposed controls and those exposed to AD alone while a significantly increased MN frequency was observed in mice exposed to CD alone. Exposure of mice to AD+CD resulted in a significant decrease in MN indices compared to those exposed to CD alone. Thus, the data suggested that pre-exposure of mice to non-ionizing RF is capable of 'protecting' the erythrocytes in the blood and bone marrow from genotoxic effects of subsequent γ-radiation. Such protective phenomenon is generally described as 'adaptive response' (AR) and is well documented in human and animal cells which were pre-exposed to very low doses of ionizing radiation. It is interesting to observe AR being induced by non-ionizing RF.

  12. 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

  13. The role of the innate and adaptive immune responses in Acanthamoeba keratitis.

    PubMed

    Niederkorn, Jerry Y

    2002-01-01

    Infections of the corneal surface are an important cause of blindness. Protozoal, viral, bacterial, and helminthic infections of the cornea account for up to 9 million cases of corneal blindness. Free-living amoebae of the genus Acanthamoeba produce a progressive infection of the cornea called Acanthamoeba keratitis. Disease is usually transmitted by Acanthamoeba trophozoites bound to soft contact lenses. Infection of the cornea is initiated when the parasite binds to the corneal epithelial surface. Recrudescence can occur and suggests that the adaptive immune response is not aroused by corneal Acanthamoeba infections. Systemic immunization with Acanthamoeba antigens elicits robust Th1 cell-mediated immunity and serum IgG antibody, yet fails to prevent the development of Acanthamoeba keratitis. However, immunization via mucosal surfaces induces anti-Acanthamoeba IgA antibodies in the tears and provides solid protection against the development of Acanthamoeba keratitis. Unlike other immune effector mechanisms that rely on cytolysis, inflammation, release of toxic molecules, or the induction of host cell death, the adaptive immune apparatus prevents Acanthamoeba infections of the cornea by simply preventing the attachment of the parasite to the epithelial surface. The beauty of this mechanism lies in its exquisite simplicity and efficacy.

  14. 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.

  15. 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

  16. 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.

  17. CD22 Regulates Adaptive and Innate Immune Responses of B Cells

    PubMed Central

    Kawasaki, Norihito; Rademacher, Christoph; Paulson, James C.

    2011-01-01

    B cells sense microenvironments through the B cell receptor (BCR) and Toll-like receptors (TLRs). While signals from BCR and TLRs synergize to distinguish self from nonself, inappropriate regulation can result in development of autoimmune disease. Here we show that CD22, an inhibitory co-receptor of BCR, also negatively regulates TLR signaling in B cells. CD22-deficient (Cd22–/–) B cells exhibit hyperactivation in response to ligands of TLRs 3, 4 and 9. Evidence suggests that this results from impaired induction of suppressors of cytokine signaling 1 and 3, well-known suppressors of TLR signaling. Antibody-mediated sequestration of CD22 on wild-type (WT) B cells augments proliferation by TLR ligands. Conversely, expression of CD22 in a Cd22–/– B cell line blunts responses to TLR ligands. We also show that lipopolysaccharide-induced transcription by nuclear factor-κB is inhibited by ectopic expression of CD22 in a TLR4 reporter cell line. Taken together, these results suggest that negative regulation of TLR signaling is an intrinsic property of CD22. Since TLRs and BCR activate B cells through different signaling pathways, and are differentially localized in B cells, CD22 exhibits a broader regulation of receptors that mediate adaptive and innate immune responses of B cells than previously recognized. PMID:21178327

  18. Evidence of bacterioplankton community adaptation in response to long-term mariculture disturbance.

    PubMed

    Xiong, Jinbo; Chen, Heping; Hu, Changju; Ye, Xiansen; Kong, Dingjiang; Zhang, Demin

    2015-10-16

    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.

  19. Adaptive immune response to lipoproteins of Staphylococcus aureus in healthy subjects

    PubMed Central

    Vu, Chi Hai; Kolata, Julia; Stentzel, Sebastian; Beyer, Anica; Gesell Salazar, Manuela; Steil, Leif; Pané‐Farré, Jan; Rühmling, Vanessa; Engelmann, Susanne; Götz, Friedrich; van Dijl, Jan Maarten; Hecker, Michael; Mäder, Ulrike; Schmidt, Frank; Völker, Uwe

    2016-01-01

    Staphylococcus aureus is a frequent commensal but also a dangerous pathogen, causing many forms of infection ranging from mild to life‐threatening conditions. Among its virulence factors are lipoproteins, which are anchored in the bacterial cell membrane. Lipoproteins perform various functions in colonization, immune evasion, and immunomodulation. These proteins are potent activators of innate immune receptors termed Toll‐like receptors 2 and 6. This study addressed the specific B‐cell and T‐cell responses directed to lipoproteins in human S. aureus carriers and non‐carriers. 2D immune proteomics and ELISA approaches revealed that titers of antibodies (IgG) binding to S. aureus lipoproteins were very low. Proliferation assays and cytokine profiling data showed only subtle responses of T cells; some lipoproteins did not elicit proliferation. Hence, the robust activation of the innate immune system by S. aureus lipoproteins does not translate into a strong adaptive immune response. Reasons for this may include inaccessibility of lipoproteins for B cells as well as ineffective processing and presentation of the antigens to T cells. PMID:27324828

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

    PubMed

    Hansen, Thomas R; Smirnova, Natalia P; Webb, Brett T; Bielefeldt-Ohmann, Helle; Sacco, Randy E; Van Campen, Hana

    2015-06-01

    Infection of pregnant cows with noncytopathic (ncp) bovine viral diarrhea virus (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 infection with ncpBVDV in the fetus has been attributed to the inability to mount an immune response before 90-150 days of gestational age. The result is 'immune tolerance', persistent viral replication and shedding of ncpBVDV. In contrast, we describe the chronic upregulation of fetal Type I interferon (IFN) pathway genes and the induction of IFN-γ pathways in fetuses of cows infected on day 75 of gestation. Persistently infected (PI) fetal IFN-γ concentrations also increased at day 97 at the peak of fetal viremia and IFN-γ mRNA was significantly elevated in fetal thymus, liver and spleen 14-22 days post maternal inoculation. PI fetuses respond to ncpBVDV infection through induction of Type I IFN and IFN-γ activated genes leading to a reduction in ncpBVDV titer. We hypothesize that fetal infection with BVDV persists because of impaired induction of IFN-γ in the face of activated Type I IFN responses. Clarification of the mechanisms involved in the IFN-associated pathways during BVDV fetal infection may lead to better detection methods, antiviral compounds and selection of genetically resistant breeding animals.

  1. Adaptive changes in echolocation sounds by Pipistrellus abramus in response to artificial jamming sounds.

    PubMed

    Takahashi, Eri; Hyomoto, Kiri; Riquimaroux, Hiroshi; Watanabe, Yoshiaki; Ohta, Tetsuo; Hiryu, Shizuko

    2014-08-15

    The echolocation behavior of Pipistrellus abramus during exposure to artificial jamming sounds during flight was investigated. Echolocation pulses emitted by the bats were recorded using a telemetry microphone mounted on the bats' backs, and their adaptation based on acoustic characteristics of emitted pulses was assessed in terms of jamming-avoidance responses (JARs). In experiment 1, frequency-modulated jamming sounds (3 ms duration) mimicking echolocation pulses of P. abramus were prepared. All bats showed significant increases in the terminal frequency of the frequency-modulated pulse by an average of 2.1-4.5 kHz when the terminal frequency of the jamming sounds was lower than the bats' own pulses. This frequency shift was not observed using jamming frequencies that overlapped with or were higher than the bats' own pulses. These findings suggest that JARs in P. abramus are sensitive to the terminal frequency of jamming pulses and that the bats' response pattern was dependent on the slight difference in stimulus frequency. In experiment 2, when bats were repeatedly exposed to a band-limited noise of 70 ms duration, the bats in flight more frequently emitted pulses during silent periods between jamming sounds, suggesting that the bats could actively change the timing of pulse emissions, even during flight, to avoid temporal overlap with jamming sounds. Our findings demonstrate that bats could adjust their vocalized frequency and emission timing during flight in response to acoustic jamming stimuli.

  2. Function-blocking ERBB3 antibody inhibits the adaptive response to RAF inhibitor

    PubMed Central

    Kugel, Curtis H.; Hartsough, Edward J.; Davies, Michael A.; Setiady, Yulius Y.; Aplin, Andrew E.

    2014-01-01

    ERBB3/HER3 expression and signaling is upregulated in mutant BRAF melanoma as an adaptive, pro-survival response to FDA-approved RAF inhibitors. Since compensatory ERBB3 signaling counteracts the effects of RAF inhibitors, co-targeting ERBB3 may increase the efficacy of RAF inhibitors in mutant BRAF models of melanoma. Here we corroborate this concept by showing that the ERBB3 function-blocking monoclonal antibody huHER3-8 can inhibit neuregulin-1 (NRG1) activation of ERBB3 and downstream signaling in RAF-inhibited melanoma cells. Targeting mutant BRAF in combination with huHER3-8 decreased cell proliferation and increased cell death in vitro, and decreased tumor burden in vivo, compared to targeting either mutant BRAF or ERBB3 alone. Further, the likelihood of a durable tumor response in vivo was increased when huHER3-8 was combined with RAF inhibitor PLX4720. Together, these results offer a preclinical proof of concept for the application of ERBB3 neutralizing antibodies to enhance the efficacy of RAF inhibitors in melanoma to delay or prevent tumor re-growth. Insofar as ERBB3 is often upregulated in response to other kinase-targeted therapeutics, findings may have implications for other cancers as well. PMID:25035390

  3. 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

  4. 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.

  5. Adaptive Response and Tolerance to Weak Acids in Saccharomyces cerevisiae: A Genome-Wide View

    PubMed Central

    Mira, Nuno P.; Teixeira, Miguel Cacho

    2010-01-01

    Abstract 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. PMID:20955006

  6. Acute and adaptive motor responses to caffeine in adolescent and adult rats.

    PubMed

    Rhoads, Dennis E; Huggler, April L; Rhoads, Lucas J

    2011-07-01

    Caffeine is a psychostimulant with intake through foods or beverages tending to increase from childhood through adolescence. The goals of the present study were to examine the effects of caffeine on young adolescent Long-Evans rats and to compare the motor-behavioral responses of adolescent and adult rats to acute and chronic caffeine. Adolescent rats had a biphasic dose-response to caffeine comparable to that reported for adult rats. The magnitude of the motor response to a challenge dose of caffeine (30mg/kg, ip) was similar between adolescent and adult rats. Administration of caffeine in the drinking water (1mg/ml) for a period of 2 weeks led to overall consumption of caffeine which was not significantly different between adolescents and adults when normalized to body mass. There were no impacts of caffeinated drinking water on volume of fluid consumed nor weight gain in either age group compared to age matched controls drinking non-caffeinated tap water. Following this period of caffeine consumption, return to regular drinking water (caffeine withdrawal) led to a significant decrease in baseline movement compared to caffeine-naïve rats. This effect inversion was observed for adolescents but not adults. In addition, the response of the adolescents to the challenge dose of caffeine (30mg/kg, ip) was reduced significantly after chronic caffeine consumption and withdrawal. This apparent tolerance to the caffeine challenge dose was not seen with the adults. Thus, the developing brain of these adolescents may show similar sensitivity to adults in acute caffeine exposure but greater responsiveness to adaptive changes associated with chronic caffeine consumption.

  7. 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

  8. Nonlinear structural response using adaptive dynamic relaxation on a massively-parallel-processing system

    NASA Technical Reports Server (NTRS)

    Oakley, David R.; Knight, Norman F., Jr.

    1994-01-01

    A parallel adaptive dynamic relaxation (ADR) algorithm has been developed for nonlinear structural analysis. This algorithm has minimal memory requirements, is easily parallelizable and scalable to many processors, and is generally very reliable and efficient for highly nonlinear problems. Performance evaluations on single-processor computers have shown that the ADR algorithm is reliable and highly vectorizable, and that it is competitive with direct solution methods for the highly nonlinear problems considered. The present algorithm is implemented on the 512-processor Intel Touchstone DELTA system at Caltech, and it is designed to minimize the extent and frequency of interprocessor communication. The algorithm has been used to solve for the nonlinear static response of two and three dimensional hyperelastic systems involving contact. Impressive relative speedups have been achieved and demonstrate the high scalability of the ADR algorithm. For the class of problems addressed, the ADR algorithm represents a very promising approach for parallel-vector processing.

  9. Statistical inference for response adaptive randomization procedures with adjusted optimal allocation proportions.

    PubMed

    Zhu, Hongjian

    2016-12-12

    Seamless phase II/III clinical trials have attracted increasing attention recently. They mainly use Bayesian response adaptive randomization (RAR) designs. There has been little research into seamless clinical trials using frequentist RAR designs because of the difficulty in performing valid statistical inference following this procedure. The well-designed frequentist RAR designs can target theoretically optimal allocation proportions, and they have explicit asymptotic results. In this paper, we study the asymptotic properties of frequentist RAR designs with adjusted target allocation proportions, and investigate statistical inference for this procedure. The properties of the proposed design provide an important theoretical foundation for advanced seamless clinical trials. Our numerical studies demonstrate that the design is ethical and efficient.

  10. 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

  11. MSG5, a novel protein phosphatase promotes adaptation to pheromone response in S. cerevisiae.

    PubMed Central

    Doi, K; Gartner, A; Ammerer, G; Errede, B; Shinkawa, H; Sugimoto, K; Matsumoto, K

    1994-01-01

    Pheromone-stimulated yeast cells and haploid gpa1 deletion mutants arrest their cell cycle in G1. Overexpression of a novel gene called MSG5 suppresses this inhibition of cell division. Loss of MSG5 function leads to a diminished adaptive response to pheromone. Genetic analysis indicates that MSG5 acts at a stage where the protein kinases STE7 and FUS3 function to transmit the pheromone-induced signal. Since loss of MSG5 function causes an increase in FUS3 enzyme activity but not STE7 activity, we propose that MSG5 impinges on the pathway at FUS3. Sequence analysis suggests that MSG5 encodes a protein tyrosine phosphatase. This is supported by the finding that recombinant MSG5 has phosphatase activity in vitro and is able to inactivate autophosphorylated FUS3. Thus MSG5 might stimulate recovery from pheromone by regulating the phosphorylation state of FUS3. Images PMID:8306972

  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. PACAP is essential for the adaptive thermogenic response of brown adipose tissue to cold exposure.

    PubMed

    Diané, Abdoulaye; Nikolic, Nikolina; Rudecki, Alexander P; King, Shannon M; Bowie, Drew J; Gray, Sarah L

    2014-09-01

    Pituitary adenylate cyclase-activating polypeptide (PACAP) is a widely distributed neuropeptide that acts as a neurotransmitter, neuromodulator, neurotropic factor, neuroprotectant, secretagogue, and neurohormone. Owing to its pleiotropic biological actions, knockout of Pacap (Adcyap1) has been shown to induce several abnormalities in mice such as impaired thermoregulation. However, the underlying physiological and molecular mechanisms remain unclear. A previous report has shown that cold-exposed Pacap null mice cannot supply appropriate levels of norepinephrine (NE) to brown adipocytes. Therefore, we hypothesized that exogenous NE would rescue the impaired thermogenic response of Pacap null mice during cold exposure. We compared the adaptive thermogenic capacity of Pacap(-/-) to Pacap(+/+) mice in response to NE when housed at room temperature (24 °C) and after a 3.5-week cold exposure (4 °C). Biochemical parameters, expression of thermogenic genes, and morphological properties of brown adipose tissue (BAT) and white adipose tissue (WAT) were also characterized. Results showed that there was a significant effect of temperature, but no effect of genotype, on the resting metabolic rate in conscious, unrestrained mice. However, the normal cold-induced increase in the basal metabolic rate and NE-induced increase in thermogenesis were severely blunted in cold-exposed Pacap(-/-) mice. These changes were associated with altered substrate utilization, reduced β3-adrenergic receptor (β3-Ar (Adrb3)) and hormone-sensitive lipase (Hsl (Lipe)) gene expression, and increased fibroblast growth factor 2 (Fgf2) gene expression in BAT. Interestingly, Pacap(-/-) mice had depleted WAT depots, associated with upregulated uncoupling protein 1 expression in inguinal WATs. These results suggest that the impairment of adaptive thermogenesis in Pacap null mice cannot be rescued by exogenous NE perhaps in part due to decreased β3-Ar-mediated BAT activation.

  14. Survival response to increased ceramide involves metabolic adaptation through novel regulators of glycolysis and lipolysis.

    PubMed

    Nirala, Niraj K; Rahman, Motiur; Walls, Stanley M; Singh, Alka; Zhu, Lihua Julie; Bamba, Takeshi; Fukusaki, Eiichiro; Srideshikan, Sargur M; Harris, Greg L; Ip, Y Tony; Bodmer, Rolf; Acharya, Usha R

    2013-06-01

    The sphingolipid ceramide elicits several stress responses, however, organisms survive despite increased ceramide but how they do so is poorly understood. We demonstrate here that the AKT/FOXO pathway regulates survival in increased ceramide environment by metabolic adaptation involving changes in glycolysis and lipolysis through novel downstream targets. We show that ceramide kinase mutants accumulate ceramide and this leads to reduction in energy levels due to compromised oxidative phosphorylation. Mutants show increased activation of Akt and a consequent decrease in FOXO levels. These changes lead to enhanced glycolysis by upregulating the activity of phosphoglyceromutase, enolase, pyruvate kinase, and lactate dehydrogenase to provide energy. A second major consequence of AKT/FOXO reprogramming in the mutants is the increased mobilization of lipid from the gut through novel lipase targets, CG8093 and CG6277 for energy contribution. Ubiquitous reduction of these targets by knockdown experiments results in semi or total lethality of the mutants, demonstrating the importance of activating them. The efficiency of these adaptive mechanisms decreases with age and leads to reduction in adult life span of the mutants. In particular, mutants develop cardiac dysfunction with age, likely reflecting the high energy requirement of a well-functioning heart. The lipases also regulate physiological triacylglycerol homeostasis and are important for energy metabolism since midgut specific reduction of them in wild type flies results in increased sensitivity to starvation and accumulation of triglycerides leading to cardiac defects. The central findings of increased AKT activation, decreased FOXO level and activation of phosphoglyceromutase and pyruvate kinase are also observed in mice heterozygous for ceramide transfer protein suggesting a conserved role of this pathway in mammals. These data reveal novel glycolytic and non-autonomous lipolytic pathways in response to increased

  15. Graded-threshold parametric response maps: towards a strategy for adaptive dose painting

    NASA Astrophysics Data System (ADS)

    Lausch, A.; Jensen, N.; Chen, J.; Lee, T. Y.; Lock, M.; Wong, E.

    2014-03-01

    Purpose: To modify the single-threshold parametric response map (ST-PRM) method for predicting treatment outcomes in order to facilitate its use for guidance of adaptive dose painting in intensity-modulated radiotherapy. Methods: Multiple graded thresholds were used to extend the ST-PRM method (Nat. Med. 2009;15(5):572-576) such that the full functional change distribution within tumours could be represented with respect to multiple confidence interval estimates for functional changes in similar healthy tissue. The ST-PRM and graded-threshold PRM (GT-PRM) methods were applied to functional imaging scans of 5 patients treated for hepatocellular carcinoma. Pre and post-radiotherapy arterial blood flow maps (ABF) were generated from CT-perfusion scans of each patient. ABF maps were rigidly registered based on aligning tumour centres of mass. ST-PRM and GT-PRM analyses were then performed on overlapping tumour regions within the registered ABF maps. Main findings: The ST-PRMs contained many disconnected clusters of voxels classified as having a significant change in function. While this may be useful to predict treatment response, it may pose challenges for identifying boost volumes or for informing dose-painting by numbers strategies. The GT-PRMs included all of the same information as ST-PRMs but also visualized the full tumour functional change distribution. Heterogeneous clusters in the ST-PRMs often became more connected in the GT-PRMs by voxels with similar functional changes. Conclusions: GT-PRMs provided additional information which helped to visualize relationships between significant functional changes identified by ST-PRMs. This may enhance ST-PRM utility for guiding adaptive dose painting.

  16. 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

  17. Phylogeny of Toll-Like Receptor Signaling: Adapting the Innate Response

    PubMed Central

    Roach, Jeffrey M.; Racioppi, Luigi; Jones, Corbin D.; Masci, Anna Maria

    2013-01-01

    The Toll-like receptors represent a largely evolutionarily conserved pathogen recognition machinery responsible for recognition of bacterial, fungal, protozoan, and viral pathogen associated microbial patterns and initiation of inflammatory response. Structurally the Toll-like receptors are comprised of an extracellular leucine rich repeat domain and a cytoplasmic Toll/Interleukin 1 receptor domain. Recognition takes place in the extracellular domain where as the cytoplasmic domain triggers a complex signal network required to sustain appropriate immune response. Signal transduction is regulated by the recruitment of different intracellular adaptors. The Toll-like receptors can be grouped depending on the usage of the adaptor, MyD88, into MyD88-dependent and MyD88 independent subsets. Herein, we present a unique phylogenetic analysis of domain regions of these receptors and their cognate signaling adaptor molecules. Although previously unclear from the phylogeny of full length receptors, these analyses indicate a separate evolutionary origin for the MyD88-dependent and MyD88-independent signaling pathway and provide evidence of a common ancestor for the vertebrate and invertebrate orthologs of the adaptor molecule MyD88. Together these observations suggest a very ancient origin of the MyD88-dependent pathway Additionally we show that early duplications gave rise to several adaptor molecule families. In some cases there is also strong pattern of parallel duplication between adaptor molecules and their corresponding TLR. Our results further support the hypothesis that phylogeny of specific domains involved in signaling pathway can shed light on key processes that link innate to adaptive immune response. PMID:23326591

  18. Rhesus Monkeys (Macaca mulatta) Adaptively Adjust Information Seeking in Response to Information Accumulated

    PubMed Central

    Tu, Hsiao-Wei; Pani, Alex A.; Hampton, Robert R.

    2015-01-01

    Metacognition consists of monitoring and control processes. Monitoring has been inferred when nonhumans use a “decline test” response to selectively escape difficult test trials. Cognitive control has been inferred from selective information seeking behavior by nonhumans ignorant of needed knowledge. Here we describe a computerized paradigm that extends previous work and begins to assess dynamic interactions between monitoring and control. Monkeys classified images as containing birds, fish, flowers, or people. To-be-classified images were initially masked, and monkeys were trained to gradually reveal the images by touching a “reveal button.” Monkeys could choose to classify images at any time or to reveal more of the images. Thus, they had the opportunity to assess when enough of an image had been revealed to support accurate classification. In Experiment 1, monkeys made more reveal responses before classifying when smaller amounts of the image were revealed by each button touch. In Experiment 2, to-be-classified images were shrunken and covered by one critical blocker among other blockers that did not provide information when removed. Monkeys made more reveal responses as the critical blocker was removed later in the trial. In Experiment 3, monkeys were re-presented with previously classified images with either more or fewer blockers obscuring the image than was the case when they chose to classify that image previously. Monkeys made more reveal responses when information was insufficient compared to when it was excessive. These results indicate that monkeys dynamically monitor evolving decision processes and adaptively collect information as necessary to maintain accuracy. PMID:26280597

  19. Insights into yeast adaptive response to the agricultural fungicide mancozeb: a toxicoproteomics approach.

    PubMed

    Santos, Pedro M; Simões, Tânia; Sá-Correia, Isabel

    2009-02-01

    Toxicogenomics has the potential to elucidate gene-environment interactions to identify genes that are affected by a particular chemical at the early stages of the toxicological response and to establish parallelisms between different organisms. The fungicide mancozeb, widely used in agriculture, is an ethylene-bis-dithiocarbamate complex with manganese and zinc. Exposure to this pesticide has been linked to the development of idiopathic Parkinson's disease and cancer. Given that many signalling pathways and their molecular components are substantially conserved among eukaryotic organisms, we used Saccharomyces cerevisiae to get insights into the molecular mechanisms of mancozeb toxicity and adaptation based on expression proteomics. The early global response to mancozeb was analysed by quantitative proteomics using 2-DE. The target genes (e.g. TSA1, TSA2, SOD1, SOD2, AHP1, GRE2, GRX1, CYS3, PRE3, PRE6, PRE8, PRE9, EFT1, RPS5, TIF11, HSP31, HSP26, HSP104, HSP60, HSP70-family) and the putative main transcription activators (e.g. Yap1, Msn2/Msn4, Met4, Hsf1, Aft1, Pdr1, Skn7, Rpn4p, Gcn4) of the complex mancozeb-induced expression changes are related with yeast response to stress, in particular to oxidative stress, protein translation initiation and protein folding, disassembling of protein aggregates and degradation of damaged proteins. Our results also suggest that this study provided powerful indications that may be useful to expand the knowledge obtained in yeast not only to the global response to mancozeb toxicity in phytopathogenic fungi but also to humans.

  20. 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

  1. 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.

  2. 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.

  3. Innate-Adaptive Crosstalk: How Dendritic Cells Shape Immune Responses in the CNS

    PubMed Central

    Héninger, Erika; Harris, Melissa G; Lee, JangEun; Sandor, Matyas; Fabry, Zsuzsanna

    2013-01-01

    Dendritic cells (DCs) are a heterogeneous group of professional antigen presenting cells that lie in a nexus between innate and adaptive immunity because they recognize and respond to danger signals and subsequently initiate and regulate effector T-cell responses. Initially thought to be absent from the CNS, both plasmacytoid and conventional DCs as well as DC precursors have recently been detected in several CNS compartments where they are seemingly poised for responding to injury and pathogens. Additionally, monocyte-derived DCs rapidly accumulate in the inflamed CNS where they, along with other DC subsets, may function to locally regulate effector T-cells and/or carry antigens to CNS-draining cervical lymph nodes. In this review we highlight recent research showing that (a) distinct inflammatory stimuli differentially recruit DC subsets to the CNS; (b) DC recruitment across the blood-brain barrier (BBB) is regulated by adhesion molecules, growth factors, and chemokines; and (c) DCs positively or negatively regulate immune responses in the CNS. PMID:21948376

  4. 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.

  5. Platelets: versatile modifiers of innate and adaptive immune responses to transplants

    PubMed Central

    Baldwin, William M; Kuo, Hsiao-Hsuan; Morrell, Craig N

    2011-01-01

    Purpose of review Over the last decade, there has been mounting experimental data demonstrating that platelets contribute to acute vascular inflammation and atherosclerosis. This review focuses on recent findings that link platelets to inflammatory responses of relevance to transplants. Recent findings Although it has been known that platelets modify vascular inflammation by secretion of soluble mediators and release of microparticles, new aspects of these mechanisms are being defined. For example, platelet-derived RANTES (CCL5) not only functions in homomers, but also forms more potent heteromers with Platelet Factor 4 (CXCL4). This heteromer formation can be inhibited with small molecules. New findings also demonstrate heterologous interactions of platelet microparticles with leukocytes that may increase their range of impact. By attaching to neutrophils, platelet microparticles appear to migrate out of blood vessels and into other compartments where they stimulate secretion of cytokines. Contact of platelets with extracellular matrix also can result in cleavage of hyaluronan into fragments that serve as an endogenous danger signal. Summary Recent findings have expanded the range of interactions by which platelets can modify innate and adaptive immune responses to transplants. PMID:21157344

  6. Gentiana asclepiadea and Armoracia rusticana can modulate the adaptive response induced by zeocin in human lymphocytes.

    PubMed

    Hudecova, A; Hasplova, K; Kellovska, L; Ikreniova, M; Miadokova, E; Galova, E; Horvathova, E; Vaculcikova, D; Gregan, F; Dusinska, M

    2012-01-01

    Zeocin is a member of bleomycin/phleomycin family of antibiotics isolated from Streptomyces verticullus. This unique radiomimetic antibiotic is known to bind to DNA and induce oxidative stress in different organisms producing predominantly single- and double- strand breaks, as well as a DNA base loss resulting in apurinic/apyrimidinic (AP) sites. The aim of this study was to induce an adaptive response (AR) by zeocin in freshly isolated human lymphocytes from blood and to observe whether plant extracts could modulate this response. The AR was evaluated by the comet assay. The optimal conditions for the AR induction and modulation were determined as: 2 h-intertreatment time (in PBS, at 4°C) given after a priming dose (50 µg/ml) of zeocin treatment. Genotoxic impact of zeocin to lymphocytes was modulated by plant extracts isolated from Gentiana asclepiadea (methanolic and aqueous haulm extracts, 0.25 mg/ml) and Armoracia rusticana (methanolic root extract, 0.025 mg/ml). These extracts enhanced the AR and also decreased DNA damage caused by zeocin (after 0, 1 and 4 h-recovery time after the test dose of zeocin application) to more than 50%. These results support important position of plants containing many biologically active compounds in the field of pharmacology and medicine.

  7. Transcription factor ATF3 links host adaptive response to breast cancer metastasis

    PubMed Central

    Wolford, Chris C.; McConoughey, Stephen J.; Jalgaonkar, Swati P.; Leon, Marino; Merchant, Anand S.; Dominick, Johnna L.; Yin, Xin; Chang, Yiseok; Zmuda, Erik J.; O’Toole, Sandra A.; Millar, Ewan K.A.; Roller, Stephanie L.; Shapiro, Charles L.; Ostrowski, Michael C.; Sutherland, Robert L.; Hai, Tsonwin

    2013-01-01

    Host response to cancer signals has emerged as a key factor in cancer development; however, the underlying molecular mechanism is not well understood. In this report, we demonstrate that activating transcription factor 3 (ATF3), a hub of the cellular adaptive response network, plays an important role in host cells to enhance breast cancer metastasis. Immunohistochemical analysis of patient tumor samples revealed that expression of ATF3 in stromal mononuclear cells, but not cancer epithelial cells, is correlated with worse clinical outcomes and is an independent predictor for breast cancer death. This finding was corroborated by data from mouse models showing less efficient breast cancer metastasis in Atf3-deficient mice than in WT mice. Further, mice with myeloid cell–selective KO of Atf3 showed fewer lung metastases, indicating that host ATF3 facilitates metastasis, at least in part, by its function in macrophage/myeloid cells. Gene profiling analyses of macrophages from mouse tumors identified an ATF3-regulated gene signature that could distinguish human tumor stroma from distant stroma and could predict clinical outcomes, lending credence to our mouse models. In conclusion, we identified ATF3 as a regulator in myeloid cells that enhances breast cancer metastasis and has predictive value for clinical outcomes. PMID:23921126

  8. The adaptation and implementation of guidelines for responsible media reporting on suicide in Slovenia

    PubMed Central

    Tančič Grum, Alenka; Poštuvan, Vita; Podlesek, Anja; De Leo, Diego

    2017-01-01

    Abstract Introduction The existing literature provides evidence of the link between media reporting and suicide in terms of either preventive or provocative effects. Hence, working with media representatives on responsible reporting on suicide is of great importance. Until recently in Slovenia, there has been an obvious lack of communication between media representatives and suicidologists. The aims of the present study were twofold; firstly, to introduce the adaptation and dissemination of intervention on responsible media reporting, and secondly, to evaluate the effectiveness of the implemented intervention on suicide reporting. Methods We used a pre-post research design. Newspaper articles were retrieved over two 12-month periods: the baseline period and the follow-up period. In between, we had a year of implementation of our intervention program (launching and disseminating the Guidelines via workshops). Each retrieved article was rated qualitatively with respect to its adherence to the Guidelines. Results The comparison of baseline and follow-up periods revealed some significant differences. Reporting in the follow-up period was less sensationalistic, there was less reporting about specific cases of suicides and more about causes of suicide and pathways out of mental distress. Furthermore, in the follow-up period, there was a significant improvement related to headlines of media articles. Contact information about where to seek help was more often included in the articles. Conclusion The findings are promising, but working with the media needs to be continuous and ongoing if sustainable results are to be achieved. PMID:28289461

  9. Adaptive Immune Responses to Zika Virus Are Important for Controlling Virus Infection and Preventing Infection in Brain and Testes.

    PubMed

    Winkler, Clayton W; Myers, Lara M; Woods, Tyson A; Messer, Ronald J; Carmody, Aaron B; McNally, Kristin L; Scott, Dana P; Hasenkrug, Kim J; Best, Sonja M; Peterson, Karin E

    2017-03-22

    The recent association between Zika virus (ZIKV) and neurologic complications, including Guillain-Barré syndrome in adults and CNS abnormalities in fetuses, highlights the importance in understanding the immunological mechanisms controlling this emerging infection. Studies have indicated that ZIKV evades the human type I IFN response, suggesting a role for the adaptive immune response in resolving infection. However, the inability of ZIKV to antagonize the mouse IFN response renders the virus highly susceptible to circulating IFN in murine models. Thus, as we show in this article, although wild-type C57BL/6 mice mount cell-mediated and humoral adaptive immune responses to ZIKV, these responses were not required to prevent disease. However, when the type I IFN response of mice was suppressed, then the adaptive immune responses became critical. For example, when type I IFN signaling was blocked by Abs in Rag1(-/-) mice, the mice showed dramatic weight loss and ZIKV infection in the brain and testes. This phenotype was not observed in Ig-treated Rag1(-/-) mice or wild-type mice treated with anti-type I IFNR alone. Furthermore, we found that the CD8(+) T cell responses of pregnant mice to ZIKV infection were diminished compared with nonpregnant mice. It is possible that diminished cell-mediated immunity during pregnancy could increase virus spread to the fetus. These results demonstrate an important role for the adaptive immune response in the control of ZIKV infection and imply that vaccination may prevent ZIKV-related disease, particularly when the type I IFN response is suppressed as it is in humans.

  10. 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…

  11. Progesterone-based contraceptives reduce adaptive immune responses and protection against sequential influenza A virus infections.

    PubMed

    Hall, Olivia J; Nachbagauer, Raffael; Vermillion, Meghan S; Fink, Ashley L; Phuong, Vanessa; Krammer, Florian; Klein, Sabra L

    2017-02-08

    In addition to their intended use, progesterone (P4)-based contraceptives promote anti-inflammatory immune responses, yet their effects on the outcome of infectious diseases, including influenza A virus (IAV), are rarely evaluated. To evaluate their impact on immune responses to sequential IAV infections, adult female mice were treated with placebo or one of two progestins, P4 or levonorgestrel (LNG), and infected with mouse adapted (ma) H1N1 virus. Treatment with P4 or LNG reduced morbidity, but had no effect on pulmonary virus titers, during primary H1N1 infection as compared to placebo treatment. In serum and bronchoalveolar lavage fluid, total anti-IAV IgG and IgA titers and virus neutralizing antibody titers, but not hemagglutinin stalk antibody titers, were lower in progestin-treated mice as compared with placebo-treated mice. Females were challenged six weeks later with either a maH1N1 drift variant (maH1N1dv) or maH3N2 IAV. Protection following infection with the maH1N1dv was similar among all groups. In contrast, following challenge with maH3N2, progestin treatment reduced survival as well as numbers and activity of H1N1- and H3N2-specific memory CD8+ T cells, including tissue resident cells, compared with placebo treatment. In contrast to primary IAV infection, progestin treatment increased neutralizing and IgG antibody titers against both challenge viruses compared with placebo treatment. While the immunomodulatory properties of progestins protected naïve females against severe outcome from IAV infection, it made them more susceptible to secondary challenge with a heterologous IAV, despite improving their antibody responses against a secondary IAV infection. Taken together, the immunomodulatory effects of progestins differentially regulate the outcome of infection depending on exposure history.IMPORTANCE The impact of hormone-based contraceptives on the outcome of infectious diseases outside of the reproductive tract is rarely considered. Using a mouse

  12. Organizational changes to thyroid regulation in Alligator mississippiensis: evidence for predictive adaptive responses.

    PubMed

    Boggs, Ashley S P; Lowers, Russell H; Cloy-McCoy, Jessica A; Guillette, Louis J

    2013-01-01

    During embryonic development, organisms are sensitive to changes in thyroid hormone signaling which can reset the hypothalamic-pituitary-thyroid axis. It has been hypothesized that this developmental programming is a 'predictive adaptive response', a physiological adjustment in accordance with the embryonic environment that will best aid an individual's survival in a similar postnatal environment. When the embryonic environment is a poor predictor of the external environment, the developmental changes are no longer adaptive and can result in disease states. We predicted that endocrine disrupting chemicals (EDCs) and environmentally-based iodide imbalance could lead to developmental changes to the thyroid axis. To explore whether iodide or EDCs could alter developmental programming, we collected American alligator eggs from an estuarine environment with high iodide availability and elevated thyroid-specific EDCs, a freshwater environment contaminated with elevated agriculturally derived EDCs, and a reference freshwater environment. We then incubated them under identical conditions. We examined plasma thyroxine and triiodothyronine concentrations, thyroid gland histology, plasma inorganic iodide, and somatic growth at one week (before external nutrition) and ten months after hatching (on identical diets). Neonates from the estuarine environment were thyrotoxic, expressing follicular cell hyperplasia (p = 0.01) and elevated plasma triiodothyronine concentrations (p = 0.0006) closely tied to plasma iodide concentrations (p = 0.003). Neonates from the freshwater contaminated site were hypothyroid, expressing thyroid follicular cell hyperplasia (p = 0.01) and depressed plasma thyroxine concentrations (p = 0.008). Following a ten month growth period under identical conditions, thyroid histology (hyperplasia p = 0.04; colloid depletion p = 0.01) and somatic growth (body mass p<0.0001; length p = 0.02) remained altered among the contaminated

  13. Adaptive responses to dasatinib-treated lung squamous cell cancer cells harboring DDR2 mutations.

    PubMed

    Bai, Yun; Kim, Jae-Young; Watters, January M; Fang, Bin; Kinose, Fumi; Song, Lanxi; Koomen, John M; Teer, Jamie K; Fisher, Kate; Chen, Yian Ann; Rix, Uwe; Haura, Eric B

    2014-12-15

    DDR2 mutations occur in approximately 4% of lung squamous cell cancer (SCC) where the tyrosine kinase inhibitor dasatinib has emerged as a new therapeutic option. We found that ERK and AKT phosphorylation was weakly inhibited by dasatinib in DDR2-mutant lung SCC cells, suggesting that dasatinib inhibits survival signals distinct from other oncogenic receptor tyrosine kinases (RTK) and/or compensatory signals exist that dampen dasatinib activity. To gain better insight into dasatinib's action in these cells, we assessed altered global tyrosine phosphorylation (pY) after dasatinib exposure using a mass spectrometry-based quantitative phosphoproteomics approach. Overlaying protein-protein interaction relationships upon this dasatinib-regulated pY network revealed decreased phosphorylation of Src family kinases and their targets. Conversely, dasatinib enhanced tyrosine phosphorylation in a panel of RTK and their signaling adaptor complexes, including EGFR, MET/GAB1, and IGF1R/IRS2, implicating a RTK-driven adaptive response associated with dasatinib. To address the significance of this observation, these results were further integrated with results from a small-molecule chemical library screen. We found that dasatinib combined with MET and insulin-like growth factor receptor (IGF1R) inhibitors had a synergistic effect, and ligand stimulation of EGFR and MET rescued DDR2-mutant lung SCC cells from dasatinib-induced loss of cell viability. Importantly, we observed high levels of tyrosine-phosphorylated EGFR and MET in a panel of human lung SCC tissues harboring DDR2 mutations. Our results highlight potential RTK-driven adaptive-resistant mechanisms upon DDR2 targeting, and they suggest new, rationale cotargeting strategies for DDR2-mutant lung SCC.

  14. 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

  15. Nitric oxide evokes an adaptive response to oxidative stress by arresting respiration.

    PubMed

    Husain, Maroof; Bourret, Travis J; McCollister, Bruce D; Jones-Carson, Jessica; Laughlin, James; Vázquez-Torres, Andrés

    2008-03-21

    Aerobic metabolism generates biologically challenging reactive oxygen species (ROS) by the endogenous autooxidation of components of the electron transport chain (ETC). Basal levels of oxidative stress can dramatically rise upon activation of the NADPH oxidase-dependent respiratory burst. To minimize ROS toxicity, prokaryotic and eukaryotic organisms express a battery of low-molecular-weight thiol scavengers, a legion of detoxifying catalases, peroxidases, and superoxide dismutases, as well as a variety of repair systems. We present herein blockage of bacterial respiration as a novel strategy that helps the intracellular pathogen Salmonella survive extreme oxidative stress conditions. A Salmonella strain bearing mutations in complex I NADH dehydrogenases is refractory to the early NADPH oxidase-dependent antimicrobial activity of IFNgamma-activated macrophages. The ability of NADH-rich, complex I-deficient Salmonella to survive oxidative stress is associated with resistance to peroxynitrite (ONOO(-)) and hydrogen peroxide (H(2)O(2)). Inhibition of respiration with nitric oxide (NO) also triggered a protective adaptive response against oxidative stress. Expression of the NDH-II dehydrogenase decreases NADH levels, thereby abrogating resistance of NO-adapted Salmonella to H(2)O(2). NADH antagonizes the hydroxyl radical (OH(.)) generated in classical Fenton chemistry or spontaneous decomposition of peroxynitrous acid (ONOOH), while fueling AhpCF alkylhydroperoxidase. Together, these findings identify the accumulation of NADH following the NO-mediated inhibition of Salmonella's ETC as a novel antioxidant strategy. NO-dependent respiratory arrest may help mitochondria and a plethora of organisms cope with oxidative stress engendered in situations as diverse as aerobic respiration, ischemia reperfusion, and inflammation.

  16. 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

  17. 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

  18. 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

  19. Modulation of Innate and Adaptive Immune Responses by Tofacitinib (CP-690,550)

    PubMed Central

    Ghoreschi, Kamran; Jesson, Michael I.; Li, Xiong; Lee, Jamie L.; Ghosh, Sarbani; Alsup, Jason W.; Warner, James D.; Tanaka, Masao; Steward-Tharp, Scott M.; Gadina, Massimo; Thomas, Craig; Minnerly, John C.; Storer, Chad E.; LaBranche, Timothy P.; Radi, Zaher A.; Dowty, Martin E.; Head, Richard D.; Meyer, Debra M.; Kishore, Nandini; O'Shea, John J.

    2011-01-01

    Inhibitors of the JAK family of non-receptor tyrosine kinases have demonstrated clinical efficacy in rheumatoid arthritis and other inflammatory disorders; however, the precise mechanisms by which JAK inhibition improves inflammatory immune responses remain unclear. Here we examined the mode of action of tofacitinib (CP-690,550) on JAK/STAT signaling pathways involved in adaptive and innate immune responses. To determine the extent of inhibition of specific JAK/STAT-dependent pathways, we analyzed cytokine stimulation of mouse and human T cells in vitro. We also investigated the consequences of CP-690,550 treatment on Th cell differentiation of naïve murine CD4+ T cells. CP-690,550 inhibited IL-4-dependent Th2 cell differentiation, and interestingly also interfered with Th17 cell differentiation. Expression of IL-23 receptor and of the Th17 cytokines IL-17A, IL-17F and IL-22 were blocked when naïve Th cells were stimulated with IL-6 and IL-23. In contrast, IL-17A-production was enhanced when Th17 cells were differentiated in the presence of TGF-β. Moreover, CP-690,550 also prevented activation of STAT1, induction of T-bet and subsequent generation of Th1 cells. In a model of established arthritis, CP-690,550 rapidly improved disease by inhibiting production of inflammatory mediators and suppressing STAT1-dependent genes in joint tissue. Furthermore, efficacy in this disease model correlated with inhibition of both JAK1 and JAK3 signaling pathways. CP-690,550 also modulated innate responses to LPS in vivo through a mechanism likely involving inhibition of STAT1 signaling. Thus, CP-690,550 may improve autoimmune diseases and prevent transplant rejection by suppressing the differentiation of pathogenic Th1 and Th17 cells, as well as innate immune cell signaling. PMID:21383241

  20. Hypoxia Inducible Factor 1α Promotes Endogenous Adaptive Response in Rat Model of Chronic Cerebral Hypoperfusion

    PubMed Central

    Yang, Ying; Ju, Jieyang; Deng, Min; Wang, Jing; Liu, Hui; Xiong, Li; Zhang, Junjian

    2017-01-01

    Hypoxia inducible factor 1α (HIF-1α), a pivotal regulator of gene expression in response to hypoxia and ischemia, is now considered to regulate both pro-survival and pro-death responses depending on the duration and severity of the stress. We previously showed that chronic global cerebral hypoperfusion (CCH) triggered long-lasting accumulation of HIF-1α protein in the hippocampus of rats. However, the role of the stabilized HIF-1α in CCH is obscure. Here, we knock down endogenous HIF-1α to determine whether and how HIF-1α affects the disease processes and phenotypes of CCH. Lentivirus expressing HIF-1α small hairpin RNA was injected into the bilateral hippocampus and bilateral ventricles to knock down HIF-1α gene expression in the hippocampus and other brain areas. Permanent bilateral common carotid artery occlusions, known as 2-vessel occlusions (2VOs), were used to induce CCH in rats. Angiogenesis, oxidative stress, histopathological changes of the brain, and cognitive function were tested. Knockdown of HIF-1α prior to 2VO significantly exacerbates the impairment of learning and memory after four weeks of CCH. Mechanically, reduced cerebral angiogenesis, increased oxidative damage, and increased density of astrocytes and microglia in the cortex and some subregions of hippocampus are also shown after four weeks of CCH. Furthermore, HIF-1α knockdown also disrupts upregulation of regulated downstream genes. Our findings suggest that HIF-1α-protects the brain from oxidative stress and inflammation response in the disease process of CCH. Accumulated HIF-1α during CCH mediates endogenous adaptive processes to defend against more severe hypoperfusion injury of the brain, which may provide a therapeutic benefit. PMID:28106731

  1. No evidence of local adaptation of immune responses to Gyrodactylus in three-spined stickleback (Gasterosteus aculeatus).

    PubMed

    Robertson, Shaun; Bradley, Janette E; MacColl, Andrew D C

    2017-01-01

    Parasitism represents one of the most widespread lifestyles in the animal kingdom, with the potential to drive coevolutionary dynamics with their host population. Where hosts and parasites evolve together, we may find local adaptation. As one of the main host defences against infection, there is the potential for the immune response to be adapted to local parasites. In this study, we used the three-spined stickleback and its Gyrodactylus parasites to examine the extent of local adaptation of parasite infection dynamics and the immune response to infection. We took two geographically isolated host populations infected with two distinct Gyrodactylus species and performed a reciprocal cross-infection experiment in controlled laboratory conditions. Parasite burdens were monitored over the course of the infection, and individuals were sampled at multiple time points for immune gene expression analysis. We found large differences in virulence between parasite species, irrespective of host, and maladaptation of parasites to their sympatric host. The immune system responded to infection, with a decrease in expression of innate and Th1-type adaptive response genes in fish infected with the less virulent parasite, representing a marker of a possible resistance mechanism. There was no evidence of local adaptation in immune gene expression levels. Our results add to the growing understanding of the extent of host-parasite local adaptation, and demonstrate a systemic immune response during infection with a common ectoparasite. Further immunological studies using the stickleback-Gyrodactylus system can continue to contribute to our understanding of the function of the immune response in natural populations.

  2. 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

  3. Growth response of Escherichia coli ATCC 35218 adapted to several concentrations of sodium benzoate and potassium sorbate.

    PubMed

    Santiesteban-López, N Angélica; Rosales, Mónica; Palou, Enrique; López-Malo, Aurelio

    2009-11-01

    Escherichia coli ATCC 35218 growth response was evaluated after repetitive cultivation in stepwise increasing antimicrobial agent concentrations (potassium sorbate or sodium benzoate) to observe its adaptation process to high weak-acid concentrations. The effect of antimicrobial (potassium sorbate or sodium benzoate) concentration (0 to 7,000 ppm) was tested using laboratory media. Cells adapted at 1,000 ppm were inoculated in media containing the same concentration of the antimicrobial; after that, cells were transferred to media containing a higher concentration, followed by repetitive cultivations. In every case, viable cells were determined by surface plating every hour up to 48 h. Logarithmic representations of survival or growing fraction were modeled using the Gompertz equation. Adapted and nonadapted cells were analyzed for plasmid presence as well as phosphofructokinase and succinate dehydrogenase activity. Bacterial growth was observed after adaptation processes in media formulated up to 7,000 ppm of potassium sorbate or sodium benzoate. Analyses of variance demonstrated that no significant difference (P > 0.05) in lag time or growth rate was observed among adapted cells cultured in media containing the studied concentrations for each of the antimicrobials tested. These results suggest that E. coli can be adapted to high weak-acid concentrations if the exposure is performed under sublethal conditions. Furthermore, there was demonstrated inhibition of the enzymes phosphofructokinase and succinate dehydrogenase by action of sodium benzoate and potassium sorbate, respectively. E. coli adaptation to antimicrobial agents was not related to plasmid presence but appears to be due to other action mechanisms.

  4. Daily rhythmicity of the thermoregulatory responses of locally adapted Brazilian sheep in a semiarid environment

    NASA Astrophysics Data System (ADS)

    da Silva, Wilma Emanuela; Leite, Jacinara Hody Gurgel Morais; de Sousa, José Ernandes Rufino; Costa, Wirton Peixoto; da Silva, Wallace Sostene Tavares; Guilhermino, Magda Maria; Asensio, Luis Alberto Bermejo; Façanha, Débora Andréa Evangelista

    2017-01-01

    approximately 5:00 p.m.; however, these findings confirm the importance of providing environmental protection during critical periods of the day, even for locally adapted breeds. These responses suggest that the use of thermal storage allowed the animals to achieve equilibrium with the environment and maintain a stable body temperature.

  5. Engrafted human cells generate adaptive immune responses to Mycobacterium bovis BCG infection in humanized mice

    PubMed Central

    2013-01-01

    Background Currently used mouse models fail to fully reflect human immunity to tuberculosis (TB), which hampers progress in research and vaccine development. Bone marrow-liver-thymus (BLT) mice, generated by engrafting human fetal liver, thymus, and hematopoietic stem cells in severely immunodeficient NOD/SCID/IL-2Rγ-/- (NSG) mice, have shown potential to model human immunity to infection. We engrafted HLA-A2-positive fetal tissues into NSG mice transgenically expressing human leukocyte antigen (HLA)-A2.1 (NSG-A2) to generate NSG-A2-BLT mice and characterized their human immune response to Mycobacterium bovis bacillus Calmette-Guerin (BCG) infection to assess the utility of this model for investigating human TB. Results NSG-A2-BLT mice were infected intravenously with BCG and the immune response of engrafted human immune cells was characterized. After ex vivo antigenic stimulation of splenocytes, interferon (IFN)-γ-producing cells were detected by ELISPOT from infected, but not uninfected NSG-A2-BLT mice. However, the levels of secreted IFN-γ, determined by ELISA, were not significantly elevated by antigenic stimulation. NSG-A2-BLT mice were susceptible to BCG infection as determined by higher lung bacillary load than the non-engrafted control NSG-A2 mice. BCG-infected NSG-A2-BLT mice developed lung lesions composed mostly of human macrophages and few human CD4+ or CD8+ T cells. The lesions did not resemble granulomas typical of human TB. Conclusions Engrafted human immune cells in NSG-A2-BLT mice showed partial function of innate and adaptive immune systems culminating in antigen-specific T cell responses to mycobacterial infection. The lack of protection was associated with low IFN-γ levels and limited numbers of T cells recruited to the lesions. The NSG-A2-BLT mouse is capable of mounting a human immune response to M. tuberculosis in vivo but a quantitatively and possibly qualitatively enhanced effector response will be needed to improve the utility of this

  6. 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

  7. Involvement of Escherichia coli DNA polymerase II in response to oxidative damage and adaptive mutation.

    PubMed

    Escarceller, M; Hicks, J; Gudmundsson, G; Trump, G; Touati, D; Lovett, S; Foster, P L; McEntee, K; Goodman, M F

    1994-10-01

    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.

  8. 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

  9. Atypical adaptive and cross-protective responses against peroxide killing in a bacterial plant pathogen, Agrobacterium tumefaciens.

    PubMed

    Vattanaviboon, Paiboon; Eiamphungporn, Warawan; Mongkolsuk, Skorn

    2003-10-01

    Physiological adaptive and cross-protection responses to oxidants were investigated in Agrobacterium tumefaciens. Exposure of A. tumefaciens to sublethal concentrations of H2O2 induced adaptive protection to lethal concentrations of H2O2. Similar treatments with organic peroxide and menadione did not produce adaptive protection to subsequent exposure to lethal concentrations of these oxidants. Pretreatment of A. tumefaciens with an inducing concentration of menadione conferred cross-protection against H2O2, but not to tert-butyl hydroperoxide (tBOOH), killing. The menadione induced cross-protection to H2O2 was due to the compound's ability to highly induce the peroxide scavenging enzyme, catalase. The levels of catalase directly correlated with the bacterium's ability to survive H2O2 treatment. Some aspects of the oxidative stress response of A. tumefaciens differ from other bacteria, and these differences may be important in plant/microbe interactions.

  10. 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.

  11. 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…

  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. Plastic and Evolutionary Gene Expression Responses Are Correlated in European Grayling (Thymallus thymallus) Subpopulations Adapted to Different Thermal Environments.

    PubMed

    Mäkinen, Hannu; Papakostas, Spiros; Vøllestad, Leif Asbjørn; Leder, Erica H; Primmer, Craig R

    2016-01-01

    Understanding how populations adapt to changing environmental conditions is a long-standing theme in evolutionary biology. Gene expression changes have been recognized as an important driver of local adaptation, but relatively little is known regarding the direction of change and in particular, about the interplay between plastic and evolutionary gene expression. We have previously shown that the gene expression profiles of European grayling (Thymallus thymallus) populations inhabiting different thermal environments include both plastic and evolutionary components. However, whether the plastic and evolutionary responses were in the same direction was not investigated in detail, nor was the identity of the specific genes involved. In this study, we show that the plastic changes in protein expression in response to different temperatures are highly correlated with the evolutionary response in grayling subpopulations adapted to different thermal environments. This finding provides preliminary evidence that the plastic response most likely facilitates adaptation during the early phases of colonization of thermal environments. The proteins that showed significant changes in expression level between warm and cold temperature treatments were mostly related to muscle development, which is consistent with earlier findings demonstrating muscle mass differentiation between cold and warm grayling populations.

  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.

    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.

  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. Perceptions of wellness to monitor adaptive responses to training and competition in elite Australian football.

    PubMed

    Gastin, Paul B; Meyer, Denny; Robinson, Dean

    2013-09-01

    Perceptions of wellness are often used by athletes and coaches to assess adaptive responses to training. The purpose of this research was to describe how players were coping with the demands of elite level Australian football over a competitive season using subjective ratings of physical and psychological wellness and to assess the ecological validity of such a monitoring approach. Twenty-seven players completed ratings for 9 items (fatigue, general muscle, hamstring, quadriceps, pain/stiffness, power, sleep quality, stress, well-being). Players subjectively rated each item as they arrived at the training or competition venue on a 1-5 visual analog scale, with 1 representing the positive end of the continuum. A total of 2,583 questionnaires were analyzed from completions on 183 days throughout the season (92 ± 24 per player, 103 ± 20 per week; mean ± SD). Descriptive statistics and multilevel modelling were used to understand how player ratings of wellness varied over the season and during the week leading into game day and whether selected player characteristics moderated these relationships. Results indicated that subjective ratings of physical and psychological wellness were sensitive to weekly training manipulations (i.e., improve steadily throughout the week to a game day low, p < 0.001), to periods of unloading during the season (i.e., a week of no competition, p < 0.05) and to individual player characteristics (e.g., muscle strain after a game was poorer in players with high maximum speed, p < 0.01). It is concluded that self-reported player ratings of wellness provide a useful tool for coaches and practitioners to monitor player responses to the rigorous demands of training, competition, and life as a professional athlete.

  19. Adaptive responses of neuronal mitochondria to bioenergetic challenges: Roles in neuroplasticity and disease resistance.

    PubMed

    Raefsky, Sophia M; Mattson, Mark P

    2017-01-01

    An important concept in neurobiology is "neurons that fire together, wire together" which means that the formation and maintenance of synapses is promoted by activation of those synapses. Very similar to the effects of the stress of exercise on muscle cells, emerging findings suggest that neurons respond to activity by activating signaling pathways (e.g., Ca(2+), CREB, PGC-1α, NF-κB) that stimulate mitochondrial biogenesis and cellular stress resistance. These pathways are also activated by aerobic exercise and food deprivation, two bioenergetic challenges of fundamental importance in the evolution of the brains of all mammals, including humans. The metabolic 'switch' in fuel source from liver glycogen store-derived glucose to adipose cell-derived fatty acids and their ketone metabolites during fasting and sustained exercise, appears to be a pivotal trigger of both brain-intrinsic and peripheral organ-derived signals that enhance learning and memory and underlying synaptic plasticity and neurogenesis. Brain-intrinsic extracellular signals include the excitatory neurotransmitter glutamate and the neurotrophic factor BDNF, and peripheral signals may include the liver-derived ketone 3-hydroxybutyrate and the muscle cell-derived protein irisin. Emerging findings suggest that fasting, exercise and an intellectually challenging lifestyle can protect neurons against the dysfunction and degeneration that they would otherwise suffer in acute brain injuries (stroke and head trauma) and neurodegenerative disorders including Alzheimer's, Parkinson's and Huntington's disease. Among the prominent intracellular responses of neurons to these bioenergetic challenges are up-regulation of antioxidant defenses, autophagy/mitophagy and DNA repair. A better understanding of such fundamental hormesis-based adaptive neuronal response mechanisms is expected to result in the development and implementation of novel interventions to promote optimal brain function and healthy brain aging.

  20. CK2 inhibition induced PDK4-AMPK axis regulates metabolic adaptation and survival responses in glioma.

    PubMed

    Dixit, Deobrat; Ahmad, Fahim; Ghildiyal, Ruchi; Joshi, Shanker Datt; Sen, Ellora

    2016-05-15

    Understanding mechanisms that link aberrant metabolic adaptation and pro-survival responses in glioma cells is crucial towards the development of new anti-glioma therapies. As we have previously reported that CK2 is associated with glioma cell survival, we evaluated its involvement in the regulation of glucose metabolism. Inhibition of CK2 increased the expression of metabolic regulators, PDK4 and AMPK along with the key cellular energy sensor CREB. This increase was concomitant with altered metabolic profile as characterized by decreased glucose uptake in a PDK4 and AMPK dependent manner. Increased PDK4 expression was CREB dependent, as exogenous inhibition of CREB functions abrogated CK2 inhibitor mediated increase in PDK4 expression. Interestingly, PDK4 regulated AMPK phosphorylation which in turn affected cell viability in CK2 inhibitor treated glioma cells. CK2 inhibitor 4,5,6,7-Tetrabromobenzotriazole (TBB) significantly retarded the growth of glioma xenografts in athymic nude mouse model. Coherent with the in vitro findings, elevated senescence, pAMPK and PDK4 levels were also observed in TBB-treated xenograft tissue. Taken together, CK2 inhibition in glioma cells drives the PDK4-AMPK axis to affect metabolic profile that has a strong bearing on their survival.

  1. Neutrophilic myeloid-derived suppressor cells in cord blood modulate innate and adaptive immune responses

    PubMed Central

    Rieber, N; Gille, C; Köstlin, N; Schäfer, I; Spring, B; Ost, M; Spieles, H; Kugel, H A; Pfeiffer, M; Heininger, V; Alkhaled, M; Hector, A; Mays, L; Kormann, M; Zundel, S; Fuchs, J; Handgretinger, R; Poets, C F; Hartl, D

    2013-01-01

    Neonates show an impaired anti-microbial host defence, but the underlying immune mechanisms are not understood fully. Myeloid-derived suppressor cells (MDSCs) represent an innate immune cell subset characterized by their capacity to suppress T cell immunity. In this study we demonstrate that a distinct MDSC subset with a neutrophilic/granulocytic phenotype (Gr-MDSCs) is highly increased in cord blood compared to peripheral blood of children and adults. Functionally, cord blood isolated Gr-MDSCs suppressed T cell proliferation efficiently as well as T helper type 1 (Th1), Th2 and Th17 cytokine secretion. Beyond T cells, cord blood Gr-MDSCs controlled natural killer (NK) cell cytotoxicity in a cell contact-dependent manner. These studies establish neutrophilic Gr-MDSCs as a novel immunosuppressive cell subset that controls innate (NK) and adaptive (T cell) immune responses in neonates. Increased MDSC activity in cord blood might serve as key fetomaternal immunosuppressive mechanism impairing neonatal host defence. Gr-MDSCs in cord blood might therefore represent a therapeutic target in neonatal infections. PMID:23701226

  2. Adaptive phenotypic plasticity of Siberian elm in response to drought stress: increased stomatal pore depth.

    PubMed

    Park, Go Eun; Kim, Ki Woo; Lee, Don Koo; Hyun, Jung Oh

    2013-08-01

    Leaf stomatal characteristics of Siberian elm (Ulmus pumila) were investigated by electron microscopy and white light scanning interferometry. On the basis of average annual precipitations, two types of tree specimens were collected from Korea, China, and Mongolia: (1) trees under normal environmental conditions and (2) trees under arid conditions. Field emission scanning electron microscopy revealed oval-shaped stomata on the lower surface, and they were ca. 20 μm in width. In-lens secondary electron imaging showed differences in electron density and stomatal pore depth between the two types. According to the line profile analysis by white light scanning interferometry, stomata under arid conditions appeared to have higher levels of the stomatal pore depth than ones under normal conditions. Focused ion beam-field emission electron microscopy supported the increased stomatal pore depth with the increasing drought stress gradient. These results suggest that complementary microscopy can be employed to unravel the adaptive phenotypic plasticity of Siberian elm in response to drought stress.

  3. A surrogate-primary replacement algorithm for response-adaptive randomization in stroke clinical trials.

    PubMed

    Nowacki, Amy S; Zhao, Wenle; Palesch, Yuko Y

    2015-01-12

    Response-adaptive randomization (RAR) offers clinical investigators benefit by modifying the treatment allocation probabilities to optimize the ethical, operational, or statistical performance of the trial. Delayed primary outcomes and their effect on RAR have been studied in the literature; however, the incorporation of surrogate outcomes has not been fully addressed. We explore the benefits and limitations of surrogate outcome utilization in RAR in the context of acute stroke clinical trials. We propose a novel surrogate-primary (S-P) replacement algorithm where a patient's surrogate outcome is used in the RAR algorithm only until their primary outcome becomes available to replace it. Computer simulations investigate the effect of both the delay in obtaining the primary outcome and the underlying surrogate and primary outcome distributional discrepancies on complete randomization, standard RAR and the S-P replacement algorithm methods. Results show that when the primary outcome is delayed, the S-P replacement algorithm reduces the variability of the treatment allocation probabilities and achieves stabilization sooner. Additionally, the S-P replacement algorithm benefit proved to be robust in that it preserved power and reduced the expected number of failures across a variety of scenarios.

  4. Documenting the remedial response: Adapting and applying administrative record guidance to Department of Defense installations

    SciTech Connect

    Savage, L.S.; Capito, B.P.

    1995-12-31

    The Administrative Record (AR) is a CERCLA-mandated collection of material that documents the selection of a remedial response at National Priority List (NPL) sites. It is a massive file that is established to serve legal as well as community relations functions. The US Environmental Protection Agency (USEPA) has promulgated guidance for those who are required to establish and maintain ARs; however, this guidance was developed for single-site, USEPA cleanups (i.e., industrial NPL sites). Department of Defense (DoD) facilities are tested on the NPL by installation; a single installation usually encompasses multiple sites, sometimes 25 or more. The USEPA Administrative Record guidance must be adapted before being applied to DoD installations. This paper will present the AR approach developed by the US Navy, Atlantic Division, Naval Facilities Engineering Command (LANTDIV) through its contractor Baker Environmental (Baker). The AR project was conducted as part of the Comprehensive Long-term Environmental Action Navy (CLEAN) contract. The CLEAN program is designed to address environmental problems resulting from past, formerly accepted waste management practices.

  5. 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.

  6. 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.

  7. 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.

  8. 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

  9. 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.

  10. Adaptive Response in Mice Exposed to 900 MHz Radiofrequency Fields: Primary DNA Damage

    PubMed Central

    Zhou, Zhen; Zhang, Jie; Tong, Jian; Cao, Yi

    2012-01-01

    The phenomenon of adaptive response (AR) in animal and human cells exposed to ionizing radiation is well documented in scientific literature. We have examined whether such AR could be induced in mice exposed to non-ionizing radiofrequency fields (RF) used for wireless communications. Mice were pre-exposed to 900 MHz RF at 120 µW/cm2 power density for 4 hours/day for 1, 3, 5, 7 and 14 days and then subjected to an acute dose of 3 Gy γ-radiation. The primary DNA damage in the form of alkali labile base damage and single strand breaks in the DNA of peripheral blood leukocytes was determined using the alkaline comet assay. The results indicated that the extent of damage in mice which were pre-exposed to RF for 1 day and then subjected to γ-radiation was similar and not significantly different from those exposed to γ-radiation alone. However, mice which were pre-exposed to RF for 3, 5, 7 and 14 days showed progressively decreased damage and was significantly different from those exposed to γ-radiation alone. Thus, the data indicated that RF pre-exposure is capable of inducing AR and suggested that the pre-exposure for more than 4 hours for 1 day is necessary to elicit such AR. PMID:22389679

  11. Neutrophilic myeloid-derived suppressor cells in cord blood modulate innate and adaptive immune responses.

    PubMed

    Rieber, N; Gille, C; Köstlin, N; Schäfer, I; Spring, B; Ost, M; Spieles, H; Kugel, H A; Pfeiffer, M; Heininger, V; Alkhaled, M; Hector, A; Mays, L; Kormann, M; Zundel, S; Fuchs, J; Handgretinger, R; Poets, C F; Hartl, D

    2013-10-01

    Neonates show an impaired anti-microbial host defence, but the underlying immune mechanisms are not understood fully. Myeloid-derived suppressor cells (MDSCs) represent an innate immune cell subset characterized by their capacity to suppress T cell immunity. In this study we demonstrate that a distinct MDSC subset with a neutrophilic/granulocytic phenotype (Gr-MDSCs) is highly increased in cord blood compared to peripheral blood of children and adults. Functionally, cord blood isolated Gr-MDSCs suppressed T cell proliferation efficiently as well as T helper type 1 (Th1), Th2 and Th17 cytokine secretion. Beyond T cells, cord blood Gr-MDSCs controlled natural killer (NK) cell cytotoxicity in a cell contact-dependent manner. These studies establish neutrophilic Gr-MDSCs as a novel immunosuppressive cell subset that controls innate (NK) and adaptive (T cell) immune responses in neonates. Increased MDSC activity in cord blood might serve as key fetomaternal immunosuppressive mechanism impairing neonatal host defence. Gr-MDSCs in cord blood might therefore represent a therapeutic target in neonatal infections.

  12. Psychological response to amniocentesis: I. Mood state and adaptation to pregnancy.

    PubMed

    Phipps, S; Zinn, A B

    1986-09-01

    The responses of a group of pregnant women undergoing amniocentesis and control women not having the procedure were studied using objective, self-report measures of mood state, attitudes toward pregnancy, and maternal-fetal attachment. Questionnaires were completed on three occasions: after genetic counseling (time-1), after amniocentesis (time-2), and 1 wk after communication of results (time-3) for amniocentesis subjects, and at comparable points in the pregnancy for control subjects. Amniocentesis and control subjects differed markedly in their pattern of change in anxiety scores over time, with amniocentesis subjects being more anxious than control subjects at time-2 and less anxious at time-3. Results were similar but less pronounced for depression scores, whereas there were smaller differences between groups on measures of anger and confusion. Unusual patterns of mood state changes were seen in the control group, which were related to a history of previous fetal loss. The groups did not differ in their attitudes toward pregnancy, but amniocentesis subjects showed a greater relative increase in attachment to the fetus than did control subjects. Overall, amniocentesis subjects were faring as well or better on every measure taken at time-3 and were showing improvement on all measures. In contrast, control subjects were demonstrating a trend toward increasing mood disturbance. These results suggest that any amniocentesis-related psychological disturbances are only transient and are outweighed by the receipt of normal results, which appear to enhance emotional adaptation to pregnancy.

  13. 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

  14. 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.

  15. 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.

  16. Cutaneous stimulation of the digits and lips evokes responses with different adaptation patterns in primary somatosensory cortex

    PubMed Central

    Popescu, Mihai; Barlow, Steven; Popescu, Elena-Anda; Estep, Meredith E.; Venkatesan, Lalit; Auer, Edward T.; Brooks, William M.

    2010-01-01

    Neuromagnetic evoked fields were recorded to compare the adaptation of the primary somatosensory cortex (SI) response to tactile stimuli delivered to the glabrous skin at the fingertips of the first three digits (condition 1) and between midline upper and lower lips (condition 2). The stimulation paradigm allowed to characterize the response adaptation in the presence of functional integration of tactile stimuli from adjacent skin areas in each condition. At each stimulation site, cutaneous stimuli (50 ms duration) were delivered in three runs, using trains of 6 pulses with regular stimulus onset asynchrony (SOA). The pulses were separated by SOAs of 500 ms, 250 ms or 125 ms in each run, respectively, while the inter-train interval was fixed (5 s) across runs. The evoked activity in SI (contralateral to the stimulated hand, and bilaterally for lips stimulation) was characterized from the best-fit dipoles of the response component peaking around 70 ms for the hand stimulation, and 8 ms earlier (on average) for the lips stimulation. The SOA-dependent long-term adaptation effects were assessed from the change in the amplitude of the responses to the first stimulus in each train. The short-term adaptation was characterized by the lifetime of an exponentially saturating model function fitted to the set of suppression ratios of the second relative to the first SI response in each train. Our results indicate: 1) the presence of a rate-dependent long-term adaptation effect induced only by the tactile stimulation of the digits; and 2) shorter recovery lifetimes for the digits compared with the lips stimulation. PMID:20561996

  17. The "adaptive responses" of low concentrations of HBCD in L02 cells and the underlying molecular mechanisms.

    PubMed

    An, Jing; Guo, Panpan; Shang, Yu; Zhong, Yufang; Zhang, Xinyu; Yu, Yingxin; Yu, Zhiqiang

    2016-02-01

    This study aimed to investigate the "adaptive responses" of hexabromocyclododecanes (HBCD) at environmentally relevant concentrations in human hepatocytes L02. L02 cells were pre-treated with low concentrations of HBCD (10(-13)-10(-11) M), followed by treatment with high concentrations of HBCD, α-hexachlorocyclohexane (α-HCH), polychlorinated biphenyls (PCBs), or polybrominated diphenyl ether-47 (BDE47). The results showed that the pre-treatment with low concentrations of HBCD induced "adaptive responses" to high concentrations of HBCD/α-HCH exposure (but not to PCBs and BDE47), as evidenced by attenuation of survival inhibition, reactive oxygen species (ROS) over-production, and deoxyribonucleic acid (DNA) damage induction. The "adaptive responses" induced by low concentrations of HBCD, which depended on the activation of the phosphatidylinositide 3-kinase/protein kinase B (PI3K/Akt) pathway, reduced the phosphorylation of adenosine monophosphate-activated kinase (AMPK) and enhanced the phosphorylation of p38 mitogen-activated protein kinases (p38 MAPK). The observations were further confirmed by the experiments with inhibitors. Moreover, the evaluation on the changes of metabolic enzymes revealed that HBCD and α-HCH shared a similar pattern of cytochrome P450 induction (CYP2B6), which was different from those of PCBs and BDE47 (CYP1A1 and CYP2B6). These results indicated that low concentrations of HBCD could induce "adaptive responses" to the subsequent treatment with high concentrations of HBCD/α-HCH in L02 cells, which was associated with the PI3K/Akt pathway, and AMPK and p38 MAPK signaling. The "adaptive responses" seemed to be dependent on the types of chemicals in terms of the metabolic patterns and chemical structures.

  18. 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

  19. Adaptation and inhibition underlie responses to time-varying interaural phase cues in a model of inferior colliculus neurons.

    PubMed

    Borisyuk, Alla; Semple, Malcolm N; Rinzel, John

    2002-10-01

    A mathematical model was developed for exploring the sensitivity of low-frequency inferior colliculus (IC) neurons to interaural phase disparity (IPD). The formulation involves a firing-rate-type model that does not include spikes per se. The model IC neuron receives IPD-tuned excitatory and inhibitory inputs (viewed as the output of a collection of cells in the medial superior olive). The model cell possesses cellular properties of firing rate adaptation and postinhibitory rebound (PIR). The descriptions of these mechanisms are biophysically reasonable, but only semi-quantitative. We seek to explain within a minimal model the experimentally observed mismatch between responses to IPD stimuli delivered dynamically and those delivered statically (McAlpine et al. 2000; Spitzer and Semple 1993). The model reproduces many features of the responses to static IPD presentations, binaural beat, and partial range sweep stimuli. These features include differences in responses to a stimulus presented in static or dynamic context: sharper tuning and phase shifts in response to binaural beats, and hysteresis and "rise-from-nowhere" in response to partial range sweeps. Our results suggest that dynamic response features are due to the structure of inputs and the presence of firing rate adaptation and PIR mechanism in IC cells, but do not depend on a specific biophysical mechanism. We demonstrate how the model's various components contribute to shaping the observed phenomena. For example, adaptation, PIR, and transmission delay shape phase advances and delays in responses to binaural beats, adaptation and PIR shape hysteresis in different ranges of IPD, and tuned inhibition underlies asymmetry in dynamic tuning properties. We also suggest experiments to test our modeling predictions: in vitro simulation of the binaural beat (phase advance at low beat frequencies, its dependence on firing rate), in vivo partial range sweep experiments (dependence of the hysteresis curve on

  20. Subversion of innate immune responses by Brucella through the targeted degradation of the TLR signaling adapter, MAL.

    PubMed

    Sengupta, Dola; Koblansky, Alicia; Gaines, Jennifer; Brown, Tim; West, A Phillip; Zhang, Dekai; Nishikawa, Tak; Park, Sung-Gyoo; Roop, R Martin; Ghosh, Sankar

    2010-01-15

    Gram-negative bacteria belonging to the Brucella species cause chronic infections that can result in undulant fever, arthritis, and osteomyelitis in humans. Remarkably, Brucella sp. genomes encode a protein, named TcpB, that bears significant homology with mammalian Toll/IL-1 receptor domains and whose expression causes degradation of the phosphorylated, signal competent form of the adapter MyD88-adapter-like (MAL). This effect of TcpB is mediated through its box 1 region and has no effect on other TLR adapter proteins such as MyD88 or TIR-domain containing adapter protein-inducing IFNbeta. TcpB also does not affect a mutant, signal-incompetent form of MAL that cannot be phosphorylated. Interestingly, the presence of TcpB leads to enhanced polyubiquitination of MAL, which is likely responsible for its accelerated degradation. A Brucella abortus mutant lacking TcpB fails to reduce levels of MAL in infected macrophages. Therefore, TcpB represents a unique pathogen-derived molecule that suppresses host innate-immune responses by specifically targeting an individual adapter molecule in the TLR signaling pathway for degradation.

  1. Adaptive phenotypic response to climate enabled by epigenetics in a K-strategy species, the fish Leucoraja ocellata (Rajidae)

    PubMed Central

    Incarnato, Danny; Ward, Ben J.; van Oosterhout, Cock; Bradbury, Ian; Hanson, Mark; Bentzen, Paul

    2016-01-01

    The relative importance of genetic versus epigenetic changes in adaptive evolution is a hotly debated topic, with studies showing that some species appear to be able to adapt rapidly without significant genetic change. Epigenetic mechanisms may be particularly important for the evolutionary potential of species with long maturation times and low reproductive potential (‘K-strategists’), particularly when faced with rapidly changing environmental conditions. Here we study the transcriptome of two populations of the winter skate (Leucoraja ocellata), a typical ‘K-strategist’, in Atlantic Canada; an endemic population in the southern Gulf of St Lawrence and a large population on the Scotian Shelf. The endemic population has been able to adapt to a 10°C higher water temperature over short evolutionary time (7000 years), dramatically reducing its body size (by 45%) significantly below the minimum maturation size of Scotian Shelf and other populations of winter skate, as well as exhibiting other adaptations in life history and physiology. We demonstrate that the adaptive response to selection has an epigenetic basis, cataloguing 3653 changes in gene expression that may have enabled this species to rapidly respond to the novel environment. We argue that the epigenetic augmentation of species evolutionary potential (its regulation though gene expression) can enable K-strategists to survive and adapt to different environments, and this mechanism may be particularly important for the persistence of sharks, skates and rays in the light of future climate change. PMID:27853546

  2. 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.

  3. Lipocalin 2 bolsters innate and adaptive immune responses to blood-stage malaria infection by reinforcing host iron metabolism.

    PubMed

    Zhao, Hong; Konishi, Aki; Fujita, Yukiko; Yagi, Masanori; Ohata, Keiichi; Aoshi, Taiki; Itagaki, Sawako; Sato, Shintaro; Narita, Hirotaka; Abdelgelil, Noha H; Inoue, Megumi; Culleton, Richard; Kaneko, Osamu; Nakagawa, Atsushi; Horii, Toshihiro; Akira, Shizuo; Ishii, Ken J; Coban, Cevayir

    2012-11-15

    Plasmodium parasites multiply within host erythrocytes, which contain high levels of iron, and parasite egress from these cells results in iron release and host anemia. Although Plasmodium requires host iron for replication, how host iron homeostasis and responses to these fluxes affect Plasmodium infection are incompletely understood. We determined that Lipocalin 2 (Lcn2), a host protein that sequesters iron, is abundantly secreted during human (P. vivax) and mouse (P. yoeliiNL) blood-stage malaria infections and is essential to control P. yoeliiNL parasitemia, anemia, and host survival. During infection, Lcn2 bolsters both host macrophage function and granulocyte recruitment and limits reticulocytosis, or the expansion of immature erythrocytes, which are the preferred target cell of P. yoeliiNL. Additionally, a chronic iron imbalance due to Lcn2 deficiency results in impaired adaptive immune responses against Plasmodium parasites. Thus, Lcn2 exerts antiparasitic effects by maintaining iron homeostasis and promoting innate and adaptive immune responses.

  4. 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.

  5. Evidence of adaptive divergence in plasticity: density- and site-dependent selection on shade-avoidance responses in Impatiens capensis.

    PubMed

    Donohue, K; Messiqua, D; Pyle, E H; Heschel, M S; Schmitt, J

    2000-12-01

    We investigated the conditions under which plastic responses to density are adaptive in natural populations of Impatiens capensis and determined whether plasticity has evolved differently in different selective environments. Previous studies showed that a population that evolved in a sunny site exhibited greater plasticity in response to density than did a population that evolved in a woodland site. Using replicate inbred lines in a reciprocal transplant that included a density manipulation, we asked whether such population differentiation was consistent with the hypothesis of adaptive divergence. We hypothesized that plasticity would be more strongly favored in the sunny site than in the woodland site; consequently, we predicted that selection would be more strongly density dependent in the sunny site, favoring the phenotype that was expressed at each density. Selection on internode length and flowering date was consistent with the hypothesis of adaptive divergence in plasticity. Few costs or benefits of plasticity were detected independently from the expressed phenotype, so plasticity was selected primarily through selection on the phenotype. Correlations between phenotypes and their plasticity varied with the environment and would cause indirect selection on plasticity to be environment dependent. We showed that an appropriate plastic response even to a rare environment can greatly increase genotypic fitness when that environment is favorable. Selection on the measured characters contributed to local adaptation and fully accounted for fitness differences between populations in all treatments except the woodland site at natural density.

  6. 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

  7. 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 ...

  8. 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...

  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. 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.

  11. Osteopontin Expression in Acute Immune Response Mediates Hippocampal Synaptogenesis and Adaptive Outcome Following Cortical Brain Injury

    PubMed Central

    Chan, Julie L.; Reeves, Thomas M.;