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Sample records for adaptive response induced

  1. Radiation-induced preventive bystander response and adaptive response

    Radiation-induced bystander response (BR) is a phenomenon not observed in cells irradiated directly but in cells nearby. Recently, the relationship between BR and adaptive response (AR) has been studied and BR is suggested to be one of important mechanisms involved in AR induction through key molecules like reactive oxygen (RO) and nitrogen species. In this paper, the possible contribution of BR to AR is discussed on recent findings including author's ones. Many biological responses in bystander cells, cultured tissues and mice by cell-cell communication molecules such as cytokines and nitrogen oxide (NO) have been elucidated for BR to involve the cell death, sister chromatid exchange, chromosome instability, mutation, increased/ decreased p53 level, etc. However, BR has been recently found to contain biologically favorable events like the increase of radio-resistance and of cellular take rate and decrease of micronucleus formation through NO by X-ray and HIMAC C-ion. AR is observed in irradiated cell population with previous exposure to low dose and involves the above mentioned biologically favorable responses, which having lead to the possible interrelationship between BR and AR. Together with findings obtained hitherto, hypothesized is that AR is induced in bystander cells through a sequence of signals of evoked radicals like RO/ NO by pre-irradiation, and of consequent intermediating molecules like transforming growth factor (TGF)-1, tumor necrosis factor (TNF), interleukin (IL)-1 and estrogen to activate NF-KB for inducing COX-2 and NO synthase, which resulting in stimulation of damaged DNA repairing mechanism and of mitogen-activated protein kinase (MAPK) cascade that constructs the signaling between plasma membrane and nucleus. (K.T.)

  2. Adaptive response induced by occupational exposures to ionizing radiation

    We have found a significant decreased sensitivity to the cytogenetic effects of ionizing radiation (IR) and bleomycin (BLM) in lymphocytes from individuals occupationally exposed to IR when compared with a control population. These results suggest that occupational exposures to IR can induce adaptive response that can be detected by a subsequent treatment by IR or by BLM. However, no correlation between the results obtained with both treatments was observed. A great heterogeneity in the frequencies of chromatid aberrations induced by BLM was observed. The study of the influence of different harvesting times showed that there was no correlation with the frequencies of chromatid breaks. Our results indicate that the use of BLM to detect adaptive response has several difficulties at the individual level. (author)

  3. Adaptive response induced by occupational exposures to ionizing radiation

    We have found a significant decreased sensitivity to the cytogenetic effects of both ionizing radiation (IR) (2 Gy of γ rays) and bleomycin (BLM, 0,03 U/ml), in lymphocytes from individuals occupationally exposed to IR when compared with controls. These results suggest that occupational exposures to IR can induce adaptive response that can be detected by a subsequent treatment either by IR or by BLM. When a comparison is made between the cytogenetic effects of both treatments, no correlation was observed at the individual level. On the other hand, the individual frequencies of chromosome aberrations induced by a challenge dose of IR were negatively correlated with the occupationally received doses during the last three years. This correlation was not observed after the challenge treatment of BLM. Moreover, the individual frequencies of chromosome aberrations induced by IR treatment were homogeneous. This is not the case of the individual frequencies of chromatid aberrations induced by BLM, where a great heterogeneity was observed. (authors)

  4. Adaptive responses induced in vivo by low level tritium contamination

    Single cells or whole organisms can often improve their ability to respond to a challenging irradiation after being previously exposed to a lower 'adaptive' amount of a similar stress. A consistent collection of experimental data exists proving that low doses of irradiation trigger adaptive responses in mammalian cells in vitro with respect to cell survival and mutation, induction of chromosome aberrations or micronuclei, DNA strand-breaks or synthesis of new proteins. Adaptive responses have been reported to occur also in vivo in bone marrow, blood cells and germ cells following low dose irradiation of animals. The investigated end-points have been the animal survival or cytogenetic effects. Doses used for the initiation of adaptive responses in vivo are within the range of 1-50 cGy with challenging doses between 0.75-6 Gy. Concerning the molecular mechanisms it is generally postulated that radioadaptation could result from activation of damage repair. Another hypothesis points to a mechanism related to the ability of cells to eliminate the toxic radicals generated through oxidative stress by the activation of antioxidant defense systems. It is however accepted that the upregulation of antioxidant defense is only partly responsible for the whole protection mechanism that governs the adaptive response. The alterations after in vivo irradiation appear to be dependent on the post-irradiation interval time and on the dose level. Very few information is available concerning the correlation between the radiosensitivity of cells or tissues and the capability to develop an adaptive reaction. Some new data were provided by our research group by examining whether adaptive response could be elicited in vivo by 7 or 35 cGy irradiation (low LET) delivered in a chronically regime (internal contamination of rats with tritiated water) and observed after subsequent 1 Gy high LET challenging irradiation (with fast neutrons). The end-points addressed to the evaluation of the

  5. Understanding the role of p53 in adaptive response to radiation-induced germline mutations

    Full text: Radiation-induced adaptive response is now a widely studied area of radiation biology. Studies have demonstrated reduced levels of radiation-induced biological damage when an 'adaptive dose' is given before a higher 'challenge dose' compared to when the challenge dose is given alone. It has been shown in some systems to be a result of inducible cellular repair systems. The adaptive response has been clearly demonstrated in many model systems, however its impact on heritable effects in the mammalian germline has never been studied. Expanded Simple Tandem Repeat (ESTR) loci have been used as markers demonstrating that induced heritable mutations in mice follow a dose-response relationship. Recent data in our laboratory show preliminary evidence of radiation-induced adaptive response suppressing germline mutations at ESTR loci in wild type mice. The frequency of heritable mutations was significantly reduced when a priming dose of 0.1 Gy was given 24 hours prior to a 1 Gy acute challenging dose. We are now conducting a follow-up study to attempt to understand the mechanism of this adaptive response. P53 is known to play a significant role in governing apoptosis, DNA repair and cancer induction. In order to determine what function p53 has in the adaptive response for heritable mutations, we have mated radiation treated Trp53+/- male mice (C57Bl) to untreated, normal females (C57Bl). Using DNA fingerprinting, we are investigating the rate of inherited radiation-induced mutations on pre- and post-meiotic radiation-treated gametocytes by examining mutation frequencies in offspring DNA. If p53 is integral in the mechanism of adaptive response, we should not see an adaptive response in radiation-induced heritable mutations in these mice. This research is significant in that it will provide insight to understanding the mechanism behind radiation-induced adaptive response in the mammalian germline

  6. Human population structure and the adaptive response to pathogen-induced selection pressures

    Novembre, John; Han, Eunjung

    2012-01-01

    The past few years of research in human evolutionary genetics have provided novel insights and questions regarding how human adaptations to recent selective pressures have taken place. Here, we review the advances most relevant to understanding human evolution in response to pathogen-induced selective pressures. Key insights come from theoretical models of adaptive evolution, particularly those that consider spatially structured populations, and from empirical population genomic studies of ad...

  7. Study on cellular survival adaptive response induced by low dose irradiation of 153Sm

    The present study engages in determining whether low dose irradiation of 153Sm could cut down the responsiveness of cellular survival to subsequent high dose exposure of 153Sm so as to make an inquiry into approach the protective action of adaptive response by second irradiation of 153Sm. Experimental results indicate that for inductive low dose of radionuclide 153Sm 3.7 kBq/ml irradiated beforehand to cells has obvious resistant effect in succession after high dose irradiation of 153Sm 3.7 x 102 kBq/ml was observed. Cells exposed to low dose irradiation of 153Sm become adapted and therefore the subsequent cellular survival rate induced by high dose of 153Sm is sufficiently higher than high dose of 153Sm merely. It is evident that cellular survival adaptive response could be induced by pure low dose irradiation of 153Sm only

  8. Effect and adaptive response of lymphocytes DNA induced by low dose irradiation

    Fluorometric analysis of DNA unwinding (FADU) was conducted and was proved to be an optimal method for studying DNA strand breaks induced by low dose irradiation. The linear dose response curve was obtained. The minimum detected dose was 0.3 Gy. There was no effect of low dose γ-rays (0.5∼8.0 cGy) on DNA strand breaks of quiescent and mitogen-induced lymphocytes. The 0.5∼4.0 cGy γ-rats could induce adaptive response of lymphocytes' DNA strand breaks, especially, at the doses of 2.0 and 4.0 cGy. The challenge doses of 5∼20 Gy could make the adaptive response appearance, and the 15 Gy was the best one. The 3-AB could powerfully inhibit the adaptive response. The repair of DNA strand breaks (37 degree C, 15∼60 min) caused by 15 Gy γ-rays could be promoted by the low dose γ-ray irradiation (2.0 cGy), but no difference was found at 37 degree C, 120 min

  9. Adaptive response to ionising radiation induced by cadmium in zebrafish embryos

    An adaptive response is a biological response where the exposure of cells or animals to a low priming exposure induces mechanisms that protect the cells or animals against the detrimental effects of a subsequent larger challenging exposure. In realistic environmental situations, living organisms can be exposed to a mixture of stressors, and the resultant effects due to such exposures are referred to as multiple stressor effects. In the present work we demonstrated, via quantification of apoptosis in the embryos, that embryos of the zebrafish (Danio rerio) subjected to a priming exposure provided by one environmental stressor (cadmium in micromolar concentrations) could undergo an adaptive response against a subsequent challenging exposure provided by another environmental stressor (alpha particles). We concluded that zebrafish embryos treated with 1 to 10 μM Cd at 5 h postfertilisation (hpf) for both 1 and 5 h could undergo an adaptive response against subsequent ∼4.4 mGy alpha-particle irradiation at 10 hpf, which could be interpreted as an antagonistic multiple stressor effect between Cd and ionising radiation. The zebrafish has become a popular vertebrate model for studying the in vivo response to ionising radiation. As such, our results suggested that multiple stressor effects should be carefully considered for human radiation risk assessment since the risk may be perturbed by another environmental stressor such as a heavy metal. (paper)

  10. Study on the adaptive response of mammalian cells induced by low dose radiation of carbon ions

    The effect of high LET carbon ions irradiation with low dose on V79 Chinese hamster cells and B16 melanoma cells were investigated. The cells were treated with inducing doses of 0.02 Gy and 0.05 Gy first, and then with challenge dose of 1 Gy after-additional culture of 4h. The adaptive responses including survival fraction and micronucleus frequency were studied. Authors' results showed that when the inducing dose was chosen as 0.02 Gy, there were marked increase of surviving fraction and decrease of micronucleus frequency in both cell lines. On the contrary, when the inducing dose was chosen as 0.05 Gy, there was no statistical change of surviving fraction, furthermore, the micronucleus frequency increased a little. This meant that high LET radiation of 0.02 Gy could induce the adaptive response of cultured cells while 0.05 Gy can not. Meanwhile, there was a good linear relationship between micronucleus frequency and surviving fraction, cells pre-exposed to low dose such as 0.02 Gy had low micronucleus frequency and high surviving fraction

  11. Influence of adaptative response to low dose radiation on radiation-induced thymic lymphoma in mice

    Objective: To search for influence of low dose radiation (LDR) on thymic lymphoma (TL) induced by carcinogenic dose radiation in C57BL /6J mice and its immunologic mechanism. Methods: The model was adopted that C57BL/6J mice were subjected to whole body irradiation with 1.75 Gy X-ray once every week for 4 weeks to induce TL. The incidence of TL was observed by microscopy 6 months after irradiation. The following indexes were examined:splenic NK cytotoxic activity, IL-2 and γ- IFN secretion activity, peritoneal macrophage phagocytosis and its TNFα secretion activity, the changes of thymocyte differentiation in mice irradiated with different dose 1 month after irradiation. Results: The incidences of Tl in mice irradiated with 25mGy or 75m Gy 6h or 12h before 1.75Gy irradiation were all lower than that in mice irradiated with 1.75Gy only, and it is more obvious in mice irradiated with 75mGy prior to carcinogenic dose radiation. Immune parameters mentioned above in mice irradiated with 75mGy 12h before 1.75Gy were higher than those in mice irradiated with 1.75 only and the majority approached to those of the sham-irradiated mice. The number of thymic CD4-CD8 cells or CD4-CD8- cells was lower and CD4+CD 8+ cells was higher in mice irradiated with 75mGy 12h before 1.75Gy than that in mice irradiated with 1.75Gy only. Conclusion: LDR can induce the adaptative response of radiation-induced TL, and prevent or reduce the onset of radiation-induced TL. The suppression mechanism may be related to the immuno-enhancement effect and the adaptive response induced by LDR, decreasing immune function damage caused by carcinogenic dose radiation, eliminating thymic pre-lymphoma cells before they from solid tumor

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

    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

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

    Turek, Ilona

    2014-11-26

    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.

  14. Plant Natriuretic Peptides induce proteins diagnostic for an adaptive response to stress

    Ilona eTurek

    2014-11-01

    Full Text Available 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-homologues 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.

  15. Inducible protective processes in animal systems XIV: Cytogenetic adaptive response induced by EMS or MMS in bone marrow cells of diabetic mouse

    B.B. Dada Khalandar

    2016-04-01

    Conclusion: (1 Methylating agents are a more effective inducer of adaptive response than ethylating agents in diabetic mouse. (2 Further, it is interesting to note that the percentage reduction of chromosomal breaks in diabetics is comparatively much less than in non diabetic mouse, inferring that there is variation in adaptive response between diseased and non diseased condition.

  16. In vivo study of the adaptive response induced by radiation of different types

    Low doses of X- and gamma-rays are known to induce the adaptive response (AR), i.e. a reduction in the damage caused by subsequent high doses. Using micronucleus test, we investigated the in vivo induction of AR in mouse bone marrow cells by low doses of radiation of different types. In our experiments we used low-LET gamma-radiation, high-LET secondary radiation from 70 GeV protons and secondary biogenic radiation. The latter is a novel type of radiation discovered only recently. Secondary biogenic radiation is known to be induced in biological objects after exposure to radiation and thought to be responsible for stimulating and protecting effects in cells in response to external irradiation. To expose mice to the secondary biogenic radiation, animals were housed in plastic cages containing gamma-irradiated oat seeds as bedding and food for 2 weeks before challenging with a high dose (1.5 Gy at a dose rate of 1 Gy/min) of 60Co gamma-radiation. It was found that the yield of cytogenetic damage in mice exposed to both secondary biogenic and gamma-radiation was significantly reduced as compared to that in animals exposed to the challenge dose alone, i.e. the AR was induced. Pretreatment of animals with a low dose of gamma-radiation (0.1 Gy at a dose rate of 0.125 Gy/min) also induced the AR. In contrast, preliminary exposure of mice to a low dose (0.09 Gy at a dose rate of 1 Gy/min) of secondary radiation from 70 GeV protons induced no AR, suggesting that triggering the cascade of events leading to the AR induction depends on the DNA single-strand to double- strand breaks ratio. The precise mechanisms underlying the AR are of great importance since the phenomenon of AR can be used for medical benefits and in assessment of risks for carcinogens. But they have not been elucidated well at present. Taken together, our results suggest the crucial role of particular types of initial DNA lesions and the secondary biogenic radiation induced in cells in response to external

  17. Adaptive response induced by low doses of ionizing radiation in human lymphocytes

    The term adaptive response (AR) applies to the phenomenon of protection or enhanced repair induced by a small dose of a mutagenic agent. In order to determine the existence of AR in human lymphocytes for two different irradiation schemes, microcultures of blood from 4 donors were irradiated. Samples were exposed 24 hours (hr) after phytohemagglutinin stimulation to an adapting dose of 0,01 Gy and to a challenging dose of 1,5 Gy either 6 or 24 hr later (irradiation scheme 24+30 or 24+48, respectively). Gamma radiation from a 2,5 MeV Linac was used in all experiments. A cytogenetic analysis of unstable chromosome aberrations was applied as the endpoint. High inter-individual variability was found for the first irradiation scheme: one expressed AR, two did not and the last showed an apparent synergistic response. For the second irradiation scheme, low mitotic indices (MI) were found, suggesting a G2 arrest. When a series of harvesting times were applied for the last donor, normal MI were obtained only harvesting after 58 hr. An AR was found when harvesting at 72 hr but not at 58 hr. (author)

  18. Radio-adaptive response

    An adaptive response to radiation stress was found as a suppressed induction of chromosomal damage including micronuclei and sister chromatid exchanges in cultured Chinese hamster V79 cells pre-exposed to very low doses of ionizing radiations. The mechanism underlying this novel chromosomal response, called 'radio-adaptive response (RAR)' has been studied progressively. The following results were obtained in recent experiments. 1. Low doses of β-rays from tritiated water (HTO) as well as tritium-thymidine can cause RAR. 2. Thermal neutrons, a high LET radiation, can not act as tritium β-rays or γ-rays. 3. The RAR expression is suppressed not only by the treatment with an inhibitor of protein synthesis but also by RNA synthesis inhibition. 4. Several proteins are newly synthesized concurrently with the RAR expression after the adapting doses, viewed by two-dimensional electrophoresis of cellular proteins. These results suggests that the RAR might be a cellular stress response to a signal produced preferentially by very low doses of low LET radiation under restricted conditions, accompany the inducible specific gene expression. (author)

  19. Interval for the expression of the adaptive response induced by gamma radiation in leucocytes of mouse In vivo

    The interval between the adaptive gamma radiation dose (0.01 Gy) and challenge (1.0 Gy) capable to induce the maximum expression of the adaptive response in lymphocytes of mouse In vivo. The animals were exposed to the mentioned doses with different intervals among both (1, 1.5, 5 or 18 hr). By means of the unicellular electrophoresis in gel technique, four damage parameters were analysed. The results showed that from the 1 hr interval an adaptive response was produced since in the pretreated organisms with 0.01 Gy the cells present lesser damage than in those not adapted. The maximum response was induced with the intervals between 2.5 and 5 hr and even though it persisted until 18 hr, the effect was reducing. (Author)

  20. The innate and adaptive immune response induced by alveolar macrophages exposed to ambient particulate matter

    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 μm or less, PM10) induce innate immune responses via endotoxin-toll-like receptor (TLR) 4 pathway while fine (2.5 μm or less, PM2.5) and ultrafine particles (0.1 μm 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)-κB and activator protein-1] and the downstream proinflammatory cytokine [interleukin (IL)-1β, IL-6, and tumor necrosis factor-α] 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-κB 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.

  1. The innate and adaptive immune response induced by alveolar macrophages exposed to ambient particulate matter

    Miyata, Ryohei; Eeden, Stephan F. van, E-mail: Stephan.vanEeden@hli.ubc.ca

    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.

  2. Adaptive Response to ionizing Radiation Induced by Low Doses of Gamma Rays in Human Lymphoblastoid Cell Lines

    When cells are exposed to low doses of a mutagenic or clastogenic agents, they often become less sensitive to the effects of a higher does administered subsequently. Such adaptive responses were first described in Escherichia coli and mammalian cells to low doses of an alkylating agent. Since most of the studies have been carried out with human lymphocytes, it is urgently necessary to study this effect in different cellular systems. Its relation with inherent cellular radiosensitivity and underlying mechanism also remain to be answered. In this study, adaptive response by 1 cGy of gamma rays was investigated in three human lymphoblastoid cell lines which were derived from ataxia telangiectasia homozygote, ataxia telangiectasia heterozygote, and normal individual. Experiments were carried out by delivering 1 cGy followed by 50 cGy of gamma radiation and chromatid breaks were scored as an endpoint. The results indicate that prior exposure to 1 cGy of gamma rays reduces the number of chromatid breaks induced by subsequent higher does (50 cGy). The expression of this adaptive response was similar among three cell lines despite of their different radiosensitivity. When 3-aminobenzamide, an inhibitor of poly (ADP-ribose) polymerase, was added after 50 cGy, adaptive responses were abolished in all the tested cell lines. Therefore it is suggested that the adaptive response can be observed in human lymphoblastoid cell lines. Which was first documented through this study. The expression of adaptive response was similar among the cell lines regardless of their radiosensitivity. The elimination of the adaptive response by 3-aminobenzamide is consistent with the proposal that this adaptive response is the result of the induction of a certain chromosomal repair mechanism

  3. Relationship between radiation induced adaptive response in human fibroblasts and changes in chromatin conformation

    Ya. Belyaev, Igor [Department of Radiation Physics, Biophysics and Ecology, Moscow Engineering Physics Institute, Moscow (Russia); Spivak, Irina M.; Kolman, Ada; Harms-Ringdahl, Mats [Department of Radiobiology, Stockholm University, Stockholm (Sweden)

    1996-11-04

    Chromatin conformation changes in the normal human fibroblasts VH-10 were studied by the method of anomalous viscosity time dependence (AVTD). Gamma-irradiation of cells in a dose range of 0.1-3 Gy caused an increase in maximal viscosity of cell lysates. Conversely, irradiation of cells with low doses of 0.5 or 2 cGy resulted in a decrease in the AVTD peaks with a maximum effect approximately 40 min after irradiation. The same exposure conditions were used to study a possible adaptive effect of low doses, measured by changes in cell survival. A primary dose of 2 cGy caused significant modification of cell response to a challenge dose. Approximately 20% protection to challenge doses of 0.5 Gy (p<0.003), 2 Gy (p<0.02) and 2.5 Gy (p<0.002) was observed. However, the direction of this effect (adaptation or synergism) was found to be dependent on a challenge dose. The combined effect of 2 cGy and 1 Gy was significantly synergistic, while no modification was observed for 1.5 Gy and 3 Gy. A partial correlation was found between the AVTD changes and cell survival when the combined effect of a primary dose of 2 cGy and challenge dose was examined. The dose of 2 cGy alone increased survival by 16% (p<0.0003). These results suggest that the low-dose induced effects on survival may be related to chromatin reorganization.

  4. Hippocampal adaptive response following extensive neuronal loss in an inducible transgenic mouse model.

    Kristoffer Myczek

    Full Text Available Neuronal loss is a common component of a variety of neurodegenerative disorders (including Alzheimer's, Parkinson's, and Huntington's disease and brain traumas (stroke, epilepsy, and traumatic brain injury. One brain region that commonly exhibits neuronal loss in several neurodegenerative disorders is the hippocampus, an area of the brain critical for the formation and retrieval of memories. Long-lasting and sometimes unrecoverable deficits caused by neuronal loss present a unique challenge for clinicians and for researchers who attempt to model these traumas in animals. Can these deficits be recovered, and if so, is the brain capable of regeneration following neuronal loss? To address this significant question, we utilized the innovative CaM/Tet-DT(A mouse model that selectively induces neuronal ablation. We found that we are able to inflict a consistent and significant lesion to the hippocampus, resulting in hippocampally-dependent behavioral deficits and a long-lasting upregulation in neurogenesis, suggesting that this process might be a critical part of hippocampal recovery. In addition, we provide novel evidence of angiogenic and vasculature changes following hippocampal neuronal loss in CaM/Tet-DTA mice. We posit that angiogenesis may be an important factor that promotes neurogenic upregulation following hippocampal neuronal loss, and both factors, angiogenesis and neurogenesis, can contribute to the adaptive response of the brain for behavioral recovery.

  5. Can previous thyroid scan induce cytogenetic radio adaptive response in patients treated by radioiodine for hyperthyroidism?

    Background: Induction of radio adaptive responses in cells pretreated with a low dose radiation before exposure to a high dose is well documented by many in investigators. The aim of this study is to determine the frequency of chromosomal aberration in peripheral blood lymphocytes of patients treated by radioiodine (131 I) for hyperthyroidism, with or without previous thyroid scan with 99m Tc. Materials and methods: venous blood samples were obtained from 35 patients one month after radioiodine therapy and cytogenetic ally evaluated using analysis of metaphase in two groups. The first group (n=15, 13 females and 2 males, mean age=44.7±11.5 years and mean weight 74.4±7.9 Kg) received 5 mCi 99m Tc for thyroid scanning 38.6±19.9 days before radioiodine therapy with 10.4±3.4 mCi 131I. The second group (n=20, 14 females and 6 males, mean age=41.0±10.8 years and mean weight=68.1±9.2 Kg) didn't have history of thyroid scanning. We also studied a control group (n=29, 11 females and 8 males age=33.7±7.4 and mean weight=70.0±8.8 Kg) who didn't have any history of diagnostic or therapeutic and also occupational exposure. Results: The mean frequency of total chromosomal aberrations in the first and second groups and controls were 1.46±1.55, 1.65±1.62 and 0.93±0.92 respectively. Results also showed that the mean frequency of total chromosome aberration in two groups were higher than controls and significantly higher in patients who had not received 99m Tc compared those who had undertaken thyroid scan before radioiodine therapy (p=0.03). Conclusion: These findings may indicate the fact that the radiation dose received from 99m Tc could induce resistance to subsequent higher radiation dose of 131 I in peripheral blood lymphocytes and it might be due to cytogenetic radio adaptive response

  6. Survival adaptive response in rats induced by some common radiographic procedures

    Complete text of publication follows. Objective: Low dose irradiation suppresses the molecular responses against a subsequent high dose irradiation. Survival adaptive response can be defined as increased survival of laboratory animals pre-exposed to a conditioning (adapting) dose after irradiation with a high (challenge) dose. In this study, the induction of survival adaptive response is investigated in rats exposed to x-rays generated by a common radiographic machine followed by a challenge irradiation. Methods: Twenty rats (average weight of 200g) were divided randomly into four groups each consisting of 5 animals. The 1st-3rd groups were pre-exposed to 3 different common diagnostic levels of x-rays; low (0.22±0.03 mGy; mean±SD), intermediate (0.43±0.05 mGy) and high (0.93±0.10 mGy). These entrance surface doses were similar to doses received in common radiographic procedures. The 4th group was only sham exposed to x-rays. Twenty four hours after conditioning dose, a Cs-137 source was used for irradiating all animals with a sublethal challenge dose of 7 Gy. Results: Two weeks after the irradiation with challenge dose, 2, 3, 5 and 2 animals survived in 1st to 4th groups respectively. Thirty days after irradiation with challenge dose, 2, 1, 4 and 2 animals survived in 1st to 4th group respectively. The observed differences in survival rates in either 1st or 2nd group with the 4th group were not statistically significant. Although the animals in the 3rd group (high adapting dose) had a higher survival rate compared to either 1st and 2nd groups or the 4th group, these differences were not statistically significant. Conclusions: These findings may confirm the previous reports that indicated the existence of a narrow window of adapting doses for induction of adaptive response.

  7. Persistence and prevention of aluminium- and paraquat-induced adaptive response to methyl mercuric chloride in plant cells in vivo.

    Patra, Jita; Sahoo, Malaya K; Panda, Brahma B

    2003-07-01

    Induction and persistence of adaptive response by aluminium (Al), 1 or 10 microM, and paraquat (PQ), 5 or 10 microM, against genotoxicity of methyl mercuric chloride (MMCl), 1.26 microM, a standard environmental genotoxin, was investigated in root meristem cells of Allium cepa. Subsequently, three metabolic inhibitors, namely, 3-aminobezamide (3-AB, 10 or 100 microM), an inhibitor of poly(ADP-ribose) polymerase (PARP) implicated in DNA repair and/or apoptosis, cycloheximide (CH, 0.1 or 1 microM), an inhibitor of protein synthesis, and buthionine sulfoximine (BSO, 100 microM or 1mM), an inhibitor of glutathione synthesis were tested for their ability to prevent the adaptive response induced by conditioning doses of Al, 10 or 100 microM; and PQ, 5 or 100 microM, against MMCl-challenge, 1.26 or 100 microM, in root meristems of A. cepa or embryonic shoots of Hordeum vulgare, respectively. The findings demonstrated that once triggered, the Al- or PQ-adaptive response to MMCl could persist for at least 48h in root meristems of A. cepa. Furthermore, the adaptive response could effectively be prevented by 3-AB, to a lesser degree by CH, and the least by BSO, suggesting primarily the involvement of PARP and implicating DNA repair in the underlying mechanisms of adaptive response in plant cells in vivo. PMID:12834754

  8. Low dose radiation induced adaptive response upon salt stress and vacuum stress: a possible mechanism for the effect of saddle-like dose response curve

    To explore mechanism for the effect of saddle-like dose-response curve, the relationship of irradiation-vacuum stress, and irradiation-salt stress, was investigated with rice seeds irradiated to 60-560 Gy by 60Co γ-rays. The dose-response curve was simulated based on seedling height data, which showed obedient to linear-quadratic model. During germination,the irradiated rice seeds were stressed by 10-3 Pa vacuum, or by NaCl in different concentrations. After that, the dose-response curve manifested a saddle-like shape. The results indicate that while low dose irradiation could retard seedling growth synergistically with vacuum stress and salt stress, it could also induce adaptive response upon vacuum stress and salt stress. Low dose irradiation induced adaptive response upon environmental adverse factors could contribute to the mechanism for the effect of saddle-like dose-response curve. (authors)

  9. The absence of radiation-induced adaptive response in lymphocytes of patients with Down's syndrome

    The adaptive syndrome and response (AR) in lymphocytes from 6 patients with Down syndrome (DS) were investigated. No AR was found to occur in all cases in DS cells pre-exposed to 3 rad of X-rays in S phase of cell cycle and then irradiated with 150 rad of gamma rays in G2 whereas the chromosome aberrations yield in cells from control donors was decreased twice under such conditions of the experiment

  10. Inbreeding and adaptive plasticity: an experimental analysis on predator-induced responses in the water flea Daphnia.

    Swillen, Ine; Vanoverbeke, Joost; De Meester, Luc

    2015-07-01

    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

  11. Neutron-induced adaptive response studied in go human lymphocytes using the comet assay.

    Gajendiran, N; Tanaka, K; Kumaravel, T S; Kamada, N

    2001-03-01

    This study demonstrates that cells adapted to ionizing radiation developed reduced initial DNA damage when compared to non-adapted cells. The results were obtained by subjecting in vitro irradiated whole blood from 10 healthy volunteers (including 2 A-bomb survivors carrying 1.5-2 Gy in vivo exposure) in an unstimulated condition (G0) using the comet assay. The intensity of DNA damage was assessed by computing the 'tail moment'. Adaptive response (AR) was noticed in only donor 3, as indicated by reduced tail moment when the blood samples received priming + challenging doses over a 4 h interval. The priming dose was either 0.01 Gy 137Cs gamma-rays or 0.0025 Gy 252Cf neutrons. The delivered challenging dose was either 1 Gy 60Co g-rays or 0.25 Gy 252Cf neutrons. The irradiation was conducted using the HIRRAC facility. A prior exposure to 0.0025 Gy 252Cf neutrons nullified the excess tail moment caused by 0.25 Gy neutrons given during a 4 h gap. In a similar way, 0.01 Gy 137Cs gamma-rays offered a cross-adaptive response to the neutron challenging dose. The tail moment of A-bomb survivors after in vitro irradiation was less than that of the age-matched control and, at the same time, was not influenced by the priming dose. An altered subset and the immunological status of blood after A-bomb exposure were cited as possible factors. Because AR can affect the outcome of RBE, its individual variability only emphasizes the need to have individual biodosimetry for better risk assessment, especially in planning for a long space voyage. PMID:11393893

  12. Effects of inhibitors of protein kinase C and NO-synthase on the radiation-induced cytogenetic adaptive response in Chinese hamster cells in culture

    The effect of the serine-threonin kinase inhibitor - staurosporine and inhibitor of NO-synthase - L-NAME on the radiation-induced adaptive response were studied in fibroblasts of Chinese hamster in culture. It is shown that staurosporine and L-NAME inhibit cytogenetic adaptive response induced by β-particles in low doses. Inhibition is not connected with radiosensitizing effect of these agents. L-NAME decreases significantly the γ-rays-induced chromosome aberration yield also. Study confirms the role of protein kinase C in induction of the adaptive response and participation of NO-synthase in this process is noticed for the first time

  13. Characterization of the adaptive response to ionizing radiation induced by low doses of X-rays to Vibrio cholerae cells

    Pretreatment with sublethal doses of X-rays induced an adaptive response in Vibrio cholerae cells as indicated by their greater resistance to the subsequent challenging doses of X-irradiation. The adaptive response was maximum following a pre-exposure dose of 1.7 Gy X-rays and an optimum incubation period of 40 min at 37C. Pre-exposure to a sublethal dose of 1.7 Gy X-rays made the Vibrio cholerae cells 3.38-fold more resistant to the subsequent challenge by X-rays. Pretreatment with a sublethal dose of hydrogen peroxide offered a similar degree of protection to the bacterial cells against subsequent treatment with challenging doses of X-ray radiation. However, exposure of Vibrio cholerae cells to mild heat (42C for 10 min) before X-ray irradiation decreased their survival following X-irradiation

  14. Low dose effects. Adaptive response

    The purpose of this work was to evaluate if there are disturbancies in adaptive response when lymphocytes of people living on the polluted with radionuclides area after Chernobyl disaster and liquidators suffered from accident have been investigated. The level of lymphocytes with micronuclei have been scored in Moscow donors and people living in Bryansk region with the degree of contamination 15 - 40 Ci/km. The doses that liquidators have been obtained were not higher then 25 cGy. The mean spontaneous level of MN in control people and people from Chernobyl zones does't differ significantly but the individual variability in the mean value between two populations does not differ significantly too. And in this case it seems that persons of exposed areas. Then another important fact in lymphocytes of people living on polluted areas the chronic low dose irradiation does not induce the adaptive response. In Moscow people in most cases (≅ 59 %) the adaptive response is observed and in some cases the demonstration of adaptive response is not significant (≅1%). In Chernobyl population exposed to chronic low level, low dose rate irradiation there are fewer people here with distinct adaptive response (≅38%). And there appear beings with increased radiosensitivity after conditioned dose. Such population with enhanced radiosensitivity have not observed in Moscow. In liquidators the same types of effects have been registered. These results have been obtained on adults. Adaptive response in children 8 - 14 old population living in Moscow and in Chernobyl zone have been investigated too. In this case the spontaneous level of MN is higher in children living in polluted areas, after the 1.0 Gy irradiation the individual variability is very large. Only 5 % of children have distinct is very large. Only 5 % of children have distinct adaptive response, the enhancement of radiosensitivity after conditioned dose is observed. (authors)

  15. Vanguards of paradigm shift in radiation biology. Radiation-induced adaptive and bystander responses

    The risks of exposure to low dose ionizing radiation (below 100 mSv) are estimated by extrapolating from data obtained after exposure to high dose radiation, using a linear no-threshold model (LNT model). However, the validity of using this dose-response model is controversial because evidence accumulated over the past decade has indicated that living organisms, including humans, respond differently to low dose/low dose-rate radiation than they do to high dose/high dose-rate radiation. In other words, there are accumulated findings which cannot be explained by the classical ''target theory'' of radiation biology. The radioadaptive response, radiation-induced bystander effects, low-dose radio-hypersensitivity, and genomic instability are specifically observed in response to low dose/low dose-rate radiation, and the mechanisms underlying these responses often involve biochemical/molecular signals that respond to targeted and non-targeted events. Recently, correlations between the radioadaptive and bystander responses have been increasingly reported. The present review focuses on the latter two phenomena by summarizing observations supporting their existence, and discussing the linkage between them from the aspect of production of reactive oxygen and nitrogen species. (author)

  16. The adaptive response of human lymphocytes to very low doses of ionizing radiation: a case of induced chromosomal repair with the induction of specific proteins

    It appears that the adaptive response of human lymphocytes to low doses of X-rays can be mimicked by exposure to low levels of a truly radiomimetic compound, bleomycin, that induces double-strand breaks in DNA. Similarly, the adaptive response can be induced by exposure to low levels of H2O2, which produces reactive species similar to those induced by ionizing radiation. This adaptive response, which is attributed to the induction of a repair mechanism, i.e. repair enzymes, can be prevented if protein synthesis, and thus enzyme synthesis, is inhibited by cycloheximide at the crucial time (4-6 h) after exposure to the adaptive dose. Two-dimensional gel electrophoresis has shown that 1 cGy of X-rays can reproducibly induce several proteins not found in unirradiated lymphocytes. These proteins are considered to be excellent candidates for the actual repair enzyme(s). (author)

  17. The threshold number of protons to induce an adaptive response in zebrafish embryos

    In this study, microbeam protons were used to provide the priming dose to induce an in vivo radioadaptive response (RAR) in the embryos of zebrafish, Danio rerio, against subsequent challenging doses provided by x-ray photons. The microbeam irradiation system (Single-Particle Irradiation System to Cell, acronym SPICE) at the National Institute of Radiological Sciences (NIRS), Japan, was employed. The embryos were dechorionated at 4 h post fertilisation (hpf) and irradiated at 5 hpf by microbeam protons. For each embryo, one irradiation point was chosen, to which 5, 10, 20, 30, 40, 50, 100, 200, 300 and 500 protons each with an energy of 3.4 MeV were delivered. The embryos were returned to the incubator until 10 hpf to further receive the challenging exposure, which was achieved using 2 Gy of x-ray irradiation, and then again returned to the incubator until 24 hpf for analyses. The levels of apoptosis in zebrafish embryos at 25 hpf were quantified through terminal dUTP transferase-mediated nick end-labelling (TUNEL) assay. The results revealed that at least 200 protons (with average radiation doses of about 300 and 650 mGy absorbed by an irradiated epithelial and deep cell, respectively) would be required to induce RAR in the zebrafish embryos in vivo. Our previous investigation showed that 5 protons delivered at 10 points on an embryo would already be sufficient to induce RAR in the zebrafish embryos. The difference was explained in terms of the radiation-induced bystander effect as well as the rescue effect. (paper)

  18. Hormesis and adaptive response of survival in Hela cells induced by low dose X-ray irradiation

    The survival fraction in HeLa cells irradiated by low dose X-rays was observed using clone method. The results showed that the survival fraction in the cells irradiated by less than 0.5 Gy X-rays was higher than control, 'hormesis' of HeLa cell survival was obtained and was significant at doses near 0.25 Gy; also, the damage degree of cells induced by the following irradiation was reduced because of pre-treating the cells with low dose D1 of 0.05, 0.75 Gy; it was found from above that 'adaptive response' of cell survival was induced by the low dose irradiation

  19. Acute adaptive immune response correlates with late radiation-induced pulmonary fibrosis in mice

    The lung response to radiation exposure can involve an immediate or early reaction to the radiation challenge, including cell death and an initial immune reaction, and can be followed by a tissue injury response, of pneumonitis or fibrosis, to this acute reaction. Herein, we aimed to determine whether markers of the initial immune response, measured within days of radiation exposure, are correlated with the lung tissue injury responses occurring weeks later. Inbred strains of mice known to be susceptible (KK/HIJ, C57BL/6J, 129S1/SvImJ) or resistant (C3H/HeJ, A/J, AKR/J) to radiation-induced pulmonary fibrosis and to vary in time to onset of respiratory distress post thoracic irradiation (from 10–23 weeks) were studied. Mice were untreated (controls) or received 18 Gy whole thorax irradiation and were euthanized at 6 h, 1d or 7 d after radiation treatment. Pulmonary CD4+ lymphocytes, bronchoalveolar cell profile & cytokine level, and serum cytokine levels were assayed. Thoracic irradiation and inbred strain background significantly affected the numbers of CD4+ cells in the lungs and the bronchoalveolar lavage cell differential of exposed mice. At the 7 day timepoint greater numbers of pulmonary Th1 and Th17 lymphocytes and reduced lavage interleukin17 and interferonγ levels were significant predictors of late stage fibrosis. Lavage levels of interleukin-10, measured at the 7 day timepoint, were inversely correlated with fibrosis score (R = −0.80, p = 0.05), while serum levels of interleukin-17 in control mice significantly correlated with post irradiation survival time (R = 0.81, p = 0.04). Lavage macrophage, lymphocyte or neutrophil counts were not significantly correlated with either of fibrosis score or time to respiratory distress in the six mouse strains. Specific cytokine and lymphocyte levels, but not strain dependent lavage cell profiles, were predictive of later radiation-induced lung injury in this panel of inbred strains. The online version of this

  20. Contribution of nitric oxide radicals in bystander and adaptive responses induced by heavy ion-beams

    The purpose of this study was to investigate whether radioadaptive responses were induced after irradiation with accelerated ion beams through nitric oxide-mediated bystander response in cultured cells in vitro and in some organs of mice in vivo. Human non-small cell lung carcinoma cells transfected with wild-type p53 (H1299/wtp53 cells) were used. The cells were irradiated with accelerated neon (400 MeV/u, 31 keV/μm) or iron (500 MeV/u, 200 keV/μm) ion beams. Then, the cells were allowed forming colonies, were cultured for 48 h to obtained samples for Western blot analysis, or were cultured for several weeks to fix mutations in the locus of hprt gene. ICR male mice (Jcl:ICR) were used. The mice were irradiated on 2 days with accelerated carbon ion beams (290 MeV/u, 13 keV/μm) or argon ion beams (500 MeV/u, 90 keV/μm). The intestine and testis were excised 2 days after the last irradiation. These excised tissues were fixed, embedded in paraffin and made of thin-sections on slide glasses. Then the TdT-mediated dUTP-biotin nick end-labeling (TUNEL)- and activated caspase-3-positive cells in the thin-sections of tissues were detected by the immunohistochemical method. A significant reduction of mutation rate of the hprt gene was observed when the cells were challengingly irradiated after the priming irradiation with accelerate neon or iron ion beams. This reduction was partially suppressed by NO radical scavenger, carboxy-PTIO. The bystander-induced apoptotic and activated caspase-3-positive cells were obviously observed in unirradiated intestine and testis when mice were irradiated with carbon or argon ion beams across the upper body. These observations were partially suppressed by carboxy-PTIO into the peritoneal cavity. (author)

  1. Contribution of nitric oxide radicals in bystander and adaptive responses induced by heavy ion-beams

    The purpose of this study was to investigate whether radioadaptive responses were induced after irradiation with accelerated ion beams through nitric oxide-mediated bystander response in cultured cells in vitro and in some organs of mice in vivo. Human non-small cell lung carcinoma cells transfected with wild-type p53 (H1299/wtp53 cells) were used. The cells were irradiated with accelerated carbon ion beams (290 MeV/u, 31 keV/μm or 135 MeV/u, 31 keV/μm). Then, the cells were allowed forming colonies. ICR male mice (Jcl: ICR) were used. The mice were irradiated on 2 days with accelerated carbon ion beams (290 MeV/u, 13 keV/μm or 135 MeV/u, 25 keV/μm) or argon ion beams (500 MeV/u, 90 keV/μm). The small intestine and testis were excised 2 days after the last irradiation. These excised tissues were fixed, embedded in paraffin and made of thin-sections on slide glasses. Then the TUNEL- and activated caspase-3-positive cells in the thin-sections of tissues were detected by the immunohistochemical method. A significant elevated surviving fractions of cells was observed when the cells were challengingly irradiated after the priming irradiation with accelerate carbon ion beams. This enhancement was partially suppressed by Nitric oxide (NO) radical scavenger, carboxy-PTIO (c-PTIO). The bystander-induced apoptotic and activated caspase-3-positive cells were obviously observed in the unirradiated small intestine and testis when mice were irradiated with carbon or argon ion beams across the upper body. In addition, a significant reduction of apoptotic cells in the intestine and testis, when mice were challengingly irradiated after the priming irradiation with accelerate carbon or argon ion beams. These observations were partially suppressed by c-PTIO into the peritoneal cavity. Furthermore, it is suggested that the apoptosis may be induced in the tissue stem cells of small intestine and testis. (author)

  2. Low-dose Radiation-Induced Adaptive Response in Polychromatic Mice Erythrocyte as Measures by Acridine Orange Stained Micronucleus Assay

    The effect of conditioning pretreatment with 0.01Gy of gamma rays on micronucleated polychromatic erythrocyte (MN-PCE) induction by 2Gy of g-rays was determined in peripheral blood of C3H/He mice. The timing of their administration of challenge doses was 6 hr. The response was determined by scoring of Acridine orange due stained MN-PCEs. The results indicate that low dose gamma ray pretreatment does protect against MN-PCE induction by the challenge g-ray dose. Introduction: an adaptive response induced by low doses of ionizing radiation in vivo reported. Some research team reports that a reduction on MN-PCE of mice caused by the pretreatment was observed (1-4). However, there was variability in the amount of the response depending on the time and adaptive dose (3). This is important because the variation of MN-PCE frequency with time could lead to differences in the interpretation. In this study, differences in the biological effects within the priming dose ranges are discussed. (Author)

  3. Low-Dose Radiation-Induced Adaptive Response in Polychromatic Mice Erythrocyte as Measured by Acridine Orange Stained Micronuleus Assay

    The effect of conditioning pretreatment with 0.01Gy of gamma rays on micronucleated polychromatic erythrocyte (MN-PCE) induction by 2Gy of g-rays was determined in peripheral blood of C3H/He mice. The timing of their administration of challenge doses was 6hr. The response was determined by scoring of Acridine orange dye stained MN-PCEs. The results indicate that low dose gamma ray pretreatment does protect against MN-PCE induction by the challenge g-ray dose. Introduction: An adaptive response induced by low doses of ionizing radiation in vivo reported. Some research team reports that a reduction on MN-PCE of mice caused by the pretreatment was observed [1- 4]. However, there was variability in the amount of the response depending on the time and adaptive dose [3]. This is important because the variation of MN-PCE frequency with time could lead to differences in the interpretation. In this study, differences in the biological effects within the priming dose ranges are discussed. Materials and Methods: Specific pathogen free 5-week-old C3H/He mice, purchased from Shizuoka Laboratory Center (Japan), were kept in clean and conventional environment. When 6 weeks old, the animal were whole body irradiated using irradiator of IBL-437 (137Cs, 0.8Gy/min). After various time intervals, the two groups were administrated to adaptation dose and challenge dose of 0.01Gy and 2Gy, respectively. For experiments, sham-irradiated, only adaptive and challenge dose irradiated groups were run concurrently. Smears were stained and scored using Acridine orange dye method [2]. Statistically significant differences in MN-PCE frequency were determined by comparing tie individual values at each group with the respective control values (challenge dose irradiated group) by using the paired ttest. Results and Discussions: Induced MN by the challenge dose (2Gy) after the pretreatment with 0.01Gy is low to the one induced by the challenge dose alone. In the present study, this estimation for the

  4. Involvement of p27CIP/KIP in HSP25 or inducible HSP70 mediated adaptive response by low dose radiation

    ThermoResistant (TR) clones of Radiation-Induced Fibrosarcoma (RIF) cells have been reported to show an adaptive response to 1cGy of low dose radiation, and HSP25 and inducible HSP70 are involved in this process. In this study, to further elucidate the mechanism by which HSP25 and inducible HSP70 regulate the adaptive response, HSP25 or inducible HSP70 overexpressed RIF cells were irradiated with 1cGy and the cell cycle was analyzed. HSP25 or inducible HSP70 overexpressed cells together with TR cells showed increased G1 phase after 1cGy irradiation, while RIF cells did not. [3H]-Thymidine and BrdU incorporation also indicated that both HSP25 and inducible HSP70 are involved in G1 arrest after 1cGy irradiation. Molecular analysis revealed upregulation of p27Cip/Kip protein in HSP25 and inducible HSP70 overexpressed cells, and cotransfection of p27Cip/Kip antisense abolished the induction of the adaptive response and 1cGy-mediated G1 arrest. The above results indicate that induction of an adaptive response by HSP25 and inducible HSP70 is mediated by upregulation of p27Cip/Kip protein, resulting in low dose radiation-induced G1 arrest

  5. p27Cip/Kip is involved in hsp25 or inducible hsp70 mediated adaptive response by low dose radiation

    Thermoresistant (TR) clone of radiation-induced fibrosarcoma (RIF) cells have been reported to show adaptive response to 1cGy of low dose radiation, and hsp25 and inducible hsp70 are involved in this process. In the present study, to further elucidate the mechanism of how hsp25 and inducible hsp70 regulate the adaptive response, hsp25 or inducible hsp70 overexpressed RIF cells were irradiated with 1cGy and cell cycle was analyzed. Hsp25 or inducible hsp70 overexpressed cells as well as TR cells showed increase of G1 phase population after γ-irradiation at 1cGy, while the parent RIF cells did not. [3H]-Thymidine and BrdU incorporation also indicated that both hsp25 and inducible hsp70 were involved in G1 arrest after 1cGy irradiation. Molecular analysis revealed upregulation of p27Cip/Kip protein in hsp25 and inducible hsp70 overexpressed cells, and cotransfection of p27Cip/Kip antisense abolished the induction of adaptive response and 1cGy-mediated G1 arrest. The above results indicate that induction of adaptive response by hsp25 and inducible hsp70 is mediated by upregulation of p27Cip/Kip protein, resulting in low dose radiation-induced G1 arrest. (author)

  6. The roles of RelA/(p)ppGpp in glucose-starvation induced adaptive response in the zoonotic Streptococcus suis.

    Zhang, Tengfei; Zhu, Jiawen; Wei, Shun; Luo, Qingping; Li, Lu; Li, Shengqing; Tucker, Alexander; Shao, Huabin; Zhou, Rui

    2016-01-01

    The (p)ppGpp signal molecules play a central role in the stringent response (SR) to adapt to nutrient starvation in bacteria, yet the carbohydrate starvation induced adaptive response and the roles of SR in this response is not well characterized, especially in Gram-positives. Here, two (p)ppGpp synthetases RelA and RelQ are identified in Streptococcus suis, an important emerging zoonotic Gram-positive bacterium, while only RelA is functional under glucose starvation. To characterize the roles of RelA/(p)ppGpp in glucose starvation response in S. suis, the growth curves and transcriptional profiles were compared between the mutant strain ΔrelA [a (p)ppGpp(0) strain under glucose starvation] and its parental strain SC-19 [(p)ppGpp(+)]. The results showed great difference between SC-19 and ΔrelA on adaptive responses when suffering glucose starvation, and demonstrated that RelA/(p)ppGpp plays important roles in adaptation to glucose starvation. Besides the classic SR including inhibition of growth and related macromolecular synthesis, the extended adaptive response also includes inhibited glycolysis, and carbon catabolite repression (CCR)-mediated carbohydrate-dependent metabolic switches. Collectively, the pheno- and genotypic characterization of the glucose starvation induced adaptive response in S. suis makes a great contribution to understanding better the mechanism of SR. PMID:27255540

  7. Adaptive response in zebrafish embryos induced using microbeam protons as priming dose and X-ray photons as challenging dose

    In the studies reported here, a high-linear-energy-transfer (high-LET)-radiation dose was used to induce adaptive response in zebrafish embryos in vivo. Microbeam protons were used to provide the priming dose and X-ray photons were employed to provide the challenging dose. The microbeam irradiation system (Single-Particle Irradiation System to Cell, acronym as SPICE) at the National Institute of Radiological Sciences (NIRS), Japan, was employed to control and accurately quantify the number of protons at very low doses, viz., about 100 μGy. The embryos were dechorionated at 4 h post fertilization (hpf) and irradiated at 5 hpf by microbeam protons. For each embryo, ten irradiation points were arbitrarily chosen without overlapping with one another. To each irradiation point, 5, 10 or 20 protons each with an energy of 3.4 MeV were delivered. The embryos were returned back to the incubator until 10 hpf to further receive the challenging exposure, which was achieved using 2 Gy of X-ray irradiation, and then again returned to the incubator until 24 hpf for analyses. The levels of apoptosis in zebrafish embryos at 25 hpf were quantified through terminal dUTP transferase-mediated nick end-labeling (TUNEL) assay, with the apoptotic signals captured by a confocal microscope. The results revealed that 5 to 20 protons delivered at 10 points each on the embryos, or equivalently 110 to 430 μGy, could induce radioadaptive response in the zebrafish embryos in vivo. (author)

  8. Accumulation of small heat shock proteins, including mitochondrial HSP22, induced by oxidative stress and adaptive response in tomato cells

    Changes in gene expression, by application of H2O2, O2.- generating agents (methyl viologen, digitonin) and gamma irradiation to tomato suspension cultures, were investigated and compared to the well-described heat shock response. Two-dimensional gel protein mapping analyses gave the first indication that at least small heat shock proteins (smHSP) accumulated in response to application of H2O2 and gamma irradiation, but not to O2.- generating agents. While some proteins seemed to be induced specifically by each treatment, only part of the heat shock response was observed. On the basis of Northern hybridization experiments performed with four heterologous cDNA, corresponding to classes I-IV of pea smHSP, it could be concluded that significant amounts of class I and II smHSP mRNA are induced by H2O2 and by irradiation. Taken together, these results demonstrate that in plants some HSP genes are inducible by oxidative stresses, as in micro-organisms and other eukaryotic cells. HSP22, the main stress protein that accumulates following H2O2 action or gamma irradiation, was also purified. Sequence homology of amino terminal and internal sequences, and immunoreactivity with Chenopodium rubrum mitochondrial smHSP antibody, indicated that the protein belongs to the recently discovered class of plant mitochondrial smHSP. Heat shock or a mild H2O2 pretreatment was also shown to lead to plant cell protection against oxidative injury. Therefore, the synthesis of these stress proteins can be considered as an adaptive mechanism in which mitochondrial protection could be essential

  9. Adaptive response to and its time effect on radiation-induced chromosome aberrations in mouse embryonic cells pre-exposed to cadmium chloride

    Objective: To observe if cadmium chloride could induce cross adaptive response to and its time effect on cytogenetic damage of mouse embryonic cells caused by ionizing radiation. Methods: The mice were pre-treated with iv injection of cadmium chloride solution on gestation d 9, then they were exposed to 1.5 cGy 60Co γ-rays at different time intervals. Chromosome preparation was made on gestation d 10. Results: 0.25-2 mg Cd/kg body weight could induce resistance to cytogenetic damage of embryonic cells of mice caused by ionizing radiation and the adaptive response appeared 4 h after pre-exposure, at 8h reached the peak, but 12 to 24 h later synergism appeared. Conclusion: Cadmium chloride could induce cross adaptive response to 60Co γ-rays which had relations with time interval of ionizing radiation

  10. Pica as an adaptive response: Kaolin consumption helps rats recover from chemotherapy-induced illness

    De Jonghe, Bart C.; Lawler, Maureen P.; Horn, Charles C.; Tordoff, Michael G.

    2009-01-01

    Clay consumption can occur during illness but there has been little work to understand why. To investigate whether consuming clay confers an advantage to the sick animal, we compared the recovery from illness of adult male rats with or without access to kaolin. Illness was induced by injection of 6 mg/kg, ip, cisplatin, a toxic chemotherapy agent, and recovery was assessed by changes in daily food intake, water intake, and body weight. Relative to saline-injected controls, cisplatin-injected ...

  11. Endogenous nitric oxide mediates He-Ne laser-induced adaptive responses in salt stressed-tall fescue leaves.

    Li, Yongfeng; Gao, Limei; Han, Rong

    2016-10-01

    The aim of this study was to investigate the role of endogenous nitric oxide in protective effects of He-Ne laser on salt stressed-tall fescue leaves. Salt stress resulted in significant increases of membrane injury, reactive oxygen species (ROS) production, polyamine accumulation, and activities of SOD, POD, and APX, while pronounced decreases of antioxidant contents, CAT activity and intracellular Ca(2+) concentration in seedlings leaves. He-Ne laser illumination caused a distinct alleviation of cellular injury that was reflected by the lower MDA amounts, polyamine accumulation and ROS levels at the stress period. In contrast, the laser treatment displayed a higher Ca(2+) concentration, antioxidant amounts, NO release, antioxidant enzyme, and NOS activities. These responses could be blocked due to the inhibition of NO biosynthesis by PTIO (NO scavenger) or LNNA (NOS inhibitor). The presented results demonstrated that endogenous NO might be involved in the progress of He-Ne laser-induced plant antioxidant system activation and ROS degradation in order to enhance adaptive responses of tall fescue to prolonged saline conditions. PMID:27309569

  12. Fatp1 deficiency affects retinal light response and dark adaptation, and induces age-related alterations.

    Karim Chekroud

    Full Text Available FATP1 is involved in lipid transport into cells and in intracellular lipid metabolism. We showed previously that this protein interacts with and inhibits the limiting-step isomerase of the visual cycle RPE65. Here, we aimed to analyze the effect of Fatp1-deficiency in vivo on the visual cycle, structure and function, and on retinal aging. Among the Fatp family members, we observed that only Fatp1 and 4 are expressed in the control retina, in both the neuroretina and the retinal pigment epithelium. In the neuroretina, Fatp1 is mostly expressed in photoreceptors. In young adult Fatp1(-/- mice, Fatp4 expression was unchanged in retinal pigment epithelium and reduced two-fold in the neuroretina as compared to Fatp1(+/+ mice. The Fatp1(-/- mice had a preserved retinal structure but a decreased electroretinogram response to light. These mice also displayed a delayed recovery of the b-wave amplitude after bleaching, however, visual cycle speed was unchanged, and both retinal pigment epithelium and photoreceptors presented the same fatty acid pattern compared to controls. In 2 year-old Fatp1(-/- mice, transmission electron microscopy studies showed specific abnormalities in the retinas comprising choroid vascularization anomalies and thickening of the Bruch membrane with material deposits, and sometimes local disorganization of the photoreceptor outer segments. These anomalies lead us to speculate that the absence of FATP1 accelerates the aging process.

  13. Participation of intracellular signal transduction in the radio-adaptive response induced by low-dose X-irradiation in human embryonic cells

    To elucidate the induction mechanism of radio-adaptive response in normal cells, we searched the literatures of the intracellular signal transduction. Furthermore, we examined the induction of radio-adaptive response with or without inhibitors of several kinds of protein kinase. The major results obtained were as follows; (1) According to the literature survey it is revealed that there are 4 intracellular signal transduction pathways which are possibly involved in the induction of radio-adaptive response: pathways depending on cAMP, calcium, cGMP, or protein-tyrosine kinase. (2) Addition of either inhibitor of protein-tyrosine kinase or protein kinase C to the cell culture medium during the low-dose X-irradiation inhibited the induction of radio-adaptive response. However, the addition of inhibitor of cAMP-dependent protein kinase, cGMP-dependent protein kinase, or Ca2+-calmodulin kinase II failed to inhibit the induction of radio-adaptive response. (3) These results suggest that the signal induced in cells by low-dose X-irradiation was transduced from protein-tyrosine kinase to protein kinase C via either pathway of phosphatidylinositol 3-kinase or splitting of profilin binding phosphatidylinositol 4,5-bisphosphate. (author)

  14. Time-effect of adaptive response of mouse thymocyte apoptosis and cell cycle progression induced by low dose radiation

    2001-01-01

    目的:观察低剂量辐射(LDR)诱导胸腺细胞凋亡及细胞周期进程适应性反应的基本规律。方法:用X射线照射昆明系雄性小鼠,其诱导剂量(D1)及其后攻击剂量(D2)分别是75 mGy 和1.5 Gy。D1和D2间隔时间分别是3、6、12、24和60 h。D2照射后18 h胸腺细胞培养4、20 和44 h用流式细胞仪检测胸腺细胞凋亡小体(TAB)和细胞周期进程的变化。结果:当D1和D2间隔3、6和12 h,在D2照射后胸腺细胞培养4和20 h,D1 + D2组 TAB 百分数明显低于D2组(P<0.05),G0/G1和G2+M期细胞百分数也不同程度地低于D2组, 而S期细胞百分数却明显高于D2组(P<0.05或P<0.01)。结论:D1和D2分别是75 mGy(剂量率,12.5 mGy/min)和1.5 Gy(剂量率,0.287 Gy/min),D1和D2间隔3~12 h, 在小鼠全身照射后其胸腺细胞培养4和20 h可诱导细胞凋亡和细胞周期进程的适应性反应。%Objective: In the present study we observed the general pattern of the adaptive response of thymocyte apoptosis and cell cycle progression induced by low dose radiation (LDR). Methods: Kunming male mice were irradiated with the inductive dose (D1, 75 mGy) and the challenging dose (D2, 1.5 Gy). The intervals between D1 and D2 were 3, 6, 12, 24 and 60 hours. The changes of thymocyte apoptotic bodies (TAB) and cell cycle progression were measured with flow cytometry with the thymocytes cultured for 4, 20 and 44 hours, respectively, 18 hours after irradiation with D2. Results: When the intervals between D1 and D2 were 3, 6 and 12 hours, the percentages of TAB in the D1 + D2 groups in the thymocytes cultured for 4 and 20 hours were significantly lower than those in the D2 groups (P<0.05) and the percentages of G0/G1 and G2 + M phase cells decreased in varying degrees, while the percentages of S phase cells increased significantly (P<0.05 or P<0.01). Conclusion: The results mentioned above indicate that when the mice were irradiated with 75 m

  15. Glucose starvation induces mutation and lineage-dependent adaptive responses in a large collection of cancer cell lines

    He, Ningning; Kim, Nayoung; JEONG, EUNA; Lu, Yiling; Mills, Gordon B.; Yoon, Sukjoon

    2015-01-01

    Tolerance of glucose deprivation is an important factor for cancer proliferation, survival, migration and progression. To systematically understand adaptive responses under glucose starvation in cancers, we analyzed reverse phase protein array (RPPA) data of 115 protein antibodies across a panel of approximately 170 heterogeneous cancer cell lines, cultured under normal and low glucose conditions. In general, glucose starvation broadly altered levels of many of the proteins and phosphoprotein...

  16. Kinetics of the early adaptive response and adaptation threshold dose

    The expression kinetics of the adaptive response (RA) in mouse leukocytes in vivo and the minimum dose of gamma radiation that induces it was determined. The mice were exposed 0.005 or 0.02 Gy of 137 Cs like adaptation and 1h later to the challenge dose (1.0 Gy), another group was only exposed at 1.0 Gy and the damage is evaluated in the DNA with the rehearsal it makes. The treatment with 0. 005 Gy didn't induce RA and 0. 02 Gy causes a similar effect to the one obtained with 0.01 Gy. The RA was show from an interval of 0.5 h being obtained the maximum expression with 5.0 h. The threshold dose to induce the RA is 0.01 Gy and in 5.0 h the biggest quantity in molecules is presented presumably that are related with the protection of the DNA. (Author)

  17. Adaptive response of spermatogenic cell apoptosis and p53 gene expression selectively induced by irradiation with low dose X-ray in mice

    Objective: The adaptive response of spermatogenic cell apoptosis and p53 gene expression induced by whole-body low dose radiation (LDR) with X-rays was studied in male Kunming mice. Methods: Different kinds of spermatogenic cells were separated using density gradient centrifugation and their apoptotic percentagcs were analysed using flow cytometry (FCM) stained with propodium iodide. At meantime, p53 protein was measured with immunohistochemical SABC. Results: When inductive dose (D1) was 75 mGy 6 h before irradiation with the challenging doses (D2) of 1.0, 2.0 or 3.0 Gy, the apoptotic percentages of the spermatogonia and spermatocytes in the D1 + D2 groups were declined rapidly as compared with those in the D2 groups , and the apoptotic percentages of spermatids and spermatozoa showed no significant changes. When inductive dose (D1) was 75 mGy 6 h before irradiation with the challenging doses (D2) of 1.0, 2.0 or 3.0 Gy, the percentages of p53 protein positive of spermatogonia and spermatocytes in the D1 + D2 groups were declined rapidly as compared with those in the D2 groups, and the positive percentages of spermatids and spermatozoa showed no significant changes. Conclusion: The adaptive response of apoptosis and p53 protein expression in spermatogonia and spermatocytes could be selectively induced by irradiation with low dose X-ray. The apoptotic adaptive response induced by LDR could closely relate to the D2 doses and interval time between D1 and D2, so we speculated that p53 gene plays a great role in molecular mechanisms of adaptive response on spermatogenic cell apoptosis induced by LDR. (authors)

  18. Glucose starvation induces mutation and lineage-dependent adaptive responses in a large collection of cancer cell lines.

    He, Ningning; Kim, Nayoung; Jeong, Euna; Lu, Yiling; Mills, Gordon B; Yoon, Sukjoon

    2016-01-01

    Tolerance of glucose deprivation is an important factor for cancer proliferation, survival, migration and progression. To systematically understand adaptive responses under glucose starvation in cancers, we analyzed reverse phase protein array (RPPA) data of 115 protein antibodies across a panel of approximately 170 heterogeneous cancer cell lines, cultured under normal and low glucose conditions. In general, glucose starvation broadly altered levels of many of the proteins and phosphoproteins assessed across the cell lines. Many mTOR pathway components were selectively sensitive to glucose stress, although the change in their levels still varied greatly across the cell line set. Furthermore, lineage- and genotype-based classification of cancer cell lines revealed mutation-specific variation of protein expression and phosphorylation in response to glucose starvation. Decreased AKT phosphorylation (S473) was significantly associated with PTEN mutation under glucose starvation conditions in lung cancer cell lines. The present study (see TCPAportal.org for data resource) provides insight into adaptive responses to glucose deprivation under diverse cellular contexts. PMID:26573869

  19. Relieved residual damage in the hematopoietic system of mice rescued by radiation-induced adaptive response (Yonezawa Effect)

    Wang, Bing; Tanaka, Kaoru; Ninomiya, Yasuharu; Maruyama, Kouichi; VarèS, Guillaume; Eguchi-Kasai, Kiyomi; Nenoi, Mitsuru

    2012-01-01

    Existence of adaptive response (AR) was previously demonstrated in C57BL/6J mice. Irradiations were performed by delivering a priming low dose of X-rays (0.50 Gy) in combination with a challenge high dose of accelerated carbon or neon ion particles. AR was characterized by significantly decreased mortality in the 30-day survival test. This mouse AR model (‘Yonezawa Effect’) was originally established by using X-rays as both the priming and challenge irradiations. The underlying mechanism was ...

  20. Inducible competitors and adaptive diversification

    Beren W. ROBINSON, David W. PFENNIG

    2013-08-01

    Full Text Available Identifying the causes of diversification is central to evolutionary biology. The ecological theory of adaptive diversification holds that the evolution of phenotypic differences between populations and species––and the formation of new species––stems from divergent natural selection, often arising from competitive interactions. Although increasing evidence suggests that phenotypic plasticity can facilitate this process, it is not generally appreciated that competitively mediated selection often also provides ideal conditions for phenotypic plasticity to evolve in the first place. Here, we discuss how competition plays at least two key roles in adaptive diversification depending on its pattern. First, heterogenous competition initially generates heterogeneity in resource use that favors adaptive plasticity in the form of “inducible competitors”. Second, once such competitively induced plasticity evolves, its capacity to rapidly generate phenotypic variation and expose phenotypes to alternate selective regimes allows populations to respond readily to selection favoring diversification, as may occur when competition generates steady diversifying selection that permanently drives the evolutionary divergence of populations that use different resources. Thus, competition plays two important roles in adaptive diversification––one well-known and the other only now emerging––mediated through its effect on the evolution of phenotypic plasticity [Current Zoology 59 (4: 537–552, 2013].

  1. Mechanisms underlying the adaptive response against spontaneous neoplastic transformation induced by low doses of low LET radiation, Final Technical Report

    J. Leslie Redpath, Ph.D.

    2006-01-23

    The goal of this project was to investigate mechanisms underlying the adaptive response seen following exposure of HeLa x skin fibroblast human hybrid cells to low doses of low LET radiation. It was proposed to investigate the contributions of three possible mechanisms. These were: 1. Upregulation of cellular antioxidant status. 2. Upregulation of DNA repair. 3. Upregulation of gap junction intracellular communication. We have completed the study of the role of upregulation of reduced glutathione (GSH) as a possible mechanism underlying our observed suppression of transformation frequency at low radiation doses. We have also completed our study of the possible role of upregulation of DNA repair in the observed adaptive response against neoplastic transformation. We concluded that upregulation of DNA repair may be more important in modulating transformation at the higher dose. A manuscript describing the above studies has been submitted published in Carcinogenesis 24:1961-1965, 2003. Finally, we have completed two studies of the possible role of upregulation of gap junction intercellular communication (GJIC) in modulating transformation frequency at low doses of low LET radiation. This research was published in Radiation Research 162:646-654, 2004. In order to optimize the opportunity for GJIC, we then carried out a study where confluent cultures were irradiated. The results indicated, that while the degree of low dose suppression was somewhat reduced compared to that seen for subconfluent cultures, it was not completely absent. This research has been submitted for publication. Our research program was of sufficient interest to generate two invited reviews, and five invited presentations.

  2. Low dose, radiation-induced adaptive response against cancer in high-dose-exposed, cancer-prone, Trp53 heterozygous mice

    Full text: Mice that are heterozygous for Trp53 are both cancer-prone and sensitive to high radiation doses. Groups of 7-8-week-old female Trp53 heterozygous mice were exposed to 4 Gy of 60Co-gamma radiation at either high (0.5 Gy/min) or low (0.5 mGy/min) dose rate. Other groups received a 10-mGy or 100-mGy dose, given at low dose rate (0.5 mGy/min) 24 h prior to the 4 Gy dose. Tumor frequency and latency were measured over the lifespan of the animals. Compared to animals receiving only 4 Gy at high dose rate, mice receiving a prior 10-mGy adapting exposure had significantly extended lifespan and increased latency for all malignant tumors taken together. However, the latency responses were tumor type specific. The prior 10-mGy exposure increased latency for lymphomas and hemangiosarcomas, but decreased latency for spinal osteosarcomas. Increasing the adapting dose to 100 mGy eliminated the tumor latency increase and significantly reduced lifespan. A 10-mGy adapting dose given prior to a 4 Gy exposure at low dose rate generally showed either a reduced effect or no effect. Adapting exposures had no significant effect on tumor frequency. We conclude that adaptive responses are induced by low doses of radiation in radiation sensitive, cancer prone Trp53 +/ - mice, and that these responses are expressed as an increase in tumor latency that reduces the carcinogenic effects of a subsequent large exposure. The dose at which protective effects give way to detrimental effects is tumor type specific

  3. Inducible Protective Processes in Animal Systems XIII: Comparative Analysis of Induction of Adaptive Response by EMS and MMS in Ehrlich Ascites Carcinoma Cells

    Periyapatna Vishwaprakash Mahadimane

    2014-01-01

    Full Text Available In order to investigate the presence of adaptive response in cancerous cells, two monofunctional alkylating agents, namely, ethyl methanesulfonate (EMS and methyl methanesulfonate (MMS, were employed to treat Ehrlich ascites carcinoma (EAC cells in vivo. Conditioning dose of 80 mg/kg body weight of EMS or 50 mg/kg body weight of MMS and challenging dose of 240 mg/kg body weight of EMS or 150 mg/kg body weight of MMS were selected by pilot toxicity studies. Conditioned EAC cells when challenged after 8 h time lag resulted in significant reduction in chromosomal aberrations compared to challenging dose of respective agents. As has been proved in earlier studies with normal organisms, even in cancerous cells (EAC, there is presence of adaptive response to methylating and ethylating agents. Furthermore, it is also interesting to note in the present studies that the methylating agent, MMS, is a stronger inducer of the adaptive response than the ethylating agent, EMS.

  4. Adaptive response of the mutagenicity of the somatic andgerm cells in mice induced by in vivo 147Pm radiation

    1999-01-01

    Effects of pretreatment of mousewith low doses of internally deposited 147Pm on the mutagenicity ofboththe bone marrow lymphocytes and the spermatoblasts induced by subsequenthigh dose of internally deposited 147Pm were studied. Kunming male mice were injected from the tail vein with low doses of 147Pm(NO3)3 of 0.37, 3.7 and 37 Bq/gbody weight. Three days later the mice were injected with a high dose of147Pm(NO3)3 of 18.5 kBq/g body weight. The animals were sacrificedat 24 hafter the high dose injection. The results show that the bone marrow lymphocytesand the spermatoblasts pre-exposed in vivo to low doses of 147Pmcan produce anadaptive response. The radioadapted cells had a resistance to themutagenicity induced by the subsequent high dose of 147Pm, that is, theproportion of both the bone marrow lymphocytes containing micronuclei andthe sperm shape abnormalities was significantly lower than those forthe pure high dose group (P<0.01). In addition, the induction of theadaptive response of the cells possesses the different dose ranges forthe different biological parameters. The 147Pm dose ranges of the adaptiveresponse are 0.37~3.7 and 0.37~37 Bq/g body weight for thefrequency of micronucleated bone marrow lymphocytes and abnormalsperms, respectively.

  5. Adaptive response and genetic instability induced by a low-dose rate radiation simulating the high-altitude flight conditions on mice in vivo

    Complete text of publication follows. In the present work, we investigated the effect of a low-dose rate of high-LET radiation that simulates the spectral and component composition of radiation fields formed in the conditions of high-altitude flights on mice in vivo. The dose dependence, adaptive response, and genetic instability in generation F1 born from males irradiated under these conditions were examined in polychromatic erythrocytes of bone marrow using the micronucleus test. Two-month-old males of SHK white mongrel mice were used. Irradiation was performed for 24 h a day in the radiation field behind the concrete shield of the U-70 accelerator of 70 GeV protons (Serpukhov), which adequately simulates radiation field formed in the atmosphere at a height of about 10 km, to accumulate doses of 11.5, 21.5 and 31.5 cGy (1 cGy/day). The experiments demonstrated that: 1) irradiation of mice in vivo with these doses of low dose rate high-LET radiation leads to an increase in cytogenetic damage in polychromatic erythrocytes; 2) irradiation of mice with these doses induces no adaptive response in polychromatic erythrocytes as opposite to γ-radiation; and 3) in mice of the F1 generation born from males irradiated with doses of 11.5, 21.5 and 31.5 cGy, an increase in sensitivity to additional irradiation with a dose of 1.5 Gy of γ-radiation and the absence of adaptive response compared with the descendants of unirradiated males occur. These data indicate a genetic instability in generation F1 born from irradiated males.

  6. Studies on adaptive responses in Chinese hamster cells

    For many years the possibility has been considered of low doses of radiation inducing adaptive responses in cells and organisms against the mutagenic effects of radiation. Currently, a number of experimental data appraise the existence of an adaptive response that is characterized by a decrease of radiation induced genetic damages. The understanding of the molecular mechanism involved in this phenomenon permits to estimate the effects and risks of low dose exposure. In this work, preliminary results of studies on the induction of adaptive response in cells subjected to different doses of ionizing radiation are presented

  7. AMPKα is essential for acute exercise-induced gene responses but not for exercise training-induced adaptations in mouse skeletal muscle

    Fentz, Joachim; Kjøbsted, Rasmus; Maag Kristensen, Caroline; Hingst, Janne Rasmuss; Birk, Jesper Bratz; Gudiksen, Anders; Foretz, Marc; Schjerling, Peter; Viollet, Benoit; Pilegaard, Henriette; Wojtaszewski, Jørgen

    2015-01-01

    . Maximal running speed was lower in AMPKα mdKO than WT mice, but increased similarly in both genotypes with exercise training. Exercise training increased quadriceps protein content of ubiquinol-cytochrome-C reductase core protein 1 (UQCRC1), cytochrome C, hexokinase II, plasma membrane fatty acid binding......Exercise training increases skeletal muscle expression of metabolic proteins improving the oxidative capacity. Adaptations in skeletal muscle by pharmacologically induced activation of 5'AMP-activated protein kinase (AMPK) are dependent on the AMPKα2 subunit. We hypothesized that exercise training......, glucose transporter 4 and VEGF in an AMPK-dependent manner, while cluster of differentiation 36 and fatty acid transport protein 1 mRNA content increased similarly in AMPKα wild type (WT) and mdKO mice. During four weeks of voluntary running wheel exercise training, the AMPKα mdKO mice ran less than WT...

  8. Interval for the expression of the adaptive response induced by gamma radiation in leucocytes of mouse In vivo; Intervalo para la expresion de la respuesta adaptativa inducida por radiacion gamma en leucocitos de raton In vivo

    Mendiola C, M.T.; Morales R, P. [Instituto Nacional de Investigaciones Nucleares, A.P. 18-1027, 11801 Mexico D.F. (Mexico)

    2002-07-01

    The interval between the adaptive gamma radiation dose (0.01 Gy) and challenge (1.0 Gy) capable to induce the maximum expression of the adaptive response in lymphocytes of mouse In vivo. The animals were exposed to the mentioned doses with different intervals among both (1, 1.5, 5 or 18 hr). By means of the unicellular electrophoresis in gel technique, four damage parameters were analysed. The results showed that from the 1 hr interval an adaptive response was produced since in the pretreated organisms with 0.01 Gy the cells present lesser damage than in those not adapted. The maximum response was induced with the intervals between 2.5 and 5 hr and even though it persisted until 18 hr, the effect was reducing. (Author)

  9. Role of x-ray-induced transcripts in adaptive responses following x-rays. Progress report, Year 2

    1993-09-01

    I will describe our recent data in which we have extracted and purified a sufficient amount of RNA from primed and unprimed U1-Mel cells to begin the search for new genes which are modulated by priming or high dose irradiation during the establishment and/or challenge of adapted cells, respectively. Gene transcripts which are altered during ASRs now include alterations in xip5 (a gene with homology to human growth hormone), xipl2 (a gene with homology to human angiogenesis factor and a gene which may be involved in apoptosis due to its possible RNase activity), cyclin A (which is altered in primed cells only after a high dose of ionizing radiation), cyclin B (which is also altered in a similar manner as cyclin A), p53 (a tumor suppressor gene involved in cell division control in G{sub 1} following ionizing radiation), and glutathionine S transferase-pi (a gene product which has been demonstrated to be involved in DNA repair and redox cycling). In contrast, the remaining xip CDNA clones [i.e., xip1-4,6-11, which were isolated following high dose ionizing radiation exposure to human U1-Mel cells], Prad-1 (a gene involved in cell cycle controlling events at the G{sub 1} portion of the cell cycle), 36B4 (a gene involved in homeostasis), and cdc2 (a gene involved in the regulation of the S-phase portion of the cell cycle), were not altered following ionizing radiation, either during the establishment or challenge of adapted human cells.

  10. Titanium dioxide nanoparticles induce an adaptive inflammatory response and invasion and proliferation of lung epithelial cells in chorioallantoic membrane

    Titanium dioxide nanoparticles (TiO2 NPs) studies have been performed using relatively high NPs concentration under acute exposure and limited studies have compared shape effects. We hypothesized that midterm exposure to low TiO2 NPs concentration in lung epithelial cells induces carcinogenic characteristics modulated partially by NPs shape. To test our hypothesis we synthesized NPs shaped as belts (TiO2-B) using TiO2 spheres (TiO2-SP) purchased from Sigma Aldrich Co. Then, lung epithelial A549 cells were low-exposed (10 µg/cm2) to both shapes during 7 days and internalization, cytokine release and invasive potential were determined. Results showed greater TiO2-B effect on agglomerates size, cell size and granularity than TiO2-SP. Agglomerates size in cell culture medium was 310 nm and 454 nm for TiO2-SP and TiO2-B, respectively; TiO2-SP and TiO2-B induced 23% and 70% cell size decrease, respectively, whilst TiO2-SP and TiO2-B induced 7 and 14-fold of granularity increase. NOx production was down-regulated (31%) by TiO2-SP and up-regulated (70%) by TiO2-B. Both NPs induced a transient cytokine release (IL-2, IL-6, IL-8, IL-4, IFN-γ, and TNF-α) after 4 days, but cytokines returned to basal levels in TiO2-SP exposed cells while TiO2-B induced a down-regulation after 7 days. Midterm exposure to both shapes of NPs induced capability to degrade cellular extracellular matrix components from chorioallantoic membrane and Ki-67 marker showed that TiO2-B had higher proliferative potential than TiO2-SP. We conclude that midterm exposure to low NPs concentration of NPs has an impact in the acquisition of new characteristics of exposed cells and NPs shape influences cellular outcome. - Graphical abstract: (A) Lung epithelial cells were low exposed (below 10 µg/cm2) to titanium dioxide nanoparticles (TiO2-NPs) shaped as spheres (TiO2-SP) and belts (TiO2-B) for midterm (7 continuous days) separately. (B) Then, cells from each cell culture were harvested and seeded on the top

  11. Titanium dioxide nanoparticles induce an adaptive inflammatory response and invasion and proliferation of lung epithelial cells in chorioallantoic membrane

    Medina-Reyes, Estefany I.; Déciga-Alcaraz, Alejandro [Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, CP 54059 Estado de México (Mexico); Freyre-Fonseca, Verónica [Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, CP 54059 Estado de México (Mexico); Doctorado en Ciencias en Alimentos, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, CP 11340 México, DF (Mexico); Delgado-Buenrostro, Norma L. [Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, CP 54059 Estado de México (Mexico); Flores-Flores, José O. [Centro de Ciencias Aplicadas y Desarrollo Tecnológico, Universidad Nacional Autónoma de México, Circuito Exterior S/N, Ciudad Universitaria AP 70-186, CP 04510 México, DF (Mexico); Gutiérrez-López, Gustavo F. [Escuela Nacional de Ciencias Biológicas del Instituto Politécnico Nacional, CP 11340 México, DF (Mexico); Sánchez-Pérez, Yesennia; García-Cuéllar, Claudia M. [Instituto Nacional de Cancerología, Subdirección de Investigación Básica, San Fernando 22, Tlalpan, CP 14080 México, DF (Mexico); and others

    2015-01-15

    Titanium dioxide nanoparticles (TiO{sub 2} NPs) studies have been performed using relatively high NPs concentration under acute exposure and limited studies have compared shape effects. We hypothesized that midterm exposure to low TiO{sub 2} NPs concentration in lung epithelial cells induces carcinogenic characteristics modulated partially by NPs shape. To test our hypothesis we synthesized NPs shaped as belts (TiO{sub 2}-B) using TiO{sub 2} spheres (TiO{sub 2}-SP) purchased from Sigma Aldrich Co. Then, lung epithelial A549 cells were low-exposed (10 µg/cm{sup 2}) to both shapes during 7 days and internalization, cytokine release and invasive potential were determined. Results showed greater TiO{sub 2}-B effect on agglomerates size, cell size and granularity than TiO{sub 2}-SP. Agglomerates size in cell culture medium was 310 nm and 454 nm for TiO{sub 2}-SP and TiO{sub 2}-B, respectively; TiO{sub 2}-SP and TiO{sub 2}-B induced 23% and 70% cell size decrease, respectively, whilst TiO{sub 2}-SP and TiO{sub 2}-B induced 7 and 14-fold of granularity increase. NO{sub x} production was down-regulated (31%) by TiO{sub 2}-SP and up-regulated (70%) by TiO{sub 2}-B. Both NPs induced a transient cytokine release (IL-2, IL-6, IL-8, IL-4, IFN-γ, and TNF-α) after 4 days, but cytokines returned to basal levels in TiO{sub 2}-SP exposed cells while TiO{sub 2}-B induced a down-regulation after 7 days. Midterm exposure to both shapes of NPs induced capability to degrade cellular extracellular matrix components from chorioallantoic membrane and Ki-67 marker showed that TiO{sub 2}-B had higher proliferative potential than TiO{sub 2}-SP. We conclude that midterm exposure to low NPs concentration of NPs has an impact in the acquisition of new characteristics of exposed cells and NPs shape influences cellular outcome. - Graphical abstract: (A) Lung epithelial cells were low exposed (below 10 µg/cm{sup 2}) to titanium dioxide nanoparticles (TiO{sub 2}-NPs) shaped as spheres (TiO{sub 2

  12. Adaptive immune responses of legumin nanoparticles.

    Mirshahi, T; Irache, J M; Nicolas, C; Mirshahi, M; Faure, J P; Gueguen, J; Hecquet, C; Orecchioni, A M

    2002-12-01

    Legumin is one of the main storage proteins in the pea seeds (Pisum sativum L.) and the molecules of this protein have the capacity of binding together to form nanoparticles after aggregation and chemical cross-linkage with glutaraldehyde. The aim of this work was to study the adaptive immune response of legumin nanoparticles in rats. Following intradermal immunisation with the native protein legumin and legumin nanoparticles of about 250 nm, the humoral and cell-mediated immune responses were analysed in rats. The humoral responses against legumin and legumin nanoparticles were examined by western blot and ELISA analysis. Both techniques clearly showed that sera from rats immunised with legumin strongly expressed antibodies against this protein. On the contrary, serum samples from rats inoculated with legumin nanoparticles did not contain detectable amounts of antibodies. These results may be explained by a reduction on the antigenic epitopes of the protein induced by the glutaraldehyde used during the cross-linking step. Concerning the cell-mediated response, neither legumin nor legumin nanoparticles stimulated an immunogenic response. This absence of response of spleen lymphocytes for legumin and legumin nanoparticles may be explained by a cytostatic effect of legumin which was corroborated by the evaluation of the middle phase of cell apoptose. In fact, both legumin and legumin nanoparticles are potent inductors of a cytostatic phenomenon and showed a significant increase of the chromatin condensation (p < 0.05) as compared with control. PMID:12683667

  13. "Adaptive response" - some underlying mechanisms and open questions

    Evgeniya G. Dimova; Bryant, Peter E.; Chankova, Stephka G

    2008-01-01

    Organisms are affected by different DNA damaging agents naturally present in the environment or released as a result of human activity. Many defense mechanisms have evolved in organisms to minimize genotoxic damage. One of them is induced radioresistance or adaptive response. The adaptive response could be considered as a nonspecific phenomenon in which exposure to minimal stress could result in increased resistance to higher levels of the same or to other types of stress some hours later. A ...

  14. Suppression Measured from Chinchilla Auditory-Nerve-Fiber Responses Following Noise-Induced Hearing Loss: Adaptive-Tracking and Systems-Identification Approaches.

    Sayles, Mark; Walls, Michael K; Heinz, Michael G

    2016-01-01

    The compressive nonlinearity of cochlear signal transduction, reflecting outer-hair-cell function, manifests as suppressive spectral interactions; e.g., two-tone suppression. Moreover, for broadband sounds, there are multiple interactions between frequency components. These frequency-dependent nonlinearities are important for neural coding of complex sounds, such as speech. Acoustic-trauma-induced outer-hair-cell damage is associated with loss of nonlinearity, which auditory prostheses attempt to restore with, e.g., "multi-channel dynamic compression" algorithms.Neurophysiological data on suppression in hearing-impaired (HI) mammals are limited. We present data on firing-rate suppression measured in auditory-nerve-fiber responses in a chinchilla model of noise-induced hearing loss, and in normal-hearing (NH) controls at equal sensation level. Hearing-impaired (HI) animals had elevated single-fiber excitatory thresholds (by ~ 20-40 dB), broadened frequency tuning, and reduced-magnitude distortion-product otoacoustic emissions; consistent with mixed inner- and outer-hair-cell pathology. We characterized suppression using two approaches: adaptive tracking of two-tone-suppression threshold (62 NH, and 35 HI fibers), and Wiener-kernel analyses of responses to broadband noise (91 NH, and 148 HI fibers). Suppression-threshold tuning curves showed sensitive low-side suppression for NH and HI animals. High-side suppression thresholds were elevated in HI animals, to the same extent as excitatory thresholds. We factored second-order Wiener-kernels into excitatory and suppressive sub-kernels to quantify the relative strength of suppression. We found a small decrease in suppression in HI fibers, which correlated with broadened tuning. These data will help guide novel amplification strategies, particularly for complex listening situations (e.g., speech in noise), in which current hearing aids struggle to restore intelligibility. PMID:27080669

  15. Genes associated with radiation adaptive response induced by low level radiation from {sup 99m}Tc in human cell line

    Kwon, An Sung; Bom, Hee Seung; Choi, Chan; Kim, Ji Yeul; Lim, Wook Bin [Chonam National Univ., Medical School, Gwangju (Korea, Republic of)

    2001-10-01

    The purpose of this study was to search activated genes that could be related to radiation adaptive response (RAR) induced by low-level radiation from {sup 99m}Tc in human cell lines. We used gene discovery array (GDA) and representational difference analysis (RDA) methods. {sup 99m}Tc-pertechnetate was added to 2 X 106/mL NC-37 cells (human lymphoblastic cells) to make concentrations ranging from 148 MBq/mL to 148Bq/mL by serial 10 fold dilutions. After 44 hours. 2 Gy gamma irradiation was given to them using a Cs-137 cell irradiator. As compared to the control (Con) group to which no {sup 99m}Tc was added, those cells to which 148 and 14.8 KBq of {sup 99m}Tc were added showed significantly lower damage to chromosomes, which was evaluated by metaphase analysis. Cells with 148 KBq {sup 99m}Tc (T148 group) showed most significant protection. Activated genes in the T148 group as compared to Con group were evaluated by GDA and RDA methods. GDA revealed genes of casein kinase 2 (CK2) beta chain, immunoglobulins (lg), human leukocyte antigen (HLA)-B, and two novel genes. Twenty RAR related clones were selected by RDA method. The size of those genes was from 234 to 603 base pairs. RAR was induced by low dose irradiation from {sup 99m}Tc in NC-37 cell lines. Genes related to the response included CK2, lg, HLA-B in human lymphoblastic cell lines.

  16. Radio-Adaptive Responses of Mouse Myocardiocytes

    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

  17. FDG-PET response-adapted therapy

    Hutchings, Martin

    2014-01-01

    Fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) is the most accurate tool for staging, treatment monitoring, and response evaluation in Hodgkin lymphoma (HL). Early determination of treatment sensitivity by FDG-PET is the best tool to guide individualized......, response-adapted treatment. Several ongoing or recently completed trials have investigated the use of FDG-PET/CT for early response-adapted HL therapy. The results are encouraging, but the data are immature, and PET response-adapted HL therapy is discouraged outside the setting of clinical trials. PET...

  18. Self-adjuvanted mRNA vaccines induce local innate immune responses that lead to a potent and boostable adaptive immunity.

    Kowalczyk, Aleksandra; Doener, Fatma; Zanzinger, Kai; Noth, Janine; Baumhof, Patrick; Fotin-Mleczek, Mariola; Heidenreich, Regina

    2016-07-19

    mRNA represents a new platform for the development of therapeutic and prophylactic vaccines with high flexibility with respect to production and application. We have previously shown that our two component self-adjuvanted mRNA-based vaccines (termed RNActive® vaccines) induce balanced immune responses comprising both humoral and cellular effector as well as memory responses. Here, we evaluated the early events upon intradermal application to gain more detailed insights into the underlying mode of action of our mRNA-based vaccine. We showed that the vaccine is taken up in the skin by both non-leukocytic and leukocytic cells, the latter being mostly represented by antigen presenting cells (APCs). mRNA was then transported to the draining lymph nodes (dLNs) by migratory dendritic cells. Moreover, the encoded protein was expressed and efficiently presented by APCs within the dLNs as shown by T cell proliferation and immune cell activation, followed by the induction of the adaptive immunity. Importantly, the immunostimulation was limited to the injection site and lymphoid organs as no proinflammatory cytokines were detected in the sera of the immunized mice indicating a favorable safety profile of the mRNA-based vaccines. Notably, a substantial boostability of the immune responses was observed, indicating that mRNA can be used effectively in repetitive immunization schedules. The evaluation of the immunostimulation following prime and boost vaccination revealed no signs of exhaustion as demonstrated by comparable levels of cytokine production at the injection site and immune cell activation within dLNs. In summary, our data provide mechanistic insight into the mode of action and a rational for the use of mRNA-based vaccines as a promising immunization platform. PMID:27269061

  19. Sterile inflammation induced by Carbopol elicits robust adaptive immune responses in the absence of pathogen-associated molecular patterns

    Gartlan, Kate H.; Krashias, George; Wegmann, Frank; Hillson, William R.; Scherer, Erin M.; Greenberg, Philip D.; Eisenbarth, Stephanie C.; Moghaddam, Amin E.; Sattentau, Quentin J.

    2016-01-01

    Carbopol is a polyanionic carbomer used in man for topical application and drug delivery purposes. However parenteral administration of Carbopol in animal models results in systemic adjuvant activity including strong pro-inflammatory type-1 T-cell (Th1) polarization. Here we investigated potential pathways of immune activation by Carbopol by comparison with other well-characterized adjuvants. Carbopol administration triggered rapid and robust leukocyte recruitment, pro-inflammatory cytokine secretion and antigen capture largely by inflammatory monocytes. The induction of antigen specific Th1 cells by Carbopol was found to occur via a non-canonical pathway, independent of MyD88/TRIF signaling and in the absence of pattern-recognition-receptor (PRR) activation typically associated with Th1/Ig2a induction. Using multispectral fluorescence imaging (Imagestream) and electron microscopy we demonstrated that phagocytic uptake of Carbopol particles followed by entry into the phagosomal/lysosomal pathway elicited conformational changes to the polymer and reactive oxygen species (ROS) production. We therefore conclude that Carbopol may mediate its adjuvant activity via novel mechanisms of antigen presenting cell activation and Th1 induction, leading to enhanced IgG2a responses independent of microbial pattern recognition. PMID:27005810

  20. Adaptive response of Peruvian Hake to overfishing

    Mendo, C.W.; Carrasco, R.G.

    2000-01-01

    Compensatory mechanisms of the Peruvian hake population (Merluccius gayi peruanus) in response to heavy exploitation and changes in species interaction are discussed. Changes in the rate of cannibalism, diet composition, maximization of fecundity and behavioral adaptation are noted.

  1. Adaptive Modeling for Security Infrastructure Fault Response

    CUI Zhong-jie; YAO Shu-ping; HU Chang-zhen

    2008-01-01

    Based on the analysis of inherent limitations in existing security response decision-making systems, a dynamic adaptive model of fault response is presented. Several security fault levels were founded, which comprise the basic level, equipment level and mechanism level. Fault damage cost is calculated using the analytic hierarchy process. Meanwhile, the model evaluates the impact of different responses upon fault repair and normal operation. Response operation cost and response negative cost are introduced through quantitative calculation. This model adopts a comprehensive response decision of security fault in three principles-the maximum and minimum principle, timeliness principle, acquiescence principle, which assure optimal response countermeasure is selected for different situations. Experimental results show that the proposed model has good self-adaptation ability, timeliness and cost-sensitiveness.

  2. Vibrational response of adaptive composites

    Parlinska, M.; Michaud, V.; Gotthardt, R. [EPFL, Lausanne (Switzerland). Inst. de Genie Atomique; Balta, J.A.; Maanson, J.A. [EPFL, Lausanne (Switzerland). Inst. de Genie Atomique; EPFL, Lausanne (Switzerland). Lab. de Technologie des Composites et Polymeres, Dept. des Materiaux; Bidaux, J.E. [EPFL, Lausanne (Switzerland). Inst. de Genie Atomique; Ecole d' Ingenieurs du Valais, Sion (Switzerland). Groupe Materiaux et Conception

    2001-11-01

    Composite laminates containing pre-deformed NiTiCu wires embedded in an epoxy matrix reinforced with Kevlar fibres were manufactured and tested. These materials change their properties, for example vibration resonance frequency or modulus in response to a temperature variation. When heated by direct electrical current above the transformation temperature, the pre-deformed shape memory alloy (SMA) wires try to recover their shape and since they are restrained by a stiff matrix and clamping, a stress is created. As a result, a change in the resonance frequency of the composite occurs. The magnitude of the recovery stress and corresponding resonance frequency shift was found to increase with the SMA wire volume fraction and to decrease with the thickness of the host composite layers between the wires and the constraining grips. (orig.)

  3. Monitoring adaptive genetic responses to environmental change

    Hansen, M.M.; Olivieri, I.; Waller, D.M.;

    2012-01-01

    Widespread environmental changes including climate change, selective harvesting and landscape alterations now greatly affect selection regimes for most organisms. How animals and plants can adapt to these altered environments via contemporary evolution is thus of strong interest. We discuss how...... for selection and establishing clear links between genetic and environmental change. We then review a few exemplary studies that explore adaptive responses to climate change in Drosophila, selective responses to hunting and fishing, and contemporary evolution in Daphnia using resurrected resting eggs. We...... further review a broader set of 44 studies to assess how well they meet the proposed criteria, and conclude that only 23% fulfill all criteria. Approximately half (43%) of these studies failed to rule out the alternative hypothesis of replacement by a different, better-adapted population. Likewise, 34...

  4. Adaptive Filters for Muscle Response Suppression

    Sennels, Søren; Biering-Soerensen, Fin; Hansen, Steffen Duus;

    1996-01-01

    are proposed, based on the observation that the shape of the muscle responses only exhibits moderate changes during a time window of up to 300 ms. The filters are derived and compared with a conventional fixed comb filter on both simulated and real data. For variations in amplitude of the muscle responses......To be able to use the voluntary EMG-signal from an electrically stimulated muscle as control signal for FES-applications, it is necessary to eliminate the muscle response evoked by the stimulation. The muscle response is a non-stationary signal, therefore a set of linear adaptive prediction filters...

  5. Adaptive Acid Tolerance Response of Streptococcus sobrinus

    Nascimento, Marcelle M.; Lemos, José A. C.; Abranches, Jacqueline; Gonçalves, Reginaldo B.; Burne, Robert A.

    2004-01-01

    Streptococcus mutans and Streptococcus sobrinus are the bacteria most commonly associated with human dental caries. A major virulence attribute of these and other cariogenic bacteria is acid tolerance. The acid tolerance mechanisms of S. mutans have begun to be investigated in detail, including the adaptive acid tolerance response (ATR), but this is not the case for S. sobrinus. An analysis of the ATR of two S. sobrinus strains was conducted with cells grown to steady state in continuous chem...

  6. Epigenetics and the Adaptive Immune Response

    Kondilis-Mangum, Hrisavgi D.; Wade, Paul A.

    2012-01-01

    Cells of the adaptive immune response undergo dynamic epigenetic changes as they develop and respond to immune challenge. Plasticity is a necessary prerequisite for the chromosomal dynamics of lineage specification, development, and the immune effector function of the mature cell types. The alterations in DNA methylation and histone modification that characterize activation may be integral to the generation of immunologic memory, thereby providing an advantage on secondary exposure to pathoge...

  7. Adaptive response: some underlying mechanisms and open questions

    Evgeniya G. Dimova

    2008-01-01

    Full Text Available Organisms are affected by different DNA damaging agents naturally present in the environment or released as a result of human activity. Many defense mechanisms have evolved in organisms to minimize genotoxic damage. One of them is induced radioresistance or adaptive response. The adaptive response could be considered as a nonspecific phenomenon in which exposure to minimal stress could result in increased resistance to higher levels of the same or to other types of stress some hours later. A better understanding of the molecular mechanism underlying the adaptive response may lead to an improvement of cancer treatment, risk assessment and risk management strategies, radiation protection, e.g. of astronauts during long-term space flights. In this mini-review we discuss some open questions and the probable underlying mechanisms involved in adaptive response: the transcription of many genes and the activation of numerous signaling pathways that trigger cell defenses - DNA repair systems, induction of proteins synthesis, enhanced detoxification of free radicals and antioxidant production.

  8. Adaptive behavior of neighboring neurons during adaptation-induced plasticity of orientation tuning in V1

    Shumikhina Svetlana

    2009-12-01

    Full Text Available Abstract Background Sensory neurons display transient changes of their response properties following prolonged exposure to an appropriate stimulus (adaptation. In adult cat primary visual cortex, orientation-selective neurons shift their preferred orientation after being adapted to a non-preferred orientation. The direction of those shifts, towards (attractive or away (repulsive from the adapter depends mostly on adaptation duration. How the adaptive behavior of a neuron is related to that of its neighbors remains unclear. Results Here we show that in most cases (75%, cells shift their preferred orientation in the same direction as their neighbors. We also found that cells shifting preferred orientation differently from their neighbors (25% display three interesting properties: (i larger variance of absolute shift amplitude, (ii wider tuning bandwidth and (iii larger range of preferred orientations among the cluster of cells. Several response properties of V1 neurons depend on their location within the cortical orientation map. Our results suggest that recording sites with both attractive and repulsive shifts following adaptation may be located in close proximity to iso-orientation domain boundaries or pinwheel centers. Indeed, those regions have a more diverse orientation distribution of local inputs that could account for the three properties above. On the other hand, sites with all cells shifting their preferred orientation in the same direction could be located within iso-orientation domains. Conclusions Our results suggest that the direction and amplitude of orientation preference shifts in V1 depend on location within the orientation map. This anisotropy of adaptation-induced plasticity, comparable to that of the visual cortex itself, could have important implications for our understanding of visual adaptation at the psychophysical level.

  9. Regulated cell death and adaptive stress responses.

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

    2016-06-01

    Eukaryotic cells react to potentially dangerous perturbations of the intracellular or extracellular microenvironment by activating rapid (transcription-independent) mechanisms that attempt to restore homeostasis. If such perturbations persist, cells may still try to cope with stress by activating delayed and robust (transcription-dependent) adaptive systems, or they may actively engage in cellular suicide. This regulated form of cell death can manifest with various morphological, biochemical and immunological correlates, and constitutes an ultimate attempt of stressed cells to maintain organismal homeostasis. Here, we dissect the general organization of adaptive cellular responses to stress, their intimate connection with regulated cell death, and how the latter operates for the preservation of organismal homeostasis. PMID:27048813

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

    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)

  11. Eccentric Contraction-Induced Muscle Fibre Adaptation

    Arabadzhiev T. I.

    2009-12-01

    Full Text Available Hard-strength training induces strength increasing and muscle damage, especially after eccentric contractions. Eccentric contractions also lead to muscle adaptation. Symptoms of damage after repeated bout of the same or similar eccentrically biased exercises are markedly reduced. The mechanism of this repeated bout effect is unknown. Since electromyographic (EMG power spectra scale to lower frequencies, the adaptation is related to neural adaptation of the central nervous system (CNS presuming activation of slow-non-fatigable motor units or synchronization of motor unit firing. However, the repeated bout effect is also observed under repeated stimulation, i.e. without participation of the CNS. The aim of this study was to compare the possible effects of changes in intracellular action potential shape and in synchronization of motor units firing on EMG power spectra. To estimate possible degree of the effects of central and peripheral changes, interferent EMG was simulated under different intracellular action potential shapes and different degrees of synchronization of motor unit firing. It was shown that the effect of changes in intracellular action potential shape and muscle fibre propagation velocity (i.e. peripheral factors on spectral characteristics of EMG signals could be stronger than the effect of synchronization of firing of different motor units (i.e. central factors.

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

    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…

  13. Adaptive Response Surface Techniques in Reliability Estimation

    Enevoldsen, I.; Faber, M. H.; Sørensen, John Dalsgaard

    1993-01-01

    Problems in connection with estimation of the reliability of a component modelled by a limit state function including noise or first order discontinuitics are considered. A gradient free adaptive response surface algorithm is developed. The algorithm applies second order polynomial surfaces...... determined from central composite designs. In a two phase algorithm the second order surface is adjusted to the domain of the most likely failure point and both FORM and SORM estimates are obtained. The algorithm is implemented as a safeguard algorithm so non-converged solutions are avoided. Furthermore, a...

  14. Adaptive response to pneumonectomy in puppies.

    Thurlbeck, W. M.; Galaugher, W; Mathers, J.

    1981-01-01

    When left pneumonectomy was performed on 9-week-old puppies, the right lung increased in weight, volume, surface area, and number of alveoli so that at age 20 weeks these variables were the same as those of both lungs of control animals and significantly larger than those of the right lung of control animals. The adaptive response of the right lung after pneumonectomy was greater in the lower lobe than in the middle or cardiac lobes. The number of alveoli per ml and the average interalveolar ...

  15. Individual differences in response conflict adaptations

    DorisKeye

    2013-12-01

    Full Text Available Conflict-monitoring theory argues for a general cognitive mechanism that monitors for con-flicts in information-processing. If that mechanism detects conflict, it engages cognitive con-trol to resolve it. A slow-down in response to incongruent trials (conflict effect, and a modu-lation 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. 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, working memory capacity showed no relation with any factors representing adaptation to conflict.

  16. The possible role of chromatin conformation changes in adaptive responses to ionizing radiation

    Organisms are affected by different DNA damaging agents naturally present in the environment or released as a result of human activity. Many defense mechanisms have evolved in organisms to minimize genotoxic damage. One of them is induced radioresistance or adaptive response. The adaptive response could be considered as a nonspecific phenomenon in which exposure to minimal stress could result in increased resistance to higher levels of the same or to other types of stress some hours later. A better understanding of the molecular mechanism underlying the adaptive response may lead to an improvement of cancer treatment, risk assessment and risk management strategies, radiation protection. The aim of current study was to study the possible role of chromatin conformation changes induced by ionizing radiation on the adaptive responses in human lymphocyte. For this aim the chromatin conformation have been studied in human lymphocytes from three non-smoking and three smoking healthy volunteers prior, and after espouser to gamma radiation (adaptive dose 0.1 Gy, challenge dose 1.5 Gy and adaptive + dose challenge). Chromosomal aberrations and micronucleus have been used as end point to study radio cytotoxicity and adaptive response. Our results indicated individual differences in radio adaptive response and the level of this response was dependent of chromatin de condensation induced by a adaptive small dose.The results showed that different dose of gamma rays induce a chromatin de condensation in human lymphocyte. The maximum chromatin relaxation were record when lymphocyte exposed to adaptive dose (0.1 Gy.). Results also showed that Adaptive dose have affected on the induction of challenge dose (1.5 Gy) of chromosome aberration and micronucleus . The comparison of results of chromatin de condensation induction as measured by flow cytometry and cytogenetic damages measured by chromosomal aberrations or micronucleus, was showed a proportionality of adaptive response with

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

    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

  18. Cross adaptive response of human blood lymphocytes in vitro, bone marrow cells and germ cells in mice in vivo induced by low doses of X-rays and low concentrations of MMC, H2O2 and CP

    Interaction of low doses of X-rays (two doses of 10 mGy and 50 mGy, a dose rate of 50 mGy/min) and low concentrations of MMC, H2O2 and CP on chromosome aberrations of human blood lymphocytes in vitro, bone marrow cells and germ cells in mice in vivo was studied in order to elucidate cross adaptive response between radiation and chemical agents. Results showed that cross adaptive response could be induced of (1) chromosome aberrations of bone marrow cells when MMC with different concentrations (0.5, 2.5 and 5.0 mg/kg) were i.p. injected into mice 3 h after irradiation to 10 mGy X-rays. (2) chromosome aberrations of germ cells in mice by radiation and MMC, H2O2 when different concentrations of MMC, H2O2 and CP were i.p. injected into mice 3 h after irradiation to 50 mGy X-rays. However, it is not the case when CP applied, there is the synergetic effect between radiation and CP. (3) chromosome aberrations of human blood lymphocytes by 1.5 Gy X-irradiation 6 h after MMC (final concentration is 35 ng/mL) applied. (4) Anti-X rays damage by 1.5 Gy X-irradiation 24 h after low concentrations of MMC and H2O2, while not by CP. It provided the same conclusion as (2). The results suggested that the cross adaptive response of X-rays and MMC was induced not only in bone marrow cells in mice, but also in human blood lymphocytes in vitro. Besides, the response of interaction could be induced in germ cells in mice in vivo between low doses of X-rays and low concentrations of MMC and H2O2. But it is not the case for low concentrations of CP, the synergetic effect was produced between low concentration of CP and low dose of X-rays

  19. Formation and Regulation of Adaptive Response in Nematode Caenorhabditis elegans

    Y.-L. Zhao

    2012-01-01

    Full Text Available 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.

  20. Stochastic switching induced adaptation in a starved Escherichia coli population.

    Shimizu, Yoshihiro; Tsuru, Saburo; Ito, Yoichiro; Ying, Bei-Wen; Yomo, Tetsuya

    2011-01-01

    Population adaptation can be determined by stochastic switching in living cells. To examine how stochastic switching contributes to the fate decision for a population under severe stress, we constructed an Escherichia coli strain crucially dependent on the expression of a rewired gene. The gene essential for tryptophan biosynthesis, trpC, was removed from the native regulatory unit, the Trp operon, and placed under the extraneous control of the lactose utilisation network. Bistability of the network provided the cells two discrete phenotypes: the induced and suppressed level of trpC. The two phenotypes permitted the cells to grow or not, respectively, under conditions of tryptophan depletion. We found that stochastic switching between the two states allowed the initially suppressed cells to form a new population with induced trpC in response to tryptophan starvation. However, the frequency of the transition from suppressed to induced state dropped off dramatically in the starved population, in comparison to that in the nourished population. This reduced switching rate was compensated by increasing the initial population size, which probably provided the cell population more chances to wait for the rarely appearing fit cells from the unfit cells. Taken together, adaptation of a starved bacterial population because of stochasticity in the gene rewired from the ancient regulon was experimentally confirmed, and the nutritional status and the population size played a great role in stochastic adaptation. PMID:21931628

  1. Stochastic switching induced adaptation in a starved Escherichia coli population.

    Yoshihiro Shimizu

    Full Text Available Population adaptation can be determined by stochastic switching in living cells. To examine how stochastic switching contributes to the fate decision for a population under severe stress, we constructed an Escherichia coli strain crucially dependent on the expression of a rewired gene. The gene essential for tryptophan biosynthesis, trpC, was removed from the native regulatory unit, the Trp operon, and placed under the extraneous control of the lactose utilisation network. Bistability of the network provided the cells two discrete phenotypes: the induced and suppressed level of trpC. The two phenotypes permitted the cells to grow or not, respectively, under conditions of tryptophan depletion. We found that stochastic switching between the two states allowed the initially suppressed cells to form a new population with induced trpC in response to tryptophan starvation. However, the frequency of the transition from suppressed to induced state dropped off dramatically in the starved population, in comparison to that in the nourished population. This reduced switching rate was compensated by increasing the initial population size, which probably provided the cell population more chances to wait for the rarely appearing fit cells from the unfit cells. Taken together, adaptation of a starved bacterial population because of stochasticity in the gene rewired from the ancient regulon was experimentally confirmed, and the nutritional status and the population size played a great role in stochastic adaptation.

  2. Plant Cell Adaptive Responses to Microgravity

    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.

  3. Molecular mechanism of radioadaptive response: A cross-adaptive response for enhanced repair of DNA damage in adapted cells

    The radioadaptive response (RAR) has been attributed to the induction of a repair mechanism by low doses of ionizing radiation, but the molecular nature of the mechanism is not yet elucidated. We have characterized RAR in a series of experiments in cultured Chinese hamster V79 cells. A 4-h interval is required for the full expression of RAR, which decays with the progression of cell proliferation. Treatments with inhibitors of poly(ADP-ribose) polymerase, protein- or RNA synthesis, and protein kinase C suppress the RAR expression. The RAR cross-reacts on clastogenic lesions induced by other physical and chemical DNA-damaging agents. The presence of newly synthesised proteins has been detected during the expression period. Experiments performed using single-cell gel electrophoresis provided more direct evidence for a faster and enhaced DNA repair rate in adapted cells. Here, using single-cell gel electrophoresis, a cross-adaptive response has been demonstrated for enhanced repair of DNA damage induced by neocarzinostatin in radio-adapted cells. (author)

  4. Plant adaptation to dynamically changing environment: the shade avoidance response.

    Ruberti, I; Sessa, G; Ciolfi, A; Possenti, M; Carabelli, M; Morelli, G

    2012-01-01

    The success of competitive interactions between plants determines the chance of survival of individuals and eventually of whole plant species. Shade-tolerant plants have adapted their photosynthesis to function optimally under low-light conditions. These plants are therefore capable of long-term survival under a canopy shade. In contrast, shade-avoiding plants adapt their growth to perceive maximum sunlight and therefore rapidly dominate gaps in a canopy. Daylight contains roughly equal proportions of red and far-red light, but within vegetation that ratio is lowered as a result of red absorption by photosynthetic pigments. This light quality change is perceived through the phytochrome system as an unambiguous signal of the proximity of neighbors resulting in a suite of developmental responses (termed the shade avoidance response) that, when successful, result in the overgrowth of those neighbors. Shoot elongation induced by low red/far-red light may confer high relative fitness in natural dense communities. However, since elongation is often achieved at the expense of leaf and root growth, shade avoidance may lead to reduction in crop plant productivity. Over the past decade, major progresses have been achieved in the understanding of the molecular basis of shade avoidance. However, uncovering the mechanisms underpinning plant response and adaptation to changes in the ratio of red to far-red light is key to design new strategies to precise modulate shade avoidance in time and space without impairing the overall crop ability to compete for light. PMID:21888962

  5. A Manganese Superoxide Dismutase (SOD2)-Mediated Adaptive Response

    David J Grdina; Murley, Jeffrey S.; Miller, Richard C.; Mauceri, Helena J.; Sutton, Harold G.; Thirman, Michael J.; Li, Jian Jian; Woloschak, Gayle E.; Weichselbaum, Ralph R.

    2012-01-01

    Very low doses of ionizing radiation, 5 to 100 mGy, can induce adaptive responses characterized by elevation in cell survival and reduction in micronuclei formation. Utilizing these end points, RKO human colon carcinoma and transformed mouse embryo fibroblasts (MEF), wild-type or knockout cells missing TNF receptors 1 and 2 (TNFR1−R2−), and C57BL/6 and TNFR1−R2− knockout mice, we demonstrate that intact TNF signaling is required for induction of elevated manganese superoxide dismutase (SOD2) ...

  6. The surgically induced stress response.

    Finnerty, Celeste C; Mabvuure, Nigel Tapiwa; Ali, Arham; Kozar, Rosemary A; Herndon, David N

    2013-09-01

    The stress response to surgery, critical illness, trauma, and burns encompasses derangements of metabolic and physiological processes that induce perturbations in the inflammatory, acute phase, hormonal, and genomic responses. Hypermetabolism and hypercatabolism result, leading to muscle wasting, impaired immune function and wound healing, organ failure, and death. The surgery-induced stress response is largely similar to that triggered by traumatic injuries; the duration of the stress response, however, varies according to the severity of injury (surgical or traumatic). This spectrum of injuries and insults ranges from small lacerations to severe insults such as large poly-traumatic and burn injuries. Burn injuries provide an extreme model of trauma induced stress responses that can be used to study the long-term effects of a prolonged stress response. Although the stress response to acute trauma evolved to confer improved chances of survival following injury, in modern surgical practice the stress response can be detrimental. PMID:24009246

  7. The Surgically Induced Stress Response

    Finnerty, Celeste C.; Mabvuure, Nigel Tapiwa; Ali, Arham; Kozar, Rosemary A.; Herndon, David N

    2013-01-01

    The stress response to surgery, critical illness, trauma, and burns encompasses derangements of metabolic and physiological processes which induce perturbations in the inflammatory, acute phase, hormonal, and genomic responses. Hypermetabolism and hypercatabolism result, leading to muscle wasting, impaired immune function and wound healing, organ failure, and death. The surgery-induced stress response is largely similar to that triggered by traumatic injuries; the duration of the stress respo...

  8. Adaptive responses to antibody based therapy.

    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. PMID:26808665

  9. Expression of protein encoded by apoptosis-associated gene p53, bcl-2, and bax in adaptive response of thymocyte apoptosis in mice induced by low dose radiation with X-rays

    Objective: To explore the regulative mechanism of apoptosis-associated gene proteins on the adaptive response of thymocyte apoptosis in mice induced by low dose radiation with X-rays. Methods: Kunming male mice were irradiated with the inductive doses (D1: 25, 50, 75, 100 and 200 mGy; dose rate: 12.5 mGy ·min-1) and the challenging dose (D2: 1.5 Gy; dose rate: 287 mGy·min-1). The time interval between D1 and D2 was 6 h. The expressive levels of thymocyte apoptosis-associated gene proteins were measured with flow cytometry. Results: As compared with the sham-irradiation, the positive percentage of thymocyte Bcl-2 protein expression decreased significantly in D2 group (P<0.05), Bax increased significantly (P<0.05), and Bcl-2/Bax decreased significantly (P<0.001); p 53 increased significantly (P<0.001). As compared with D2 group, the positive percentage of thymocyte Bcl-2 protein expression increased in varying degree in D1+ D2 group of 25-75 mGy D1, Bax decreased in varying degree, and Bcl-2/Bax increased significantly (P<0.01); p53 decreased significantly (P<0.001 or P<0.05). Conclusion: The apoptotic thymocytes in the adaptive response of thymocyte apoptosis in mice induced by irradiation with 25-75 mGy decrease significantly due to the increase of apoptosis-associated gene Bcl-2 protein expression and Bcl-2/Bax, the decrease of Bax and p53 protein expressions. (authors)

  10. How relevant to radiation protection is the adaptive response mechanism?

    There is evidence that the phenomenon of adaptive response (AR) which results from a low dose exposure could modify the risk of a subsequent radiation exposure, and conceivably could even provide a net benefit rather than the putative radiation detriment at low doses. The AR has been widely observed in human and other mammalian cells exposed to low doses and low-dose rates. The phenomenon has been demonstrated at the level of one track per cell, the lowest insult a cell can receive. The AR to radiation has been shown to: (i) protect against the DNA damaging effects of radiation and many chemical carcinogens; (ii) increase the probability that improperly repaired cells will die by apoptosis, thereby reducing risk to the whole organism; (iii) suppress both spontaneous- and radiation-induced neoplastic transformation in vitro; and (iv) reduce life-shortening in mice that develop myeloid leukemia as a result of a radiation exposure. It remains unclear, however, if the AR will be relevant to either risk assessment or radiation protection. There is currently no evidence of AR's influence on the incidence of radiogenic cancer in vivo although recent data indicate that adapting doses could lead to reduced risk in animal or human populations. Currently the existing dose control and dose management programs attempt to limit or eliminate even very low exposures, without evidence that such an approach has economic and societal benefits. Indeed, if adaptation from exposure to low doses provides the same responses in vivo as have been shown in vitro, then the current approach to protection against low doses may be counterproductive However, the demonstrated principles of the adaptive response to radiation in vitro will not likely influence the long held current formulation of radiation protection practices until the biological action of accumulated low doses of radiation in vivo and its impact on the modulation of radiation carcinogenesis are better understood. (author)

  11. Determination of the adaptive response induced In vivo by gamma radiation and its relation with the sensibility to the damage induction in the DNA and with the repairing capacity

    The kinetics of damage induction and repair at different doses as well as the adaptive response induced by gamma ray exposure were determined in murine leukocytes in vivo. The damage-repair kinetics were established after the exposure to 0.5, 1.0 or 2.0 Gy in a 137Cs source. Peripheral blood samples were obtained from the tails of mice, the percentage of damaged cells and the DNA migration in each one were analyzed by the single cell gel electrophoresis (SCG) technique or comet assay. Results indicated that there was an induction of approximately 75% comets with the doses of 1.0 and 2.0 Gy, which was considerably reduced to 22% and 42% respectively during the first 15 minutes. This evidences the presence of a rapid repair process and suggests that leucocytes are genetically well prepared to repair this kind of damage. After 15 minutes, a second increase in the percentage of damaged cells that was proportional to dose occurred, which seems to represent the breaks produced during the repair of other kind of lesions. After that a second reduction was observed, reaching values near to the basal ones, except with the dose of 2.0 Gy. The kinetics obtained with the dose of 0.5 Gy was similar to that established with 1.0 Gy, but in this case the initial damage was 50 % lower. Besides, the adaptive response was observed after the exposure of the mice to an adaptive dose of 0.01 Gy and to a challenge dose of 1.0 Gy 60 minutes later. The pretreatment reduced the percentage of damaged cells caused by the challenge dose to one third approximately, and also diminished this parameter produced during the late repair process. This indicates that the early adaptive response is caused, instead of by an increment in repair, by the induction of a process that protects DNA from damage induction by radiation, i.e synthesis of substances that increase the scavenging of free radicals. (Author)

  12. Akt and MAPK signaling mediate pregnancy-induced cardiac adaptation.

    Chung, Eunhee; Yeung, Fan; Leinwand, Leslie A

    2012-05-01

    Although the signaling pathways underlying exercise-induced cardiac adaptation have been extensively studied, little is known about the molecular mechanisms that result in the response of the heart to pregnancy. The objective of this study was to define the morphological, functional, and gene expression patterns that define the hearts of pregnant mice, and to identify the signaling pathways that mediate this response. Mice were divided into three groups: nonpregnant diestrus control, midpregnancy, and late pregnancy. Both time points of pregnancy were associated with significant cardiac hypertrophy. The prosurvival signaling cascades of Akt and ERK1/2 were activated in the hearts of pregnant mice, while the stress kinase, p38, was decreased. Given the activation of Akt in pregnancy and its known role in cardiac hypertrophy, the hypertrophic response to pregnancy was tested in mice expressing a cardiac-specific activated (myristoylated) form of Akt (myrAkt) or a cardiac-specific constitutively active (antipathologic hypertrophic) form of its downstream target, glycogen synthase kinase 3β (caGSK3β). The pregnancy-induced hypertrophic responses of hearts from these mice were significantly attenuated. Finally, we tested whether pregnancy-associated sex hormones could induce hypertrophy and alter signaling pathways in isolated neonatal rat ventricular myocytes (NRVMs). In fact, progesterone, but not estradiol treatment increased NRVM cell size via phosphorylation of ERK1/2. Inhibition of MEK1 effectively blocked progesterone-induced cellular hypertrophy. Taken together, our study demonstrates that pregnancy-induced cardiac hypertrophy is mediated by activation of Akt and ERK1/2 pathways. PMID:22345431

  13. "I know, therefore I adapt?" Complexities of individual adaptation to climate-induced forest dieback in Alaska

    Lauren E. Oakes

    2016-06-01

    Full Text Available Individual actions to avoid, benefit from, or cope with climate change impacts partly shape adaptation; much research on adaptation has focused at the systems level, overlooking drivers of individual responses. Theoretical frameworks and empirical studies of environmental behavior identify a complex web of cognitive, affective, and evaluative factors that motivate stewardship. We explore the relationship between knowledge of, and adaptation to, widespread, climate-induced tree mortality to understand the cognitive (i.e., knowledge and learning, affective (i.e., attitudes and place attachment, and evaluative (i.e., use values factors that influence how individuals respond to climate-change impacts. From 43 semistructured interviews with forest managers and users in a temperate forest, we identified distinct responses to local, climate-induced environmental changes that we then categorized as either behavioral or psychological adaptations. Interviewees developed a depth of knowledge about the dieback through a combination of direct, place-based experiences and indirect, mediated learning through social interactions. Knowing that the dieback was associated with climate change led to different adaptive responses among the interviewees, although knowledge alone did not explain this variation. Forest users reported psychological adaptations to process negative attitudes; these adaptations were spurred by knowledge of the causes, losses of intangible values, and impacts to a species to which they held attachment. Behavioral adaptations exclusive to a high level of knowledge included actions such as using the forests to educate others or changing transportation behaviors to reduce personal energy consumption. Managers integrated awareness of the dieback and its dynamics across spatial scales into current management objectives. Our findings suggest that adaptive management may occur from the bottom up, as individual managers implement new practices in

  14. Adaptive response to ionizing radiation in normal and aneuploid human lymphocytes

    The ability to induce an adaptive response with low doses of gamma rays was studied in normal and trisomic lymphocytes (47, XX or XY, +21). The results indicate the presence of an adaptive response in lymphocytes of 3 normal donors, but in lymphocytes of 5 donors with trisomy 21 no significant adaptive response was found after irradiation with a low dose of gamma rays. In normal and trisomic lymphocytes (47, XX or XY, +21) irradiated with 1.50 Gy, a similar chromosomal radiosensitivity was observed at the 48th hour after stimulation. (author) 2 tabs., 15 ref

  15. Characterization of recombinant B. abortus strain RB51SOD towards understanding the uncorrelated innate and adaptive immune responses induced by RB51SOD compared to its parent vaccine strain RB51

    Jianguo eZhu

    2011-11-01

    Full Text Available Brucella abortus is a Gram-negative, facultative intracellular pathogen for several mammals, including humans. Live attenuated B. abortus strain RB51 is currently the official vaccine used against bovine brucellosis in the United States and several other countries. Overexpression of protective B. abortus antigen Cu/Zn superoxide dismutase (SOD in a recombinant strain of RB51 (strain RB51SOD significantly increases its vaccine efficacy against virulent B. abortus challenge in a mouse model. An attempt has been made to better understand the mechanism of the enhanced protective immunity of RB51SOD compared to its parent strain RB51. We previously reported that RB51SOD stimulated enhanced Th1 immune response. In this study, we further found that T effector cells derived from RB51SOD-immunized mice exhibited significantly higher cytotoxic T lymphocyte (CTL activity than T effector cells derived from RB51-immunized mice against virulent B. abortus-infected target cells. Meanwhile, the macrophage responses to these two strains were also studied. Compared to RB51, RB51SOD cells had a lower survival rate in macrophages and induced lower levels of macrophage apoptosis and necrosis. The decreased survival of RB51SOD cells correlates with the higher sensitivity of RB51SOD, compared to RB51, to the bactericidal action of either Polymyxin B or sodium dodecyl sulfate (SDS. Furthermore, a physical damage to the outer membrane of RB51SOD was observed by electron microscopy. Possibly due to the physical damage, overexpressed Cu/Zn SOD in RB51SOD was found to be released into the bacterial cell culture medium. Therefore, the stronger adaptive immunity induced by RB51SOD did not correlate with the low level of innate immunity induced by RB51SOD compared to RB51. This unique and apparently contradictory profile is likely associated with the differences in outer membrane integrity and Cu/Zn SOD release.

  16. Training induced adaptation in horse skeletal muscle

    van Dam, K.G.

    2006-01-01

    It appears that the physiological and biochemical adaptation of skeletal muscle to training in equine species shows a lot of similarities with human and rodent physiological adaptation. On the other hand it is becoming increasingly clear that intra-cellular mechanisms of adaptation (substrate transport, enzyme activity, etc) differ considerably between species. The major drawbacks in equine training physiological research are the lack of an appropriate training model and the lack of control o...

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

    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 ...

  18. Gene 33/Mig-6, a transcriptionally inducible adapter protein that binds GTP-Cdc42 and activates SAPK/JNK. A potential marker transcript for chronic pathologic conditions, such as diabetic nephropathy. Possible role in the response to persistent stress.

    Makkinje, A; Quinn, D A; Chen, A; Cadilla, C L; Force, T; Bonventre, J V; Kyriakis, J M

    2000-06-01

    Chronic stresses, including the mechanical strain caused by hypertension or excess pulmonary ventilation pressure, lead to important clinical consequences, including hypertrophy and acute respiratory distress syndrome. Pathologic hypertrophy contributes to decreased organ function and, ultimately, organ failure; and cardiac and diabetic renal hypertrophy are major causes of morbidity and morality in the developed world. Likewise, acute respiratory distress syndrome is a serious potential side effect of mechanical pulmonary ventilation. Whereas the deleterious effects of chronic stress are well established, the molecular mechanisms by which these stresses affect cell function are still poorly characterized. gene 33 (also called mitogen-inducible gene-6, mig-6) is an immediate early gene that is transcriptionally induced by a divergent array of extracellular stimuli. The physiologic function of Gene 33 is unknown. Here we show that gene 33 mRNA levels increase sharply in response to a set of commonly occurring chronic stress stimuli: mechanical strain, vasoactive peptides, and diabetic nephropathy. Induction of gene 33 requires the stress-activated protein kinases (SAPKs)/c-Jun NH(2)-terminal kinases. This expression pattern suggests that gene 33 is a potential marker for diabetic nephropathy and other pathologic responses to persistent sublethal stress. The structure of Gene 33 indicates an adapter protein capable of binding monomeric GTPases of the Rho subfamily. Consistent with this, Gene 33 interacts in vivo and, in a GTP-dependent manner, in vitro with Cdc42Hs; and transient expression of Gene 33 results in the selective activation of the SAPKs. These results imply a reciprocal, positive feedback relationship between Gene 33 expression and SAPK activation. Expression of Gene 33 at sufficient levels may enable a compensatory reprogramming of cellular function in response to chronic stress, which may have pathophysiological consequences. PMID:10749885

  19. A Dynamic Analysis of the Shade-induced Plasticity in Arabidopsis thaliana Rosette Leaf Development Reveals New Components of the Shade-adaptative Response

    Cookson, Sarah Jane; Granier, Christine

    2006-01-01

    • Background and Aims It is well known that plant aerial development is affected by light intensity in terms of the date of flowering, the length of stems and petioles, and the final individual leaf area. The aim of the work presented here was to analyse how shade-induced changes in leaf development occur on a dynamic basis from the whole rosette level to that of the cells.

  20. The Surgically Induced Stress Response

    Finnerty, Celeste C.; Mabvuure, Nigel Tapiwa; Ali, Arham; Kozar, Rosemary A.; Herndon, David N.

    2013-01-01

    The stress response to surgery, critical illness, trauma, and burns encompasses derangements of metabolic and physiological processes which induce perturbations in the inflammatory, acute phase, hormonal, and genomic responses. Hypermetabolism and hypercatabolism result, leading to muscle wasting, impaired immune function and wound healing, organ failure, and death. The surgery-induced stress response is largely similar to that triggered by traumatic injuries; the duration of the stress response, however, varies according to the severity of injury (surgical or traumatic). This spectrum of injuries and insults ranges from small lacerations to severe insults such as large poly-traumatic and burn injuries. Although the stress response to acute trauma evolved to improve chances of survival following injury, in modern surgical practice the stress response can be detrimental. PMID:24009246

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

    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…

  2. Molecular mechanism of adaptive response to low dose radiation

    Adaptive response is a term used to describe the ability of a low, priming dose of ionizing radiation to modify the effects of a subsequent higher, challenge dose. Molecular mechanism of adaptive response to low dose radiation is involved in signal transduction pathway, reactive oxygen species, DNA damage repair

  3. Pancreatic adaptive responses in alcohol abuse: Role of the unfolded protein response.

    Lugea, Aurelia; Waldron, Richard T; Pandol, Stephen J

    2015-07-01

    The majority of those who drink excessive amounts of alcohol do not develop pancreatic disease. One overarching hypothesis is that alcohol abuse requires additional risk factors, either environmental or genetic, for disease to occur. However, another reason be a result of alcohol-induced activation of adaptive systems that protect the pancreas from the toxic effects of alcohol. We show that mechanisms within the unfolded protein response (UPR) of the endoplasmic reticulum (ER) that can lead to protection of the pancreas from pancreatic diseases with alcohol abuse. The remarkable ability of the pancreas to adapt its machinery to alcohol abuse using UPR systems and continue functioning is the likely reason that pancreatitis from alcohol abuse does not occur in the majority of heavy drinkers. These findings indicate that methods to enhance the protective responses of the UPR can provide opportunities for prevention and treatment of pancreatic diseases. PMID:25736240

  4. Adaptive Queue Management with Restraint on Non-Responsive Flows

    Lan Li

    2003-12-01

    Full Text Available This paper proposes an adaptive queue management scheme (adaptive RED to improve Random Early Detection (RED on restraining non-responsive flows. Due to a lack of flow control mechanism, non-responsive flows can starve responsive flows for buffer and bandwidth at the gateway. In order to solve the disproportionate resource problem, RED framework is modified in this way: on detecting when the non-responsive flows starve the queue, packet-drop intensity (Max_p in RED can be adaptively adjusted to curb non-responsive flows for resource fair-sharing, such as buffer and bandwidth fair-sharing. Based on detection of traffic behaviors, intentionally restraining nonresponsive flows is to increase the throughput and decrease the drop rate of responsive flows. Our experimental results based on adaptive RED shows that the enhancement of responsive traffic and the better sharing of buffer and bandwidth can be achieved under a variety of traffic scenarios.

  5. Adaptive Filtering for Aeroservoelastic Response Suppression Project

    National Aeronautics and Space Administration — CSA Engineering proposes the design of an adaptive aeroelastic mode suppression for advanced fly-by-wire aircraft, which will partition the modal suppression...

  6. Vascular adaptive responses to physical exercise and to stress are affected differently by nandrolone administration

    T. Bruder-Nascimento

    2011-04-01

    Full Text Available Androgenic anabolic steroid, physical exercise and stress induce cardiovascular adaptations including increased endothelial function. The present study investigated the effects of these conditions alone and in combination on the vascular responses of male Wistar rats. Exercise was started at 8 weeks of life (60-min swimming sessions 5 days per week for 8 weeks, while carrying a 5% body-weight load. One group received nandrolone (5 mg/kg, twice per week for 8 weeks, im. Acute immobilization stress (2 h was induced immediately before the experimental protocol. Curves for noradrenaline were obtained for thoracic aorta, with and without endothelium from sedentary and trained rats, submitted or not to stress, treated or not with nandrolone. None of the procedures altered the vascular reactivity to noradrenaline in denuded aorta. In intact aorta, stress and exercise produced vascular adaptive responses characterized by endothelium-dependent hyporeactivity to noradrenaline. These conditions in combination did not potentiate the vascular adaptive response. Exercise-induced vascular adaptive response was abolished by nandrolone. In contrast, the aortal reactivity to noradrenaline of sedentary rats and the vascular adaptive response to stress of sedentary and trained rats were not affected by nandrolone. Maximum response for 7-10 rats/group (g: sedentary 3.8 ± 0.2 vs trained 3.0 ± 0.2*; sedentary/stress 2.7 ± 0.2 vs trained/stress 3.1 ± 0.1*; sedentary/nandrolone 3.6 ± 0.1 vs trained/nandrolone 3.8 ± 0.1; sedentary/stress/nandrolone 3.2 ± 0.1 vs trained/stress/nandrolone 2.5 ± 0.1*; *P < 0.05 compared to its respective control. Stress and physical exercise determine similar vascular adaptive response involving distinct mechanisms as indicated by the observation that only the physical exercise-induced adaptive response was abolished by nandrolone.

  7. Heat shock response and mammal adaptation to high elevation (hypoxia)

    WANG Xiaolin; XU Cunshuan; WANG Xiujie; WANG Dongjie; WANG Qingshang; ZHANG Baochen

    2006-01-01

    The mammal's high elevation (hypoxia) adaptation was studied by using the immunological and the molecular biological methods to understand the significance of Hsp (hypoxia) adaptation in the organic high elevation, through the mammal heat shock response. (1) From high elevation to low elevation (natural hypoxia): Western blot and conventional RT-PCR and real-time fluorescence quota PCR were adopted. Expression difference of heat shock protein of 70 (Hsp70) and natural expression of brain tissue of Hsp70 gene was determined in the cardiac muscle tissue among the different elevation mammals (yak). (2)From low elevation to high elevation (hypoxia induction):The mammals (domestic rabbits) from the low elevation were sent directly to the areas with different high elevations like 2300, 3300 and 5000 m above sea level to be raised for a period of 3 weeks before being slaughtered and the genetic inductive expression of the brain tissue of Hsp70 was determined with RT-PCR. The result indicated that all of the mammals at different elevations possessed their heat shock response gene. Hsp70 of the high elevation mammal rose abruptly under stress and might be induced to come into being by high elevation (hypoxia). The speedy synthesis of Hsp70 in the process of heat shock response is suitable to maintain the cells' normal physiological functions under stress. The Hsp70 has its threshold value. The altitude of 5000 m above sea level is the best condition for the heat shock response, and it starts to reduce when the altitude is over 6000 m above sea level. The Hsp70 production quantity and the cell hypoxia bearing capacity have their direct ratio.

  8. Chemotactic response and adaptation dynamics in Escherichia coli.

    Diana Clausznitzer

    2010-05-01

    Full Text Available Adaptation of the chemotaxis sensory pathway of the bacterium Escherichia coli is integral for detecting chemicals over a wide range of background concentrations, ultimately allowing cells to swim towards sources of attractant and away from repellents. Its biochemical mechanism based on methylation and demethylation of chemoreceptors has long been known. Despite the importance of adaptation for cell memory and behavior, the dynamics of adaptation are difficult to reconcile with current models of precise adaptation. Here, we follow time courses of signaling in response to concentration step changes of attractant using in vivo fluorescence resonance energy transfer measurements. Specifically, we use a condensed representation of adaptation time courses for efficient evaluation of different adaptation models. To quantitatively explain the data, we finally develop a dynamic model for signaling and adaptation based on the attractant flow in the experiment, signaling by cooperative receptor complexes, and multiple layers of feedback regulation for adaptation. We experimentally confirm the predicted effects of changing the enzyme-expression level and bypassing the negative feedback for demethylation. Our data analysis suggests significant imprecision in adaptation for large additions. Furthermore, our model predicts highly regulated, ultrafast adaptation in response to removal of attractant, which may be useful for fast reorientation of the cell and noise reduction in adaptation.

  9. Antibody Response to Serpin B13 Induces Adaptive Changes in Mouse Pancreatic Islets and Slows Down the Decline in the Residual Beta Cell Function in Children with Recent Onset of Type 1 Diabetes Mellitus.

    Kryvalap, Yury; Lo, Chi-Wen; Manuylova, Ekaterina; Baldzizhar, Raman; Jospe, Nicholas; Czyzyk, Jan

    2016-01-01

    Type 1 diabetes mellitus (T1D) is characterized by a heightened antibody (Ab) response to pancreatic islet self-antigens, which is a biomarker of progressive islet pathology. We recently identified a novel antibody to clade B serpin that reduces islet-associated T cell accumulation and is linked to the delayed onset of T1D. As natural immunity to clade B arises early in life, we hypothesized that it may influence islet development during that time. To test this possibility healthy young Balb/c male mice were injected with serpin B13 mAb or IgG control and examined for the number and cellularity of pancreatic islets by immunofluorescence and FACS. Beta cell proliferation was assessed by measuring nucleotide analog 5-ethynyl-2'-deoxyuridine (5-EdU) incorporation into the DNA and islet Reg gene expression was measured by real time PCR. Human studies involved measuring anti-serpin B13 autoantibodies by Luminex. We found that injecting anti-serpin B13 monoclonal Ab enhanced beta cell proliferation and Reg gene expression, induced the generation of ∼80 pancreatic islets per animal, and ultimately led to increase in the beta cell mass. These findings are relevant to human T1D because our analysis of subjects just diagnosed with T1D revealed an association between baseline anti-serpin activity and slower residual beta cell function decline in the first year after the onset of diabetes. Our findings reveal a new role for the anti-serpin immunological response in promoting adaptive changes in the endocrine pancreas and suggests that enhancement of this response could potentially help impede the progression of T1D in humans. PMID:26578518

  10. Perceptual task induces saccadic adaptation by target selection

    Alexander Christian Schütz

    2015-10-01

    We replicated our finding that a perceptual task can drive adaptation of saccades. Adaptation showed no effect of feedback reliability, nor an effect of the perceptual task beyond target selection. Adaptation was induced by a top-down signal since it was absent when there was no target selection instruction and no perceptual task. The immediate error correction was larger for the difficult than for the easy condition, suggesting that task difficulty affects mainly voluntary saccade targeting. In addition, the repetition of experiments one week later increased the magnitude of the gradual error correction. The results dissociate two distinct components of adaptation: an immediate and a gradual error correction. We conclude that perceptual-task induced adaptation is most likely due to top-down target selection within a larger object.

  11. Stimuli for municipal responses to climate adaptation: insights from Philadelphia – an early adapter

    Uittenbroek, C.J.; Janssen-Jansen, Leonie; Runhaar, H.A.C.

    2016-01-01

    An in-depth understanding of these stimuli is currently lacking in literature as most research has focussed on overcoming barriers to climate adaptation. The aim of this paper is to identify stimuli for municipal responses to climate adaptation and examine how they influence the governance approach

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

    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.

  13. Proteasome function shapes innate and adaptive immune responses.

    Kammerl, Ilona E; Meiners, Silke

    2016-08-01

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

  14. Responsibility for private sector adaptation to climate change

    Tina Schneider

    2014-06-01

    Full Text Available The Intergovernmental Panel on Climate Change (2007 indicates that vulnerable industries should adapt to the increasing likelihood of extreme weather events along with slowly shifting mean annual temperatures and precipitation patterns, to prevent major damages or periods of inoperability in the future. Most articles in the literature on business management frame organizational adaptation to climate change as a private action. This makes adaptation the sole responsibility of a company, for its sole benefit, and overlooks the fact that some companies provide critical goods and services such a food, water, electricity, and medical care, that are so vital to society that even a short-term setback in operations could put public security at risk. This raises the following questions: (1 Who is responsible for climate change adaptation by private-sector suppliers of critical infrastructure? (2 How can those who are identified to be responsible, actually be held to assume their responsibility for adapting to climate change? These questions will be addressed through a comprehensive review of the literature on business management, complemented by a review of specialized literature on public management. This review leads to several conclusions. Even though tasks that formerly belonged to the state have been taken over by private companies, the state still holds ultimate responsibility in the event of failure of private-sector owned utilities, insofar as they are “critical infrastructure.” Therefore, it remains the state’s responsibility to foster adaptation to climate change with appropriate action. In theory, effective ways of assuming this responsibility, while enabling critical infrastructure providers the flexibility adapt to climate change, would be to delegate adaptation to an agency, or to conduct negotiations with stakeholders. In view of this theory, Germany will be used as a case study to demonstrate how private-sector critical

  15. Using response times for item selection in adaptive testing

    Linden, van der Wim J.

    2008-01-01

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

  16. Exposure to stressful environments - Strategy of adaptive responses

    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.

  17. Adaptive workflow simulation of emergency response

    Bruinsma, Guido Wybe Jan

    2010-01-01

    Recent incidents and major training exercises in and outside the Netherlands have persistently shown that not having or not sharing information during emergency response are major sources of emergency response inefficiency and error, and affect incident mitigation outcomes through workflow planning

  18. Responsible Climate Change Adaptation : Exploring, analysing and evaluating public and private responsibilities for urban adaptation to climate change

    Mees, Heleen

    2014-01-01

    Cities are vulnerable to climate change. To deal with climate change, city governments and private actors such as businesses and citizens need to adapt to its effects, such as sea level rise, storm surges, intense rainfall and heatwaves. However, adaptation planning and action is often hampered when the relevant public and private actors have only vague and ambiguous responsibilities. Some exploration on the issue of public and private responsibilities has been undertaken in the literature, b...

  19. Relation between radio-adaptive response and cell to cell communication

    Ionizing radiation has been considered to cause severe damages to DNA and do harm to cells in proportion to the dose, however low it might be. In 1984, Wolff et al. showed that human peripheral lymphocytes adapted to the low-dose radiation from 3H-TdR added in culture medium and became resistant to the subsequent irradiation with high-doses of X-rays. This response, which is called radio-adaptive response, is also induced by X-rays and gamma-rays in human lymphocytes and Chinese hamster V79 cells. However, the mechanisms of and conditions for adaptive responses to radiation have not been clarified. With an objective of clarifying the conditions for adaptive responses of cells to radiation, we examined how the cell to cell communication is involved in the adaptive responses. We irradiated normal human embryo-derived (HE) cells and cancer cells (HeLa) in culture at high density with low-dose X-ray and examined their radio-adaptive responses by measuring the changes in sensitivity to subsequent high-dose X-ray irradiation using the Trypan Blue dye-exclusion test method. We also conducted experiments to examine the effects of Ca2+ ions and Phorbol 12-Myristate 13-Acetate (TPA) which are supposed to be involved in cell to cell communication. (author)

  20. The adaptive response of E. coli to low levels of alkylating agent

    In an attempt to characterise which gene products may be involved in the repair system induced in E. coli by growth on low levels of alkylating agent (the adaptive response) we have analysed mutants deficient in other known pathways of DNA repair for the ability to adapt to MNNG. Adaptive resistance to the killing effects of MNNG seems to require a functional DNA polymerase I whereas resistance to the mutagenic effects can occur in polymerase I deficient strains; similarly killing adaptation could not be observed in a dam3 mutant, which was nonetheless able to show mutational adaptation. These results suggest that these two parts of the adaptive response must, at least to some extent, be separable. Both adaptive responses can be seen in the absence of uvrD+ uvrE+-dependent mismatch repair, DNA polymerase II activity, or recF-mediated recombination and they are not affected by decreased levels of adenyl cyclase. The data presented support our earlier conclusion that adaptive resistance to the killing and mutagenic effect of MNNG is the result of previously uncharacterised repair pathways. (orig.)

  1. Adaptation or Manipulation? Unpacking Climate Change Response Strategies

    Timothy F. Smith

    2012-09-01

    Full Text Available Adaptation is a key feature of sustainable social–ecological systems. As societies traverse various temporal and spatial scales, they are exposed to differing contexts and precursors for adaptation. A cursory view of the response to these differing contexts and precursors suggests the particular ability of persistent societies to adapt to changing circumstances. Yet a closer examination into the meaning of adaptation and its relationship to concepts of resilience, vulnerability, and sustainability illustrates that, in many cases, societies actually manipulate their social–ecological contexts rather than adapt to them. It could be argued that manipulative behaviors are a subset of a broader suite of adaptive behaviors; however, this paper suggests that manipulative behaviors have fundamentally different intentions and outcomes. Specifically, adaptive behaviors are respectful of the intrinsic integrity of social–ecological systems and change is directed toward internal or self-regulating modification. By way of contrast, manipulative behaviors tend to disregard the integrity of social–ecological systems and focus on external change or manipulating the broader system with the aim of making self-regulation unnecessary. It is argued that adaptive behaviors represent long-term strategies for building resilience, whereas manipulative behaviors represent short-term strategies with uncertain consequences for resilience, vulnerability, and the sustainability of social–ecological systems. Of greatest significance; however, is that manipulative strategies have the potential to avoid authentic experiences of system dynamics, obscure valuable learning opportunities, create adverse path dependencies, and lessen the likelihood of effective adaptation in future contexts.

  2. The Nominal Response Model in Computerized Adaptive Testing.

    De Ayala, R. J.

    One important and promising application of item response theory (IRT) is computerized adaptive testing (CAT). The implementation of a nominal response model-based CAT (NRCAT) was studied. Item pool characteristics for the NRCAT as well as the comparative performance of the NRCAT and a CAT based on the three-parameter logistic (3PL) model were…

  3. Bacterial genomic adaptation and response to metals

    The beta-proteobacterium Cupriavidus metallidurans CH34 (formerly Ralstonia metallidurans) has been intensively studied since 1976 in SCK-CEN and VITO, for its adaptation capacity to survive in harsh (mostly industrial) environments, to overcome acute environmental stresses, for its resistance to a variety of heavy metals and for applications in environmental biotechnology. Recently, CH34 has become a model bacterium to study the effect of spaceflight conditions in several space flight experiments conducted by SCK-CEN (e.g. MESSAGE, BASE). Furthermore, Cupriavidus and Ralstonia species are isolated from the floor, air and surfaces of spacecraft assembly rooms; were found prior-to-flight on surfaces of space robots such as the Mars Odyssey Orbiter and even in-flight in ISS cooling water and Shuttle drinking water, vindicating its role as model bacterium in space research. In addition, Ralstonia species are also the causative agent of nosocomial infections and are among the unusual species recovered from cystic fibrosis (CF) patients. The genomic organization of Cuprivavidus metallidurans CH34 was studied in-depth to identify the genetic and regulatory structures involved in the resistance to heavy metals

  4. Exposure to Stressful Environments: Strategy of Adaptive Responses

    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.

  5. Oxazolone-induced contact hypersensitivity reduces lymphatic drainage but enhances the induction of adaptive immunity.

    David Aebischer

    Full Text Available Contact hypersensitivity (CHS induced by topical application of haptens is a commonly used model to study dermal inflammatory responses in mice. Several recent studies have indicated that CHS-induced skin inflammation triggers lymphangiogenesis but may negatively impact the immune-function of lymphatic vessels, namely fluid drainage and dendritic cell (DC migration to draining lymph nodes (dLNs. On the other hand, haptens have been shown to exert immune-stimulatory activity by inducing DC maturation. In this study we investigated how the presence of pre-established CHS-induced skin inflammation affects the induction of adaptive immunity in dLNs. Using a mouse model of oxazolone-induced skin inflammation we observed that lymphatic drainage was reduced and DC migration from skin to dLNs was partially compromised. At the same time, a significantly stronger adaptive immune response towards ovalbumin (OVA was induced when immunization had occurred in CHS-inflamed skin as compared to uninflamed control skin. In fact, immunization with sterile OVA in CHS-inflamed skin evoked a delayed-type hypersensitivity (DTH response comparable to the one induced by conventional immunization with OVA and adjuvant in uninflamed skin. Striking phenotypic and functional differences were observed when comparing DCs from LNs draining uninflamed or CHS-inflamed skin. DCs from LNs draining CHS-inflamed skin expressed higher levels of co-stimulatory molecules and MHC molecules, produced higher levels of the interleukin-12/23 p40 subunit (IL-12/23-p40 and more potently induced T cell activation in vitro. Immunization experiments revealed that blockade of IL-12/23-p40 during the priming phase partially reverted the CHS-induced enhancement of the adaptive immune response. Collectively, our findings indicate that CHS-induced skin inflammation generates an overall immune-stimulatory milieu, which outweighs the potentially suppressive effect of reduced lymphatic vessel function.

  6. Load Cell Response Correction Using Analog Adaptive Techniques

    Jafaripanah, Mehdi; Al-Hashimi, Bashir; White, Neil M.

    2003-01-01

    Load cell response correction can be used to speed up the process of measurement. This paper investigates the application of analog adaptive techniques in load cell response correction. The load cell is a sensor with an oscillatory output in which the measurand contributes to response parameters. Thus, a compensation filter needs to track variation in measurand whereas a simple, fixed filter is only valid at one load value. To facilitate this investigation, computer models for the load cell a...

  7. Space Mapping With Adaptive Response Correction for Microwave Design Optimization

    Koziel, S.; Bandler, J.W.; Madsen, Kaj

    2009-01-01

    microwave area where the typical model response (e.g., vertical bar S-21 vertical bar) is a highly nonlinear function of the free parameter (e.g., frequency), the output space-mapping correction term may actually increase the mismatch between the surrogate and fine models for points other than the one at...... mapping by adaptive adjustment of the response correction term according to the changes of the space-mapped coarse model response. Examples indicate the robustness of our approach....

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

    Adrienne B. Nicotra; 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 ...

  9. p53-Dependent Adaptive Responses in Human Cells Exposed to Space Radiations

    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.

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

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

  11. REM SLEEP REBOUND AS AN ADAPTIVE RESPONSE TO STRESSFUL SITUATIONS

    Deborah eSuchecki

    2012-04-01

    Full Text Available 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 form to cope with the adverse stimuli. Chronic stress, conversely, 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, which confer 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 REM 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.

  12. Adaptation responses of crops to climate change

    Seino, Hiroshi [National Inst. of Agro-Environmental Sciences, Tsukuba, Ibaraki (Japan)

    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.

  13. Adaptive response and split-dose effect of radiation on the survival of mice

    Ashu Bhan Tiku; R K Kale

    2004-03-01

    Although the importance of radiation-induced adaptive response has been recognized in human health, risk assessment and clinical application, the phenomenon has not been understood well in terms of survival of animals. To examine this aspect Swiss albino mice were irradiated with different doses (2–10 Gy) at 0.015 Gy/s dose rate and observed on a regular basis for 30 days. Since almost 50% lethality was seen with 8 Gy, it was selected as the challenging dose for further studies. Irradiation of mice with conditioning doses (0.25 or 0.5 Gy) and subsequent exposure to 8 Gy caused significant increase in the survival of mice compared to irradiated control. The splitting of challenging dose did not influence the efficiency of conditioning doses (0.25 Gy and 0.5 Gy) to induce an adaptive response. However conditioning doses given in fractions (0.25 Gy + 0.25 Gy) or (0.5 Gy + 0.5 Gy) were able to modulate the response of challenging dose of 8 Gy. These results clearly showed the occurrence of adaptive response in terms of survival of animals. The conditioning dose given in small fractions seemed to be more effective. The findings have been discussed from a mechanistic point of view. The possible biological implications, potential medical benefits, uncertainties and controversies related to adaptive response have also been addressed.

  14. Adaptation responses to climate change differ between global megacities

    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.

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

    Peter R Murphy

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

  16. Impact of Global Changes on Mountains: Responses and Adaptation

    Stephan Harrison

    2016-05-01

    Full Text Available Reviewed: Impact of Global Changes on Mountains: Responses and Adaptation. Edited by Velma I. Grover, Axel Borsdorf, Jürgen Breuste, Prakash Chandra Tiwari, Flavia Witkowski Frangetto, . Boca Raton, FL: CRC Press, 2015. ix + 517 pp. £ 103.00. Also available as an e-book. ISBN 978-1-4822-0890-0.

  17. Adaptive Patterns of Stress Responsivity: A Preliminary Investigation

    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…

  18. Zinc-Induced Transposition of Insertion Sequence Elements Contributes to Increased Adaptability of Cupriavidus metallidurans

    Vandecraen, Joachim; Monsieurs, Pieter; Mergeay, Max; Leys, Natalie; Aertsen, Abram; Van Houdt, Rob

    2016-01-01

    Bacteria can respond to adverse environments by increasing their genomic variability and subsequently facilitating adaptive evolution. To demonstrate this, the contribution of Insertion Sequence (IS) elements to the genetic adaptation of Cupriavidus metallidurans AE126 to toxic zinc concentrations was determined. This derivative of type strain CH34, devoid of its main zinc resistance determinant, is still able to increase its zinc resistance level. Specifically, upon plating on medium supplemented with a toxic zinc concentration, resistant variants arose in which a compromised cnrYX regulatory locus caused derepression of CnrH sigma factor activity and concomitant induction of the corresponding RND-driven cnrCBA efflux system. Late-occurring zinc resistant variants likely arose in response to the selective conditions, as they were enriched in cnrYX disruptions caused by specific IS elements whose transposase expression was found to be zinc-responsive. Interestingly, deletion of cnrH, and consequently the CnrH-dependent adaptation potential, still enabled adaptation by transposition of IS elements (ISRme5 and IS1086) that provided outward-directed promoters driving cnrCBAT transcription. Finally, adaptation to zinc by IS reshuffling can also enhance the adaptation to subsequent environmental challenges. Thus, transposition of IS elements can be induced by stress conditions and play a multifaceted, pivotal role in the adaptation to these and subsequent stress conditions. PMID:27047473

  19. Nanoparticles for nasal delivery of vaccines : monitoring adaptive immune responses

    Keijzer, C.

    2013-01-01

    The continuous emergence of new pathogens and growing drug resistance of microorganisms asks for innovative vaccination strategies. An alternative to conventional multiple injection vaccines is the nasal route of vaccine delivery. The immune response induced following nasal antigen delivery depends

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

    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.

  1. Infinite impulse response modal filtering in visible adaptive optics

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

    2012-01-01

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

  2. Infinite impulse response modal filtering in visible adaptive optics

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

    2012-07-01

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

  3. Frequency Response Adaptive Control of a Refrigeration Cycle

    Jens G. Balchen

    1989-01-01

    Full Text Available A technique for the adaptation of controller parameters in a single control loop based upon the estimation of frequency response parameters has been presented in an earlier paper. This paper contains an extension and a generalization of the first method and results in a more versatile solution which is applicable to a wider range of process characteristics. The application of this adaptive control technique is illustrated by a laboratory refrigeration cycle in which the evaporator pressure controls the speed of the compressor.

  4. Aspects of the adaptive response to very low doses of radiation and other agents

    When human lymphocytes and other cells are pre-exposed to very low doses of ionizing radiation and subsequently exposed to a high dose, less genetic damage, i.e., fewer chromosome aberrations, is found than is observed in cells that had not been pre-exposed. This has been termed the adaptive response and has been attributed to the induction of a repair mechanism by the low dose exposure. Several experiments have now been carried out on this adaptive response to better characterize the phenomenon. (A) Experiments with differential display of mRNAs indicate that human lymphocytes exposed to 2 cGy of X-rays have somewhat different mRNAs expressed than do unexposed cells. This is providing access to DNA that might be involved in adaptation. (B) Other experiments with embryonic cells from transgenic mice that are deficient in superoxide dismutase (SOD) have shown that the adaptive response is unrelated to the amount of SOD in the cells, and thus is independent of superoxide radicals. (C) Experiments in which very low doses of various restriction enzymes were electroporated into human lymphocytes have shown that low levels of double-strand DNA breaks alone are able to induce the adaptive response. (D) Experiments in which human male lymphocytes (XY chromosome constitution) and human female lymphocytes (XX chromosome constitution) were cocultivated have shown that adaptation is not caused by a change in the rate of cell progression to mitosis after a challenge dose, and is a further indication that cell stage sensitivity is not a factor in the adaptive response

  5. Multigenerational epigenetic adaptation of the hepatic wound-healing response.

    Zeybel, Müjdat; Hardy, Timothy; Wong, Yi K; Mathers, John C; Fox, Christopher R; Gackowska, Agata; Oakley, Fiona; Burt, Alastair D; Wilson, Caroline L; Anstee, Quentin M; Barter, Matt J; Masson, Steven; Elsharkawy, Ahmed M; Mann, Derek A; Mann, Jelena

    2012-09-01

    We investigated whether ancestral liver damage leads to heritable reprogramming of hepatic wound healing in male rats. We found that a history of liver damage corresponds with transmission of an epigenetic suppressive adaptation of the fibrogenic component of wound healing to the male F1 and F2 generations. Underlying this adaptation was less generation of liver myofibroblasts, higher hepatic expression of the antifibrogenic factor peroxisome proliferator-activated receptor γ (PPAR-γ) and lower expression of the profibrogenic factor transforming growth factor β1 (TGF-β1) compared to rats without this adaptation. Remodeling of DNA methylation and histone acetylation underpinned these alterations in gene expression. Sperm from rats with liver fibrosis were enriched for the histone variant H2A.Z and trimethylation of histone H3 at Lys27 (H3K27me3) at PPAR-γ chromatin. These modifications to the sperm chromatin were transmittable by adaptive serum transfer from fibrotic rats to naive rats and similar modifications were induced in mesenchymal stem cells exposed to conditioned media from cultured rat or human myofibroblasts. Thus, it is probable that a myofibroblast-secreted soluble factor stimulates heritable epigenetic signatures in sperm so that the resulting offspring better adapt to future fibrogenic hepatic insults. Adding possible relevance to humans, we found that people with mild liver fibrosis have hypomethylation of the PPARG promoter compared to others with severe fibrosis. PMID:22941276

  6. Filoviruses and the balance of innate, adaptive, and inflammatory responses.

    Mohamadzadeh, Mansour; Chen, Lieping; Olinger, Gene G; Pratt, William D; Schmaljohn, Alan L

    2006-01-01

    The Filoviruses Marburg virus and Ebola virus are among the deadliest of human pathogens, causing fulminant hemorrhagic fevers typified by overmatched specific immune responses and profuse inflammatory responses. Keys to both vaccination and treatment may reside, first, in the understanding of immune dysfunctions that parallel Filoviral disease and, second, in devising ways to redirect and restore normal immune function as well as to mitigate inflammation. Here, we describe how Filoviral infections may subvert innate immune responses through perturbances of dendritic cells and neutrophils, with particular emphasis on the downstream effects on adaptive immunity and inflammation. We suggest that pivotal events may be subject to therapeutic intervention as Filoviruses encounter immune processes. PMID:17201655

  7. Adaptive radiation-induced epigenetic alterations mitigated by antioxidants

    Bernal, Autumn J.; Dolinoy, Dana C; Huang, Dale; Skaar, David A.; Weinhouse, Caren; Jirtle, Randy L

    2013-01-01

    Humans are exposed to low-dose ionizing radiation (LDIR) from a number of environmental and medical sources. In addition to inducing genetic mutations, there is concern that LDIR may also alter the epigenome. Such heritable effects early in life can either be positively adaptive or result in the enhanced formation of diseases, including cancer, diabetes, and obesity. Herein, we show that LDIR significantly increased DNA methylation at the viable yellow agouti (Avy) locus in a sex-specific man...

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

    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. PMID:26074470

  9. Sequential monitoring of response-adaptive randomized clinical trials

    Zhu, Hongjian; 10.1214/10-AOS796

    2010-01-01

    Clinical trials are complex and usually involve multiple objectives such as controlling type I error rate, increasing power to detect treatment difference, assigning more patients to better treatment, and more. In literature, both response-adaptive randomization (RAR) procedures (by changing randomization procedure sequentially) and sequential monitoring (by changing analysis procedure sequentially) have been proposed to achieve these objectives to some degree. In this paper, we propose to sequentially monitor response-adaptive randomized clinical trial and study it's properties. We prove that the sequential test statistics of the new procedure converge to a Brownian motion in distribution. Further, we show that the sequential test statistics asymptotically satisfy the canonical joint distribution defined in Jennison and Turnbull (\\citeyearJT00). Therefore, type I error and other objectives can be achieved theoretically by selecting appropriate boundaries. These results open a door to sequentially monitor res...

  10. The adaptive value of parental responsiveness to nestling begging

    Grodzinski, Uri; Lotem, Arnon

    2007-01-01

    Despite extensive theoretical and empirical research into offspring food solicitation behaviour as a model for parent–offspring conflict and communication, the adaptive value of parental responsiveness to begging has never been tested experimentally. Game theory models, as well as empirical studies, suggest that begging conveys information on offspring state, which implies that parental investment can be better translated to fitness by responding to begging when allocating resources rather th...

  11. Comparison of adaptive response to γ-radiation and nickel sulfate treatment in human cells

    The comparison of the adaptive response to the impact of the γ-irradiation and nickel sulfate treatment in human cells, as the adaptive factors relative to these mutagens in the challenging doses by the cells survival criterium, is carried out. The pretreatment of human fibroblasts (the rhabdomyosarcoma line) with the low dose γ-radiation (10-14 cGy) formed increased viability of human cells to the nickel sulfate high concentrations (10-5-10-3 M). The adaptive response observed was similar to the radioadaptive response in human fibroblasts pretreated with low doses of γ-radiation with subsequent impact of high dose radiation. The pretreatment of human cells with the nickel sulfate low concentrations induced the DNA increased stability by impact of challenging doses of the γ-radiation and stimulated the DNA reparative synthesis by impact of both NiSO4 and 4-nitroquinoline-1-oxide. These data confirm the existence of the cross-sectional adaptive response in the experiments with the nickel sulfate

  12. Temporal recalibration in vocalization induced by adaptation of delayed auditory feedback.

    Kosuke Yamamoto

    Full Text Available BACKGROUND: We ordinarily perceive our voice sound as occurring simultaneously with vocal production, but the sense of simultaneity in vocalization can be easily interrupted by delayed auditory feedback (DAF. DAF causes normal people to have difficulty speaking fluently but helps people with stuttering to improve speech fluency. However, the underlying temporal mechanism for integrating the motor production of voice and the auditory perception of vocal sound remains unclear. In this study, we investigated the temporal tuning mechanism integrating vocal sensory and voice sounds under DAF with an adaptation technique. METHODS AND FINDINGS: Participants produced a single voice sound repeatedly with specific delay times of DAF (0, 66, 133 ms during three minutes to induce 'Lag Adaptation'. They then judged the simultaneity between motor sensation and vocal sound given feedback. We found that lag adaptation induced a shift in simultaneity responses toward the adapted auditory delays. This indicates that the temporal tuning mechanism in vocalization can be temporally recalibrated after prolonged exposure to delayed vocal sounds. Furthermore, we found that the temporal recalibration in vocalization can be affected by averaging delay times in the adaptation phase. CONCLUSIONS: These findings suggest vocalization is finely tuned by the temporal recalibration mechanism, which acutely monitors the integration of temporal delays between motor sensation and vocal sound.

  13. Cellular adaptation as an important response during chemical carcinogenesis

    Since disease processes are largely expressions of how living organisms react and respond to perturbations in the external and internal environments, adaptive or protective responses and their modulations and mechanisms are of the greatest concern in fundamental studies of disease pathogenesis. Such considerations are also of the greatest relevance in toxicology, including how living organisms respond to low levels of single and multiple xenobiotics and radiations. As the steps and mechanisms during cancer development are studied in greater depth, phenomena become apparent that suggest that adaptive reactions and responses may play important or even critical roles in the process of carcinogenesis. The question becomes whether the process of carcinogenesis is fundamentally an adversarial one (i.e., an abnormal cell in a vulnerable host), or is it more in the nature of a physiological selection or differentiation, which has survival value for the host as an adaptive phenomena? The very early initial interactions of mutagenic chemical carcinogens, radiations and viruses with DNA prejudice most to consider the adversarial 'abnormal' view as the appropriate one. Yet, the unusually common nature of the earliest altered rare cells that appear during carcinogenesis, their unusually bland nature, and their spontaneous differentiation to normal-appearing adult liver should be carefully considered

  14. Prolonged stress induces adaptation of drosophila population to ionizing radiation

    We studied natural populations of Drosophila melanogaster from radio-contaminated area (Vetka district of Gomel region with 24 Ci/km2 of 137Cs and 0.5 Cu/km2 of 90Sr) and from Berezynski Natural Reserve as a control area (region of Chernobyl catastrophe). Population samples were caught in 2000-2001 years. Natural insect populations from radio-contaminated areas are more resistant to additional irradiation than control populations. Keeping of natural populations under laboratory or vivarium conditions is a strong stress (limited space, overpopulation, other than in nature temperature and light conditions), which increases mutation process and induces unspecific adaptation. (authors)

  15. Central adaptation of pain perception in response to rehabilitation of musculoskeletal pain

    Andersen, Lars L; Andersen, Christoffer H; Sundstrup, Emil;

    2012-01-01

    Understanding the mechanisms of long-standing musculoskeletal pain and adaptations in response to physical rehabilitation is important for developing optimal treatment strategies. The influence of central adaptations of pain perception in response to rehabilitation of musculoskeletal pain remains...

  16. Receptor-Induced Dilatation in the Systemic and Intrarenal Adaptation to Pregnancy in Rats

    Ferreira, Vanessa M.; Gomes, Thiago S.; Reis, Luciana A.; Ferreira, Alice T.; Razvickas, Clara V.; Schor, Nestor; Boim, Mirian A.

    2009-01-01

    Normal pregnancy is associated with systemic and intrarenal vasodilatation resulting in an increased glomerular filtration rate. This adaptive response occurs in spite of elevated circulating levels of angiotensin II (Ang II). In the present study, we evaluated the potential mechanisms responsible for this adaptation. The reactivity of the mesangial cells (MCs) cultured from 14-day-pregnant rats to Ang II was measured through changes in the intracellular calcium concentration ([Cai]). The expression levels of inducible nitric oxide synthase (iNOS), the Ang II-induced vasodilatation receptor AT2, and the relaxin (LGR7) receptor were evaluated in cultured MCs and in the aorta, renal artery and kidney cortex by real time-PCR. The intrarenal distribution of LGR7 was further analyzed by immunohistochemistry. The MCs displayed a relative insensitivity to Ang II, which was paralleled by an impressive increase in the expression level of iNOS, AT2 and LGR7. These results suggest that the MCs also adapt to the pregnancy, thereby contributing to the maintenance of the glomerular surface area even in the presence of high levels of Ang II. The mRNA expression levels of AT2 and LGR7 also increased in the aorta, renal artery and kidney of the pregnant animals, whereas the expression of the AT1 did not significantly change. This further suggests a role of these vasodilatation-induced receptors in the systemic and intrarenal adaptation during pregnancy. LGR7 was localized in the glomeruli and on the apical membrane of the tubular cells, with stronger labeling in the kidneys of pregnant rats. These results suggest a role of iNOS, AT2, and LGR7 in the systemic vasodilatation and intrarenal adaptation to pregnancy and also suggest a pivotal role for relaxin in the tubular function during gestation. PMID:19287481

  17. Evidence of cross-stressor - induced adaptive gastric cytoprotection

    Glavin, G.B.; Lockhart, L.K.; Rockman, G.E.; Hall, A.M.; Kiernan, K.M.

    1987-11-09

    Rats were given 7 days pre-treatment with either water (p.o.), 1 h immobilization or 20% ethanol (p.o.) with or without concomitant indomethacin injection. Following the pre-treatment phase, rats from each pre-treatment group were exposed to either 3 h cold-restraint stress or to 100% ethanol p.o. Results indicated that immobilization and 20% ethanol pre-treatment significantly reduce both cold-restraint stress ulcer formation and 100% ethanol-induced ulcers. Indomethacin co-treatment attenuated the reduction of ulcer formation of both pretreatments. These results suggest that cross-stressor adaptive cytoprotection occurs. Indomethacin abolished these effects, implicating the involvement of endogenous prostaglandins in the mediation of cross-stressor - induced gastric cytoprotection. 12 references, 2 figures.

  18. Inducible heat shock protein 70 (HSP70) Involves in radioadaptive response

    Radiation induced fibrosarcoma (RIF) cells did not show the adaptive response, i.e. a reduced effect from a higher challenging dose (4 Gy) of a radiation when a priming dose (1 cGy) had been applied 4 or 7 hrs earlier, but its thermoresistant clone (TR) did. Since inducible HSP70 expression was different between two cell lines, the role of inducible HSP70 in adaptive response was examined. When inducible hsp70 was transfected to RIF cells, the adaptive response was acquired. Inducible hsp70 transfected NIH3T3 mouse embryo cells also conferred radioresistance when detected by clonogenic survival, [3H]-thymidine incoporation, and ELISA cell death detection kit, as well as increased tendency of induction adaptive response. Interestingly, basal levels of Ca2+-dependent and Ca2+-independent PKC activities were increased by inducible HSP70, when compared to those of control vector cells. Irradiation of g-ray induced PKC activation within minutes in control vector cells, while it did not by inducible HSP70. Cellular redistribution to particulate fraction of PKCa, d and z by g-rays was not detected either. Furthermore, radioresistance by inducible HSP70 was disappeared by pre-treatment of PKC inhibitors, 1-(5-isoquinolinesulfomyI)-2-methylpepirazine (H7), prolonged treatment of 12-O-tetradecanoylphorbol-13-acetate (TPA), and GF109203X in clonogenic survival assay. Taken together, these data suggest that inducible HSP70-induced radioresistance is associated with its elevated level of PKC activity

  19. Roles of chemical signals in regulation of the adaptive responses to iron deficiency.

    Liu, Xing Xing; He, Xiao Lin; Jin, Chong Wei

    2016-05-01

    Iron is an essential micronutrient for plants but is not readily accessible in most calcareous soils. Although the adaptive responses of plants to iron deficiency have been well documented, the signals involved in the regulatory cascade leading to their activation are not well understood to date. Recent studies revealed that chemical compounds, including sucrose, auxin, ethylene and nitric oxide, positively regulated the Fe-deficiency-induced Fe uptake processes in a cooperative manner. Nevertheless, cytokinins, jasmonate and abscisic acid were shown to act as negative signals in transmitting the iron deficiency information. The present mini review is to briefly address the roles of chemical signals in regulation of the adaptive responses to iron deficiency based on the literatures published in recent years. PMID:27110729

  20. Adaptive response in frogs chronically exposed to low doses of ionizing radiation in the environment

    Using the micronucleus assay, decreased levels of DNA damage were found after high dose ionizing radiation exposure of liver cells taken from frogs inhabiting a natural environment with above-background levels of ionizing radiation, compared to cells taken from frogs inhabiting background areas. The data obtained from a small number of animals suggest that stress present in the above-background environment could induce an adaptive response to ionizing radiation. This study did not reveal harmful effects of exposure to low levels of radioactivity. On the contrary, stress present in the above-background area may serve to enhance cellular defense mechanisms. - Highlights: → Frogs were collected from background and higher tritium level habitats. → The micronucleus assay was conducted on liver cells obtained from the frogs. → No detrimental effects were noted in frogs exposed to elevated tritium. → Adaptive responses were observed in frogs exposed to elevated tritium.

  1. Distributed Demand Response and User Adaptation in Smart Grids

    Fan, Zhong

    2010-01-01

    This paper proposes a distributed framework for demand response and user adaptation in smart grid networks. In particular, we borrow the concept of congestion pricing in Internet traffic control and show that pricing information is very useful to regulate user demand and hence balance network load. User preference is modeled as a willingness to pay parameter which can be seen as an indicator of differential quality of service. Both analysis and simulation results are presented to demonstrate the dynamics and convergence behavior of the algorithm.

  2. Adaptive governance and institutional strategies for climate-induced community relocations in Alaska.

    Bronen, Robin; Chapin, F Stuart

    2013-06-01

    This article presents governance and institutional strategies for climate-induced community relocations. In Alaska, repeated extreme weather events coupled with climate change-induced coastal erosion impact the habitability of entire communities. Community residents and government agencies concur that relocation is the only adaptation strategy that can protect lives and infrastructure. Community relocation stretches the financial and institutional capacity of existing governance institutions. Based on a comparative analysis of three Alaskan communities, Kivalina, Newtok, and Shishmaref, which have chosen to relocate, we examine the institutional constraints to relocation in the United States. We identify policy changes and components of a toolkit that can facilitate community-based adaptation when environmental events threaten people's lives and protection in place is not possible. Policy changes include amendment of the Stafford Act to include gradual geophysical processes, such as erosion, in the statutory definition of disaster and the creation of an adaptive governance framework to allow communities a continuum of responses from protection in place to community relocation. Key components of the toolkit are local leadership and integration of social and ecological well-being into adaptation planning. PMID:23690592

  3. Role of SHIP-1 in the adaptive immune responses to aeroallergen in the airway.

    Sukit Roongapinun

    Full Text Available BACKGROUND: Th2-dominated inflammatory response in the airway is an integral component in the pathogenesis of allergic asthma. Accumulating evidence supports the notion that the phosphoinositide 3-kinase (PI3K pathway is involved in the process. We previously reported that SHIP-1, a negative regulator of the PI3K pathway, is essential in maintaining lung immunohomeostasis, potentially through regulation of innate immune cells. However, the function of SHIP-1 in adaptive immune response in the lung has not been defined. We sought to determine the role of SHIP-1 in adaptive immunity in response to aeroallergen stimulation in the airway. METHODOLOGY/PRINCIPAL FINDINGS: SHIP-1 knockout (SHIP-1-/- mice on BALB/c background were immunized with ovalbumin (OVA plus aluminum hydroxide, a strong Th2-inducing immunization, and challenged with OVA. Airway and lung inflammation, immunoglobulin response, Th2 cytokine production and lymphocyte response were analyzed and compared with wild type mice. Even though there was mild spontaneous inflammation in the lung at baseline, SHIP-1-/- mice showed altered responses, including less cell infiltration around the airways but more in the parenchyma, less mucus production, decreased Th2 cytokine production, and diminished serum OVA-specific IgE, IgG1, but not IgG2a. Naïve and OVA sensitized SHIP-1-/- T cells produced a lower amount of IL-4. In vitro differentiated SHIP-1-/- Th2 cells produced less IL-4 compared to wild type Th2 cells upon T cell receptor stimulation. CONCLUSIONS/SIGNIFICANCE: These findings indicate that, in contrast to its role as a negative regulator in the innate immune cells, SHIP-1 acts as a positive regulator in Th2 cells in the adaptive immune response to aeroallergen. Thus any potential manipulation of SHIP-1 activity should be adjusted according to the specific immune response.

  4. 2.5D induced polarization forward modeling using the adaptive finite-element method

    Ye Yi-Xin; Li Yu-Guo; Deng Ju-Zhi; Li Ze-Lin

    2014-01-01

    The conventional finite-element (FE) method often uses a structured mesh, which is designed according to the user’s experience, and it is not sufficiently accurate and flexible to accommodate complex structures such as dipping interfaces and rough topography. We present an adaptive FE method for 2.5D forward modeling of induced polarization (IP). In the presented method, an unstructured triangulation mesh that allows for local mesh refinement and flexible description of arbitrary model geometries is used. Furthermore, the mesh refinement process is guided by dual error estimate weighting to bias the refinement towards elements that affect the solution at the receiver locations. After the final mesh is generated, the Jacobian matrix is used to obtain the IP response on 2D structure models. We validate the adaptive FE algorithm using a vertical contact model. The validation shows that the elements near the receivers are highly refined and the average relative error of the potentials converges to 0.4%and 1.2%for the IP response. This suggests that the numerical solution of the adaptive FE algorithm converges to an accurate solution with the refined mesh. Finally, the accuracy and flexibility of the adaptive FE procedure are also validated using more complex models.

  5. Complement activation pathways: a bridge between innate and adaptive immune responses in asthma.

    Wills-Karp, Marsha

    2007-07-01

    Although it is widely accepted that allergic asthma is driven by T helper type 2 (Th2)-polarized immune responses to innocuous environmental allergens, the mechanisms driving these aberrant immune responses remain elusive. Recent recognition of the importance of innate immune pathways in regulating adaptive immune responses have fueled investigation into the role of innate immune pathways in the pathogenesis of asthma. The phylogenetically ancient innate immune system, the complement system, is no exception. The emerging paradigm is that C3a production at the airway surface serves as a common pathway for the induction of Th2-mediated inflammatory responses to a variety of environmental triggers of asthma (i.e., allergens, pollutants, viral infections, cigarette smoke). In contrast, C5a plays a dual immunoregulatory role by protecting against the initial development of a Th2-polarized adaptive immune response via its ability to induce tolerogenic dendritic cell subsets. On the other hand, C5a drives type 2-mediated inflammatory responses once inflammation ensues. Thus, alterations in the balance of generation of the various components of the complement pathway either due to environmental exposure changes or genetic alterations in genes of the complement cascade may underlie the recent rise in asthma prevalence in westernized countries. PMID:17607007

  6. Biological Stress Response Terminology: Integrating the Concepts of Adaptive Response and Preconditioning Stress Within a Hormetic Dose-Response Framework

    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 stres...

  7. Adaptation-Induced Compression of Event Time Occurs Only for Translational Motion

    Michele Fornaciai; Roberto Arrighi; Burr, David C.

    2016-01-01

    Adaptation to fast motion reduces the perceived duration of stimuli displayed at the same location as the adapting stimuli. Here we show that the adaptation-induced compression of time is specific for translational motion. Adaptation to complex motion, either circular or radial, did not affect perceived duration of subsequently viewed stimuli. Adaptation with multiple patches of translating motion caused compression of duration only when the motion of all patches was in the same direction. Th...

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

    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…

  9. Detection of plant adaptation responses to saline environment in rhizosphere using microwave sensing

    The physiological adaptation responses in plants to environmental stress, such as water stress and salt stress induce changes in physicochemical conditions of the plant, since formation of osmotic-regulatory substances can be formed during the environmental adaptation responses. Strong electrolytes, amino acids, proteins and saccharides are well-known as osmoregulatory substances. Since these substances are ionic conductors and their molecules are electrically dipolar, it can be considered that these substances cause changes in the dielectric properties of the plant, which can be detected by microwave sensing. The dielectric properties (0.3 to 3GHz), water content and water potential of plant leaves which reflect the physiological condition of the plant under salt stress were measured and analyzed. Experimental results showed the potential of the microwave sensing as a method for monitoring adaptation responses in plants under saline environment and that suggested the saline environment in rhizosphere can be detected noninvasively and quantitatively by the microwave sensing which detects the changes in complex dielectric properties of the plant

  10. Cytogenetic monitoring, radiosensitivity study and adaptive response of workers exposed to low level ionizing radiation

    The objectives of the present study were: To determine the frequencies of chromosome aberrations in lymphocytes from individuals belonging to professionally exposed groups, under normal conditions; to determine the possible differences in radiosensitivity between the lymphocytes of technicians and controls after in vitro irradiation with gamma rays during the G1 phase of the cell cycle (radiosensitivity study), and to examine the influence of in vivo and in vitro pre-exposure to low doses of radiation on the frequency of chromosome aberrations induced in vitro by high doses (study of the adaptive response) in a group of technicians (T) compared to controls (C). (author)

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

    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

  12. Comparative characteristics of electroretinograms induced by light and x-ray stimulation under different adaptation conditions

    It has been demonstrated previously that the administration of certain chemicals reveals in the X-ray-induced electroretinogram (X-ERG) two electrical processes that are not found in photoinduced electroretinograms. A question arises whether the revealed first and second X-ray reactions are natural and physiological, or whether they are the response to the chemical effect upon the retina or the entire organism of the test animal. The present study investigates changes in electroretinograms induced by X-rays and by red and blue light in the process of the natural dark adaptation of the animals eyes from standard illumination. The results show that the two-component character of X-ERG may be the result not only of the introduction of some specific chemicals, e.g., of sodium axide, monoiodoacetate, or some other specific retinal poisons, but also the result of the natural adaptation of the retina to darkness. They also provide evidence in favor of the earlier hypothesis that postulates that the summary ERG, induced by short X-ray exposure, also includes responses specific for ionizing stimuli

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

    Nuñez, P; Arguelles, J; Perillan, C

    2015-12-01

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

  14. The dependence of the magnitude of induced adaptive responseon on the dose of pre-irradiation of cultured human lymphocytes under the optimum irradiation time scheme

    Human lymphocytes exposed to low doses of X-rays, become less susceptible to the induction of chromosome aberrations by subsequent exposure to high doses of X-rays. This has been termed the radioadaptive response. One of the most important questions in the adaptive response studies was that of the possible existence of an optimum adapting dose. Early experiments indicated that this response could be induced by low doses of X-rays from 1 cGy to 20 cGy. Recently, it has been interestingly shown that the time scheme of exposure to adapting and challenge doses plays an important role in determination of the magnitude of the induced adaptive response. In this study, using the optimum irradiation time scheme (24-48), we have monitored the cytogenetic endpoint of chromosome aberrations to assess the magnitude of adaptation to ionizing radiation in the cultured human lymphocytes. Lymphocytes were pre-exposed to an adapting dose of 1-20 cGy at 24 hours, before an acute challenge dose of 1 or 2 Gy at 48 hours. Cells were fixed at 54 hours. Lymphocytes, which were pretreated with 5 as well as 10 cGy adapting doses, had significantly fewer chromosome aberrations. In spite of the fact that lymphocytes of some of our blood donors which were pre-treated with 1 or 20 cGy adapting doses, showed an adaptive response, the pooled data (all donors) indicated that such an induction of adaptive response can not be observed in these lymphocytes. The overall pattern of the induced adaptive response, indicated that in human lymphocyte (at least under the above mentioned irradiation scheme), 5 cGy and 10 cGy adapting doses are the optimum doses. (author)

  15. Radiation-induced gene responses

    In the process of identifying genes that are differentially regulated in cells exposed to ultraviolet radiation (UV), we identified a transcript that was repressed following the exposure of cells to a combination of UV and salicylate, a known inhibitor of NF-kappaB. Sequencing this band determined that it has identify to lactate dehydrogenase, and Northern blots confirmed the initial expression pattern. Analysis of the sequence of the LDH 5' region established the presence of NF-kappaB, Sp1, and two Ap-2 elements; two partial AP- 1; one partial RE, and two halves of E-UV elements were also found. Electromobility shift assays were then performed for the AP-1, NF- kappaB, and E-UV elements. These experiments revealed that binding to NF-kappaB was induced by UV but repressed with salicylic acid; UV did not affect AP-1 binding, but salicylic acid inhibited it alone or following UV exposure; and E-UV binding was repressed by UV, and salicylic acid had little effect. Since the binding of no single element correlated with the expression pattern of LDH, it is likely that multiple elements govern UV/salicylate-mediated expression

  16. Phenotypic plasticity as an adaptive response to predictable and unpredictable environmental changes

    Manenti, Tommaso

    such as anti-predator behaviours or the activation of mechanisms to prevent thermal stress injuries suggest that plasticity is an adaptive response, favoured by natural selection. At the same time, organisms do show limited plastic responses, indicating that this ability is not for free. Costs and...... benefits of a plastic response are expected to depend on the environmental conditions experienced by organisms. Thus, in populations exposed to a non-changing environment, the plastic machinery might be a waste of resources. Contrary, in populations experiencing varying environmental conditions, plasticity...... selected Drosophila simulans for many generations in three thermal regimes, specifically designed to affect the levels of plasticity. The three environments were found to induce high levels of plasticity and to affect stress resistance and life history traits differently. However, flies selected in...

  17. Adaptive response of Chironomus riparius populations exposed to uranium contaminated sediments during consecutive generations

    The intensity of selection on populations caused by polluted environment often exceeds which is caused by an unpolluted environment. Therefore, micro evolution can occur in response to this anthropic-directional force over a short period. In this context, this thesis focused on studying phenotypic changes in Chironomus riparius populations exposed during several consecutive generations to uranium-contaminated sediments. In laboratory-controlled conditions experiments were conducted with same origin populations exposed to a range of uranium concentration inducing toxic effects. Over eight-generations of exposure, life-history traits measures revealed micro evolution in exposed populations, including increase of adult reproductive success. Other experiments (acute toxicity test, common garden experiment) performed in parallel enabled to link these micro evolution with a tolerance induction, as a consequence of genetic adaptation. Nonetheless this adaptation also induced cost in terms of fitness and genetic diversity for pre-exposed populations. These results lead to the hypothesis of a selection by uranium that acted sequentially on populations. They also underline the need to better-understand the adaptive mechanisms to better assess the ecological consequences of chronic exposure of populations to a pollutant. (author)

  18. Fast response and high sensitivity to microsaccades in a cascading-adaptation neural network with short-term synaptic depression

    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.

  19. EXERCISE-INDUCED ARTERIAL ADAPTATIONS IN ELITE JUDO ATHLETES

    Panagiotis Karagounis

    2009-09-01

    Full Text Available The purpose of this study was to examine exercise-induced arterial adaptations in elite Judo male and female athletes. 27 male Judo athletes (age 24.06 ± 2 years, 11 female Judoka (age 24.27 ± 1 years, 27 sedentary healthy men (age 24.01 ± 2 years and 11 women (age 24.21 ± 1 years participated in the current study. The examined vessels included brachial, radial, ulnar, popliteal, anterior and posterior tibial arteries. The experimental parameters were recorded with the use of Duplex ultrasound at rest. Diastolic diameter and blood mean flow velocity of the examined arteries in Judo athletes were found to be both significantly increased (p < 0.05 compared to the findings of the control groups. In male Judo athletes the brachial (p < 0.001, radial (p < 0.001, and anterior tibial artery (p < 0.001 presented the highest difference on the diastolic diameter, compared with the control male group. In female Judo athletes, ulnar (p < 0.001, radial (p < 0.001, and brachial (p < 0.001 arteries illustrated the highest diastolic diameter. The highest blood mean flow velocity was recorded in ulnar (p < 0.001 and popliteal arteries (p < 0.001 of the Judo athletes groups. Recording differences between the two genders, male participants presented larger arteries than females. Conclusively, Judo has been found to be a highly demanding physical sport, involving upper and lower limbs leading to significant arterial adaptations. Obtaining vascular parameters provide a useful tool to the medical team, not only in the direction of enhancement of the efficacy of physical training, but in unknown so far parameters that may influence athletic performance of both male and female elite Judokas

  20. Control of the adaptive immune response by tumor vasculature

    Laetitia eMauge

    2014-03-01

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

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

    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.

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

    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.

  3. Synchrony between orientation-selective neurons is modulated during adaptation-induced plasticity in cat visual cortex

    Shumikhina Svetlana

    2008-07-01

    Full Text Available Abstract Background Visual neurons respond essentially to luminance variations occurring within their receptive fields. In primary visual cortex, each neuron is a filter for stimulus features such as orientation, motion direction and velocity, with the appropriate combination of features eliciting maximal firing rate. Temporal correlation of spike trains was proposed as a potential code for linking the neuronal responses evoked by various features of a same object. In the present study, synchrony strength was measured between cells following an adaptation protocol (prolonged exposure to a non-preferred stimulus which induce plasticity of neurons' orientation preference. Results Multi-unit activity from area 17 of anesthetized adult cats was recorded. Single cells were sorted out and (1 orientation tuning curves were measured before and following 12 min adaptation and 60 min after adaptation (2 pairwise synchrony was measured by an index that was normalized in relation to the cells' firing rate. We first observed that the prolonged presentation of a non-preferred stimulus produces attractive (58% and repulsive (42% shifts of cell's tuning curves. It follows that the adaptation-induced plasticity leads to changes in preferred orientation difference, i.e. increase or decrease in tuning properties between neurons. We report here that, after adaptation, the neuron pairs that shared closer tuning properties display a significant increase of synchronization. Recovery from adaptation was accompanied by a return to the initial synchrony level. Conclusion We conclude that synchrony reflects the similarity in neurons' response properties, and varies accordingly when these properties change.

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

    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

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

    Millet, Grégoire P; Millet, Guillaume Y

    2012-01-01

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

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

    Millet Grégoire P

    2012-07-01

    Full Text Available Abstract 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

  7. Crosstalk between innate and adaptive immune responses to infectious bronchitis virus after vaccination and challenge of chickens varying in serum mannose-binding lectin concentrations

    Juul-Madsen, Helle R.; Norup, Liselotte R.; Jørgensen, Poul Henrik;

    2011-01-01

    . Serum MBL levels also influenced IBV vaccine-induced changes in circulating T-cell populations. Moreover, addition of mannose to an IBV vaccine altered both vaccine-induced changes in circulating T-cell populations and IBV specific vaccine and infection-induced antibody responses in chickens with high...... serum MBL levels. These data demonstrate that MBL is involved in the regulation of the adaptive immune response to IBV....

  8. Fisheries-induced neutral and adaptive evolution in exploited fish populations and consequences for their adaptive potential

    Marty, Lise; Dieckmann, Ulf; Ernande, Bruno

    2015-01-01

    Fishing may induce neutral and adaptive evolution affecting life-history traits, and molecular evidence has shown that neutral genetic diversity has declined in some exploited populations. Here, we theoretically study the interplay between neutral and adaptive evolution caused by fishing. An...... individual-based eco-genetic model is devised that includes neutral and functional loci in a realistic ecological setting. In line with theoretical expectations, we find that fishing induces evolution towards slow growth, early maturation at small size and higher reproductive investment. We show, first, that...

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

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

    2016-06-01

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

  10. Adaptive magnetorheological shock isolation mounts for drop-induced impacts

    Non-dimensional analysis and optimal control design of adaptive magnetorheological shock isolation (MRSI) mounts are addressed for drop-induced impacts. The governing equation of motion of a single degree-of-freedom under impact was derived, where a magnetorheological energy absorber (MREA), which has controllable stroking load and a passive linear spring, isolate the payload mass from the base that impacts the ground. During the impact event, the payload experiences both a compression and a rebound stroke. During the compression stroke, the payload descends as the MREA dissipates and the spring stores, the energy of impact. During the rebound stroke, the spring releases its stored energy under the control of the MREA. The Bingham number, defined as the ratio of the MREA yield force to its viscous force, is utilized as the control variable. A non-dimensional analysis was conducted using key parameters such as available MREA stroke and Bingham number. The first control objective was to ensure that the payload achieved a soft landing (i.e., comes to rest) at the end of the compression stroke by fully utilizing the available stroke of the MREA. The second control objective was to completely recover the available MREA stroke during rebound, with no overshoot of the equilibrium point, i.e. dead-beat control. It is shown that the optimal MRSI control strategy implies the selection of two distinct Bingham numbers, one for the compression stroke and one for the rebound stroke, which achieve the control objectives. (fast track communication)

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

    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. PMID:24187667

  12. Determination of the adaptive response induced In vivo by gamma radiation and its relation with the sensibility to the damage induction in the DNA and with the repairing capacity; Determinacion de la respuesta adaptativa inducida In vivo por radiacion gamma y su relacion con la sensibilidad a la induccion de dano en el ADN y con la capacidad de reparacion

    Mendiola C, M.T

    2002-07-01

    The kinetics of damage induction and repair at different doses as well as the adaptive response induced by gamma ray exposure were determined in murine leukocytes in vivo. The damage-repair kinetics were established after the exposure to 0.5, 1.0 or 2.0 Gy in a {sup 137}Cs source. Peripheral blood samples were obtained from the tails of mice, the percentage of damaged cells and the DNA migration in each one were analyzed by the single cell gel electrophoresis (SCG) technique or comet assay. Results indicated that there was an induction of approximately 75% comets with the doses of 1.0 and 2.0 Gy, which was considerably reduced to 22% and 42% respectively during the first 15 minutes. This evidences the presence of a rapid repair process and suggests that leucocytes are genetically well prepared to repair this kind of damage. After 15 minutes, a second increase in the percentage of damaged cells that was proportional to dose occurred, which seems to represent the breaks produced during the repair of other kind of lesions. After that a second reduction was observed, reaching values near to the basal ones, except with the dose of 2.0 Gy. The kinetics obtained with the dose of 0.5 Gy was similar to that established with 1.0 Gy, but in this case the initial damage was 50 % lower. Besides, the adaptive response was observed after the exposure of the mice to an adaptive dose of 0.01 Gy and to a challenge dose of 1.0 Gy 60 minutes later. The pretreatment reduced the percentage of damaged cells caused by the challenge dose to one third approximately, and also diminished this parameter produced during the late repair process. This indicates that the early adaptive response is caused, instead of by an increment in repair, by the induction of a process that protects DNA from damage induction by radiation, i.e synthesis of substances that increase the scavenging of free radicals. (Author)

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

    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.

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

    Ketelhuth, Daniel F J; Hansson, Göran K

    2016-02-19

    Atherosclerosis is a chronic inflammatory disease that is initiated by the retention and accumulation of cholesterol-containing lipoproteins, particularly low-density lipoprotein, in the artery wall. In the arterial intima, lipoprotein components that are generated through oxidative, lipolytic, and proteolytic activities lead to the formation of several danger-associated molecular patterns, which can activate innate immune cells as well as vascular cells. Moreover, self- and non-self-antigens, such as apolipoprotein B-100 and heat shock proteins, can contribute to vascular inflammation by triggering the response of T and B cells locally. This process can influence the initiation, progression, and stability of plaques. Substantial clinical and experimental data support that the modulation of adaptive immune system may be used for treating and preventing atherosclerosis. This may lead to the development of more selective and less harmful interventions, while keeping host defense mechanisms against infections and tumors intact. Approaches such as vaccination might become a realistic option for cardiovascular disease, especially if they can elicit regulatory T and B cells and the secretion of atheroprotective antibodies. Nevertheless, difficulties in translating certain experimental data into new clinical therapies remain a challenge. In this review, we discuss important studies on the function of T- and B-cell immunity in atherosclerosis and their manipulation to develop novel therapeutic strategies against cardiovascular disease. PMID:26892965

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

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

    2015-08-01

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

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

    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.

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

    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. PMID:26688241

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

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

    2015-09-01

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

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

    Kaluza, Pablo

    2016-01-01

    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.

  20. Adaptive responses of mitochondria to mild copper deprivation involve changes in morphology, OXPHOS remodeling and bioenergetics.

    Ruiz, Lina María; Jensen, Erik L; Bustos, Rodrigo I; Argüelloa, Graciela; Gutierrez-Garcia, Ricardo; González, Mauricio; Hernández, Claudia; Paredes, Rodolfo; Simon, Felipe; Riedel, Claudia; Ferrick, David; Elorza, Alvaro A

    2014-05-01

    Copper is an essential cofactor of complex IV of the electron transfer chain, and it is directly involved in the generation of mitochondrial membrane potential. Its deficiency induces the formation of ROS, large mitochondria and anemia. Thus, there is a connection between copper metabolism and bioenergetics, mitochondrial dynamics and erythropoiesis. Copper depletion might end in cellular apoptosis or necrosis. However, before entering into those irreversible processes, mitochondria may execute a series of adaptive responses. Mitochondrial adaptive responses (MAR) may involve multiple and diverse mechanisms for preserving cell life, such as mitochondrial dynamics, OXPHOS remodeling and bioenergetics output. In this study, a mild copper deficiency was produced in an animal model through intraperitoneal injections of bathocuproine disulfonate in order to study the MAR. Under these conditions, a new type of mitochondrial morphology was discovered in the liver. Termed the "butternut squash" mitochondria, it coexisted with normal and swollen mitochondria. Western blot analyses of mitochondrial dynamics proteins showed an up-regulation of MFN-2 and OPA1 fusion proteins. Furthermore, isolated liver mitochondria displayed OXPHOS remodeling through a decrease in supercomplex activity with a concomitant increase at an individual level of complexes I and IV, higher respiratory rates at complex I and II levels, higher oligomycin-insensitive respiration, and lower respiratory control ratio values when compared to the control group. As expected, total ATP and ATP/ADP values were not significantly different, since animal's health was not compromised. As a whole, these results describe a compensatory and adaptive response of metabolism and bioenergetics under copper deprivation. PMID:24446197

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

    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. PMID:25056115

  2. Neural correlates of adaptive social responses to real-life frustrating situations: a functional MRI study

    Sekiguchi, Atsushi; Sugiura, Motoaki; Yokoyama, Satoru; Sassa, Yuko; HORIE, Kaoru; Sato, Shigeru; Kawashima, Ryuta

    2013-01-01

    Background Frustrating situations are encountered daily, and it is necessary to respond in an adaptive fashion. A psychological definition states that adaptive social behaviors are “self-performing” and “contain a solution.” The present study investigated the neural correlates of adaptive social responses to frustrating situations by assessing the dimension of causal attribution. Based on attribution theory, internal causality refers to one’s aptitudes that cause natural responses in real-lif...

  3. Adaptations in muscle activity to induced, short-term hindlimb lameness in trotting dogs.

    Fischer, Stefanie; Nolte, Ingo; Schilling, Nadja

    2013-01-01

    Muscle tissue has a great intrinsic adaptability to changing functional demands. Triggering more gradual responses such as tissue growth, the immediate responses to altered loading conditions involve changes in the activity. Because the reduction in a limb's function is associated with marked deviations in the gait pattern, understanding the muscular responses in laming animals will provide further insight into their compensatory mechanisms as well as help to improve treatment options to prevent musculoskeletal sequelae in chronic patients. Therefore, this study evaluated the changes in muscle activity in adaptation to a moderate, short-term, weight-bearing hindlimb lameness in two leg and one back muscle using surface electromyography (SEMG). In eight sound adult dogs that trotted on an instrumented treadmill, bilateral, bipolar recordings of the m. triceps brachii, the m. vastus lateralis and the m. longissimus dorsi were obtained before and after lameness was induced. Consistent with the unchanged vertical forces as well as temporal parameters, neither the timing nor the level of activity changed significantly in the m. triceps brachii. In the ipsilateral m. vastus lateralis, peak activity and integrated SEMG area were decreased, while they were significantly increased in the contralateral hindlimb. In both sides, the duration of the muscle activity was significantly longer due to a delayed offset. These observations are in accordance with previously described kinetic and kinematic changes as well as changes in muscle mass. Adaptations in the activity of the m. longissimus dorsi concerned primarily the unilateral activity and are discussed regarding known alterations in trunk and limb motions. PMID:24236207

  4. Participation of intercellular communication and intracellular signal transduction in the radio-adaptive response of human fibroblastic cells

    To investigate the radio-adaptive response of normal cells to low-dose radiation, we irradiated human embryonic cells with low-dose X-rays and examined the changes in sensitivity to subsequent high-dose X-irradiation. When the cells were irradiated by 200 cGy, the growth ratio of the viable cells five days after the irradiation decreased to 37% of that of the cells which received no X-irradiation. When the cells received a conditioning irradiation of 10 to 20 cGy four hours before the irradiation of 200 cGy, the growth ratio increased significantly to 45-53%, and a peak was reached at a conditioning dose of 13 cGy. Cells blocked off intercellular communication either in Ca2+ ion-free medium or in TPA added medium during the conditioning irradiation of 13 cGy did not show the improvement of growth ratio. Addition of H-7, as an inhibitor of PKC, to the medium during the conditioning irradiation inhibited the induction of the radio-adaptive response. However, addition of either inhibitor of A kinase, H-89, or inhibitor of G kinase, H-8, failed to inhibit the induction of the radio-adaptive response. These results suggest that: (1) normal cells show an adaptive response to low-dose radiation, (2) intercellular communication may play a role in radio-adaptive responses, (3) the transduction of the signal induced in cells by low-dose X-irradiation via protein kinase C was involved in radio-adaptive responses, not via A kinase nor G kinase. (author)

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

    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

  6. Dependence of the adaptive response value in rat bone marrow cells on chronic γ-radiation dose in vivo

    Dependence of cytogenetic adaptive response (AR) induction in rat bone marrow cells on chronic γ-radiation dose (3, 9, 21 and 40 cGy, 0.13 cGy/h dose rate) with subsequent acute γ-irradiation in vivo conditions was studied. It was shown that preliminary chronic irradiation might induce essential AR within the dose examined range. 40 cGy dose was the most efficient for AR induction

  7. Responsible Climate Change Adaptation : Exploring, analysing and evaluating public and private responsibilities for urban adaptation to climate change

    Mees, Heleen

    2014-01-01

    Cities are vulnerable to climate change. To deal with climate change, city governments and private actors such as businesses and citizens need to adapt to its effects, such as sea level rise, storm surges, intense rainfall and heatwaves. However, adaptation planning and action is often hampered when

  8. Effect of low-dose X-ray radiation on adaptive response in gastric cancer cell

    Shukai Wang; Gang Jiang; Hongsheng Yu; Xiangping Liu; Chang Xu

    2013-01-01

    Objective: We aimed to study the effect and mechanism of low-dose radiation (LDR) on adaptive response of gastric cancer cell. Methods: SGC7901 cells were cultured in vitro, and divided into 4 groups: control group (D0 group), low-dose radiation group (D1 group, 75 mGy), high-dose radiation group (D2 group, 2 Gy), low-dose plus high-dose radiation group (D1 + D2 group, 75 mGy + 2 Gy, the interval of low and high-dose radiation being 8 h). Cell inhibition rate was detected by cytometry and CCK8 method; the proportion of cell cycle at different times after irradiation was determined by using a flow cytometry. The ATM mRNA levels were detected by using quantitative real-time reverse transcription polymerase chain reaction (RT-PCR). Results: There was no significant different between groups D0 and D1, groups D2 and D1 + D2 cell inhibition rate (P > 0.05). There was a significant increase G2/M arrest in groups D2 and D1 + D2 than groups D0 and D1 after 6 h of radiation and did not recover at 48 h (P 0.05). Conclusion: LDR cannot induce adaptive response in SGC7901 cells in vitro, which may be associated the regulation of cell cycle, and its ATM mRNA expression cannot be affected by 75 mGy X-ray radiation.

  9. Multigenerational Epigenetic Adaptation of the Hepatic Wound-Healing Response

    Zeybel, Müjdat; Hardy, Timothy; Wong, Yi K.; Mathers, John C; Fox, Christopher R.; Gackowska, Agata; Oakley, Fiona; Burt, Alastair D; Wilson, Caroline L.; Anstee, Quentin M.; Barter, Matt J; Masson, Steven; Elsharkawy, Ahmed M.; Mann, Derek A.; Mann, Jelena

    2012-01-01

    We asked if ancestral liver damage leads to heritable reprogramming of hepatic wound-healing. We discovered that male rats with a history of liver damage transmit epigenetic suppressive adaptation of the fibrogenic component of wound-healing through male F1 and F2 generations. Underlying this adaptation was reduced generation of liver myofibroblasts, increased hepatic expression of antifibrogenic PPAR-γ and decreased expression of profibrogenic TGF-β1. Remodelling of DNA methylation and histo...

  10. New concepts in immunity to Neisseria gonorrhoeae: innate responses and suppression of adaptive immunity favor the pathogen, not the host

    Yingru eLiu

    2011-03-01

    Full Text Available It is well known that gonorrhea can be acquired repeatedly with no apparent development of protective immunity arising from previous episodes of infection. Symptomatic infection is characterized by a purulent exudate, but the host response mechanisms are poorly understood. While the remarkable antigenic variability displayed by Neisseria gonorrhoeae and its capacity to inhibit complement activation allow it to evade destruction by the host’s immune defenses, we propose that it also has the capacity to avoid inducing specific immune responses. In a mouse model of vaginal gonococcal infection, N. gonorrhoeae elicits Th17-driven inflammatory- immune responses, which recruit innate defense mechanisms including an influx of neutrophils. Concomitantly, N. gonorrhoeae suppresses Th1- and Th2-dependent adaptive immunity, including specific antibody responses, through a mechanism involving TGF-β and regulatory T cells. Blockade of TGF-β alleviates the suppression of specific anti-gonococcal responses and allows Th1 and Th2 responses to emerge with the generation of immune memory and protective immunity. Genital tract tissues are naturally rich in TGF-β, which fosters an immunosuppressive environment that is important in reproduction. In exploiting this niche, N. gonorrhoeae exemplifies a well-adapted pathogen that proactively elicits from its host innate responses that it can survive and concomitantly suppresses adaptive immunity. Comprehension of these mechanisms of gonococcal pathogenesis should allow the development of novel approaches to therapy and facilitate the development of an effective vaccine.

  11. New concepts in immunity to Neisseria gonorrhoeae: innate responses and suppression of adaptive immunity favor the pathogen, not the host.

    Liu, Yingru; Feinen, Brandon; Russell, Michael W

    2011-01-01

    It is well-known that gonorrhea can be acquired repeatedly with no apparent development of protective immunity arising from previous episodes of infection. Symptomatic infection is characterized by a purulent exudate, but the host response mechanisms are poorly understood. While the remarkable antigenic variability displayed by Neisseria gonorrhoeae and its capacity to inhibit complement activation allow it to evade destruction by the host's immune defenses, we propose that it also has the capacity to avoid inducing specific immune responses. In a mouse model of vaginal gonococcal infection, N. gonorrhoeae elicits Th17-driven inflammatory-immune responses, which recruit innate defense mechanisms including an influx of neutrophils. Concomitantly, N. gonorrhoeae suppresses Th1- and Th2-dependent adaptive immunity, including specific antibody responses, through a mechanism involving TGF-β and regulatory T cells. Blockade of TGF-β alleviates the suppression of specific anti-gonococcal responses and allows Th1 and Th2 responses to emerge with the generation of immune memory and protective immunity. Genital tract tissues are naturally rich in TGF-β, which fosters an immunosuppressive environment that is important in reproduction. In exploiting this niche, N. gonorrhoeae exemplifies a well-adapted pathogen that proactively elicits from its host innate responses that it can survive and concomitantly suppresses adaptive immunity. Comprehension of these mechanisms of gonococcal pathogenesis should allow the development of novel approaches to therapy and facilitate the development of an effective vaccine. PMID:21833308

  12. The study on adaptive response at various spermatogenesis stages in Drosophila melanogaster

    Applying the test of recessive sex-linked lethal mutations we studied radioadaptive response (at various spermatogenesis stages) in Drosophila melanogaster represented by the Canton-S stock, as well as by w stock and w; Canton stock marked with the white gene. The adaptive response was revealed in the s stock marked with the white gene but was not detected in the Canton-S stock. The obtained results confirmed the existence of the relation between the Drosophila melanogaster adaptive response and X chromosome carrying the mutant white gene; they also witness to the probability of the absence of the relation between this adaptive response and autosomes. (authors)

  13. Hypercapnia Suppresses the HIF-dependent Adaptive Response to Hypoxia.

    Selfridge, Andrew C; Cavadas, Miguel A S; Scholz, Carsten C; Campbell, Eric L; Welch, Lynn C; Lecuona, Emilia; Colgan, Sean P; Barrett, Kim E; Sporn, Peter H S; Sznajder, Jacob I; Cummins, Eoin P; Taylor, Cormac T

    2016-05-27

    Molecular oxygen and carbon dioxide are the primary gaseous substrate and product of oxidative metabolism, respectively. Hypoxia (low oxygen) and hypercapnia (high carbon dioxide) are co-incidental features of the tissue microenvironment in a range of pathophysiologic states, including acute and chronic respiratory diseases. The hypoxia-inducible factor (HIF) is the master regulator of the transcriptional response to hypoxia; however, little is known about the impact of hypercapnia on gene transcription. Because of the relationship between hypoxia and hypercapnia, we investigated the effect of hypercapnia on the HIF pathway. Hypercapnia suppressed HIF-α protein stability and HIF target gene expression both in mice and cultured cells in a manner that was at least in part independent of the canonical O2-dependent HIF degradation pathway. The suppressive effects of hypercapnia on HIF-α protein stability could be mimicked by reducing intracellular pH at a constant level of partial pressure of CO2 Bafilomycin A1, a specific inhibitor of vacuolar-type H(+)-ATPase that blocks lysosomal degradation, prevented the hypercapnic suppression of HIF-α protein. Based on these results, we hypothesize that hypercapnia counter-regulates activation of the HIF pathway by reducing intracellular pH and promoting lysosomal degradation of HIF-α subunits. Therefore, hypercapnia may play a key role in the pathophysiology of diseases where HIF is implicated. PMID:27044749

  14. Delayed adaptive immunity is related to higher MMR vaccine-induced antibody titers in children.

    Strömbeck, Anna; Lundell, Anna-Carin; Nordström, Inger; Andersson, Kerstin; Adlerberth, Ingegerd; Wold, Agnes E; Rudin, Anna

    2016-04-01

    There are notable inter-individual variations in vaccine-specific antibody responses in vaccinated children. The aim of our study was to investigate whether early-life environmental factors and adaptive immune maturation prior and close to measles-mumps-rubella (MMR) immunization relate to magnitudes of vaccine-specific antibody titers. In the FARMFLORA birth cohort, including both farming and non-farming families, children were immunized with the MMR vaccine at 18 months of age. MMR vaccine-induced antibody titers were measured in plasma samples obtained at 36 months of age. Infants' blood samples obtained at birth, 3-5 days and at 4 and 18 months of age were analyzed for T- and B-cell numbers, proportions of naive and memory T and B cells, and fractions of putative regulatory T cells. Multivariate factor analyses show that higher anti-MMR antibody titers were associated with a lower degree of adaptive immune maturation, that is, lower proportions of memory T cells and a lower capacity of mononuclear cells to produce cytokines, but with higher proportions of putative regulatory T cells. Further, children born by cesarean section (CS) had significantly higher anti-measles titers than vaginally-born children; and CS was found to be associated with delayed adaptive immunity. Also, girls presented with significantly higher anti-mumps and anti-rubella antibody levels than boys at 36 months of age. These results indicate that delayed adaptive immune maturation before and in close proximity to immunization seems to be advantageous for the ability of children to respond with higher anti-MMR antibody levels after vaccination. PMID:27195118

  15. Injury-induced immune responses in Hydra.

    Wenger, Yvan; Buzgariu, Wanda; Reiter, Silke; Galliot, Brigitte

    2014-08-01

    The impact of injury-induced immune responses on animal regenerative processes is highly variable, positive or negative depending on the context. This likely reflects the complexity of the innate immune system that behaves as a sentinel in the transition from injury to regeneration. Early-branching invertebrates with high regenerative potential as Hydra provide a unique framework to dissect how injury-induced immune responses impact regeneration. A series of early cellular events likely require an efficient immune response after amputation, as antimicrobial defence, epithelial cell stretching for wound closure, migration of interstitial progenitors toward the wound, cell death, phagocytosis of cell debris, or reconstruction of the extracellular matrix. The analysis of the injury-induced transcriptomic modulations of 2636 genes annotated as immune genes in Hydra identified 43 genes showing an immediate/early pulse regulation in all regenerative contexts examined. These regulations point to an enhanced cytoprotection via ROS signaling (Nrf, C/EBP, p62/SQSMT1-l2), TNFR and TLR signaling (TNFR16-like, TRAF2l, TRAF5l, jun, fos-related, SIK2, ATF1/CREB, LRRC28, LRRC40, LRRK2), proteasomal activity (p62/SQSMT1-l1, Ced6/Gulf, NEDD8-conjugating enzyme Ubc12), stress proteins (CRYAB1, CRYAB2, HSP16.2, DnaJB9, HSP90a1), all potentially regulating NF-κB activity. Other genes encoding immune-annotated proteins such as NPYR4, GTPases, Swap70, the antiproliferative BTG1, enzymes involved in lipid metabolism (5-lipoxygenase, ACSF4), secreted clotting factors, secreted peptidases are also pulse regulated upon bisection. By contrast, metalloproteinases and antimicrobial peptide genes largely follow a context-dependent regulation, whereas the protease inhibitor α2macroglobulin gene exhibits a sustained up-regulation. Hence a complex immune response to injury is linked to wound healing and regeneration in Hydra. PMID:25086685

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

    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.

  17. The study on relation between adaptive response and genotype of drosophila melanogaster

    The paper deals with the study on radioadaptive response in Drosophila melanogaster of the different stocks at various spermiogenesis stages by the test of recessive sex-linked lethal mutations. The adaptive response was revealed in the stocks marked with gene white but was not detected in the stock Can-ton-S. The results obtained can point to the relation between the adaptive response in Drosophila melanogaster and X chromosome carrying a gene white but not autosoms. (Authors)

  18. Photosynthetic responses mediate the adaptation of two Lotus japonicus ecotypes to low temperature.

    Calzadilla, Pablo Ignacio; Signorelli, Santiago; Escaray, Francisco Jose; Menéndez, Ana Bernardina; Monza, Jorge; Ruiz, Oscar Adolfo; Maiale, Santiago Javier

    2016-09-01

    Lotus species are important forage legumes due to their high nutritional value and adaptability to marginal conditions. However, the dry matter production and regrowth rate of cultivable Lotus spp. is drastically reduced during colder seasons. In this work, we evaluated the chilling response of Lotus japonicus ecotypes MG-1 and MG-20. No significant increases were observed in reactive oxygen species and nitric oxide production or in lipid peroxidation, although a chilling-induced redox imbalance was suggested through NADPH/NADP(+) ratio alterations. Antioxidant enzyme catalase, ascorbate peroxidase, and superoxide dismutase activities were also measured. Superoxide dismutase, in particular the chloroplastic isoform, showed different activity for different ecotypes and treatments. Stress-induced photoinhibition also differentially influenced both ecotypes, with MG-1 more affected than MG-20. Data showed that the D2 PSII subunit was more affected than D1 after 1 d of low temperature exposure, although its protein levels recovered over the course of the experiment. Interestingly, D2 recovery was accompanied by improvements in photosynthetic parameters (Asat and Fv/Fm) and the NADPH/NADP(+) ratio. Our results suggest that the D2 protein is involved in the acclimation response of L. japonicus to low temperature. This may provide a deeper insight into the chilling tolerance mechanisms of the Lotus genus. PMID:27457984

  19. A Comparison of the Adaptive Immune Response between Recovered Anthrax Patients and Individuals Receiving Three Different Anthrax Vaccines.

    Laws, Thomas R; Kuchuloria, Tinatin; Chitadze, Nazibriola; Little, Stephen F; Webster, Wendy M; Debes, Amanda K; Saginadze, Salome; Tsertsvadze, Nikoloz; Chubinidze, Mariam; Rivard, Robert G; Tsanava, Shota; Dyson, Edward H; Simpson, Andrew J H; Hepburn, Matthew J; Trapaidze, Nino

    2016-01-01

    Several different human vaccines are available to protect against anthrax. We compared the human adaptive immune responses generated by three different anthrax vaccines or by previous exposure to cutaneous anthrax. Adaptive immunity was measured by ELISPOT to count cells that produce interferon (IFN)-γ in response to restimulation ex vivo with the anthrax toxin components PA, LF and EF and by measuring circulating IgG specific to these antigens. Neutralising activity of antisera against anthrax toxin was also assayed. We found that the different exposures to anthrax antigens promoted varying immune responses. Cutaneous anthrax promoted strong IFN-γ responses to all three antigens and antibody responses to PA and LF. The American AVA and Russian LAAV vaccines induced antibody responses to PA only. The British AVP vaccine produced IFN-γ responses to EF and antibody responses to all three antigens. Anti-PA (in AVA and LAAV vaccinees) or anti-LF (in AVP vaccinees) antibody titres correlated with toxin neutralisation activities. Our study is the first to compare all three vaccines in humans and show the diversity of responses against anthrax antigens. PMID:27007118

  20. A Comparison of the Adaptive Immune Response between Recovered Anthrax Patients and Individuals Receiving Three Different Anthrax Vaccines.

    Thomas R Laws

    Full Text Available Several different human vaccines are available to protect against anthrax. We compared the human adaptive immune responses generated by three different anthrax vaccines or by previous exposure to cutaneous anthrax. Adaptive immunity was measured by ELISPOT to count cells that produce interferon (IFN-γ in response to restimulation ex vivo with the anthrax toxin components PA, LF and EF and by measuring circulating IgG specific to these antigens. Neutralising activity of antisera against anthrax toxin was also assayed. We found that the different exposures to anthrax antigens promoted varying immune responses. Cutaneous anthrax promoted strong IFN-γ responses to all three antigens and antibody responses to PA and LF. The American AVA and Russian LAAV vaccines induced antibody responses to PA only. The British AVP vaccine produced IFN-γ responses to EF and antibody responses to all three antigens. Anti-PA (in AVA and LAAV vaccinees or anti-LF (in AVP vaccinees antibody titres correlated with toxin neutralisation activities. Our study is the first to compare all three vaccines in humans and show the diversity of responses against anthrax antigens.

  1. A Comparison of the Adaptive Immune Response between Recovered Anthrax Patients and Individuals Receiving Three Different Anthrax Vaccines

    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

  2. Molecular mechanisms involved in adaptive responses to radiation, UV light, and heat

    Viable organisms recognize and respond to environmental changes or stresses. When these environmental changes and their responses by organisms are extreme, they can limit viability. However, organisms can adapt to these different stresses by utilizing different possible responses via signal transduction pathways when the stress is not lethal. In particular, prior mild stresses can provide some aid to prepare organisms for subsequent more severe stresses. These adjustments or adaptations for future stresses have been called adaptive responses. These responses are present in bacteria, plants and animals. The following review covers recent research which can help describe or postulate possible mechanisms which may be active in producing adaptive responses to radiation, ultraviolet light, and heat. (author)

  3. Adapting responsibilities: an ethical analysis of the United Nations Framework Convention on Climate Change

    Harry, Rebecca Jane

    2010-01-01

    The United Nations Framework Convention on Climate Change is the seminal international agreement that provides a commitment and a corresponding responsibility framework to assist the least developed countries (LDCs) adapt to the adverse effects of climate change. To operationalize these commitments the National Adaptation Programmes of Action was created to assist LDCs implement adaptation projects. This programme has been severely hampered by the limited resources provided by Parties to the ...

  4. Adaptation-induced Tourism for Consumers of Literature on Screen: the Experience of Jane Austen Fans

    Maddalena Pennacchia

    2015-01-01

    My aim in this article is that of starting to relate the expanding research field of adaptation studies to the subject area of film-induced tourism. Adaptations are a specific typology of films: that is, films whose story was not originally intended for the screen but, more often than not, for the written page, and has, therefore, been ‘translated’ into a new medium. The phenomenon of adaptation has been at the center of a heated debate for a few years now, but the specific link between adapt...

  5. Brevity of haptic force perturbations induces heightened adaptive sensitivity

    Wanda, Paul A.; Fine, Michael S.; Weeks, Heidi M.; Gross, Andrew M.; Macy, Jenny L.; Thoroughman, Kurt A.

    2013-01-01

    We have exposed human participants to both full-movement and pulsatile viscous force perturbations to study the effect of force duration on the incremental transformation of sensation into adaptation. Traditional views of movement biomechanics could suggest that pulsatile forces would largely be attenuated as stiffness and viscosity act as a natural low-pass filter. Sensory transduction, however, tends to react to changes in stimuli and therefore could underlie heightened sensitivity to briefer, pulsatile forces. Here, participants adapted within perturbation duration conditions in a manner proportionate to sensed force and positional errors. Across perturbation conditions, we found participants had greater adaptive sensitivity when experiencing pulsatile forces rather than full-movement forces. In a follow-up experiment, we employed error-clamped, force channel trials to determine changes in predictive force generation. We found that while participants learned to closely compensate for the amplitude and breadth of full-movement forces, they exhibited a persistent mismatch in amplitude and breadth between adapted motor output and experienced pulsatile forces. This mismatch could generate higher salience of error signals that contribute to heightened sensitivity to pulsatile forces. PMID:23468159

  6. Kinetics of the early adaptive response and adaptation threshold dose; Cinetica de la respuesta adaptativa temprana y dosis umbral de adaptacion

    Mendiola C, M.T.; Morales R, P. [ININ, 52045 Ocoyoacac, Estado de Mexico (Mexico)

    2003-07-01

    The expression kinetics of the adaptive response (RA) in mouse leukocytes in vivo and the minimum dose of gamma radiation that induces it was determined. The mice were exposed 0.005 or 0.02 Gy of {sup 137} Cs like adaptation and 1h later to the challenge dose (1.0 Gy), another group was only exposed at 1.0 Gy and the damage is evaluated in the DNA with the rehearsal it makes. The treatment with 0. 005 Gy didn't induce RA and 0. 02 Gy causes a similar effect to the one obtained with 0.01 Gy. The RA was show from an interval of 0.5 h being obtained the maximum expression with 5.0 h. The threshold dose to induce the RA is 0.01 Gy and in 5.0 h the biggest quantity in molecules is presented presumably that are related with the protection of the DNA. (Author) =.

  7. Fire-Induced Response in Foam Encapsulants

    Borek, T.T.; Chu, T.Y.; Erickson, K.L.; Gill, W.; Hobbs, M.L.; Humphries, L.L.; Renlund, A.M.; Ulibarri, T.A.

    1999-04-02

    The paper provides a concise overview of a coordinated experimental/theoretical/numerical program at Sandia National Laboratories to develop an experimentally validated model of fire-induced response of foam-filled engineered systems for nuclear and transportation safety applications. Integral experiments are performed to investigate the thermal response of polyurethane foam-filled systems exposed to fire-like heat fluxes. A suite of laboratory experiments is performed to characterize the decomposition chemistry of polyurethane. Mass loss and energy associated with foam decomposition and chemical structures of the virgin and decomposed foam are determined. Decomposition chemistry is modeled as the degradation of macromolecular structures by bond breaking followed by vaporization of small fragments of the macromolecule with high vapor pressures. The chemical decomposition model is validated against the laboratory data. Data from integral experiments is used to assess and validate a FEM foam thermal response model with the chemistry model developed from the decomposition experiments. Good agreement was achieved both in the progression of the decomposition front and the in-depth thermal response.

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

    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…

  9. Detection of the radioadaptive response in mouse bone marrow in remote terms after adaptation

    Duration of the adaptive response (AR) reservation in various times after exposure to adaptive dose (including delayed times) in the system in vivo is studied. Mice-males were used for experiments. 60Co source was used for irradiation. It is shown that the AR remains for a long time after single acute low dose gamma-irradiation

  10. Control of Dichotomic Innate and Adaptive Immune Responses by Artery Tertiary Lymphoid Organs in Atherosclerosis

    Falk eWeih

    2012-07-01

    Full Text Available Tertiary lymphoid organs (TLOs emerge in tissues in response to nonresolving inflammation such as chronic infection, graft rejection, and autoimmune disease. We identified artery TLOs (ATLOs in the adventitia adjacent to atherosclerotic plaques of aged hyperlipidemic ApoE-/- mice. ATLOs are structured into T cell areas harboring conventional dendritic cells (cDCs and monocyte-derived DCs (mDCs; B cell follicles containing follicular dendritic cells (FDCs within activated germinal centers; and peripheral niches of plasma cells. ATLOs also show extensive neoangiogenesis, aberrant lymphangiogenesis, and high endothelial venule (HEV neogenesis. Newly formed conduit networks connect the external lamina of the artery with HEVs in T cell areas. ATLOs recruit and generate lymphocyte subsets with opposing activities including activated CD4+ and CD8+ effector T cells, natural and induced CD4+ T regulatory cells (nTregs; iTregs as well as B-1 and B-2 cells at different stages of differentiation. These data indicate that ATLOs organize dichotomic innate and adaptive immune responses in atherosclerosis. In this review we discuss the novel concept that dichotomic immune responses towards atherosclerosis-specific antigens are carried out by ATLOs in the adventitia of the arterial wall and that malfunction of the tolerogenic arm of ATLO immunity triggers transition from silent autoimmune reactivity to clinically overt disease.

  11. Dynamic Condition Response Graphs for Trustworthy Adaptive Case Management

    Mukkamala, Raghava Rao; Hildebrandt, Thomas; Slaats, Tijs;

    2013-01-01

    semantics that supports both run time changes and formal verification. We show how these techniques are being implemented in industry as a component of the Exformatics case management tools. Finally we discuss the planned future work, which will aim to allow changes to be tested for conformance wrt policies......By trustworthy adaptive case management we mean that it should be possible to adapt processes and goals at runtime while guaranteeing that no deadlocks and livelocks are introduced. We propose to support this by applying a formal declarative process model, DCR Graphs, and exemplify its operational...... specified either as linear time logic (LTL) or DCR Graphs, extend the language with time and data and offer extended support for cross-organizational case management systems....

  12. Adaptive responses to environmental changes in Lake Victoria cichlids

    Rijssel, Jacobus Cornelis van (Jacco)

    2014-01-01

    Lake Victoria cichlids show the fastest vertebrate adaptive radiation known which is why they function as a model organism to study evolution. In the past 40 years, Lake Victoria experienced severe environmental changes including the boom of the introduced, predatory Nile perch and eutrophication. Both environmental changes resulted in a decline of haplochromine cichlid species and numbers during the 1980s. However, during the 1990s and 2000s, some haplochromine species recovered. With the us...

  13. Visfatin induces sickness responses in the brain.

    Byong Seo Park

    Full Text Available BACKGROUND/OBJECTIVE: Visfatin, also known as nicotiamide phosphoribosyltransferase or pre-B cell colony enhancing factor, is a pro-inflammatory cytokine whose serum level is increased in sepsis and cancer as well as in obesity. Here we report a pro-inflammatory role of visfatin in the brain, to mediate sickness responses including anorexia, hyperthermia and hypoactivity. METHODOLOGY: Rats were intracerebroventricularly (ICV injected with visfatin, and changes in food intake, body weight, body temperature and locomotor activity were monitored. Real-time PCR was applied to determine the expressions of pro-inflammatory cytokines, proopiomelanocortin (POMC and prostaglandin-synthesizing enzymes in their brain. To determine the roles of cyclooxygenase (COX and melanocortin in the visfatin action, rats were ICV-injected with visfatin with or without SHU9119, a melanocortin receptor antagonist, or indomethacin, a COX inhibitor, and their sickness behaviors were evaluated. PRINCIPAL FINDINGS: Administration of visfatin decreased food intake, body weight and locomotor activity and increased body temperature. Visfatin evoked significant increases in the levels of pro-inflammatory cytokines, prostaglandin-synthesizing enzymes and POMC, an anorexigenic neuropeptide. Indomethacin attenuated the effects of visfatin on hyperthermia and hypoactivity, but not anorexia. Further, SHU9119 blocked visfatin-induced anorexia but did not affect hyperthermia or hypoactivity. CONCLUSIONS: Visfatin induced sickness responses via regulation of COX and the melanocortin pathway in the brain.

  14. Adaptive governance and institutional strategies for climate-induced community relocations in Alaska

    Bronen, Robin; Chapin, F Stuart

    2013-01-01

    This article presents governance and institutional strategies for climate-induced community relocations. In Alaska, repeated extreme weather events coupled with climate change-induced coastal erosion impact the habitability of entire communities. Community residents and government agencies concur that relocation is the only adaptation strategy that can protect lives and infrastructure. Community relocation stretches the financial and institutional capacity of existing governance institutions....

  15. Influence of MIGI-K preparation on adaptive response of the steam cells from murine bone-marrow

    Radioprotective action of MIGI-K hydrolizate on adaptive response of the steam cells from murine bone-marrow was studied. It was shown that this preparation protecting animals under lethal and sub-lethal doses of irradiation can also modify adaptive response. It was supposed that adaptive response model can be applied for studying possibilities of radioprotectors use under low doses irradiation

  16. Conjugative DNA Transfer Induces the Bacterial SOS Response and Promotes Antibiotic Resistance Development through Integron Activation

    Baharoglu, Zeynep; Bikard, David; Mazel, Didier

    2010-01-01

    Conjugation is one mechanism for intra- and inter-species horizontal gene transfer among bacteria. Conjugative elements have been instrumental in many bacterial species to face the threat of antibiotics, by allowing them to evolve and adapt to these hostile conditions. Conjugative plasmids are transferred to plasmidless recipient cells as single-stranded DNA. We used lacZ and gfp fusions to address whether conjugation induces the SOS response and the integron integrase. The SOS response contr...

  17. Prospective study on adaptive response induction by heavy-ion radiation in human lymphoblastoid cell lines and cultured mouse fetal cells

    We investigated radiation-induced response to X-rays and heavy-ions in lymphoblastoid cells. As pre-exposure to low priming dose of ionizing radiations decreases the biological effects of a subsequent higher challenging dose in a variety of models, we wondered whether adaptive response could be observed when using accelerated heavy ions radiation. For the first time, we demonstrated the existence of a mutagenic adaptive response to both low and high-linear energy transfer (LET) radiation in cultured human lymphoblastoid cells, which might be linked with a modulation of DNA repair. (author)

  18. Receptor-Induced Dilatation in the Systemic and Intrarenal Adaptation to Pregnancy in Rats

    Ferreira, Vanessa M; Gomes, Thiago S.; Luciana A. Reis; Ferreira, Alice T.; Razvickas, Clara V.; Schor, Nestor; Mirian A. Boim

    2009-01-01

    Normal pregnancy is associated with systemic and intrarenal vasodilatation resulting in an increased glomerular filtration rate. This adaptive response occurs in spite of elevated circulating levels of angiotensin II (Ang II). In the present study, we evaluated the potential mechanisms responsible for this adaptation. The reactivity of the mesangial cells (MCs) cultured from 14-day-pregnant rats to Ang II was measured through changes in the intracellular calcium concentration ([Cai]). The exp...

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

    Stålhand, Jonas; Holzapfel, Gerhard A

    2016-05-21

    Airway and bladder smooth muscles are known to undergo length adaptation under sustained contraction. This adaptation process entails a remodelling of the intracellular actin and myosin filaments which shifts the peak of the active force-length curve towards the current length. Smooth muscles are therefore able to generate the maximum force over a wide range of lengths. In contrast, length adaptation of vascular smooth muscle has attracted very little attention and only a handful of studies have been reported. Although their results are conflicting on the existence of a length adaptation process in vascular smooth muscle, it seems that, at least, peripheral arteries and arterioles undergo such adaptation. This is of interest since peripheral vessels are responsible for pressure regulation, and a length adaptation will affect the function of the cardiovascular system. It has, e.g., been suggested that the inward remodelling of resistance vessels associated with hypertension disorders may be related to smooth muscle adaptation. In this study we develop a continuum mechanical model for vascular smooth muscle length adaptation by assuming that the muscle cells remodel the actomyosin network such that the peak of the active stress-stretch curve is shifted towards the operating point. The model is specialised to hamster cheek pouch arterioles and the simulated response to stepwise length changes under contraction. The results show that the model is able to recover the salient features of length adaptation reported in the literature. PMID:26925813

  20. Dispersal, behavioral responses and thermal adaptation in Musca domestica

    Kjaersgaard, Anders; Blackenhorn, Wolf U.; Pertoldi, Cino;

    Behavioral traits can have great impact on an organism’s ability to cope with or avoidance of thermal stress, and are therefore of evolutionary importance for thermal adaptation. We compared the morphology, heat resistance, locomotor (walking and flying) activity and flight performance of three......) Spanish flies flew longest and Danish flies shortest. Swiss flies were the most active in terms of locomotor activity at the benign temperature (24°C), whereas the Spanish flies were able to stay active longer at the high temperature (43°C). Population differences in behavioral traits and heat resistance...

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

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

    2015-04-01

    functional type. Assigning plant functional types does not allow for local plant adaptation to be reflected in the model parameters, nor does it allow for correlations that might exist between root parameters and soil type. [1] Seibert, J. 2000. Multi-criteria calibration of a conceptual runoff model using a genetic algorithm. Hydrology and Earth System Sciences 4(2): 215-224. [2] Van der Ploeg, M.J., H.P.A. Gooren, G. Bakker, C.W. Hoogendam, C. Huiskes, L.K. Koopal, H. Kruidhof and G.H. de Rooij. 2010. Polymer tensiometers with ceramic cones: performance in drying soils and comparison with water-filled tensiometers and time domain reflectometry. Hydrol. Earth Syst. Sci. 14: 1787-1799, doi: 10.5194/hess-14-1787-2010. [3] McClintock B. The significance of responses of the genome to challenge. Science 1984; 226: 792-801 [4] Ries G, Heller W, Puchta H, Sandermann H, Seldlitz HK, Hohn B. Elevated UV-B radiation reduces genome stability in plants. Nature 2000; 406: 98-101 [5] Lucht JM, Mauch-Mani B, Steiner H-Y, Metraux J-P, Ryals, J, Hohn B. Pathogen stress increases somatic recombination frequency in Arabidopsis. Nature Genet. 2002; 30: 311-314 [6] Kovalchuk I, Kovalchuk O, Kalck V., Boyko V, Filkowski J, Heinlein M, Hohn B. Pathogen-induced systemic plant signal triggers DNA rearrangements. Nature 2003; 423: 760-762 [7] Cullis C A. Mechanisms and control of rapid genomic changes in flax. Ann. Bot. (Lond.) 2005; 95: 201-206

  2. Adaptive response in mice exposed to 900 MHz radiofrequency fields: primary DNA damage.

    Bingcheng Jiang

    Full Text Available 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/cm(2 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.

  3. Mitochondrial fission is an acute and adaptive response in injured motor neurons

    Kiryu-Seo, Sumiko; Tamada, Hiromi; Kato, Yukina; Yasuda, Katsura; Ishihara, Naotada; Nomura, Masatoshi; Mihara, Katsuyoshi; Kiyama, Hiroshi

    2016-01-01

    Successful recovery from neuronal damage requires a huge energy supply, which is provided by mitochondria. However, the physiological relevance of mitochondrial dynamics in damaged neurons in vivo is poorly understood. To address this issue, we established unique bacterial artificial chromosome transgenic (BAC Tg) mice, which develop and function normally, but in which neuronal injury induces labelling of mitochondria with green fluorescent protein (GFP) and expression of cre recombinase. GFP-labelled mitochondria in BAC Tg mice appear shorter in regenerating motor axons soon after nerve injury compared with mitochondria in non-injured axons, suggesting the importance of increased mitochondrial fission during the early phase of nerve regeneration. Crossing the BAC Tg mice with mice carrying a floxed dynamin-related protein 1 gene (Drp1), which is necessary for mitochondrial fission, ablates mitochondrial fission specifically in injured neurons. Injury-induced Drp1-deficient motor neurons show elongated or abnormally gigantic mitochondria, which have impaired membrane potential and axonal transport velocity during the early phase after injury, and eventually promote neuronal death. Our in vivo data suggest that acute and prominent mitochondrial fission during the early stage after nerve injury is an adaptive response and is involved in the maintenance of mitochondrial and neuronal integrity to prevent neurodegeneration. PMID:27319806

  4. Mitochondrial fission is an acute and adaptive response in injured motor neurons.

    Kiryu-Seo, Sumiko; Tamada, Hiromi; Kato, Yukina; Yasuda, Katsura; Ishihara, Naotada; Nomura, Masatoshi; Mihara, Katsuyoshi; Kiyama, Hiroshi

    2016-01-01

    Successful recovery from neuronal damage requires a huge energy supply, which is provided by mitochondria. However, the physiological relevance of mitochondrial dynamics in damaged neurons in vivo is poorly understood. To address this issue, we established unique bacterial artificial chromosome transgenic (BAC Tg) mice, which develop and function normally, but in which neuronal injury induces labelling of mitochondria with green fluorescent protein (GFP) and expression of cre recombinase. GFP-labelled mitochondria in BAC Tg mice appear shorter in regenerating motor axons soon after nerve injury compared with mitochondria in non-injured axons, suggesting the importance of increased mitochondrial fission during the early phase of nerve regeneration. Crossing the BAC Tg mice with mice carrying a floxed dynamin-related protein 1 gene (Drp1), which is necessary for mitochondrial fission, ablates mitochondrial fission specifically in injured neurons. Injury-induced Drp1-deficient motor neurons show elongated or abnormally gigantic mitochondria, which have impaired membrane potential and axonal transport velocity during the early phase after injury, and eventually promote neuronal death. Our in vivo data suggest that acute and prominent mitochondrial fission during the early stage after nerve injury is an adaptive response and is involved in the maintenance of mitochondrial and neuronal integrity to prevent neurodegeneration. PMID:27319806

  5. Adaptative nitric oxide overproduction in perivascular adipose tissue during early diet-induced obesity.

    Gil-Ortega, Marta; Stucchi, Paula; Guzmán-Ruiz, Rocío; Cano, Victoria; Arribas, Silvia; González, M Carmen; Ruiz-Gayo, Mariano; Fernández-Alfonso, Maria S; Somoza, Beatriz

    2010-07-01

    Perivascular adipose tissue (PVAT) plays a paracrine role in regulating vascular tone. We hypothesize that PVAT undergoes adaptative mechanisms during initial steps of diet-induced obesity (DIO) which contribute to preserve vascular function. Four-week-old male C57BL/6J mice were assigned either to a control [low-fat (LF); 10% kcal from fat] or to a high-fat diet (HF; 45% kcal from fat). After 8 wk of dietary treatment vascular function was analyzed in the whole perfused mesenteric bed (MB) and in isolated mesenteric arteries cleaned of PVAT. Relaxant responses to acetylcholine (10(-9)-10(-4) m) and sodium nitroprusside (10(-12)-10(-5) m) were significantly ameliorated in the whole MB from HF animals. However, there was no difference between HF and LF groups in isolated mesenteric arteries devoid of PVAT. The enhancement of relaxant responses detected in HF mice was not attributable to an increased release of nitric oxide (NO) from the endothelium nor to an increased sensitivity and/or activity of muscular guanilylcyclase. Mesenteric PVAT of HF animals showed an increased bioavailability of NO, detected by 4,5-diaminofluorescein diacetate (DAF2-DA) staining, which positively correlated with plasma leptin levels. DAF-2DA staining was absent in PVAT from ob/ob mice but was detected in these animals after 4-wk leptin replacement. The main finding in this study is that adaptative NO overproduction occurs in PVAT during early DIO which might be aimed at preserving vascular function. PMID:20410199

  6. Simulation of tumor induced angiogenesis using an analytical adaptive modeling including dynamic sprouting and blood flow modeling.

    Naghavi, Nadia; Hosseini, Farideh S; Sardarabadi, Mohammad; Kalani, Hadi

    2016-09-01

    In this paper, an adaptive model for tumor induced angiogenesis is developed that integrates generation and diffusion of a growth factor originated from hypoxic cells, adaptive sprouting from a parent vessel, blood flow and structural adaptation. The proposed adaptive sprout spacing model (ASS) determines position, time and number of sprouts which are activated from a parent vessel and also the developed vascular network is modified by a novel sprout branching prediction algorithm. This algorithm couples local vascular endothelial growth factor (VEGF) concentrations, stresses due to the blood flow and stochastic branching to the structural reactions of each vessel segment in response to mechanical and biochemical stimuli. The results provide predictions for the time-dependent development of the network structure, including the position and diameters of each segment and the resulting distributions of blood flow and VEGF. Considering time delays between sprout progressions and number of sprouts activated at different time durations provides information about micro-vessel density in the network. Resulting insights could be useful for motivating experimental investigations of vascular pattern in tumor induced angiogenesis and development of therapies targeting angiogenesis. PMID:27179697

  7. Central adaptation of pain perception in response to rehabilitation of musculoskeletal pain

    Andersen, Lars L; Andersen, Christoffer H; Sundstrup, Emil;

    2012-01-01

    BACKGROUND: Understanding the mechanisms of long-standing musculoskeletal pain and adaptations in response to physical rehabilitation is important for developing optimal treatment strategies. The influence of central adaptations of pain perception in response to rehabilitation of musculoskeletal...... 2 min group, respectively, and 29 (1 to 58) kPa and 36 (7 to 64) kPa in the 12 min group. LIMITATIONS: Blinding of participants is not possible in behavioural interventions. CONCLUSION: Central adaptations of pain perception occur in response to rehabilitation of musculoskeletal pain. Thus, treating...... pain in one region of the body reduces sensitivity to pressure in other regions of the body. Clinicians and researchers may use this knowledge to better understand adaptations of pain perception in patients with musculoskeletal pain....

  8. Adaptive response and genomic instability: allosteric response of genome to negative impact

    Currently, there is an upsurge concern on the unique response of living cells to low dose ionizing radiation for its inconformity to the existing paradigm of the biological action of radiation and its impact on the current understanding of risk evaluation of health effect of radiation in our workplace and environment. For the allosteric response to have significance, the cells must have an excellent sensing mechanism to discriminate tolerable and intolerable signals. In a series of experiments with mammalian, including human, cells, we demonstrated a novel sensing and signaling mechanism in the low-dose irradiated cells that was mediated by a PKCα-p3BMAPK-PLCδ1 feedback regulatory loop. Upon irradiation, PKCα is immediately activated, which in turn activate p38MAPK. The activation of p38MAPK is feedbacked to the activation of PKCα via PLCδ1, which catalyzes the hydrolysis of PtdInsP2 to generate PKCα-directed second messengers DAG and lnsP3. At low doses, the PKCα and p38MAPK continue to be activated for long time through this feedback loop, but when the cells encounter the high dose (>10 cGy or equivalent), the feedback loop is immediately comes to shutdown by deprivation of PKCα protein, known as down-regulation of PKC signaling. Thus, PKCα plays a key role in the long lasting nature of adaptive response to low doses and a binary switch to the genomic instability by too much signals. Tumor suppressor protein, p53, is a downstream effecter

  9. Adapt

    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

  10. Adaptive and cross-protective responses against cadmium and zinc toxicity in cadmium-resistant bacterium isolated from a zinc mine

    Benjaphorn Prapagdee

    2009-12-01

    Full Text Available Cadmium (Cd is a major environmental hazard, which usually is detected in its ionic form of Cd2+. It also causes adverse toxic effects on human health and other living organisms. Cd-resistant bacteria were isolated from Cd-contaminated soils. One isolate, TAK1, was highly resistance level to Cd toxicity. TAK1 was isolated from soil contaminated with a high Cd concentration (204.1 mg.kg-1. The result of 16S rDNA sequence analysis found that the TAK1 showed the similarity to Ralstonia sp. Physiological adaptive and cross-protective responses to Cd and Zn killing were investigated in Ralstonia sp.TAK1. Exposure to a low concentration of Cd induced adaptive resistance to higher concentrations of Cd. In addition, pretreatment of Ralstonia sp.TAK1 with an inducing concentration of Cd conferred cross-protective response against subsequent exposure to the lethal concentrations of Zn. The induced adaptive and cross-protective response Ralstonia sp.TAK1 required newly synthesized protein(s. Cd-induced adaptive and cross-protective responses against Cd and Zn toxicity are the important mechanisms used by Ralstonia sp.TAK1 to survive in the heavy metal contaminated environments. These findings might lead to the use of Ralstonia sp.TAK1 for microbial based remediation in Cd and Zn-contaminated soils.

  11. Human Skeletal Muscle Mitochondrial Uncoupling Is Associated with Cold Induced Adaptive Thermogenesis

    Sander L J Wijers; Schrauwen, Patrick; Saris, Wim H. M.; van Marken Lichtenbelt, Wouter D.

    2008-01-01

    Background Mild cold exposure and overfeeding are known to elevate energy expenditure in mammals, including humans. This process is called adaptive thermogenesis. In small animals, adaptive thermogenesis is mainly caused by mitochondrial uncoupling in brown adipose tissue and regulated via the sympathetic nervous system. In humans, skeletal muscle is a candidate tissue, known to account for a large part of the epinephrine-induced increase in energy expenditure. However, mitochondrial uncoupli...

  12. Sucralose induces biochemical responses in Daphnia magna.

    Ann-Kristin Eriksson Wiklund

    Full Text Available The intense artificial sweetener sucralose has no bioconcentration properties, and no adverse acute toxic effects have been observed in standard ecotoxicity tests, suggesting negligible environmental risk. However, significant feeding and behavioural alterations have been reported in non-standard tests using aquatic crustaceans, indicating possible sublethal effects. We hypothesized that these effects are related to alterations in acetylcholinesterase (AChE and oxidative status in the exposed animals and investigated changes in AChE and oxidative biomarkers (oxygen radical absorbing capacity, ORAC, and lipid peroxidation, TBARS in the crustacean Daphnia magna exposed to sucralose (0.0001-5 mg L(-1. The sucralose concentration was a significant positive predictor for ORAC, TBARS and AChE in the daphnids. Moreover, the AChE response was linked to both oxidative biomarkers, with positive and negative relationships for TBARS and ORAC, respectively. These joint responses support our hypothesis and suggest that exposure to sucralose may induce neurological and oxidative mechanisms with potentially important consequences for animal behaviour and physiology.

  13. Studying of the DNA DSBs repair in the adaptive response of human lymphocytes

    Human lymphocytes exposed to very low doses of DNA damaging agents may become less sensitive to subsequent higher doses of the DNA damaging agent. This phenomenon is called the adaptive response. The aim of this project was to study the significance of DNA double-strand break (DSBs) repair in the adaptive response of human lymphocytes exposed to ionizing radiation. Human lymphocytes isolated from whole blood and stimulated with hemagglutynin (PHA) were irradiated with adaptive dose (5 cGy of X-rays) and then challenge dose of 2 Gy in case of micronuclei assay and 10 Gy in case of comet assay. The frequency of micronuclei in adapted lymphocytes was about 30% lower than expected for an additive effect of both, adaptive and challenge doses, applied separately. Estimation of DSBs was carried out with the use of single cell gel electrophoresis assay (comet assay) in neutral pH and to complement these results with pulse-field gel electrophoresis (PFGE). The use of both PFGE and comet assay allowed us to suggest that lower damage revealed in the adapted lymphocytes at the chromosomal level was unrelated to initial level of DSBs in DNA. The differences between kinetics of DNA repair in the adapted and non-adapted lymphocytes were not significant. (author)

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

    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

  15. FDG-PET/CT based response-adapted treatment

    de Geus-Oei, Lioe-Fee; Vriens, Dennis; Arens, Anne I J;

    2012-01-01

    It has been shown that [(18)F]fluorodeoxyglucose (FDG)-positron emission tomography (PET) provides robust and reproducible data for early metabolic response assessment in various malignancies. This led to the initiation of several prospective multicenter trials in malignant lymphoma and adenocarc...

  16. Dysregulation of adaptive immune responses in complement C3-deficient patients

    Pekkarinen, Pirkka T.; Heikkila, Nelli; Kisand, Kai; Peterson, Paert; Botto, Marina; Daha, Mohamed R.; Drouet, Christian; Isaac, Lourdes; Helminen, Merja; Haahtela, Tari; Meri, Seppo; Jarva, Hanna; Arstila, T. Petteri

    2015-01-01

    In addition to its effector functions, complement is an important regulator of adaptive immune responses. Murine studies suggest that complement modulates helper T-cell differentiation, and Th1 responses in particular are impaired in the absence of functional complement. Here, we have studied humora

  17. Radio-adaptive Response: An Implication for the Biological Consequences of Low Dose-rate Exposure to X-Ray

    Radiation induced adaptive response is described as the reduced damaging effect of a challenging radiation dose when induced by a previous low priming dose. To verify the radio-adaptive response that can be induced by occupationally (in vivo) received chronic low dose of X-ray, chromosomal aberration (CA) analysis, micronucleus test (MN), interleukin-1β (IL-1β) and nitric oxide (NO) concentrations were investigated for both the occupationally exposed and control groups before and after exposure to 2 Gy γ-rays as a challenge dose. The results showed that an elevated frequency of CA, MN and nucleoplasmic bridge (NPB) was recorded in radiation workers (exposed group) compared to control group. However, after 2Gy in vitro irradiation of lymphocytes of exposed and control groups, the exposed group was found to be lower than that of control group. On the other hand, IL-1β and NO concentrations in plasma were elevated in exposed group more than in control group. While, after 2Gy irradiation for both groups, there are higher increment in the concentrations of IL-1β and NO in exposed group than the increment difference observed for control group after in vitro irradiation as compared to the same group before irradiation. The present results suggested the existence of an in vivo cytogenetic adaptive response in individuals occupationally exposed to low dose of X-ray. In addition, the results showed that NO radicals and IL-1β have a role in the induction of radio-resistance due to in vivo exposure that may intermediate this radiation.

  18. Studies on kinetics of radio adaptive responses in BALB/c mice

    Radio adaptive response is a phenomenon by which exposure to sub-lethal doses of ionizing radiation, known as conditioning or priming dose (PD), leads to increased resistance to a subsequent exposure to a higher dose, known as challenge dose (CD). The characterization of radio adaptive response exhibited by immune cells is of prime importance as it can directly influence various biological mechanisms like immune response against antigen, neoplastic growth and auto immunity. In this study, we have investigated radio adaptive response following whole body radiation of BALB/c mice. Mice were irradiated with 10 cGy PD, 2 Gy CD and priming and challenging dose (P+CD) with an interval of 4 hr. Unirradiated mice served as controls. Mice were sacrificed immediately; 24 h or 72 h after challenging dose, and single cell suspension of splenocytes were prepared. The cells were cultured in presence of concanavalin A (Con A) to assess apoptosis (propidium iodide staining), expression of early activation markers, CD71 and CD69 (flow cytometry), cytokine secretion (IL-2 and IFN-γ, ELISA) and proliferation (CFSE dilution and 3H thymidine incorporation). A three fold increase in apoptosis was observed in CD and P+CD groups compared to control or PD when mice were sacrificed immediately or 24 h after CD. Twenty four hours after CD, a significant increase was found in the expression of CD69 and CD71 in P+CD as compared to CD. Similar results were obtained in terms of proliferation response and secretion of IL-2 and IFN-γ, suggesting radio adaptive response. This was observed 72 h after CD also but not immediately after CD. This pattern of radio-adaptive response was obtained in six week old mice and was different in 4-6 month old mice. In conclusion, these results demonstrate the narrow window of radio adaptive response in splenocytes of BALB/c mice following exposure to whole body irradiation. (author)

  19. Adaptation of the immune system as a response to pregnancy

    Milašinović Ljubomir; Bulatović Sanja; Ilić Đorđe; Ivanović Ljiljana; Županski Mirjana

    2002-01-01

    Introduction Pregnancy is an intriguing immunologic phenomenon. In spite of genetic differences, maternal and fetal cells are in close contact over the whole course of pregnancy with no evidence of either humoral and/or cellular immunologic response of mother to fetus as an allotransplant. The general opinion is that the fundamental protective mechanism must be located locally at the contact-plate, between the maternal and fetal tissues. Immunologic investigations proved the presence of speci...

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

    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. PMID:27115249

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

    Knapp Roland A

    2007-02-01

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

  2. Complement Activation Pathways: A Bridge between Innate and Adaptive Immune Responses in Asthma

    Wills-Karp, Marsha

    2007-01-01

    Although it is widely accepted that allergic asthma is driven by T helper type 2 (Th2)-polarized immune responses to innocuous environmental allergens, the mechanisms driving these aberrant immune responses remain elusive. Recent recognition of the importance of innate immune pathways in regulating adaptive immune responses have fueled investigation into the role of innate immune pathways in the pathogenesis of asthma. The phylogenetically ancient innate immune system, the complement system, ...

  3. Adaptation-induced Tourism for Consumers of Literature on Screen: the Experience of Jane Austen Fans

    Maddalena Pennacchia

    2015-03-01

    Full Text Available My aim in this article is that of starting to relate the expanding research field of adaptation studies to the subject area of film-induced tourism. Adaptations are a specific typology of films: that is, films whose story was not originally intended for the screen but, more often than not, for the written page, and has, therefore, been ‘translated’ into a new medium. The phenomenon of adaptation has been at the center of a heated debate for a few years now, but the specific link between adaptation and tourism has not yet been studied in its own right. In my article I question why and how adaptations of literary texts for the screen can induce a desire to visit film locations (actual geographical places in readers who are also inclined to enjoy the experience of “literature on screen”. In order to do this, I focus on the case study of adaptations from Jane Austen’s novels and on a specific kind of tourists, the so called ‘Janeites’, or Austen fans.

  4. Cellular adaptive immune response against porcine circovirus type 2 in subclinically infected pigs

    Gerber Heidi

    2009-12-01

    Full Text Available Abstract Background Porcine circovirus type 2 (PCV2 is a dominant causative agent of postweaning multisystemic wasting syndrome (PMWS, a multifactorial disease complex with putative immunosuppressive characteristics. Little is known about adaptive PCV2-specific immune responses in infected pigs. Therefore, the T and B cell responses following PCV2 infection in 3-week old SPF piglets infected with PCV2 or PCV2 plus porcine parvovirus (PPV were studied. Results All animals were asymptomatically infected. At 7 days post infection (d p.i., B lymphocyte and T lymphocyte numbers decreased in the dual infected, but not in the single infected piglets. At this time point a transient PCV2 viraemia was noted in the PCV2 infected groups. Antibodies against the infecting virus were detectable at day 24-28 p.i. for anti-PCV2 antibodies and at day 10 p.i. for anti-PPV antibodies, with no apparent influence of PCV2 on the early PPV antibody development. In the animals infected with PPV alone, IFN-γ secreting cells (SC that were not specific for PCV2 were detected by ELISPOT assay at day 7 p.i. Interestingly, this response was absent in the PCV2/PPV dual infected animals. PCV2-specific IFN-γ SC were observed in the PCV2/PPV infected group at 7 d p.i. and in the PCV2 single infected group at 21 d p.i. A reduction in the numbers of IFN-γ SC was observed following anti-CD4 and anti-CD8 antibody treatment, suggesting roles for both CD4+ and CD8+ T cells in the response against PCV2 infection. This was supported by an observed increase in the percentage of IFN-γ positive CD8hi cytotoxic T cells as well as IFN-γ positive CD8-/low helper T cells after PCV2 in vitro re-stimulation. Conclusions Infection of weaned SPF piglets with PCV2 alone or combined with PPV does not induce disease and in both cases a relatively slow anti-PCV2 antibody response and weak T lymphocyte responses were found. Knowledge on such immunological characteristics is important for both PCV2

  5. Adaptations in Muscle Activity to Induced, Short-Term Hindlimb Lameness in Trotting Dogs

    Fischer, Stefanie; Nolte, Ingo; Schilling, Nadja

    2013-01-01

    Muscle tissue has a great intrinsic adaptability to changing functional demands. Triggering more gradual responses such as tissue growth, the immediate responses to altered loading conditions involve changes in the activity. Because the reduction in a limb’s function is associated with marked deviations in the gait pattern, understanding the muscular responses in laming animals will provide further insight into their compensatory mechanisms as well as help to improve treatment options to prev...

  6. Oral quercetin supplementation hampers skeletal muscle adaptations in response to exercise training

    Casuso, R A; Martínez-López, E J; Nordsborg, Nikolai Baastrup;

    2014-01-01

    We aimed to test exercise-induced adaptations on skeletal muscle when quercetin is supplemented. Four groups of rats were tested: quercetin sedentary, quercetin exercised, placebo sedentary, and placebo exercised. Treadmill exercise training took place 5 days a week for 6 weeks. Quercetin groups ...

  7. the Adaptive Response, Genetic Haplo-Insufficiency and Genomic Instability

    Geard, Charles R.

    2014-12-12

    The linear no-threshold (LNT) hypothesis is the driving force in the establishment of radiation protection standards. However, the scientific basis for linearity has been brought into question, particularly due to the concerns about induced radiation resistance as it pertains to oxidative stress. Specifically, we investigated the observation that tumor hypoxia is associated with malignant progression, increased metastases, chemo- and radioresistance and poor prognosis. Experiments were conducted with non-malignant 3T3/NIH cells and normal human lung fibroblasts (NHLF) that were subjected to γ-irradiation under the levels of oxygen resembling those in growing tumors, and related our data to the concentrations of dissolved oxygen (DO), which is a better indicator of the amounts of residual oxygen inside the cells cultured in the hypoxic or anoxic atmosphere. We found that at DO levels about 0.5 mg/L cells subjected to both short-term (17 hours) and prolonged (48-72 hours) hypoxia continued to proliferate, and that apoptotic events were decreased at the early hours of hypoxic treatment. We showed that the short-term hypoxia up-regulated p53-binding protein 1 (53BP1) and resulted in facilitated 53BP1 nuclear foci formation and disappearance, thus indicating the higher efficiency of DNA double strand breaks repair processes. The latter was confirmed by the lower micronuclei incidence in irradiated hypoxic cells.

  8. The adaptive response of lichens to mercury exposure involves changes in the photosynthetic machinery

    Lichens are an excellent model to study the bioaccumulation of heavy metals but limited information is available on the molecular mechanisms occurring during bioaccumulation. We investigated the changes of the lichen proteome during exposure to constant concentrations of mercury. We found that most of changes involves proteins of the photosynthetic pathway, such as the chloroplastic photosystem I reaction center subunit II, the oxygen-evolving protein and the chloroplastic ATP synthase β-subunit. This suggests that photosynthesis is a target of the toxic effects of mercury. These findings are also supported by changes in the content of photosynthetic pigments (chlorophyll a and b, and β-carotene). Alterations to the photosynthetic machinery also reflect on the structure of thylakoid membranes of algal cells. Response of lichens to mercury also involves stress-related proteins (such as Hsp70) but not cytoskeletal proteins. Results suggest that lichens adapt to mercury exposure by changing the metabolic production of energy. - Highlights: ► Lichens exposed to Hg° vapors accumulate this metal irreversibly. ► Hg° interferes with physiological processes of the epiphytic lichen Evernia prunastri. ► Hg° promotes changes in the concentration of photosynthetic pigments. ► Hg° treatment causes changes in the ultrastructure of the photobiont plastids. ► Hg° induces changes in the protein machinery involved in the photosynthesis pathway. - Mercury affects the photosynthetic protein machinery of lichens.

  9. Anaphylatoxins coordinate innate and adaptive immune responses in allergic asthma.

    Schmudde, Inken; Laumonnier, Yves; Köhl, Jörg

    2013-02-01

    Allergic asthma is a chronic disease of the airways in which maladaptive Th2 and Th17 immune responses drive airway hyperresponsiveness (AHR), eosinophilic and neutrophilic airway inflammation and mucus overproduction. Airway epithelial and pulmonary vascular endothelial cells in concert with different resident and monocyte-derived dendritic cells (DC) play critical roles in allergen sensing and consecutive activation of TH cells and their differentiation toward TH2 and TH17 effector or regulatory T cells (Treg). Further, myeloid-derived regulatory cells (MDRC) act on TH cells and either suppress or enhance their activation. The complement-derived anaphylatoxins (AT) C3a and C5a are generated during initial antigen encounter and regulate the development of maladaptive immunity at allergen sensitization. Here, we will review the complex role of ATs in activation and modulation of different DC populations, MDRCs and CD4⁺ TH cells. We will also discuss the potential impact of ATs on the regulation of the pulmonary stromal compartment as an important means to regulate DC functions. PMID:23694705

  10. Androgen Induces Adaptation to Oxidative Stress in Prostate Cancer: Implications for Treatment with Radiation Therapy

    Jehonathan H. Pinthus

    2007-01-01

    Full Text Available Radiation therapy is a standard treatment for prostate cancer (PC. The postulated mechanism of action for radiation therapy is the generation of reactive oxygen species (ROS. Adjuvant androgen deprivation (AD therapy has been shown to confer a survival advantage over radiation alone in high-risk localized PC. However, the mechanism of this interaction is unclear. We hypothesize that androgens modify the radioresponsiveness of PC through the regulation of cellular oxidative homeostasis. Using androgen receptor (AR+ 22rv1 and AR− PC3 human PC cell lines, we demonstrated that testosterone increased basal reactive oxygen species (bROS levels, resulting in dose-dependent activation of phospho-p38 and pAKT, increased expression of clusterin, catalase, manganese superoxide dismutase. Similar data were obtained in three human PC xenografts; WISH-PC14, WISH-PC23, CWR22, growing in testosterone-supplemented or castrated SCID mice. These effects were reversible through AD or through incubation with a reducing agent. Moreover, testosterone increased the activity of catalase, superoxide dismutases, glutathione reductase. Consequently, AD significantly facilitated the response of AR+ cells to oxidative stress challenge. Thus, testosterone induces a preset cellular adaptation to radiation through the generation of elevated bROS, which is modified by AD. These findings provide a rational for combined hormonal and radiation therapy for localized PC.

  11. DMPD: ITAM-based signaling beyond the adaptive immune response. [Dynamic Macrophage Pathway CSML Database

    Full Text Available AM-based signaling beyond the adaptive immune response. PubmedID 16332394 Title ITAM-based signaling beyond...16332394 ITAM-based signaling beyond the adaptive immune response. Fodor S, Jakus Z..., Mocsai A. Immunol Lett. 2006 Apr 15;104(1-2):29-37. Epub 2005 Nov 28. (.png) (.svg) (.html) (.csml) Show IT...e (.html) CSML File (.csml) Open .csml file with CIOPlayer Open .csml file with CIOPlayer - ※CIO Playerのご利用上の注意 Open .csml file with CIO Open .csml file with CIO - ※CIOのご利用上の注意 ...

  12. Computational characterization of visually-induced auditory spatial adaptation

    David R Wozny

    2011-11-01

    Full Text Available Recent research investigating the principles governing human perception has provided increasing evidence for probabilistic inference in human perception. For example, human auditory and visual localization judgments closely resemble that of a Bayesian causal inference observer, where the underlying causal structure of the stimuli are inferred based on both the available sensory evidence and prior knowledge. However, most previous studies have focused on characterization of perceptual inference within a static environment, and therefore, little is known about how this inference process changes when observers are exposed to a new environment. In this study we aimed to computationally characterize the change in auditory spatial perception induced by repeated auditory-visual spatial conflict, known as the Ventriloquist Aftereffect. In theory, this change could reflect a shift in the auditory sensory representations (i.e., shift in auditory likelihood distribution, a decrease in the precision of the auditory estimates (i.e., increase in spread of likelihood distribution, a shift in the auditory bias (i.e., shift in prior distribution, or an increase/decrease in strength of the auditory bias (i.e., the spread of prior distribution, or a combination of these. By quantitatively estimating the parameters of the perceptual process for each individual observer using a Bayesian causal inference model, we found that the shift in the perceived locations after exposure was associated with a shift in the mean of the auditory likelihood functions in the direction of the experienced visual offset. The results suggest that repeated exposure to a fixed auditory-visual discrepancy is attributed by the nervous system to sensory representation error and as a result, the sensory map of space is recalibrated to correct the error.

  13. Extensive adaptive changes occur in the transcriptome of Streptococcus agalactiae (group B streptococcus in response to incubation with human blood.

    Laurent Mereghetti

    Full Text Available To enhance understanding of how Streptococcus agalactiae (group B streptococcus, GBS adapts during invasive infection, we performed a whole-genome transcriptome analysis after incubation with whole human blood. Global changes occurred in the GBS transcriptome rapidly in response to blood contact following shift from growth in a rich laboratory medium. Most (83% of the significantly altered transcripts were down-regulated after 30 minutes of incubation in blood, and all functional categories of genes were abundantly represented. We observed complex dynamic changes in the expression of transcriptional regulators and stress response genes that allow GBS to rapidly adapt to blood. The transcripts of relatively few proven virulence genes were up-regulated during the first 90 minutes. However, a key discovery was that genes encoding proteins involved in interaction with the host coagulation/fibrinolysis system and bacterial-host interactions were rapidly up-regulated. Extensive transcript changes also occurred for genes involved in carbohydrate metabolism, including multi-functional proteins and regulators putatively involved in pathogenesis. Finally, we discovered that an incubation temperature closer to that occurring in patients with severe infection and high fever (40 degrees C induced additional differences in the GBS transcriptome relative to normal body temperature (37 degrees C. Taken together, the data provide extensive new information about transcriptional adaptation of GBS exposed to human blood, a crucial step during GBS pathogenesis in invasive diseases, and identify many new leads for molecular pathogenesis research.

  14. Stress-induced adaptive islet cell identity changes.

    Cigliola, V; Thorel, F; Chera, S; Herrera, P L

    2016-09-01

    The different forms of diabetes mellitus differ in their pathogenesis but, ultimately, they are all characterized by progressive islet β-cell loss. Restoring the β-cell mass is therefore a major goal for future therapeutic approaches. The number of β-cells found at birth is determined by proliferation and differentiation of pancreatic progenitor cells, and it has been considered to remain mostly unchanged throughout adult life. Recent studies in mice have revealed an unexpected plasticity in islet endocrine cells in response to stress; under certain conditions, islet non-β-cells have the potential to reprogram into insulin producers, thus contributing to restore the β-cell mass. Here, we discuss the latest findings on pancreas and islet cell plasticity upon physiological, pathological and experimental conditions of stress. Understanding the mechanisms involved in cell reprogramming in these models will allow the development of new strategies for the treatment of diabetes, by exploiting the intrinsic regeneration capacity of the pancreas. PMID:27615136

  15. Peripheral dendritic cells are essential for both the innate and adaptive antiviral immune responses in the central nervous system

    Intranasal application of vesicular stomatitis virus (VSV) causes acute infection of the central nervous system (CNS). However, VSV encephalitis is not invariably fatal, suggesting that the CNS may contain a professional antigen-presenting cell (APC) capable of inducing or propagating a protective antiviral immune response. To examine this possibility, we first characterized the cellular elements that infiltrate the brain as well as the activation status of resident microglia in the brains of normal and transgenic mice acutely ablated of peripheral dendritic cells (DCs) in vivo. VSV encephalitis was characterized by a pronounced infiltrate of myeloid cells (CD45highCD11b+) and CD8+ T cells containing a subset that was specific for the immunodominant VSV nuclear protein epitope. This T cell response correlated temporally with a rapid and sustained upregulation of MHC class I expression on microglia, whereas class II expression was markedly delayed. Ablation of peripheral DCs profoundly inhibited the inflammatory response as well as infiltration of virus-specific CD8+ T cells. Unexpectedly, the VSV-induced interferon-gamma (IFN-γ) response in the CNS remained intact in DC-deficient mice. Thus, both the inflammatory and certain components of the adaptive primary antiviral immune response in the CNS are dependent on peripheral DCs in vivo.

  16. Exercise-induced ROS in heat shock proteins response.

    Dimauro, Ivan; Mercatelli, Neri; Caporossi, Daniela

    2016-09-01

    Cells have evolved multiple and sophisticated stress response mechanisms aiming to prevent macromolecular (including proteins, lipids, and nucleic acids) damage and to maintain or re-establish cellular homeostasis. Heat shock proteins (HSPs) are among the most highly conserved, ubiquitous, and abundant proteins in all organisms. Originally discovered more than 50 years ago through heat shock stress, they display multiple, remarkable roles inside and outside cells under a variety of stresses, including also oxidative stress and radiation, recognizing unfolded or misfolded proteins and facilitating their restructuring. Exercise consists in a combination of physiological stresses, such as metabolic disturbances, changes in circulating levels of hormones, increased temperature, induction of mild to severe inflammatory state, increased production of reactive oxygen and nitrogen species (ROS and RNS). As a consequence, exercise is one of the main stimuli associated with a robust increase in different HSPs in several tissues, which appears to be also fundamental in facilitating the cellular remodeling processes related to the training regime. Among all factors involved in the exercise-related modulation of HSPs level, the ROS production in the contracting muscle or in other tissues represents one of the most attracting, but still under discussion, mechanism. Following exhaustive or damaging muscle exercise, major oxidative damage to proteins and lipids is likely involved in HSP expression, together with mechanically induced damage to muscle proteins and the inflammatory response occurring several days into the recovery period. Instead, the transient and reversible oxidation of proteins by physiological concentrations of ROS seems to be involved in the activation of stress response following non-damaging muscle exercise. This review aims to provide a critical update on the role of HSPs response in exercise-induced adaptation or damage in humans, focusing on experimental

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

    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

  18. Suppression of adaptive immunity to heterologous antigens during Plasmodium infection through hemozoin-induced failure of dendritic cell function

    Phillips R

    2006-04-01

    Full Text Available Abstract Background Dendritic cells (DCs are central to the initiation and regulation of the adaptive immune response during infection. Modulation of DC function may therefore allow evasion of the immune system by pathogens. Significant depression of the host's systemic immune response to both concurrent infections and heterologous vaccines has been observed during malaria infection, but the mechanisms underlying this immune hyporesponsiveness are controversial. Results Here, we demonstrate that the blood stages of malaria infection induce a failure of DC function in vitro and in vivo, causing suboptimal activation of T cells involved in heterologous immune responses. This effect on T-cell activation can be transferred to uninfected recipients by DCs isolated from infected mice. Significantly, T cells activated by these DCs subsequently lack effector function, as demonstrated by a failure to migrate to lymphoid-organ follicles, resulting in an absence of B-cell responses to heterologous antigens. Fractionation studies show that hemozoin, rather than infected erythrocyte (red blood cell membranes, reproduces the effect of intact infected red blood cells on DCs. Furthermore, hemozoin-containing DCs could be identified in T-cell areas of the spleen in vivo. Conclusion Plasmodium infection inhibits the induction of adaptive immunity to heterologous antigens by modulating DC function, providing a potential explanation for epidemiological studies linking endemic malaria with secondary infections and reduced vaccine efficacy.

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

    Yevgen Ryeznik; Oleksandr Sverdlov; Weng Kee Wong

    2015-01-01

    Response-adaptive randomization designs are becoming increasingly popular in clinical trial practice. In this paper, we present RARtool, a user interface software developed in MATLAB for designing response-adaptive randomized comparative clinical trials with censored time-to-event outcomes. The RARtool software can compute different types of optimal treatment allocation designs, and it can simulate response-adaptive randomization procedures targeting selected optimal allocations. Through simu...

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

    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

  1. Hypoxia Inducible Factor Pathway and Physiological Adaptation: A Cell Survival Pathway?

    Kumar, Hemant; Choi, Dong-Kug

    2015-01-01

    Oxygen homeostasis reflects the constant body requirement to generate energy. Hypoxia (0.1-1% O2), physioxia or physoxia (∼1-13%), and normoxia (∼20%) are terms used to define oxygen concentration in the cellular environment. A decrease in oxygen (hypoxia) or excess oxygen (hyperoxia) could be deleterious for cellular adaptation and survival. Hypoxia can occur under both physiological (e.g., exercise, embryonic development, underwater diving, or high altitude) and pathological conditions (e.g., inflammation, solid tumor formation, lung disease, or myocardial infarction). Hypoxia plays a key role in the pathophysiology of heart disease, cancers, stroke, and other causes of mortality. Hypoxia inducible factor(s) (HIFs) are key oxygen sensors that mediate the ability of the cell to cope with decreased oxygen tension. These transcription factors regulate cellular adaptation to hypoxia and protect cells by responding acutely and inducing production of endogenous metabolites and proteins to promptly regulate metabolic pathways. Here, we review the role of the HIF pathway as a metabolic adaptation pathway and how this pathway plays a role in cell survival. We emphasize the roles of the HIF pathway in physiological adaptation, cell death, pH regulation, and adaptation during exercise. PMID:26491231

  2. The RBE of tritium-beta exposure for the induction of the adaptive response and apoptosis; cellular defense mechanisms against the biological effects of ionizing radiation

    Adaption to radiation is one of a few biological responses that has been demonstrated to occur in mammalian cells exposed to doses of ionizing radiation in the occupational exposure range. The adaptive response has been well characterized in the yeast Saccharomyces cerevisiae, although the doses required to induce the response are higher than in mammalian cells. When yeast cells are primed with sublethal doses of gamma-radiation, they subsequently undergo an adaptive response and develop resistance to radiation, heat the chemical mutagens in a time and dose dependent manner. We have used this model system to assess the relative ability of tritium-beta radiation to induce the adaptive response the examined tritium-induced radiation resistance, thermal tolerance and suppression of mutation. The results show that sublethal priming doses of tritium caused yeast cells to develop resistance to radiation, heat, and a chemical mutagen MNNG. The magnitude and kinetics of the response, per unit dose, were the same for tritium and gamma-radiation. Therefore, the relative biological effectiveness (RBE) of tritium induction of the adaptive response was about 1.0. Apoptosis is a genetically programmed cell death or cell suicide. Cells damaged by radiation can be selectively removed from the population by apoptosis and therefore eliminated as a potential cancer risk to the organism. Since we have previously shown that apoptosis is a sensitive indicator of radiation damage in human lymphocytes exposed to low doses, we have used this endpoint to investigate the potency of tritium-beta radiation. Initially, tritium was compared to X-rays for relative effectiveness at inducing apoptosis. The results showed the lymphocytes irradiated in vitro with X-rays or tritium had similar levels of apoptosis per unit dose. Therefore the relative biology effectiveness of tritium for induction of apoptosis in human lymphocytes was also about 1. In the work presented here, we have demonstrated that

  3. Error Decomposition and Adaptivity for Response Surface Approximations from PDEs with Parametric Uncertainty

    Bryant, C. M.

    2015-01-01

    In this work, we investigate adaptive approaches to control errors in response surface approximations computed from numerical approximations of differential equations with uncertain or random data and coefficients. The adaptivity of the response surface approximation is based on a posteriori error estimation, and the approach relies on the ability to decompose the a posteriori error estimate into contributions from the physical discretization and the approximation in parameter space. Errors are evaluated in terms of linear quantities of interest using adjoint-based methodologies. We demonstrate that a significant reduction in the computational cost required to reach a given error tolerance can be achieved by refining the dominant error contributions rather than uniformly refining both the physical and stochastic discretization. Error decomposition is demonstrated for a two-dimensional flow problem, and adaptive procedures are tested on a convection-diffusion problem with discontinuous parameter dependence and a diffusion problem, where the diffusion coefficient is characterized by a 10-dimensional parameter space.

  4. Chemokine-guided cell positioning in the lymph node orchestrates the generation of adaptive immune responses.

    Lian, Jeffrey; Luster, Andrew D

    2015-10-01

    The generation of adaptive immune responses occurs in the lymph node (LN) and requires that lymphocytes locate and interact with cognate antigen-bearing dendritic cells. This process requires the coordinated movement of both innate and adaptive immune cells, and is orchestrated by the chemokine family of chemotactic cytokines. Upon initiation of inflammation, the LN undergoes dramatic changes that include the marked induction of specific chemokines in distinct regions of the reactive LN. These chemokine rich domains establish LN niches that facilitate the differentiation of CD4+ T cells into effector cell subsets and the rapid activation of memory CD8+ T cells. This review will focus on recent advances highlighting the importance of LN chemokines for shaping adaptive immune responses by controlling immune cell migration, positioning, and interactions in the reactive LN. PMID:26067148

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

    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.

  6. Sliding mode control of wind-induced vibrations using fuzzy sliding surface and gain adaptation

    Thenozhi, Suresh; Yu, Wen

    2016-04-01

    Although fuzzy/adaptive sliding mode control can reduce the chattering problem in structural vibration control applications, they require the equivalent control and the upper bounds of the system uncertainties. In this paper, we used fuzzy logic to approximate the standard sliding surface and designed a dead-zone adaptive law for tuning the switching gain of the sliding mode control. The stability of the proposed controller is established using Lyapunov stability theory. A six-storey building prototype equipped with an active mass damper has been used to demonstrate the effectiveness of the proposed controller towards the wind-induced vibrations.

  7. Human response and adaptation to drought in the arid zone: lessons from southern Africa

    W. R.J. Dean; S. J. Milton; P.J. O'Farrell; P. M.L. Anderson

    2009-01-01

    Human adaptation and response to drought is primarily through evasion or endurance. A review of historical agricultural practices in southern Africa demonstrates evidence of drought evasion response strategies in well-established transhumance routes, where herders move livestock on a seasonal basis in order to exploit resources subject to different climatic regimes. European settlers to the arid regions of South Africa quickly recognised the necessity of these evasion options to survive droug...

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

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

    2015-01-01

    Extensive research has been carried out to decipher the function of the adaptive immune response in atherosclerosis, with the expectation that it will pave the road for the design of immunomodulatory therapies that will prevent or reverse the progression of the disease. All this work has led to the concept that some T- and B-cell subsets are proatherogenic, whereas others are atheroprotective. In addition to the immune response occurring in the spleen and lymph nodes, it has been shown that l...

  9. Adaptive response of single and binary biofilms formed in the presence of benzalkonium chloride

    Pereira, Maria Olívia; Machado, Idalina; Lopes, Susana Patrícia; H. Costa

    2009-01-01

    In actual situations bacteria can live nicely in hostile environments in part due to its ability to live in biofilms and to regulate gene expression as an adaptive response to a variety of stresses. This altered profile, compared to planktonic counterparts, as well as the interactions amongst the several strains existing within the biofilm seems to be responsible for the gradual loss of susceptibility to antimicrobials. The presence of biofilms on the surfaces of various types of medical surf...

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

    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...

  11. Computerized Adaptive Testing: A Comparison of the Nominal Response Model and the Three Parameter Logistic Model.

    DeAyala, R. J.; Koch, William R.

    A nominal response model-based computerized adaptive testing procedure (nominal CAT) was implemented using simulated data. Ability estimates from the nominal CAT were compared to those from a CAT based upon the three-parameter logistic model (3PL CAT). Furthermore, estimates from both CAT procedures were compared with the known true abilities used…

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

    Alleman, Rick J.; Stewart, Luke M; Tsang, Alvin M.; Brown, David A.

    2015-01-01

    Numerous epidemiological studies suggest that individuals who exercise have decreased cardiac morbidity and mortality. Pre-clinical studies in animal models also find clear cardioprotective phenotypes in animals that exercise, specifically characterized by lower myocardial infarction and arrhythmia. Despite the clear benefits, the underlying cellular and molecular mechanisms that are responsible for exercise preconditioning are not fully understood. In particular, the adaptive signaling event...

  13. Adaptive and innate immune reactions regulating mast cell activation: from receptor-mediated signaling to responses

    Tkaczyk, Christine; Jensen, Bettina M; Iwaki, Shoko; Gilfillan, Alasdair M

    2006-01-01

    In this article, we have described studies that have demonstrated that mast cells can be activated as a consequence of adaptive and innate immune reactions and that these responses can be modified by ligands for other receptors expressed on the surface of mast cells. These various stimuli differe...

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

    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…

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

    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...

  16. How Magnetotactic Bacteria Respond to Radiation Induced Stress and Damage: Comparative Genomics Evidences for Evolutionary Adaptation

    Wang, Y.; Pan, Y.

    2015-12-01

    Solar radiation and galactic cosmic radiation is believed to be major restriction factors influencing survival and evolution of life. On planet earth, geomagnetic field along with atmosphere protect living beings from the harmful radiation. During a geomagnetic reversal or excursion, however, the efflux of charged particles on earth surface would increase as the shielding effect of magnetic field decrease. The stratospheric ozone can also be partially stripped away by solar wind when the strength of the field is weak, leading to an increasing ultraviolet radiation penetration to the earth surface. However, studies on the mechanism of radiation induced stress and damage are focused only on bacteria that have no response to magnetic field. This study was motivated by the need to fill the gap upon knowledge of that on magnetic field sensitive microorganism. Magnetotactic bacteria (MTB) are a group of microbes that are able to synthesis intracellular nano-sized magnetic particles (named magnetosomes). These chain-arranged magnetosomes help MTB sense and swim along the magnetic field to find their optimal living environment efficiently. In this paper, in silico prediction of stress and damage repair genes in response to different radiation were carried out on the complete genome of four nonmagnetotactic and four magnetotactic spirilla. In silico analyses of the genomes of magnetic field sensitive and non-sensitive spirilla revealed: 1) all strains contain genes for regulate responses superoxide and peroxide stress, DNA pyrimidine dimer and string breaks; 2) non-magnetotactic spirilla have more genes dealing with oxidative stress, while magnetotactic spirilla may benefit from magnetotaxis by swimming into oxic-anoxic zone away from oxidative stress and direct radiation damage; yet, the lipid hydroperoxide peroxidase gene in MTB may be responsible for possible ROS generated by the membrane enveloped magnetite magnetosome; 3) magnetotactic spirilla possess SOS rec

  17. Interleukin-7 receptor blockade suppresses adaptive and innate inflammatory responses in experimental colitis

    Willis Cynthia R

    2012-10-01

    Full Text Available Abstract Background Interleukin-7 (IL-7 acts primarily on T cells to promote their differentiation, survival, and homeostasis. Under disease conditions, IL-7 mediates inflammation through several mechanisms and cell types. In humans, IL-7 and its receptor (IL-7R are increased in diseases characterized by inflammation such as atherosclerosis, rheumatoid arthritis, psoriasis, multiple sclerosis, and inflammatory bowel disease. In mice, overexpression of IL-7 results in chronic colitis, and T-cell adoptive transfer studies suggest that memory T cells expressing high amounts of IL-7R drive colitis and are maintained and expanded with IL-7. The studies presented here were undertaken to better understand the contribution of IL-7R in inflammatory bowel disease in which colitis was induced with a bacterial trigger rather than with adoptive transfer. Methods We examined the contribution of IL-7R on inflammation and disease development in two models of experimental colitis: Helicobacter bilis (Hb-induced colitis in immune-sufficient Mdr1a−/− mice and in T- and B-cell-deficient Rag2−/− mice. We used pharmacological blockade of IL-7R to understand the mechanisms involved in IL-7R-mediated inflammatory bowel disease by analyzing immune cell profiles, circulating and colon proteins, and colon gene expression. Results Treatment of mice with an anti-IL-7R antibody was effective in reducing colitis in Hb-infected Mdr1a−/− mice by reducing T-cell numbers as well as T-cell function. Down regulation of the innate immune response was also detected in Hb-infected Mdr1a−/− mice treated with an anti-IL-7R antibody. In Rag2−/− mice where colitis was triggered by Hb-infection, treatment with an anti-IL-7R antibody controlled innate inflammatory responses by reducing macrophage and dendritic cell numbers and their activity. Conclusions Results from our studies showed that inhibition of IL-7R successfully ameliorated inflammation and disease development

  18. The colitis-associated transcriptional profile of commensal Bacteroides thetaiotaomicron enhances adaptive immune responses to a bacterial antigen.

    Jonathan J Hansen

    Full Text Available BACKGROUND: Inflammatory bowel diseases (IBD may be caused in part by aberrant immune responses to commensal intestinal microbes including the well-characterized anaerobic gut commensal Bacteroides thetaiotaomicron (B. theta. Healthy, germ-free HLA-B27 transgenic (Tg rats develop chronic colitis when colonized with complex gut commensal bacteria whereas non-transgenic (nTg rats remain disease-free. However, the role of B. theta in causing disease in Tg rats is unknown nor is much known about how gut microbes respond to host inflammation. METHODS: Tg and nTg rats were monoassociated with a human isolate of B. theta. Colonic inflammation was assessed by histologic scoring and tissue pro-inflammatory cytokine measurement. Whole genome transcriptional profiling of B. theta recovered from ceca was performed using custom GeneChips and data analyzed using dChip, Significance Analysis of Microarrays, and Gene Set Enrichment Analysis (GSEA software. Western Blots were used to determine adaptive immune responses to a differentially expressed B. theta gene. RESULTS: B. theta monoassociated Tg rats, but not nTg or germ-free controls, developed chronic colitis. Transcriptional profiles of cecal B. theta were significantly different in Tg vs. nTg rats. GSEA revealed that genes in KEGG canonical pathways involved in bacterial growth and metabolism were downregulated in B. theta from Tg rats with colitis though luminal bacterial concentrations were unaffected. Bacterial genes in the Gene Ontology molecular function "receptor activity", most of which encode nutrient binding proteins, were significantly upregulated in B. theta from Tg rats and include a SusC homolog that induces adaptive immune responses in Tg rats. CONCLUSIONS: B. theta induces colitis in HLA-B27 Tg rats, which is associated with regulation of bacterial genes in metabolic and nutrient binding pathways that may affect host immune responses. These studies of the host-microbial dialogue may lead to

  19. Hyaluronic Acid Inhibits Polycation Induced Cellular Responses

    lalenti, A.; Lanaro, A.; Brignola, G.; Marotta, P; Di Rosa, M.

    1994-01-01

    Positively charged macromolecules cause a variety of pathological events through their electrostatic interaction with anionic sites present on the membrane of target cells. In the present study we have investigated the effect of hyaluronic acid, a negatively charged molecule, on rat paw oedema induced by poly-L-lysine as well as on histamine release from rat mast cells and nitric oxide formation from rabbit aorta, both induced by this polycation. The results indicate that hyaluronic acid is a...

  20. Occupants' adaptive responses and perception of thermal environment in naturally conditioned university classrooms

    Yao, Runming [The School of Construction Management and Engineering, The University of Reading, Whiteknights, PO Box 219, Reading RG6 6AW (United Kingdom); The Faculty of Urban Construction and Environmental Engineering, Chongqing University, Chongqing 400042 (China); Liu, Jing [The School of Construction Management and Engineering, The University of Reading, Whiteknights, PO Box 219, Reading RG6 6AW (United Kingdom); Li, Baizhan [The Faculty of Urban Construction and Environmental Engineering, Chongqing University, Chongqing 400042 (China); Key Laboratory of the Three Gorges Reservoir Region' s Eco-Environment (Ministry of Education), Chongqing University, Chongqing 400042 (China)

    2010-03-15

    A year-long field study of the thermal environment in university classrooms was conducted from March 2005 to May 2006 in Chongqing, China. This paper presents the occupants' thermal sensation votes and discusses the occupants' adaptive response and perception of the thermal environment in a naturally conditioned space. Comparisons between the Actual Mean Vote (AMV) and Predicted Mean Vote (PMV) have been made as well as between the Actual Percentage of Dissatisfied (APD) and Predicted Percentage of Dissatisfied (PPD). The adaptive thermal comfort zone for the naturally conditioned space for Chongqing, which has hot summer and cold winter climatic characteristics, has been proposed based on the field study results. The Chongqing adaptive comfort range is broader than that of the ASHRAE Standard 55-2004 in general, but in the extreme cold and hot months, it is narrower. The thermal conditions in classrooms in Chongqing in summer and winter are severe. Behavioural adaptation such as changing clothing, adjusting indoor air velocity, taking hot/cold drinks, etc., as well as psychological adaptation, has played a role in adapting to the thermal environment. (author)

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

    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. -- Highlights: ► I find the region of stability for a realistic adaptive cruise control system. ► Vehicle response time and explicit delay are included in the analysis. ► Delayed-feedback enlarges the parameter space that gives string stability.

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

    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.

  3. Prediction of nuclear submariner adaptability from autonomic indices and Rorschach Inkblot responses. Interim report

    Weybrew, B.B.; Molish, H.B.

    1986-09-09

    To identify the most valid predictors of submariner adaptability, the authors derived 23 indices from the responses of 170 nuclear submariners to the Rorschach Inkblot Test, 11 measures of Autonomic Nervous System (ANS) reactivity to contrived stress, and five adjustment criteria. Factor analysis of this 39x39 correlation matrix yielded two Rorschach Factors, one of which correlated with three criterion dimensions. Two unique factors were also discovered, one, a structured ANS factor, and the other, a complex criterion scale. Selected Rorschach scores and, to a lesser extent, certain ANS indices emanating from this study, may be usefully-valid predictors of the adaptability of nuclear submariners during long patrols.

  4. Micro-evolutionary responses and adaptive costs of Caenorhabditis elegans populations exposed to environmental stress

    The contemporary evolution of organisms is largely dependent on anthropogenic disturbances. In particular, pollution amplifies the intensity or the quantity of selection pressures on populations. However, these changes may have negative effects on the life, growth and reproduction of individuals, the demographics of the population, and its phenotypic and genetic characteristics over generations. Thus, micro-evolutionary changes are likely to occur in response to selection pressures. These phenomenon lead to collateral damages: adaptive costs. For example, a reduction of genetic diversity in a population entails a decrease in its potential to adapt to other stressors. Populations can be more susceptible to many environmental changes, especially with the increase of human activities. Hence in an ecological risk assessment, studying the mechanisms of action and immediate adverse effects of pollutants on organisms is no longer sufficient. It is also necessary to expand our knowledge on the evolution of populations in polluted environment. In this context, our study aims to determine the micro-evolutionary response of Caenorhabditis elegans populations exposed to environmental stressors, and to measure their costs of adaptation. Populations were experimentally exposed for 22 generations to a high concentration of uranium, sodium chloride or an alternation of both these pollutants. The analysis of phenotypic and genetic changes, observed through measures of life history traits, was accomplished using several quantitative genetics techniques. In particular, we confirmed the genetic differentiation between populations with an increase of resistance in populations exposed to different pollutions. The speed of evolutionary responses depended on the conditions of exposure and their effects on the expression of the genetic structure of traits (e.g. G matrix). Micro-evolutionary changes were linked to costs of adaptation, such as reduced fertility in stressful novel

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

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

    1985-01-01

    Rats fed a reduced sulfur amino acid diet (LTD) or a high-taurine diet (HTD) demonstrate a renal adaptive response. The LTD results in hypotaurinuria and enhanced brush border membrane vesicle (BBMV) accumulation of taurine. The HTD causes hypertaurinuria and reduced BBMV uptake. This adaptation may relate to changes in plasma or renal cortex taurine concentration. Rats were fed a normal-taurine diet (NTD), LTD, or HTD for 14 d or they underwent: (a) 3% beta-alanine for the last 8 d of each d...

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

    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

  7. The significance of dynamical architecture for adaptive responses to mechanical loads during rhythmic behavior.

    Shaw, Kendrick M; Lyttle, David N; Gill, Jeffrey P; Cullins, Miranda J; McManus, Jeffrey M; Lu, Hui; Thomas, Peter J; Chiel, Hillel J

    2015-02-01

    Many behaviors require reliably generating sequences of motor activity while adapting the activity to incoming sensory information. This process has often been conceptually explained as either fully dependent on sensory input (a chain reflex) or fully independent of sensory input (an idealized central pattern generator, or CPG), although the consensus of the field is that most neural pattern generators lie somewhere between these two extremes. Many mathematical models of neural pattern generators use limit cycles to generate the sequence of behaviors, but other models, such as a heteroclinic channel (an attracting chain of saddle points), have been suggested. To explore the range of intermediate behaviors between CPGs and chain reflexes, in this paper we describe a nominal model of swallowing in Aplysia californica. Depending upon the value of a single parameter, the model can transition from a generic limit cycle regime to a heteroclinic regime (where the trajectory slows as it passes near saddle points). We then study the behavior of the system in these two regimes and compare the behavior of the models with behavior recorded in the animal in vivo and in vitro. We show that while both pattern generators can generate similar behavior, the stable heteroclinic channel can better respond to changes in sensory input induced by load, and that the response matches the changes seen when a load is added in vivo. We then show that the underlying stable heteroclinic channel architecture exhibits dramatic slowing of activity when sensory and endogenous input is reduced, and show that similar slowing with removal of proprioception is seen in vitro. Finally, we show that the distributions of burst lengths seen in vivo are better matched by the distribution expected from a system operating in the heteroclinic regime than that expected from a generic limit cycle. These observations suggest that generic limit cycle models may fail to capture key aspects of Aplysia feeding

  8. Stress-induced activation of brown adipose tissue prevents obesity in conditions of low adaptive thermogenesis

    Maria Razzoli; Andrea Frontini; Allison Gurney; Eleonora Mondini; Cankut Cubuk; Katz, Liora S.; Cheryl Cero; Bolan, Patrick J.; Joaquin Dopazo; Antonio Vidal-Puig; Saverio Cinti; Alessandro Bartolomucci

    2016-01-01

    Background: Stress-associated conditions such as psychoemotional reactivity and depression have been paradoxically linked to either weight gain or weight loss. This bi-directional effect of stress is not understood at the functional level. Here we tested the hypothesis that pre-stress level of adaptive thermogenesis and brown adipose tissue (BAT) functions explain the vulnerability or resilience to stress-induced obesity. Methods: We used wt and triple β1,β2,β3−Adrenergic Receptors knockou...

  9. Vagal afferents are essential for maximal resection-induced intestinal adaptive growth in orally fed rats

    Nelson, David W; Liu, Xiaowen; Holst, Jens Juul; Raybould, Helen E; Ney, Denise M

    2006-01-01

    in mucosal mass, protein, DNA, and histology. Both systemic and perivagal capsaicin significantly attenuated by 48-100% resection-induced increases in ileal mucosal mass, protein, and DNA in rats fed orally. Villus height was significantly reduced in resected rats given capsaicin compared with...... of bioactive GLP-2 resulting from resection in orally fed rats. Ablation of spinal/splanchnic innervation by ganglionectomy failed to attenuate resection-induced adaptive growth. In TPN rats, capsaicin did not attenuate resection-induced mucosal growth. We conclude that vagal afferents are not...... essential for maximal resection-induced intestinal growth. Rats received systemic or perivagal capsaicin or ganglionectomy before 70% midjejunoileal resection or transection and were fed orally or by total parenteral nutrition (TPN) for 7 days after surgery. Growth of residual bowel was assessed by changes...

  10. Adaptive responses to osmotic stress in kidney-derived cell lines from Scatophagus argus, a euryhaline fish.

    Gui, Lang; Zhang, Peipei; Liang, Xuemei; Su, Maoliang; Wu, Di; Zhang, Junbin

    2016-06-01

    The euryhaline fish, the spotted scat (Scatophagus argus), is exceptional for its ability to tolerate rapid fluctuations in salinity. To better understand fish osmoregulation and enable more precise analyses of specific features of adaptive responses to the osmotic stress in fish, a S. argus kidney-derived cell line (SK) was developed and subcultured for more than 70 passages. The cells were mostly fibroblast-like, with a normal diploid karyotype (2n=48). A low-osmolarity-adapted SK cell line (SK-la) was induced by growth in a hypotonic solution (150 mOsm). Effects of different osmotic stresses (150, 300 and 450 mOsm) on cell growth, cell morphology, cell volume changes and cell damage in SK, SK-la and CIK (a kidney-derived cell line from freshwater grass carp) cells were studied. These were compared by use of microscopic observation, flow cytometry and a Na-K-ATPase (NKA) assay. SK cells became smaller and grew rapidly in response to hypotonic stress (150 mOsm), and exhibited no visible morphological changes in response to hypertonic stress (450 mOsm). SK-la grew well by moderate hypertonicity (300 mOsm) but depressed in severe hypertonicity (450 mOsm), the number of unhealthy SK-la cells rose as osmolarity increased. In contrast, CIK cells became unhealthy with anisotonic challenge. The NKA activities of SK and CIK cells were assayed after exposure to anisotonic conditions, and rapid decreases were detected immediately except SK cells which were not affected in hypotonicity. Unlike in SK and CIK, an increase following a down-regulation of NKA activity was observed in SK-la cells upon moderate hypertonic stress. These results suggested that SK and SK-la cells had stronger osmoregulatory capacity than CIK cells, and provided new insights on the osmosensing and osmotic adaption in euryhaline fish kidney. PMID:26911257

  11. Effects of Copper-phenanthroline on Pentschlorophenol-induced Adaptation and Cell Death of Escherichia coli

    XUE-WEN ZHANG; RONG-GUI LI; XIN WANG; SHUAN-HU ZHOU

    2007-01-01

    Objective To evaluate the effects of copper-phenanthroline (CuOP) on pentachlorophenol (PCP)-induced adaptation and cell death of Escherichia coli. Methods Bacterial growth and adaptation to PCP were monitored spectrophotometrically at 600 nm. Inactivation of bacterial cells was determined from colony count on agar dishes. Cellular ATP content and accumulation of PCP were assessed by chemiluminescence and HPLC analysis respectively. The formation of PCP-Cu-OP complex was shown by UV-visible spectra. Results Escherichia coli (E. coli) could adapt to PCP, a wood preservative and insecticide used in agriculture. The adaptation of E. coli to PCP prevented its death to the synergistic cytotoxicity of CuOP plus PCP and declined cellular accumulation and uncoupling of oxidative phosphorylafion of PCP. Furthermore, CuOP and PCP neither produced reactive oxygen species (ROS) nor had a synergistic effect on uncoupling of oxidative phosphorylation in E.coli. The synergistic cytotoxicity of CuOP and PCP in E. coli might be due to the formation of lipophillc PCP-Cu-OP complex.Conclsion Our data suggested that adaptation of E. coli to PCP decreased the synergistic effects of CuOP and PCP on prokaryotic cell death due to the formation of lipophilic PCP-Cu-OP complex, but it had no effect on the uncoupling of oxidative phosphorylation and production of reactive oxygen species in E. coli.

  12. The Adaptive Response in p53 Cancer Prone Mice: Loss of heterozygosity and Genomic Instability

    Josee, Lavoie [McMaster Univ., Hamilton, ON (Canada). Medical Physics and Applied Radiation Sciences; Dolling, Jo-Anna [Credit Valley Hospital, Missassauga, ON (Canada); Mitchel, Ron E.J. [Atomic Energy of Canada (AECL), Limited, Chalk River, ON (Canada); Boreham, Douglas R. [McMaster Univ., Hamilton, ON (Canada). Medical Physics and Applied Radiation Sciences

    2004-09-28

    mice, only numerical aberrations were observed in 5 to 20% of the cells. There seem to be an age related increase in numerical aberrations as mice grow old. The results indicate that the presence of a defective copy of the Trp53 gene does not seem to affect spontaneous chromosomal instability or in response to chronic low dose exposure to g-radiation. In previous studies it was speculated that low dose and low dose rate in vivo exposure to g-radiation induces an adaptive response, which reduces the risk of cancer death generated by subsequent DNA damage from either spontaneous or radiation induced events due to enhanced recombinational repair. Induced recombination could result from reversion to homozygosity at Trp53 gene locus (Trp53 +/- to +/+) or loss of heterozygosity in unexposed mice (Trp53 +/- to -/-). This hypothesis was investigated using the quantitative real-time Polymerase Chain Reaction (QRT-PCR) quantification method and the novel Rolling Circle Amplification technique (RCA). For these purposes, spleenocytes and bone marrow cells from all the mice were isolated for cell fixation and DNA extraction. The defective Trp53 allele is generated by integration of a portion of the cloning vector pKONEO DNA into the coding sequence. Therefore, the genotypic changes are monitored based on the detection of the NEO allele and the normal Trp53 allele in the cells. To evaluate loss of heterozygosity at the Trp53 gene locus in a cell, detection of the NEO allele and the normal Trp53 allele using the dual color RCA was utilized. In our hands, this protocol did not give the required sensitivity. The gene signal enumeration was inconsistent and not reproducible. The protocol was modified and could not be optimized. Therefore, the QRT-PCR method was selected to evaluate the loss of heterozygosity with greater sensitivity and efficiency. A set of 4 primers was designed to target the NEO allele and the normal Trp53 allele in a PCR experiment using the LightCycler instrument

  13. Targeted drug induces responses in aggressive lymphomas

    Preliminary results from clinical trials in a subtype of lymphoma show that for a number of patients whose disease was not cured by other treatments, the drug ibrutinib can provide significant anti-cancer responses with modest side effects.

  14. Mutagenic adaptive response to high-LET radiation in human lymphoblastoid cells exposed to X-rays

    The ability of cells to adapt low-dose or low-dose rate radiation is well known. High-LET radiation has unique characteristics, and the data concerning low doses effects and high-LET radiation remain fragmented. In this study, we assessed in vitro the ability of low doses of X-rays to induce an adaptive response (AR) to a subsequent challenging dose of heavy-ion radiation. Lymphoblastoid cells (TK6, AHH-1, NH32) were exposed to priming 0.02-0.1 Gy X-rays, followed 6 h later by challenging 1 Gy heavy-ion radiation (carbon-ion: 20 and 40 keV/μm, neon-ion: 150 keV/μm). Pre-exposure of p53-competent cells resulted in decreased mutation frequencies at hypoxanthine-guanine phosphoribosyl transferase locus and different H2AX phosphorylation kinetics, as compared to cells exposed to challenging radiation alone. This phenomenon did not seem to be linked with cell cycle effects or radiation-induced apoptosis. Taken together, our results suggested the existence of an AR to mutagenic effects of heavy-ion radiation in lymphoblastoid cells and the involvement of double-strand break repair mechanisms.

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

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

    2016-02-01

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

  16. Institutional adaptation to climate change: flood responses at the municipal level in Norway

    The article examines the role institutions play in climate adaptation in Norway. Using examples from two municipalities in the context of institutional responses to floods, we find, first, that the institutional framework for flood management in Norway gives weak incentives for proactive local flood management. Second, when strong local political and economic interests coincide with national level willingness to pay and provide support, measures are often carried out rapidly at the expense of weaker environmental interests. Third, we find that new perspectives on flood management are more apparent at the national than the municipal level, as new perspectives are filtered by local power structures. The findings have important implications for vulnerability and adaptation to climate change in terms of policy options and the local level as the optimal level for adaptation. (author)

  17. p53 dependency of radio-adaptive responses in endogenous spleen colonies and peripheral blood-cell counts in C57BL mice

    Horie, Kiyohito; Kubo, Kihei [Osaka Prefectural Univ., Sakai (Japan). Graduate School of Agriculture and Biological Sciences; Yonezawa, Morio [Osaka Prefectural Univ., Sakai (Japan). Research Inst. for Advanced Science and Technology

    2002-12-01

    Radio-adaptive responses at a conditioning X-ray dose of 0.45 Gy and a challenging dose of 5.0 Gy on hematopoietic indices were studied in C57BL mice with p53 (Trp53) wild, heterogenous and knockout allele. The conditioning irradiation, given 2 weeks before the challenging irradiation, induced radio-adaptive responses observed as a recovery of the peripheral blood-cell counts of leukocytes, thrombocytes and erythrocytes on day 14 after challenging irradiation in C57BL mice of the wild-type p53(+/+). The pre-irradiation also increased the endogenous spleen colonies (endo-CFU-S) on day 12 and the spleen weight on day 14. On the contrary, the knockout p53(-/-) mice gave no such radio-adaptive response. The heterogenous p53(+/-) mice gave an intermediate response. The radio-adaptive response in hematopoiesis at a challenge dose of 5.0 Gy seems to be a p53-dependent phenomenon. The possible role of induction in radioresistance through the reduction of p53-drived apoptosis in hematopoietic stem cells in pre-irradiated mice is discussed. (author)

  18. Conjugative DNA transfer induces the bacterial SOS response and promotes antibiotic resistance development through integron activation.

    Zeynep Baharoglu

    2010-10-01

    Full Text Available Conjugation is one mechanism for intra- and inter-species horizontal gene transfer among bacteria. Conjugative elements have been instrumental in many bacterial species to face the threat of antibiotics, by allowing them to evolve and adapt to these hostile conditions. Conjugative plasmids are transferred to plasmidless recipient cells as single-stranded DNA. We used lacZ and gfp fusions to address whether conjugation induces the SOS response and the integron integrase. The SOS response controls a series of genes responsible for DNA damage repair, which can lead to recombination and mutagenesis. In this manuscript, we show that conjugative transfer of ssDNA induces the bacterial SOS stress response, unless an anti-SOS factor is present to alleviate this response. We also show that integron integrases are up-regulated during this process, resulting in increased cassette rearrangements. Moreover, the data we obtained using broad and narrow host range plasmids strongly suggests that plasmid transfer, even abortive, can trigger chromosomal gene rearrangements and transcriptional switches in the recipient cell. Our results highlight the importance of environments concentrating disparate bacterial communities as reactors for extensive genetic adaptation of bacteria.

  19. Nonlinear self-training adaptive equalization for partial-response systems

    Cherubini, Giovanni

    1994-02-01

    In this paper we discuss a new self-training algorithm for adaptive equalization of multilevel partial-response class-4 (PRIV) systems. Adaptive distributed-arithmetic equalizers are considered, where the process of multiplying the tap signals with tap gains and summing the resulting products is replaced by a procedure involving only table look-up and shift-and-add operations. Classical self-training adaptation schemes for linear adaptive equalizers do not converge if applied to distributed-arithmetic equalizers, because of the inherent nonlinearity of the system during the adaptation process. Here we show that, by adopting a generalized stochastic gradient to adjust the look-up tables, the mean-square error converges to a value which depends on the system parameters. For practical system implementation, a two-step modified algorithm is proposed to closely approach in the steady state the minimum achievable mean-square error. Numerical results are presented for multilevel PRIV systems for high-rate data transmission over twisted-pair cables.

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

    Hurlbert, Margot; Gupta, Joyeeta

    2016-02-01

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

  1. Androgen deprivation modulates the inflammatory response induced by irradiation

    The aim of this study was to determine whether radiation (RT)-induced inflammatory responses and organ damage might be modulated by androgen deprivation therapies. The mRNA and tissue sections obtained from the lungs, intestines and livers of irradiated mice with or without androgen deprivation were analyzed by real-time PCR and histological analysis. Activation of NF-kappa B was examined by measuring nuclear protein levels in the intestine and lung 24 h after irradiation. We also examined the levels of cyclooxygenase-2 (COX-2), TGF-β1 and p-AKT to elucidate the related pathway responsible to irradiation (RT) -induced fibrosis. We found androgen deprivation by castration significantly augmented RT-induced inflammation, associated with the increase NF-κB activation and COX-2 expression. However, administration of flutamide had no obvious effect on the radiation-induced inflammation response in the lung and intestine. These different responses were probably due to the increase of RT-induced NF-κB activation and COX-2 expression by castration or lupron treatment. In addition, our data suggest that TGF-β1 and the induced epithelial-mesenchymal transition (EMT) via the PI3K/Akt signaling pathway may contribute to RT-induced fibrosis. When irradiation was given to patients with total androgen deprivation, the augmenting effects on the RT-induced inflammation and fibrosis should take into consideration for complications associated with radiotherapy

  2. Androgen deprivation modulates the inflammatory response induced by irradiation

    Lin Paul-Yang

    2009-03-01

    Full Text Available Abstract Background The aim of this study was to determine whether radiation (RT-induced inflammatory responses and organ damage might be modulated by androgen deprivation therapies. Methods The mRNA and tissue sections obtained from the lungs, intestines and livers of irradiated mice with or without androgen deprivation were analyzed by real-time PCR and histological analysis. Activation of NF-kappa B was examined by measuring nuclear protein levels in the intestine and lung 24 h after irradiation. We also examined the levels of cyclooxygenase-2 (COX-2, TGF-β1 and p-AKT to elucidate the related pathway responsible to irradiation (RT -induced fibrosis. Results We found androgen deprivation by castration significantly augmented RT-induced inflammation, associated with the increase NF-κB activation and COX-2 expression. However, administration of flutamide had no obvious effect on the radiation-induced inflammation response in the lung and intestine. These different responses were probably due to the increase of RT-induced NF-κB activation and COX-2 expression by castration or lupron treatment. In addition, our data suggest that TGF-β1 and the induced epithelial-mesenchymal transition (EMT via the PI3K/Akt signaling pathway may contribute to RT-induced fibrosis. Conclusion When irradiation was given to patients with total androgen deprivation, the augmenting effects on the RT-induced inflammation and fibrosis should take into consideration for complications associated with radiotherapy.

  3. Cytogenetic radiation adaptive response assessed by metaphase analysis and micronuclei test in human lymphocytes and mouse bone marrow cells

    Radiation adaptive response in human peripheral lymphocytes and mouse bone marrow cells was investigated using both metaphase analysis and micronucleus assay. We assessed the correlation between both tests. Two groups of the human peripheral lymphocytes and mouse bone marrow cells were exposed to low dose (conditioning dose, 0.18 Gy) or high dose (challenging dose, 2 Gy) Υ-rays. The other 4 groups were exposed to low dose followed by high dose after several time intervals (4, 7, 12, and 24 hours, respectively). The frequencies of chromosomal aberrations in metaphase analysis and micronuclei in micronucleus assay were counted. Chromosomal aberrations and micronuclei of preexposed group were lower than those of the group only exposed to high dose radiation. Maximal reduction in frequencies of chromosomal aberrations were observed in the group to which challenging dose was given at 7 hour after a conditioning dose (p<0.001). Metaphase analysis and micronucleus assay revealed very good correlation in both human lymphocytes and mouse bone marrow cells (r=0.98, p<0.001; r=0.99, p=0.001, respectively). Radiation adaptive response could be induced by low dose irradiation in both human lymphocytes and mouse bone marrow cells. There was a significant correlation between metaphase analysis and micronucleus assay

  4. Analysis of time-dependent adaptations in whole-body energy balance in obesity induced by high-fat diet in rats

    Maghdoori Babak; Gaidhu Mandeep P; So Mandy; Ceddia Rolando B

    2011-01-01

    Abstract Background High-fat (HF) diet has been extensively used as a model to study metabolic disorders of human obesity in rodents. However, the adaptive whole-body metabolic responses that drive the development of obesity with chronically feeding a HF diet are not fully understood. Therefore, this study investigated the physiological mechanisms by which whole-body energy balance and substrate partitioning are adjusted in the course of HF diet-induced obesity. Methods Male Wistar rats were ...

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

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

    2016-08-16

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

  6. Adaptive-impulsive synchronization in drive-response networks of continuous systems and its application

    Based on the comparison theorem for the stability of impulsive control system, adaptive-impulsive synchronization in drive-response networks of continuous systems with time-delay and non-time-delay is investigated. And the continuous control input, the simple updated laws and a linear impulsive controller are proposed. Moreover, two numerical examples are presented to verify the effectiveness and correctness of the theorem, using the energy resource system and Lue's system as the nodes of the networks.

  7. Modeling cooperative and autonomous adaptive cruise control dynamic responses using experimental data

    Milanés, Vicente; Shladover, Steven E.

    2014-01-01

    Vehicle longitudinal control systems such as (commercially available) autonomous Adaptive Cruise Control (ACC) and its more sophisticated variant Cooperative ACC (CACC) could potentially have significant impacts on traffic flow. Accurate models of the dynamic responses of both of these systems are needed to produce realistic predictions of their effects on highway capacity and traffic flow dynamics. This paper describes the develop-ment of models of both ACC and CACC control systems that are ...

  8. TCP-ADaLR: TCP with adaptive delay and loss response for broadband GEO satellite networks

    Omueti, Modupe Omogbohun

    2007-01-01

    Transmission Control Protocol (TCP) performance degrades in broadband geostationary satellite networks due to long propagation delays and high bit error rates. In this thesis, we propose TCP with algorithm modifications for adaptive delay and loss response (TCP-ADaLR) to improve TCP performance. TCP-ADaLR incorporates delayed acknowledgement mechanism recommended for Internet hosts. We evaluate and compare the performance of TCP-ADaLR, TCP SACK, and TCP NewReno, with and without delayed ackno...

  9. Adaptive-impulsive synchronization in drive-response networks of continuous systems and its application

    Sun, Mei; Zeng, Changyan; Tao, Yangwei; Tian, Lixin

    2009-08-01

    Based on the comparison theorem for the stability of impulsive control system, adaptive-impulsive synchronization in drive-response networks of continuous systems with time-delay and non-time-delay is investigated. And the continuous control input, the simple updated laws and a linear impulsive controller are proposed. Moreover, two numerical examples are presented to verify the effectiveness and correctness of the theorem, using the energy resource system and Lü's system as the nodes of the networks.

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

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

    2007-01-01

    Abstract Background Introductions of non-native species can significantly alter the selective environment for populations of native species, which can respond through phenotypic plasticity or genetic adaptation. We examined phenotypic and genetic responses of Daphnia populations to recent introductions of non-native fish to assess the relative roles of phenotypic plasticity versus genetic change in causing the observed patterns. The Daphnia community in alpine lakes throughout the Sierra Neva...

  11. Swimming training induces liver mitochondrial adaptations to oxidative stress in rats submitted to repeated exhaustive swimming bouts.

    Frederico D Lima

    Full Text Available BACKGROUND AND AIMS: Although acute exhaustive exercise is known to increase liver reactive oxygen species (ROS production and aerobic training has shown to improve the antioxidant status in the liver, little is known about mitochondria adaptations to aerobic training. The main objective of this study was to investigate the effects of the aerobic training on oxidative stress markers and antioxidant defense in liver mitochondria both after training and in response to three repeated exhaustive swimming bouts. METHODS: Wistar rats were divided into training (n = 14 and control (n = 14 groups. Training group performed a 6-week swimming training protocol. Subsets of training (n = 7 and control (n = 7 rats performed 3 repeated exhaustive swimming bouts with 72 h rest in between. Oxidative stress biomarkers, antioxidant activity, and mitochondria functionality were assessed. RESULTS: Trained group showed increased reduced glutathione (GSH content and reduced/oxidized (GSH/GSSG ratio, higher superoxide dismutase (MnSOD activity, and decreased lipid peroxidation in liver mitochondria. Aerobic training protected against exhaustive swimming ROS production herein characterized by decreased oxidative stress markers, higher antioxidant defenses, and increases in methyl-tetrazolium reduction and membrane potential. Trained group also presented higher time to exhaustion compared to control group. CONCLUSIONS: Swimming training induced positive adaptations in liver mitochondria of rats. Increased antioxidant defense after training coped well with exercise-produced ROS and liver mitochondria were less affected by exhaustive exercise. Therefore, liver mitochondria also adapt to exercise-induced ROS and may play an important role in exercise performance.

  12. Scaling of the Transient Hydroelastic Response and Failure Mechanisms of Self-Adaptive Composite Marine Propellers

    Michael R. Motley

    2012-01-01

    Full Text Available The load dependent deformation responses and complex failure mechanisms of self-adaptive composite propeller blades make the design, analysis, and scaling of these structures nontrivial. The objective of this work is to investigate and verify the dynamic similarity relationships for the hydroelastic response and potential failure mechanisms of self-adaptive composite marine propellers. A fully coupled, three-dimensional boundary element method-finite element method is used to compare the model and full-scale responses of a self-adaptive composite propeller. The effects of spatially varying inflow, transient sheet cavitation, and load-dependent blade deformation are considered. Three types of scaling are discussed: Reynolds scale, Froude scale, and Mach scale. The results show that Mach scaling, which requires the model inflow speed to be the same as the full scale, will lead to discrepancies in the spatial load distributions at low speeds due to differences in Froude number, but the differences between model and full-scale results become negligible at high speeds. Thus, Mach scaling is recommended for a composite marine propeller because it allows the same material and layering scheme to be used between the model and the full scale, leading to similar 3D stress distributions, and hence similar failure mechanisms, between the model and the full scale.

  13. Delayed adaptive immunity is related to higher MMR vaccine-induced antibody titers in children

    Strömbeck, Anna; Lundell, Anna-Carin; Nordström, Inger; Andersson, Kerstin; Adlerberth, Ingegerd; Wold, Agnes E.; Rudin, Anna

    2016-01-01

    There are notable inter-individual variations in vaccine-specific antibody responses in vaccinated children. The aim of our study was to investigate whether early-life environmental factors and adaptive immune maturation prior and close to measles–mumps–rubella (MMR) immunization relate to magnitudes of vaccine-specific antibody titers. In the FARMFLORA birth cohort, including both farming and non-farming families, children were immunized with the MMR vaccine at 18 months of age. MMR vaccine-...

  14. A bacterial carbohydrate links innate and adaptive responses through Toll-like receptor 2

    Wang, Qun; McLoughlin, Rachel M.; Cobb, Brian A; Charrel-Dennis, Marie; Zaleski, Kathleen J.; Golenbock, Douglas; Tzianabos, Arthur O.; Kasper, Dennis L.

    2006-01-01

    Commensalism is critical to a healthy Th1/Th2 cell balance. Polysaccharide A (PSA), which is produced by the intestinal commensal Bacteroides fragilis, activates CD4+ T cells, resulting in a Th1 response correcting the Th2 cell skew of germ-free mice. We identify Toll-like receptors as crucial to the convergence of innate and adaptive responses stimulated by PSA. Optimization of the Th1 cytokine interferon-γ in PSA-stimulated dendritic cell–CD4+ T cell co-cultures depends on both Toll-like re...

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

    Belujon, Pauline; Grace, Anthony A.

    2015-01-01

    Although, historically, the norepinephrine system has attracted the majority of attention in the study of the stress response, the dopamine system has also been consistently implicated. It has long been established that stress plays a crucial role in the pathogenesis of psychiatric disorders. However, the neurobiological mechanisms that mediate the stress response and its effect in psychiatric diseases are not well understood. The dopamine system can play distinct roles in stress and psychiat...

  16. Delay-induced diversity of firing behavior and ordered chaotic firing in adaptive neuronal networks

    In this paper, we study the effect of time delay on the firing behavior and temporal coherence and synchronization in Newman–Watts thermosensitive neuron networks with adaptive coupling. At beginning, the firing exhibit disordered spiking in absence of time delay. As time delay is increased, the neurons exhibit diversity of firing behaviors including bursting with multiple spikes in a burst, spiking, bursting with four, three and two spikes, firing death, and bursting with increasing amplitude. The spiking is the most ordered, exhibiting coherence resonance (CR)-like behavior, and the firing synchronization becomes enhanced with the increase of time delay. As growth rate of coupling strength or network randomness increases, CR-like behavior shifts to smaller time delay and the synchronization of firing increases. These results show that time delay can induce diversity of firing behaviors in adaptive neuronal networks, and can order the chaotic firing by enhancing and optimizing the temporal coherence and enhancing the synchronization of firing. However, the phenomenon of firing death shows that time delay may inhibit the firing of adaptive neuronal networks. These findings provide new insight into the role of time delay in the firing activity of adaptive neuronal networks, and can help to better understand the complex firing phenomena in neural networks.

  17. Characterization of capsaicin induced responses in mice vas deferens

    Sheykhzade, Majid; Gupta, Saurabh; Sørensen, Tinne;

    2011-01-01

    isolated preparations. The present study sets out to study and characterize the capsaicin as well as CGRP-induced responses in isolated mouse vas deferens. The effects of capsaicin and CGRP family of peptides were studied on electrically-induced twitch responses in the absence or presence of transient...... receptor potential cation channel vanilloid subfamily member 1 (TRPV1) antagonist and CGRP receptor antagonists. Twitch responses were attenuated by capsaicin (1nM-30nM) and CGRP family of peptides. The potency order was CGRP>intermedin-long (IMDL)~[Cys(Et)(2,7)]aCGRP~adrenomedullin (AM)>[Cys(ACM)(2,7)]a...

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

    Ruiz-Ramos, Margarita; Ferrise, Roberto

    2016-04-01

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

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

    Ruiz-Ramos, Margarita; Ferrise, Roberto

    2016-04-01

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

  20. Characterization of the Adaptive Response to Trichloroethylene-Mediated Stresses in Ralstonia pickettii PKO1

    Park, Joonhong; Kukor, Jerome J.; Abriola, Linda M.

    2002-01-01

    In Ralstonia pickettii PKO1, a denitrifying toluene oxidizer that carries a toluene-3-monooxygenase (T3MO) pathway, the biodegradation of toluene and trichloroethylene (TCE) by the organism is induced by TCE at high concentrations. In this study, the effect of TCE preexposure was studied in the context of bacterial protective response to TCE-mediated toxicity in this organism. The results of TCE degradation experiments showed that cells induced by TCE at 110 mg/liter were more tolerant to TCE...

  1. Radio-adaptive response using transcriptional status of DNA damage response genes in human peripheral blood lymphocytes

    Venous blood samples were collected from random healthy male individuals with informed consent. Peripheral Blood Mono Nuclear cells (PBMCs) were separated at 1 hour and 5 hours post-irradiation. Dose response was studied using 30 cGy, 60 cGy, 1.0 Gy and 2.0 Gy. For adaptive response study two priming doses (30 cGy and 60 cGy) was used followed by a challenging dose of 2.0 Gy after 4 hours. Total RNA was isolated and cDNA was synthesized. Relative quantitation was performed using a SYBR green based real time PCR with respect to beta actin. The results have shown significant up-regulation of DNA damage response genes like P53, GADD45A, CDKN1A and also in H2B, CTP Synthase and PLK3 at 5 hours post irradiation (P<0.001) as compared to 1 hour. In contrast, the transcriptional expression of ATM, ATR, MDM2, CDK2, cyclin E and cytokine genes remained same at both the time points (1 hour and 5 hours). Few genes like CDKN1A, GADD45A and P53 showed down regulation with 2 Gy at 5 hrs. Transcription profile at priming dose of 0.3 and 0.6 Gy followed by a challenging dose 2.0 Gy was studied. Adaptive response was observed at most of the DNA damage response genes. However, no difference was observed at master regulator ATM and P53. Similarly cytokines and histone modification gene also did not show any change. Detailed results will be discussed during the presentation

  2. IL-6 regulates exercise and training-induced adaptations in subcutaneous adipose tissue in mice

    Brandt, Claus; Jakobsen, Anne Hviid; Hassing, Helle Adser;

    2012-01-01

    Aim: The aim of this study was to test the hypothesis that IL-6 regulates exercise-induced gene responses in subcutaneous adipose tissue in mice. Methods: Four months old male IL-6 whole body knockout (KO) mice and C57B wild-type (WT) mice performed 1h of treadmill exercise, where subcutaneous ad...... regulating exercise and training-induced leptin and PPAR¿ expression in adipose tissue. In addition, while IL-6 is required for TNF-a mRNA reduction in response to acute exercise, IL-6 does not appear to be mandatory for anti-inflammatory effects of exercise training in adipose tissue....

  3. Adaptive microbial population shifts in response to a continuous ethanol blend release increases biodegradation potential

    The fate of fuel releases largely depends on the poorly-understood response in microbial community structure and function. Here, we evaluate the impacts to the microbial community resulting from a pilot-scale continuous release (10 months) of a 10% v:v ethanol solution mixed with benzene and toluene (50 mg/L each). Microbial population shifts were characterized by pyrosequencing-based 16S rRNA analysis and by quantitative PCR targeting Bacteria, Archaea, and functional genes for methanogenesis (mcrA), acetogenesis (fhs) and aerobic degradation of aromatic hydrocarbons (PHE), which could occur in hypoxic micro-environments. The release stimulated microbial growth, increased species richness and diversity, and selected for genotypes involved in fermentative degradation (the relative abundance of mcrA and fhs increased 18- and 6-fold, respectively). The growth of putative hydrocarbon degraders and commensal anaerobes, and increases in microbial diversity and in degradation rates suggest an adaptive response that increases the potential for natural attenuation of ethanol blend releases. -- Highlights: •Pyrosequencing discerned microbial community changes after an ethanol blend release. •Adaptive microbial population shifts that enhance bioremediation were observed. •Hydrocarbon degraders and fermentation syntrophs proliferated. •Surprisingly, both species richness and taxonomic diversity increased. -- Pyrosequencing analysis discerned adaptive microbial population shifts that increase natural attenuation potential of an ethanol-blended fuel release

  4. Cocaine-induced adaptations in cellular redox balance contributes to enduring behavioral plasticity.

    Uys, Joachim D; Knackstedt, Lori; Hurt, Phelipe; Tew, Kenneth D; Manevich, Yefim; Hutchens, Steven; Townsend, Danyelle M; Kalivas, Peter W

    2011-11-01

    Impaired glutamate homeostasis in the nucleus accumbens has been linked to cocaine relapse in animal models, and results in part from cocaine-induced downregulation of the cystine-glutamate exchanger. In addition to regulating extracellular glutamate, the uptake of cystine by the exchanger is a rate-limiting step in the synthesis of glutathione (GSH). GSH is critical for balancing cellular redox in response to oxidative stress. Cocaine administration induces oxidative stress, and we first determined if downregulated cystine-glutamate exchange alters redox homeostasis in rats withdrawn from daily cocaine injections and then challenged with acute cocaine. Among the daily cocaine-induced changes in redox homeostasis were an increase in protein S-glutathionylation and a decrease in expression of GSH-S-transferase pi (GSTpi). To mimic reduced GSTpi, a genetic mouse model of GSTpi deletion or pharmacological inhibition of GSTpi by administering ketoprofen during daily cocaine administration was used. The capacity of cocaine to induce conditioned place preference or locomotor sensitization was augmented, indicating that reducing GSTpi may contribute to cocaine-induced behavioral neuroplasticity. Conversely, an acute cocaine challenge after withdrawal from daily cocaine elicited a marked increase in accumbens GSTpi, and the expression of behavioral sensitization to a cocaine challenge injection was inhibited by ketoprofen pretreatment; supporting a protective effect by the acute cocaine-induced rise in GSTpi. Together, these data indicate that cocaine-induced oxidative stress induces changes in GSTpi that contribute to cocaine-induced behavioral plasticity. PMID:21796101

  5. Can We Translate Vitamin D Immunomodulating Effect on Innate and Adaptive Immunity to Vaccine Response?

    Pierre Olivier Lang

    2015-03-01

    Full Text Available Vitamin D (VitD, which is well known for its classic role in the maintenance of bone mineral density, has now become increasingly studied for its extra-skeletal roles. It has an important influence on the body’s immune system and modulates both innate and adaptive immunity and regulates the inflammatory cascade. In this review our aim was to describe how VitD might influence immune responsiveness and its potential modulating role in vaccine immunogenicity. In the first instance, we consider the literature that may provide molecular and genetic support to the idea that VitD status may be related to innate and/or adaptive immune response with a particular focus on vaccine immunogenicity and then discuss observational studies and controlled trials of VitD supplementation conducted in humans. Finally, we conclude with some knowledge gaps surrounding VitD and vaccine response, and that it is still premature to recommend “booster” of VitD at vaccination time to enhance vaccine response.

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

    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.

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

    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. PMID:26555860

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

    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.

  9. Responsiveness, adaptability, transformability: the new quality requirements of the built environment

    Filippo Angelucci

    2013-05-01

    Full Text Available In light of the recently emerged situation of resource shortage, a reasonably 'sustainable' recovery process and qualification of the built environment can be realized at various scales and levels of intervention, only through returning to the project’s inter-systemic and performance based concept. In this sense, a significant contribution can be made by the technological planning field, from defining the resilience of a complex socio-ecological system, interpreted as «dynamic capacity of adaptation and reorganization as a result of a change», through interpreting the attitudes of responsiveness, adaptability and transformability as necessary requirements to be able to achieve the integrated quality of settlement systems.

  10. Implementation of high-speed–low-power adaptive finite impulse response filter with novel architecture

    Manish Jaiswal

    2015-03-01

    Full Text Available An energy efficient high-speed adaptive finite impulse response filter with novel architecture is developed. Synthesis results along with novel architecture on different complementary metal–oxide semiconductor (CMOS families are presented. Analysis is performed using Artix-7, Spartan-6 and Virtex-4 for most popular adaptive least mean square filter for different orders such as N = 8, 16, 32. The presented work is done using MATLAB (2013b and Xilinx (14.2. From the synthesis results, it can be found that CMOS (28 nm achieves the lowest power and critical path delay compared to others, and thus proves its efficiency in terms of energy. Different parameters are considered such as look up tables and input–output blocks, along with their optimised results.

  11. Nanomaterial Induced Immune Responses and Cytotoxicity.

    Ali, Ashraf; Suhail, Mohd; Mathew, Shilu; Shah, Muhammad Ali; Harakeh, Steve M; Ahmad, Sultan; Kazmi, Zulqarnain; Alhamdan, Mohammed Abdul Rahman; Chaudhary, Adeel; Damanhouri, Ghazi Abdullah; Qadri, Ishtiaq

    2016-01-01

    Nanomaterials are utilized in a wide array of end user products such as pharmaceuticals, electronics, clothes and cosmetic products. Due to its size (< 100 nm), nanoparticles have the propensity to enter through the airway and skin, making its path perilous with the potential to cause damages of varying severity. Once within the body, these particles have unconstrained access to different tissues and organs including the brain, liver, and kidney. As a result, nanomaterials may cause the perturbation of the immune system eliciting an inflammatory response and cytotoxicity. This potential role is dependent on many factors such as the characteristics of the nanomaterials, presence or absence of diseases, and genetic predisposition. Cobalt and nickel nanoparticles, for example, were shown to have inflammogenic properties, while silver nanoparticles were shown to reduce allergic inflammation. Just as asbestos fibers, carbon nanotubes were shown to cause lungs damage. Some nanomaterials were shown, based on animal studies, to result in cell damage, leading to the formation of pre-cancerous lesions. This review highlights the impact of nanomaterials on immune system and its effect on human health with toxicity consideration. It recommends the development of suitable animal models to study the toxicity and bio-clearance of nanomaterials and propose safety guidelines. PMID:27398432

  12. Are grazer-induced adaptations of bacterial abundance and morphology timedependent?

    Gianluca CORNO

    2006-02-01

    Full Text Available Predation by protists is a well known force that shapes bacterial communities and can lead to filamentous forms and aggregations of large cell clusters. These classic resistance strategies were observed as a direct consequence of predation by heteroand mixotrophic flagellates (the main group of bacteria predators in water on natural assemblages of bacteria and on single plastic strains. Recently it was shown that a long time exposure (about 30 days of a bacterial strain, characterized by high degree of phenotypic plasticity, to flagellates, without direct predation, enhanced the formation of resistant forms (filaments in a continuous culture system. Target prey populations and predators were separated by a dialysis membrane. Moreover, the positive impact on bacterial growth, due to the chemical excretes released by flagellates was demonstrated for exudates of photosynthetic activity. The same positive impact may also be seen in response to exudates related to grazing. In this study, two short-term experiments (<100 hours were conducted to test for modifications in the morphology and productivity of three different bacterial strains that were induced by the presence of active predators, but without direct predation. The growth and morphological distribution of each of the selected strains was tested separately using batch cultures. Cultures were either enriched with carbon in the presence or absence of flagellate predators, or included pre-filtered exudates from flagellate activity. In a second experiment, bottles were provided with a central dialysis bag that contained active flagellates, and were inoculated with the selected bacterial strains. In this way, bacteria were exposed to the presence of predators without direct predation. The bacterial strains used in this experience were characterised by a high degree of phenotypic plasticity and exhibited different successful strategies of resistance against grazing. The flagellates selected as

  13. Ozone-Induced Hypertussive Responses in Rabbits and Guinea Pigs.

    Clay, Emlyn; Patacchini, Riccardo; Trevisani, Marcello; Preti, Delia; Branà, Maria Pia; Spina, Domenico; Page, Clive

    2016-04-01

    Cough remains a major unmet clinical need, and preclinical animal models are not predictive for new antitussive agents. We have investigated the mechanisms and pharmacological sensitivity of ozone-induced hypertussive responses in rabbits and guinea pigs. Ozone induced a significant increase in cough frequency and a decrease in time to first cough to inhaled citric acid in both conscious guinea pigs and rabbits. This response was inhibited by the established antitussive drugs codeine and levodropropizine. In contrast to the guinea pig, hypertussive responses in the rabbit were not inhibited by bronchodilator drugs (β2 agonists or muscarinic receptor antagonists), suggesting that the observed hypertussive state was not secondary to bronchoconstriction in this species. The ozone-induced hypertussive response in the rabbit was inhibited by chronic pretreatment with capsaicin, suggestive of a sensitization of airway sensory nerve fibers. However, we could find no evidence for a role of TRPA1 in this response, suggesting that ozone was not sensitizing airway sensory nerves via activation of this receptor. Whereas the ozone-induced hypertussive response was accompanied by a significant influx of neutrophils into the airway, the hypertussive response was not inhibited by the anti-inflammatory phosphodiesterase 4 inhibitor roflumilast at a dose that clearly exhibited anti-inflammatory activity. In summary, our results suggest that ozone-induced hypertussive responses to citric acid may provide a useful model for the investigation of novel drugs for the treatment of cough, but some important differences were noted between the two species with respect to sensitivity to bronchodilator drugs. PMID:26837703

  14. Evidence for an adaptive response to radiation damage in plant cells conditioned with X-rays or incorporated tritium

    Allium cepa root-tips were first exposed to low 'conditioning' doses of ionizing radiation: to X-rays (0.06 or 0.26 Gy) or incorporated tritium (1.8 x 104 or 7.2 x 104 Bq/ml; specific activity: 740.0 GBq/mmol) and subsequently given a 'challenge' dose of 1.5 Gy of X-rays. Reduction in X-ray-induced chromosomal damage was brought about by prior exposure to 0.26 Gy of X-rays, while cells receiving the lower conditioning dose (0.06 Gy of X-rays) did not show significant reduction. In cells grown in the presence of [3H]TdR, the adaptive response was evident after both doses given. Results are essentially in agreement with those published by Wolff's group for human lymphocytes in showing that plant cells in vivo can become 'adapted' by exposure to low-level irradiation so that they become more resistant to the clastogenic effects of X-rays delivered subsequently. (author)

  15. Divergent adaptive and innate immunological responses are observed in humans following blunt trauma

    Lentsch Alex B

    2010-01-01

    Full Text Available Abstract Background The immune response to trauma has traditionally been modeled to consist of the systemic inflammatory response syndrome (SIRS followed by the compensatory anti-inflammatory response syndrome (CARS. We investigated these responses in a homogenous cohort of male, severe blunt trauma patients admitted to a University Hospital surgical intensive care unit (SICU. After obtaining consent, peripheral blood was drawn up to 96 hours following injury. The enumeration and functionality of both myeloid and lymphocyte cell populations were determined. Results Neutrophil numbers were observed to be elevated in trauma patients as compared to healthy controls. Further, neutrophils isolated from trauma patients had increased raft formation and phospho-Akt. Consistent with this, the neutrophils had increased oxidative burst compared to healthy controls. In direct contrast, blood from trauma patients contained decreased naïve T cell numbers. Upon activation with a T cell specific mitogen, trauma patient T cells produced less IFN-gamma as compared to those from healthy controls. Consistent with these results, upon activation, trauma patient T cells were observed to have decreased T cell receptor mediated signaling. Conclusions These results suggest that following trauma, there are concurrent and divergent immunological responses. These consist of a hyper-inflammatory response by the innate arm of the immune system concurrent with a hypo-inflammatory response by the adaptive arm.

  16. Learning theories reveal loss of pancreatic electrical connectivity in diabetes as an adaptive response

    Goel, Pranay

    2013-01-01

    Cells of almost all solid tissues are connected with gap junctions which permit the direct transfer of ions and small molecules, integral to regulating coordinated function in the tissue. The pancreatic islets of Langerhans are responsible for secreting the hormone insulin in response to glucose stimulation. Gap junctions are the only electrical contacts between the beta-cells in the tissue of these excitable islets. It is generally believed that they are responsible for synchrony of the membrane voltage oscillations among beta-cells, and thereby pulsatility of insulin secretion. Most attempts to understand connectivity in islets are often interpreted, bottom-up, in terms of measurements of gap junctional conductance. This does not, however explain systematic changes, such as a diminished junctional conductance in type 2 diabetes. We attempt to address this deficit via the model presented here, which is a learning theory of gap junctional adaptation derived with analogy to neural systems. Here, gap junctions ...

  17. Biologically Inspired Design Principles for Scalable, Robust, Adaptive, Decentralized Search and Automated Response (RADAR)

    Moses, Melanie

    2010-01-01

    Distributed search problems are ubiquitous in Artificial Life (ALife). Many distributed search problems require identifying a rare and previously unseen event and producing a rapid response. This challenge amounts to finding and removing an unknown needle in a very large haystack. Traditional computational search models are unlikely to find, nonetheless, appropriately respond to, novel events, particularly given data distributed across multiple platforms in a variety of formats and sources with variable and unknown reliability. Biological systems have evolved solutions to distributed search and response under uncertainty. Immune systems and ant colonies efficiently scale up massively parallel search with automated response in highly dynamic environments, and both do so using distributed coordination without centralized control. These properties are relevant to ALife, where distributed, autonomous, robust and adaptive control is needed to design robot swarms, mobile computing networks, computer security system...

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

    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

  19. Adaptive response of human lymphocytes exposed to low dose of gamma radiation

    The main goals of the present work are: (a) to study the induction of radioadaptive response in human lymphocytes and to establish the experimental conditions for which this response is optimized; (b) to evidence the relationship between the observed effect and the phase of the cell cycle. The radioadaptive response was assessed by the chromosome aberration test. Human lymphocytes were pre-irradiated with 1 cGy or 5 cGy (1 cGy/min) either before stimulation by phytohemagglutinin (for G0 study) or 20 h after stimulation by PHA (for G1), followed by 1 Gy (1 Gy/min) irradiation 46 h after stimulation by PHA. After the irradiation with high dose, the cultures were kept for 2 h in the incubator and then the colcemide was added to the cultures (at 48 h). The cultures incubated 2 h with colcemide were exposed to potassium chloride and then fixed in acetic acid:methanol (1:3). The fixed cells were dropped onto wet glass slides and dried. Slides were stained with Giemsa for the scoring of chromatid aberrations. Fifty cells were scored from replicate cultures for each treatment. We considered only those metaphases that contained 46 chromosomes. The following results have been obtained: - the human lymphocytes pre-exposed in G0 to 1 cGy and 5 cGy exhibit an adaptive response to the subsequent exposure at 1 Gy; - the evolution of cytogenetic parameter chromosomal aberration in the case of lymphocytes pre-irradiated in G1 is similar with that obtained for lymphocytes pre-irradiated in G0; - the maximal expression of adaptive response was determined by delivering 1 cGy; - the time interval between both types of successive irradiations is optimal for the induction of the repair processes; - the lymphocytes respond adaptively at low doses of irradiation, regardless the stimulation by phytohemagglutinin. These results are in agreement with other reported data which prove that human lymphocytes are able to adapt to low dose irradiation so that they undergo less damages at the

  20. Inhibition of adaptive immune responses leads to a fatal clinical outcome in SIV-infected pigtailed macaques but not vervet African green monkeys.

    Jörn E Schmitz

    2009-12-01

    Full Text Available African green monkeys (AGM and other natural hosts for simian immunodeficiency virus (SIV do not develop an AIDS-like disease following SIV infection. To evaluate differences in the role of SIV-specific adaptive immune responses between natural and nonnatural hosts, we used SIV(agmVer90 to infect vervet AGM and pigtailed macaques (PTM. This infection results in robust viral replication in both vervet AGM and pigtailed macaques (PTM but only induces AIDS in the latter species. We delayed the development of adaptive immune responses through combined administration of anti-CD8 and anti-CD20 lymphocyte-depleting antibodies during primary infection of PTM (n = 4 and AGM (n = 4, and compared these animals to historical controls infected with the same virus. Lymphocyte depletion resulted in a 1-log increase in primary viremia and a 4-log increase in post-acute viremia in PTM. Three of the four PTM had to be euthanized within 6 weeks of inoculation due to massive CMV reactivation and disease. In contrast, all four lymphocyte-depleted AGM remained healthy. The lymphocyte-depleted AGM showed only a trend toward a prolongation in peak viremia but the groups were indistinguishable during chronic infection. These data show that adaptive immune responses are critical for controlling disease progression in pathogenic SIV infection in PTM. However, the maintenance of a disease-free course of SIV infection in AGM likely depends on a number of mechanisms including non-adaptive immune mechanisms.

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

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

    2016-01-01

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

  2. Skeletal adaptation to intramedullary pressure-induced interstitial fluid flow is enhanced in mice subjected to targeted osteocyte ablation.

    Kwon, Ronald Y; Meays, Diana R; Meilan, Alexander S; Jones, Jeremiah; Miramontes, Rosa; Kardos, Natalie; Yeh, Jiunn-Chern; Frangos, John A

    2012-01-01

    Interstitial fluid flow (IFF) is a potent regulatory signal in bone. During mechanical loading, IFF is generated through two distinct mechanisms that result in spatially distinct flow profiles: poroelastic interactions within the lacunar-canalicular system, and intramedullary pressurization. While the former generates IFF primarily within the lacunar-canalicular network, the latter generates significant flow at the endosteal surface as well as within the tissue. This gives rise to the intriguing possibility that loading-induced IFF may differentially activate osteocytes or surface-residing cells depending on the generating mechanism, and that sensation of IFF generated via intramedullary pressurization may be mediated by a non-osteocytic bone cell population. To begin to explore this possibility, we used the Dmp1-HBEGF inducible osteocyte ablation mouse model and a microfluidic system for modulating intramedullary pressure (ImP) to assess whether structural adaptation to ImP-driven IFF is altered by partial osteocyte depletion. Canalicular convective velocities during pressurization were estimated through the use of fluorescence recovery after photobleaching and computational modeling. Following osteocyte ablation, transgenic mice exhibited severe losses in bone structure and altered responses to hindlimb suspension in a compartment-specific manner. In pressure-loaded limbs, transgenic mice displayed similar or significantly enhanced structural adaptation to Imp-driven IFF, particularly in the trabecular compartment, despite up to ∼50% of trabecular lacunae being uninhabited following ablation. Interestingly, regression analysis revealed relative gains in bone structure in pressure-loaded limbs were correlated with reductions in bone structure in unpressurized control limbs, suggesting that adaptation to ImP-driven IFF was potentiated by increases in osteoclastic activity and/or reductions in osteoblastic activity incurred independently of pressure loading

  3. Skeletal adaptation to intramedullary pressure-induced interstitial fluid flow is enhanced in mice subjected to targeted osteocyte ablation.

    Ronald Y Kwon

    Full Text Available Interstitial fluid flow (IFF is a potent regulatory signal in bone. During mechanical loading, IFF is generated through two distinct mechanisms that result in spatially distinct flow profiles: poroelastic interactions within the lacunar-canalicular system, and intramedullary pressurization. While the former generates IFF primarily within the lacunar-canalicular network, the latter generates significant flow at the endosteal surface as well as within the tissue. This gives rise to the intriguing possibility that loading-induced IFF may differentially activate osteocytes or surface-residing cells depending on the generating mechanism, and that sensation of IFF generated via intramedullary pressurization may be mediated by a non-osteocytic bone cell population. To begin to explore this possibility, we used the Dmp1-HBEGF inducible osteocyte ablation mouse model and a microfluidic system for modulating intramedullary pressure (ImP to assess whether structural adaptation to ImP-driven IFF is altered by partial osteocyte depletion. Canalicular convective velocities during pressurization were estimated through the use of fluorescence recovery after photobleaching and computational modeling. Following osteocyte ablation, transgenic mice exhibited severe losses in bone structure and altered responses to hindlimb suspension in a compartment-specific manner. In pressure-loaded limbs, transgenic mice displayed similar or significantly enhanced structural adaptation to Imp-driven IFF, particularly in the trabecular compartment, despite up to ∼50% of trabecular lacunae being uninhabited following ablation. Interestingly, regression analysis revealed relative gains in bone structure in pressure-loaded limbs were correlated with reductions in bone structure in unpressurized control limbs, suggesting that adaptation to ImP-driven IFF was potentiated by increases in osteoclastic activity and/or reductions in osteoblastic activity incurred independently of

  4. Unfolded protein response is required for Aspergillus oryzae growth under conditions inducing secretory hydrolytic enzyme production.

    Tanaka, Mizuki; Shintani, Takahiro; Gomi, Katsuya

    2015-12-01

    Unfolded protein response (UPR) is an intracellular signaling pathway for adaptation to endoplasmic reticulum (ER) stress. In yeast UPR, Ire1 cleaves the unconventional intron of HAC1 mRNA, and the functional Hac1 protein translated from the spliced HAC1 mRNA induces the expression of ER chaperone genes and ER-associated degradation genes for the refolding or degradation of unfolded proteins. In this study, we constructed an ireA (IRE1 ortholog) conditionally expressing strain of Aspergillus oryzae, a filamentous fungus producing a large amount of amylolytic enzymes, and examined the contribution of UPR to ER stress adaptation under physiological conditions. Repression of ireA completely blocked A. oryzae growth under conditions inducing the production of hydrolytic enzymes, such as amylases and proteases. This growth defect was restored by the introduction of unconventional intronless hacA (hacA-i). Furthermore, UPR was observed to be induced by amylolytic gene expression, and the disruption of the transcriptional activator for amylolytic genes resulted in partial growth restoration of the ireA-repressing strain. In addition, a homokaryotic ireA disruption mutant was successfully generated using the strain harboring hacA-i as a parental host. These results indicated that UPR is required for A. oryzae growth to alleviate ER stress induced by excessive production of hydrolytic enzymes. PMID:26496881

  5. Bronchial, alveolar, and vascular-induced anaphylaxis and irritant-induced cardiovascular and pulmonary responses.

    Yeates, D B; Mussatto, D J; Hameister, W M; Daza, A.; Chandra, T; Wong, L B

    2001-01-01

    We examine the respiratory, bronchomotor, cardiac, and vascular responses to histamine and ragweed allergen delivered to the bronchi or alveoli compartments and the potential role of sensory nerves and reflexes mediating the histamine-induced responses. The masses of aerosols deposited in the bronchi and alveoli were quantitated using radioaerosol techniques. Activation of sensory nerves and/or histamine-induced mediator release were characterized by depositing nedocromil sodium aerosol prior...

  6. PGC-1alpha in exercise- and exercise training-induced metabolic adaptations

    Jørgensen, Stine Ringholm

    training, respectively, in WT mice while there was no change in PGC-1α KO mice. Furthermore, fasting increased G6Pase and PEPCK mRNA content in both WT and PGC-1α KO mice. This implies that exercise- and exercise training-induced improvements in hepatic oxidative capacity, but not regulation......The aim of the present thesis was to investigate the hypotheses that 1) bed rest reduces metabolic and angiogenic proteins and changes microRNA (miRNA) content as well as alters exercise-induced mRNA responses in human skeletal muscle, 2) Peroxisome proliferator-activated receptor-γ coactivator...... (PGC)-1α is required for exercise-, exercise training- and fasting-induced mRNA and protein responses, respectively, of metabolic, angiogenic and gluconeogenic proteins in liver and adipose tissue in mice, 3) PGC-1α is required for both exercise training and resveratrol mediated prevention of age...

  7. Genotypic variation in growth and physiological response to drought stress and re-watering reveals the critical role of recovery in drought adaptation in maize seedlings

    Daoqian eChen

    2016-01-01

    Full Text Available Non-irrigated crops in temperate climates and irrigated crops in arid climates are subjected to continuous cycles of water stress and re-watering. Thus, fast and efficient recovery from water stress may be among the key determinants of plant drought adaptation. The present study was designed to comparatively analyze the roles of drought resistance and drought recovery in drought adaptation and to investigate the physiological basis of genotypic variation in drought adaptation in maize (Zea mays seedlings. As the seedlings behavior in growth associate with yield under drought, it could partly reflect the potential of drought adaptability. Growth and physiological responses to progressive drought stress and recovery were observed in seedlings of ten maize lines. The results showed that drought adaptability is closely related to drought recovery (r = 0.714**, but not to drought resistance (r = 0.332. Drought induced decreases in leaf water content, water potential, osmotic potential, gas exchange parameters, chlorophyll content, Fv/Fm and nitrogen content, and increased H2O2 accumulation and lipid peroxidation. After recovery, most of these physiological parameters rapidly returned to normal levels. The physiological responses varied between lines. Further correlation analysis indicated that the physiological bases of drought resistance and drought recovery are definitely different, and that maintaining higher chlorophyll content (r = 0.874*** and Fv/Fm (r = 0.626* under drought stress contributes to drought recovery. Our results suggest that both drought resistance and recovery are key determinants of plant drought adaptation, and that drought recovery may play a more important role than previously thought. In addition, leaf water potential, chlorophyll content and Fv/Fm could be used as efficient reference indicators in the selection of drought-adaptive genotypes.

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

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

    2015-01-01

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

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

    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.

  10. Cellular Responses to Cisplatin-Induced DNA Damage

    Alakananda Basu

    2010-01-01

    Full Text Available Cisplatin is one of the most effective anticancer agents widely used in the treatment of solid tumors. It is generally considered as a cytotoxic drug which kills cancer cells by damaging DNA and inhibiting DNA synthesis. How cells respond to cisplatin-induced DNA damage plays a critical role in deciding cisplatin sensitivity. Cisplatin-induced DNA damage activates various signaling pathways to prevent or promote cell death. This paper summarizes our current understandings regarding the mechanisms by which cisplatin induces cell death and the bases of cisplatin resistance. We have discussed various steps, including the entry of cisplatin inside cells, DNA repair, drug detoxification, DNA damage response, and regulation of cisplatin-induced apoptosis by protein kinases. An understanding of how various signaling pathways regulate cisplatin-induced cell death should aid in the development of more effective therapeutic strategies for the treatment of cancer.

  11. Force-induced bone growth and adaptation: A system theoretical approach to understanding bone mechanotransduction

    The modeling, analysis, and design of treatment therapies for bone disorders based on the paradigm of force-induced bone growth and adaptation is a challenging task. Mathematical models provide, in comparison to clinical, medical and biological approaches an structured alternative framework to understand the concurrent effects of the multiple factors involved in bone remodeling. By now, there are few mathematical models describing the appearing complex interactions. However, the resulting models are complex and difficult to analyze, due to the strong nonlinearities appearing in the equations, the wide range of variability of the states, and the uncertainties in parameters. In this work, we focus on analyzing the effects of changes in model structure and parameters/inputs variations on the overall steady state behavior using systems theoretical methods. Based on an briefly reviewed existing model that describes force-induced bone adaptation, the main objective of this work is to analyze the stationary behavior and to identify plausible treatment targets for remodeling related bone disorders. Identifying plausible targets can help in the development of optimal treatments combining both physical activity and drug-medication. Such treatments help to improve/maintain/restore bone strength, which deteriorates under bone disorder conditions, such as estrogen deficiency.

  12. Climate adaptation in NVE's areas of responsibility - Strategy 2010 - 2014; Klimatilpasning innen NVEs ansvarsomraader - Strategi 2010 - 2014

    Hamarsland, Arne T. (ed.)

    2010-09-15

    NVE has developed a comprehensive climate change strategies within their areas of responsibility. There is a systematic review of how a future climate change will affect NVE management areas; how to meet challenges, vulnerabilities, opportunities and proposals for adaptation measures. Climate adaptation is a dynamic process. It is therefore necessary to follow up the work continuously and correct direction at regular intervals. Climate change adaptation strategy of adaptation measures is a foundation and a direction sensor in NVE's business planning. (AG)

  13. Impaired vascular responses to relaxin in diet-induced overweight female rats.

    van Drongelen, Joris; van Koppen, Arianne; Pertijs, Jeanne; Gooi, Jonathan H; Parry, Laura J; Sweep, Fred C G J; Lotgering, Frederik K; Smits, Paul; Spaanderman, Marc E A

    2012-03-01

    Relaxin mediates renal and mesenteric vascular adaptations to pregnancy by increasing endothelium-dependent vasodilation and compliance and decreasing myogenic reactivity. Diet-induced overweight and obesity are associated with impaired endothelial dysfunction and vascular remodeling leading to a reduction in arterial diameter. In this study, we tested the hypothesis that local vascular responses to relaxin are impaired in diet-induced overweight female rats on a high-fat cafeteria-style diet for 9 wk. Rats were chronically infused with either relaxin or placebo for 5 days, and vascular responses were measured in isolated mesenteric arteries and the perfused kidney. Diet-induced overweight significantly increased sensitivity to phenylephrine (by 17%) and vessel wall thickness, and reduced renal perfusion flow (RPFF; by 16%), but did not affect flow-mediated vasodilation, myogenic reactivity, and vascular compliance. In the normal weight rats, relaxin treatment significantly enhanced flow-mediated vasodilation (2.67-fold), decreased myogenic reactivity, and reduced sensitivity to phenylephrine (by 28%), but had no effect on compliance or RPFF. NO blockade by l-NAME diminished most relaxin-mediated effects. In diet-induced overweight rats, the vasodilator effects of relaxin were markedly reduced for flow-mediated vasodilation, sensitivity to phenylephrine, and myogenic response compared with the normal diet rats, mostly persistent under l-NAME. Our data demonstrate that some of the vasodilator responses to in vivo relaxin administration are impaired in isolated mesenteric arteries and the perfused kidney in diet-induced overweight female rats. This does not result from a decrease in Rxfp1 (relaxin family peptide receptor) expression but is likely to result from downstream disruption to endothelial-dependent mechanisms in diet-induced overweight animals. PMID:22174401

  14. The Business Case for Responsible Corporate Adaptation: Strengthening Private Sector and Community Resilience

    Frey, Bernhard; Gardaz, Adrienne; Karbass, Lila;

    play in supporting social, ecological and economic resilience to climate change impacts and a responsibility to protect their value chain and serve their customers. To date, climate action in the private sector has been largely focused on reducing greenhouse gas emissions within corporate operations...... and associated with purchased energy, and through the development and deployment of low-carbon and resource-efficient technologies and services. While carbon management remains a crucial pillar of corporate climate action, implementing measures to anticipate for and adapt to climate impacts must also...

  15. Clock recovering characteristics of adaptive finite-impulse-response filters in digital coherent optical receivers.

    Kikuchi, Kazuro

    2011-03-14

    We analyze the clock-recovery process based on adaptive finite-impulse-response (FIR) filtering in digital coherent optical receivers. When the clock frequency is synchronized between the transmitter and the receiver, only five taps in half-symbol-spaced FIR filters can adjust the sampling phase of analog-to-digital conversion optimally, enabling bit-error rate performance independent of the initial sampling phase. Even if the clock frequency is not synchronized between them, the clock-frequency misalignment can be adjusted within an appropriate block interval; thus, we can achieve an asynchronous clock mode of operation of digital coherent receivers with block processing of the symbol sequence. PMID:21445201

  16. A response surface method based on support vector machines trained with an adaptive experimental design

    Structural reliability is nowadays largely used to take into account uncertainties related to the input data of a structural model. When the structural response becomes complex, the mechanical model is designed within the framework of the finite element method and therefore, the computational time required by a coupling reliability/finite element analysis is driven by the number of performance function calls. This paper aims at proposing an original approach to approximate implicit limit state functions. It is based on the support vector machine used in regression trained with an adaptive experimental design. Several numerical examples proposed in the published literature are considered to assess the efficiency of the proposed method. (authors)

  17. A Comparison of the Adaptive Immune Response between Recovered Anthrax Patients and Individuals Receiving Three Different Anthrax Vaccines

    Thomas R. Laws; Tinatin Kuchuloria; Nazibriola Chitadze; Little, Stephen F.; Webster, Wendy M.; Debes, Amanda K; Salome Saginadze; Nikoloz Tsertsvadze; Mariam Chubinidze; Robert G Rivard; Shota Tsanava; Dyson, Edward H.; Andrew J H Simpson; Hepburn, Matthew J; Nino Trapaidze

    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 anthr...

  18. Relaxin deficiency attenuates pregnancy-induced adaptation of the mesenteric artery to angiotensin II in mice.

    Marshall, Sarah A; Leo, Chen Huei; Senadheera, Sevvandi N; Girling, Jane E; Tare, Marianne; Parry, Laura J

    2016-05-01

    Pregnancy is associated with reduced peripheral vascular resistance, underpinned by changes in endothelial and smooth muscle function. Failure of the maternal vasculature to adapt correctly leads to serious pregnancy complications, such as preeclampsia. The peptide hormone relaxin regulates the maternal renal vasculature during pregnancy; however, little is known about its effects in other vascular beds. This study tested the hypothesis that functional adaptation of the mesenteric and uterine arteries during pregnancy will be compromised in relaxin-deficient (Rln(-/-)) mice. Smooth muscle and endothelial reactivity were examined in small mesenteric and uterine arteries of nonpregnant (estrus) and late-pregnant (day 17.5) wild-type (Rln(+/+)) and Rln(-/-) mice using wire myography. Pregnancy per se was associated with significant reductions in contraction to phenylephrine, endothelin-1, and ANG II in small mesenteric arteries, while sensitivity to endothelin-1 was reduced in uterine arteries of Rln(+/+) mice. The normal pregnancy-associated attenuation of ANG II-mediated vasoconstriction in mesenteric arteries did not occur in Rln(-/-) mice. This adaptive failure was endothelium-independent and did not result from altered expression of ANG II receptors or regulator of G protein signaling 5 (Rgs5) or increases in reactive oxygen species generation. Inhibition of nitric oxide synthase with l-NAME enhanced ANG II-mediated contraction in mesenteric arteries of both genotypes, whereas blockade of prostanoid production with indomethacin only increased ANG II-induced contraction in arteries of pregnant Rln(+/+) mice. In conclusion, relaxin deficiency prevents the normal pregnancy-induced attenuation of ANG II-mediated vasoconstriction in small mesenteric arteries. This is associated with reduced smooth muscle-derived vasodilator prostanoids. PMID:26936785

  19. Clarithromycin attenuates mastectomy-induced acute inflammatory response

    Chow, Louis W. C.; Yuen, Kwok-Yung; Woo, Patrick C. Y.; Wei, William I.

    2000-01-01

    Based on the observation that administration of clarithromycin led to an attenuation of the inflammatory response induced by surgical trauma in a guinea pig model, we investigated the potential beneficial effects of clarithromycin on the local and systemic inflammatory response in patients undergoing mastectomy in an open-label prospective study. During a 16-month period, 54 patients who underwent mastectomy were randomly divided into two groups. In one group, the patients received oral clari...

  20. α-Actinin-3 deficiency alters muscle adaptation in response to denervation and immobilization.

    Garton, F C; Seto, J T; Quinlan, K G R; Yang, N; Houweling, P J; North, K N

    2014-04-01

    Homozygosity for a common null polymorphism (R577X) in the ACTN3 gene results in the absence of the fast fibre-specific protein, α-actinin-3 in ∼16% of humans worldwide. α-Actinin-3 deficiency is detrimental to optimal sprint performance and benefits endurance performance in elite athletes. In the general population, α-actinin-3 deficiency is associated with reduced muscle mass, strength and fast muscle fibre area, and poorer muscle function with age. The Actn3 knock-out (KO) mouse model mimics the human phenotype, with fast fibres showing a shift towards slow/oxidative metabolism without a change in myosin heavy chain (MyHC) isoform. We have recently shown that these changes are attributable to increased activity of the calcineurin-dependent signalling pathway in α-actinin-3 deficient muscle, resulting in enhanced response to exercise training. This led us to hypothesize that the Actn3 genotype influences muscle adaptation to disuse, irrespective of neural innervation. Separate cohorts of KO and wild-type mice underwent 2 weeks immobilization and 2 and 8 weeks of denervation. Absence of α-actinin-3 resulted in reduced atrophic response and altered adaptation to disuse, as measured by a change in MyHC isoform. KO mice had a lower threshold to switch from the predominantly fast to a slower muscle phenotype (in response to immobilization) and a higher threshold to switch to a faster muscle phenotype (in response to denervation). We propose that this change is mediated through baseline alterations in the calcineurin signalling pathway of Actn3 KO muscle. Our findings have important implications for understanding individual responses to muscle disuse/disease and training in the general population. PMID:24234654

  1. Endotoxemia is associated with altered innate and adaptive immune responses in untreated HIV-1 infected individuals.

    Anne Roslev Bukh

    Full Text Available BACKGROUND: Microbial translocation may contribute to the immunopathogenesis in HIV infection. We investigated if microbial translocation and inflammation were associated with innate and adaptive immune responses in adults with HIV. METHODOLOGY/PRINCIPAL FINDINGS: This was an observational cohort study. Sera from HIV-infected and HIV-uninfected individuals were analyzed for microbial translocation (soluble CD14, lipopolysaccharides [LPS], endotoxin core antibody, and anti-α-galactosyl antibodies and inflammatory markers (high sensitivity C-reactive protein, IL-6, IL-1 receptor antagonist, soluble tumor necrosis factor receptor II, and IL-10 with enzyme-linked immunosorbent assays. Peripheral blood mononuclear cells (PBMC from HIV-infected persons and healthy controls (primed with single-stranded HIV-1-derived RNA were stimulated with LPS, and cytokine production was measured. Finally, HIV-infected patients were immunized with Prevnar 7vPnC±CpG 7909 followed by Pneumo Novum PPV-23. Effects of microbial translocation and inflammation on immunization were analyzed in a predictive regression model. We included 96 HIV-infected individuals, 76 on highly active antiretroviral therapy (HAART, 20 HAART-naive, and 50 healthy controls. Microbial translocation and inflammatory markers were higher among HIV-infected persons than controls. Cytokine levels following LPS stimulation were increased in PBMCs from HAART-naive compared to HAART-treated HIV-infected persons. Further, RNA-priming of PBMCs from controls acted synergistically with LPS to augment cytokine responses. Finally, high serum LPS levels predicted poor vaccine responses among HAART-naive, but not among HAART-treated HIV-infected individuals. CONCLUSIONS/SIGNIFICANCE: LPS acts synergistically with HIV RNA to stimulate innate immune responses in vitro and increasing serum LPS levels seem to predict poor antibody responses after vaccination among HAART-naive HIV-infected persons. Thus, our

  2. Drought and flooding have distinct effects on herbivore-induced responses and resistance in Solanum dulcamara.

    Nguyen, Duy; D'Agostino, Nunzio; Tytgat, Tom O G; Sun, Pulu; Lortzing, Tobias; Visser, Eric J W; Cristescu, Simona M; Steppuhn, Anke; Mariani, Celestina; van Dam, Nicole M; Rieu, Ivo

    2016-07-01

    In the field, biotic and abiotic stresses frequently co-occur. As a consequence, common molecular signalling pathways governing adaptive responses to individual stresses can interact, resulting in compromised phenotypes. How plant signalling pathways interact under combined stresses is poorly understood. To assess this, we studied the consequence of drought and soil flooding on resistance of Solanum dulcamara to Spodoptera exigua and their effects on hormonal and transcriptomic profiles. The results showed that S. exigua larvae performed less well on drought-stressed plants than on well-watered and flooded plants. Both drought and insect feeding increased abscisic acid and jasmonic acid (JA) levels, whereas flooding did not induce JA accumulation. RNA sequencing analyses corroborated this pattern: drought and herbivory induced many biological processes that were repressed by flooding. When applied in combination, drought and herbivory had an additive effect on specific processes involved in secondary metabolism and defence responses, including protease inhibitor activity. In conclusion, drought and flooding have distinct effects on herbivore-induced responses and resistance. Especially, the interaction between abscisic acid and JA signalling may be important to optimize plant responses to combined drought and insect herbivory, making drought-stressed plants more resistant to insects than well-watered and flooded plants. PMID:26759219

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

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

    2016-02-01

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

  4. Adaptive Response of the Heart and Peripheral Vasculature on Single Physical Exercises in Experiment

    O.V. Biryukova

    2015-06-01

    Full Text Available The aim of the investigation was to assess the parameters of urgent adaptation of the heart and peripheral vasculature to single physical exercises to determine an individually safe value of motor activity. Materials and Methods. The experiments were carried out on 84 mongrel male dogs. Physical exercises were modeled in laboratory environment by treadmill run. Three types of exercises were used in the experiment: mild, optimal and excessive. Exercise duration was controlled individually, for each animal considering cardio-respiratory system state by heart rate. Cardiac work was assessed by echocardiography and electrocardiography, peripheral circulation — by hindleg rheovasogram. Results. Experimental findings indicate significant alterations in cardiac conducting system under single physical exercises. A single mild exercise causes the increase of minute blood output due to heart rate increase. Hind leg muscular blood filling decreases. An optimal exercise results in minute blood output increase due to stroke blood volume growth. Myocardial contractility increases. Muscular blood filling rises. In excessive load increased stroke output is accompanied by left ventricular cavity dilatation. Pulse volume decreases, peripheral vasculature elasticity reduces, and hind leg muscular venous outflow gets worse. Conclusion. Urgent adaptation of the heart and peripheral vasculature in single physical exercises shows as a marked response to a simulated factor. The technique to assess the body adaptation considering cardiovascular system condition enables to calculate individual volume of physical activity and develop recommendations for it to be used efficiently in medicine.

  5. A Bayesian decision-theoretic sequential response-adaptive randomization design.

    Jiang, Fei; Jack Lee, J; Müller, Peter

    2013-05-30

    We propose a class of phase II clinical trial designs with sequential stopping and adaptive treatment allocation to evaluate treatment efficacy. Our work is based on two-arm (control and experimental treatment) designs with binary endpoints. Our overall goal is to construct more efficient and ethical randomized phase II trials by reducing the average sample sizes and increasing the percentage of patients assigned to the better treatment arms of the trials. The designs combine the Bayesian decision-theoretic sequential approach with adaptive randomization procedures in order to achieve simultaneous goals of improved efficiency and ethics. The design parameters represent the costs of different decisions, for example, the decisions for stopping or continuing the trials. The parameters enable us to incorporate the actual costs of the decisions in practice. The proposed designs allow the clinical trials to stop early for either efficacy or futility. Furthermore, the designs assign more patients to better treatment arms by applying adaptive randomization procedures. We develop an algorithm based on the constrained backward induction and forward simulation to implement the designs. The algorithm overcomes the computational difficulty of the backward induction method, thereby making our approach practicable. The designs result in trials with desirable operating characteristics under the simulated settings. Moreover, the designs are robust with respect to the response rate of the control group. PMID:23315678

  6. Channel Impulse Response Length and Noise Variance Estimation for OFDM Systems with Adaptive Guard Interval

    Van Duc Nguyen

    2007-02-01

    Full Text Available A new algorithm estimating channel impulse response (CIR length and noise variance for orthogonal frequency-division multiplexing (OFDM systems with adaptive guard interval (GI length is proposed. To estimate the CIR length and the noise variance, the different statistical characteristics of the additive noise and the mobile radio channels are exploited. This difference is due to the fact that the variance of the channel coefficients depends on the position within the CIR, whereas the noise variance of each estimated channel tap is equal. Moreover, the channel can vary rapidly, but its length changes more slowly than its coefficients. An auxiliary function is established to distinguish these characteristics. The CIR length and the noise variance are estimated by varying the parameters of this function. The proposed method provides reliable information of the estimated CIR length and the noise variance even at signal-to-noise ratio (SNR of 0 dB. This information can be applied to an OFDM system with adaptive GI length, where the length of the GI is adapted to the current length of the CIR. The length of the GI can therefore be optimized. Consequently, the spectral efficiency of the system is increased.

  7. Channel Impulse Response Length and Noise Variance Estimation for OFDM Systems with Adaptive Guard Interval

    Gelle Guillaume

    2007-01-01

    Full Text Available A new algorithm estimating channel impulse response (CIR length and noise variance for orthogonal frequency-division multiplexing (OFDM systems with adaptive guard interval (GI length is proposed. To estimate the CIR length and the noise variance, the different statistical characteristics of the additive noise and the mobile radio channels are exploited. This difference is due to the fact that the variance of the channel coefficients depends on the position within the CIR, whereas the noise variance of each estimated channel tap is equal. Moreover, the channel can vary rapidly, but its length changes more slowly than its coefficients. An auxiliary function is established to distinguish these characteristics. The CIR length and the noise variance are estimated by varying the parameters of this function. The proposed method provides reliable information of the estimated CIR length and the noise variance even at signal-to-noise ratio (SNR of 0 dB. This information can be applied to an OFDM system with adaptive GI length, where the length of the GI is adapted to the current length of the CIR. The length of the GI can therefore be optimized. Consequently, the spectral efficiency of the system is increased.

  8. A Cotton MYB Transcription Factor, GbMYB5, is Positively Involved in Plant Adaptive Response to Drought Stress.

    Chen, Tianzi; Li, Wenjuan; Hu, Xuehong; Guo, Jiaru; Liu, Aimin; Zhang, Baolong

    2015-05-01

    Drought stress negatively affects plant growth and limits plant productivity. Genes functioning in plant responses to drought stress are essential for the development of drought-tolerant crops. Here, we report that an R2R3-type MYB transcription factor gene in Gossypium barbadense, GbMYB5, confers drought tolerance in cotton and transgenic tobacco. Virus-induced gene silencing of GbMYB5 compromised the tolerance of cotton plantlets to drought stress and reduced the post-rewatering water recovery survival rate to 50% as compared with the 90% survival rate in the wild type (WT). Silencing GbMYB5 decreased proline content and antioxidant enzyme activities and increased malondialdehyde (MDA) content in cotton under drought stress. The expression levels of drought-inducible genes NCED3, RD22 and RD26 were not affected by the silencing of GbMYB5. However, GbMYB5-overexpressing tobacco lines displayed hypersensitivity to ABA and improved survival rates as well as reduced water loss rates under drought stress. Furthermore, stomatal size and the rate of opening of stomata were markedly decreased in transgenic tobacco. The overexpression of GbMYB5 enhanced the accumulation of proline and antioxidant enzymes while it reduced production of MDA in transgenic tobacco as compared with the WT under drought stress. The transcript levels of the antioxidant genes SOD, CAT and GST, polyamine biosynthesis genes ADC1 and SAMDC, the late embryogenesis abundant protein-encoding gene ERD10D and drought-responsive genes NCED3, BG and RD26 were generally higher in GbMYB5-overexpressing tobacco than in the WT under drought stress. Collectively, our data suggested that GbMYB5 was positively involved in the plant adaptive response to drought stress. PMID:25657343

  9. Persistence of the immune response induced by BCG vaccination

    Blitz Rose

    2008-01-01

    Full Text Available Abstract Background Although BCG vaccination is recommended in most countries of the world, little is known of the persistence of BCG-induced immune responses. As novel TB vaccines may be given to boost the immunity induced by neonatal BCG vaccination, evidence concerning the persistence of the BCG vaccine-induced response would help inform decisions about when such boosting would be most effective. Methods A randomised control study of UK adolescents was carried out to investigate persistence of BCG immune responses. Adolescents were tested for interferon-gamma (IFN-γ response to Mycobacterium tuberculosis purified protein derivative (M.tb PPD in a whole blood assay before, 3 months, 12 months (n = 148 and 3 years (n = 19 after receiving teenage BCG vaccination or 14 years after receiving infant BCG vaccination (n = 16. Results A gradual reduction in magnitude of response was evident from 3 months to 1 year and from 1 year to 3 years following teenage vaccination, but responses 3 years after vaccination were still on average 6 times higher than before vaccination among vaccinees. Some individuals (11/86; 13% failed to make a detectable antigen-specific response three months after vaccination, or lost the response after 1 (11/86; 13% or 3 (3/19; 16% years. IFN-γ response to Ag85 was measured in a subgroup of adolescents and appeared to be better maintained with no decline from 3 to 12 months. A smaller group of adolescents were tested 14 years after receiving infant BCG vaccination and 13/16 (81% made a detectable IFN-γ response to M.tb PPD 14 years after infant vaccination as compared to 6/16 (38% matched unvaccinated controls (p = 0.012; teenagers vaccinated in infancy were 19 times more likely to make an IFN-γ response of > 500 pg/ml than unvaccinated teenagers. Conclusion BCG vaccination in infancy and adolescence induces immunological memory to mycobacterial antigens that is still present and measurable for at least 14 years in the

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

    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

  11. Gene 33/Mig-6, a Transcriptionally Inducible Adapter Protein That Binds GTP-Cdc42 and Activates SAPK/JNK*

    Makkinje, Anthony; Quinn, Deborah A.; Chen, Ang; Cadilla, Carmen L.; Force, Thomas; Bonventre, Joseph V.; Kyriakis, John M.

    2013-01-01

    Chronic stresses, including the mechanical strain caused by hypertension or excess pulmonary ventilation pressure, lead to important clinical consequences, including hypertrophy and acute respiratory distress syndrome. Pathologic hypertrophy contributes to decreased organ function and, ultimately, organ failure; and cardiac and diabetic renal hypertrophy are major causes of morbidity and morality in the developed world. Likewise, acute respiratory distress syndrome is a serious potential side effect of mechanical pulmonary ventilation. Whereas the deleterious effects of chronic stress are well established, the molecular mechanisms by which these stresses affect cell function are still poorly characterized. gene 33 (also called mitogen-inducible gene-6, mig-6) is an immediate early gene that is transcriptionally induced by a divergent array of extra-cellular stimuli. The physiologic function of Gene 33 is unknown. Here we show that gene 33 mRNA levels increase sharply in response to a set of commonly occurring chronic stress stimuli: mechanical strain, vasoactive peptides, and diabetic nephropathy. Induction of gene 33 requires the stress-activated protein kinases (SAPKs)/c-Jun NH2-terminal kinases. This expression pattern suggests that gene 33 is a potential marker for diabetic nephropathy and other pathologic responses to persistent sublethal stress. The structure of Gene 33 indicates an adapter protein capable of binding monomeric GTPases of the Rho subfamily. Consistent with this, Gene 33 interacts in vivo and, in a GTP-dependent manner, in vitro with Cdc42Hs; and transient expression of Gene 33 results in the selective activation of the SAPKs. These results imply a reciprocal, positive feedback relationship between Gene 33 expression and SAPK activation. Expression of Gene 33 at sufficient levels may enable a compensatory reprogramming of cellular function in response to chronic stress, which may have pathophysiological consequences. PMID:10749885

  12. Natural background radiation induces cytogenetic radioadaptive response more effectively than occupational exposure in human peripheral blood lymphocytes

    Ramsar, a city in the north part of Iran, has the highest level of natural background radiation in the world. We compared induction of cytogenetic radioadaptive response by High Natural Background Radiation (HNBR) in Ramsar and X-Ray occupational exposure as inducing doses in human peripheral blood lymphocytes. 30 healthy control individuals, living in Ramsar but in ordinary background radiation areas (inducing dose = 0), 15 healthy individuals from Talesh Mahalleh, a region with extraordinary level of background radiation (max. inducing dose = 260 mGy/year) and 7 X-Ray radiographers working in Ramsar hospital located in normal natural background of ionising radiation (max. inducing dose = 20 mGy/year) were evaluated. Peripheral blood samples were prepared and exposed to challenge dose of 0 and 2 Gy. Lymphocytes were scored using analysis of metaphase, for the presence of chromosomal aberrations (simple deletion, dicentrics and rings). An adaptive response was observed in HNBR and radiation workers groups in comparison with sham controls. Also, compared with occupationally exposed group a significant marked increase in adaptive response was observed in HNBR group. These findings indicate that both natural background radiation and occupational exposure could induce cytogenetic radioadaptive response and it is more significant regarding to natural background ionising radiation. (author)

  13. Responses of leaf traits to climatic gradients: adaptive variation vs. compositional shifts

    T.-T. Meng

    2015-05-01

    Full Text Available 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

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

    Siri eFjellheim

    2014-08-01

    Full Text Available Grasses of the subfamily Pooideae, which includes 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 favourable 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.

  15. Early and late rate of force development: differential adaptive responses to resistance training?

    Andersen, L L; Andersen, Jesper Løvind; Zebis, M K;

    2010-01-01

    The objective of this study is to investigate the potentially opposing influence of qualitative and quantitative muscular adaptations in response to high-intensity resistance training on contractile rate of force development (RFD) in the early (200 ms) of rising muscle force. Fifteen healthy young...... males participated in a 14-week resistance training intervention for the lower body and 10 matched subjects participated as controls. Maximal muscle strength (MVC) and RFD were measured during maximal voluntary isometric contraction of the quadriceps femoris muscle. Muscle biopsies were obtained from...... the vastus lateralis. The main findings were that RFD in the late phase of rising muscle force increased in response to resistance training whereas early RFD remained unchanged and early relative RFD (i.e., RFD/MVC) decreased. Quantitatively, muscle fiber cross-sectional area and MVC increased whereas...

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

    Sergio eGiannattasio

    2013-02-01

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

  17. On optimal allocation in binary response trials; is adaptive design really necessary?

    Azriel, David; Rinott, Yosef

    2011-01-01

    We consider the classical problem of selecting the best of two treatments in clinical trials with binary response. The target is to find the design that maximizes the power of the relevant test. Many papers use a normal approximation to the power function and claim that \\textit{Neyman allocation} that assigns subjects to treatment groups according to the ratio of the responses' standard deviations, should be used. As the standard deviations are unknown, an adaptive design is often recommended. The asymptotic justification of this approach is arguable, since it uses the normal approximation in tails where the error in the approximation is larger than the estimated quantity. We consider two different approaches for optimality of designs that are related to Pitman and Bahadur definitions of relative efficiency of tests. We prove that the optimal allocation according to the Pitman criterion is the balanced allocation and that the optimal allocation according to the Bahadur approach depends on the unknown paramete...

  18. Extracytoplasmic Stress Responses Induced by Antimicrobial Cationic Polyethylenimines

    Lander, Blaine A.; Checchi, Kyle D.; Koplin, Stephen A.; Smith, Virginia F.; Domanski, Tammy L.; Isaac, Daniel D.; Lin, Shirley

    2012-01-01

    The ability of an antimicrobial, cationic polyethylenimine (PEI+) to induce the three known extracytoplasmic stress responses of Escherichia coli was quantified. Exposure of E. coli to PEI+ in solution revealed specific, concentration-dependent induction of the Cpx extracytoplasmic cellular stress response, ~2.0-2.5 fold at 320 μg/mL after 1.5 hours without significant induction of the σE or Bae stress responses. In comparison, exposure of E. coli to a non-antimicrobial polymer, polyethylene ...

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

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

    2016-04-01

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

  20. Adaptive response of the chicken embryo to low doses of x-irradiation

    Chicken embryos were x-irradiated in ovo with 5-30 cGy (=priming dose) at the 13th-15th day of development. After 3-48 h, brain- and liver-cell suspensions were x-irradiated in vitro with (challenge) doses of 4-32 Gy. Significantly less radiation damage was observed when the radiation response was measured by scheduled DNA synthesis, nucleoid sedimentation and viscosity of alkaline cell lysates 12-36 h after the priming exposure. In vivo, pre-irradiation with 10 cGy enhanced regeneration as evidenced by the DNA content of chicken embryo brain and liver 24 h following a challenge dose of 4 Gy. From nucleoid sedimentation analyses in brain and liver cells immediately after irradiation with 16 Gy and after a 30-min repair period in the presence of aphidicolin, dideoxythymidine and 3-aminobenzamide or in the absence of these DNA repair inhibitors, it is concluded that a reduction of the initial radiation damage is the dominant mechanism of the ''radio-adaptive'' response of the chicken embryo. Sedimentation of nucleoids from ethidium bromide (EB) (0.75-400 μg/ml)-treated cells suggests a higher tendency of ''radio-adapted'' cells to undergo positive DNA supercoiling in the presence of high EB concentrations. (orig.)

  1. Characterization of host responses induced by Toll-like receptor ligands in chicken cecal tonsil cells.

    Taha-Abdelaziz, Khaled; Alkie, Tamiru Negash; Hodgins, Douglas C; Shojadoost, Bahram; Sharif, Shayan

    2016-06-01

    The innate responses of cecal tonsils against invading microorganisms are mediated by conserved pattern recognition receptors (PRRs) such as the Toll-like receptors (TLRs). TLRs expressed by mammalian and avian immune system cells have the capability to recognize pathogen-associated molecular patterns (PAMPs). Although, the role of TLR ligands in innate and adaptive responses in chickens has been characterized in spleen and bursa of Fabricius, considerably less is known about responses in cecal tonsils. The aim of the current study was to assess responses of mononuclear cells from cecal tonsils to treatment with the TLR2, TLR4 and TLR21 ligands, Pam3CSK4, lipopolysaccharide (LPS), and CpG oligodeoxynucleotide (ODN), respectively. All three ligands induced significant up-regulation of interferon (IFN)-γ, interleukin (IL)-1β, IL-6 and CxCLi2/IL-8, whereas no significant changes were observed in expression of IL-13 or the antimicrobial peptides, avian β-defensin (AvBD) 1, AvBD2 and cathelicidin 3 (CATHL-3). In general, CpG ODN elicited the highest cytokine responses by cecal tonsil mononuclear cells, inducing significantly higher expression compared to LPS and Pam3CSK4, for IFNγ, IL-1β, IL-6 and CxCLi2 at various time points. These findings suggest the potential use of TLR21 ligands as mucosal vaccine adjuvants, especially in the context of pathogens of the intestinal tract. PMID:27185259

  2. Adaptation mechanisms of bacteria during the degradation of polychlorinated biphenyls in the presence of natural and synthetic terpenes as potential degradation inducers

    Zoradova-Murinova, Slavomira; Dudasova, Hana; Lukacova, Lucia; Certik, Milan; Dercova, Katarina [Slovak Univ. of Technology, Bratislava (Slovakia). Inst. of Biotechnology and Food Science; Silharova, Katarina; Vrana, Branislav [Water Research Institute, Bratislava (Slovakia)

    2012-06-15

    In this study, we examined the effect of polychlorinated biphenyls (PCBs) in the presence of natural and synthetic terpenes and biphenyl on biomass production, lipid accumulation, and membrane adaptation mechanisms of two PCB-degrading bacterial strains Pseudomonas stutzeri and Burkholderia xenovorans LB400. According to the results obtained, it could be concluded that natural terpenes, mainly those contained in ivy leaves and pine needles, decreased adaptation responses induced by PCBs in these strains. The adaptation processes under investigation included growth inhibition, lipid accumulation, composition of fatty acids, cis/trans isomerization, and membrane saturation. Growth inhibition effect decreased upon addition of these natural compounds to the medium. The amount of unsaturated fatty acids that can lead to elevated membrane fluidity increased in both strains after the addition of the two natural terpene sources. The cells adaptation changes were more prominent in the presence of carvone, limonene, and biphenyl than in the presence of natural terpenes, as indicated by growth inhibition, lipid accumulation, and cis/trans isomerization. Addition of biphenyl and carvone simultaneously with PCBs increased the trans/cis ratio of fatty acids in membrane fractions probably as a result of fluidizing effects of PCBs. This stimulation is more pronounced in the presence of PCBs as a sole carbon source. This suggests that PCBs alone have a stronger effect on bacterial membrane adaptation mechanisms than when added together with biphenyl or natural or synthetic terpenes. (orig.)

  3. Adenylyl cyclase 6 mediates loading-induced bone adaptation in vivo.

    Lee, Kristen L; Hoey, David A; Spasic, Milos; Tang, Tong; Hammond, H Kirk; Jacobs, Christopher R

    2014-03-01

    Primary cilia are single, nonmotile, antenna-like structures extending from the apical membrane of most mammalian cells. They may mediate mechanotransduction, the conversion of external mechanical stimuli into biochemical intracellular signals. Previously we demonstrated that adenylyl cyclase 6 (AC6), a membrane-bound enzyme enriched in primary cilia of MLO-Y4 osteocyte-like cells, may play a role in a primary cilium-dependent mechanism of osteocyte mechanotransduction in vitro. In this study, we determined whether AC6 deletion impairs loading-induced bone formation in vivo. Skeletally mature mice with a global knockout of AC6 exhibited normal bone morphology and responded to osteogenic chemical stimuli similar to wild-type mice. Following ulnar loading over 3 consecutive days, bone formation parameters were assessed using dynamic histomorphometry. Mice lacking AC6 formed significantly less bone than control animals (41% lower bone formation rate). Furthermore, there was an attenuated flow-induced increase in COX-2 mRNA expression levels in primary bone cells isolated from AC6 knockout mice compared to controls (1.3±0.1- vs. 2.6±0.2-fold increase). Collectively, these data indicate that AC6 plays a role in loading-induced bone adaptation, and these findings are consistent with our previous studies implicating primary cilia and AC6 in a novel mechanism of osteocyte mechanotransduction. PMID:24277577

  4. Immune-inflammatory responses in atherosclerosis: Role of an adaptive immunity mainly driven by T and B cells.

    Chistiakov, Dimitry A; Orekhov, Alexander N; Bobryshev, Yuri V

    2016-09-01

    Adaptive immune response plays an important role in atherogenesis. In atherosclerosis, the proinflammatory immune response driven by Th1 is predominant but the anti-inflammatory response mediated mainly by regulatory T cells is also present. The role of Th2 and Th17 cells in atherogenesis is still debated. In the plaque, other T helper cells can be observed such as Th9 and Th22 but is little is known about their impact in atherosclerosis. Heterogeneity of CD4(+) T cell subsets presented in the plaque may suggest for plasticity of T cell that can switch the phenotype dependening on the local microenvironment and activating/blocking stimuli. Effector T cells are able to recognize self-antigens released by necrotic and apoptotic vascular cells and induce a humoral immune reaction. Tth cells resided in the germinal centers help B cells to switch the antibody class to the production of high-affinity antibodies. Humoral immunity is mediated by B cells that release antigen-specific antibodies. A variety of B cell subsets were found in human and murine atherosclerotic plaques. In mice, B1 cells could spontaneously produce atheroprotective natural IgM antibodies. Conventional B2 lymphocytes secrete either proatherogenic IgG, IgA, and IgE or atheroprotective IgG and IgM antibodies reactive with oxidation-specific epitopes on atherosclerosis-associated antigens. A small population of innate response activator (IRA) B cells, which is phenotypically intermediate between B1 and B2 cells, produces IgM but possesses proatherosclerotic properties. Finally, there is a minor subset of splenic regulatory B cells (Bregs) that protect against atherosclerotic inflammation through support of generation of Tregs and production of anti-inflammatory cytokines IL-10 and TGF-β and proapoptotic molecules. PMID:27262513

  5. Adaptive immunity alters distinct host feeding pathways during nematode induced inflammation, a novel mechanism in parasite expulsion.

    John J Worthington

    2013-01-01

    Full Text Available Gastrointestinal infection is often associated with hypophagia and weight loss; however, the precise mechanisms governing these responses remain poorly defined. Furthermore, the possibility that alterations in feeding during infection may be beneficial to the host requires further study. We used the nematode Trichinella spiralis, which transiently inhabits the small intestine before migrating to skeletal muscle, as a biphasic model of infection to determine the cellular and molecular pathways controlling feeding during enteric and peripheral inflammation. Through the infection of genetically modified mice lacking cholecystokinin, Tumor necrosis factor α receptors and T and B-cells, we observed a biphasic hypophagic response to infection resulting from two separate immune-driven mechanisms. The enteroendocrine I-cell derived hormone cholecystokinin is an essential mediator of initial hypophagia and is induced by CD4+ T-cells during enteritis. In contrast, the second hypophagic response is extra-intestinal and due to the anorectic effects of TNFα during peripheral infection of the muscle. Moreover, via maintaining naive levels of the adipose secreted hormone leptin throughout infection we demonstrate a novel feedback loop in the immunoendocrine axis. Immune driven I-cell hyperplasia and resultant weight loss leads to a reduction in the inflammatory adipokine leptin, which in turn heightens protective immunity during infection. These results characterize specific immune mediated mechanisms which reduce feeding during intestinal or peripheral inflammation. Importantly, the molecular mediators of each phase are entirely separate. The data also introduce the first evidence that I-cell hyperplasia is an adaptively driven immune response that directly impinges on the outcome to infection.

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

    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

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

    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

  8. A microcosm test of adaptation and species specific responses to polluted sediments applicable to indigenous chironomids (Diptera)

    Chironomids may adapt to pollution stress but data are confined to species that can be reared in the laboratory. A microcosm approach was used to test for adaptation and species differences in heavy metal tolerance. In one experiment, microcosms containing different levels of contaminants were placed in polluted and reference locations. The response of Chironomus februarius to metal contaminants suggested local adaptation: relatively more flies emerged from clean sediment at the reference site and the reverse pattern occurred at the polluted site. However, maternal effects were not specifically ruled out. In another species, Kiefferulus intertinctus, there was no evidence for adaptation. In a second experiment, microcosms with different contaminant levels were placed at two polluted and two unpolluted sites. Species responded differently to contaminants, but there was no evidence for adaptation in the species where this could be tested. Adaptation to heavy metals may be uncommon and species specific, but more sensitive species need to be tested across a range of pollution levels. Factors influencing the likelihood of adaptation are briefly discussed. - A field test for adaptation applicable to indigenous chironomids suggests adaptation to metal contaminants in one species but not in other species

  9. The Nuclear Receptor, Nor-1, Induces the Physiological Responses Associated With Exercise.

    Goode, Joel M; Pearen, Michael A; Tuong, Zewen K; Wang, Shu-Ching M; Oh, Tae Gyu; Shao, Emily X; Muscat, George E O

    2016-06-01

    Skeletal muscle remodels metabolic capacity, contractile and exercise phenotype in response to physiological demands. This adaptive remodeling response to physical activity can ameliorate/prevent diseases associated with poor diet and lifestyle. Our previous work demonstrated that skeletal muscle-specific transgenic expression of the neuron-derived orphan nuclear receptor, Nor-1 drives muscle reprogramming, improves exercise endurance, and oxidative metabolism. The current manuscript investigates the association between exercise, Nor-1 expression and the role of Nor-1 in adaptive remodeling. We demonstrate that Nor-1 expression is induced by exercise and is dependent on calcium/calcineurin signaling (in vitro and in vivo). Analysis of fatigue-resistant transgenic mice that express Nor-1 in skeletal muscle revealed increased hypertrophy and vascularization of muscle tissue. Moreover, we demonstrate that transgenic Nor-1 expression is associated with increased intracellular recycling, ie, autophagy, involving 1) increased expression of light chain 3A or LC3A-II, autophagy protein 5, and autophagy protein 12 in quadriceps femoris muscle extracts from Tg-Nor-1 (relative to Wild-type (WT) littermates); 2) decreased p62 expression indicative of increased autophagolysosome assembly; and 3) decreased mammalian target of rapamycin complex 1 activity. Transfection of LC3A-GFP-RFP chimeric plasmid demonstrated that autophagolysosome formation was significantly increased by Nor-1 expression. Furthermore, we demonstrated a single bout of exercise induced LC3A-II expression in skeletal muscle from C57BL/6 WT mice. This study, when combined with our previous studies, demonstrates that Nor-1 expression drives multiple physiological changes/pathways that are critical to the beneficial responses of muscle to exercise and provides insights into potential pharmacological manipulation of muscle reprogramming for the treatment of lifestyle induced chronic diseases. PMID:27144290

  10. Polysaccharides isolated from Acai fruit induce innate immune responses.

    Jeff Holderness

    Full Text Available The Açaí (Acai fruit is a popular nutritional supplement that purportedly enhances immune system function. These anecdotal claims are supported by limited studies describing immune responses to the Acai polyphenol fraction. Previously, we characterized γδ T cell responses to both polyphenol and polysaccharide fractions from several plant-derived nutritional supplements. Similar polyphenol and polysaccharide fractions are found in Acai fruit. Thus, we hypothesized that one or both of these fractions could activate γδ T cells. Contrary to previous reports, we did not identify agonist activity in the polyphenol fraction; however, the Acai polysaccharide fraction induced robust γδ T cell stimulatory activity in human, mouse, and bovine PBMC cultures. To characterize the immune response to Acai polysaccharides, we fractionated the crude polysaccharide preparation and tested these fractions for activity in human PBMC cultures. The largest Acai polysaccharides were the most active in vitro as indicated by activation of myeloid and γδ T cells. When delivered in vivo, Acai polysaccharide induced myeloid cell recruitment and IL-12 production. These results define innate immune responses induced by the polysaccharide component of Acai and have implications for the treatment of asthma and infectious disease.

  11. Skeletal nutrient vascular adaptation induced by external oscillatory intramedullary fluid pressure intervention

    Qin Yi-Xian

    2010-03-01

    Full Text Available Abstract Background Interstitial fluid flow induced by loading has demonstrated to be an important mediator for regulating bone mass and morphology. It is shown that the fluid movement generated by the intramedullary pressure (ImP provides a source for pressure gradient in bone. Such dynamic ImP may alter the blood flow within nutrient vessel adjacent to bone and directly connected to the marrow cavity, further initiating nutrient vessel adaptation. It is hypothesized that oscillatory ImP can mediate the blood flow in the skeletal nutrient vessels and trigger vasculature remodeling. The objective of this study was then to evaluate the vasculature remodeling induced by dynamic ImP stimulation as a function of ImP frequency. Methods Using an avian model, dynamics physiological fluid ImP (70 mmHg, peak-peak was applied in the marrow cavity of the left ulna at either 3 Hz or 30 Hz, 10 minutes/day, 5 days/week for 3 or 4 weeks. The histomorphometric measurements of the principal nutrient arteries were done to quantify the arterial wall area, lumen area, wall thickness, and smooth muscle cell layer numbers for comparison. Results The preliminary results indicated that the acute cyclic ImP stimuli can significantly enlarge the nutrient arterial wall area up to 50%, wall thickness up to 20%, and smooth muscle cell layer numbers up to 37%. In addition, 3-week of acute stimulation was sufficient to alter the arterial structural properties, i.e., increase of arterial wall area, whereas 4-week of loading showed only minimal changes regardless of the loading frequency. Conclusions These data indicate a potential mechanism in the interrelationship between vasculature adaptation and applied ImP alteration. Acute ImP could possibly initiate the remodeling in the bone nutrient vasculature, which may ultimately alter blood supply to bone.

  12. Protein kinase Cη activates NF-κB in response to camptothecin-induced DNA damage

    Highlights: → Protein kinase C-eta (PKCη) is an upstream regulator of the NF-κB signaling pathway. → PKCη activates NF-κB in non-stressed conditions and in response to DNA damage. → PKCη regulates NF-κB by activating IκB kinase (IKK) and inducing IκB degradation. -- Abstract: The nuclear factor κB (NF-κB) family of transcription factors participates in the regulation of genes involved in innate- and adaptive-immune responses, cell death and inflammation. The involvement of the Protein kinase C (PKC) family in the regulation of NF-κB in inflammation and immune-related signaling has been extensively studied. However, not much is known on the role of PKC in NF-κB regulation in response to DNA damage. Here we demonstrate for the first time that PKC-eta (PKCη) regulates NF-κB upstream signaling by activating the IκB kinase (IKK) and the degradation of IκB. Furthermore, PKCη enhances the nuclear translocation and transactivation of NF-κB under non-stressed conditions and in response to the anticancer drug camptothecin. We and others have previously shown that PKCη confers protection against DNA damage-induced apoptosis. Our present study suggests that PKCη is involved in NF-κB signaling leading to drug resistance.

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

    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. (letter)

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

    Aravindhan, Vivekanandhan; Madhumitha, Haridoss

    2016-01-01

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

  15. Managing urban water crises: adaptive policy responses to drought and flood in Southeast Queensland, Australia

    Brian W. Head

    2014-06-01

    Full Text Available In this case study, I examine the quality of decision-making under conditions of rapidly evolving urban water crises, and the adaptive policy challenges of building regional resilience in response to both drought and flood. Like other regions of Australia, Southeast Queensland has been subject to substantial cycles of drought and flood. I draw on resilience literature concerning sustainability, together with governance literature on policy change, to explain the changing awareness of urban water crises and the strategic options available for addressing these crises in this case study. The problem of resilience thinking opens up a number of important questions about the efficacy and adaptability of the policy system. The case provides insights into the interplay between the ways in which problems are framed, the knowledge bases required for planning and decision-making, the collaborative governance processes required for managing complex and rapidly evolving issues, and the overall capacity for policy learning over time. Regional resilience was proclaimed as a policy goal by government, but the practices remained largely anchored in traditional technical frameworks. Centralized investment decisions and governance restructures provoked conflict between levels of government, undermining the capacity of stakeholders to create more consensual approaches to problem-solving and limiting the collective learning that could have emerged.

  16. Wave-induced Hydroelastic response of fast monohull ships

    Jensen, Jørgen Juncher

    1996-01-01

    of a quadratic strip theory formulated in the frequency domain. The springing response is thereby excited partly be resonance and partly by non-linear excitation. Special emphasis is given to the influence of springing on fatigue damage as the extreme responses even for very flexible ships are quite...... natural frequencies of the global hull modes can be relatively low compared to the frequency of wave encounter. In the present paper the effect of hull flexibility on the wave-induced springing vibrations is investigated in stationary stochastic seaways. The calculations are performed within the framework...

  17. Clearance of low levels of HCV viremia in the absence of a strong adaptive immune response

    Manns Michael P

    2007-06-01

    Full Text Available Abstract Spontaneous clearance of hepatitis C virus (HCV has frequently been associated with the presence of HCV-specific cellular immunity. However, there had been also reports in chimpanzees demonstrating clearance of HCV-viremia in the absence of significant levels of detectable HCV-specific cellular immune responses. We here report seven asymptomatic acute hepatitis C cases with peak HCV-RNA levels between 300 and 100.000 copies/ml who all cleared HCV-RNA spontaneously. Patients were identified by a systematic screening of 1176 consecutive new incoming offenders in a German young offender institution. Four of the seven patients never developed anti-HCV antibodies and had normal ALT levels throughout follow-up. Transient weak HCV-specific CD4+ T cell responses were detectable in five individuals which did not differ in strength and breadth from age- and sex-matched patients with chronic hepatitis C and long-term recovered patients. In contrast, HCV-specific MHC-class-I-tetramer-positive cells were found in 3 of 4 HLA-A2-positive patients. Thus, these cases highlight that clearance of low levels of HCV viremia is possible in the absence of a strong adaptive immune response which might explain the low seroconversion rate after occupational exposure to HCV.

  18. Tamoxifen persistently disrupts the humoral adaptive immune response of gilthead seabream (Sparus aurata L.).

    Rodenas, M C; Cabas, I; Abellán, E; Meseguer, J; Mulero, V; García-Ayala, A

    2015-12-01

    There is increasing concern about the possible effect of pharmaceutical compounds may have on the fish immune system. Bath exposition of 17α-ethynylestradiol (EE2), a synthetic estrogen used in oral contraceptives, altered the immune response of the gilthead seabream (Sparus aurata L.), a marine hermaphrodite teleost. Tamoxifen (Tmx) is a selective estrogen-receptor modulator used in hormone replacement therapy, the effects of which are unknown in fish immunity. This study aims to investigate the effects of dietary administration of EE2 (5 μg/g food) and Tmx (100 μg/g food) on the immune response of gilthead seabream, and the capacity of the immune system to recover its functionality after a recovery period. The results show for the first time the reversibility of the effect of EE2 and Tmx on the fish immune response. Tmx promoted a transient alteration in hepatic vitellogenin gene expression of a different magnitude to that produced by EE2. Both, EE2 and Tmx inhibited the induction of interleukin-1β gene expression while reversed the inhibition of ROI production in leukocytes following vaccination. However, none of these effects were observed after ceasing EE2 and Tmx exposure. EE2 and Tmx stimulated the antibody response of vaccinated fish although Tmx, but not EE2, altered the antibody response and modulated the percentage of IgM(+) B lymphocytes of vaccinated fish during the recovery phase. Taken together, our results suggest that EE2 and Tmx might alter the capacity of fish to appropriately respond to infection and show that Tmx has a long-lasting effect on humoral adaptive immunity. PMID:26234710

  19. Adaptation of perceptual responses to low load blood flow restriction training

    Martín-Hernández, Juan; Ruiz-Aguado, Jorge; Herrero, Juan Azael;

    2016-01-01

    The purpose of this study was to determine the adaptive response of ratings of perceived exertion (RPE) and pain over six consecutive training sessions. Thirty subjects were assigned to either a blood flow restricted training group (BFRT) or a high intensity group (HIT). BFRT group performed four...... set. Per-session RPE and pain were considered as the average value throughout all sets. RPE dropped from Session 4 following HIT (8.5 to 7.6, p<0.05) and from Session 5 following BFRT (7.4 to 6.0, p<0.01). Perceived pain dropped from Session 5 in both groups (HIT: 6.2 to 5.4 and BFRT: 8.1 to 6.3, p<0...

  20. Subjectivity: A Case of Biological Individuation and an Adaptive Response to Informational Overflow

    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

  1. In vivo adaptive response of the peripheral conduit artery in patients with borderline systolic hypertension

    陶军; 靳亚非; 王礼春; 唐安丽; 廖新学; 杨震; 马虹

    2003-01-01

    Objective To investigate elastic changes of the radial artery, a medium-sized muscular peripheral conduit artery, in patients with borderline systolic hypertension. Methods Using a non-invasive high-resolution echo-tracking device coupled to a photoplethysmography (Finapres system) allowing simultaneous arterial diameter and finger blood pressure monitoring, we measured radial artery elastic parameters of 20 patients with borderline systolic hypertension and 20 normal subjects according to Langewouters model.Results The diameter of the radial artery of control subjects and those with borderline systolic hypertension at the isobaric level of 100 mmHg and mean arterial pressure was similar, but the compliance and distensibility at similar conditions in patients with borderline systolic hypertension did not further reduced and even increased. Conclusion In patients with borderline systolic hypertension, the adaptive responses of the radial artery compliance and distensibility to increased pressure were directed to maintain its elasticity, contributing to the homeostasis of the cardiovascular system.

  2. Impacts of climate change on tourism in the Mediterranean. Adaptive responses

    Key sensitivities to Mediterranean tourism include drought and heat waves, both of which are likely to increase with projected greenhouse warming. Adaptive responses must include lengthening of the present season and particularly taking care to cater for the increasing number of older people in the population of Northern European countries who will demand high environmental and accommodation standards and look for more bespoke holidays than the mass market tourist. Climate change in Northern Europe may affect the push-pull factors which currently favour a summer peak of tourists in many Mediterranean destinations. Infra structure and beaches may well be at risk from sea level rise and there are likely to be increased problems from forest fires, water supplies and hygiene

  3. Age aspect of adaptive response of the central nervous system in the state of emotional pain

    Demchenko Ye.M.

    2014-11-01

    Full Text Available The formation of higher adaptive response in the postoperative period was investigated in experiments on rats of two age groups. It was found inhibition of the orientation-motor and emotional activity in young (5-6 months and old rats (20-24 months with the greatear effect in animals of the first age group. In young rats the inhibition of spatial memory was observed – number of food-getting depleted reactions decreased by 28%. Cognitive deficit was accompanied by opposite changes in the content of free unsaturated fatty acids (C18: 2.3, respectively to age features: decreased by 46% in the cortex of young rats and increased by 2.5-fold in the hippocampus of old animals.

  4. Bone sarcoma in humans induced by radium: A threshold response?

    The radium 226 and radium 228 have induced malignancies in the skeleton (primarily bone sarcomas) of humans. They have also induced carcinomas in the paranasal sinuses and mastoid air cells. There is no evidence that any leukemias or any other solid cancers have been induced by internally deposited radium. This paper discuses a study conducted on the dial painter population. This study made a concerted effort to verify, for each of the measured radium cases, the published values of the skeletal dose and the initial intake of radium. These were derived from body content measurements made some 40 years after the radium intake. Corrections to the assumed radium retention function resulted in a considerable number of dose changes. These changes have changed the shape of the dose response function. It now appears that the induction of bone sarcomas is a threshold process

  5. Cause–effect relationship among morphological adaptations, growth, and gas exchange response of pedunculate oak seedlings to waterlogging

    Tatin Froux, Fabienne; Capelli, Nicolas; Parelle, Julien

    2014-01-01

    & Context In response to waterlogging, pedunculate oak is known to develop adventitious roots and hypertrophied lenti-cels. However, to date, a link between these adaptations and the ability to maintain net CO 2 assimilation rates and growth has not been demonstrated. & Aims The aim of this study was to explore the cause–effect relationship between the ability to form morphological adap-tations (hypertrophied lenticels and adventitious roots) and the capacity to maintain high assimilation rat...

  6. Depressive Symptoms Enhance Stress-induced Inflammatory Responses

    Fagundes, Christopher P.; Glaser, Ronald; Hwang, Beom Seuk; Malarkey, William B.; Kiecolt-Glaser, Janice K.

    2012-01-01

    Depression is a risk factor for morbidity and mortality, and immune dysregulation may be partially responsible for this link. Proinflammatory cytokines such as interleukin 6 (IL-6) are reliable predictors of quality of life, morbidity, and many causes of mortality. The current study evaluated relationships between depressive symptoms, as assessed by the CES-D, and stress-induced inflammation. The participants, 138 healthy adults, were evaluated at rest, and after a standardized laboratory spe...

  7. Local and Systemic Inflammatory Responses to Experimentally Induced Gingivitis

    Leishman, Shaneen J.; Seymour, Gregory J.; Ford, Pauline J.

    2013-01-01

    This study profiled the local and systemic inflammatory responses to experimentally induced gingivitis. Eight females participated in a 21-day experimental gingivitis model followed by a 14-day resolution phase. Bleeding on probing and plaque index scores were assessed before, during, and after resolution of gingival inflammation, and samples of saliva, GCF, and plasma were collected. Samples were assessed for biomarkers of inflammation using the BioPlex platform and ELISA. There were no sign...

  8. Food-induced brain responses and eating behaviour

    Smeets, P.A.M.; CHARBONNIER, L.; Meer, van der, D; Laan, van der, Paul Maarten; Spetter, M.S.

    2012-01-01

    The brain governs food intake behaviour by integrating many different internal and external state and trait-related signals. Understanding how the decisions to start and to stop eating are made is crucial to our understanding of (maladaptive patterns of) eating behaviour. Here, we aim to (1) review the current state of the field of 'nutritional neuroscience' with a focus on the interplay between food-induced brain responses and eating behaviour and (2) highlight research needs and techniques ...

  9. Mechanisms and biological importance of photon-induced bystander responses. Do they have an impact on low-dose radiation responses

    Elucidating the biological effect of low linear energy transfer (LET), low-dose and/or low-dose-rate ionizing radiation is essential in ensuring radiation safety. Over the past two decades, non-targeted effects, which are not only a direct consequence of radiation-induced initial lesions produced in cellular DNA but also of intra- and inter-cellular communications involving both targeted and non-targeted cells, have been reported and are currently defining a new paradigm in radiation biology. These effects include radiation-induced adaptive response, low-dose hypersensitivity, genomic instability, and radiation-induced bystander response (RIBR). RIBR is generally defined as a cellular response that is induced in non-irradiated cells that receive bystander signals from directly irradiated cells. RIBR could thus play an important biological role in low-dose irradiation conditions. However, this suggestion was mainly based on findings obtained using high-LET charged-particle radiations. The human population (especially the Japanese, who are exposed to lower doses of radon than the world average) is more frequently exposed to low-LET photons (X-rays or γ-rays) than to high-LET charged-particle radiation on a daily basis. There are currently a growing number of reports describing a distinguishing feature between photon-induced bystander response and high-LET RIBR. In particular, photon-induced by-stander response is strongly influenced by irradiation dose, the irradiated region of the targeted cells, and p53 status. The present review focuses on the photon-induced bystander response, and discusses its impact on the low-dose radiation effect. (author)

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

    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.

  11. Characterization of homologous and heterologous adaptive immune responses in porcine reproductive and respiratory syndrome virus infection.

    Díaz, Ivan; Gimeno, Mariona; Darwich, Laila; Navarro, Nuria; Kuzemtseva, Liudmila; López, Sergio; Galindo, Ivan; Segalés, Joaquim; Martín, Margarita; Pujols, Joan; Mateu, Enric

    2012-01-01

    The present study characterized the homologous and heterologous immune response in type-I porcine reproductive and respiratory syndrome virus (PRRSV) infection. Two experiments were conducted: in experiment 1, eight pigs were inoculated with PRRSV strain 3262 and 84 days post-inoculation (dpi) they were challenged with either strain 3262 or strain 3267 and followed for the next 14 days (98 dpi). In experiment 2, eight pigs were inoculated with strain 3267 and challenged at 84 dpi as above. Clinical course, viremia, humoral response (neutralizing and non-neutralizing antibodies, NA) and virus-specific IFN-γ responses (ELISPOT) were evaluated all throughout the study. Serum levels of IL-1, IL-6, IL-8, TNF-α and TGF-β were determined (ELISA) after the second challenge. In experiment 1 primo-inoculation with strain 3262 induced viremia of ≤ 28 days, low titres of homologous NA but strong IFN-γ responses. In contrast, strain 3267 induced longer viremias (up to 56 days), higher NA titres (≤ 6 log2) and lower IFN-γ responses. Inoculation with 3267 produced higher serum IL-8 levels. After the re-challenge at 84 dpi, pigs in experiment 1 developed mostly a one week viremia regardless of the strain used. In experiment 2, neither the homologous nor the heterologous challenge resulted in detectable viremia although PRRSV was present in tonsils of some animals. Homologous re-inoculation with 3267 produced elevated TGF-β levels in serum for 7-14 days but this did not occur with the heterologous re-inoculation. In conclusion, inoculation with different PRRSV strains result in different virological and immunological outcomes and in different degrees of homologous and heterologous protection. PMID:22515169

  12. Characterization of homologous and heterologous adaptive immune responses in porcine reproductive and respiratory syndrome virus infection

    Díaz Ivan

    2012-04-01

    Full Text Available Abstract The present study characterized the homologous and heterologous immune response in type-I porcine reproductive and respiratory syndrome virus (PRRSV infection. Two experiments were conducted: in experiment 1, eight pigs were inoculated with PRRSV strain 3262 and 84 days post-inoculation (dpi they were challenged with either strain 3262 or strain 3267 and followed for the next 14 days (98 dpi. In experiment 2, eight pigs were inoculated with strain 3267 and challenged at 84 dpi as above. Clinical course, viremia, humoral response (neutralizing and non-neutralizing antibodies, NA and virus-specific IFN-γ responses (ELISPOT were evaluated all throughout the study. Serum levels of IL-1, IL-6, IL-8, TNF-α and TGF-β were determined (ELISA after the second challenge. In experiment 1 primo-inoculation with strain 3262 induced viremia of ≤ 28 days, low titres of homologous NA but strong IFN-γ responses. In contrast, strain 3267 induced longer viremias (up to 56 days, higher NA titres (≤ 6 log2 and lower IFN-γ responses. Inoculation with 3267 produced higher serum IL-8 levels. After the re-challenge at 84 dpi, pigs in experiment 1 developed mostly a one week viremia regardless of the strain used. In experiment 2, neither the homologous nor the heterologous challenge resulted in detectable viremia although PRRSV was present in tonsils of some animals. Homologous re-inoculation with 3267 produced elevated TGF-β levels in serum for 7–14 days but this did not occur with the heterologous re-inoculation. In conclusion, inoculation with different PRRSV strains result in different virological and immunological outcomes and in different degrees of homologous and heterologous protection.

  13. Dose response of micronuclei induced by combination radiation of α-particles and γ-rays in human lymphoblast cells

    Ren, Ruiping; He, Mingyuan; Dong, Chen; Xie, Yuexia; Ye, Shuang; Yuan, Dexiao [Institute of Radiation Medicine, Fudan University, No. 2094 Xie-Tu Road, Shanghai 200032 (China); Shao, Chunlin, E-mail: clshao@shmu.edu.cn [Institute of Radiation Medicine, Fudan University, No. 2094 Xie-Tu Road, Shanghai 200032 (China)

    2013-01-15

    Highlights: ► α-Particle induced MN had a biphasic dose–response followed by a bystander model. ► MN dose–response of α- and γ-combination IR was similar to that of α-particle. ► α-Particles followed by γ-rays yielded a synergistic effect on MN induction. ► Low dose γ-rays triggered antagonistic and adaptive responses against α-particle. - Abstract: Combination radiation is a real situation of both nuclear accident exposure and space radiation environment, but its biological dosimetry is still not established. This study investigated the dose–response of micronuclei (MN) induction in lymphocyte by irradiating HMy2.CIR lymphoblast cells with α-particles, γ-rays, and their combinations. Results showed that the dose–response of MN induced by γ-rays was well-fitted with the linear-quadratic model. But for α-particle irradiation, the MN induction had a biphasic phenomenon containing a low dose hypersensitivity characteristic and its dose response could be well-stimulated with a state vector model where radiation-induced bystander effect (RIBE) was involved. For the combination exposure, the dose response of MN was similar to that of α-irradiation. However, the yield of MN was closely related to the sequence of irradiations. When the cells were irradiated with α-particles at first and then γ-rays, a synergistic effect of MN induction was observed. But when the cells were irradiated with γ-rays followed by α-particles, an antagonistic effect of MN was observed in the low dose range although this combination radiation also yielded a synergistic effect at high doses. When the interval between two irradiations was extended to 4 h, a cross-adaptive response against the other irradiation was induced by a low dose of γ-rays but not α-particles.

  14. Dose response of micronuclei induced by combination radiation of α-particles and γ-rays in human lymphoblast cells

    Highlights: ► α-Particle induced MN had a biphasic dose–response followed by a bystander model. ► MN dose–response of α- and γ-combination IR was similar to that of α-particle. ► α-Particles followed by γ-rays yielded a synergistic effect on MN induction. ► Low dose γ-rays triggered antagonistic and adaptive responses against α-particle. - Abstract: Combination radiation is a real situation of both nuclear accident exposure and space radiation environment, but its biological dosimetry is still not established. This study investigated the dose–response of micronuclei (MN) induction in lymphocyte by irradiating HMy2.CIR lymphoblast cells with α-particles, γ-rays, and their combinations. Results showed that the dose–response of MN induced by γ-rays was well-fitted with the linear-quadratic model. But for α-particle irradiation, the MN induction had a biphasic phenomenon containing a low dose hypersensitivity characteristic and its dose response could be well-stimulated with a state vector model where radiation-induced bystander effect (RIBE) was involved. For the combination exposure, the dose response of MN was similar to that of α-irradiation. However, the yield of MN was closely related to the sequence of irradiations. When the cells were irradiated with α-particles at first and then γ-rays, a synergistic effect of MN induction was observed. But when the cells were irradiated with γ-rays followed by α-particles, an antagonistic effect of MN was observed in the low dose range although this combination radiation also yielded a synergistic effect at high doses. When the interval between two irradiations was extended to 4 h, a cross-adaptive response against the other irradiation was induced by a low dose of γ-rays but not α-particles

  15. Phylogeny of Toll-like receptor signaling: adapting the innate response.

    Jeffrey M Roach

    Full Text Available 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.

  16. Developing a Gene Biomarker at the Tipping Point of Adaptive and Adverse Responses in Human Bronchial Epithelial Cells.

    Jenna M Currier

    Full Text Available 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

  17. Fore-aft ground force adaptations to induced forelimb lameness in walking and trotting dogs.

    Abdelhadi, Jalal; Wefstaedt, Patrick; Nolte, Ingo; Schilling, Nadja

    2012-01-01

    Animals alter their locomotor mechanics to adapt to a loss of limb function. To better understand their compensatory mechanisms, this study evaluated the changes in the fore-aft ground forces to forelimb lameness and tested the hypothesis that dogs unload the affected limb by producing a nose-up pitching moment via the exertion of a net-propulsive force when the lame limb is on the ground. Seven healthy Beagles walked and trotted at steady speed on an instrumented treadmill while horizontal force data were collected before and after a moderate lameness was induced. Peak, mean and summed braking and propulsive forces as well as the duration each force was exerted and the time to reach maximum force were evaluated for both the sound and the lame condition. Compared with the sound condition, a net-propulsive force was produced by the lame diagonal limbs due to a reduced braking force in the affected forelimb and an increased propulsive force in the contralateral hindlimb when the dogs walked and trotted. To regain pitch stability and ensure steady speed for a given locomotor cycle, the dogs produced a net-braking force when the sound diagonal limbs were on the ground by exerting greater braking forces in both limbs during walking and additionally reducing the propulsive force in the hindlimb during trotting. Consistent with the proposed mechanism, dogs maximize their double support phases when walking. Likely associated with the fore-aft force adaptations to lameness are changes in muscle recruitment that potentially result in short- and long-term effects on the limb and trunk muscles. PMID:23300614

  18. Mitigation of peroxynitrite-mediated nitric oxide (NO) toxicity as a mechanism of induced adaptive NO resistance in the CNS.

    Bishop, Amy; Gooch, Renea; Eguchi, Asuka; Jeffrey, Stephanie; Smallwood, Lorraine; Anderson, James; Estevez, Alvaro G

    2009-04-01

    During CNS injury and diseases, nitric oxide (NO) is released at a high flux rate leading to formation of peroxynitrite (ONOO(*)) and other reactive nitrogenous species, which nitrate tyrosines of proteins to form 3-nitrotyrosine (3NY), leading to cell death. Previously, we have found that motor neurons exposed to low levels of NO become resistant to subsequent cytotoxic NO challenge; an effect dubbed induced adaptive resistance (IAR). Here, we report IAR mitigates, not only cell death, but 3NY formation in response to cytotoxic NO. Addition of an NO scavenger before NO challenge duplicates IAR, implicating reactive nitrogenous species in cell death. Addition of uric acid (a peroxynitrite scavenger) before cytotoxic NO challenge, duplicates IAR, implicating peroxynitrite, with subsequent 3NY formation, in cell death, and abrogation of this pathway as a mechanism of IAR. IAR is dependent on the heme-metabolizing enzyme, heme oxygenase-1 (HO1), as indicated by the elimination of IAR by a specific HO1 inhibitor, and by the finding that neurons isolated from HO1 null mice have increased NO sensitivity with concomitant increased 3NY formation. This data indicate that IAR is an HO1-dependent mechanism that prevents peroxynitrite-mediated NO toxicity in motor neurons, thereby elucidating therapeutic targets for the mitigation of CNS disease and injury. PMID:19183270

  19. Rod-Driven OFF Pathway Responses in the Distal Retina: Dark-Adapted Flicker Electroretinogram in Mouse

    Lei, Bo

    2012-01-01

    Purpose The rodent retina does not exhibit a positive OFF-response in the electroretinogram (ERG), which makes it difficult to evaluate its OFF-pathway functions in vivo. We studied the rod-driven OFF pathway responses by using a dark-adapted 10-Hz flicker ERG procedure in mouse. Materials and Methods Conventional ERGs and 10-Hz dark-adapted flicker ERGs were obtained in wild-type mice (C57BL/6), in mice with pure rod (cpfl1) or pure cone (rho−/− ) function, and in nob1 mice which have a sele...

  20. Topical CpG Oligodeoxynucleotide Adjuvant Enhances the Adaptive Immune Response against Influenza A Infections.

    Cheng, Wing Ki; Plumb, Adam William; Lai, Jacqueline Cheuk-Yan; Abraham, Ninan; Dutz, Jan Peter

    2016-01-01

    Current influenza vaccines generate humoral immunity, targeting highly variable epitopes and thus fail to achieve long-term protection. T cells recognize and respond to several highly conserved epitopes across influenza serotypes. A strategy of raising strong cytotoxic T cell memory responses to epitopes conserved across serotypes would provide cross serotype protection, eliminating the need for annual vaccination. We explored the adjuvant potential of epicutaneous (ec) and subcutaneous (sc) delivery of CpG oligodeoxynucleotide in conjunction with sc protein immunization to improve protection against influenza A virus (IAV) infections using a mouse model. We found enhanced long-term protection with epicutaneous CpG ODN (ecCpG) compared to subcutaneous CpG ODN (scCpG) as demonstrated by reduced viral titers in the lungs. This correlated with increased antigen-specific CD8 T cells in the airways and the lungs. The memory T cell response after immunization with ecCpG adjuvant was comparable to memory response by priming with IAV infection in the lungs. In addition, ecCpG was more efficient than scCpG in inducing the generation of IFN-γ producing CD4 T cells. The adjuvant effect of ecCpG was accompanied with its ability to modulate tissue-homing molecules on T cells that may direct them to the site of infection. Together, this work provides evidence for using ecCpG to induce strong antibody and memory T cell responses to confer protection against IAV infection. PMID:27524984

  1. Responses of the autonomic nervous system in altitude adapted and high altitude pulmonary oedema subjects

    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. Fluid flow induced calcium response in osteoblasts: mathematical modeling.

    Su, J H; Xu, F; Lu, X L; Lu, T J

    2011-07-28

    Fluid flow in the bone lacuno-canalicular network can induce dynamic fluctuation of intracellular calcium concentration ([Ca(2+)](i)) in osteoblasts, which plays an important role in bone remodeling. There has been limited progress in the mathematical modeling of this process probably due to its complexity, which is controlled by various factors such as Ca(2+) channels and extracellular messengers. In this study we developed a mathematical model to describe [Ca(2+)](i) response induced by fluid shear stress (SS) by integrating the major factors involved and analyzed the effects of different experimental setups (e.g. [Ca(2+)](i) baseline, pretreatment with ATP). In this model we considered the ATP release process and the activities of multiple ion channels and purinergic receptors. The model was further verified quantitatively by comparing the simulation results with experimental data reported in literature. The results showed that: (i) extracellular ATP concentration has more significant effect on [Ca(2+)](i) baseline (73% increase in [Ca(2+)](i) with extracellular ATP concentration varying between 0 and 10 μM), as compared to that induced by SS (25% variation in [Ca(2+)](i) with SS varying from 0 to 3.5 Pa); (ii) Pretreatment with ATP-medium results in different [Ca(2+)](i) response as compared to the control group (ATP-free medium) under SS; (iii) Relative [Ca(2+)](i) fluctuation over baseline is more reliable to show the [Ca(2+)](i) response process than the absolute [Ca(2+)](i) response peak. The developed model may improve the experimental design and facilitate our understanding of the mechanotransduction process in osteoblasts. PMID:21665208

  3. A Drosophila immune response against Ras-induced overgrowth

    Thomas Hauling

    2014-03-01

    Full Text Available Our goal is to characterize the innate immune response against the early stage of tumor development. For this, animal models where genetic changes in specific cells and tissues can be performed in a controlled way have become increasingly important, including the fruitfly Drosophila melanogaster. Many tumor mutants in Drosophila affect the germline and, as a consequence, also the immune system itself, making it difficult to ascribe their phenotype to a specific tissue. Only during the past decade, mutations have been induced systematically in somatic cells to study the control of tumorous growth by neighboring cells and by immune cells. Here we show that upon ectopic expression of a dominant-active form of the Ras oncogene (RasV12, both imaginal discs and salivary glands are affected. Particularly, the glands increase in size, express metalloproteinases and display apoptotic markers. This leads to a strong cellular response, which has many hallmarks of the granuloma-like encapsulation reaction, usually mounted by the insect against larger foreign objects. RNA sequencing of the fat body reveals a characteristic humoral immune response. In addition we also identify genes that are specifically induced upon expression of RasV12. As a proof-of-principle, we show that one of the induced genes (santa-maria, which encodes a scavenger receptor, modulates damage to the salivary glands. The list of genes we have identified provides a rich source for further functional characterization. Our hope is that this will lead to a better understanding of the earliest stage of innate immune responses against tumors with implications for mammalian immunity.

  4. Insurance Companies’ Responses to Climate Change: Adaptation, Dynamic Capabilities and Competitive Advantage

    Kristin Stechemesser; Jan Endrikat; Nico Grasshoff; Edeltraud Guenther

    2015-01-01

    Drawing on the dynamic capability view, we analyse how insurers adapt to climate change impacts and how adaptation relates to corporate financial performance. Based on a comprehensive literature review, we deduce seven categories of adaptation measures associated with three dynamic capability dimensions of climate change adaptation (i.e. climate knowledge absorption, climate-related operational flexibility and strategic climate integration). Using this framework, we conduct a content analysis...

  5. Cholic acid induces a Cftr dependent biliary secretion and liver growth response in mice.

    Frank A J A Bodewes

    Full Text Available The cause of Cystic fibrosis liver disease (CFLD, is unknown. It is well recognized that hepatic exposure to hydrophobic bile salts is associated with the development of liver disease. For this reason, we hypothesize that, CFTR dependent variations, in the hepatic handling of hydrophobic bile salts, are related to the development CFLD. To test our hypothesis we studied, in Cftr-/- and control mice, bile production, bile composition and liver pathology, in normal feeding condition and during cholate exposure, either acute (intravenous or chronic (three weeks via the diet. In Cftr-/- and control mice the basal bile production was comparable. Intravenous taurocholate increased bile production to the same extent in Cftr-/- and control mice. However, chronic cholate exposure increased the bile flow significantly less in Cftr-/- mice than in controls, together with significantly higher biliary bile salt concentration in Cftr-/- mice. Prolonged cholate exposure, however, did not induce CFLD like pathology in Cftr-/- mice. Chronic cholate exposure did induce a significant increase in liver mass in controls that was absent in Cftr-/- mice. Chronic cholate administration induces a cystic fibrosis-specific hepatobiliary phenotype, including changes in bile composition. These changes could not be associated with CFLD like pathological changes in CF mouse livers. However, chronic cholate administration induces liver growth in controls that is absent in Cftr-/- mice. Our findings point to an impaired adaptive homeotrophic liver response to prolonged hydrophobic bile salt exposure in CF conditions.

  6. Adaptability: How Students' Responses to Uncertainty and Novelty Predict Their Academic and Non-Academic Outcomes

    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…

  7. Tissue mechanics govern the rapidly adapting and symmetrical response to touch.

    Eastwood, Amy L; Sanzeni, Alessandro; Petzold, Bryan C; Park, Sung-Jin; Vergassola, Massimo; Pruitt, Beth L; Goodman, Miriam B

    2015-12-15

    Interactions with the physical world are deeply rooted in our sense of touch and depend on ensembles of somatosensory neurons that invade and innervate the skin. Somatosensory neurons convert the mechanical energy delivered in each touch into excitatory membrane currents carried by mechanoelectrical transduction (MeT) channels. Pacinian corpuscles in mammals and touch receptor neurons (TRNs) in Caenorhabditis elegans nematodes are embedded in distinctive specialized accessory structures, have low thresholds for activation, and adapt rapidly to the application and removal of mechanical loads. Recently, many of the protein partners that form native MeT channels in these and other somatosensory neurons have been identified. However, the biophysical mechanism of symmetric responses to the onset and offset of mechanical stimulation has eluded understanding for decades. Moreover, it is not known whether applied force or the resulting indentation activate MeT channels. Here, we introduce a system for simultaneously recording membrane current, applied force, and the resulting indentation in living C. elegans (Feedback-controlled Application of mechanical Loads Combined with in vivo Neurophysiology, FALCON) and use it, together with modeling, to study these questions. We show that current amplitude increases with indentation, not force, and that fast stimuli evoke larger currents than slower stimuli producing the same or smaller indentation. A model linking body indentation to MeT channel activation through an embedded viscoelastic element reproduces the experimental findings, predicts that the TRNs function as a band-pass mechanical filter, and provides a general mechanism for symmetrical and rapidly adapting MeT channel activation relevant to somatosensory neurons across phyla and submodalities. PMID:26627717

  8. Hurricane Sandy: Caught in the eye of the storm and a city's adaptation response

    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

  9. Testing the ability of viral haemorrhagic septicaemia virus to evade the protective immune response induced in rainbow trout by DNA vaccination

    Sepulveda, Dagoberto; Lorenzen, Niels

    2013-01-01

    glycoprotein, the only surface protein of the VHSV, has been successful as an experimental prophylactic treatment against this disease, because it induces a strong innate (interferon) and adaptive (cellular and humoral) immune response. However, since RNA viruses are known to possess high variability, this...

  10. Human response and adaptation to drought in the arid zone: lessons from southern Africa

    W. R.J. Dean

    2009-12-01

    Full Text Available Human adaptation and response to drought is primarily through evasion or endurance. A review of historical agricultural practices in southern Africa demonstrates evidence of drought evasion response strategies in well-established transhumance routes, where herders move livestock on a seasonal basis in order to exploit resources subject to different climatic regimes. European settlers to the arid regions of South Africa quickly recognised the necessity of these evasion options to survive drought, and adopted the transhumance practices of indigenous farmers. Areas of geographically diverse resource bases became hotly contested by settlers and indigenous farmers. The success of evasion systems are shown to hinge on good social and institutional support structures. When movement is not an option, drought endurance is pursued by attempting to limit the damage to the natural resource base. This is through a number of means such as forage conservation, varying livestock types and numbers, water and soil conservation and taking up alternative livelihood options. State responses to drought over the last century reflect the general South African pattern of racially divided and unjust policies relating to resource access. Historically the state provided considerable support to white commercial farmers. This support was frequently contradictory in its aims and generally was inadequate to enable farmers to cope with drought. Since the advent of democracy in 1994, the state has intervened less, with some support extended to previously disadvantaged and poor communal farmers. Climate change predictions suggest an increase in drought, suggesting that the adoption of mitigating strategies should be a matter of urgency. To do this South Africa needs to build social and institutional capacity, strive for better economic and environmental sustainability, embed drought-coping mechanisms into land restitution policy to ensure the success of this programme, and

  11. Adaptation of the Agrobacterium tumefaciens VirG response regulator to activate transcription in plants.

    Czarnecka-Verner, Eva; Salem, Tarek A; Gurley, William B

    2016-02-01

    The Agrobacterium tumefaciens VirG response regulator of the VirA/VirG two-component system was adapted to function in tobacco protoplasts. The subcellular localization of VirG and VirA proteins transiently expressed in onion cells was determined using GFP fusions. Preliminary studies using Gal4DBD-VP16 fusions with VirG and Escherichia coli UhpA, and NarL response regulators indicated compatibility of these bacterial proteins with the eukaryotic transcriptional apparatus. A strong transcriptional activator based on tandem activation domains from the Drosophila fushi tarazu and Herpes simplex VP16 was created. Selected configurations of the two-site Gal4-vir box GUS reporters were activated by chimeric effectors dependent on either the yeast Gal4 DNA-binding domain or that of VirG. Transcriptional induction of the GUS reporter was highest for the VirE19-element promoter with both constitutive and wild-type VirG-tandem activation domain effectors. Multiple VirE19 elements increased the reporter activity proportionately, indicating that the VirG DNA binding domain was functional in plants. The VirG constitutive-Q-VP16 effector was more active than the VirG wild-type. In both the constitutive and wild-type forms of VirG, Q-VP16 activated transcription of the GUS reporter best when located at the C-terminus, i.e. juxtaposed to the VirG DNA binding domain. These results demonstrate the possibility of using DNA binding domains from bacterial response regulators and their cognate binding elements in the engineering of plant gene expression. PMID:26646288

  12. Natural and Induced Humoral Responses to MUC1

    MUC1 is a membrane-tethered mucin expressed on the ductal cell surface of glandular epithelial cells. Loss of polarization, overexpression and aberrant glycosylation of MUC1 in mucosal inflammation and in adenocarcinomas induces humoral immune responses to the mucin. MUC1 IgG responses have been associated with a benefit in survival in patients with breast, lung, pancreatic, ovarian and gastric carcinomas. Antibodies bound to the mucin may curb tumor progression by restoring cell-cell interactions altered by tumor-associated MUC1, thus preventing metastatic dissemination, as well as counteracting the immune suppression exerted by the molecule. Furthermore, anti-MUC1 antibodies are capable of effecting tumor cell killing by antibody-dependent cell-mediated cytotoxicity. Although cytotoxic T cells are indispensable to achieve anti-tumor responses in advanced disease, abs to tumor-associated antigens are ideally suited to address minimal residual disease and may be sufficient to exert adequate immune surveillance in an adjuvant setting, destroying tumor cells as they arise or maintaining occult disease in an equilibrium state. Initial evaluation of MUC1 peptide/glycopeptide mono and polyvalent vaccines has shown them to be immunogenic and safe; anti-tumor responses are scarce. Progress in carbohydrate synthesis has yielded a number of sophisticated substrates that include MUC1 glycopeptide epitopes that are at present in preclinical testing. Adjuvant vaccination with MUC1 glycopeptide polyvalent vaccines that induce strong humoral responses may prevent recurrence of disease in patients with early stage carcinomas. Furthermore, prophylactic immunotherapy targeting MUC1 may be a strategy to strengthen immune surveillance and prevent disease in subjects at hereditary high risk of breast, ovarian and colon cancer

  13. Natural and Induced Humoral Responses to MUC1

    Mensdorff-Pouilly, Silvia von, E-mail: s.vonmensdorff@vumc.nl; Moreno, Maria [Department of Obstetrics and Gynecology, VU University Medical Center, De Boelelaan 1117, Amsterdam 1081 HV (Netherlands); Verheijen, René H. M. [Department of Woman & Baby, Division of Surgical & Oncological Gynaecology, University Medical Center Utrecht, Heidelberglaan 100, Utrecht 3508 GA (Netherlands)

    2011-07-29

    MUC1 is a membrane-tethered mucin expressed on the ductal cell surface of glandular epithelial cells. Loss of polarization, overexpression and aberrant glycosylation of MUC1 in mucosal inflammation and in adenocarcinomas induces humoral immune responses to the mucin. MUC1 IgG responses have been associated with a benefit in survival in patients with breast, lung, pancreatic, ovarian and gastric carcinomas. Antibodies bound to the mucin may curb tumor progression by restoring cell-cell interactions altered by tumor-associated MUC1, thus preventing metastatic dissemination, as well as counteracting the immune suppression exerted by the molecule. Furthermore, anti-MUC1 antibodies are capable of effecting tumor cell killing by antibody-dependent cell-mediated cytotoxicity. Although cytotoxic T cells are indispensable to achieve anti-tumor responses in advanced disease, abs to tumor-associated antigens are ideally suited to address minimal residual disease and may be sufficient to exert adequate immune surveillance in an adjuvant setting, destroying tumor cells as they arise or maintaining occult disease in an equilibrium state. Initial evaluation of MUC1 peptide/glycopeptide mono and polyvalent vaccines has shown them to be immunogenic and safe; anti-tumor responses are scarce. Progress in carbohydrate synthesis has yielded a number of sophisticated substrates that include MUC1 glycopeptide epitopes that are at present in preclinical testing. Adjuvant vaccination with MUC1 glycopeptide polyvalent vaccines that induce strong humoral responses may prevent recurrence of disease in patients with early stage carcinomas. Furthermore, prophylactic immunotherapy targeting MUC1 may be a strategy to strengthen immune surveillance and prevent disease in subjects at hereditary high risk of breast, ovarian and colon cancer.

  14. Nonlinear dose-response relationships and inducible cellular defence mechanisms

    With the inclusion of inducible radioprotective mechanisms in a radiobiological state-vector model it was possible to explain plateaus in dose-response relationships for neoplastic transformation produced by in vitro irradiation of different cell lines with low-LET irradiation at high dose rates. The current study repeated the simulation of one data set that contains a plateau at mid doses. In contrast to earlier studies, the new one did not model the repair of double-strand breaks (DSBs) located in bulk DNA (likely via non-homologous end joining) as being inducible. Repair of specific DSBs located in actively transcribed genes was assumed to occur via homologous recombination and was considered to be inducible. This reduced the number of parameters that have to be determined by fitting the model to data. In addition, all types of radical scavengers were formerly considered to be inducible by radiation. This was redefined in the current work and the effectiveness of scavengers was implemented in a refined way. The current work investigated whether these and other model adjustments lead to an improved fit of the data set. (author)

  15. Vitamin E-enriched diet reduces adaptive responses to training determining respiratory capacity and redox homeostasis in rat heart.

    Venditti, Paola; Napolitano, Gaetana; Barone, Daniela; Pervito, Emanuela; Di Meo, Sergio

    2016-01-01

    We investigated whether reactive oxygen species (ROS) are involved in heart adaptive responses administering a vitamin E-enriched diet to trained rats. Using the homogenates and/or mitochondria from rat hearts we determined the aerobic capacity, tissue level of mitochondrial proteins, and expression of cytochrome c and factors (PGC-1, NRF-1, and NRF-2) involved in mitochondrial biogenesis. We also determined the oxidative damage, glutathione peroxidase (GPX) and reductase activities, glutathione content, mitochondrial ROS release rate, and susceptibility to in vitro oxidative challenge. Glutathione (GSH) content was not affected by both training and antioxidant supplementation. Conversely, antioxidant supplementation prevented metabolic adaptations to training, such as the increases in oxidative capacity, tissue content of mitochondrial proteins, and cytochrome c expression, attenuated some protective adaptations, such as the increase in antioxidant enzyme activities, and did not modify the decrease in ROS release by succinate supplemented mitochondria. Moreover, vitamin E prevented the training-linked increase in tissue capacity to oppose an oxidative attach. The antioxidant effects were associated with decreased levels of PGC-1, NRF-1, and NRF-2 expression. Our results support the idea that some heart adaptive responses to training depend on ROS produced during the exercise sessions and are mediated by the increase in PGC-1 expression which is involved in both the regulation of respiratory capacity and antioxidant protection. However, vitamin inability to prevent some adaptations suggests that other signaling pathways impinging on PGC-1 can modify the response to the antioxidant integration. PMID:26467971

  16. Prolonged inorganic arsenite exposure suppresses insulin-stimulated AKT S473 phosphorylation and glucose uptake in 3T3-L1 adipocytes: Involvement of the adaptive antioxidant response

    Highlights: → In 3T3-L1 adipocytes iAs3+ decreases insulin-stimulated glucose uptake. → iAs3+ attenuates insulin-induced phosphorylation of AKT S473. → iAs3+ activates the cellular adaptive oxidative stress response. → iAs3+ impairs insulin-stimulated ROS signaling. → iAs3+ decreases expression of adipogenic genes and GLUT4. -- Abstract: There is growing evidence that chronic exposure of humans to inorganic arsenic, a potent environmental oxidative stressor, is associated with the incidence of type 2 diabetes (T2D). One critical feature of T2D is insulin resistance in peripheral tissues, especially in mature adipocytes, the hallmark of which is decreased insulin-stimulated glucose uptake (ISGU). Despite the deleterious effects of reactive oxygen species (ROS), they have been recognized as a second messenger serving an intracellular signaling role for insulin action. Nuclear factor erythroid 2-related factor 2 (NRF2) is a central transcription factor regulating cellular adaptive response to oxidative stress. This study proposes that in response to arsenic exposure, the NRF2-mediated adaptive induction of endogenous antioxidant enzymes blunts insulin-stimulated ROS signaling and thus impairs ISGU. Exposure of differentiated 3T3-L1 cells to low-level (up to 2 μM) inorganic arsenite (iAs3+) led to decreased ISGU in a dose- and time-dependent manner. Concomitant to the impairment of ISGU, iAs3+ exposure significantly attenuated insulin-stimulated intracellular ROS accumulation and AKT S473 phosphorylation, which could be attributed to the activation of NRF2 and induction of a battery of endogenous antioxidant enzymes. In addition, prolonged iAs3+ exposure of 3T3-L1 adipocytes resulted in significant induction of inflammatory response genes and decreased expression of adipogenic genes and glucose transporter type 4 (GLUT4), suggesting chronic inflammation and reduction in GLUT4 expression may also be involved in arsenic-induced insulin resistance in adipocytes

  17. Prolonged inorganic arsenite exposure suppresses insulin-stimulated AKT S473 phosphorylation and glucose uptake in 3T3-L1 adipocytes: Involvement of the adaptive antioxidant response

    Xue, Peng [The Hamner Institutes for Health Sciences, Research Triangle Park, NC 27709 (United States); School of Public Health, China Medical University, Shenyang 110001 (China); Hou, Yongyong; Zhang, Qiang; Woods, Courtney G.; Yarborough, Kathy; Liu, Huiyu [The Hamner Institutes for Health Sciences, Research Triangle Park, NC 27709 (United States); Sun, Guifan [School of Public Health, China Medical University, Shenyang 110001 (China); Andersen, Melvin E. [The Hamner Institutes for Health Sciences, Research Triangle Park, NC 27709 (United States); Pi, Jingbo, E-mail: jpi@thehamner.org [The Hamner Institutes for Health Sciences, Research Triangle Park, NC 27709 (United States)

    2011-04-08

    Highlights: {yields} In 3T3-L1 adipocytes iAs{sup 3+} decreases insulin-stimulated glucose uptake. {yields} iAs{sup 3+} attenuates insulin-induced phosphorylation of AKT S473. {yields} iAs{sup 3+} activates the cellular adaptive oxidative stress response. {yields} iAs{sup 3+} impairs insulin-stimulated ROS signaling. {yields} iAs{sup 3+} decreases expression of adipogenic genes and GLUT4. -- Abstract: There is growing evidence that chronic exposure of humans to inorganic arsenic, a potent environmental oxidative stressor, is associated with the incidence of type 2 diabetes (T2D). One critical feature of T2D is insulin resistance in peripheral tissues, especially in mature adipocytes, the hallmark of which is decreased insulin-stimulated glucose uptake (ISGU). Despite the deleterious effects of reactive oxygen species (ROS), they have been recognized as a second messenger serving an intracellular signaling role for insulin action. Nuclear factor erythroid 2-related factor 2 (NRF2) is a central transcription factor regulating cellular adaptive response to oxidative stress. This study proposes that in response to arsenic exposure, the NRF2-mediated adaptive induction of endogenous antioxidant enzymes blunts insulin-stimulated ROS signaling and thus impairs ISGU. Exposure of differentiated 3T3-L1 cells to low-level (up to 2 {mu}M) inorganic arsenite (iAs{sup 3+}) led to decreased ISGU in a dose- and time-dependent manner. Concomitant to the impairment of ISGU, iAs{sup 3+} exposure significantly attenuated insulin-stimulated intracellular ROS accumulation and AKT S473 phosphorylation, which could be attributed to the activation of NRF2 and induction of a battery of endogenous antioxidant enzymes. In addition, prolonged iAs{sup 3+} exposure of 3T3-L1 adipocytes resulted in significant induction of inflammatory response genes and decreased expression of adipogenic genes and glucose transporter type 4 (GLUT4), suggesting chronic inflammation and reduction in GLUT4

  18. SOS response induces persistence to fluoroquinolones in Escherichia coli.

    Tobias Dörr

    2009-12-01

    Full Text Available Bacteria can survive antibiotic treatment without acquiring heritable antibiotic resistance. We investigated persistence to the fluoroquinolone ciprofloxacin in Escherichia coli. Our data show that a majority of persisters to ciprofloxacin were formed upon exposure to the antibiotic, in a manner dependent on the SOS gene network. These findings reveal an active and inducible mechanism of persister formation mediated by the SOS response, challenging the prevailing view that persisters are pre-existing and formed purely by stochastic means. SOS-induced persistence is a novel mechanism by which cells can counteract DNA damage and promote survival to fluoroquinolones. This unique survival mechanism may be an important factor influencing the outcome of antibiotic therapy in vivo.

  19. Transcriptome and proteome analyses of adaptive responses to methyl methanesulfonate in Escherichia coli K-12 and ada mutant strains

    Lee Sang Yup

    2009-09-01

    Full Text Available Abstract Background The Ada-dependent adaptive response system in Escherichia coli is important for increasing resistance to alkylation damage. However, the global transcriptional and translational changes during this response have not been reported. Here we present time-dependent global gene and protein expression profiles following treatment with methyl methanesulfonate (MMS in E. coli W3110 and its ada mutant strains. Results Transcriptome profiling showed that 1138 and 2177 genes were differentially expressed in response to MMS treatment in the wild-type and mutant strains, respectively. A total of 81 protein spots representing 76 nonredundant proteins differentially expressed were identified using 2-DE and LC-MS/MS. In the wild-type strain, many genes were differentially expressed upon long-exposure to MMS, due to both adaptive responses and stationary phase responses. In the ada mutant strain, the genes involved in DNA replication, recombination, modification and repair were up-regulated 0.5 h after MMS treatment, indicating its connection to the SOS and other DNA repair systems. Interestingly, expression of the genes involved in flagellar biosynthesis, chemotaxis, and two-component regulatory systems related to drug or antibiotic resistance, was found to be controlled by Ada. Conclusion These results show in detail the regulatory components and pathways controlling adaptive response and how the related genes including the Ada regulon are expressed with this response.

  20. Synergistic innate and adaptive immune response to combination immunotherapy with anti-tumor antigen antibodies and extended serum half-life IL-2.

    Zhu, Eric F; Gai, Shuning A; Opel, Cary F; Kwan, Byron H; Surana, Rishi; Mihm, Martin C; Kauke, Monique J; Moynihan, Kelly D; Angelini, Alessandro; Williams, Robert T; Stephan, Matthias T; Kim, Jacob S; Yaffe, Michael B; Irvine, Darrell J; Weiner, Louis M; Dranoff, Glenn; Wittrup, K Dane

    2015-04-13

    Cancer immunotherapies under development have generally focused on either stimulating T cell immunity or driving antibody-directed effector functions of the innate immune system such as antibody-dependent cell-mediated cytotoxicity (ADCC). We find that a combination of an anti-tumor antigen antibody and an untargeted IL-2 fusion protein with delayed systemic clearance induces significant tumor control in aggressive isogenic tumor models via a concerted innate and adaptive response involving neutrophils, NK cells, macrophages, and CD8(+) T cells. This combination therapy induces an intratumoral "cytokine storm" and extensive lymphocyte infiltration. Adoptive transfer of anti-tumor T cells together with this combination therapy leads to robust cures of established tumors and development of immunological memory. PMID:25873172

  1. Global Megacities Differing Adaptation Responses to Climate Change: an Analysis of Annual Spend of Ten Major cities on the adaptation economy

    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

  2. Acid stress adaptation protects saccharomyces cerevisiae from acetic acid-induced programme cell death

    Giannattasio, Sergio; Guaragnella, Nicoletta; Côrte-Real, Manuela; Passarella, Salvatore; Marra, Ersilia

    2005-01-01

    In this work evidence is presented that acid stress adaptation protects Saccharomyces cerevisiae from acetic acid-mediated programmed cell death. Exponential-phase yeast cells, non-adapted or adapted to acid stress by 30 min incubation in rich medium set at pH 3.0 with HCl, have been exposed to increasing concentrations of acetic acid and time course changes of cell viability have been assessed. Adapted cells, in contrast to non-adapted cells, when exposed to 80 mM acetic acid for 200 min ...

  3. Deep-sea pennatulaceans (sea pens) - recent discoveries, morphological adaptations, and responses to benthic oceanographic parameters

    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

  4. MIMO adaptive control of thruster-firing-induced vibration of satellites using multifunctional platforms

    Ma, Kougen; Ghasemi-Nejhad, Mehrdad N.

    2005-05-01

    This paper presents the concept, control strategy, and simulations of suppressing the thruster-firing-induced vibration of satellites. First, a satellite vibration reduction concept of utilizing the UHM multifunctional platform is discussed, and the structural configurations of the platform as well as the combination of the platform and a satellite are described. A satellite-like frame with the platform is analyzed, and the predominant modes of the frame are determined. A MIMO adaptive control scheme is then developed to suppress the frame vibration, and a convergence factor vector concept is introduced to ease the multi-channel convergence rate control. This controller is adjusted based on the vibration information of the frame and drives the platform to isolate the vibration transmission from the firing thruster to the satellite structure. The entire system has ten actuators: four piezoelectric stack actuators and six piezoelectric patch actuators. Eleven vibration components of the frame and platform are controlled. Nine components are in the frame for the satellite vibration suppression, and two are in the top-device plate of the platform for the thruster vibration suppression. Finally, simulations are performed to suppress the vibration of the frame for three platform positions to simulate the misalignment correction of the satellite thrust vector. The results demonstrate that the entire frame vibration at its dominant frequency decreases to 7-10% of its uncontrolled value in the three platform positions, and the thruster vibration decreases to 7.5% of its uncontrolled value.

  5. Acute psychological stress induces short-term variable immune response.

    Breen, Michael S; Beliakova-Bethell, Nadejda; Mujica-Parodi, Lilianne R; Carlson, Joshua M; Ensign, Wayne Y; Woelk, Christopher H; Rana, Brinda K

    2016-03-01

    In spite of advances in understanding the cross-talk between the peripheral immune system and the brain, the molecular mechanisms underlying the rapid adaptation of the immune system to an acute psychological stressor remain largely unknown. Conventional approaches to classify molecular factors mediating these responses have targeted relatively few biological measurements or explored cross-sectional study designs, and therefore have restricted characterization of stress-immune interactions. This exploratory study analyzed transcriptional profiles and flow cytometric data of peripheral blood leukocytes with physiological (endocrine, autonomic) measurements collected throughout the sequence of events leading up to, during, and after short-term exposure to physical danger in humans. Immediate immunomodulation to acute psychological stress was defined as a short-term selective up-regulation of natural killer (NK) cell-associated cytotoxic and IL-12 mediated signaling genes that correlated with increased cortisol, catecholamines and NK cells into the periphery. In parallel, we observed down-regulation of innate immune toll-like receptor genes and genes of the MyD88-dependent signaling pathway. Correcting gene expression for an influx of NK cells revealed a molecular signature specific to the adrenal cortex. Subsequently, focusing analyses on discrete groups of coordinately expressed genes (modules) throughout the time-series revealed immune stress responses in modules associated to immune/defense response, response to wounding, cytokine production, TCR signaling and NK cell cytotoxicity which differed between males and females. These results offer a spring-board for future research towards improved treatment of stress-related disease including the impact of stress on cardiovascular and autoimmune disorders, and identifies an immune mechanism by which vulnerabilities to these diseases may be gender-specific. PMID:26476140

  6. Silver nanoparticles induce endoplasmatic reticulum stress response in zebrafish

    Christen, Verena [University of Applied Sciences and Arts Northwestern Switzerland, School of Life Sciences, Gründenstrasse 40, CH-4132 Muttenz (Switzerland); Capelle, Martinus [Crucell, P.O. Box 2048, NL-2301 Leiden (Netherlands); Fent, Karl, E-mail: karl.fent@fhnw.ch [University of Applied Sciences and Arts Northwestern Switzerland, School of Life Sciences, Gründenstrasse 40, CH-4132 Muttenz (Switzerland); Swiss Federal Institute of Technology Zürich, Department of Environmental Systems Science, CH-8092 Zürich (Switzerland)

    2013-10-15

    Silver nanoparticles (AgNPs) find increasing applications, and therefore humans and the environment are increasingly exposed to them. However, potential toxicological implications are not sufficiently known. Here we investigate effects of AgNPs (average size 120 nm) on zebrafish in vitro and in vivo, and compare them to human hepatoma cells (Huh7). AgNPs are incorporated in zebrafish liver cells (ZFL) and Huh7, and in zebrafish embryos. In ZFL cells AgNPs lead to induction of reactive oxygen species (ROS), endoplasmatic reticulum (ER) stress response, and TNF-α. Transcriptional alterations also occur in pro-apoptotic genes p53 and Bax. The transcriptional profile differed in ZFL and Huh7 cells. In ZFL cells, the ER stress marker BiP is induced, concomitant with the ER stress marker ATF-6 and spliced XBP-1 after 6 h and 24 h exposure to 0.5 g/L and 0.05 g/L AgNPs, respectively. This indicates the induction of different pathways of the ER stress response. Moreover, AgNPs induce TNF-α. In zebrafish embryos exposed to 0.01, 0.1, 1 and 5 mg/L AgNPs hatching was affected and morphological defects occurred at high concentrations. ER stress related gene transcripts BiP and Synv are significantly up-regulated after 24 h at 0.1 and 5 mg/L AgNPs. Furthermore, transcriptional alterations occurred in the pro-apoptotic genes Noxa and p21. The ER stress response was strong in ZFL cells and occurred in zebrafish embryos as well. Our data demonstrate for the first time that AgNPs lead to induction of ER stress in zebrafish. The induction of ER stress can have several consequences including the activation of apoptotic and inflammatory pathways. - Highlights: • Effects of silver nanoparticles (120 nm AgNPs) are investigated in zebrafish. • AgNPs induce all ER stress reponses in vitro in zebrafish liver cells. • AgNPs induce weak ER stress in zebrafish embryos. • AgNPs induce oxidative stress and transcripts of pro-apoptosis genes.

  7. Wind-induced response analysis of conical membrane structures

    CHEN Bo; WU Yue; SHEN Shi-zhao

    2005-01-01

    Conical membrane structures are a typical form of tensile membrane structures. In the past, most studies focused on the static performance, but few on dynamic performance. In this paper, systematic parameter analysis of wind-induced response of conical membrane structures has been performed with nonlinear random simulation method in a time domain, by considering some parameters, such as span, rise-span ratio, prestress of membrane, and characteristic of the approaching wind flow. Moreover, formulas of the dynamic coefficient and nonlinear adjustment factor are advised, which can be conveniently used in wind-resistant design of conical membrane structures.

  8. Ribosome biogenesis adaptation in resistance training-induced human skeletal muscle hypertrophy.

    Figueiredo, Vandre C; Caldow, Marissa K; Massie, Vivien; Markworth, James F; Cameron-Smith, David; Blazevich, Anthony J

    2015-07-01

    Resistance training (RT) has the capacity to increase skeletal muscle mass, which is due in part to transient increases in the rate of muscle protein synthesis during postexercise recovery. The role of ribosome biogenesis in supporting the increased muscle protein synthetic demands is not known. This study examined the effect of both a single acute bout of resistance exercise (RE) and a chronic RT program on the muscle ribosome biogenesis response. Fourteen healthy young men performed a single bout of RE both before and after 8 wk of chronic RT. Muscle cross-sectional area was increased by 6 ± 4.5% in response to 8 wk of RT. Acute RE-induced activation of the ERK and mTOR pathways were similar before and after RT, as assessed by phosphorylation of ERK, MNK1, p70S6K, and S6 ribosomal protein 1 h postexercise. Phosphorylation of TIF-IA was also similarly elevated following both RE sessions. Cyclin D1 protein levels, which appeared to be regulated at the translational rather than transcriptional level, were acutely increased after RE. UBF was the only protein found to be highly phosphorylated at rest after 8 wk of training. Also, muscle levels of the rRNAs, including the precursor 45S and the mature transcripts (28S, 18S, and 5.8S), were increased in response to RT. We propose that ribosome biogenesis is an important yet overlooked event in RE-induced muscle hypertrophy that warrants further investigation. PMID:25968575

  9. Cellular, physiological, and molecular adaptive responses of Erwinia amylovora to starvation.

    Santander, Ricardo D; Oliver, James D; Biosca, Elena G

    2014-05-01

    Erwinia amylovora causes fire blight, a destructive disease of rosaceous plants distributed worldwide. This bacterium is a nonobligate pathogen able to survive outside the host under starvation conditions, allowing its spread by various means such as rainwater. We studied E. amylovora responses to starvation using water microcosms to mimic natural oligotrophy. Initially, survivability under optimal (28 °C) and suboptimal (20 °C) growth temperatures was compared. Starvation induced a loss of culturability much more pronounced at 28 °C than at 20 °C. Natural water microcosms at 20 °C were then used to characterize cellular, physiological, and molecular starvation responses of E. amylovora. Challenged cells developed starvation-survival and viable but nonculturable responses, reduced their size, acquired rounded shapes and developed surface vesicles. Starved cells lost motility in a few days, but a fraction retained flagella. The expression of genes related to starvation, oxidative stress, motility, pathogenicity, and virulence was detected during the entire experimental period with different regulation patterns observed during the first 24 h. Further, starved cells remained as virulent as nonstressed cells. Overall, these results provide new knowledge on the biology of E. amylovora under conditions prevailing in nature, which could contribute to a better understanding of the life cycle of this pathogen. PMID:24476337

  10. The effects of an adaptive directional BEAM microphone on the mismatch negativity responses of cochlear implant users in noise

    ERDOĞAN*, Asuman; Akdaş, Ferda

    2013-01-01

    To investigate the effects of noise on mismatch negativity (MMN) responses and the possible benefits of an adaptive directional BEAM microphone in noise during MMN recordings, and to compare the cochlear implant-evoked potential results with normal hearing subjects. Materials and methods: /da/ and /di/ speech stimuli were used to elicit MMN responses in 11 Freedom cochlear implant users and in 11 normal hearing subjects. Speech noise was delivered at 80 dB sound pressure level (-10 dB signa...

  11. Quantitative analysis of population heterogeneity of the adaptive salt stress response and growth capacity of Bacillus cereus ATCC 14579

    Besten, den H.M.W.; Ingham, C.J.; Hylckama Vlieg, van J.E.T.; Beerthuyzen, M.M.; Zwietering, M.H.; Abee, T.

    2007-01-01

    Bacterial populations can display heterogeneity with respect to both the adaptive stress response and growth capacity of individual cells. The growth dynamics of Bacillus cereus ATCC 14579 during mild and severe salt stress exposure were investigated for the population as a whole in liquid culture.

  12. Klinefelter syndrome has increased brain responses to auditory stimuli and motor output, but not to visual stimuli or Stroop adaptation

    Wallentin, Mikkel; Skakkebæk, Anne; Bojesen, Anders;

    2016-01-01

    widespread dyslexia in the group. No neural differences were found in inhibitory control (Stroop) or in adaptation to differences in stimulus frequencies. Across groups we found a strong positive correlation between age and BOLD response in the brain’s motor network with no difference between groups. No...

  13. Protein supplementation augments the adaptive response of skeletal muscle to resistance-type exercise training: a meta-analysis

    Cermak, N.M.; Res, P.T.; Groot, de C.P.G.M.; Saris, W.H.M.; Loon, van L.J.C.

    2012-01-01

    Background: Protein ingestion after a single bout of resistance-type exercise stimulates net muscle protein accretion during acute postexercise recovery. Consequently, it is generally accepted that protein supplementation is required to maximize the adaptive response of the skeletal muscle to prolon

  14. Muscle Plasticity and β2-Adrenergic Receptors: Adaptive Responses of β2-Adrenergic Receptor Expression to Muscle Hypertrophy and Atrophy

    Shogo Sato; Ken Shirato; Kaoru Tachiyashiki; Kazuhiko Imaizumi

    2011-01-01

    We discuss the functional roles of β2-adrenergic receptors in skeletal muscle hypertrophy and atrophy as well as the adaptive responses of β2-adrenergic receptor expression to anabolic and catabolic conditions. β2-Adrenergic receptor stimulation using anabolic drugs increases muscle mass by promoting muscle protein synthesis and/or attenuating protein degradation. These effects are prevented ...

  15. Bacterial Outer Membrane Vesicles Induce Plant Immune Responses.

    Bahar, Ofir; Mordukhovich, Gideon; Luu, Dee Dee; Schwessinger, Benjamin; Daudi, Arsalan; Jehle, Anna Kristina; Felix, Georg; Ronald, Pamela C

    2016-05-01

    Gram-negative bacteria continuously pinch off portions of their outer membrane, releasing membrane vesicles. These outer membrane vesicles (OMVs) are involved in multiple processes including cell-to-cell communication, biofilm formation, stress tolerance, horizontal gene transfer, and virulence. OMVs are also known modulators of the mammalian immune response. Despite the well-documented role of OMVs in mammalian-bacterial communication, their interaction with plants is not well studied. To examine whether OMVs of plant pathogens modulate the plant immune response, we purified OMVs from four different plant pathogens and used them to treat Arabidopsis thaliana. OMVs rapidly induced a reactive oxygen species burst, medium alkalinization, and defense gene expression in A. thaliana leaf discs, cell cultures, and seedlings, respectively. Western blot analysis revealed that EF-Tu is present in OMVs and that it serves as an elicitor of the plant immune response in this form. Our results further show that the immune coreceptors BAK1 and SOBIR1 mediate OMV perception and response. Taken together, our results demonstrate that plants can detect and respond to OMV-associated molecules by activation of their immune system, revealing a new facet of plant-bacterial interactions. PMID:26926999

  16. Adaptive stress response in segmental progeria resembles long-lived dwarfism and calorie restriction in mice.

    Marieke van de Ven

    2006-12-01

    Full Text Available How congenital defects causing genome instability can result in the pleiotropic symptoms reminiscent of aging but in a segmental and accelerated fashion remains largely unknown. Most segmental progerias are associated with accelerated fibroblast senescence, suggesting that cellular senescence is a likely contributing mechanism. Contrary to expectations, neither accelerated senescence nor acute oxidative stress hypersensitivity was detected in primary fibroblast or erythroblast cultures from multiple progeroid mouse models for defects in the nucleotide excision DNA repair pathway, which share premature aging features including postnatal growth retardation, cerebellar ataxia, and death before weaning. Instead, we report a prominent phenotypic overlap with long-lived dwarfism and calorie restriction during postnatal development (2 wk of age, including reduced size, reduced body temperature, hypoglycemia, and perturbation of the growth hormone/insulin-like growth factor 1 neuroendocrine axis. These symptoms were also present at 2 wk of age in a novel progeroid nucleotide excision repair-deficient mouse model (XPD(G602D/R722W/XPA(-/- that survived weaning with high penetrance. However, despite persistent cachectic dwarfism, blood glucose and serum insulin-like growth factor 1 levels returned to normal by 10 wk, with hypoglycemia reappearing near premature death at 5 mo of age. These data strongly suggest changes in energy metabolism as part of an adaptive response during the stressful period of postnatal growth. Interestingly, a similar perturbation of the postnatal growth axis was not detected in another progeroid mouse model, the double-strand DNA break repair deficient Ku80(-/- mouse. Specific (but not all types of genome instability may thus engage a conserved response to stress that evolved to cope with environmental pressures such as food shortage.

  17. Prolonged ozone exposure in an allergic airway disease model: Adaptation of airway responsiveness and airway remodeling

    Park Chang-Soo

    2006-02-01

    Full Text Available Abstract Background Short-term exposure to high concentrations of ozone has been shown to increase airway hyper-responsiveness (AHR. Because the changes in AHR and airway inflammation and structure after chronic ozone exposure need to be determined, the goal of this study was to investigate these effects in a murine model of allergic airway disease. Methods We exposed BALB/c mice to 2 ppm ozone for 4, 8, and 12 weeks. We measured the enhanced pause (Penh to methacholine and performed cell differentials in bronchoalveolar lavage fluid. We quantified the levels of IL-4 and IFN-γ in the supernatants of the bronchoalveolar lavage fluids using enzyme immunoassays, and examined the airway architecture under light and electron microscopy. Results The groups exposed to ozone for 4, 8, and 12 weeks demonstrated decreased Penh at methacholine concentrations of 12.5, 25, and 50 mg/ml, with a dose-response curve to the right of that for the filtered-air group. Neutrophils and eosinophils increased in the group exposed to ozone for 4 weeks compared to those in the filtered-air group. The ratio of IL-4 to INF-γ increased significantly after exposure to ozone for 8 and 12 weeks compared to the ratio for the filtered-air group. The numbers of goblet cells, myofibroblasts, and smooth muscle cells showed time-dependent increases in lung tissue sections from the groups exposed to ozone for 4, 8, and 12 weeks. Conclusion These findings demonstrate that the increase in AHR associated with the allergic airway does not persist during chronic ozone exposure, indicating that airway remodeling and adaptation following repeated exposure to air pollutants can provide protection against AHR.

  18. Dynamic lipidomic insights into the adaptive responses of Saccharomyces cerevisiae to the repeated vacuum fermentation.

    Zhou, Xiao; Zhou, Jian; Tian, Hongchi; Yuan, Yingjin

    2010-10-01

    Vacuum fermentation is utilized in a wide range of life science industries and biomedical R&D. Little is known, however, on the effects of the vacuum on the yeast, and in particular, on the yeast lipidome that plays a central role in maintaining cell membrane and other vital (yeast) cell functions. The present study evaluated the adaptive responses of Saccharomyces cerevisiae to repeated vacuum fermentation by lipidomic analysis. We employed gas chromatography coupled to time-of-flight mass spectrometry (GC-TOF-MS) and liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI/MS(n)) to quantify a total of 13 intermediate sterols and 139 phospholipid species of yeast cells. Principal components analysis found that the PI (phosphatidylinositol) 26:0, PI 28:0, PE (phosphatidylethanolamine) 32:1, and PE 34:1 were potential biomarkers to distinguish the vacuum fermentation process. Quantitative analysis showed that vacuum fermentation increased the synthesis of PI and the PC (phosphatidylcholine) species with short saturated acyl chains. The synthesis of PC via CDP-choline and turnover of PC were enhanced, instead of formation via methylation of PE. Additionally, increased PI at the expense of PE and PG (phosphatidylglycerol) was associated with enhancement of ethanol productivity. Vacuum fermentation caused eburicol accumulation, suggesting that vacuum can activate the branch of the ergosterol biosynthesis pathway. Eburicol decrease and PI increase contributed to recovery of cellular activities with oxygenating treatment. Ethanol productivity was increased by sixfold in vacuum-treated cells. These observations may allow the development of future mechanistic approaches to optimization of yeast fermentation under vacuum for bioindustry and life science applications. In particular, our findings on changes in lipid molecular species and the ergosterol biosynthesis pathway elucidate the defense responses of yeast cell membranes during the repeated

  19. Climate-smart technologies. Integrating renewable energy and energy efficiency in mitigation and adaptation responses

    Leal Filho, Walter; Mannke, Franziska; Schulte, Veronika [Hamburg Univ. of Applied Sciences (Germany). Faculty of Life Sciences; Mohee, Romeela; Surroop, Dinesh (eds.) [Mauritius Univ., Reduit (Mauritius). Chemical and Environmental Engineering Dept.

    2013-11-01

    Explores the links between climate change and technologies. Relates to the links between renewable energy and climate change. Documents and promotes a collection of experiences from island nations. Has a strong international focus and value to developing countries. The book addresses the perceived need for a publication with looks at both, climate smart technologies and the integration of renewable energy and energy efficiency in mitigation and adaptation responses. Based on a set of papers submitted as part of the fifth on-line climate conference (CLIMATE 2012) and a major conference on renewable energy on island States held in Mauritius in 2012, the book provides a wealth of information on climate change strategies and the role of smart technologies. The book has been produced in the context of the project ''Small Developing Island Renewable Energy Knowledge and Technology Transfer Network'' (DIREKT), funded by the ACP Science and Technology Programme, an EU programme for cooperation between the European Union and the ACP region.

  20. Temperature-responsive release of thyroxine and its environmental adaptation in Australians

    Qi, Xiaoqiang; Chan, Wee Lee; Read, Randy J.; Zhou, Aiwu; Carrell, Robin W.

    2014-01-01

    The hormone thyroxine that regulates mammalian metabolism is carried and stored in the blood by thyroxine-binding globulin (TBG). We demonstrate here that the release of thyroxine from TBG occurs by a temperature-sensitive mechanism and show how this will provide a homoeostatic adjustment of the concentration of thyroxine to match metabolic needs, as with the hypothermia and torpor of small animals. In humans, a rise in temperature, as in infections, will trigger an accelerated release of thyroxine, resulting in a predictable 23% increase in the concentration of free thyroxine at 39°C. The in vivo relevance of this fever-response is affirmed in an environmental adaptation in aboriginal Australians. We show how two mutations incorporated in their TBG interact in a way that will halve the surge in thyroxine release, and hence the boost in metabolic rate that would otherwise occur as body temperatures exceed 37°C. The overall findings open insights into physiological changes that accompany variations in body temperature, as notably in fevers. PMID:24478298