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Sample records for adaptive response induced

  1. Cytogenetic adaptive response induced by EMS or MMS in bone

    African Journals Online (AJOL)

    B.B. Dada Khalandar

    2016-01-14

    Jan 14, 2016 ... Abstract Background: Adaptive response has been well studied by employing physical and chem- ical agents in normal test systems, whereas in diseased conditions very little data are available. Aim of the study: To know the presence or absence of adaptive response in diseased condition, alkylating ...

  2. Multiple factors participating in radiation-induced adaptive response

    International Nuclear Information System (INIS)

    Nenoi, Mitsuru; Vares, G.; Wang, Bing

    2009-01-01

    Radiation-induced adaptive response (RAR) is essentially the acquisition of radiation resistance by pre-exposed low dose radiation (priming). In this paper, in vitro findings on RAR-related factors are reviewed and authors' studies of RAR-related gene analysis in lethality and malformation of mouse fetus are described for future view. Studies on in vitro RAR have involved such participating factors as signal transduction, response appearance and bystander effect, and gene expression profiling. In RAR, DNA double strand break (DSB) by priming is conceivably the initial stimulation. In various cell systems including p53-knockout cells and in enzyme inhibition studies, intracellular signaling factors like protein kinase C, p38 MAPK, phospholipase C have been shown to participate. Increased activities of antioxidant and of damaged DNA repairing system, modulation of cell cycle, heat-shock reactions and apoptosis are suggested to concern to RAR appearance. Relationship between RAR and bystander effect is conceived to be important based on findings of cell lethality, mutagenesis, gap junction and NO radical. Genes relating to DSB repair, stress response, cell cycle and apoptosis have been shown to be specifically changed in RAR by their expression profile. Authors have conducted in vivo studies on RAR using embryogenetic system in the mouse. They have shown by gene profiling that signaling evoked by priming is important when the fetal lethality and malformation are used as RAR measures, and that in the subsequent process to RAR appearance, many signaling factors, particularly the transcription factor like p53, play a role. Database construction according to measures employed in individual studies, classification of living systems studied, radiation factors like linear energy transfer (LET), dose and dose rate, and functional genes concerned is thought useful for understanding the ultimate molecular mechanisms involved in ARA. (K.T.)

  3. Radiation-induced adaptive response in human lymphoblast

    International Nuclear Information System (INIS)

    Yatagai, Fumio; Sugasawa, Kaoru

    2009-01-01

    Described are the genetic analysis of variant strains obtained by the optimal condition for radiation-induced adaptive response (AR), and molecular elucidation of the suppression of concomitant mutation. The TK6 cells (heterozygous thymidine kinase, +/-) were used for detection of mutation by loss of heterozygosity (LOH). The optimal conditions for reducing the mutation by subsequent irradiation (SI) to its rate of about 60% (vs control 100%, no PI) were found to be 5 cGy of pre-irradiation (PI) of X-ray and 2 Gy of SI with the interval of 6 hr, where mutated cells were of non-LOH type in around 25% and homo-LOH type by homologous recombination (HR) in 60%. By cDNA sequencing, the former cells having changed bases were found to be in variant strain ratio of 1/8 vs control 7/18, suggesting that the mutation was decreased mainly by suppression of base change. Expression of XPC protein, an important component for recognition of the base damage in global genome nucleotide excision repair, was studied by Western blotting as the possible mechanism of suppressing the mutation, which revealed different time dynamics of the protein in cells with PI+SI and SI alone (control). To see the effect of PI on the double strand break (DSB) repair, cells with PI were infected with restriction enzyme I-SceI vector to yield DSB instead of SI, which revealed more efficient repair (70% increase) by HR than control, without significant difference in non-homologous end-joining repair. Micro-array analysis to study the gene expression in the present experimental conditions for AR is in progress. The TK6 cells used here were thought useful for additional studies of the mechanism of AR as mutation by direct or indirect irradiation can be tested. (K.T.)

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

    International Nuclear Information System (INIS)

    Langlois, N.L.; Quinn, J.S.; Somers, C.M.; Boreham, D.R.; Mitchel, R.E.J.

    2003-01-01

    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

  5. Role of X-ray-inducible genes and proteins in adaptive survival responses

    International Nuclear Information System (INIS)

    Meyers, M.; Schea, R.A.; Petrowski, A.E.; Seabury, H.; McLaughlin, P.W.; Lee, I.; Lee, S.W.; Boothman, D.A.

    1992-01-01

    Certain X-ray-inducible genes and their corresponding protein products, appearing following low priming doses of ionizing radiation may subsequently give rise to an adaptive survival response, ultimately leading to increased radioresistance. Further, this adaptive radioresistance may be due to increased DNA repair (or misrepair) processes. Ultimately, the function of low-dose-induced cDNA clones within the cell is hoped to elucidate to follow the effects of specific gene turn-off on adaptive responses. Future research must determine the various functions of adaptive response gene products so that the beneficial or deleterious consequences of adaptive responses, which increases resistance to ionizing radiation, can be determined. (author). 19 refs., 1 fig

  6. Metabolic and adaptive immune responses induced in mice infected ...

    African Journals Online (AJOL)

    This study investigated metabolic and immuno-inflammatory responses of mice infected with tissue-dwelling larvae of Trichinella zimbabwensis and explored the relationship between infection, metabolic parameters and Th1/Th17 immune responses. Sixty (60) female BALB/c mice aged between 6 to 8 weeks old were ...

  7. Extremely low doses of X-radiation can induce adaptive responses in mouse prostate

    International Nuclear Information System (INIS)

    Day, T.K.; Zeng, G.; Hooker, A.M.; Turner, D.R.; Sykes, P.J.; Baht, M.

    2006-01-01

    Full text: The pKZl mouse chromosomal inversion assay is the only assay which has detected modulation of a mutagenic endpoint after single whole body X-irradiation with doses lower than 1 mGy. A non-linear dose response for chromosomal inversion has been observed between 1 jaGy and 10 mGy with doses between 5-10 uGy causing an induction in inversions and doses between 1-10 mGy causing a reduction below endogenous inversion frequency (Hooker et al, 2004. Radiat. Res. 162:447-52.) An adaptive response is a decreased biological effect induced by a priming radiation dose given prior to a challenge dose. Adaptive responses contradict the linear-no-threshold model of risk estimation. pKZl mice were exposed to priming radiation doses which by themselves either induced or reduced inversion frequency. Four hours later mice received a challenge dose of 1000 mGy. The inversion frequency was quantified in prostate three days later. We demonstrated that very low (10 mGy, 1 mGy and 10 )J,Gy) priming doses of X-radiation induced a chromosomal inversion adaptive response. These are the lowest X-radiation doses reported to induce an adaptive response for any endpoint. Reverse adaptive response experiments will also be discussed where the challenge dose studied was lower than the priming dose. Analysis of the distribution of inversions in 50 prostatic glands screened/animal suggested that there are two types of damage induced by the high challenge dose and only one of these types of damage is modified by the priming dose. Identification of the modifying factors involved in the adaptive response may provide candidates for radioprotection. This work was funded by the Low Dose Radiation Research Program, U.S. Department of Energy, grant no. DE-FG02-01ER63227 and DE-FG02-05ER64104

  8. Radioadaptive response. Efficient repair of radiation-induced DNA damage in adapted cells

    International Nuclear Information System (INIS)

    Ikushima, Takaji; Aritomi, Hisako; Morisita, Jun

    1996-01-01

    To verify the hypothesis that the induction of a novel, efficient repair mechanism for chromosomal DNA breaks may be involved in the radioadaptive response, the repair kinetics of DNA damage has been studied in cultured Chinese hamster V79 cells with single-cell gel electrophoresis. The cells were adapted by priming exposure with 5 cGy of γ-rays and 4-h incubation at 37C. There were no indication of any difference in the initial yields of DNA double-strand breaks induced by challenging doses from non-adapted cells and from adapted cells. The rejoining of DNA double-strand breaks was monitored over 120 min after the adapted cells were challenged with 5 or 1.5 Gy, doses at the same level to those used in the cytogenetical adaptive response. The rate of DNA damage repair in adapted cells was higher than that in non-adapted cells, and the residual damage was less in adapted cells than in non-adapted cells. These results indicate that the radioadaptive response may result from the induction of a novel, efficient DNA repair mechanism which leads to less residual damage, but not from the induction of protective functions that reduce the initial DNA damage

  9. Radiation-induced adaptive response in fetal mice: a micro-array study

    International Nuclear Information System (INIS)

    Vares, G.; Bing, Wang; Mitsuru, Nenoi; Tetsuo, Nakajima; Kaoru, Tanaka; Isamu, Hayata

    2006-01-01

    Exposure of sublethal doses of ionizing radiation can induce protective mechanisms against a subsequent higher dose irradiation. This phenomenon called radio-adaptation (or adaptive response - AR), has been described in a wide range of biological models. In a series of studies, we demonstrated the existence of a radiation-induced AR in mice during late organogenesis. For better understanding of molecular mechanisms underlying AR in our model, we performed a global analysis of transcriptome regulations in cells collected from whole mouse fetuses. Using cDNA micro-arrays, we studied gene expression in these cells after in utero priming exposure to irradiation. Several combinations of radiation dose and dose-rate were applied to induce or not an AR in our system. Gene regulation was observed after exposure to priming radiation in each condition. Student's t-test was performed in order to identify genes whose expression modulation was specifically different in AR-inducing an( non-AR-inducing conditions. Genes were ranked according to their ability in discriminating AR-specific modulations. Since AR genes were implicated in variety of functions and cellular processes, we applied a functional classification algorithm, which clustered genes in a limited number of functionally related group: We established that AR genes are significantly enriched for specific keywords. Our results show a significant modulation of genes implicated in signal transduction pathways. No AR-specific alteration of DNA repair could be observed. Nevertheless, it is likely that modulation of DNA repair activity results, at least partly, from post-transcriptional regulation. One major hypothesis is that de-regulations of signal transduction pathways and apoptosis may be responsible for AR phenotype. In previous work, we demonstrated that radiation-induced AR in mice during organogenesis is related to Trp53 gene status and to the occurrence of radiation-induced apoptosis. Other work proposed that p53

  10. Low-Dose UVA Radiation-Induced Adaptive Response in Cultured Human Dermal Fibroblasts

    Directory of Open Access Journals (Sweden)

    Zhongrong Liu

    2012-01-01

    Full Text Available Objective. To investigate the mechanism of the adaptive response induced by low-dose ultraviolet A (UVA radiation. Methods. Cultured dermal fibroblasts were irradiated by a lethal dose of UVA (86.4 J/cm2 with preirradiation of single or repetitive low dose of UVA (7.2 J/cm2. Alterations of cellular morphology were observed by light microscope and electron microscope. Cell cycle and cellular apoptosis were assayed by flow cytometer. The extent of DNA damage was determined by single-cell gel electrophoresis (SCGE. Results. The cultured dermal fibroblasts, with pretreatment of single or repetitive irradiation of 7.2 J/cm2 UVA relieved toxic reaction of cellular morphology and arrest of cell cycle, decreased apoptosis ratio, reduced DNA chain breakage, and accelerated DNA repair caused by subsequent 86.4 J/cm2 UVA irradiation. Compared with nonpretreatment groups, all those differences were significant (P<0.01 or P<0.05. Conclusions. The adaptation reaction might depend on the accumulated dose of low-dose UVA irradiation. Low-dose UVA radiation might induce adaptive response that may protect cultured dermal fibroblasts from the subsequent challenged dose of UVA damage. The duration and protective capability of the adaptive reaction might be related to the accumulated dose of low-dose UVA Irradiation.

  11. Radiation-induced apoptosis in human tumor cell lines: adaptive response and split-dose effect.

    Science.gov (United States)

    Filippovich, I V; Sorokina, N I; Robillard, N; Lisbona, A; Chatal, J F

    1998-07-03

    Irradiation of human ovarian carcinoma cells (OVCAR 3) and myeloma cells (RPMI 8226) with graded doses of 137Cs-gamma-rays led to a 35-40% increase in time-dependent apoptosis 72 hr after 6-8 Gy irradiation. Large individual variations in sensitivity to radiation-induced apoptosis were noted in human lymphocytes obtained from 5 donors. Pretreatment of OVCAR 3 and RPMI 8226 cells with 0.01 Gy increased their resistance to apoptosis after subsequent 6 Gy irradiation several hours or 48 and 72 hr later. A dose of 4 or 8 Gy given in 2 equal fractions at an interval of a few hours produced a low level of apoptosis compared to that resulting from a single administration of the same total dose. Adaptive response was demonstrated in 2 out of 3 samples of human lymphocytes isolated from different donors, and no split-dose effect for apoptosis was noted in 2 other donors. In split-dose experiments, there was no correlation between the sensitivity of cells to apoptosis and their position in the cell cycle, after the first half-dose. No G1 block was observed in irradiated cell lines. Adaptive response and split-dose effect were prevented by 3-aminobenzamide and okadaic acid which inhibit poly(ADP-ribose)polymerase and protein phosphatase, respectively. These results imply a common mechanism for acquired resistance to radiation-induced apoptosis in adaptive response and the split-dose effect.

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

    Science.gov (United States)

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

    2015-10-15

    Tattooing is becoming increasingly popular, particularly amongst young people. However, tattoo inks contain a complex mixture of chemical impurities that may pose a long-term risk for human health. As a first step towards the risk assessment of these complex mixtures we propose to assess the toxicological hazard potential of tattoo ink chemicals with cell-based bioassays. Targeted modes of toxic action and cellular endpoints included cytotoxicity, genotoxicity and adaptive stress response pathways. The studied tattoo inks, which were extracted with hexane as a proxy for the bioavailable fraction, caused effects in all bioassays, with the red and yellow tattoo inks having the greatest response, particularly inducing genotoxicity and oxidative stress response endpoints. Chemical analysis revealed the presence of polycyclic aromatic hydrocarbons in the tested black tattoo ink at concentrations twice the recommended level. The detected polycyclic aromatic hydrocarbons only explained 0.06% of the oxidative stress response of the black tattoo ink, thus the majority of the effect was caused by unidentified components. The study indicates that currently available tattoo inks contain components that induce adaptive stress response pathways, but to evaluate the risk to human health further work is required to understand the toxicokinetics of tattoo ink chemicals in the body. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Circumvention of camptothecin-induced resistance during the adaptive cellular stress response.

    Science.gov (United States)

    Tiligada, Ekaterini; Papamichael, Konstantinos; Vovou, Ioanna; Delitheos, Andreas

    2006-01-01

    Camptothecin-11 (CPT-11) induces the adaptive stress response in yeast, conferring resistance via not fully characterized mechanisms. This study aimed at exploring, pharmacologically, the mechanisms underlying the CPT-11-induced resistance in yeast. Post-logarithmic yeast cultures were submitted to heat shock following preconditioning with suramin and with CPT-11, either alone or in combination with suramin, cycloheximide, sodium molybdate, okadaic acid, or verapamil. The stress response was evaluated by determining cell viability after heat shock. Preconditioning with CPT-11 or suramin conferred thermotolerance to yeast cells. Co-administration of CPT-11 with suramin, cycloheximide or okadaic acid reversed the CPT-11-induced thermotolerant phenotype, while sodium molybdate and verapamil had no effect on CPT-11-induced resistance. The antagonistic effect of the thermotolerance-inducers and the possible contribution of topoisomerase II activity and post-translational modifications mediated by the phosphatases PP1/2A in CPT-11-induced resistance may have important implications on the acquisition of resistance to stress in eukaryotic cells.

  14. Adaptive Response Induced by Pre-Exposure to 915 MHz Radiofrequency: A Possible Role for Antioxidant Enzyme Activity

    OpenAIRE

    Mortazavi, S.M.J.; Mostafavi-Pour, Z.; Daneshmand, M.; Zal, F.; Zare, R.; Mosleh-Shirazi, M.A.

    2017-01-01

    Background: Over the past few years, the rapid use of high frequency electromagnetic fields like mobile phones has raised global concerns about the negative health effects of its use. Adaptive response is the ability of a cell or tissue to better resist stress damage by prior exposure to a lesser amount of stress. This study aimed to assess whether radiofrequency radiation can induce adaptive response by changing the antioxidant balance. Materials and Methods: In order to assess RF-induced a...

  15. Effect of modeled microgravity on radiation-induced adaptive response of root growth in Arabidopsis thaliana

    International Nuclear Information System (INIS)

    Deng, Chenguang; Wang, Ting; Wu, Jingjing; Xu, Wei; Li, Huasheng; Liu, Min

    2017-01-01

    Highlights: • The radio-adaptive response (RAR) of A. thaliana root growth is modulated in microgravity. • The DNA damage repairs in RAR are regulated by microgravity. • The phytohormone auxin plays a regulatory role in the modulation of microgravity on RAR of root growth. - Abstract: Space particles have an inevitable impact on organisms during space missions; radio-adaptive response (RAR) is a critical radiation effect due to both low-dose background and sudden high-dose radiation exposure during solar storms. Although it is relevant to consider RAR within the context of microgravity, another major space environmental factor, there is no existing evidence as to its effects on RAR. In the present study, we established an experimental method for detecting the effects of gamma-irradiation on the primary root growth of Arabidopsis thaliana, in which RAR of root growth was significantly induced by several dose combinations. Microgravity was simulated using a two-dimensional rotation clinostat. It was shown that RAR of root growth was significantly inhibited under the modeled microgravity condition, and was absent in pgm-1 plants that had impaired gravity sensing in root tips. These results suggest that RAR could be modulated in microgravity. Time course analysis showed that microgravity affected either the development of radio-resistance induced by priming irradiation, or the responses of plants to challenging irradiation. After treatment with the modeled microgravity, attenuation in priming irradiation-induced expressions of DNA repair genes (AtKu70 and AtRAD54), and reduced DNA repair efficiency in response to challenging irradiation were observed. In plant roots, the polar transportation of the phytohormone auxin is regulated by gravity, and treatment with an exogenous auxin (indole-3-acetic acid) prevented the induction of RAR of root growth, suggesting that auxin might play a regulatory role in the interaction between microgravity and RAR of root growth.

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

    KAUST Repository

    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.

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

    International Nuclear Information System (INIS)

    Klokov, D.Yu.; Zaichkina, S.I.; Rozanova, O.M.; Aptikaeva, G.F.; Akhmadieva, A.Kh.; Smirnova, E.N.; Surkenova, G.N.; Kuzin, A.M.

    2000-01-01

    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 60 Co 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

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

    International Nuclear Information System (INIS)

    Frati, Diego Libkind; Bunge, Maria M.

    2001-01-01

    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)

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    International Nuclear Information System (INIS)

    Miyata, Ryohei; Eeden, Stephan F. van

    2011-01-01

    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, PM 10 ) induce innate immune responses via endotoxin-toll-like receptor (TLR) 4 pathway while fine (2.5 μm or less, PM 2.5 ) 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. Interval for the expression of the adaptive response induced by gamma radiation in leucocytes of mouse In vivo

    International Nuclear Information System (INIS)

    Mendiola C, M.T.; Morales R, P.

    2002-01-01

    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)

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

    Directory of Open Access Journals (Sweden)

    Ying Yang

    2017-01-01

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

  3. Increased innate and adaptive immune responses in induced sputum of young smokers

    Directory of Open Access Journals (Sweden)

    Agnese Kislina

    2015-01-01

    Conclusions: This study demonstrates that young smokers have early inflammatory changes in their airways that not only initiate nonspecific mechanisms recruiting neutrophils, but also involve specific immune mechanisms with recruitment of T regulatory lymphocytes. The lymphocyte response is probably adaptive.

  4. Radio-adaptive response

    International Nuclear Information System (INIS)

    Ikushima, T.

    1992-01-01

    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)

  5. Inducible protective processes in animal systems XV: Hyperthermia enhances the Ethyl methanesulfonate induced adaptive response in meiotic cells of grasshopper Poecilocerus pictus

    Directory of Open Access Journals (Sweden)

    R. Venu

    2016-04-01

    Conclusion: There is a protection against EMS induced anomalies by hyperthermia in in vivo P. pictus. As far as our knowledge is concerned, this is the first report to demonstrate that hyperthermia enhances the EMS induced adaptive response in in vivo meiotic cells.

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

    International Nuclear Information System (INIS)

    Seong, Jin Sil; Suh, Chang Ok; Kim, Gwi Eon

    1994-01-01

    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

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

    Directory of Open Access Journals (Sweden)

    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.

  8. Strains of bacterial species induce a greatly varied acute adaptive immune response: The contribution of the accessory genome.

    Science.gov (United States)

    Sela, Uri; Euler, Chad W; Correa da Rosa, Joel; Fischetti, Vincent A

    2018-01-01

    A fundamental question in human susceptibility to bacterial infections is to what extent variability is a function of differences in the pathogen species or in individual humans. To focus on the pathogen species, we compared in the same individual the human adaptive T and B cell immune response to multiple strains of two major human pathogens, Staphylococcus aureus and Streptococcus pyogenes. We found wide variability in the acute adaptive immune response induced by various strains of a species, with a unique combination of activation within the two arms of the adaptive response. Further, this was also accompanied by a dramatic difference in the intensity of the specific protective T helper (Th) response. Importantly, the same immune response differences induced by the individual strains were maintained across multiple healthy human donors. A comparison of isogenic phage KO strains, demonstrated that of the pangenome, prophages were the major contributor to inter-strain immune heterogeneity, as the T cell response to the remaining "core genome" was noticeably blunted. Therefore, these findings extend and modify the notion of an adaptive response to a pathogenic bacterium, by implying that the adaptive immune response signature of a bacterial species should be defined either per strain or alternatively to the species' 'core genome', common to all of its strains. Further, our results demonstrate that the acquired immune response variation is as wide among different strains within a single pathogenic species as it is among different humans, and therefore may explain in part the clinical heterogeneity observed in patients infected with the same species.

  9. Strains of bacterial species induce a greatly varied acute adaptive immune response: The contribution of the accessory genome.

    Directory of Open Access Journals (Sweden)

    Uri Sela

    2018-01-01

    Full Text Available A fundamental question in human susceptibility to bacterial infections is to what extent variability is a function of differences in the pathogen species or in individual humans. To focus on the pathogen species, we compared in the same individual the human adaptive T and B cell immune response to multiple strains of two major human pathogens, Staphylococcus aureus and Streptococcus pyogenes. We found wide variability in the acute adaptive immune response induced by various strains of a species, with a unique combination of activation within the two arms of the adaptive response. Further, this was also accompanied by a dramatic difference in the intensity of the specific protective T helper (Th response. Importantly, the same immune response differences induced by the individual strains were maintained across multiple healthy human donors. A comparison of isogenic phage KO strains, demonstrated that of the pangenome, prophages were the major contributor to inter-strain immune heterogeneity, as the T cell response to the remaining "core genome" was noticeably blunted. Therefore, these findings extend and modify the notion of an adaptive response to a pathogenic bacterium, by implying that the adaptive immune response signature of a bacterial species should be defined either per strain or alternatively to the species' 'core genome', common to all of its strains. Further, our results demonstrate that the acquired immune response variation is as wide among different strains within a single pathogenic species as it is among different humans, and therefore may explain in part the clinical heterogeneity observed in patients infected with the same species.

  10. Adaptive Response Induced by PreExposure to 915 MHz Radiofrequency: A Possible Role for Antioxidant Enzyme Activity

    Directory of Open Access Journals (Sweden)

    Mortazavi S. M. J.

    2017-06-01

    Full Text Available Background: Over the past few years, the rapid use of high frequency electromagnetic fields like mobile phones has raised global concerns about the negative health effects of its use. Adaptive response is the ability of a cell or tissue to better resist stress damage by prior exposure to a lesser amount of stress. This study aimed to assess whether radiofrequency radiation can induce adaptive response by changing the antioxidant balance. Materials and Methods: In order to assess RF-induced adaptive response in tissues, we evaluated the level of GSH and the activity of GR in liver. 50 rats were divided into 5 groups. Three groups were pre-exposed to 915 MHz RF radiation, 4 hours per day for one week at different powers, as low, medium and high. 24 hours after the last exposure to radiation, they were exposed to 4 Gy sublethal dose of gamma radiation and then sacrificed after 5 hours. Their livers were removed, washed and were kept at -80o C until used. Results: Our finding showed that pre-exposure to 915 MHz radiofrequency radiation with specific power could induce adaptive response in liver by inducing changes in the activity and level of antioxidant enzymes. Conclusion: It can be concluded that pre-exposure to microwave radiation could increase the level of GSH and the activity of GR enzyme, although these increases were seen just in low power group, and the GR activity was indicated in medium power group. This increase protects tissue from oxidative damage induced by sublethal dose of gamma radiation.

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

    International Nuclear Information System (INIS)

    Khandogina, E.K.; Mutovin, G.R.; Zvereva, S.V.; Zverev, D.O.; Neudakhin, E.V.; Arkhipov, B.A.; Akif'ev, A.P.; AN SSSR, Moscow

    1991-01-01

    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

  12. Adaptive response in human blood lymphocytes exposed to non-ionizing radiofrequency fields: resistance to ionizing radiation-induced damage.

    Science.gov (United States)

    Sannino, Anna; Zeni, Olga; Romeo, Stefania; Massa, Rita; Gialanella, Giancarlo; Grossi, Gianfranco; Manti, Lorenzo; Vijayalaxmi; Scarfì, Maria Rosaria

    2014-03-01

    The aim of this preliminary investigation was to assess whether human peripheral blood lymphocytes which have been pre-exposed to non-ionizing radiofrequency fields exhibit an adaptive response (AR) by resisting the induction of genetic damage from subsequent exposure to ionizing radiation. Peripheral blood lymphocytes from four healthy donors were stimulated with phytohemagglutinin for 24 h and then exposed for 20 h to 1950 MHz radiofrequency fields (RF, adaptive dose, AD) at an average specific absorption rate of 0.3 W/kg. At 48 h, the cells were subjected to a challenge dose (CD) of 1.0 or 1.5 Gy X-irradiation (XR, challenge dose, CD). After a 72 h total culture period, cells were collected to examine the incidence of micronuclei (MN). There was a significant decrease in the number of MN in lymphocytes exposed to RF + XR (AD + CD) as compared with those subjected to XR alone (CD). These observations thus suggested a RF-induced AR and induction of resistance to subsequent damage from XR. There was variability between the donors in RF-induced AR. The data reported in our earlier investigations also indicated a similar induction of AR in human blood lymphocytes that had been pre-exposed to RF (AD) and subsequently treated with a chemical mutagen, mitomycin C (CD). Since XR and mitomycin-C induce different kinds of lesions in cellular DNA, further studies are required to understand the mechanism(s) involved in the RF-induced adaptive response.

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

    Science.gov (United States)

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

    2004-01-01

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

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

    Science.gov (United States)

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

    2015-01-01

    Several studies have emphasized that inbreeding depression (ID) is enhanced under stressful conditions. Additionally, one might imagine a loss of adaptively plastic responses which may further contribute to a reduction in fitness under environmental stress. Here, we quantified ID in inbred families of the cyclical parthenogen Daphnia magna in the absence and presence of fish predation risk. We test whether predator stress affects the degree of ID and if inbred families have a reduced capacity to respond to predator stress by adaptive phenotypic plasticity. We obtained two inbred families through clonal selfing within clones isolated from a fish pond. After mild purging under standardized conditions, we compared life history traits and adaptive plasticity between inbred and outbred lineages (directly hatched from the natural dormant egg bank of the same pond). Initial purging of lineages under standardized conditions differed among inbred families and exceeded that in outbreds. The least purged inbred family exhibited strong ID for most life history traits. Predator-induced stress hardly affected the severity of ID, but the degree to which the capacity for adaptive phenotypic plasticity was retained varied strongly among the inbred families. The least purged family overall lacked the capacity for adaptive phenotypic plasticity, whereas the family that suffered only mild purging exhibited a potential for adaptive plasticity that was comparable to the outbred population. We thus found that inbred offspring may retain the capacity to respond to the presence of fish by adaptive phenotypic plasticity, but this strongly depends on the parental clone engaging in selfing. PMID:26257883

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

    International Nuclear Information System (INIS)

    Basak, Jayasri

    1996-01-01

    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

  16. IR-inducible clusterin gene expression: a protein with potential roles in ionizing radiation-induced adaptive responses, genomic instability, and bystander effects

    Energy Technology Data Exchange (ETDEWEB)

    Klokov, Dmitry [Laboratory of Molecular Stress Responses, Department of Radiation Oncology, Case Western Reserve University, 2103 Cornell Road, Wolstein Research Building 3-531, Cleveland, OH 44106-4942 (United States); Criswell, Tracy [Laboratory of Molecular Stress Responses, Department of Radiation Oncology, Case Western Reserve University, 2103 Cornell Road, Wolstein Research Building 3-531, Cleveland, OH 44106-4942 (United States); Program in Molecular and Cellular Basis of Disease, Case Western Reserve University School of Medicine, Cleveland, OH 44106-4942 (United States); Leskov, Konstantin S. [Laboratory of Molecular Stress Responses, Department of Radiation Oncology, Case Western Reserve University, 2103 Cornell Road, Wolstein Research Building 3-531, Cleveland, OH 44106-4942 (United States); Araki, Shinako [Laboratory of Molecular Stress Responses, Department of Radiation Oncology, Case Western Reserve University, 2103 Cornell Road, Wolstein Research Building 3-531, Cleveland, OH 44106-4942 (United States); Mayo, Lindsey [Laboratory of Molecular Stress Responses, Department of Radiation Oncology, Case Western Reserve University, 2103 Cornell Road, Wolstein Research Building 3-531, Cleveland, OH 44106-4942 (United States); Boothman, David A. [Laboratory of Molecular Stress Responses, Department of Radiation Oncology, Case Western Reserve University, 2103 Cornell Road, Wolstein Research Building 3-531, Cleveland, OH 44106-4942 (United States) and Program in Molecular and Cellular Basis of Disease, Case Western Reserve University School of Medicine, Cleveland, OH 44106-4942 (United States)]. E-mail: dab30@po.cwru.edu

    2004-12-02

    Clusterin (CLU) plays numerous roles in mammalian cells after stress. A review of the recent literature strongly suggests potential roles for CLU proteins in low dose ionizing radiation (IR)-inducible adaptive responses, bystander effects, and delayed death and genomic instability. Its most striking and evident feature is the inducibility of the CLU promoter after low, as well as high, doses of IR. Two major forms of CLU, secreted (sCLU) and nuclear (nCLU), possess opposite functions in cellular responses to IR: sCLU is cytoprotective, whereas nCLU (a byproduct of alternative splicing) is a pro-death factor. Recent studies from our laboratory and others demonstrated that down-regulation of sCLU by specific siRNA increased cytotoxic responses to chemotherapy and IR. sCLU was induced after low non-toxic doses of IR (0.02-0.5 Gy) in human cultured cells and in mice in vivo. The low dose inducibility of this survival protein suggests a possible role for sCLU in radiation adaptive responses, characterized by increased cell radioresistance after exposure to low adapting IR doses. Although it is still unclear whether the adaptive response is beneficial or not to cells, survival of damaged cells after IR may lead to genomic instability in the descendants of surviving cells. Recent studies indicate a link between sCLU accumulation and cancer incidence, as well as aging, supporting involvement of the protein in the development of genomic instability. Secreted after IR, sCLU may also alter intracellular communication due to its ability to bind cell surface receptors, such as the TGF-{beta} receptors (types I and II). This interference with signaling pathways may contribute to IR-induced bystander effects. We hypothesize that activation of the TGF-{beta} signaling pathway, which often occurs after IR exposure, can in turn activate the CLU promoter. TGF-{beta} and IR-inducible de novo synthesized sCLU may then bind the TGF-{beta} receptors and suppress downstream growth arrest

  17. Dietary consumption of monosodium L-glutamate induces adaptive response and reduction in the life span of Drosophila melanogaster.

    Science.gov (United States)

    Abolaji, Amos O; Olaiya, Charles O; Oluwadahunsi, Oluwagbenga J; Farombi, Ebenezer O

    2017-04-01

    Adaptive response is the ability of an organism to better counterattack stress-induced damage in response to a number of different cytotoxic agents. Monosodium L-glutamate (MSG), the sodium salt of amino acid glutamate, is commonly used as a food additive. We investigated the effects of MSG on the life span and antioxidant response in Drosophila melanogaster (D. melanogaster). Both genders (1 to 3 days old) of flies were fed with diet containing MSG (0.1, 0.5, and 2.5-g/kg diet) for 5 days to assess selected antioxidant and oxidative stress markers, while flies for longevity were fed for lifetime. Thereafter, the longevity assay, hydrogen peroxide (H 2 O 2 ), and reactive oxygen and nitrogen species levels were determined. Also, catalase, glutathione S-transferase and acetylcholinesterase activities, and total thiol content were evaluated in the flies. We found that MSG reduced the life span of the flies by up to 23% after continuous exposure. Also, MSG increased reactive oxygen and nitrogen species and H 2 O 2 generations and total thiol content as well as the activities of catalase and glutathione S-transferase in D. melanogaster (P melanogaster induced adaptive response, but long-term exposure reduced life span of flies. This study may therefore have public health significance in humans, and thus, moderate consumption of MSG is advocated by the authors. Copyright © 2017 John Wiley & Sons, Ltd.

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

    DEFF Research Database (Denmark)

    Fentz, Joachim; Kjøbsted, Rasmus; Maag Kristensen, Caroline

    2015-01-01

    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 trainin......-induced mRNA responses of some genes and may be involved in regulating basal metabolic protein expression, but seem to be less important in exercise training-induced adaptations in metabolic proteins.......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......-induced increases in exercise capacity and expression of metabolic proteins as well as acute exercise-induced gene regulation would be compromised in AMPKα1 and -α2 muscle-specific double knockout (mdKO) mice. An acute bout of exercise increased skeletal muscle mRNA content of cytochrome C oxidase subunit I...

  19. Collaboratively Adaptive Vibration Sensing System for High-fidelity Monitoring of Structural Responses Induced by Pedestrians

    Directory of Open Access Journals (Sweden)

    Shijia Pan

    2017-05-01

    Full Text Available This paper presents a collaboratively adaptive vibration monitoring system that captures high-fidelity structural vibration signals induced by pedestrians. These signals can be used for various human activities’ monitoring by inferring information about the impact sources, such as pedestrian footsteps, door opening and closing, and dragging objects. Such applications often require high-fidelity (high resolution and low distortion signals. Traditionally, expensive high resolution and high dynamic range sensors are adopted to ensure sufficient resolution. However, for sensing systems that use low-cost sensing devices, the resolution and dynamic range are often limited; hence this type of sensing methods is not well explored ubiquitously. We propose a low-cost sensing system that utilizes (1 a heuristic model of the investigating excitations and (2 shared information through networked devices to adapt hardware configurations and obtain high-fidelity structural vibration signals. To further explain the system, we use indoor pedestrian footstep sensing through ambient structural vibration as an example to demonstrate the system performance. We evaluate the application with three metrics that measure the signal quality from different aspects: the sufficient resolution rate to present signal resolution improvement without clipping, the clipping rate to measure the distortion of the footstep signal, and the signal magnitude to quantify the detailed resolution of the detected footstep signal. In experiments conducted in a school building, our system demonstrated up to 2× increase on the sufficient resolution rate and 2× less error rate when used to locate the pedestrians as they walk along the hallway, compared to a fixed sensing setting.

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

    Science.gov (United States)

    Paun, Alexandra; Kunwar, Amit; Haston, Christina K

    2015-02-20

    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.

  1. Role of x-ray-induced transcripts in adaptive responses following x-rays

    Energy Technology Data Exchange (ETDEWEB)

    Boothman, D.A.

    1992-01-01

    Potentially lethal damage repair (PLDR) and sublethal damage repair, may be the same manifestations of a series of common enzymatic steps. PLDR, has two distinct phases based upon DNA lesion repair and survival recovery studies. The first phase of PLDR occurs very quickly (t{sub {1/2}}:2--20 mins) to increase the survival of X-irradiated cells by mending the vast array of DNA lesions created by ionizing radiation. The second slower phase of PLDR proceeds much later (i.e., >1--2 hrs) following X-irradiation, during which the remaining double-stranded DNA breaks are completely repaired. This second phase of repair closely corresponds to the restructuring of gross chromosomal damage, and can be partially blocked in some human cells by inhibiting protein synthesis. This slower phase of PLDR correlated with a rapid decline in X-ray-induced transformation of normal cells. The fast component of PLDR may be due to constitutively synthesized DNA ligases, topoisomerases, or polymerases, which act immediately to repair damaged, DNA. In contrast, the slow phase of PLDR in human cells may require the induction of specific genes and gene product's involved in the repair of potentially lethal or carcinogenic DNA lesions. Induced gene products (i.e., proteins) specifically synthesized in response to physiological doses of ionizing radiation in radioresistant human melanoma (U1-Mel) cells, and in a variety of other human normal and cancer-prone cells, were identified using two-dimensional gel electrophoresis. We identified and partially characterized ten proteins synthesized by U1-Mel cells. The synthesis of eight of these proteins were specifically induced by ionizing radiation and two proteins were repressed Neither heat shock, UV-irradiation, nor bifunctional alkylating agent treatments resulted in the induction of these proteins. The expression of one protein, XIP269, correlated very well with PLDR capacity.

  2. Competitive apnea diving sessions induces an adaptative antioxidant response in mononucleated blood cells.

    Science.gov (United States)

    Sureda, A; Batle, J M; Tur, J A; Pons, A

    2015-09-01

    The aim was evaluating the effects of hypoxia/reoxygenation repetitive episodes during 5 days of apnea diving (3-day training/2-day competition) on peripheral blood mononuclear cells (PBMCs) antioxidant defenses, oxidative damage, and plasma xanthine oxidase activity. Blood samples, from seven professional apnea divers, were taken under basal conditions the previous morning to the first training session (pre-diving basal), 4 h after ending the competition (4 h post-diving) and the following morning (15 h after last dive) in basal conditions (post-diving basal). Glucose levels significantly decreased whereas triglycerides increased at 4 h post-diving, both returning to basal values at post-diving basal. Glutathione reductase and catalase activity significantly increased after 4 h post-diving remaining elevated at post-diving basal. Glutathione peroxidase and superoxide dismutase activities and catalase protein levels progressively increased after diving with significant differences respect to initial values at post-diving basal. No significant differences were observed in circulating PBMCs and oxidative damage markers. Plasma xanthine oxidase activity and nitrite levels, but not the inducible nitric oxide synthetase, significantly increased 4 h post-diving, returning to the basal values after 15 h. In conclusion, chronic and repetitive episodes of diving apnea during five consecutive days increased plasma xanthine oxidase activity and nitric oxide production which could enhance the signalling role of reactive oxygen and nitrogen species for PBMCs antioxidant adaptation against hypoxia/reoxygenation.

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

    International Nuclear Information System (INIS)

    Hee-Sun, K.; Kwang-Hee, Y.; Cha-Soom, K.; Jung-Mi, C.; Gu-Choul, S.; Suk-Young, P.; Kyoung-H, C.; Chong-Soom, K.; Young-Khi, L.; Jae-Ho, W.

    2004-01-01

    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. Role of DNA damage repair capacity in radiation induced adaptive response

    International Nuclear Information System (INIS)

    Yuan Dexiao; Pan Yan; Zhao Meijia; Chen Honghong; Shao Cunlin

    2009-01-01

    This work was to explore γ-ray induced radioadaptive response (RAR) in Chinese hamster ovary(CHO) cell lines of different DNA damage repair capacities. CHO-9 cells and the two repair-deficient strains, EM-C11(DNA single strand break repair deficient) and XR-C1(DNA double strand break repair deficient), were irradiated with a priming dose of 0.08 Gy or 0.016 Gy. After 4 or 7 hours, they were irradiated again with a challenging dose of 1 Gy. The micronucleus induction and plating efficiency of the cells were assayed. Under 0.08 Gy priming dose and 4-h interval, just the CHO-9 cells showed RAR, while with the 7-h interval the CHO-9 and EM-C11 showed RAR, but XR-C1 did not. When the cells were pretreated with a lower priming dose of 0.016 Gy in a 4-h time interval, all the three cell lines showed RAR to subsequent 1 Gy irradiation. It can be concluded that RAR is not only related to the priming dose and time interval, but also has close dependence on the ability of DNA damage repair. (authors)

  5. Periodontitis induced by Porphyromonas gingivalis drives periodontal microbiota dysbiosis and insulin resistance via an impaired adaptive immune response.

    Science.gov (United States)

    Blasco-Baque, Vincent; Garidou, Lucile; Pomié, Céline; Escoula, Quentin; Loubieres, Pascale; Le Gall-David, Sandrine; Lemaitre, Mathieu; Nicolas, Simon; Klopp, Pascale; Waget, Aurélie; Azalbert, Vincent; Colom, André; Bonnaure-Mallet, Martine; Kemoun, Philippe; Serino, Matteo; Burcelin, Rémy

    2017-05-01

    To identify a causal mechanism responsible for the enhancement of insulin resistance and hyperglycaemia following periodontitis in mice fed a fat-enriched diet. We set-up a unique animal model of periodontitis in C57Bl/6 female mice by infecting the periodontal tissue with specific and alive pathogens like Porphyromonas gingivalis ( Pg ), Fusobacterium nucleatum and Prevotella intermedia . The mice were then fed with a diabetogenic/non-obesogenic fat-enriched diet for up to 3 months. Alveolar bone loss, periodontal microbiota dysbiosis and features of glucose metabolism were quantified. Eventually, adoptive transfer of cervical (regional) and systemic immune cells was performed to demonstrate the causal role of the cervical immune system. Periodontitis induced a periodontal microbiota dysbiosis without mainly affecting gut microbiota. The disease concomitantly impacted on the regional and systemic immune response impairing glucose metabolism. The transfer of cervical lymph-node cells from infected mice to naive recipients guarded against periodontitis-aggravated metabolic disease. A treatment with inactivated Pg prior to the periodontal infection induced specific antibodies against Pg and protected the mouse from periodontitis-induced dysmetabolism. Finally, a 1-month subcutaneous chronic infusion of low rates of lipopolysaccharides from Pg mimicked the impact of periodontitis on immune and metabolic parameters. We identified that insulin resistance in the high-fat fed mouse is enhanced by pathogen-induced periodontitis. This is caused by an adaptive immune response specifically directed against pathogens and associated with a periodontal dysbiosis. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

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

    International Nuclear Information System (INIS)

    Banzet, N.; Richaud, C.; Deveaux, Y.; Kazmaier, M.; Gagnon, J.; Triantaphylides, C.

    1998-01-01

    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

  7. Cancer: brain-regulated biphasic stress response induces cell growth or cell death to adapt to psychological stressors.

    Science.gov (United States)

    Thomas, Charles; Bhatia, Shruti

    2014-01-01

    According to Indian Vedic philosophy, a human being contains 3 major bodies: (1) the matter body--brain, organs, and senses; (2) the mental body--mind, individual consciousness, intellect, and ego; and (3) the soul or causal body--universal consciousness. The third, which is located in the heart according to all spiritual traditions and recent scientific literature, can be seen as the information body that contains all memories. The mental body, which can interface with the matter and information bodies, can be seen as a field of immaterial energy that can carry, regulate, and strengthen all information (eg, thoughts or emotions) both positively and negatively. This body of information may store ancestral and/or autobiographical memories: unconscious memories from inner traumas--inner information (Ii) or samskaras in Vedic philosophy--and conscious memories from outer traumas--outer information (Io). These conscious and unconscious memories can be seen as potential psychological stressors. Resonance between Ii and Io may induce active conflicts if resistance occurs in the mental body; this conflict may cause specific metabolic activity in the brain and a stress response in the physical body, which permits adjustment to psychological stressors. The brainregulated stress response may be biphasic: cell death or growth induced by adrenergic molecular pathways during the conflict's unresolved phase and reversion to cell growth or death induced by cholinergic molecular pathways during the conflict's resolved phase. Case studies and data mining from PubMed suggest that this concept complies with the principles of holistic medicine and the scientific literature supporting its benefits. We suggest that the evolution of cancer can be seen as a biphasic stress response regulated by the brain to adapt to psychological stressors, which produce imbalance among the physical, mental, and information bodies.

  8. Hemeoxygenase-1 Mediates an Adaptive Response to Spermidine-Induced Cell Death in Human Endothelial Cells

    Directory of Open Access Journals (Sweden)

    Hana Yang

    2013-01-01

    Full Text Available Spermidine (SPD is a ubiquitous polycation that is commonly distributed in living organisms. Intracellular levels of SPD are tightly regulated, and SPD controls cell proliferation and death. However, SPD undergoes oxidation in the presence of serum, producing aldehydes, hydrogen peroxide, and ammonia, which exert cytotoxic effect on cells. Hemeoxygenase-1 (HO-1 is thought to have a protective effect against oxidative stress. Upregulation of HO-1 in endothelial cells is considered to be beneficial in the cardiovascular disease. In the present study, we demonstrate that the ubiquitous polyamine, SPD, induces HO-1 in human umbilical vein endothelial cells (HUVECs. SPD-induced HO-1 expression was examined by Western blot and reverse transcription-polymerase chain reaction (RT-PCR. Involvement of reactive oxygen species, serum amine oxidase, PI3K/Akt signaling pathway, and transcription factor Nrf2 in the induction of HO-1 by SPD was also investigated. Furthermore, small interfering RNA knockdown of Nrf2 or HO-1 and treatment with the specific HO-1 inhibitor ZnPP exhibited a noteworthy increase of death of SPD-stimulated HUVECs. In conclusion, these results suggest that SPD induces PI3K/Akt-Nrf2-mediated HO-1 expression in human endothelial cells, which may have a role in cytoprotection of the cells against oxidative stress-induced death.

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

    Science.gov (United States)

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

  10. Temporal specificity of the initial adaptive response in motor adaptation.

    Directory of Open Access Journals (Sweden)

    Wilsaan M Joiner

    2017-07-01

    Full Text Available Repeated exposure to a novel physical environment eventually leads to a mature adaptive response whereby feedforward changes in motor output mirror both the amplitude and temporal structure of the environmental perturbations. However, adaptive responses at the earliest stages of learning have been found to be not only smaller, but systematically less specific in their temporal structure compared to later stages of learning. This observation has spawned a lively debate as to whether the temporal structure of the initial adaptive response is, in fact, stereotyped and non-specific. To settle this debate, we directly measured the adaptive responses to velocity-dependent and position-dependent force-field perturbations (vFFs and pFFs at the earliest possible stage of motor learning in humans-after just a single-movement exposure. In line with previous work, we found these earliest stage adaptive responses to be more similar than the perturbations that induced them. However, the single-trial adaptive responses for vFF and pFF perturbations were clearly distinct, and the disparity between them reflected the difference between the temporal structure of the perturbations that drove them. Critically, we observed these differences between single-trial adaptive responses when vFF and pFF perturbations were randomly intermingled from one trial to the next within the same block, indicating perturbation response specificity at the single trial level. These findings demonstrate that the initial adaptive responses to physical perturbations are not stereotyped. Instead, the neural plasticity in sensorimotor areas is sensitive to the temporal structure of a movement perturbation even at the earliest stage in learning. This insight has direct implications for the development of computational models of early-stage motor adaptation and the evolution of this adaptive response with continued training.

  11. Nano-Pulse Stimulation induces immunogenic cell death in human papillomavirus-transformed tumors and initiates an adaptive immune response.

    Directory of Open Access Journals (Sweden)

    Joseph G Skeate

    Full Text Available Nano-Pulse Stimulation (NPS is a non-thermal pulsed electric field modality that has been shown to have cancer therapeutic effects. Here we applied NPS treatment to the human papillomavirus type 16 (HPV 16-transformed C3.43 mouse tumor cell model and showed that it is effective at eliminating primary tumors through the induction of immunogenic cell death while subsequently increasing the number of tumor-infiltrating lymphocytes within the tumor microenvironment. In vitro NPS treatment of C3.43 cells resulted in a doubling of activated caspase 3/7 along with the translocation of phosphatidylserine (PS to the outer leaflet of the plasma membrane, indicating programmed cell death activity. Tumor-bearing mice receiving standard NPS treatment showed an initial decrease in tumor volume followed by clearing of tumors in most mice, and a significant increase in overall survival. Intra-tumor analysis of mice that were unable to clear tumors showed an inverse correlation between the number of tumor infiltrating lymphocytes and the size of the tumor. Approximately half of the mice that cleared established tumors were protected against tumor re-challenge on the opposite flank. Selective depletion of CD8+ T cells eliminated this protection, suggesting that NPS treatment induces an adaptive immune response generating CD8+ T cells that recognize tumor antigen(s associated with the C3.43 tumor model. This method may be utilized in the future to not only ablate primary tumors, but also to induce an anti-tumor response driven by effector CD8+ T cells capable of protecting individuals from disease recurrence.

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

    Directory of Open Access Journals (Sweden)

    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. Renal overexpression of atrial natriuretic peptide and hypoxia inducible factor-1α as adaptive response to a high salt diet.

    Science.gov (United States)

    Della Penna, Silvana Lorena; Cao, Gabriel; Carranza, Andrea; Zotta, Elsa; Gorzalczany, Susana; Cerrudo, Carolina Susana; Rukavina Mikusic, Natalia Lucía; Correa, Alicia; Trida, Verónica; Toblli, Jorge Eduardo; Rosón, María Inés; Fernández, Belisario Enrique

    2014-01-01

    In the kidney, a high salt intake favors oxidative stress and hypoxia and causes the development of fibrosis. Both atrial natriuretic peptide (ANP) and hypoxia inducible factor (HIF-1α) exert cytoprotective effects. We tested the hypothesis that renal expression of ANP and HIF-1α is involved in a mechanism responding to the oxidative stress produced in the kidneys of rats chronically fed a high sodium diet. Sprague-Dawley rats were fed with a normal salt (0.4% NaCl) (NS) or a high salt (8% NaCl) (HS) diet for 3 weeks, with or without the administration of tempol (T), an inhibitor of oxidative stress, in the drinking water. We measured the mean arterial pressure (MAP), glomerular filtration rate (GFR), and urinary sodium excretion (UVNa). We evaluated the expression of ANP, HIF-1α, and transforming growth factor (TGF-β1) in renal tissues by western blot and immunohistochemistry. The animals fed a high salt diet showed increased MAP and UVNa levels and enhanced renal immunostaining of ANP, HIF-1α, and TGF-β1. The administration of tempol together with the sodium overload increased the natriuresis further and prevented the elevation of blood pressure and the increased expression of ANP, TGF-β1, and HIF-1α compared to their control. These findings suggest that HIF-1α and ANP, synthesized by the kidney, are involved in an adaptive mechanism in response to a sodium overload to prevent or attenuate the deleterious effects of the oxidative stress and the hypoxia on the development of fibrosis.

  14. Renal Overexpression of Atrial Natriuretic Peptide and Hypoxia Inducible Factor-1α as Adaptive Response to a High Salt Diet

    Directory of Open Access Journals (Sweden)

    Silvana Lorena Della Penna

    2014-01-01

    Full Text Available In the kidney, a high salt intake favors oxidative stress and hypoxia and causes the development of fibrosis. Both atrial natriuretic peptide (ANP and hypoxia inducible factor (HIF-1α exert cytoprotective effects. We tested the hypothesis that renal expression of ANP and HIF-1α is involved in a mechanism responding to the oxidative stress produced in the kidneys of rats chronically fed a high sodium diet. Sprague-Dawley rats were fed with a normal salt (0.4% NaCl (NS or a high salt (8% NaCl (HS diet for 3 weeks, with or without the administration of tempol (T, an inhibitor of oxidative stress, in the drinking water. We measured the mean arterial pressure (MAP, glomerular filtration rate (GFR, and urinary sodium excretion (UVNa. We evaluated the expression of ANP, HIF-1α, and transforming growth factor (TGF-β1 in renal tissues by western blot and immunohistochemistry. The animals fed a high salt diet showed increased MAP and UVNa levels and enhanced renal immunostaining of ANP, HIF-1α, and TGF-β1. The administration of tempol together with the sodium overload increased the natriuresis further and prevented the elevation of blood pressure and the increased expression of ANP, TGF-β1, and HIF-1α compared to their control. These findings suggest that HIF-1α and ANP, synthesized by the kidney, are involved in an adaptive mechanism in response to a sodium overload to prevent or attenuate the deleterious effects of the oxidative stress and the hypoxia on the development of fibrosis.

  15. Innate inhibition of adaptive immunity: Mycobacterium tuberculosis-induced IL-6 inhibits macrophage responses to IFN-gamma.

    Science.gov (United States)

    Nagabhushanam, Vijaya; Solache, Alejandra; Ting, Li-Min; Escaron, Claire J; Zhang, Jennifer Y; Ernst, Joel D

    2003-11-01

    In humans and in mice, control of the intracellular pathogen, Mycobacterium tuberculosis (Mtb), requires IFN-gamma. Although the adaptive immune response results in production of substantial amounts of IFN-gamma in response to Mtb, the immune response is unable to eradicate the infection in most cases. We have previously reported evidence that Mtb inhibits macrophage responses to IFN-gamma, suggesting that this may limit the ability of IFN-gamma to stimulate macrophages to kill Mtb. We have also observed that uninfected macrophages, adjacent to infected macrophages in culture, exhibit decreased responses to IFN-gamma. Here we report that IL-6 secreted by Mtb-infected macrophages inhibits the responses of uninfected macrophages to IFN-gamma. IL-6 selectively inhibits a subset of IFN-gamma-responsive genes at the level of transcriptional activation without inhibiting activation or function of STAT1. Inhibition of macrophage responses to IFN-gamma by IL-6 requires new protein synthesis, but this effect is not attributable to suppressor of cytokine signaling 1 or 3. These results reveal a novel function for IL-6 and indicate that IL-6 secreted by Mtb-infected macrophages may contribute to the inability of the cellular immune response to eradicate infection.

  16. Dose-rate effect of adaptive response of apoptosis and cell cycle progression induced by low-dose ionizing radiation in EL-4 lymphoma cells in vitro

    International Nuclear Information System (INIS)

    Liu Shuchun; Lu Zhe; Li Yanbo; Kang Shunai; Gong Shouliang; Zhao Wenju

    2008-01-01

    Objective: To observe the dose-rate effect of adaptive response of apoptosis and cell cycle progression induced by low-dose ionizing radiation in EL-4 lymphoma cells in vitro in order to reveal the possible mechanism of biological effect and adaptive response induced by low dose radiation. Methods: The experiment was divided into D2 (challenging dose), D1 (inductive dose) + D2 and sham-irradiation groups. EL-4 lymphoma cells were irradiated with D1 (75 mGy, 6.25-200.00 mGy·mm -1 ) and D2(1.5 Gy, 287 mGy·min -1 ), the time interval between D1 and D2 was 6 h. The percentage of apoptosis and each cell cycle phase were measured with flow cytometry. Results: When the dose rates of D1 were 6.25-50.00 mGy·min -1 , the percentages of apoptosis in the D1 + D2 group were significantly lower than those in the D2 group (P 0 /G 1 phase cells decreased significantly (P -1 , D2 is 1.5 Gy (287 mGy·min -1 ), and the time interval between D1 and D2 is 6 h, the adaptive response of apoptosis and cell cycle progression in EL-4 lymphoma cells in vitro could be induced. (authors)

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

    International Nuclear Information System (INIS)

    Mendiola C, M.T.; Morales R, P.

    2003-01-01

    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 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)

  18. Inducible competitors and adaptive diversification

    Directory of Open Access Journals (Sweden)

    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].

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

    Science.gov (United States)

    Mahadimane, Periyapatna Vishwaprakash; Vasudev, Venkateshaiah

    2014-01-01

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  1. Adaptive T cell responses induced by oncolytic Herpes Simplex Virus-granulocyte macrophage-colony-stimulating factor therapy expanded by dendritic cell and cytokine-induced killer cell adoptive therapy.

    Science.gov (United States)

    Ren, Jun; Gwin, William R; Zhou, Xinna; Wang, Xiaoli; Huang, Hongyan; Jiang, Ni; Zhou, Lei; Agarwal, Pankaj; Hobeika, Amy; Crosby, Erika; Hartman, Zachary C; Morse, Michael A; H Eng, Kevin; Lyerly, H Kim

    2017-01-01

    Purpose : Although local oncolytic viral therapy (OVT) may enhance tumor lysis, antigen release, and adaptive immune responses, systemic antitumor responses post-therapy are limited. Adoptive immunotherapy with autologous dendritic cells (DC) and cytokine-induced killer cells (DC-CIK) synergizes with systemic therapies. We hypothesized that OVT with Herpes Simplex Virus-granulocyte macrophage-colony-stimulating factor (HSV-GM-CSF) would induce adaptive T cell responses that could be expanded systemically with sequential DC-CIK therapy. Patients and Methods : We performed a pilot study of intratumoral HSV-GM-CSF OVT followed by autologous DC-CIK cell therapy. In addition to safety and clinical endpoints, we monitored adaptive T cell responses by quantifying T cell receptor (TCR) populations in pre-oncolytic therapy, post-oncolytic therapy, and after DC-CIK therapy. Results : Nine patients with advanced malignancy were treated with OVT (OrienX010), of whom seven experienced stable disease (SD). Five of the OVT treated patients underwent leukapheresis, generation, and delivery of DC-CIKs, and two had SD, whereas three progressed. T cell receptor sequencing of TCR β sequences one month after OVT therapy demonstrates a dynamic TCR repertoire in response to OVT therapy in the majority of patients with the systematic expansion of multiple T cell clone populations following DC-CIK therapy. This treatment was well tolerated and long-term event free and overall survival was observed in six of the nine patients. Conclusions : Strategies inducing the local activation of tumor-specific immune responses can be combined with adoptive cellular therapies to expand the adaptive T cell responses systemically and further studies are warranted.

  2. Priming of hypoxia-inducible factor by neuronal nitric oxide synthase is essential for adaptive responses to severe anemia.

    Science.gov (United States)

    Tsui, Albert K Y; Marsden, Philip A; Mazer, C David; Adamson, S Lee; Henkelman, R Mark; Ho, J J David; Wilson, David F; Heximer, Scott P; Connelly, Kim A; Bolz, Steffen-Sebastian; Lidington, Darcy; El-Beheiry, Mostafa H; Dattani, Neil D; Chen, Kevin M; Hare, Gregory M T

    2011-10-18

    Cells sense and respond to changes in oxygen concentration through gene regulatory processes that are fundamental to survival. Surprisingly, little is known about how anemia affects hypoxia signaling. Because nitric oxide synthases (NOSs) figure prominently in the cellular responses to acute hypoxia, we defined the effects of NOS deficiency in acute anemia. In contrast to endothelial NOS or inducible NOS deficiency, neuronal NOS (nNOS)(-/-) mice demonstrated increased mortality during anemia. Unlike wild-type (WT) animals, anemia did not increase cardiac output (CO) or reduce systemic vascular resistance (SVR) in nNOS(-/-) mice. At the cellular level, anemia increased expression of HIF-1α protein and HIF-responsive mRNA levels (EPO, VEGF, GLUT1, PDK1) in the brain of WT, but not nNOS(-/-) mice, despite comparable reductions in tissue PO(2). Paradoxically, nNOS(-/-) mice survived longer during hypoxia, retained the ability to regulate CO and SVR, and increased brain HIF-α protein levels and HIF-responsive mRNA transcripts. Real-time imaging of transgenic animals expressing a reporter HIF-α(ODD)-luciferase chimeric protein confirmed that nNOS was essential for anemia-mediated increases in HIF-α protein stability in vivo. S-nitrosylation effects the functional interaction between HIF and pVHL. We found that anemia led to nNOS-dependent S-nitrosylation of pVHL in vivo and, of interest, led to decreased expression of GSNO reductase. These findings identify nNOS effects on the HIF/pVHL signaling pathway as critically important in the physiological responses to anemia in vivo and provide essential mechanistic insight into the differences between anemia and hypoxia.

  3. Leaf Physiological and Proteomic Analysis to Elucidate Silicon Induced Adaptive Response under Salt Stress in Rosa hybrida 'Rock Fire'.

    Science.gov (United States)

    Soundararajan, Prabhakaran; Manivannan, Abinaya; Ko, Chung Ho; Muneer, Sowbiya; Jeong, Byoung Ryong

    2017-08-14

    Beneficial effects of silicon (Si) on growth and development have been witnessed in several plants. Nevertheless, studies on roses are merely reported. Therefore, the present investigation was carried out to illustrate the impact of Si on photosynthesis, antioxidant defense and leaf proteome of rose under salinity stress. In vitro-grown, acclimatized Rosa hybrida 'Rock Fire' were hydroponically treated with four treatments, such as control, Si (1.8 mM), NaCl (50 mM), and Si+NaCl. After 15 days, the consequences of salinity stress and the response of Si addition were analyzed. Scorching of leaf edges and stomatal damages occurred due to salt stress was ameliorated under Si supplementation. Similarly, reduction of gas exchange, photosynthetic pigments, higher lipid peroxidation rate, and accumulation of reactive oxygen species under salinity stress were mitigated in Si treatment. Lesser oxidative stress observed was correlated with the enhanced activity and expression of antioxidant enzymes, such as superoxide dismutase, catalase, and ascorbate peroxidase in Si+NaCl treatment. Importantly, sodium transportation was synergistically restricted with the stimulated counter-uptake of potassium in Si+NaCl treatment. Furthermore, two-dimensional electrophoresis (2-DE) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) results showed that out of 40 identified proteins, on comparison with control 34 proteins were down-accumulated and six proteins were up-accumulated due to salinity stress. Meanwhile, addition of Si with NaCl treatment enhanced the abundance of 30 proteins and downregulated five proteins. Differentially-expressed proteins were functionally classified into six groups, such as photosynthesis (22%), carbohydrate/energy metabolism (20%), transcription/translation (20%), stress/redox homeostasis (12%), ion binding (13%), and ubiquitination (8%). Hence, the findings reported in this work could facilitate a deeper

  4. Adaptive response of low linear energy transfer X-rays for protection against high linear energy transfer accelerated heavy ion-induced teratogenesis.

    Science.gov (United States)

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

    2012-12-01

    Adaptive response (AR) of low linear energy transfer (LET) irradiations for protection against teratogenesis induced by high LET irradiations is not well documented. In this study, induction of AR by X-rays against teratogenesis induced by accelerated heavy ions was examined in fetal mice. Irradiations of pregnant C57BL/6J mice were performed by delivering a priming low dose from X-rays at 0.05 or 0.30 Gy on gestation day 11 followed one day later by a challenge high dose from either X-rays or accelerated heavy ions. Monoenergetic beams of carbon, neon, silicon, and iron with the LET values of about 15, 30, 55, and 200 keV/μm, respectively, were examined. Significant suppression of teratogenic effects (fetal death, malformation of live fetuses, or low body weight) was used as the endpoint for judgment of a successful AR induction. Existence of AR induced by low-LET X-rays against teratogenic effect induced by high-LET accelerated heavy ions was demonstrated. The priming low dose of X-rays significantly reduced the occurrence of prenatal fetal death, malformation, and/or low body weight induced by the challenge high dose from either X-rays or accelerated heavy ions of carbon, neon or silicon but not iron particles. Successful AR induction appears to be a radiation quality event, depending on the LET value and/or the particle species of the challenge irradiations. These findings would provide a new insight into the study on radiation-induced AR in utero. © 2012 Wiley Periodicals, Inc.

  5. Autophagy suppresses host adaptive immune responses toward Borrelia burgdorferi

    NARCIS (Netherlands)

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

    Inhibition of autophagy increases the severity of murine Lyme arthritis and human adaptive immune responses against B. burgdorferi. We have previously demonstrated that inhibition of autophagy increased the Borrelia burgdorferi induced innate cytokine production in vitro, but little is known

  6. Initial Characterization of the Growth Stimulation and Heat-Shock-Induced Adaptive Response in Developing Lake Whitefish Embryos after Ionizing Radiation Exposure.

    Science.gov (United States)

    Thome, Christopher; Mitz, Charles; Hulley, Emily N; Somers, Christopher M; Manzon, Richard G; Wilson, Joanna Y; Boreham, Douglas R

    2017-10-01

    Ionizing radiation is known to effect development during early life stages. Lake whitefish (Coregonus clupeaformis) represent a unique model organism for examining such effects. The purpose of this study was to examine how ionizing radiation affects development in lake whitefish embryos and to investigate the presence of an adaptive response induced by heat shock. Acute exposure to 137 Cs gamma rays was administered at five time points corresponding to major developmental stages, with doses ranging from 0.008 to 15.5 Gy. Chronic gamma-ray exposures were delivered throughout embryogenesis within a custom-built irradiator at dose rates between 0.06 and 4.4 mGy/day. Additionally, embryos were given a heat shock of 3, 6 or 9°C prior to a single acute exposure. Radiation effects were assessed based on survival, development rate, morphometric measurements and growth efficiency. Embryos showed high resistance to acute exposures with an LD 50/hatch of 5.0 ± 0.7 Gy immediately after fertilization, increasing to 14.2 ± 0.1 Gy later in development. Chronic irradiation at all dose rates stimulated growth, with treated embryos up to 60% larger in body mass during development compared to unirradiated controls. Chronic irradiation also accelerated the time-to-hatch. A heat shock administered 6 h prior to irradiation reduced mortality by up to 25%. Overall, low-dose chronic irradiation caused growth stimulation in developing lake whitefish embryos and acute radiation mortality was reduced by a heat-shock-induced adaptive response.

  7. FGF21 induces PGC-1α and regulates carbohydrate and fatty acid metabolism during the adaptive starvation response

    OpenAIRE

    Potthoff, Matthew J.; Inagaki, Takeshi; Satapati, Santhosh; Ding, Xunshan; He, Tianteng; Goetz, Regina; Mohammadi, Moosa; Finck, Brian N.; Mangelsdorf, David J.; Kliewer, Steven A.; Burgess, Shawn C.

    2009-01-01

    The liver plays a crucial role in mobilizing energy during nutritional deprivation. During the early stages of fasting, hepatic glycogenolysis is a primary energy source. As fasting progresses and glycogen stores are depleted, hepatic gluconeogenesis and ketogenesis become major energy sources. Here, we show that fibroblast growth factor 21 (FGF21), a hormone that is induced in liver by fasting, induces hepatic expression of peroxisome proliferator-activated receptor γ coactivator protein-1α ...

  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

    Energy Technology Data Exchange (ETDEWEB)

    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. Local adaptation in transgenerational responses to predators

    Science.gov (United States)

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

    2016-01-01

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

  10. Studies on adaptive responses in Chinese hamster cells

    International Nuclear Information System (INIS)

    Michelin, S.C.; Perez, M.R. Del; Dubner, D.; Gisone, P.A.

    1997-01-01

    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

  11. Physiological response of Pichia pastoris GS115 to methanol-induced high level production of the Hepatitis B surface antigen: catabolic adaptation, stress responses, and autophagic processes.

    Science.gov (United States)

    Vanz, Ana Leticia; Lünsdorf, Heinrich; Adnan, Ahmad; Nimtz, Manfred; Gurramkonda, Chandrasekhar; Khanna, Navin; Rinas, Ursula

    2012-08-08

    Pichia pastoris is an established eukaryotic host for the production of recombinant proteins. Most often, protein production is under the control of the strong methanol-inducible aox1 promoter. However, detailed information about the physiological alterations in P. pastoris accompanying the shift from growth on glycerol to methanol-induced protein production under industrial relevant conditions is missing. Here, we provide an analysis of the physiological response of P. pastoris GS115 to methanol-induced high-level production of the Hepatitis B virus surface antigen (HBsAg). High product titers and the retention of the protein in the endoplasmic reticulum (ER) are supposedly of major impact on the host physiology. For a more detailed understanding of the cellular response to methanol-induced HBsAg production, the time-dependent changes in the yeast proteome and ultrastructural cell morphology were analyzed during the production process. The shift from growth on glycerol to growth and HBsAg production on methanol was accompanied by a drastic change in the yeast proteome. In particular, enzymes from the methanol dissimilation pathway started to dominate the proteome while enzymes from the methanol assimilation pathway, e.g. the transketolase DAS1, increased only moderately. The majority of methanol was metabolized via the energy generating dissimilatory pathway leading to a corresponding increase in mitochondrial size and numbers. The methanol-metabolism related generation of reactive oxygen species induced a pronounced oxidative stress response (e.g. strong increase of the peroxiredoxin PMP20). Moreover, the accumulation of HBsAg in the ER resulted in the induction of the unfolded protein response (e.g. strong increase of the ER-resident disulfide isomerase, PDI) and the ER associated degradation (ERAD) pathway (e.g. increase of two cytosolic chaperones and members of the AAA ATPase superfamily) indicating that potential degradation of HBsAg could proceed via the

  12. Physiological response of Pichia pastoris GS115 to methanol-induced high level production of the Hepatitis B surface antigen: catabolic adaptation, stress responses, and autophagic processes

    Science.gov (United States)

    2012-01-01

    Background Pichia pastoris is an established eukaryotic host for the production of recombinant proteins. Most often, protein production is under the control of the strong methanol-inducible aox1 promoter. However, detailed information about the physiological alterations in P. pastoris accompanying the shift from growth on glycerol to methanol-induced protein production under industrial relevant conditions is missing. Here, we provide an analysis of the physiological response of P. pastoris GS115 to methanol-induced high-level production of the Hepatitis B virus surface antigen (HBsAg). High product titers and the retention of the protein in the endoplasmic reticulum (ER) are supposedly of major impact on the host physiology. For a more detailed understanding of the cellular response to methanol-induced HBsAg production, the time-dependent changes in the yeast proteome and ultrastructural cell morphology were analyzed during the production process. Results The shift from growth on glycerol to growth and HBsAg production on methanol was accompanied by a drastic change in the yeast proteome. In particular, enzymes from the methanol dissimilation pathway started to dominate the proteome while enzymes from the methanol assimilation pathway, e.g. the transketolase DAS1, increased only moderately. The majority of methanol was metabolized via the energy generating dissimilatory pathway leading to a corresponding increase in mitochondrial size and numbers. The methanol-metabolism related generation of reactive oxygen species induced a pronounced oxidative stress response (e.g. strong increase of the peroxiredoxin PMP20). Moreover, the accumulation of HBsAg in the ER resulted in the induction of the unfolded protein response (e.g. strong increase of the ER-resident disulfide isomerase, PDI) and the ER associated degradation (ERAD) pathway (e.g. increase of two cytosolic chaperones and members of the AAA ATPase superfamily) indicating that potential degradation of HBsAg could

  13. The roles of ATF3, an adaptive-response gene, in high-fat-diet-induced diabetes and pancreatic beta-cell dysfunction.

    Science.gov (United States)

    Zmuda, Erik J; Qi, Ling; Zhu, Michael X; Mirmira, Raghavendra G; Montminy, Marc R; Hai, Tsonwin

    2010-07-01

    Most people with type 2 diabetes (T2D) have reduced beta-cell mass, and apoptosis is a key factor for this reduction. Previously, we showed that ATF3, an adaptive-response gene, is induced by various stress signals relevant to T2D, such as high glucose and high fatty acid. Because ATF3 is proapoptotic in beta-cells, we tested the hypothesis that ATF3 plays a detrimental role and contributes to the development of T2D. We compared wild-type (WT) and ATF3 knockout (KO) mice in an animal model for T2D, high-fat diet-induced diabetes. We also used INS-1 beta-cells and primary islets to analyze the roles of ATF3 in beta-cell function, including insulin gene expression and glucose-induced insulin secretion. Surprisingly, WT mice performed better in glucose tolerance test than KO mice, suggesting a protective, rather than detrimental, role of ATF3. At 12 wk on high-fat diet, no beta-cell apoptosis was observed, and the WT and KO mice had comparable beta-cell areas. However, ATF3 deficiency significantly reduced serum insulin levels in the KO mice without affecting insulin sensitivity, suggesting reduced beta-cell function in the KO mice. Analyses using INS-1 cells and primary islets support the notion that this defect is due, at least partly, to reduced insulin gene transcription in the KO islets without detectable reduction in glucose-induced calcium influx, a critical step for insulin secretion. In conclusion, our results support a model in which, before apoptosis becomes obvious, expression of ATF3 can be beneficial by helping beta-cells to cope with higher metabolic demand.

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

    International Nuclear Information System (INIS)

    Medina-Reyes, Estefany I.; Déciga-Alcaraz, Alejandro; Freyre-Fonseca, Verónica; Delgado-Buenrostro, Norma L.; Flores-Flores, José O.; Gutiérrez-López, Gustavo F.; Sánchez-Pérez, Yesennia; García-Cuéllar, Claudia M.

    2015-01-01

    Titanium dioxide nanoparticles (TiO 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 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 2 -B) using TiO 2 spheres (TiO 2 -SP) purchased from Sigma Aldrich Co. Then, lung epithelial A549 cells were low-exposed (10 µg/cm 2 ) to both shapes during 7 days and internalization, cytokine release and invasive potential were determined. Results showed greater TiO 2 -B effect on agglomerates size, cell size and granularity than TiO 2 -SP. Agglomerates size in cell culture medium was 310 nm and 454 nm for TiO 2 -SP and TiO 2 -B, respectively; TiO 2 -SP and TiO 2 -B induced 23% and 70% cell size decrease, respectively, whilst TiO 2 -SP and TiO 2 -B induced 7 and 14-fold of granularity increase. NO x production was down-regulated (31%) by TiO 2 -SP and up-regulated (70%) by TiO 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 2 -SP exposed cells while TiO 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 2 -B had higher proliferative potential than TiO 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 2 ) to titanium dioxide nanoparticles (TiO 2 -NPs) shaped as spheres (TiO 2 -SP) and belts (TiO 2 -B) for midterm (7 continuous days) separately. (B) Then, cells from each cell

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

    Energy Technology Data Exchange (ETDEWEB)

    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

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  17. Phenomenon of adaptive response of cells in radiobiology

    International Nuclear Information System (INIS)

    Fillipovich, I.V.

    1991-01-01

    Consideration is given to various adaptive reactions to low-level radiation, their association with an absorbed dose, dose rate, radiation quality and time-interval between exposures, as well as with a cell cycle phase. Possible mechanisms of the adaptive response and the character and role of DNA damages, that can induce gene expression of the adaptive response, are discussed. The data on the influence of a preliminary long-term exposure to low-level radiation on the radiosensitivity of biological objects are analyzed with due regard for the adaptive cell response. It is concluded that the adaptive response of cells to ionizing radiation is a particular case of the phenomenon of cell adaptation of the effect of genotoxic factors of the environment

  18. Effect of Scoparia dulcis on noise stress induced adaptive immunity and cytokine response in immunized Wistar rats.

    Science.gov (United States)

    Sundareswaran, Loganathan; Srinivasan, Sakthivel; Wankhar, Wankupar; Sheeladevi, Rathinasamy

    Noise acts as a stressor and is reported to have impact on individual health depending on nature, type, intensity and perception. Modern medicine has no effective drugs or cure to prevent its consequences. Being an environmental stressor noise cannot be avoided; instead minimizing its exposure or consuming anti-stressor and adaptogens from plants can be considered. The present study was carried out to evaluate the anti-stressor, adaptogen and immunostimulatory activity of Scoparia dulcis against noise-induced stress in Wistar rat models. Noise stress in rats was created by broadband white noise generator, 100 dB A/4 h daily/15 days and S. dulcis (200 mg/kg b.w.) was administered orally. 8 groups of rats were used consisting of 6 animals each; 4 groups for unimmunized and 4 groups for immunized. For immunization, sheep red blood cells (5 × 10 9  cells/ml) were injected intraperitoneally. Sub-acute noise exposed rats showed a significant increase in corticosterone and IL-4 levels in both immunized and unimmunized rats whereas lymphocytes, antibody titration, soluble immune complex, IL-4 showed a marked increase with a significant decrease in IL-2, TNF-α, IFN-γ cytokines only in unimmunized rats. Immunized noise exposed rats presented increased leukocyte migration index and decreased foot pad thickness, IL-2, TNF-α, IFN-γ with no changes in the lymphocytes. S. dulcis (SD) has normalized and prevented the noise induced changes in cell-mediated and humoral immunity and it could be the presence of anti-stressor and immuno stimulant activity of the plant. Copyright © 2016 Transdisciplinary University, Bangalore and World Ayurveda Foundation. Published by Elsevier B.V. All rights reserved.

  19. Adaptive response to high LET radiations

    International Nuclear Information System (INIS)

    Dam, Annamaria; Bogdandi, E. Noemi; Polonyi, Istvan; Sardy, M. Marta; Balashazy, Imre; Palfalvy, Jozsef

    2001-01-01

    The biological consequences of exposure to ionizing radiation include gene mutation, chromosome aberrations, cellular transformation and cell death. These effects are attributed to the DNA damaging effects of the irradiation resulting in irreversible changes during DNA replication or during the processing of the DNA damage by enzymatic repair processes. These repair processes could initiate some adaptive mechanisms in the cell, which could lead to radioadaptive response (RAR). Adaptive responses have typically been detected by exposing cells to a low radiation dose (1-50 mGy) and then challenging the cells with a higher dose of radiation (2-4 Gy) and comparing the outcome to that seen with the challenge dose only. For adaptive response to be seen the challenge dose must be delivered within 24 hour of the inducing dose. Radio-adaptation is extensively studied for low LET radiation. Nevertheless, few data are available for high LET radiation at very low doses and dose rate. Our study was aimed to investigate the radioadaptive response to low-dose neutron irradiation by detection of the genotoxic damage i.e.: hprt-mutant colonies induced. Altered protein synthesis was also studied to identify stress proteins may responsible for radio-adaptation. New alpha particle irradiator system was also built up to study the biological effects of low dose alpha irradiation. The experiments were carried out on monolayers of human melanoma and CHO (Chines Hamster Ovary) cells irradiated by neutrons produced in the biological irradiation channel of the Research Reactor of Budapest Neutron Center. Cells were exposed to 0.5-50 mGy neutron doses with dose rates of 1.59-10 mGy/min. The challenge doses of 2-4 Gy gamma rays were administrated within 1-48 hours after priming treatment. The induced mutants at hprt locus were selected by adding 6-thioguanine and allow to grow for 10 days for expression of the phenotype. The protein synthesis was studied by PAGE, the molecular mass of specific

  20. Factors influencing induction of adaptive response

    International Nuclear Information System (INIS)

    Misonoh, Jun; Ojima, Mitsuaki; Yonezawa, Morio

    2000-01-01

    Exposure to low doses of X-rays makes ICR mice resistant to subsequent sublethal irradiation and decrease mortality from hematopoietic death. Many factors, however, influence the induction of radioresistance. For instances, in ICR mice, the priming irradiation with 0.50 Gy was effective in the induction of radioresistance, when it is given at 6-week old, 2 weeks prior to subsequent sublethal irradiation. One hundred-fifty kV X-ray filtered off the soft component through 1.0 mm aluminum and 0.2 mm copper induces radioadaptive response as well as the harder radiation such as 260 kV X-ray filtered through 0.5 mm aluminum and 0.3 mm copper. Dose rate of priming irradiation also seemed to influence the induction of radioresistance. Priming irradiation with 0.50 Gy at 0.50 Gy/min and 0.25 Gy/min induced adaptive response, while same 0.50 Gy given at 0.063 Gy/min didn't. To make the matter complicated, when mice were pre-irradiated with 0.50 Gy at 0.013 Gy/min in the irradiation cell which was 1.2 x 1.2 x 1.4 times larger than the usual one, adaptive response was induced again. These results suggested that mice felt more uncomfortable when they were packing in the irradiation cell with little free space even for several minutes than when they were placed in the cell with much free space for about 40 minutes, and such a stress might give the mice some resistance to the subsequent sublethal irradiation. (author)

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

    Science.gov (United States)

    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. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Modeling adaptive and non-adaptive responses to environmental change

    DEFF Research Database (Denmark)

    Coulson, Tim; Kendall, Bruce E; Barthold, Julia A.

    2017-01-01

    Understanding how the natural world will be impacted by environmental change over the coming decades is one of the most pressing challenges facing humanity. Addressing this challenge is difficult because environmental change can generate both population level plastic and evolutionary responses...... construct a number of example models to demonstrate that evolutionary responses to environmental change over the short-term will be considerably slower than plastic responses, and that the rate of adaptive evolution to a new environment depends upon whether plastic responses are adaptive or non...... machinery of the evolutionarily explicit models we develop will be needed to predict responses to environmental change, or whether simpler non-evolutionary models that are now widely constructed may be sufficient....

  3. Monitoring adaptive genetic responses to environmental change

    Science.gov (United States)

    Michael M. Hansen; Isabelle Olivieri; Donald M. Waller; Einar E. Nielsen; F. W. Allendorf; M. K. Schwartz; C. S. Baker; D. P. Gregovich; J. A. Jackson; K. C. Kendall; L. Laikre; K. McKelvey; M. C. Neel; N. Ryman; R. Short Bull; J. B. Stetz; D. A. Tallmon; C. D. Vojta; R. S. Waples

    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 to use genetic monitoring to study adaptive responses via repeated analysis...

  4. CpG ODN 1668 induce innate and adaptive immune responses in rock bream (Oplegnathus fasciatus) against rock bream iridovirus (RBIV) infection.

    Science.gov (United States)

    Jung, Myung-Hwa; Jung, Sung-Ju

    2017-10-01

    Rock bream iridovirus (RBIV) causes severe mass mortalities in rock bream in Korea. CpG ODN 1668 showed promise as immunoprotective agents against RBIV infection in rock bream. In this study, we assessed innate/adaptive-related gene expression patterns in RBIV-infected rock bream with and without CpG ODN 1668 administration to determine important immune defense related factors that may affect fish survival. In the CpG ODN 1668+virus-injected group, virus copies were more than 7.4- to 790591-fold lower than in the virus-injected group at 4 d (8.79 × 10 4 and 6.58 × 10 5 /μl, respectively), 7 d (5.30 × 10 2 and 2.29 × 10 7 /μl, respectively) and 10 dpi (7.79 × 10 1 and 6.16 × 10 7 /μl, respectively). Furthermore, in the CpG ODN 1668+virus-injected group, significantly higher levels of MyD88 (6 h, 1 d, 4 d and 7 dpi), IL1β (1 d, 2 d and 7 dpi) and perforin/granzyme (1 dpi) expression were observed, whereas these genes were not significantly expressed in the virus-injected group at that time points. Mx, ISG15 and PKR were significantly highly expressed at 4 d and 7 dpi and reduced when low viral loads at 10 dpi in the CpG ODN 1668+virus-injected group. Conversely, in the virus-injected group, Mx, ISG15 and PKR expression were significantly higher than the control group until 10 dpi. However, MHC class I, CD8, Fas, Fas ligand and caspases (3, 8 and 9) expression levels showed no statistically significant differences between virus- and CpG ODN 1668+virus-injected group. In summary, CpG ODN 1668 administration in fish induces innate immune response or cell death pathway, which could be a major contributing factor to effective fish control over viral transcription on 4 d to 10 dpi. Expression of MyD88, IL1β, perforin and granzyme-related immune gene response is critical factor for inhibition of RBIV replication. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Adaptive response of Peruvian Hake to overfishing

    OpenAIRE

    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.

  6. Monitoring adaptive genetic responses to environmental change

    DEFF Research Database (Denmark)

    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...... to use genetic monitoring to study adaptive responses via repeated analysis of the same populations over time, distinguishing between phenotypic and molecular genetics approaches. After describing monitoring designs, we develop explicit criteria for demonstrating adaptive responses, which include testing...... for selection and establishing clear links between genetic and environmental change. We then review a few exemplary studies that explore adaptive responses to climate change in Drosophila, selective responses to hunting and fishing, and contemporary evolution in Daphnia using resurrected resting eggs. We...

  7. Linear ubiquitination signals in adaptive immune responses.

    Science.gov (United States)

    Ikeda, Fumiyo

    2015-07-01

    Ubiquitin can form eight different linkage types of chains using the intrinsic Met 1 residue or one of the seven intrinsic Lys residues. Each linkage type of ubiquitin chain has a distinct three-dimensional topology, functioning as a tag to attract specific signaling molecules, which are so-called ubiquitin readers, and regulates various biological functions. Ubiquitin chains linked via Met 1 in a head-to-tail manner are called linear ubiquitin chains. Linear ubiquitination plays an important role in the regulation of cellular signaling, including the best-characterized tumor necrosis factor (TNF)-induced canonical nuclear factor-κB (NF-κB) pathway. Linear ubiquitin chains are specifically generated by an E3 ligase complex called the linear ubiquitin chain assembly complex (LUBAC) and hydrolyzed by a deubiquitinase (DUB) called ovarian tumor (OTU) DUB with linear linkage specificity (OTULIN). LUBAC linearly ubiquitinates critical molecules in the TNF pathway, such as NEMO and RIPK1. The linear ubiquitin chains are then recognized by the ubiquitin readers, including NEMO, which control the TNF pathway. Accumulating evidence indicates an importance of the LUBAC complex in the regulation of apoptosis, development, and inflammation in mice. In this article, I focus on the role of linear ubiquitin chains in adaptive immune responses with an emphasis on the TNF-induced signaling pathways. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. Biological Bases for Radiation Adaptive Responses in the Lung

    Energy Technology Data Exchange (ETDEWEB)

    Scott, Bobby R. [Lovelace Biomedical and Environmental Research Inst., Albuquerque, NM (United States); Lin, Yong [Lovelace Biomedical and Environmental Research Inst., Albuquerque, NM (United States); Wilder, Julie [Lovelace Biomedical and Environmental Research Inst., Albuquerque, NM (United States); Belinsky, Steven [Lovelace Biomedical and Environmental Research Inst., Albuquerque, NM (United States)

    2015-03-01

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

  9. Cross-Adaptation: Heat and Cold Adaptation to Improve Physiological and Cellular Responses to Hypoxia.

    Science.gov (United States)

    Gibson, Oliver R; Taylor, Lee; Watt, Peter W; Maxwell, Neil S

    2017-09-01

    To prepare for extremes of heat, cold or low partial pressures of oxygen (O 2 ), humans can undertake a period of acclimation or acclimatization to induce environment-specific adaptations, e.g. heat acclimation (HA), cold acclimation (CA), or altitude training. While these strategies are effective, they are not always feasible due to logistical impracticalities. Cross-adaptation is a term used to describe the phenomenon whereby alternative environmental interventions, e.g. HA or CA, may be a beneficial alternative to altitude interventions, providing physiological stress and inducing adaptations observable at altitude. HA can attenuate physiological strain at rest and during moderate-intensity exercise at altitude via adaptations allied to improved O 2 delivery to metabolically active tissue, likely following increases in plasma volume and reductions in body temperature. CA appears to improve physiological responses to altitude by attenuating the autonomic response to altitude. While no cross-acclimation-derived exercise performance/capacity data have been measured following CA, post-HA improvements in performance underpinned by aerobic metabolism, and therefore dependent on O 2 delivery at altitude, are likely. At a cellular level, heat shock protein responses to altitude are attenuated by prior HA, suggesting that an attenuation of the cellular stress response and therefore a reduced disruption to homeostasis at altitude has occurred. This process is known as cross-tolerance. The effects of CA on markers of cross-tolerance is an area requiring further investigation. Because much of the evidence relating to cross-adaptation to altitude has examined the benefits at moderate to high altitudes, future research examining responses at lower altitudes should be conducted, given that these environments are more frequently visited by athletes and workers. Mechanistic work to identify the specific physiological and cellular pathways responsible for cross-adaptation between

  10. Adaptive Response Surface Techniques in Reliability Estimation

    DEFF Research Database (Denmark)

    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...

  11. Adaptive neural control of aeroelastic response

    Science.gov (United States)

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

    1996-05-01

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

  12. Adaptive response of human lymphocytes to low dose radiation on DNA synthesis

    International Nuclear Information System (INIS)

    Du Zeji; Su Liaoyuan; Tian Hailin

    1995-01-01

    Human peripheral blood lymphocytes PHA-stimulated in vitro for 24 h were exposed to low dose γ-ray irradiation (adaptive dose), they showed an adaptive response to the inhibition of DNA synthesis by subsequent higher acute doses of γ-ray (challenge dose). At the interval of 24 h between adaptive dose and challenge dose, the most obvious adaptive response induced by low dose irradiation was found. It was also found that the response induced by 1.0 cGy of adaptive dose was more obvious than that by other doses. In the challenge doses range of 1.0∼7.0 Gy, the adaptive response was observed and that 3.0 Gy was more obvious. The adaptive response disappeared with the challenge doses further increased

  13. Meditation-induced cognitive-control states regulate response-conflict adaptation: Evidence from trial-to-trial adjustments in the Simon task.

    Science.gov (United States)

    Colzato, Lorenza S; Sellaro, Roberta; Samara, Iliana; Hommel, Bernhard

    2015-09-01

    Here we consider the possibility that meditation has an immediate impact on information processing. Moreover, we were interested to see whether this impact affects attentional input control, as previous observations suggest, or the handling of response conflict. Healthy adults underwent a brief single session of either focused attention meditation (FAM), which is assumed to increase top-down control, or open monitoring meditation (OMM), which is assumed to weaken top-down control, before performing a Simon task-which assesses conflict-resolution efficiency. While the size of the Simon effect (reflecting the efficiency of handling response conflict) was unaffected by type of meditation, the amount of dynamic behavioral adjustments (i.e., trial-to-trial variability of the Simon effect: the Gratton effect) was considerably smaller after OMM than after FAM. Our findings suggest that engaging in meditation instantly creates a cognitive-control state that has a specific impact on conflict-driven control adaptations. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Target Response Adaptation for Correlation Filter Tracking

    KAUST Repository

    Bibi, Adel Aamer

    2016-09-16

    Most correlation filter (CF) based trackers utilize the circulant structure of the training data to learn a linear filter that best regresses this data to a hand-crafted target response. These circularly shifted patches are only approximations to actual translations in the image, which become unreliable in many realistic tracking scenarios including fast motion, occlusion, etc. In these cases, the traditional use of a single centered Gaussian as the target response impedes tracker performance and can lead to unrecoverable drift. To circumvent this major drawback, we propose a generic framework that can adaptively change the target response from frame to frame, so that the tracker is less sensitive to the cases where circular shifts do not reliably approximate translations. To do that, we reformulate the underlying optimization to solve for both the filter and target response jointly, where the latter is regularized by measurements made using actual translations. This joint problem has a closed form solution and thus allows for multiple templates, kernels, and multi-dimensional features. Extensive experiments on the popular OTB100 benchmark show that our target adaptive framework can be combined with many CF trackers to realize significant overall performance improvement (ranging from 3 %-13.5% in precision and 3.2 %-13% in accuracy), especially in categories where this adaptation is necessary (e.g. fast motion, motion blur, etc.). © Springer International Publishing AG 2016.

  15. Evidence for adaptive evolution of low-temperature stress response genes in a Pooideae grass ancestor

    DEFF Research Database (Denmark)

    Vigeland, Magnus D; Spannagl, Manuel; Asp, Torben

    2013-01-01

    Adaptation to temperate environments is common in the grass subfamily Pooideae, suggesting an ancestral origin of cold climate adaptation. Here, we investigated substitution rates of genes involved in low-temperature-induced (LTI) stress responses to test the hypothesis that adaptive molecular ev...... evidence for a link between adaptation to cold habitats and adaptive evolution of LTI stress responses in early Pooideae evolution and shed light on a poorly understood chapter in the evolutionary history of some of the world's most important temperate crops......Adaptation to temperate environments is common in the grass subfamily Pooideae, suggesting an ancestral origin of cold climate adaptation. Here, we investigated substitution rates of genes involved in low-temperature-induced (LTI) stress responses to test the hypothesis that adaptive molecular...

  16. Eccentric Contraction-Induced Muscle Fibre Adaptation

    Directory of Open Access Journals (Sweden)

    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.

  17. Evidence for adaptive evolution of low-temperature stress response genes in a Pooideae grass ancestor

    OpenAIRE

    Vigeland, Magnus Dehli; Spannagl, Manuel; Asp, Torben; Paina, Cristiana; Rudi, Heidi; Rognli, Odd Arne; Fjellheim, Siri; Sandve, Simen Rød

    2013-01-01

    Adaptation to temperate environments is common in the grass subfamily Pooideae, suggesting an ancestral origin of cold climate adaptation. Here, we investigated substitution rates of genes involved in low-temperature-induced (LTI) stress responses to test the hypothesis that adaptive molecular evolution of LTI pathway genes was important for Pooideae evolution. Substitution rates and signatures of positive selection were analyzed using 4330 gene trees including three warm climate-adapted spec...

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

    Directory of Open Access Journals (Sweden)

    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.

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

    International Nuclear Information System (INIS)

    Ekhtiar, A.; Ammer, A.; Jbawi, A.; Othman, A.

    2012-05-01

    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 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

  20. Response of Estrogen-related Receptor Alpha (ERRα to Endurance Training and its Participation in Endurance Training-induced Adaptations in Lipid Metabolism in Skeletal Muscle of Male Wistar rats

    Directory of Open Access Journals (Sweden)

    Soheil Aminizadeh

    2017-08-01

    Conclusion: In sum, expression of ERRα is a trainable factor and its changes are parallel with the increase in expression of lipid metabolism indexes; so, it could have a direct role in endurance training-induced adaptation in fat metabolism.

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

    International Nuclear Information System (INIS)

    Takaji Ikushima

    1997-01-01

    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)

  2. Plant Cell Adaptive Responses to Microgravity

    Science.gov (United States)

    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-CII and PsHSP18.1-CI, 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. Lung glutathione adaptive responses to cigarette smoke exposure

    Directory of Open Access Journals (Sweden)

    Gauthier Steve

    2011-10-01

    Full Text Available Abstract Background Smoking tobacco is a leading cause of chronic obstructive pulmonary disease (COPD, but although the majority of COPD cases can be directly related to smoking, only a quarter of smokers actually develop the disease. A potential reason for the disparity between smoking and COPD may involve an individual's ability to mount a protective adaptive response to cigarette smoke (CS. Glutathione (GSH is highly concentrated in the lung epithelial lining fluid (ELF and protects against many inhaled oxidants. The changes in GSH that occur with CS are not well investigated; therefore the GSH adaptive response that occurs with a commonly utilized CS exposure was examined in mice. Methods Mice were exposed to CS for 5 h after which they were rested in filtered air for up to 16 h. GSH levels were measured in the ELF, bronchoalveolar lavage cells, plasma, and tissues. GSH synthesis was assessed by measuring γ-glutamylcysteine ligase (GCL activity in lung and liver tissue. Results GSH levels in the ELF, plasma, and liver were decreased by as much as 50% during the 5 h CS exposure period whereas the lung GSH levels were unchanged. Next, the time course of rebound in GSH levels after the CS exposure was examined. CS exposure initially decreased ELF GSH levels by 50% but within 2 h GSH levels rebound to about 3 times basal levels and peaked at 16 h with a 6-fold increase and over repeat exposures were maintained at a 3-fold elevation for up to 2 months. Similar changes were observed in tissue GCL activity which is the rate limiting step in GSH synthesis. Furthermore, elevation in ELF GSH levels was not arbitrary since the CS induced GSH adaptive response after a 3d exposure period prevented GSH levels from dropping below basal levels. Conclusions CS exposures evoke a powerful GSH adaptive response in the lung and systemically. These data suggests there may be a sensor that sets the ELF GSH adaptive response to prevent GSH levels from dipping

  4. Regulation of PGC-1α and exercise training-induced metabolic adaptations in skeletal muscle

    DEFF Research Database (Denmark)

    Brandt, Nina

    and intracellular signalling in human skeletal muscle depend on adrenaline levels or metabolic stress. 2) PGC-1α mediated exercise and exercise training-induced adaptive metabolic responses in mouse skeletal muscle depend on exercise intensity. 3) β-adrenergic signalling contributes to exercise training......-induced metabolic adaptations in mouse skeletal muscle through PGC-1α . Paper I demonstrated that di erences in plasma adrenaline and muscle metabolic stress during exercise do not reinforce exercise-induced PGC-1 α mRNA response in human skeletal muscle. In addition, di erences in exercise-induced AMPK and p38......-adrenergic signaling mediates exercise-induced PGC-1α mRNA responses with most potent stimulation of the alternative promoter of the PGC-1α gene in mouse skeletal muscle but, neither elevated plasma adrenaline nor metabolic stress augment exercise-induced PGC-1α mRNA response in human skeletal muscle. While...

  5. 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

    International Nuclear Information System (INIS)

    Mendiola C, M.T.

    2002-01-01

    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 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)

  6. 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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    Zhu, Jianguo; Larson, Charles B; Ramaker, Megan Ann; Quandt, Kimberly; Wendte, Jered M; Ku, Kimberly P; Chen, Fang; Jourdian, George W; Vemulapalli, Ramesh; Schurig, Gerhardt G; He, Yongqun

    2011-01-01

    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 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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-01-06

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

  9. Adaptive hormetic response of pre-exposure of mouse brain with low-dose 12C 6+ ion or 60Co γ-ray on growth hormone (GH) and body weight induced by subsequent high-dose irradiation

    Science.gov (United States)

    Zhang, Hong; Xie, Yi; Zhou, Qingming; Liu, Bing; Li, Wenjian; Li, Xiaoda; Duan, Xin; Yuan, Zhigang; Zhou, Guangming; Min, Fengling

    2006-01-01

    The brain of the Kun-Ming strain mice were irradiated with 0.05 Gy of 12C 6+ ion or 60Co γ-ray as the pre-exposure dose, and were then irradiated with 2 Gy of 12C 6+ ion or 60Co γ-ray as challenging irradiation dose at 4 h after per-exposure. Body weight and serum growth hormone (GH) concentration were measured at 35th day after irradiation. The results showed that irradiation of mouse brain with 2 Gy of 12C 6+ ion or 60Co γ-ray significantly diminished mouse body weight and level of serum GH. The relative biological effectiveness values of a 2 Gy dose of 12C 6+ ion calculated with respect to 60Co γ-ray were 1.47 and 1.34 for body weight and serum GH concentration, respectively. Pre-exposure with a low-dose (0.05 Gy) of 12C 6+ ion or 60Co γ-ray significantly alleviated reductions of mouse body weight and level of serum GH induced by a subsequent high-dose (2 Gy) irradiation. The data suggested that low-dose ionizing irradiation can induce adaptive hormetic responses to the harmful effects of pituitary by subsequent high-dose exposure.

  10. Induced polarization response of microbial induced sulfideprecipitation

    Energy Technology Data Exchange (ETDEWEB)

    Ntarlagiannis, Dimitrios; Williams, Kenneth Hurst; Slater, Lee; Hubbard, Susan

    2004-06-04

    A laboratory scale experiment was conducted to examine the use of induced polarization and electrical conductivity to monitor microbial induced sulfide precipitation under anaerobic conditions in sand filled columns. Three columns were fabricated; one for electrical measurements, one for geochemical sampling and a third non-inoculated column was used as a control. A continual upward flow of nutrients and metals in solution was established in each column. Desulfovibrio vulgaris microbes were injected into the middle of the geochemical and electrical columns. Iron and zinc sulfides precipitated along a microbial action front as a result of sulfate reduction due by Desulfovibrio vulgaris. The precipitation front initially developed near the microbial injection location, and subsequently migrated towards the nutrient inlet, as a result of chemotaxis by Desulfovibrio vulgaris. Sampling during and subsequent to the experiment revealed spatiotemporal changes in the biogeochemical measurements associated with microbial sulfate reduction. Conductivity measurements were insensitive to all biogeochemical changes occurred within the column. Changes in the IP response (of up to 14 mrad)were observed to coincide in place and in time with the active microbe respiration/sulfide precipitation front as determined from geochemical sampling. The IP response is correlated with the lactate concentration gradient, an indirect measurement of microbial metabolism, suggesting the potential of IP as a method for monitoring microbial respiration/activity. Post experimental destructive sample analysis and SEM imaging verified the geochemical results and supported our hypothesis that microbe induced sulfide precipitation is directly detectable using electrical methods. Although the processes not fully understood, the IP response appears to be sensitive to this anaerobic microbial precipitation, suggesting a possible novel application for the IP method.

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

    Directory of Open Access Journals (Sweden)

    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

  12. cyclooxygenase inhibitors and the exercise-induced stress response

    African Journals Online (AJOL)

    homeostatic shift intended to facilitate the demands put on the body by physical exertion. Most stressors, including ... nervous system response7 and in the increase in body tem- perature and other metabolic adaptations.14 ... cyclooxygenase-1 (COX-1) in the exercise-induced cortisol and temperature response to exercise.

  13. Towards Trustworthy Adaptive Case Management with Dynamic Condition Response Graphs

    DEFF Research Database (Denmark)

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

    2013-01-01

    We describe how the declarative Dynamic Condition Response (DCR) Graphs process model can be used for trustworthy adaptive case management by leveraging the flexible execution, dynamic composition and adaptation supported by DCR Graphs. The dynamically composed and adapted graphs are verified for...

  14. Aortic Function's Adaptation in Response to Exercise-Induced Stress Assessing by 1.5T MRI: A Pilot Study in Healthy Volunteers.

    Directory of Open Access Journals (Sweden)

    Laurence Bal-Theoleyre

    Full Text Available Evaluation of the aortic "elastic reserve" might be a relevant marker to assess the risk of aortic event. Our aim was to compare regional aortic elasticity at rest and during supine bicycle exercise at 1.5 T MRI in healthy individuals.Fifteen volunteers (8 men, with a mean age of 29 (23-41 years, completed the entire protocol. Images were acquired immediately following maximal exercise. Retrospective cine sequences were acquired to assess compliance, distensibility, maximum rates of systolic distension and diastolic recoil at four different locations: ascending aorta, proximal descending aorta, distal descending aorta and aorta above the coeliac trunk level. Segmental aortic pulse wave velocity (PWV was assessed by through plane velocity-encoded MRI.Exercise induced a significant decrease of aortic compliance and distensibility, and a significant increase of the absolute values of maximum rates of systolic distension and diastolic recoil at all sites (p<10-3. At rest and during stress, ascending aortic compliance was statistically higher compared to the whole descending aorta (p≤0.0007. We found a strong correlation between the rate pressure product and aortic distensibility at all sites (r = - 0.6 to -0.75 according to the site, p<10-4. PWV measured at the proximal and distal descending aorta increased significantly during stress (p = 0.02 and p = 0.008, respectively.Assessment of regional aortic function during exercise is feasible using MRI. During stress, aortic elasticity decreases significantly in correlation with an increase of the PWV. Further studies are required to create thresholds for ascending aorta dysfunction among patients with aneurysms, and to monitor the impact of medication on aortic remodeling.

  15. Evasion of influenza A viruses from innate and adaptive immune responses

    NARCIS (Netherlands)

    C.E. van de Sandt (Carolien); J.H.C.M. Kreijtz (Joost); G.F. Rimmelzwaan (Guus)

    2012-01-01

    textabstractThe influenza A virus is one of the leading causes of respiratory tract infections in humans. Upon infection with an influenza A virus, both innate and adaptive immune responses are induced. Here we discuss various strategies used by influenza A viruses to evade innate immune responses

  16. Pilot-Induced Oscillation Suppression by Using 1 Adaptive Control

    Directory of Open Access Journals (Sweden)

    Chuan Wang

    2012-01-01

    research activities that aim to alleviate this problem. In this paper, the L1 adaptive controller has been introduced to suppress the PIO, which is caused by rate limiting and pure time delay. Due to its architecture, the L1 adaptive controller will achieve a desired response with fast adaptation. The analysis of PIO and its suppression by L1 adaptive controller are presented in detail in the paper. The simulation results indicate that the L1 adaptive control is efficient in solving this kind of problem.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    Dušan Šuput

    2012-08-01

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

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

    Directory of Open Access Journals (Sweden)

    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.

  20. Cardiovascular and hemodynamic responses to adapted physical exercises in very old adults.

    Science.gov (United States)

    Panzarino, Michele; Gravina, Angela; Carosi, Veronica; Crobeddu, Patrizio; Tiroli, Alessia; Lombardi, Roberto; D'Ottavio, Stefano; Galante, Alberto; Legramante, Jacopo M

    2017-06-01

    Aging is characterized by a physiological reduction in physical activity, which is inversely correlated with survival. Aim of the present study is to evaluate the cardiovascular, central hemodynamic and autonomic responses to a single bout of adapted physical exercise in octogenarian subjects. We studied cardiovascular, hemodynamic and autonomic responses to adapted physical activity in 33 subjects by a noninvasive methodology (Nexfin ® , Edwards Lifesciences Corporation). Our octogenarians presented a significant increase in mean arterial pressure (p cardiovascular system and to induce a postexercise hypotension similarly to adults. The baroreflex control of sinus node seems to contribute in the physiological mechanism of these cardiovascular adaptations. In very old people, physical activity induces cardiovascular and hemodynamic responses not significantly different from those induced in adult even though some cautions particularly in the early recovery phase after exercise should be exercised.

  1. Adaptive response in Drosophila melanogaster heat shock proteins mutant strains

    International Nuclear Information System (INIS)

    Shaposhnikov, M.V.; Moskalev, A.A.; Turysheva, E.V.

    2007-01-01

    Complete text of publication follows. The members of the heat shock proteins (Hsp) family function as molecular chaperones and assist intracellular folding of newly synthesized proteins. Also it is possible that molecular chaperones are induced during adaptive response to oxidative stress and radiation. The aim of our research was to exam the role of heat shock proteins in adaptive response to oxidative stress after low dose rate gamma-irradiation in Drosophila melanogaster. Drosophilamelanogaster strains were kindly provided by Bloomington Drosophila Stock Center (University of state of Indiana, Bloomington, USA). We used wild type strain (CS), heat shock protein mutant strains (Hsp22, Hsp70, Hsp83), and heat shock factor mutant strain (Hsf). Strains were chronically exposured to adaptive dose of gamma-irradiation in dose rate of 0.17 cGy/h during all stages of life history (from the embrional stage to the stage of matured imago). The rate of absorbed dose was 60 cGy. For oxidative-stress challenge twodays old flies were starved in empty vials for 6 h and then transferred to vials containing only filter paper soaked with 20 mM paraquat in 5% sucrose solution. Survival data were collected after 26 h of treatment. Dead flies were counted daily. The obtained data were subjected to survival analysis by Kaplan and Meier method and presented as survival curves. Statistical analysis was held by non-parametric methods. To test the significance of the difference between the two age distributions Kolmogorov-Smirnov test was applied. Gehan-Braslow- Wilcoxon and Cox-Mantel tests were used for estimation of median life span differences. In addition the minimal and maximal life span, time of 90% death, and mortality rate doubling time (MRDT) were estimated. The obtained results will be discussed in presentation.

  2. Chemotactic response and adaptation dynamics in Escherichia coli.

    Directory of Open Access Journals (Sweden)

    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.

  3. Adaptive Response- A Universal Phenomenon for Radiological Protection

    International Nuclear Information System (INIS)

    Streffer, C.

    2004-01-01

    Predominantly with cells in vitro but also with whole animals in vivo it bas been shown that small radiation doses like other stress factors can render cells or organisms to a stage of higher radioresistance. This has been demonstrated with chromosomal aberrations gene mutation, cell transformation and survival. However, it is necessary to keep the appropriate conditions in a very stringent way. This implies radiation dose ranges, time factors and others. The adaptive response is transient and keeps for about three cell cycles or two to three days for mammalian cells. Most studies have been performed with low LET radiation. From the few data with high LET radiation it can be concluded that the adaptive response is much less or does not occur at all. Cellular and molecular studies indicate that the DNA repair is most important for the induction of adaptive response although the understanding of the mechanisms is certainly incomplete. In vivo other biological phenomena like the immune system also play a significant role. A high individual variability exists with respect to the extent of the adaptive response. No adaptive response apparently occurs with cells from individuals with repair-and immune-deficiencies. Several experiments during the prenatal development indicate that there is no or only little adaptive response during wide developmental stages in utero. Therefore it must be concluded that the adaptive response has limitations and is not a universal principle. Due to these restrictions of the validity and strength of adaptive response it is doubtful whether adaptive response can generally be applied in the practice of radiological protection. (Author) 42 refs

  4. War and peace: Factor VIII and the adaptive immune response.

    Science.gov (United States)

    Georgescu, Maria T; Lai, Jesse D; Hough, Christine; Lillicrap, David

    2016-03-01

    The development of neutralizing anti-factor VIII (FVIII) antibodies (inhibitors) remains a major challenge for FVIII replacement therapy in hemophilia A patients. The adaptive immune response plays a crucial role in the development and maintenance of inhibitors. In this review, we focus on our current understanding of FVIII interactions with cells of the adaptive immune system and the phenotype of the resultant response. Additionally, we examine both current and novel FVIII tolerance induction methods that function at the level of the adaptive immune response. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Does occupational exposure to ionizing radiation induce adaptation

    International Nuclear Information System (INIS)

    Djurovic, B.; Selakovic, V.; Radjen, S.; Radakovic, S.; Spasic-Jokic, V.

    2008-01-01

    (183±22 vs 183±21, p=0.67). Results also confirmed significantly higher MDA production in OE to IR (0.000028), significant increase in every group after irradiation and the lack of significant difference between groups after (p=0.408). The activity of SOD was also significantly increased in OE (p=0.01), and in each group after irradiation and lack of differences between groups after irradiation (p=0.35). There is no differences in GSH values between OE and non exposed before as well as after irradiation (p=0.825, p=0.41, respectively), and in each group before and after irradiation.Our results indicated that occupational exposure to LD of IR did not induced adaptive response. The incidence of DNA damage is correlated to the oxidative stress and the activity of anti oxidative enzymes. (author)

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

    OpenAIRE

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

    2012-01-01

    textabstractThe influenza A virus is one of the leading causes of respiratory tract infections in humans. Upon infection with an influenza A virus, both innate and adaptive immune responses are induced. Here we discuss various strategies used by influenza A viruses to evade innate immune responses and recognition by components of the humoral and cellular immune response, which consequently may result in reduced clearing of the virus and virus-infected cells. Finally, we discuss how the curren...

  7. Responsibility for private sector adaptation to climate change

    Directory of Open Access Journals (Sweden)

    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 infrastructure

  8. Induced adaptation of Bacillus sp. to antimicrobial nanosilver.

    Science.gov (United States)

    Gunawan, Cindy; Teoh, Wey Yang; Marquis, Christopher P; Amal, Rose

    2013-11-11

    The natural ability of Bacillus sp. to adapt to nanosilver cytotoxicity upon prolonged exposure is reported for the first time. The combined adaptive effects of nanosilver resistance and enhanced growth are induced under various intensities of nanosilver-stimulated cellular oxidative stress, ranging from only minimal cellular redox imbalance to the lethal levels of cellular ROS stimulation. An important implication of the present work is that such adaptive effects lead to the ultimate domination of nanosilver-resistant Bacillus sp. in the microbiota, to which nanosilver cytotoxicity is continuously applied. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Adaptive workflow simulation of emergency response

    NARCIS (Netherlands)

    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

  10. Adaptive response of yeast cultures (Saccharomyces Cerevisiae) exposed to low dose of gamma radiation

    International Nuclear Information System (INIS)

    Kulcsar, Agnes; Savu, D.; Petcu, I.; Gherasim, Raluca

    2003-01-01

    The present study was planned as follows: (i) setting up of standard experimental conditions for investigation of radio-induced adaptive response in lower Eucaryotes; (ii) developing of procedures for synchronizing Saccharomyces cerevisiae X 310 D cell cultures and cell cycle stages monitoring; (iii) investigation of gamma (Co-60) and UV irradiation effects on the viability of synchronized and non-synchronized cell cultures of Saccharomyces cerevisiae; the effects were correlated with the cell density and cell cycle stage; (iv) study of the adaptive response induced by irradiation and setting up of the experimental conditions for which this response is optimized. The irradiations were performed by using a Co-60 with doses of 10 2 - 10 4 Gy and dose rates ranging from 2.2 x 10 2 Gy/h to 8.7 x 10 3 Gy/h. The study of radioinduced adaptive response was performed by applying a pre-irradiation treatment of 100-500 Gy, followed by challenge doses of 2-4 kGy delivered at different time intervals, ranging from 1 h to 4 h. The survival rate of synchronized and non-synchronized cultures as a function of exposure dose shows an exponential decay shape. No difference in viability of the cells occurred between synchronized and non-synchronized cultures. The pre-irradiation of cells with 100 and 200 Gy were most efficient to induce an adaptive response for the yeast cells. In this stage of work we proved the occurrence of the adaptive response in the case of synchronized yeast cultures exposed to gamma radiation. The results will be used in the future to investigate the dependence of this response on the cell cycle and the possibility to induce such a response by a low level electromagnetic field. (authors)

  11. Contour adaptation reduces the spreading of edge induced colors.

    Science.gov (United States)

    Coia, Andrew J; Crognale, Michael A

    2017-04-25

    Brief exposure to flickering achromatic outlines of an area causes a reduction in the brightness contrast of the surface inside the area. This contour adaptation to achromatic contours does not reduce surface contrast when the surface is chromatic (the saturation or colorimetric purity of the surface is maintained). In addition to reducing the brightness of physical luminance contrast, contour adaptation also reduces (or even reverses) the illusory brightness contrast seen in the Craik-O'Brien-Cornsweet illusion, in which two physically identical grey areas appear different brightness because of a sharp luminance edge separating them. Chromatic color spreading illusions also occur with chromatic inducing edges, and an unanswered question is whether contour adaptation can reduce the perceived contrast of illusory color spreading from edges, even though it cannot reduce the perceived contrast of physical surface color. The current studies use a color spreading illusion known as the watercolor effect in order to test whether illusory color spreading is affected by contour adaptation. The general findings of physical achromatic contrast being reduced and chromatic contrast being robust to contour adaptation were replicated. However, both illusory brightness and color were reduced by contour adaptation, even when the illusion edges only differed in chromatic contrast with each other and the background. Additional studies adapting to chromatic contours showed opposite effects on illusory color contrast than achromatic adaptation. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    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.

  13. Proteins induced during adaptation of Acetobacter aceti to high acetate concentrations.

    Science.gov (United States)

    Steiner, P; Sauer, U

    2001-12-01

    As a typical product of microbial metabolism, the weak acid acetate is well known for its cytotoxic effects. In contrast to most other microbes, the so-called acetic acid bacteria can acquire significant resistance to high acetate concentrations when properly adapted to such hostile conditions. To characterize the molecular events that are associated with this adaptation, we analyzed global protein expression levels during adaptation of Acetobacter aceti by two-dimensional gel electrophoresis. Adaptation was achieved by using serial batch and continuous cultivations with increasing acetate supplementation. Computer-aided analysis revealed a complex proteome response with at least 50 proteins that are specifically induced by adaptation to acetate but not by other stress conditions, such as heat or oxidative or osmotic stress. Of these proteins, 19 were significantly induced in serial batch and continuous cultures and were thus noted as acetate adaptation proteins (Aaps). Here we present first microsequence information on such Aaps from A. aceti. Membrane-associated processes appear to be of major importance for adaptation, because some of the Aap bear N-terminal sequence homology to membrane proteins and 11 of about 40 resolved proteins from membrane protein-enriched fractions are significantly induced.

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

    Indian Academy of Sciences (India)

    Unknown

    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 ani- mals. To examine this aspect Swiss albino mice were irradiated with different doses (2–10 Gy) at 0⋅015 ...

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

    Indian Academy of Sciences (India)

    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 ...

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

    International Nuclear Information System (INIS)

    Keiichiro Ishii

    1996-01-01

    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 3 H-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 Ca 2+ ions and Phorbol 12-Myristate 13-Acetate (TPA) which are supposed to be involved in cell to cell communication. (author)

  17. An adaptive response to alkylating agents in Aspergillus nidulans.

    Science.gov (United States)

    Hooley, P; Shawcross, S G; Strike, P

    1988-11-01

    A simple method is described for demonstrating adaptation to alkylation damage in Aspergillus nidulans. One wild type, two MNNG-sensitive, and one MNNG-resistant strain all showed improvement in colony growth when challenged with MNNG following appropriate inducing pretreatments. Other alkylating agents (MMS, EMS) could also adapt mycelium to later MNNG challenge, while 4NQO and UV could not. The inducible effect was not transmissible through conidia. A standard reversion assay based upon methG proved impractical for studying mutation frequencies during alkylation treatments owing to variations in MNNG resistance amongst revertants.

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

    International Nuclear Information System (INIS)

    Jeggo, P.; Defais, M.; Samson, L.; Schendel, P.

    1978-01-01

    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.) [de

  19. Bacterial genomic adaptation and response to metals

    International Nuclear Information System (INIS)

    Van Houdt, R.

    2009-01-01

    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

  20. Modeling Adaptive and Nonadaptive Responses of Populations to Environmental Change.

    Science.gov (United States)

    Coulson, Tim; Kendall, Bruce E; Barthold, Julia; Plard, Floriane; Schindler, Susanne; Ozgul, Arpat; Gaillard, Jean-Michel

    2017-09-01

    Understanding how the natural world will be impacted by environmental change over the coming decades is one of the most pressing challenges facing humanity. Addressing this challenge is difficult because environmental change can generate both population-level plastic and evolutionary responses, with plastic responses being either adaptive or nonadaptive. We develop an approach that links quantitative genetic theory with data-driven structured models to allow prediction of population responses to environmental change via plasticity and adaptive evolution. After introducing general new theory, we construct a number of example models to demonstrate that evolutionary responses to environmental change over the short-term will be considerably slower than plastic responses and that the rate of adaptive evolution to a new environment depends on whether plastic responses are adaptive or nonadaptive. Parameterization of the models we develop requires information on genetic and phenotypic variation and demography that will not always be available, meaning that simpler models will often be required to predict responses to environmental change. We consequently develop a method to examine whether the full machinery of the evolutionarily explicit models we develop will be needed to predict responses to environmental change or whether simpler nonevolutionary models that are now widely constructed may be sufficient.

  1. Possible adaptive growth responses of Chromolaena odorata during ...

    African Journals Online (AJOL)

    The changes in morphological and crude protein content of Chromolaena odorata to heavy metal-induced stress were investigated. This was with a view to providing information on the test plant adaptation potential during remediation of contaminated with . Stems of C. odorata were planted in soils treated with Cd (as CdCl) ...

  2. Frequent adaptive immune responses against arginase-1

    DEFF Research Database (Denmark)

    Martinenaite, Evelina; Mortensen, Rasmus Erik Johansson; Hansen, Morten

    2018-01-01

    was examined in PBMCs from cancer patients and healthy individuals. IFNγ ELISPOT revealed frequent immune responses against multiple arginase-1-derived peptides. We further identified a hot-spot region within the arginase-1 protein sequence containing multiple epitopes recognized by T cells. Next, we examined......, and further demonstrated the specificity and reactivity of these T cells. Overall, we showed that arginase-1-specific T cells were capable of recognizing arginase-1-expressing cells. The activation of arginase-1-specific T cells by vaccination is an attractive approach to target arginase-1-expressing...... macrophages (TAMs), and its expression is associated with poor prognosis. In the present study, we divided the arginase-1 protein sequence into overlapping 20-amino-acid-long peptides, generating a library of 31 peptides covering the whole arginase-1 sequence. Reactivity towards this peptide library...

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

    Directory of Open Access Journals (Sweden)

    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.

  4. Exercise-Induced Oxidative Stress Responses in the Pediatric Population

    Directory of Open Access Journals (Sweden)

    Alexandra Avloniti

    2017-01-01

    Full Text Available Adults demonstrate an upregulation of their pro- and anti-oxidant mechanisms in response to acute exercise while systematic exercise training enhances their antioxidant capacity, thereby leading to a reduced generation of free radicals both at rest and in response to exercise stress. However, less information exists regarding oxidative stress responses and the underlying mechanisms in the pediatric population. Evidence suggests that exercise-induced redox perturbations may be valuable in order to monitor exercise-induced inflammatory responses and as such training overload in children and adolescents as well as monitor optimal growth and development. The purpose of this review was to provide an update on oxidative stress responses to acute and chronic exercise in youth. It has been documented that acute exercise induces age-specific transient alterations in both oxidant and antioxidant markers in children and adolescents. However, these responses seem to be affected by factors such as training phase, training load, fitness level, mode of exercise etc. In relation to chronic adaptation, the role of training on oxidative stress adaptation has not been adequately investigated. The two studies performed so far indicate that children and adolescents exhibit positive adaptations of their antioxidant system, as adults do. More studies are needed in order to shed light on oxidative stress and antioxidant responses, following acute exercise and training adaptations in youth. Available evidence suggests that small amounts of oxidative stress may be necessary for growth whereas the transition to adolescence from childhood may promote maturation of pro- and anti-oxidant mechanisms. Available evidence also suggests that obesity may negatively affect basal and exercise-related antioxidant responses in the peripubertal period during pre- and early-puberty.

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

    Science.gov (United States)

    Cao, Yi; Tong, Jian

    2014-04-22

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

  6. Adaptive Response in Animals Exposed to Non-Ionizing Radiofrequency Fields: Some Underlying Mechanisms

    Directory of Open Access Journals (Sweden)

    Yi Cao

    2014-04-01

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

  7. Rapid adaptive responses to climate change in corals

    KAUST Repository

    Torda, Gergely

    2017-09-01

    Pivotal to projecting the fate of coral reefs is the capacity of reef-building corals to acclimatize and adapt to climate change. Transgenerational plasticity may enable some marine organisms to acclimatize over several generations and it has been hypothesized that epigenetic processes and microbial associations might facilitate adaptive responses. However, current evidence is equivocal and understanding of the underlying processes is limited. Here, we discuss prospects for observing transgenerational plasticity in corals and the mechanisms that could enable adaptive plasticity in the coral holobiont, including the potential role of epigenetics and coral-associated microbes. Well-designed and strictly controlled experiments are needed to distinguish transgenerational plasticity from other forms of plasticity, and to elucidate the underlying mechanisms and their relative importance compared with genetic adaptation.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    NARCIS (Netherlands)

    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

  10. Morphological Adaptation of Cercis Griffithii Seedlings in Response ...

    African Journals Online (AJOL)

    ADOWIE PERE

    2017-12-03

    Dec 3, 2017 ... Morphological Adaptation of Cercis Griffithii Seedlings in Response to Progressive. Drought ... 2Department of Forest Sciences, Research Division of Natural Resources, Isfahan Agricultural and Natural Resources Research and. Education .... each seedling five leaf selection of basic randomized to using ...

  11. Innate, adaptive and regulatory responses in schistosomiasis: Relationship to allergy

    NARCIS (Netherlands)

    Hartgers, F.C.; Smits, H.H.; Kleij, D. van der; Yazdanbakhsh, M.

    2006-01-01

    Helminth infections have profound effects on the immune system. Here, recent insights in the molecular interactions between schistosomes and the host are described with respect to adaptive but also with respect to innate immune responses. Furthermore, the different mechanisms of immune

  12. Dynamic Nature of Noncoding RNA Regulation of Adaptive Immune Response

    Directory of Open Access Journals (Sweden)

    Franca Citarella

    2013-08-01

    Full Text Available Immune response plays a fundamental role in protecting the organism from infections; however, dysregulation often occurs and can be detrimental for the organism, leading to a variety of immune-mediated diseases. Recently our understanding of the molecular and cellular networks regulating the immune response, and, in particular, adaptive immunity, has improved dramatically. For many years, much of the focus has been on the study of protein regulators; nevertheless, recent evidence points to a fundamental role for specific classes of noncoding RNAs (ncRNAs in regulating development, activation and homeostasis of the immune system. Although microRNAs (miRNAs are the most comprehensive and well-studied, a number of reports suggest the exciting possibility that long ncRNAs (lncRNAs could mediate host response and immune function. Finally, evidence is also accumulating that suggests a role for miRNAs and other small ncRNAs in autocrine, paracrine and exocrine signaling events, thus highlighting an elaborate network of regulatory interactions mediated by different classes of ncRNAs during immune response. This review will explore the multifaceted roles of ncRNAs in the adaptive immune response. In particular, we will focus on the well-established role of miRNAs and on the emerging role of lncRNAs and circulating ncRNAs, which all make indispensable contributions to the understanding of the multilayered modulation of the adaptive immune response.

  13. High fructose intake fails to induce symptomatic adaptation but may induce intestinal carriers

    Directory of Open Access Journals (Sweden)

    Debra Heilpern

    2010-01-01

    Full Text Available Fructose has several interactions in man, including intolerance and promotion of some diseases. However, fructose in fruits and in prebiotics may be associated with benefits. Adaptation to regular fructose ingestion as defined for lactose could support a beneficial rather than a deleterious effect. This study was undertaken to evaluate symptomatic response and potential underlying mechanisms of fecal bacterial change and breath hydrogen response to short term regular fructose supplementation. Forty-five participants were recruited for a 3 day recall diet questionnaire and a 50 g fructose challenge. Breath hydrogen was measured for 4.5 hrs and symptoms were recorded. Thirty-eight subjects provided stool samples for analysis by selective culture of 4 groups of bacteria, including bifidobacteria and lactobacilli. Intolerant subjects returned a second time 15 days later. Ten of these served as controls and 16 received 30 g fructose twice a day. Ten of the latter returned 27 days later, after stopping fructose for a third challenge test. Student’s paired, unpaired t-tests and Pearson correlations were used. Significance was accepted at P<0.05. After fructose rechallenge there were no significant reductions in symptoms scores in volunteers in either the fructose supplemented or non supplemented groups. However, total breath hydrogen was reduced between test 1 and test 2 (P=0.03 or test 3 (P=0.04 in the group given fructose then discontinued, compared with controls. There were no statistically significant changes in bacterial numbers between test 2 and 1. This study shows that regular consumption of high dose fructose does not follow the lactose model of adaptation. Observed changes in hydrogen breath tests raise the possibility that intestinal carriers of fructose may be induced potentially aggravating medical problems attributed to fructose.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  15. Adaptation of perceptual responses to low-load blood flow restriction training

    DEFF Research Database (Denmark)

    Martín-Hernández, Juan; Ruiz-Aguado, Jorge; Herrero, Azael Juan

    2017-01-01

    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.......01). No between-group differences were found at any time point. In summary, BFRT induces a high perceptual response to training. However, this perceptual response is rapidly attenuated, leading to values similar to those experienced during HIT. Low load BFRT should not be limited to highly motivated individuals...

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

    Directory of Open Access Journals (Sweden)

    Guus F. Rimmelzwaan

    2012-09-01

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

  17. Evasion of influenza A viruses from innate and adaptive immune responses.

    Science.gov (United States)

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

    2012-09-01

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

  18. Subversion of innate and adaptive immune activation induced by structurally modified lipopolysaccharide from Salmonella typhimurium.

    Science.gov (United States)

    Pastelin-Palacios, Rodolfo; Gil-Cruz, Cristina; Pérez-Shibayama, Christian I; Moreno-Eutimio, Mario A; Cervantes-Barragán, Luisa; Arriaga-Pizano, Lourdes; Ludewig, Burkhard; Cunningham, Adam F; García-Zepeda, Eduardo A; Becker, Ingeborg; Alpuche-Aranda, Celia; Bonifaz, Laura; Gunn, John S; Isibasi, Armando; López-Macías, Constantino

    2011-08-01

    Salmonella are successful pathogens that infect millions of people every year. During infection, Salmonella typhimurium changes the structure of its lipopolysaccharide (LPS) in response to the host environment, rendering bacteria resistant to cationic peptide lysis in vitro. However, the role of these structural changes in LPS as in vivo virulence factors and their effects on immune responses and the generation of immunity are largely unknown. We report that modified LPS are less efficient than wild-type LPS at inducing pro-inflammatory responses. The impact of this LPS-mediated subversion of innate immune responses was demonstrated by increased mortality in mice infected with a non-lethal dose of an attenuated S. typhimurium strain mixed with the modified LPS moieties. Up-regulation of co-stimulatory molecules on antigen-presenting cells and CD4(+) T-cell activation were affected by these modified LPS. Strains of S. typhimurium carrying structurally modified LPS are markedly less efficient at inducing specific antibody responses. Immunization with modified LPS moiety preparations combined with experimental antigens, induced an impaired Toll-like receptor 4-mediated adjuvant effect. Strains of S. typhimurium carrying structurally modified LPS are markedly less efficient at inducing immunity against challenge with virulent S. typhimurium. Hence, changes in S. typhimurium LPS structure impact not only on innate immune responses but also on both humoral and cellular adaptive immune responses. © 2011 The Authors. Immunology © 2011 Blackwell Publishing Ltd.

  19. Adaptive endoplasmic reticulum stress alters cellular responses to the extracellular milieu.

    Science.gov (United States)

    Liu, Yiting; Neely, Elizabeth; Simmons, Zachary; Connor, James R

    2015-05-01

    The ability to respond to perturbations in endoplasmic reticulum (ER) function is a critical property for all cells. In the presence of chronic ER stress, the cell must adapt so that cell survival is favored or the stress may promote apoptosis. In some pathological processes, such as neurodengeneration, persistent ER stress can be tolerated for an extended period, but eventually cell death occurs. It is not known how an adaptive response converts from survival into apoptosis. To gain a better understanding of the role of adaptive ER stress in neurodegeneration, in this study, with a neuronal cell line SH-SY5Y and primary motor neuron-glia cell mixed cultures, we induced adaptive ER stress and modified the extracellular environment with physiologically relevant changes that alone did not activate ER stress. Our data demonstrate that an adaptive ER stress favored neuronal cell survival, but when cells were exposed to additional physiological insults the level of ER stress was increased, followed by activation of the caspase pathway. Our results indicate that an adaptive ER stress response could be converted to apoptosis when the external cellular milieu changed, suggesting that the conversion from prosurvival to proapoptotic pathways can be driven by the external milieu. This conversion was due at least partially to an increased level of ER stress. © 2015 Wiley Periodicals, Inc.

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

    Directory of Open Access Journals (Sweden)

    Susana Gómez-González

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

  1. Adaptation.

    Science.gov (United States)

    Broom, Donald M

    2006-01-01

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

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

    International Nuclear Information System (INIS)

    Mosse, I. B.; Glushkova, I. V.; Aksyutik, T. V.

    2003-01-01

    We studied natural populations of Drosophila melanogaster from radio-contaminated area (Vetka district of Gomel region with 24 Ci/km 2 of 137 Cs and 0.5 Cu/km 2 of 90 Sr) 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)

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

    Science.gov (United States)

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

    2017-04-01

    The objective of this study was the assessment of the stationary-phase, low-pH-inducible acid tolerance response (ATR) of different Salmonella enterica strains. For this purpose, 30 strains of the pathogen were grown in tryptone soy broth in the absence (non-adapted cultures) and presence (1% w/v; acid-adapted cultures) of glucose, and then subjected to 4-h acid challenge trials at pH 3.0. Surviving populations of each strain were determined at 1-h intervals, and the Weibull model was fitted to the derived microbiological data. Extensive variability in the acid stress responses of the tested S. enterica strains was observed, with the total population reductions (log CFU/ml) attained in 4 h of acid challenge ranging from 0.9 to 5.5 and from 0.6 to 7.0 for the non-adapted and acid-adapted cultures, respectively. As demonstrated by the model scale parameter δ and shape parameter p, the effect of acid adaptation on the inactivation curves was strain-specific. Although acid adaptation resulted in enhanced acid survival for the majority of the tested strains, there were strains exhibiting similar or decreased acid resistance compared to their non-adapted counterparts. Moreover, acid adaptation appeared to decrease the strain variability of δ whereas increasing the strain variability of p: the coefficient of variation of δ among the tested strains was 97.2 and 54.9% for the non-adapted and acid-adapted cultures, respectively, while the corresponding values for p were 12.7 and 48.1%. The data of the present study, which is the first one to systematically evaluate the adaptive ATR of multiple S. enterica strains, clearly demonstrate that this phenotype (attempted to be induced by growing the pathogen in the presence of glucose) is strain-dependent. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. p53-dependent adaptive responses in human cells exposed to space radiations.

    Science.gov (United States)

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

    2010-11-15

    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. 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. 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. 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. Copyright © 2010 Elsevier Inc. All rights reserved.

  5. Relationship between neural response and adaptation selectivity to form and color: an ERP study

    Directory of Open Access Journals (Sweden)

    Ilias eRentzeperis

    2012-04-01

    Full Text Available Adaptation is widely used as a tool for studying selectivity to visual features. In these studies it is usually assumed that the loci of feature selective neural responses and adaptation coincide. We used an adaptation paradigm to investigate the relationship between response and adaptation selectivity in event-related potentials (ERP. ERPs were evoked by the presentation of colored Glass patterns in a form discrimination task. Response selectivities to form and, to some extent, color of the patterns were reflected in the C1 and N1 ERP components. Adaptation selectivity to color was reflected in N1 and was followed by a late (300-500 ms after stimulus onset effect of form adaptation. Thus for form, response and adaptation selectivity were manifested in non-overlapping intervals. These results indicate that adaptation and response selectivity can be associated with different processes. Therefore inferring selectivity from an adaptation paradigm requires analysis of both adaptation and neural response data.

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

    Science.gov (United States)

    Rivera-Brown, Anita M; Frontera, Walter R

    2012-11-01

    Physical activity and fitness are associated with a lower prevalence of chronic diseases, such as heart disease, cancer, high blood pressure, and diabetes. This review discusses the body's response to an acute bout of exercise and long-term physiological adaptations to exercise training with an emphasis on endurance exercise. An overview is provided of skeletal muscle actions, muscle fiber types, and the major metabolic pathways involved in energy production. The importance of adequate fluid intake during exercise sessions to prevent impairments induced by dehydration on endurance exercise, muscular power, and strength is discussed. Physiological adaptations that result from regular exercise training such as increases in cardiorespiratory capacity and strength are mentioned. The review emphasizes the cardiovascular and metabolic adaptations that lead to improvements in maximal oxygen capacity. Copyright © 2012 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

  7. Molecular mechanisms of the yeast adaptive response and tolerance to stresses encountered during ethanol fermentation.

    Science.gov (United States)

    Auesukaree, Choowong

    2017-08-01

    During ethanol fermentation, yeast cells encounter various stresses including sugar substrates-induced high osmolarity, increased ethanol concentration, oxygen metabolism-derived reactive oxygen species (ROS), and elevated temperature. To cope with these fermentation-associated stresses, appropriate adaptive responses are required to prevent stress-induced cellular dysfunctions and to acquire stress tolerances. This review will focus on the cellular effects of these stresses, molecular basis of the adaptive response to each stress, and the cellular mechanisms contributing to stress tolerance. Since a single stress can cause diverse effects, including specific and non-specific effects, both specific and general stress responses are needed for achieving comprehensive protection. For instance, the high-osmolarity glycerol (HOG) pathway and the Yap1/Skn7-mediated pathways are specifically involved in responses to osmotic and oxidative stresses, respectively. On the other hand, due to the common effect of these stresses on disturbing protein structures, the upregulation of heat shock proteins (HSPs) and trehalose is induced upon exposures to all of these stresses. A better understanding of molecular mechanisms underlying yeast tolerance to these fermentation-associated stresses is essential for improvement of yeast stress tolerance by genetic engineering approaches. Copyright © 2017 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  8. Cellular adaptation as an important response during chemical carcinogenesis

    International Nuclear Information System (INIS)

    Farber, E.

    1992-01-01

    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

  9. Radiation-induced gene responses

    Energy Technology Data Exchange (ETDEWEB)

    Woloschak, G.E.; Paunesku, T.; Shearin-Jones, P.; Oryhon, J.

    1996-12-31

    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.

  10. Radiation-induced gene responses

    International Nuclear Information System (INIS)

    Woloschak, G.E.; Paunesku, T.; Shearin-Jones, P.; Oryhon, J.

    1996-01-01

    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

  11. Adaptations to endurance training depend on exercise-induced oxidative stress: exploiting redox interindividual variability.

    Science.gov (United States)

    Margaritelis, N V; Theodorou, A A; Paschalis, V; Veskoukis, A S; Dipla, K; Zafeiridis, A; Panayiotou, G; Vrabas, I S; Kyparos, A; Nikolaidis, M G

    2018-02-01

    The aim of this study was to reveal the role of reactive oxygen and nitrogen species (RONS) in exercise adaptations under physiological in vivo conditions and without the interference from other exogenous redox agents (e.g. a pro-oxidant or antioxidant). We invented a novel methodological set-up that exploited the large redox interindividual variability in exercise responses. More specifically, we used exercise-induced oxidative stress as the 'classifier' measure (i.e. low, moderate and high) and investigated the physiological and redox adaptations after a 6-week endurance training protocol. We demonstrated that the group with the low exercise-induced oxidative stress exhibited the lowest improvements in a battery of classic adaptations to endurance training (VO 2 max, time trial and Wingate test) as well as in a set of redox biomarkers (oxidative stress biomarkers and antioxidants), compared to the high and moderate oxidative stress groups. The findings of this study substantiate, for the first time in a human in vivo physiological context, and in the absence of any exogenous redox manipulation, the vital role of RONS produced during exercise in adaptations. The stratification approach, based on a redox phenotype, implemented in this study could be a useful experimental strategy to reveal the role of RONS and antioxidants in other biological manifestations as well. © 2017 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

  12. Adaptation to Delayed Speech Feedback Induces Temporal Recalibration between Vocal Sensory and Auditory Modalities

    Directory of Open Access Journals (Sweden)

    Kosuke Yamamoto

    2011-10-01

    Full Text Available 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. Participants read some sentences with specific delay times of DAF (0, 30, 75, 120 ms during three minutes to induce ‘Lag Adaptation’. After the adaptation, they then judged the simultaneity between motor sensation and vocal sound given feedback in producing simple voice but not speech. We found that speech production with 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. 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. Studies of adaptive response and mutation induction in MCF-10A cells following exposure to chronic or acute ionizing radiation

    Energy Technology Data Exchange (ETDEWEB)

    Manesh, Sara Shakeri; Sangsuwan, Traimate; Wojcik, Andrzej; Haghdoost, Siamak, E-mail: Siamak.haghdoost@su.se

    2015-10-15

    Highlights: • 50 mGy at 1.4 mGy/h induces adaptive response in MCF-10A at mutation level. • Low dose rate γ-radiation does not induce adaptive response at survival level. • Overall, a dose rate effect is absent at the level of mutation in MCF-10A cells. - Abstract: A phenomenon in which exposure to a low adapting dose of radiation makes cells more resistant to the effects of a subsequent high dose exposure is termed radio-adaptive response. Adaptive response could hypothetically reduce the risk of late adverse effects of chronic or acute radiation exposures in humans. Understanding the underlying mechanisms of such responses is of relevance for radiation protection as well as for the clinical applications of radiation in medicine. However, due to the variability of responses depending on the model system and radiation condition, there is a need to further study under what conditions adaptive response can be induced. In this study, we analyzed if there is a dose rate dependence for the adapting dose, assuming that the adapting dose induces DNA response/repair pathways that are dose rate dependent. MCF-10A cells were exposed to a 50 mGy adapting dose administered acutely (0.40 Gy/min) or chronically (1.4 mGy/h or 4.1 mGy/h) and then irradiated by high acute challenging doses. The endpoints of study include clonogenic cell survival and mutation frequency at X-linked hprt locus. In another series of experiment, cells were exposed to 100 mGy and 1 Gy at different dose rates (acutely and chronically) and then the mutation frequencies were studied. Adaptive response was absent at the level of clonogenic survival. The mutation frequencies were significantly decreased in the cells pre-exposed to 50 mGy at 1.4 mGy/h followed by 1 Gy acute exposure as challenging dose. Importantly, at single dose exposures (1 Gy or 100 mGy), no differences at the level of mutation were found comparing different dose rates.

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

    DEFF Research Database (Denmark)

    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...

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

    International Nuclear Information System (INIS)

    Audette-Stuart, M.; Kim, S.B.; McMullin, D.; Festarini, A.; Yankovich, T.L.; Carr, J.; Mulpuru, S.

    2011-01-01

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Audette-Stuart, M., E-mail: stuartm@aecl.ca [Environmental Technologies Branch, Atomic Energy of Canada Limited, Chalk River Laboratories, Chalk River, Ontario, K0J 1P0 (Canada); Kim, S.B.; McMullin, D.; Festarini, A.; Yankovich, T.L.; Carr, J.; Mulpuru, S. [Environmental Technologies Branch, Atomic Energy of Canada Limited, Chalk River Laboratories, Chalk River, Ontario, K0J 1P0 (Canada)

    2011-06-15

    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.

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

    Science.gov (United States)

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

    2016-01-01

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

  18. Metabolic and hypoxic adaptation to anti-angiogenic therapy: a target for induced essentiality.

    Science.gov (United States)

    McIntyre, Alan; Harris, Adrian L

    2015-04-01

    Anti-angiogenic therapy has increased the progression-free survival of many cancer patients but has had little effect on overall survival, even in colon cancer (average 6-8 weeks) due to resistance. The current licensed targeted therapies all inhibit VEGF signalling (Table 1). Many mechanisms of resistance to anti-VEGF therapy have been identified that enable cancers to bypass the angiogenic blockade. In addition, over the last decade, there has been increasing evidence for the role that the hypoxic and metabolic responses play in tumour adaptation to anti-angiogenic therapy. The hypoxic tumour response, through the transcription factor hypoxia-inducible factors (HIFs), induces major gene expression, metabolic and phenotypic changes, including increased invasion and metastasis. Pre-clinical studies combining anti-angiogenics with inhibitors of tumour hypoxic and metabolic adaptation have shown great promise, and combination clinical trials have been instigated. Understanding individual patient response and the response timing, given the opposing effects of vascular normalisation versus reduced perfusion seen with anti-angiogenics, provides a further hurdle in the paradigm of personalised therapeutic intervention. Additional approaches for targeting the hypoxic tumour microenvironment are being investigated in pre-clinical and clinical studies that have potential for producing synthetic lethality in combination with anti-angiogenic therapy as a future therapeutic strategy. © 2015 The Authors. Published under the terms of the CC BY 4.0 license.

  19. Mouse retinal adaptive response to proton irradiation: correlation with increase in DNA repair and decrease in photoreceptor cell death

    International Nuclear Information System (INIS)

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

    2015-01-01

    Retina, the visual organ, that is permanently undergone aggressive environmental influence. This implies the existence in retina of intrinsic protective and recovery mechanisms. The presence of retinal genotoxic threshold, nonlinear dose response and adaptive response of retina to genotoxicants suggest this assumption. In this article, using the model of MNU-induced degeneration of retina in mice, we investigated the adaptive response of the retina in vivo after proton irradiation and a participation of Muller glial cells in it. It was showed that the retinal recovery after the genotoxic isults correlated with increase in efficacy of DNA-damage repair and decrease in death of retinal photoreceptor cells.

  20. Enhancement of human adaptive immune responses by administration of a high-molecular-weight polysaccharide extract from the cyanobacterium Arthrospira platensis

    DEFF Research Database (Denmark)

    Løbner, Morten; Walsted, Anette; Larsen, Rune

    2008-01-01

    The effect of consumption of Immulina, a high-molecular-weight polysaccharide extract from the cyanobacterium Arthrospira platensis, on adaptive immune responses was investigated by evaluation of changes in leukocyte responsiveness to two foreign recall antigens, Candida albicans (CA) and tetanus......beta, and IL-6 responses, indicating that it acts by inducing a pro-inflammatory state. Taken together, the data suggest that Immulina causes an age-dependent, temporary enhancement of adaptive immune responses....

  1. Transcultural adaptation of the filial responsibility interview schedule for Brazil.

    Science.gov (United States)

    Aires, M; Weissheimer, A-M; Rosset, I; de Oliveira, F A; de Morais, E P; Paskulin, L M G

    2012-06-01

    In developed countries, filial responsibility in relation to caring for elderly parents has been systematically studied. In Brazil and other developing countries, however, it is a relatively new topic and has not yet been included in the research agenda on ageing. To describe the process of cross-cultural adaptation of the qualitative phase of the filial responsibility interview schedule into Brazilian Portuguese. An expert committee of six team members participated in the study. In addition, individual interviews were held with 11 caregivers of older persons to evaluate the quality of the final Portuguese version of the schedule. The process included examining conceptual, item, semantic and operational equivalencies. Conceptual and item equivalencies were based on a literature review and on discussions with the expert committee. Semantic equivalence was attained through translation, back-translation, expert committee evaluation and pre-testing. The final version was pre-tested in caregivers of older persons enrolled in the home care programme of a primary health care service in Southern Brazil. Conceptual, item, semantic and operational equivalencies were attained. Through the interviews, responses to the open-ended questions concerning filial responsibility in the care for elderly parents pertained to the following categories: possibility of institutionalization of elderly parents, caregiver expectations, difficulties in being a child caregiver and responsibility as a natural process. The Portuguese version presented good semantic equivalence and the results showed that the concepts and items are applicable to the Brazilian context. © 2012 The Authors. International Nursing Review © 2012 International Council of Nurses.

  2. Innate and adaptive immune responses in neurodegeneration and repair

    Science.gov (United States)

    Amor, Sandra; Woodroofe, M Nicola

    2014-01-01

    Emerging evidence suggests important roles of the innate and adaptive immune responses in the central nervous system (CNS) in neurodegenerative diseases. In this special review issue, five leading researchers discuss the evidence for the beneficial as well as the detrimental impact of the immune system in the CNS in disorders including Alzheimer's disease, multiple sclerosis and CNS injury. Several common pathological mechanisms emerge indicating that these pathways could provide important targets for manipulating the immune reposes in neurodegenerative disorders. The articles highlight the role of the traditional resident immune cell of the CNS - the microglia - as well as the role of other glia astrocytes and oligodendrocytes in immune responses and their interplay with other immune cells including, mast cells, T cells and B cells. Future research should lead to new discoveries which highlight targets for therapeutic interventions which may be applicable to a range of neurodegenerative diseases. PMID:23758741

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

    Science.gov (United States)

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

    2017-03-01

    Glycerol synthesis is key to central metabolism and stress biology in Saccharomyces cerevisiae, yet the cellular adjustments needed to respond and adapt to glycerol stress are little understood. Here, we determined impacts of acute and chronic exposures to glycerol stress in S. cerevisiae. Glycerol stress can result from an increase of glycerol concentration in the medium due to the S. cerevisiae fermenting activity or other metabolic activities. Acute glycerol-stress led to a 50% decline in growth rate and altered transcription of more than 40% of genes. The increased genetic diversity in S. cerevisiae population, which had evolved in the standard nutrient medium for hundreds of generations, led to an increase in growth rate and altered transcriptome when such population was transferred to stressful media containing a high concentration of glycerol; 0.41 M (0.990 water activity). Evolution of S. cerevisiae populations during a 10-day period in the glycerol-containing medium led to transcriptome changes and readjustments to improve control of glycerol flux across the membrane, regulation of cell cycle, and more robust stress response; and a remarkable increase of growth rate under glycerol stress. Most of the observed regulatory changes arose in duplicated genes. These findings elucidate the physiological mechanisms, which underlie glycerol-stress response, and longer-term adaptations, in S. cerevisiae; they also have implications for enigmatic aspects of the ecology of this otherwise well-characterized yeast. © 2016 Society for Applied Microbiology and John Wiley & Sons Ltd.

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

    Science.gov (United States)

    Convertino, Victor A.

    1991-01-01

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

  5. Covariate-adjusted response-adaptive designs for longitudinal treatment responses: PEMF trial revisited.

    Science.gov (United States)

    Biswas, Atanu; Park, Eunsik; Bhattacharya, Rahul

    2012-08-01

    Response-adaptive designs have become popular for allocation of the entering patients among two or more competing treatments in a phase III clinical trial. Although there are a lot of designs for binary treatment responses, the number of designs involving covariates is very small. Sometimes the patients give repeated responses. The only available response-adaptive allocation design for repeated binary responses is the urn design by Biswas and Dewanji [Biswas A and Dewanji AA. Randomized longitudinal play-the-winner design for repeated binary data. ANZJS 2004; 46: 675-684; Biswas A and Dewanji A. Inference for a RPW-type clinical trial with repeated monitoring for the treatment of rheumatoid arthritis. Biometr J 2004; 46: 769-779.], although it does not take care of the covariates of the patients in the allocation design. In this article, a covariate-adjusted response-adaptive randomisation procedure is developed using the log-odds ratio within the Bayesian framework for longitudinal binary responses. The small sample performance of the proposed allocation procedure is assessed through a simulation study. The proposed procedure is illustrated using some real data set.

  6. CD8+lineage dendritic cells determine adaptive immune responses to inflammasome activation upon sterile skin injury.

    Science.gov (United States)

    Chakraborty, Rituparna; Chandra, Janin; Cui, Shuai; Tolley, Lynn; Cooper, Matthew A; Kendall, Mark; Frazer, Ian H

    2018-01-01

    The molecular links between sterile inflammation and induction of adaptive immunity have not been fully identified. Here, we examine how damage-associated molecular patterns (DAMPs), as opposed to pathogen-associated molecules (PAMPs), regulate the immune response to non-self-antigens presented at the site of a physical injury. Heat applied briefly to the skin invokes sterile inflammation, characterized by local cell death and caspase-1 activation without demonstrably disrupting skin integrity. Co-delivery of ovalbumin (OVA) with heat injury induces OVA-specific CD8 + T-cell responses, and this is dependent on caspase-1 activation and MyD88 signalling. Using Id2flox/flox-CD11cCre+ mice, we demonstrate that CD8 + lineage DCs are required to induce OVA-specific CD8 + T-cell responses following heat injury. Consistent with this observation, intradermal administration of CD8 + lineage DCs but not CD11b + lineage DCs restores priming of CD8 + T-cell responses in Casp-1 -/- mice. Thus, we conclude that a sterile injury induces CD8 + T-cell immune responses to local antigen through caspase-1 activation and requires CD8 + lineage DCs, a finding of significance for immunotherapy and for the pathogenesis of autoimmunity. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. Physiological responses induced by pleasant stimuli.

    Science.gov (United States)

    Watanuki, Shigeki; Kim, Yeon-Kyu

    2005-01-01

    The specific physiological responses induced by pleasant stimuli were investigated in this study. Various physiological responses of the brain (encephaloelectrogram; EEG), autonomic nervous system (ANS), immune system and endocrine system were monitored when pleasant stimuli such as odors, emotional pictures and rakugo, a typical Japanese comical story-telling, were presented to subjects. The results revealed that (i) EEG activities of the left frontal brain region were enhanced by a pleasant odor; (ii) emotional pictures related to primitive element such as nudes and erotic couples elevated vasomotor sympathetic nervous activity; and (iii) an increase in secretory immunoglobulin A (s-IgA) and a decrease in salivary cortisol (s-cortisol) were induced by rakugo-derived linguistic pleasant emotion. Pleasant emotion is complicated state. However, by considering the evolutionary history of human being, it is possible to assess and evaluate pleasant emotion from certain physiological responses by appropriately summating various physiological parameters.

  8. EXERCISE-INDUCED ARTERIAL ADAPTATIONS IN ELITE JUDO ATHLETES

    Directory of Open Access Journals (Sweden)

    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

  9. Transposable elements as stress adaptive capacitors induce genomic instability in fungal pathogen Magnaporthe oryzae.

    Directory of Open Access Journals (Sweden)

    Sonia Chadha

    Full Text Available A fundamental problem in fungal pathogenesis is to elucidate the evolutionary forces responsible for genomic rearrangements leading to races with fitter genotypes. Understanding the adaptive evolutionary mechanisms requires identification of genomic components and environmental factors reshaping the genome of fungal pathogens to adapt. Herein, Magnaporthe oryzae, a model fungal plant pathogen is used to demonstrate the impact of environmental cues on transposable elements (TE based genome dynamics. For heat shock and copper stress exposed samples, eight TEs belonging to class I and II family were employed to obtain DNA profiles. Stress induced mutant bands showed a positive correlation with dose/duration of stress and provided evidences of TEs role in stress adaptiveness. Further, we demonstrate that genome dynamics differ for the type/family of TEs upon stress exposition and previous reports of stress induced MAGGY transposition has underestimated the role of TEs in M. oryzae. Here, we identified Pyret, MAGGY, Pot3, MINE, Mg-SINE, Grasshopper and MGLR3 as contributors of high genomic instability in M. oryzae in respective order. Sequencing of mutated bands led to the identification of LTR-retrotransposon sequences within regulatory regions of psuedogenes. DNA transposon Pot3 was identified in the coding regions of chromatin remodelling protein containing tyrosinase copper-binding and PWWP domains. LTR-retrotransposons Pyret and MAGGY are identified as key components responsible for the high genomic instability and perhaps these TEs are utilized by M. oryzae for its acclimatization to adverse environmental conditions. Our results demonstrate how common field stresses change genome dynamics of pathogen and provide perspective to explore the role of TEs in genome adaptability, signalling network and its impact on the virulence of fungal pathogens.

  10. 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

    International Nuclear Information System (INIS)

    Mortazavi, S.M.J.; Mozdarani, H.

    2000-01-01

    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)

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

    International Nuclear Information System (INIS)

    Peitl Junior, Paulo

    1996-01-01

    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 G 1 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)

  12. Adaptive and maladaptive cortisol responses to pediatric obesity.

    Science.gov (United States)

    Soros, Arlette; Zadik, Zvi; Chalew, Stuart

    2008-09-01

    The recent unprecedented increase of childhood obesity has led to an alarming rise in type 2 diabetes mellitus (T2D) among these children. The process underlying the progression from simple obesity to T2D is not well understood. Cortisol is a candidate factor in the pathogenesis of T2D, as it can exacerbate insulin resistance and provoke other disturbances of the metabolic syndrome. The 24-h integrated concentration (IC) of cortisol is suppressed in non-diabetic obese children compared to lean children. This difference in IC-cortisol is not due to changes in cortisol binding globulin or plasma cortisol to cortisone ratio between groups. In obese individuals, IC-cortisol suppression disappears with age after adolescence, which corresponds with increasing occurrence of T2D and other metabolic disorders of obesity. We consider the IC-cortisol levels of lean insulin sensitive children to be metabolically inappropriate for obese insulin resistant children. Thus, we hypothesize that suppression of IC-cortisol is an important adaptive response to obesity (cortisol adaptive suppression) in childhood that prevents pediatric T2D while failure to suppress IC-cortisol (cortisol suppression failure) exacerbates insulin resistance and contributes to the development of T2D. In further support of this hypothesis is early pilot data suggesting that cortisol suppression failure occurs in obese children with impaired fasting glucose levels. The mechanism(s) underlying cortisol adaptive suppression, how and why these mechanism(s) fail are unknown. Elucidation of these mechanisms may lead to interventions to prevent the development of T2D and its complications in obese individuals.

  13. Autologous Stem Cell Transplantation Disrupts Adaptive Immune Responses during Rebound Simian/Human Immunodeficiency Virus Viremia.

    Science.gov (United States)

    Reeves, Daniel B; Peterson, Christopher W; Kiem, Hans-Peter; Schiffer, Joshua T

    2017-07-01

    Primary HIV-1 infection induces a virus-specific adaptive/cytolytic immune response that impacts the plasma viral load set point and the rate of progression to AIDS. Combination antiretroviral therapy (cART) suppresses plasma viremia to undetectable levels that rebound upon cART treatment interruption. Following cART withdrawal, the memory component of the virus-specific adaptive immune response may improve viral control compared to primary infection. Here, using primary infection and treatment interruption data from macaques infected with simian/human immunodeficiency virus (SHIV), we observe a lower peak viral load but an unchanged viral set point during viral rebound. The addition of an autologous stem cell transplant before cART withdrawal alters viral dynamics: we found a higher rebound set point but similar peak viral loads compared to the primary infection. Mathematical modeling of the data that accounts for fundamental immune parameters achieves excellent fit to heterogeneous viral loads. Analysis of model output suggests that the rapid memory immune response following treatment interruption does not ultimately lead to better viral containment. Transplantation decreases the durability of the adaptive immune response following cART withdrawal and viral rebound. Our model's results highlight the impact of the endogenous adaptive immune response during primary SHIV infection. Moreover, because we capture adaptive immune memory and the impact of transplantation, this model will provide insight into further studies of cure strategies inspired by the Berlin patient. IMPORTANCE HIV patients who interrupt combination antiretroviral therapy (cART) eventually experience viral rebound, the return of viral loads to pretreatment levels. However, the "Berlin patient" remained free of HIV rebound over a decade after stopping cART. His cure is attributed to leukemia treatment that included an HIV-resistant stem cell transplant. Inspired by this case, we studied the impact

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

    International Nuclear Information System (INIS)

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

    2007-01-01

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

  15. Adaptation response of Arabidopsis thaliana to random positioning

    Science.gov (United States)

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

    2013-10-01

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

  16. Local adaptation of aboveground herbivores towards plant phenotypes induced by soil biota.

    Directory of Open Access Journals (Sweden)

    Dries Bonte

    2010-06-01

    Full Text Available Soil biota may trigger strong physiological responses in plants and consequently induce distinct phenotypes. Plant phenotype, in turn, has a strong impact on herbivore performance. Here, we tested the hypothesis that aboveground herbivores are able to adapt to plant phenotypes induced by soil biota.We bred spider mites for 15 generations on snap beans with three different belowground biotic interactions: (i no biota (to serve as control, (ii arbuscular mycorrhizal fungi and (ii root-feeding nematodes. Subsequently, we conducted a reciprocal selection experiment using these spider mites, which had been kept on the differently treated plants. Belowground treatments induced changes in plant biomass, nutrient composition and water content. No direct chemical defence through cyanogenesis was detected in any of the plant groups. Growth rates of spider mites were higher on the ecotypes on which they were bred for 15 generations, although the statistical significance disappeared for mites from the nematode treatment when corrected for all multiple comparisons.These results demonstrate that belowground biota may indeed impose selection on the aboveground insect herbivores mediated by the host plant. The observed adaptation was driven by variable quantitative changes of the different separately studied life history traits (i.e. fecundity, longevity, sex-ratio, time to maturity.

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

    International Nuclear Information System (INIS)

    Dias, V.

    2010-01-01

    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. Inducement and responsibility in the energy turnaround

    International Nuclear Information System (INIS)

    Loewer, Wolfgang

    2013-01-01

    The book includes several contributions concerning the Bonn discussion on energy legislation (volume 7): inducement and responsibility -in terms of constitutional law; between Europe and re-regulation - what is the regulation framework? Continuity requirement as legislative action directive; the future of the nuclear fuel tax after the nuclear phaseout - problems of the constitutional finance and the European tax legislation, strategy and energy markets; regulatory challenges in the realization of the energy turnaround policy.

  19. Political commitment in organising municipal responses to climate adaptation: the dedicated approach versus the mainstreaming approach

    NARCIS (Netherlands)

    Uittenbroek, C.J.; Janssen-Jansen, L.B.; Spit, T.J.M.; Salet, W.G.M.; Runhaar, H.A.C.

    2014-01-01

    We develop conceptual understanding of political commitment in two approaches to organising municipal responses to climate adaptation. The dedicated approach, based on direct political commitment to climate adaptation, implies political agenda setting, resource allocation, and clear policy

  20. Radiation adaptive response for the growth of cultured glial cells

    International Nuclear Information System (INIS)

    Suzuki, S.; Miura, Y.; Kano, M.; Toda, T.; Urano, S.

    2003-01-01

    Full text: To examine the molecular mechanism of radiation adaptive response (RAR) for the growth of cultured glial cells and to investigate the influence of aging on the response, glial cells were cultured from young and aged rats (1 month and 24 months old). RAR for the growth of glial cells conditioned with a low dose of X-rays and subsequently exposed to a high dose of X-rays was examined for cell number and BrdU incorporation. Involvement of the subcellular signaling pathway factors in RAR was investigated using their inhibitors, activators and mutated glial cells. RAR was observed in cells cultured from young rats, but was not in cells from aged rats. The inhibitors of protein kinase C (PKC) and DNA-dependent protein kinase (DNA-PK) or phosphatidylinositol 3-kinase (PI3K) suppressed RAR. The activators of PKC instead of low dose irradiation also caused RAR. Moreover, glial cells cultured from severe combined immunodeficiency (scid) mice (CB-17 scid) and ataxia-telangiectasia (AT) cells from AT patients showed no RAR. These results indicated that PKC, ATM, DNAPK and/or PI3K were involved in RAR for growth and BrdU incorporation of cultured glial cells and RAR decreased with aging. Proteomics data of glial cells exposed to severe stress of H 2 O 2 or X-rays also will be presented in the conference since little or no difference has not been observed with slight stress yet

  1. 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

    Energy Technology Data Exchange (ETDEWEB)

    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)

  2. Insult-induced adaptive plasticity of the auditory system

    Directory of Open Access Journals (Sweden)

    Joshua R Gold

    2014-05-01

    Full Text Available The brain displays a remarkable capacity for both widespread and region-specific modifications in response to environmental challenges, with adaptive processes bringing about the reweighting of connections in neural networks putatively required for optimising performance and behaviour. As an avenue for investigation, studies centred around changes in the mammalian auditory system, extending from the brainstem to the cortex, have revealed a plethora of mechanisms that operate in the context of sensory disruption after insult, be it lesion-, noise trauma, drug-, or age-related. Of particular interest in recent work are those aspects of auditory processing which, after sensory disruption, change at multiple – if not all – levels of the auditory hierarchy. These include changes in excitatory, inhibitory and neuromodulatory networks, consistent with theories of homeostatic plasticity; functional alterations in gene expression and in protein levels; as well as broader network processing effects with cognitive and behavioural implications. Nevertheless, there abounds substantial debate regarding which of these processes may only be sequelae of the original insult, and which may, in fact, be maladaptively compelling further degradation of the organism’s competence to cope with its disrupted sensory context. In this review, we aim to examine how the mammalian auditory system responds in the wake of particular insults, and to disambiguate how the changes that develop might underlie a correlated class of phantom disorders, including tinnitus and hyperacusis, which putatively are brought about through maladaptive neuroplastic disruptions to auditory networks governing the spatial and temporal processing of acoustic sensory information.

  3. Skeletal Muscle Remodeling in Response to Eccentric vs. Concentric Loading: Morphological, Molecular, and Metabolic Adaptations.

    Science.gov (United States)

    Franchi, Martino V; Reeves, Neil D; Narici, Marco V

    2017-01-01

    Skeletal muscle contracts either by shortening or lengthening (concentrically or eccentrically, respectively); however, the two contractions substantially differ from one another in terms of mechanisms of force generation, maximum force production and energy cost. It is generally known that eccentric actions generate greater force than isometric and concentric contractions and at a lower metabolic cost. Hence, by virtue of the greater mechanical loading involved in active lengthening, eccentric resistance training (ECC RT) is assumed to produce greater hypertrophy than concentric resistance training (CON RT). Nonetheless, prevalence of either ECC RT or CON RT in inducing gains in muscle mass is still an open issue, with some studies reporting greater hypertrophy with eccentric, some with concentric and some with similar hypertrophy within both training modes. Recent observations suggest that such hypertrophic responses to lengthening vs. shortening contractions are achieved by different adaptations in muscle architecture. Whilst the changes in muscle protein synthesis in response to acute and chronic concentric and eccentric exercise bouts seem very similar, the molecular mechanisms regulating the myogenic adaptations to the two distinct loading stimuli are still incompletely understood. Thus, the present review aims to, (a) critically discuss the literature on the contribution of eccentric vs. concentric loading to muscular hypertrophy and structural remodeling, and, (b) clarify the molecular mechanisms that may regulate such adaptations. We conclude that, when matched for either maximum load or work, similar increase in muscle size is found between ECC and CON RT. However, such hypertrophic changes appear to be achieved through distinct structural adaptations, which may be regulated by different myogenic and molecular responses observed between lengthening and shortening contractions.

  4. Skeletal Muscle Remodeling in Response to Eccentric vs. Concentric Loading: Morphological, Molecular, and Metabolic Adaptations

    Directory of Open Access Journals (Sweden)

    Martino V. Franchi

    2017-07-01

    Full Text Available Skeletal muscle contracts either by shortening or lengthening (concentrically or eccentrically, respectively; however, the two contractions substantially differ from one another in terms of mechanisms of force generation, maximum force production and energy cost. It is generally known that eccentric actions generate greater force than isometric and concentric contractions and at a lower metabolic cost. Hence, by virtue of the greater mechanical loading involved in active lengthening, eccentric resistance training (ECC RT is assumed to produce greater hypertrophy than concentric resistance training (CON RT. Nonetheless, prevalence of either ECC RT or CON RT in inducing gains in muscle mass is still an open issue, with some studies reporting greater hypertrophy with eccentric, some with concentric and some with similar hypertrophy within both training modes. Recent observations suggest that such hypertrophic responses to lengthening vs. shortening contractions are achieved by different adaptations in muscle architecture. Whilst the changes in muscle protein synthesis in response to acute and chronic concentric and eccentric exercise bouts seem very similar, the molecular mechanisms regulating the myogenic adaptations to the two distinct loading stimuli are still incompletely understood.Thus, the present review aims to, (a critically discuss the literature on the contribution of eccentric vs. concentric loading to muscular hypertrophy and structural remodeling, and, (b clarify the molecular mechanisms that may regulate such adaptations.We conclude that, when matched for either maximum load or work, similar increase in muscle size is found between ECC and CON RT. However, such hypertrophic changes appear to be achieved through distinct structural adaptations, which may be regulated by different myogenic and molecular responses observed between lengthening and shortening contractions.

  5. Proteomic study on X-irradiation-responsive proteins and ageing. Search for responsible proteins for radiation adaptive response

    International Nuclear Information System (INIS)

    Miura, Yuri; Kano, Mayumi; Suzuki, Shozo; Endo, Tamao; Toda, Tosifusa; Yamada, Masaki; Nishine, Tsutomu; Urano, Shiro

    2007-01-01

    We investigated high- or low-dose irradiation-responsive proteins using proteomics on two-dimensional (2D) polyacrylamide gel electrophoresis (PAGE), and the effects of ageing on cell responses to radiation in variously aged rat astrocytes. After 5 Gy irradiation, the relative abundance of peroxiredoxin 2, an antioxidant enzyme, and latexin, an inhibitor of carboxypeptidase, increased. The induction of these proteins was suppressed by ageing, suggesting that the response to high-dose radiation decreased with ageing. The relative abundance of elongation factor 2 (EF-2) fragment increased 3 h and reduced 24 h after 0.1 Gy irradiation. Temporal enhancement of the EF-2 fragment due to low-dose irradiation was suppressed by ageing. Since radiation adaptive response in cultured astrocytes was observed 3 h but not 24 h after 0.1 Gy irradiation and suppressed by ageing as previously reported, alteration of the EF-2 fragment corresponded to the radiation adaptive response. We also examined phospho-protein profiles, resulting in the relative abundance of phospho-EF-1β and phospho-β-actin being altered by 0.1 Gy irradiation; however, ageing did not affect the alteration of phospho-EF-1β and phospho-β-actin, unlike the EF-2 fragment. The results suggested that the EF-2 fragment was a possible candidate for the protein responsible for the radiation adaptive response in cultured astrocytes. (author)

  6. Injury-induced immune responses in Hydra.

    Science.gov (United States)

    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. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights

  7. Climate-induced community relocations: using integrated social-ecological assessments to foster adaptation and resilience

    Directory of Open Access Journals (Sweden)

    Robin Bronen

    2015-09-01

    Full Text Available Extreme weather events coupled with sea level rise and erosion will cause coastal and riverine areas where people live and maintain livelihoods to disappear permanently. Adaptation to these environmental changes, including the permanent relocation of millions of people, requires new governance tools. In the USA, local governments, often with state-level and national-level support, will be primarily responsible for protecting residents from climate-change impacts and implementing policies needed to protect their welfare. Government agencies have a variety of tools to facilitate protection in place and managed coastal retreat but have very limited tools to facilitate community relocation. In addition, no institutional mechanism currently exists to determine whether and when preventive relocation needs to occur to protect people from climate change impacts. Based on research involving four Alaska Native communities threatened by climate-induced environmental impacts, I propose the design and implementation of an adaptive governance framework to respond to the need to relocate populations. In this context, adaptive governance means the ability of institutions to dynamically respond to climate change impacts. A component of this adaptive governance framework is a social-ecological monitoring and assessment tool that can facilitate collaborative knowledge production by community residents and governance institutions to guide sustainable adaptation strategies and determine whether and when relocation needs to occur. The framework, including the monitoring and assessment tool, has not been systematically tested. However, the potential use of this tool is discussed by drawing on empirical examples of Alaskan communities faced with accelerating rates of erosion.

  8. Evidence for adaptive response and implication in pulse-simulated low-dose-rate radiotherapy

    International Nuclear Information System (INIS)

    Raaphorst, G.P.; Ng, C.E.; Smith, D.; Niedbala, M.

    2000-01-01

    Purpose: Pulsed-dose-rate (PDR) brachytherapy as a substitute for continuous low-dose-rate (LDR) brachytherapy has a number of clinical advantages. However, early results show that some cells can exhibit an adaptive response to radiation and in PDR where many pulses are given such an adaptive response may play an important role in the outcome. Methods and Materials: Nine human cell lines (two normal fibroblast and seven tumor) were evaluated for an adaptive response. Cells were given either a single adapting dose before a challenge dose or given PDR sequences for which the average dose rate matched the LDR dose rate. Response was assessed using the colony survival assay. Results: Five of the nine cell lines showed an adapting response to single small doses of radiation. Three of these cell lines were further investigated for adapting response to PDR and two of the three lines (one ovarian carcinoma and one glioma) showed an adaptive response which was dependent on pulse size and interval. Conclusion: The data show that an adaptive response can occur in human cells and that it can vary among cell lines. In addition, PDR sequences also produced an adaptive response which could have an affect on PDR therapy if such a response is found in tissues

  9. Mild hyperthermia can induce adaptation to cytogenetic damage caused by subsequent X irradiation

    International Nuclear Information System (INIS)

    Cai, Lu.; Jiang, Jie.

    1995-01-01

    Many low-level environmental agents are able to induce an increased resistance to subsequent mutagenic effects induced by ionizing radiation. In this paper, an induced cytogenetic adaptation to radiation in human lymphocytes was studied with mild hyperthermia as the adaptive treatment and compared with that induced by low-dose radiation. We found that this adaptation could be induced not only in PHA-stimulated human lymphocytes (at 14, 38 and 42 h after addition of PHA), but also in unstimulated G 0 -phase cells (before addition of PHA) by mild hyperthermia (41 degrees C for 1 h) as well as 50 mGy X rays. When the two adaptive treatments were combined, no additive effects on the magnitude of the adaptation induced were observed, suggesting that low-dose radiation and hyperthermia may share one mechanism of induction of adaptation to cytogenetic damage. Some mechanisms which may be involved in the induction of adaptation to cytogenetic damage by low-dose radiation are discussed and compared with the effects of mild hyperthermia in inducing thermotolerance and radioresistance. 56 refs., 4 figs., 3 tabs

  10. Mild hyperthermia can induce adaptation to cytogenetic damage caused by subsequent X irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Cai, Lu.; Jiang, Jie. [Norman Bethune Univ. of Medical Sciences, Changchun (China)

    1995-07-01

    Many low-level environmental agents are able to induce an increased resistance to subsequent mutagenic effects induced by ionizing radiation. In this paper, an induced cytogenetic adaptation to radiation in human lymphocytes was studied with mild hyperthermia as the adaptive treatment and compared with that induced by low-dose radiation. We found that this adaptation could be induced not only in PHA-stimulated human lymphocytes (at 14, 38 and 42 h after addition of PHA), but also in unstimulated G{sub 0}-phase cells (before addition of PHA) by mild hyperthermia (41{degrees}C for 1 h) as well as 50 mGy X rays. When the two adaptive treatments were combined, no additive effects on the magnitude of the adaptation induced were observed, suggesting that low-dose radiation and hyperthermia may share one mechanism of induction of adaptation to cytogenetic damage. Some mechanisms which may be involved in the induction of adaptation to cytogenetic damage by low-dose radiation are discussed and compared with the effects of mild hyperthermia in inducing thermotolerance and radioresistance. 56 refs., 4 figs., 3 tabs.

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

    Science.gov (United States)

    Dragos, Kosmas; Smarsly, Kay

    2016-10-01

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

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    Narise K

    2014-06-01

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

  14. Adaptation of exercise-induced stress in well-trained healthy young men.

    Science.gov (United States)

    JanssenDuijghuijsen, Lonneke M; Keijer, Jaap; Mensink, Marco; Lenaerts, Kaatje; Ridder, Lars; Nierkens, Stefan; Kartaram, Shirley W; Verschuren, Martie C M; Pieters, Raymond H H; Bas, Richard; Witkamp, Renger F; Wichers, Harry J; van Norren, Klaske

    2017-01-01

    What is the central question of this study? Exercise is known to induce stress-related physiological responses, such as changes in intestinal barrier function. Our aim was to determine the test-retest repeatability of these responses in well-trained individuals. What is the main finding and its importance? Responses to strenuous exercise, as indicated by stress-related markers such as intestinal integrity markers and myokines, showed high test-retest variation. Even in well-trained young men an adapted response is seen after a single repetition after 1 week. This finding has implications for the design of studies aimed at evaluating physiological responses to exercise. Strenuous exercise induces different stress-related physiological changes, potentially including changes in intestinal barrier function. In the Protégé Study (ISRCTN14236739; www.isrctn.com), we determined the test-retest repeatability in responses to exercise in well-trained individuals. Eleven well-trained men (27 ± 4 years old) completed an exercise protocol that consisted of intensive cycling intervals, followed by an overnight fast and an additional 90 min cycling phase at 50% of maximal workload the next morning. The day before (rest), and immediately after the exercise protocol (exercise) a lactulose and rhamnose solution was ingested. Markers of energy metabolism, lactulose-to-rhamnose ratio, several cytokines and potential stress-related markers were measured at rest and during exercise. In addition, untargeted urine metabolite profiles were obtained. The complete procedure (Test) was repeated 1 week later (Retest) to assess repeatability. Metabolic effect parameters with regard to energy metabolism and urine metabolomics were similar for both the Test and Retest period, underlining comparable exercise load. Following exercise, intestinal permeability (1 h plasma lactulose-to-rhamnose ratio) and the serum interleukin-6, interleukin-10, fibroblast growth factor-21 and muscle creatine

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

    Directory of Open Access Journals (Sweden)

    Stefanie Fischer

    Full Text Available 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.

  16. Household Adaptive Behavior in Response to Coastal Flood Risk and External Stressors

    Science.gov (United States)

    Buchanan, M. K.

    2017-12-01

    Approximately forty percent of the world's population sits along ocean coastlines. This urban exposure to flooding is increasing due to population growth and sea level rise resulting from anthropogenic climate change. Recent research improving the characterization of physical hazards from climate change on the coastal zone has helped cities assess their risks. This work includes improving our understanding of the rate and magnitude of sea level rise, the change in distribution of tropical cyclones, and the resulting frequency and severity of flooding on global to local scales. However, the ability of settlements to cope or thrive under changing climate conditions will likely depend on the cooperation and initiative of households, regardless of any governmental efforts to reduce risk. Understanding individuals' likely responses to changing coastal hazards is thus critical for decision-makers to plan for a sustainable future. Individuals may be motivated not only by information regarding emerging flood hazards, but also by cognitive and contextual factors. For governments to develop effective adaptation policies, it is important to understand what factors tend to motivate household adaptation. We apply principles from economics and psychology to investigate how people respond to various existing adaptation options and policies, using a household survey with experiments in New York City neighborhoods affected by Hurricane Sandy. We investigate a comprehensive set of factors that may influence household adaptive behavior. A striking 64% of homeowners and 83% of renters intend to relocate among different plausible future conditions, such as frequent nuisance flooding and the adaptation of peers. This amount is substantial considering the political sensitivity of `retreat' and the lack of regional and federal preparation for large-scale climate-induced migration.

  17. Ontogeny of adaptive antibody response to a model antigen in captive altricial zebra finches.

    Directory of Open Access Journals (Sweden)

    Tess L Killpack

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

  18. Adaptive governance : Towards a stable, accountable and responsive government

    NARCIS (Netherlands)

    Janssen, M.F.W.H.A.; van der Voort, H.G.

    2016-01-01

    Organizations are expected to adapt within a short time to deal with changes that might become disruptive if not adequately dealt with. Yet many organizations are unable to adapt effectively or quickly due to the established institutional arrangements and patterns of decision-making and

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

    Science.gov (United States)

    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. © 2014 Society for

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

    Directory of Open Access Journals (Sweden)

    Hoi-Kuan Kong

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

  1. Temporal partitioning of adaptive responses of the murine heart to fasting.

    Science.gov (United States)

    Brewer, Rachel A; Collins, Helen E; Berry, Ryan D; Brahma, Manoja K; Tirado, Brian A; Peliciari-Garcia, Rodrigo A; Stanley, Haley L; Wende, Adam R; Taegtmeyer, Heinrich; Rajasekaran, Namakkal Soorappan; Darley-Usmar, Victor; Zhang, Jianhua; Frank, Stuart J; Chatham, John C; Young, Martin E

    2018-03-15

    Recent studies suggest that the time of day at which food is consumed dramatically influences clinically-relevant cardiometabolic parameters (e.g., adiposity, insulin sensitivity, and cardiac function). Meal feeding benefits may be the result of daily periods of feeding and/or fasting, highlighting the need for improved understanding of the temporal adaptation of cardiometabolic tissues (e.g., heart) to fasting. Such studies may provide mechanistic insight regarding how time-of-day-dependent feeding/fasting cycles influence cardiac function. We hypothesized that fasting during the sleep period elicits beneficial adaptation of the heart at transcriptional, translational, and metabolic levels. To test this hypothesis, temporal adaptation was investigated in wild-type mice fasted for 24-h, or for either the 12-h light/sleep phase or the 12-h dark/awake phase. Fasting maximally induced fatty acid responsive genes (e.g., Pdk4) during the dark/active phase; transcriptional changes were mirrored at translational (e.g., PDK4) and metabolic flux (e.g., glucose/oleate oxidation) levels. Similarly, maximal repression of myocardial p-mTOR and protein synthesis rates occurred during the dark phase; both parameters remained elevated in the heart of fasted mice during the light phase. In contrast, markers of autophagy (e.g., LC3II) exhibited peak responses to fasting during the light phase. Collectively, these data show that responsiveness of the heart to fasting is temporally partitioned. Autophagy peaks during the light/sleep phase, while repression of glucose utilization and protein synthesis is maximized during the dark/active phase. We speculate that sleep phase fasting may benefit cardiac function through augmentation of protein/cellular constituent turnover. Copyright © 2018 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

    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 gamma radiation. However, pre-exposure to 5cGy gamma radiation appears to facilitate a radio-adaptive response that mitigates the reduction in genetic expression associated with single high-dose gamma radiation exposure. This radio-adaptive response may serve as a potential countermeasure to radiation-induced myocardial remodeling and preserve the cardiovascular health of astronauts; thus, reducing the risks of human space exploration.

  3. Age-related adaptation of pituitary-adrenocortical responses to stress.

    Science.gov (United States)

    Odio, M; Brodish, A

    1989-04-01

    It has been reported that aged rats show impaired feedback regulatory control of pituitary adrenocorticotropic hormone release by adrenal glucocorticoids, yet, show no age-related deficit in eliciting an adrenocortical stress response when compared to younger animals. However, the effects of age on the capacity of the pituitary-adrenocortical system to adapt from an acute to a chronic stress situation have not been fully resolved. In the present study, groups of 6-month-old (young) and 22-month-old (old) F-344 rats were sacrificed at various times during the 1st (day 1) and 3rd (day 3) acute exposure to a two-way electric shock-escape stress procedure and subsequently during the 28th (day 28) and 56th (day 56) chronic exposure. Determinations of stress-induced corticosterone and adrenocorticotropic hormone responses indicated that: (1) adrenocortical responses were similar between young and old rats on the first stress exposure, whereas by the third stress session corticosterone responses were higher in young than in old rats; (2) attenuation of pituitary-adrenal responses to chronic stress was less in old compared to young rats, and (3) environmental factors may delay the development of age-related physiological alterations in the pituitary-adrenocortical system.

  4. R-citalopram prevents the neuronal adaptive changes induced by escitalopram.

    Science.gov (United States)

    Mnie-Filali, Ouissame; Faure, Céline; Mansari, Mostafa El; Lambás-Señas, Laura; Bérod, Anne; Zimmer, Luc; Sánchez, Connie; Haddjeri, Nasser

    2007-10-08

    This study examined the long-term effects of the antidepressant escitalopram on rat serotonin (5-HT) neuronal activity and hippocampal neuroplasticity. In the dorsal raphe nucleus, a 2-week treatment with escitalopram (10 mg/kg/day, subcutaneous) did not modify the firing activity of 5-HT neurons, whereas a cotreatment with R-citalopram (20 mg/kg/day, subcutaneous) decreased it. In the dentate gyrus of dorsal hippocampus, escitalopram increased significantly (57%) the number of de novo cells and this was prevented by a cotreatment with R-citalopram. The present results support the role of the allosteric modulation of the 5-HT transporter in the regulation of the recovery of 5-HT neuronal activity and long-lasting hippocampal cellular plasticity induced by escitalopram, two adaptive changes presumably associated with the antidepressant response.

  5. Computerized Adaptive Test (CAT) Applications and Item Response Theory Models for Polytomous Items

    Science.gov (United States)

    Aybek, Eren Can; Demirtasli, R. Nukhet

    2017-01-01

    This article aims to provide a theoretical framework for computerized adaptive tests (CAT) and item response theory models for polytomous items. Besides that, it aims to introduce the simulation and live CAT software to the related researchers. Computerized adaptive test algorithm, assumptions of item response theory models, nominal response…

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

    Lifescience Database Archive (English)

    Full Text Available 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 ITAM-based sign...aling beyond the adaptive immune response. PubmedID 16332394 Title ITAM-based signaling beyond

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

    Indian Academy of Sciences (India)

    Unknown

    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. [Tiku A B and Kale R K 2004 Adaptive response and split-dose effect of radiation on the survival of ...

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

    International Nuclear Information System (INIS)

    Ishii, Keiichiro; Hoshi, Yuko; Iwasaki, Toshiyasu; Watanabe, Masami

    1997-01-01

    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 Ca 2+ 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)

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

    Science.gov (United States)

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

    2011-04-01

    We examined the impact of training-induced improvements in self-regulation, operationalized in terms of response inhibition, on longitudinal changes in self-reported adaptive socioemotional functioning. Data were collected from participants undergoing 3 months of intensive meditation training in an isolated retreat setting (Retreat 1) and a wait-list control group that later underwent identical training (Retreat 2). A 32-min response inhibition task (RIT) was designed to assess sustained self-regulatory control. Adaptive functioning (AF) was operationalized as a single latent factor underlying self-report measures of anxious and avoidant attachment, mindfulness, ego resilience, empathy, the five major personality traits (extroversion, agreeableness, conscientiousness, neuroticism, and openness to experience), difficulties in emotion regulation, depression, anxiety, and psychological well-being. Participants in Retreat 1 improved in RIT performance and AF over time whereas the controls did not. The control participants later also improved on both dimensions during their own retreat (Retreat 2). These improved levels of RIT performance and AF were sustained in follow-up assessments conducted approximately 5 months after the training. Longitudinal dynamic models with combined data from both retreats showed that improvement in RIT performance during training influenced the change in AF over time, which is consistent with a key claim in the Buddhist literature that enhanced capacity for self-regulation is an important precursor of changes in emotional well-being. PsycINFO Database Record (c) 2011 APA, all rights reserved.

  10. Adaptive Filtering for Aeroservoelastic Response Suppression, Phase I

    Data.gov (United States)

    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...

  11. Adapting to climate change : the public policy response - public infrastructure

    Science.gov (United States)

    2009-06-01

    This paper assesses the threats and needs that multidimensional climate change imposes for : public infrastructure, reviews the existing adaptive capacity that could be applied to respond : to these threats and needs, and presents options for enhanci...

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

    DEFF Research Database (Denmark)

    Marty, Lise; Dieckmann, Ulf; Ernande, Bruno

    2015-01-01

    . 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......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......, that the choice of genetic model (based on either quantitative genetics or gametic inheritance) influences the evolutionary recovery of traits after fishing ceases. Second, we analyse the influence of three factors possibly involved in the lack of evolutionary recovery: the strength of selection, the effect...

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

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

    2012-09-01

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

  15. A differential role for neuropeptides in acute and chronic adaptive responses to alcohol: behavioural and genetic analysis in Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Philippa Mitchell

    2010-05-01

    Full Text Available Prolonged alcohol consumption in humans followed by abstinence precipitates a withdrawal syndrome consisting of anxiety, agitation and in severe cases, seizures. Withdrawal is relieved by a low dose of alcohol, a negative reinforcement that contributes to alcohol dependency. This phenomenon of 'withdrawal relief' provides evidence of an ethanol-induced adaptation which resets the balance of signalling in neural circuits. We have used this as a criterion to distinguish between direct and indirect ethanol-induced adaptive behavioural responses in C. elegans with the goal of investigating the genetic basis of ethanol-induced neural plasticity. The paradigm employs a 'food race assay' which tests sensorimotor performance of animals acutely and chronically treated with ethanol. We describe a multifaceted C. elegans 'withdrawal syndrome'. One feature, decrease reversal frequency is not relieved by a low dose of ethanol and most likely results from an indirect adaptation to ethanol caused by inhibition of feeding and a food-deprived behavioural state. However another aspect, an aberrant behaviour consisting of spontaneous deep body bends, did show withdrawal relief and therefore we suggest this is the expression of ethanol-induced plasticity. The potassium channel, slo-1, which is a candidate ethanol effector in C. elegans, is not required for the responses described here. However a mutant deficient in neuropeptides, egl-3, is resistant to withdrawal (although it still exhibits acute responses to ethanol. This dependence on neuropeptides does not involve the NPY-like receptor npr-1, previously implicated in C. elegans ethanol withdrawal. Therefore other neuropeptide pathways mediate this effect. These data resonate with mammalian studies which report involvement of a number of neuropeptides in chronic responses to alcohol including corticotrophin-releasing-factor (CRF, opioids, tachykinins as well as NPY. This suggests an evolutionarily conserved role

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

    Science.gov (United States)

    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. Sucralose Induces Biochemical Responses in Daphnia magna

    Science.gov (United States)

    Eriksson Wiklund, Ann-Kristin; Adolfsson-Erici, Margaretha; Liewenborg, Birgitta; Gorokhova, Elena

    2014-01-01

    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. PMID:24699280

  18. Stability of sublethal acid stress adaptation and induced cross protection against lauric arginate in Listeria monocytogenes.

    Science.gov (United States)

    Shen, Qian; Soni, Kamlesh A; Nannapaneni, Ramakrishna

    2015-06-16

    The stability of acid stress adaptation in Listeria monocytogenes and its induced cross protection effect against GRAS (generally recognized as safe) antimicrobial compounds has never been investigated before. In the present study, the acid stress adaptation in L. monocytogenes was initially induced in pH 5.0 tryptic soy broth supplemented with 0.6% yeast extract (TSB-YE) at 37 °C. Subsequently, the stability of acid stress adaptation, which was defined as the capacity to maintain its acquired acid adaptation after induction in the absence of sublethal acid stress, was determined at 37 °C, 22 °C or 4 °C in broth and in different food substrates. Then, the acid stress adaptation induced cross protection against lauric arginate (LAE) and its stability was investigated in TSB-YE, milk and carrot juice. Our findings show that the acid stress adaptation was stable at 4 °C up to 24h but was reversed at 37 °C or 22 °C within 2h. In the cross protection assay with LAE, the acid stress adapted cells had approximately 2 log CFU/ml greater survival than non-adapted cells in broth at 22 °C or in milk and carrot juice at 4 °C. The acid adaptation induced cross protection against LAE in L. monocytogenes was reversible within 1h at 4 °C in the absence of sublethal acid stress. Our findings suggest that the stability of acid adaptation in L. monocytogenes under cold conditions should be taken into account when the risk analysis is performed during food processing. Copyright © 2015. Published by Elsevier B.V.

  19. Effects of surround suppression on response adaptation of V1 neurons to visual stimuli.

    Science.gov (United States)

    Li, Peng; Jin, Cai-Hong; Jiang, San; Li, Miao-Miao; Wang, Zi-Lu; Zhu, Hui; Chen, Cui-Yun; Hua, Tian-Miao

    2014-09-01

    The influence of intracortical inhibition on the response adaptation of visual cortical neurons remains in debate. To clarify this issue, in the present study the influence of surround suppression evoked through the local inhibitory interneurons on the adaptation effects of neurons in the primary visual cortex (V1) were observed. Moreover, the adaptations of V1 neurons to both the high-contrast visual stimuli presented in the classical receptive field (CRF) and to the costimulation presented in the CRF and the surrounding nonclassical receptive field (nCRF) were compared. The intensities of surround suppression were modulated with different sized grating stimuli. The results showed that the response adaptation of V1 neurons decreased significantly with the increase of surround suppression and this adaptation decrease was due to the reduction of the initial response of V1 neurons to visual stimuli. However, the plateau response during adaptation showed no significant changes. These findings indicate that the adaptation effects of V1 neurons may not be directly affected by surround suppression, but may be dynamically regulated by a negative feedback network and be finely adjusted by its initial spiking response to stimulus. This adaptive regulation is not only energy efficient for the central nervous system, but also beneficially acts to maintain the homeostasis of neuronal response to long-presenting visual signals.

  20. Color adaptation induced from linguistic description of color.

    Directory of Open Access Journals (Sweden)

    Liling Zheng

    Full Text Available Recent theories propose that language comprehension can influence perception at the low level of perceptual system. Here, we used an adaptation paradigm to test whether processing language caused color adaptation in the visual system. After prolonged exposure to a color linguistic context, which depicted red, green, or non-specific color scenes, participants immediately performed a color detection task, indicating whether they saw a green color square in the middle of a white screen or not. We found that participants were more likely to perceive the green color square after listening to discourses denoting red compared to discourses denoting green or conveying non-specific color information, revealing that language comprehension caused an adaptation aftereffect at the perceptual level. Therefore, semantic representation of color may have a common neural substrate with color perception. These results are in line with the simulation view of embodied language comprehension theory, which predicts that processing language reactivates the sensorimotor systems that are engaged during real experience.

  1. Pressure Induced Changes in Adaptive Immune Function in Belugas (Delphinapterus leucas; implications for dive physiology and health

    Directory of Open Access Journals (Sweden)

    Laura A Thompson

    2016-09-01

    Full Text Available Increased pressure, associated with diving, can alter cell function through several mechanisms and has been shown to impact immune functions performed by peripheral blood mononuclear cells (PBMC in humans. While marine mammals possess specific adaptations which protect them from dive related injury, it is unknown how their immune system is adapted to the challenges associated with diving. The purpose of this study was to measure PBMC activation (IL2R expression and Concanavalin A induced lymphocyte proliferation (BrdU incorporation in belugas following in vitro pressure exposures during baseline, Out of Water Examination (OWE and capture/release conditions. Beluga blood samples (n=4 were obtained from animals at the Mystic Aquarium and from free ranging animals in Alaska (n=9. Human blood samples (n=4 (Biological Specialty Corporation were run for comparison. In vivo catecholamines and cortisol were measured in belugas to characterize the neuroendocrine response. Comparison of cellular responses between controls and pressure exposed cells, between conditions in belugas, between belugas and humans as well as between dive profiles, were run using mixed generalized linear models (α=0.05. Cortisol was significantly higher in wild belugas and OWE samples as compared with baseline for aquarium animals. Both IL2R expression and proliferation displayed significant pressure induced changes, and these responses varied between conditions in belugas. Both belugas and humans displayed increased IL2R expression, while lymphocyte proliferation decreased for aquarium animals and increased for humans and wild belugas. Results suggest beluga PBMC function is altered during diving and changes may represent dive adaptation as the response differs from humans, a non-dive adapted mammal. In addition, characteristics of a dive (i.e., duration, depth as well as neuroendocrine activity can alter the response of beluga cells, potentially impacting the ability of animals

  2. The adaptative response of jaw muscles to varying functional demands

    NARCIS (Netherlands)

    Grünheid, T.; Langenbach, G.E.J.; Korfage, J.A.M.; Zentner, A.; van Eijden, T.M.G.J.

    2009-01-01

    Jaw muscles are versatile entities that are able to adapt their anatomical characteristics, such as size, cross-sectional area, and fibre properties, to altered functional demands. The dynamic nature of muscle fibres allows them to change their phenotype to optimize the required contractile function

  3. Adaptive responses to environmental changes in Lake Victoria cichlids

    NARCIS (Netherlands)

    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.

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

    DEFF Research Database (Denmark)

    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...

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

    Science.gov (United States)

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

    2010-01-15

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

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

    Science.gov (United States)

    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. © The Author 2015. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please email: journals.permissions@oup.com.

  7. Adaptive Feeding behavior and functional responses in pelagic copepods

    DEFF Research Database (Denmark)

    Kiørboe, Thomas; Saiz, Enrico; Tiselius, Peter

    2018-01-01

    Zooplankton may modify their feeding behavior in response to prey availability and presence of predators with implications to populations of both predators and prey. Optimal foraging theory predicts that such responses result in a type II functional response for passive foragers and a type III re...

  8. The role of the commensal microbiota in adaptive and maladaptive stressor-induced immunomodulation.

    Science.gov (United States)

    Mackos, Amy R; Maltz, Ross; Bailey, Michael T

    2017-02-01

    Over the past decade, it has become increasingly evident that there are extensive bidirectional interactions between the body and its microbiota. These interactions are evident during stressful periods, where it is recognized that commensal microbiota community structure is significantly changed. Many different stressors, ranging from early life stressors to stressors administered during adulthood, lead to significant, community-wide differences in the microbiota. The mechanisms through which this occurs are not yet known, but it is known that commensal microbes can recognize, and respond to, mammalian hormones and neurotransmitters, including those that are involved with the physiological response to stressful stimuli. In addition, the physiological stress response also changes many aspects of gastrointestinal physiology that can impact microbial community composition. Thus, there are many routes through which microbial community composition might be disrupted during stressful periods. The implications of these disruptions in commensal microbial communities for host health are still not well understood, but the commensal microbiota have been linked to stressor-induced immunopotentiation. The role of the microbiota in stressor-induced immunopotentiation can be adaptive, such as when these microbes stimulate innate defenses against bacterial infection. However, the commensal microbiota can also lead to maladaptive immune responses during stressor-exposure. This is evident in animal models of colonic inflammation where stressor exposure increases the inflammation through mechanisms involving the microbiota. It is likely that during stressor exposure, immune cell functioning is regulated by combined effects of both neurotransmitters/hormones and commensal microbes. Defining this regulation should be a focus of future studies. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Exercise-induced metacarpophalangeal joint adaptation in the Thoroughbred racehorse

    Science.gov (United States)

    Muir, P; Peterson, A L; Sample, S J; Scollay, M C; Markel, M D; Kalscheur, V L

    2008-01-01

    Repetitive bone injury and development of stress fracture is a common problem in humans and animals. The Thoroughbred racehorse is a model in which adaptive failure and associated development of stress fracture is common. We performed a histologic study of the distal end of the third metacarpal bone in two groups of horses: young Thoroughbreds that were actively racing (n = 10) and a group of non-athletic horses (n = 8). The purpose of this study was to determine whether development of articular microcracks was associated with specific alterations to subchondral plate osteocytes. Morphometric measurements were made in five regions of the joint surface: lateral condyle, lateral condylar groove, sagittal ridge, medial condylar groove, and medial condyle. The following variables were quantified: hyaline cartilage width; calcified cartilage width; the number of tidemarks; microcrack density at the articular surface; blood vessel density entering articular cartilage; the presence of atypical bone matrix in the subchondral plate; bone volume fraction; and osteocyte density. Adaptation of articular cartilage was similar in both groups of horses. Vascularization of articular cartilage was increased in the group of non-athletic horses. Microcracks, which typically had an oblique orientation to the joint surface, were co-localized with blood vessels, and resorption spaces. Microcracking was increased in the condylar grooves of athletic horses compared with the other joint regions and was also increased compared with the condylar groove regions of non-athletic horses. Coalescence of microcracks also led to development of an intracortical articular condylar stress fracture in some joints and targeted remodeling of affected subchondral plate. The subchondral plate of the condyles in athletic horses was sclerotic, and contained atypically stained bone matrix with increased numbers of osteocytes with atypical morphology. However, osteocyte numbers were not significantly different

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

    Energy Technology Data Exchange (ETDEWEB)

    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) =.

  11. Energy Sector Adaptation in Response to Water Scarcity

    Science.gov (United States)

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

    2015-12-01

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

  12. Adaptation response surfaces for managing wheat under perturbed climate and CO2 in a Mediterranean environment

    DEFF Research Database (Denmark)

    Ruiz-Ramos, M.; Ferrise, Roberto; Rodríguez, A

    2018-01-01

    Adaptation of crops to climate change has to be addressed locally due to the variability of soil, climate and the specific socio-economic settings influencing farm management decisions. Adaptation of rainfed cropping systems in the Mediterranean is especially challenging due to the projected...... decline in precipitation in the coming decades, which will increase the risk of droughts. Methods that can help explore uncertainties in climate projections and crop modelling, such as impact response surfaces (IRSs) and ensemble modelling, can then be valuable for identifying effective adaptations. Here......, a combination of adaptations for dealing with climate change demonstrated that effective adaptation is possible at Lleida. Combinations based on a cultivar without vernalization requirements showed good and wide adaptation potential. Few combined adaptation options performed well under rainfed conditions...

  13. Effects of surround suppression on response adaptation of V1 neurons to visual stimuli

    OpenAIRE

    LI, Peng; JIN, Cai-Hong; JIANG, San; LI, Miao-Miao; WANG, Zi-Lu; ZHU, Hui; CHEN, Cui-Yun; HUA, Tian-Miao

    2014-01-01

    The influence of intracortical inhibition on the response adaptation of visual cortical neurons remains in debate. To clarify this issue, in the present study the influence of surround suppression evoked through the local inhibitory interneurons on the adaptation effects of neurons in the primary visual cortex (V1) were observed. Moreover, the adaptations of V1 neurons to both the high-contrast visual stimuli presented in the classical receptive field (CRF) and to the costimulation presented ...

  14. ADAPTIVE RESPONSE OF RICE MARKETS TO CLIMATE IMPACTS IN INDONESIA

    OpenAIRE

    KAWANISHI, Masato; MIMURA, Nobuo

    2014-01-01

    Van der Eng (2009) assessed how rice markets responded to variations in rainfall during1935-40 in Java, Indonesia. The study finds that, while the unusually low rainfalls in El Nino years causeddeficiencies in paddy production in some locations, they did not have a negative effect on variations in riceprices across Java. The finding indicates that, if well integrated, the market is able to adapt to climate stressby providing incentives that direct flows of rice from surplus to deficit areas. ...

  15. Hepatic adaptations to maintain metabolic homeostasis in response to fasting and refeeding in mice.

    Science.gov (United States)

    Geisler, C E; Hepler, C; Higgins, M R; Renquist, B J

    2016-01-01

    The increased incidence of obesity and associated metabolic diseases has driven research focused on genetically or pharmacologically alleviating metabolic dysfunction. These studies employ a range of fasting-refeeding models including 4-24 h fasts, "overnight" fasts, or meal feeding. Still, we lack literature that describes the physiologically relevant adaptations that accompany changes in the duration of fasting and re-feeding. Since the liver is central to whole body metabolic homeostasis, we investigated the timing of the fast-induced shift toward glycogenolysis, gluconeogenesis, and ketogenesis and the meal-induced switch toward glycogenesis and away from ketogenesis. Twelve to fourteen week old male C57BL/6J mice were fasted for 0, 4, 8, 12, or 16 h and sacrificed 4 h after lights on. In a second study, designed to understand the response to a meal, we gave fasted mice access to feed for 1 or 2 h before sacrifice. We analyzed the data using mixed model analysis of variance. Fasting initiated robust metabolic shifts, evidenced by changes in serum glucose, non-esterified fatty acids (NEFAs), triacylglycerol, and β-OH butyrate, as well as, liver triacylglycerol, non-esterified fatty acid, and glycogen content. Glycogenolysis is the primary source to maintain serum glucose during the first 8 h of fasting, while de novo gluconeogenesis is the primary source thereafter. The increase in serum β-OH butyrate results from increased enzymatic capacity for fatty acid flux through β-oxidation and shunting of acetyl-CoA toward ketone body synthesis (increased CPT1 (Carnitine Palmitoyltransferase 1) and HMGCS2 (3-Hydroxy-3-Methylglutaryl-CoA Synthase 2) expression, respectively). In opposition to the relatively slow metabolic adaptation to fasting, feeding of a meal results in rapid metabolic changes including full depression of serum β-OH butyrate and NEFAs within an hour. Herein, we provide a detailed description of timing of the metabolic adaptations in response

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

    Science.gov (United States)

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

    2010-10-01

    Neuromagnetic evoked fields were recorded to compare the adaptation of the primary somatosensory cortex (SI) response to tactile stimuli delivered to the glabrous skin at the fingertips of the first three digits (condition 1) and between midline upper and lower lips (condition 2). The stimulation paradigm allowed to characterize the response adaptation in the presence of functional integration of tactile stimuli from adjacent skin areas in each condition. At each stimulation site, cutaneous stimuli (50 ms duration) were delivered in three runs, using trains of 6 pulses with regular stimulus onset asynchrony (SOA). The pulses were separated by SOAs of 500 ms, 250 ms or 125 ms in each run, respectively, while the inter-train interval was fixed (5s) across runs. The evoked activity in SI (contralateral to the stimulated hand, and bilaterally for lips stimulation) was characterized from the best-fit dipoles of the response component peaking around 70 ms for the hand stimulation, and 8 ms earlier (on average) for the lips stimulation. The SOA-dependent long-term adaptation effects were assessed from the change in the amplitude of the responses to the first stimulus in each train. The short-term adaptation was characterized by the lifetime of an exponentially saturating model function fitted to the set of suppression ratios of the second relative to the first SI response in each train. Our results indicate: 1) the presence of a rate-dependent long-term adaptation effect induced only by the tactile stimulation of the digits; and 2) shorter recovery lifetimes for the digits compared with the lips stimulation. Copyright 2010 Elsevier Inc. All rights reserved.

  17. Adaptive removal of gradients-induced artefacts on ECG in MRI: a performance analysis of RLS filtering.

    Science.gov (United States)

    Sansone, Mario; Mirarchi, Luciano; Bracale, Marcello

    2010-05-01

    One of the main vital signs used in patient monitoring during Magnetic Resonance Imaging (MRI) is Electro-Cardio-Gram (ECG). Unfortunately, magnetic fields gradients induce artefacts which severely affect ECG quality. Adaptive Noise Cancelling (ANC) is one of the preferred techniques for artefact removal. ANC involves the adaptive estimation of the impulse response of the system constituted by the MRI equipment, the patient and the ECG recording device. Least Mean Square (LMS) adaptive filtering has been traditionally employed because of its simplicity: anyway, it requires the choice of a step-size parameter, whose proper value for the specific application must be estimated case by case: an improper choice could yield slow convergence and unsatisfactory behaviour. Recursive Least Square (RLS) algorithm has, potentially, faster convergence while not requiring any parameter. As far as the authors' knowledge, there is no systematic analysis of performances of RLS in this scenario. In this study we evaluated the performance of RLS for adaptive removal of artefacts induced by magnetic field gradients on ECG in MRI, in terms of efficacy of suppression. Tests have been made on real signals, acquired via an expressly developed system. A comparison with LMS was made on the basis of opportune performance indices. Results indicate that RLS is superior to LMS in several respects.

  18. Direct Adaptive Rejection of Vortex-Induced Disturbances for a Powered SPAR Platform

    Science.gov (United States)

    VanZwieten, Tannen S.; Balas, Mark J.; VanZwieten, James H.; Driscoll, Frederick R.

    2009-01-01

    The Rapidly Deployable Stable Platform (RDSP) is a novel vessel designed to be a reconfigurable, stable at-sea platform. It consists of a detachable catamaran and spar, performing missions with the spar extending vertically below the catamaran and hoisting it completely out of the water. Multiple thrusters located along the spar allow it to be actively controlled in this configuration. A controller is presented in this work that uses an adaptive feedback algorithm in conjunction with Direct Adaptive Disturbance Rejection (DADR) to mitigate persistent, vortex-induced disturbances. Given the frequency of a disturbance, the nominal DADR scheme adaptively compensates for its unknown amplitude and phase. This algorithm is extended to adapt to a disturbance frequency that is only coarsely known by including a Phase Locked Loop (PLL). The PLL improves the frequency estimate on-line, allowing the modified controller to reduce vortex-induced motions by more than 95% using achievable thrust inputs.

  19. Region-Specific Suppression of Hypothalamic Responses to Insulin To Adapt to Elevated Maternal Insulin Secretion During Pregnancy.

    Science.gov (United States)

    Ladyman, Sharon R; Grattan, David R

    2017-12-01

    As part of the adaptation of maternal glucose regulation during pregnancy to ensure glucose provision to the fetus, maternal insulin concentrations become elevated. However, increased central actions of insulin, such as suppression of appetite, would be maladaptive during pregnancy. We hypothesized that central nervous system targets of insulin become less responsive during pregnancy to prevent overstimulation by the increased circulating insulin concentrations. To test this hypothesis, we have measured insulin-induced phosphorylation of Akt (pAkt) in specific hypothalamic nuclei as an index of hypothalamic insulin responsiveness. Despite higher endogenous insulin concentrations following feeding, arcuate nucleus pAkt levels were significantly lower in the pregnant group compared with the nonpregnant group. In response to an intracerebroventricular injection of insulin, insulin-induced pAkt was significantly reduced in the arcuate nucleus and ventromedial nucleus of pregnant rats compared with nonpregnant rats. Similar levels of insulin receptor β and PTEN, a negative regulator of the phosphoinositide 3-kinase/Akt pathway, were detected in hypothalamic areas of nonpregnant and pregnant rats. In the ventromedial nucleus, however, levels of phosphorylated PTEN were significantly lower in pregnancy, suggesting that reduced inactivation of PTEN may contribute to the attenuated insulin signaling in this area during pregnancy. In conclusion, these results demonstrate region-specific changes in responsiveness to insulin in the hypothalamus during pregnancy that may represent an adaptive response to minimize the impact of elevated circulating insulin on the maternal brain. Copyright © 2017 Endocrine Society.

  20. When not every response to climate change is a good one: identifying principles for sustainable adaptation

    CSIR Research Space (South Africa)

    Eriksen, S

    2011-01-01

    Full Text Available ; third, integrate local knowledge into adaptation responses; and fourth, consider potential feedbacks between local and global processes. We argue that fundamental societal transformations are required in order to achieve sustainable development pathways...

  1. Predicting adaptation to parenthood: The role of responsiveness, gratitude, and trust

    NARCIS (Netherlands)

    Kuile, H. ter; Kluwer, E.S.; Finkenauer, C.; Lippe, A.G. van der

    2017-01-01

    The influence of positive relationship processes, specifically perceived responsiveness, felt gratitude, and felt trust, on perceived adaptation to parenthood was investigated. It was hypothesized that both higher initial levels prior to pregnancy as well as increases over time in perceived

  2. Contextualizing Individual Competencies for Managing the Corporate Social Responsibility Adaptation Process

    NARCIS (Netherlands)

    Osagie, E.R.; Wesselink, R.; Blok, V.; Mulder, M.

    2016-01-01

    Companies committed to corporate social responsibility (CSR) should ensure that their managers possess the appropriate competencies to effectively manage the CSR adaptation process. The literature provides insights into the individual competencies these managers need but fails to prioritize them and

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

    Science.gov (United States)

    Inoue, Masayo; Kaneko, Kunihiko

    2013-04-01

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

  4. Adaptive responses of living cells towards low-doses of radiation. Induction of endogenous antioxidant system and its applicable possibility for treatment of diseases

    International Nuclear Information System (INIS)

    Kojima, Shuji; Yamaoka, Kiyonori

    1999-01-01

    Bacteria and mammalian cells show an adaptive response to oxidative stress. Pre-treatment with small amounts of oxidant induces resistance to the subsequent, otherwise lethal, doses of oxidant. Previous studies have shown that this adaptive response involves the induction of superoxide dismutase (SOD), glutathione peroxidase (GPX), metallothionein, heat shock proteins, and other factors. The toxicity of ionizing radiation, particularly at low doses, to living cells, is thought to be due to reactive oxygen species (ROS) formation. Thus, adaptive responses to low doses of ionizing radiation and to oxidants are likely to be similar. In this paper, the induction of endogenous glutathione (GSH) together with antioxidant enzymes induced by low-dose radiation was reviewed. Furthermore, the applicable possibility of this efficacy for the prevention of and/or therapy of various reactive oxygen species (ROS)-related diseases including Parkinson's diseases, aging, and diabetes, was discussed. (author)

  5. The immunoreceptor adapter protein DAP12 suppresses B lymphocyte?driven adaptive immune responses

    OpenAIRE

    Nakano-Yokomizo, Takako; Tahara-Hanaoka, Satoko; Nakahashi-Oda, Chigusa; Nabekura, Tsukasa; Tchao, Nadia K.; Kadosaki, Momoko; Totsuka, Naoya; Kurita, Naoki; Nakamagoe, Kiyotaka; Tamaoka, Akira; Takai, Toshiyuki; Yasui, Teruhito; Kikutani, Hitoshi; Honda, Shin-ichiro; Shibuya, Kazuko

    2011-01-01

    DAP12, an immunoreceptor tyrosine-based activation motif?bearing adapter protein, is involved in innate immunity mediated by natural killer cells and myeloid cells. We show that DAP12-deficient mouse B cells and B cells from a patient with Nasu-Hakola disease, a recessive genetic disorder resulting from loss of DAP12, showed enhanced proliferation after stimulation with anti-IgM or CpG. Myeloid-associated immunoglobulin-like receptor (MAIR) II (Cd300d) is a DAP12-associated immune receptor. L...

  6. Thioredoxin binding protein-2 mediates metabolic adaptation in response to lipopolysaccharide in vivo.

    OpenAIRE

    Oka, Shin-ichi; Liu, Wenrui; Yoshihara, Eiji; Ahsan, Md Kaimul; Ramos, Dorys Adriana Lopez; Son, Aoi; Okuyama, Hiroaki; Zhang, Li; Masutani, Hiroshi; Nakamura, Hajime; Yodoi, Junji

    2010-01-01

    Endotoxin triggers a reorganization of the energy metabolic pathway, including the promotion of fatty acid utilization to adapt to a high energy demand during endotoxemia. However, the factors responsible for the metabolic adaptation and characteristic pathologies resulting from defective utilization fatty acids during endotoxin response have not been fully clarified. The thioredoxin binding protein-2 (TBP-2) knockout (TBP-2) mouse is an animal model of fatty acid oxidation disorder. The aim ...

  7. Understanding How Space Travel Affects Blood Vessels: Arterial Remodeling and Functional Adaptations Induced by Microgravity

    Science.gov (United States)

    Delp, Michael; Vasques, Marilyn; Aquilina, Rudy (Technical Monitor)

    2002-01-01

    Ever rise quickly from the couch to get something from the kitchen and suddenly feel dizzy? With a low heart rate and relaxed muscles, the cardiovascular system does not immediately provide the resistance necessary to keep enough blood going to your head. Gravity wins, at least for a short time, before your heart and blood vessels can respond to the sudden change in position and correct the situation. Actually, the human cardiovascular system is quite well adapted to the constant gravitational force of the Earth. When standing, vessels in the legs constrict to prevent blood from collecting in the lower extremities. In the space environment, the usual head-to-foot blood pressure and tissue fluid gradients that exist during the upright posture on Earth are removed. The subsequent shift in fluids from the lower to the upper portions of the body triggers adaptations within the cardiovascular system to accommodate the new pressure and fluid gradients. In animal models that simulate microgravity, the vessels in the head become more robust while those in the lower limbs become thin and lax. Similar changes may also occur in humans during spaceflight and while these adaptations are appropriate for a microgravity environment, they can cause problems when the astronauts return to Earth or perhaps another planet. Astronauts often develop orthostatic intolerance which means they become dizzy or faint when standing upright. This dizziness can persist for a number of days making routine activities difficult. In an effort to understand the physiological details of these cardiovascular adaptations, Dr. Michael Delp at Texas A&M University, uses the rat as a model for his studies. For the experiment flown on STS-107, he will test the hypothesis that blood vessels in the rats' hindlimbs become thinner, weaker, and constrict less in response to pressure changes and to chemical signals when exposed to microgravity. In addition, he will test the hypothesis that arteries in the brain

  8. Differential Roles of Hydrogen Peroxide in Adaptive and Inflammatory Gene Expression Induced by Exposure of Human Airway Epithelial Cells to Zn2+

    Science.gov (United States)

    Oxidant stress is believed to play an important role in particulate matter (PM)–mediated toxicity in the respiratory tract. Zinc (Zn2+) is a ubiquitous component of PM that has been shown to induce adverse responses such as inflammatory and adaptive gene expression in airway epit...

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

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

    2012-01-01

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

  11. Adaptive response to 2 low doses of X-rays in human blood lymphocytes

    International Nuclear Information System (INIS)

    Fan, S.; Vijayalaxmi; Burkart, W.; Mindek, G.

    1990-01-01

    Human peripheral blood lymphocytes exposed to a single adaptive dose of 1 cGy X-rays or 2 adaptive doses, each of 1 cGy, were found to be equally resistant to the induction of chromosome damage by subsequent challenge with a high dose of 1 Gy X-rays, as compared to cells that were not pre-exposed. They responded with a significantly reduced incidence of chromatid and isochromatid breaks. These results indicate the presence of an inducible chromosomal repair mechanism in human blood lymphocytes and confirm the observations made by earlier investigators. The incidence of chromosome damage was found to be similar in the lymphocytes pre-exposed to a single or 2 adaptive doses, suggesting that, under the conditions tested, the second adaptive dose did not offer any additional protection against the chromosome damage induced by the challenge dose. (author). 14 refs.; 1 tab

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

    International Nuclear Information System (INIS)

    Sasaki, Masao S.

    2010-01-01

    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

  13. Dietary methionine restriction in mice elicits an adaptive cardiovascular response to hyperhomocysteinemia.

    Science.gov (United States)

    Ables, Gene P; Ouattara, Amadou; Hampton, Thomas G; Cooke, Diana; Perodin, Frantz; Augie, Ines; Orentreich, David S

    2015-03-06

    Dietary methionine restriction (MR) in rodents increased lifespan despite higher heart-to-body weight ratio (w/w) and hyperhomocysteinemia, which are symptoms associated with increased risk for cardiovascular disease. We investigated this paradoxical effect of MR on cardiac function using young, old, and apolipoprotein E-deficient (ApoE-KO) mice. Indeed, MR animals exhibited higher heart-to-body weight ratio (w/w) and hyperhomocysteinemia with a molecular pattern consistent with cardiac stress while maintaining the integrity of cardiac structure. Baseline cardiac function, which was measured by non-invasive electrocardiography (ECG), showed that young MR mice had prolonged QRS intervals compared with control-fed (CF) mice, whereas old and ApoE-KO mice showed similar results for both groups. Following β-adrenergic challenge, responses of MR mice were either similar or attenuated compared with CF mice. Cardiac contractility, which was measured by isolated heart retrograde perfusion, was similar in both groups of old mice. Finally, the MR diet induced secretion of cardioprotective hormones, adiponectin and fibroblast growth factor 21 (FGF21), in MR mice with concomitant alterations in cardiac metabolic molecular signatures. Our findings demonstrate that MR diet does not alter cardiac function in mice despite the presence of hyperhomocysteinemia because of the adaptive responses of increased adiponectin and FGF21 levels.

  14. Plant's adaptive response under UV-B-radiation influence

    International Nuclear Information System (INIS)

    Danil'chenko, O.A.; Grodzinskij, D.M.

    2002-01-01

    Reduction of ozone layer, owing to anthropogenic contamination of an atmosphere results in increase of intensity of UV-radiation and shift of its spectrum in the short-wave side that causes strengthening of various biological effects of irradiation. Consequences of these processes may include increase of injuring of plants and decrease of productivity of agricultural crops to increased UV levels. The important significance in the plant's adaptation to different unfavorable factors has the plant's radioadaptive answer. It has been shown that radioadaptation of plants occurred not only after irradiation with g-radiation in low doses but after UV-rays action . Reaction of radioadaptation it seems to be nonspecific phenomenon in relation to type radiations

  15. Adaptation

    International Development Research Centre (IDRC) Digital Library (Canada)

    . Dar es Salaam. Durban. Bloemfontein. Antananarivo. Cape Town. Ifrane ... program strategy. A number of CCAA-supported projects have relevance to other important adaptation-related themes such as disaster preparedness and climate.

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

    Directory of Open Access Journals (Sweden)

    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.

  17. Short-Term Adaptation of Conditioned Fear Responses Through Endocannabinoid Signaling in the Central Amygdala

    Science.gov (United States)

    Kamprath, Kornelia; Romo-Parra, Hector; Häring, Martin; Gaburro, Stefano; Doengi, Michael; Lutz, Beat; Pape, Hans-Christian

    2011-01-01

    The cannabinoid receptor type 1 (CB1) and the central nucleus of the amygdala (CeA) are both known to have crucial roles in the processing of fear and anxiety, whereby they appear to be especially involved in the control of fear states. However, in contrast to many other brain regions including the cortical subregions of the amygdala, the existence of CB1 in the CeA remains enigmatic. In this study we show that CB1 is expressed in the CeA of mice and that CB1 in the CeA mediates short-term synaptic plasticity, namely depolarization-induced suppression of excitation (DSE) and inhibition (DSI). Moreover, the CB1 antagonist AM251 increased both excitatory and inhibitory postsynaptic responses in CeA neurons. Local application of AM251 in the CeA in vivo resulted in an acutely increased fear response in an auditory fear conditioning paradigm. Upon application of AM251 in the basolateral nucleus of the amygdala (BLA) in an otherwise identical protocol, no such acute behavioral effects were detected, but CB1 blockade resulted in increased fear responses during tone exposures on the subsequent days. Moreover, we observed that the efficacy of DSE and DSI in the CeA was increased on the day following fear conditioning, indicating that a single tone-shock pairing resulted in changes in endocannabinoid signaling in the CeA. Taken together, our data show the existence of CB1 proteins in the CeA, and their critical role for ensuring short-term adaptation of responses to fearful events, thereby suggesting a potential therapeutic target to accompany habituation-based therapies of post-traumatic symptoms. PMID:20980994

  18. Sorbitol treatment extends lifespan and induces the osmotic stress response in Caenorhabditis elegans

    Directory of Open Access Journals (Sweden)

    Devon eChandler-Brown

    2015-10-01

    Full Text Available The response to osmotic stress is a highly conserved process for adapting to changing environmental conditions. Prior studies have shown that hyperosmolarity by addition of sorbitol to the growth medium is sufficient to increase both chronological and replicative lifespan in the budding yeast, Saccharomyces cerevisiae. Here we report a similar phenomenon in the nematode Caenorhabditis elegans. Addition of sorbitol to the nematode growth medium induces an adaptive osmotic response and increases C. elegans lifespan by about 35%. Lifespan extension from 5% sorbitol behaves similarly to dietary restriction in a variety of genetic backgrounds, increasing lifespan additively with mutation of daf-2(e1370 and independently of daf-16(mu86, sir-2.1(ok434, aak-2(ok524, and hif-1(ia04. Dietary restriction by bacterial deprivation or mutation of eat-2(ad1113 fails to further extend lifespan in the presence of 5% sorbitol. Two mutants with constitutive activation of the osmotic response, osm-5(p813 and osm-7(n1515, were found to be long-lived, and lifespan extension from sorbitol required the glycerol biosynthetic enzymes GPDH-1 and GPDH-2. Taken together, these observations demonstrate that exposure to sorbitol at levels sufficient to induce an adaptive osmotic response extends lifespan in worms and define the osmotic stress response pathway as a longevity pathway conserved between yeast and nematodes.

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

    DEFF Research Database (Denmark)

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

    2009-01-01

    in the 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...

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

    DEFF Research Database (Denmark)

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

    2012-01-01

    identification of metabolic non-responders in order to intensify treatment to improve survival. Other studies aim at reducing toxicity without adversely affecting cure rates by safely de-escalating therapy in metabolic responders. In solid tumors the first PET response-adjusted treatment trials have been...

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

    Science.gov (United States)

    Jianbang Gan; Adam Jarrett; Cassandra Johnson Gaither

    2015-01-01

    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...

  2. Subversion of innate and adaptive immune responses by Toxoplasma gondii.

    Science.gov (United States)

    Lang, Christine; Gross, Uwe; Lüder, Carsten G K

    2007-01-01

    The intracellular apicomplexan parasite Toxoplasma gondii is able to survive and persist in immunocompetent intermediate hosts for the host's life span. This is despite the induction of a vigorous humoral and -- more importantly -- cell-mediated immune response during infection. In order to establish and maintain such chronic infections, however, T. gondii has evolved multiple strategies to avoid or to interfere with potentially efficient anti-parasitic immune responses of the host. Such immune evasion includes (1) indirect mechanisms by altering the expression and secretion of immunomodulatory cytokines or by altering the viability of immune cells and (2) direct mechanisms by establishing a lifestyle within a suitable intracellular niche and by interference with intracellular signaling cascades, thereby abolishing a number of antimicrobial effector mechanisms of the host. Despite the parasite's ability to interfere successfully with the host's efforts to eradicate the infection, the immune response is, however, not completely abrogated but is rather partially diminished after infection. T. gondii thus keeps a delicate balance between induction and suppression of the host's immune response in order to guarantee the survival of the host as a safe harbor for parasite development and to allow its transmission to the definitive host.

  3. Accelerated ion irradiation induced retinal response

    International Nuclear Information System (INIS)

    Mizota, Atsushi; Miyahara, Nobuyuki; Nojima, Kumie

    2006-01-01

    The purpose of this study is to investigate the retinal response to accelerated carbon ion irradiation. Eight-week-old rats were used in this experiment. Under anesthesia, a positive electrode was attached on the cornea and a negative electrode was attached on the nasal bone. Carbon ion was irradiated though collimator with 2 mm φ and 5 mm φ. Carbon ion was irradiated without absorber. Positive responses were recorded with irradiation area of 5 mm φ, but with 2 mm φ, no remarkable responses were recorded. We think this corneal positive responses were originated from electrode itself and photo baric phenomenon may cause these responses. (author)

  4. Investigating the adaptive immune response in influenza and secondary bacterial pneumonia and nanoparticle based therapeutic delivery

    Science.gov (United States)

    Chakravarthy, Krishnan V.

    In early 2000, influenza and its associated complications were the 7 th leading cause of death in the United States[1-4]. As of today, this major health problem has become even more of a concern, with the possibility of a potentially devastating avian flu (H5N1) or swine flu pandemic (H1N1). According to the Centers for Disease Control (CDC), over 10 countries have reported transmission of influenza A (H5N1) virus to humans as of June 2006 [5]. In response to this growing concern, the United States pledged over $334 million dollars in international aid for battling influenza[1-4]. The major flu pandemic of the early 1900's provided the first evidence that secondary bacterial pneumonia (not primary viral pneumonia) was the major cause of death in both community and hospital-based settings. Secondary bacterial infections currently account for 35-40% mortality following a primary influenza viral infection [1, 6]. The first component of this work addresses the immunological mechanisms that predispose patients to secondary bacterial infections following a primary influenza viral infection. By assessing host immune responses through various immune-modulatory tools, such as use of volatile anesthetics (i.e. halothane) and Apilimod/STA-5326 (an IL-12/Il-23 transcription blocker), we provide experimental evidence that demonstrates that the overactive adaptive Th1 immune response is critical in mediating increased susceptibility to secondary bacterial infections. We also present data that shows that suppressing the adaptive Th1 immune response enhances innate immunity, specifically in alveolar macrophages, by favoring a pro anti-bacterial phenotype. The second component of this work addresses the use of nanotechnology to deliver therapeutic modalities that affect the primary viral and associated secondary bacterial infections post influenza. First, we used surface functionalized quantum dots for selective targeting of lung alveolar macrophages both in vitro and in vivo

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

    Directory of Open Access Journals (Sweden)

    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.

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

    International Nuclear Information System (INIS)

    Wojewodzka, M.; Gradzka, I.; Buraczewska, I.

    2000-01-01

    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)

  7. Altered G{sub 1} checkpoint control determines adaptive survival responses to ionizing radiation

    Energy Technology Data Exchange (ETDEWEB)

    Boothman, David A.; Meyers, Mark; Odegaard, Eric; Wang, Meizhi [Department of Human Oncology, University of Wisconsin-Madison, Madison, WI (United States)

    1996-11-04

    Adaptive survival responses (ASRs) are observed when cells become more resistant to a high dose of a cytotoxic agent after repeated low dose exposures to that agent or another genotoxic agent. Confluent (G{sub 0}/G{sub 1}) human normal (GM2936B, GM2937A, AG2603, IMR-90), cancer-prone (XPV2359), and neoplastic (U1-Mel, HEp-2, HTB-152) cells were primed with repeated low doses of X-rays (ranging from 0.05-10 cGy/day for 4 days), then challenged with a high dose (290-450 cGy) on day 5. U1-Mel and HEp-2 cells showed greater than 2-fold transient survival enhancement when primed with 1-10 cGy. ASRs in U1-Mel or HEp-2 cells were blocked by cycloheximide or actinomycin D. Increases in cyclins A and D1 mRNAs were noted in primed compared to unirradiated U1-Mel and HEp-2 cells; however, only cyclin A protein levels increased. Cyclin D1 and proliferating cell nuclear antigen (PCNA) protein levels were constitutively elevated in HEp-2 and U1-Mel cells, compared to the other human normal and neoplastic cells examined, and were not altered by low or high doses of radiation. Low dose primed U1-Mel cells entered S-phase 4-6 h faster than unprimed U1-Mel cells upon low-density replating. Similar responses in terms of survival recovery, transcript and protein induction, and altered cell cycle regulation were not observed in the other human normal, cancer-prone or neoplastic cells examined. We hypothesize that only certain human cells can adapt to ionizing radiation by progressing to a point later in G{sub 1} (the A point) where DNA repair processes and radioresistance can be induced. ASRs in human cells correlated well with constitutively elevated levels of PCNA and cyclin D1, as well as inducibility of cyclin A. We propose that a protein complex composed of cyclin D1, PCNA, and possibly cyclin A may play a role in cell cycle regulation and DNA repair, which determine ASRs in human cells.

  8. Altered G1 checkpoint control determines adaptive survival responses to ionizing radiation

    International Nuclear Information System (INIS)

    Boothman, David A.; Meyers, Mark; Odegaard, Eric; Wang, Meizhi

    1996-01-01

    Adaptive survival responses (ASRs) are observed when cells become more resistant to a high dose of a cytotoxic agent after repeated low dose exposures to that agent or another genotoxic agent. Confluent (G 0 /G 1 ) human normal (GM2936B, GM2937A, AG2603, IMR-90), cancer-prone (XPV2359), and neoplastic (U1-Mel, HEp-2, HTB-152) cells were primed with repeated low doses of X-rays (ranging from 0.05-10 cGy/day for 4 days), then challenged with a high dose (290-450 cGy) on day 5. U1-Mel and HEp-2 cells showed greater than 2-fold transient survival enhancement when primed with 1-10 cGy. ASRs in U1-Mel or HEp-2 cells were blocked by cycloheximide or actinomycin D. Increases in cyclins A and D1 mRNAs were noted in primed compared to unirradiated U1-Mel and HEp-2 cells; however, only cyclin A protein levels increased. Cyclin D1 and proliferating cell nuclear antigen (PCNA) protein levels were constitutively elevated in HEp-2 and U1-Mel cells, compared to the other human normal and neoplastic cells examined, and were not altered by low or high doses of radiation. Low dose primed U1-Mel cells entered S-phase 4-6 h faster than unprimed U1-Mel cells upon low-density replating. Similar responses in terms of survival recovery, transcript and protein induction, and altered cell cycle regulation were not observed in the other human normal, cancer-prone or neoplastic cells examined. We hypothesize that only certain human cells can adapt to ionizing radiation by progressing to a point later in G 1 (the A point) where DNA repair processes and radioresistance can be induced. ASRs in human cells correlated well with constitutively elevated levels of PCNA and cyclin D1, as well as inducibility of cyclin A. We propose that a protein complex composed of cyclin D1, PCNA, and possibly cyclin A may play a role in cell cycle regulation and DNA repair, which determine ASRs in human cells

  9. Adaptive Neuroplastic Responses in Early and Late Hemispherectomized Monkeys

    Directory of Open Access Journals (Sweden)

    Mark W. Burke

    2012-01-01

    Full Text Available Behavioural recovery in children who undergo medically required hemispherectomy showcase the remarkable ability of the cerebral cortex to adapt and reorganize following insult early in life. Case study data suggest that lesions sustained early in childhood lead to better recovery compared to those that occur later in life. In these children, it is possible that neural reorganization had begun prior to surgery but was masked by the dysfunctional hemisphere. The degree of neural reorganization has been difficult to study systematically in human infants. Here we present a 20-year culmination of data on our nonhuman primate model (Chlorocebus sabeus of early-life hemispherectomy in which behavioral recovery is interpreted in light of plastic processes that lead to the anatomical reorganization of the early-damaged brain. The model presented here suggests that significant functional recovery occurs after the removal of one hemisphere in monkeys with no preexisting neurological dysfunctions. Human and primate studies suggest a critical role for subcortical and brainstem structures as well as corticospinal tracts in the neuroanatomical reorganization which result in the remarkable behavioral recovery following hemispherectomy. The non-human primate model presented here offers a unique opportunity for studying the behavioral and functional neuroanatomical reorganization that underlies developmental plasticity.

  10. The adaptive response of the rat lung after bilobectomy.

    Science.gov (United States)

    Burri, P H; Sehovic, S

    1979-05-01

    Rats 23 days of age were subjected to resection of the upper and middle lobes of the right lung. After 45 days of recovery, their lungs were fixed and the tissue was processed for quantitative light and electron microscopic analysis. Normal and sham-operated animals of identical age served as control animals. At death, the lobectomized rats had normal body weights and lung volumes; both the left lung and the remainder of the right lung participated proportionally in the restoration of the original lung volume. Air space, tissue and capillary volumes, and alveolar and capillary surface areas were as large as those of the control lungs. Tissue composition was slightly altered: the volume proportion of the interstitium was increased at the cost of the epithelium; endothelial volume density and air-blood barrier thicknesses were normal. Nonparenchymal structures had a smaller potential to adapt than the gas-exchanging parenchyma: the volume of conducting airways was smaller than expected for a normal lung. An analogous trend was observed for the larger blood vessels. Based on the recreated dimensions of the gas-exchange apparatus in operated animals, one can assume that the organ fully restores the conditions for adequate gas diffusion.

  11. A Community-Responsive Adaptation to Reach and Engage Latino Families Affected by Maternal Depression.

    Science.gov (United States)

    Valdez, Carmen R; Ramirez Stege, Alyssa; Martinez, Elizabeth; D'Costa, Stephanie; Chavez, Thomas

    2017-07-23

    As family researchers and practitioners seek to improve the quality and accessibility of mental health services for immigrant families, they have turned to culturally adapted interventions. Although many advancements have been made in adapting interventions for such families, we have yet to understand how the adaptation can ensure that the intervention is reaching families identified to be in greatest need within a local system of care and community. We argue that reaching, engaging, and understanding the needs of families entails a collaborative approach with multiple community partners to ensure that adaptations to intervention content and delivery are responsive to the sociocultural trajectory of families within a community. We describe a cultural adaptation framework that is responsive to the unique opportunities and challenges of identifying and recruiting vulnerable families through community partnerships, and of addressing the needs of families by incorporating multiple community perspectives. Specifically, we apply these principles to the cultural adaptation of an intervention originally developed for low-income African American and White families facing maternal depression. The new intervention, Fortalezas Familiares (Family Strengths), was targeted to Latino immigrant families whose mothers were in treatment for depression in mental health and primary care clinics. We conclude with key recommendations and directions for how family researchers and practitioners can design the cultural adaptation of interventions to be responsive to the practices, preferences, and needs of underserved communities, including families and service providers. © 2017 Family Process Institute.

  12. Adapt

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    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.

  14. Long-term high air pollution exposure induced metabolic adaptations in traffic policemen.

    Science.gov (United States)

    Tan, Chaochao; Wang, Yupeng; Lin, Mingyue; Wang, Zhu; He, Li; Li, Zhiyi; Li, Yu; Xu, Keqian

    2018-03-01

    To assess the adverse physiological changes induced by long-term exposure to PM2.5. Totally 183 traffic policemen and 88 office policemen as the control group, were enrolled in this study. The concentrations of PM2.5 in both the working places of traffic and office policemen were obtained. Detailed personal questionnaires and conventional laboratory tests including hematology, fasting blood glucose, blood lipids, liver, kidney, immunity and tumor-related markers were conducted on all participants of this study. A dose-response relationship between the FBG, HDL-c and CEA values and the PM2.5 exposure duration was observed. Multivariate analysis confirmed that one hour on duty outdoor per day for one year was associated with an increase in FBG of 0.005% (95% CI: 0.0004% to 0.009%), CEA of 0.012% (95% CI: 0.006% to 0.017%), and a decrease in HDL-C of 0.001% (95% CI: 0.00034% to 0.002%). Long-term high air pollution exposure may lead to metabolism adaptation and it is likely involved in the development of cardiovascular disease and diabetes mellitus. Copyright © 2018 Elsevier B.V. All rights reserved.

  15. The Predictive Adaptive Response: Modeling the Life-History Evolution of the Butterfly

    NARCIS (Netherlands)

    Heuvel, van den J.; Saastamoinen, M.; Brakefield, P.M.; Kirkwood, T.B.; Zwaan, B.J.; Shanley, D.P.

    2013-01-01

    A predictive adaptive response (PAR) is a type of developmental plasticity where the response to an environmental cue is not immediately advantageous but instead is later in life. The PAR is a way for organisms to maximize fitness in varying environments. Insects living in seasonal environments are

  16. Community responses and adaption strategies toward flood hazard in Jakarta, Indonesia

    NARCIS (Netherlands)

    Marfai, M.A.; Sekaranom, A.B.; Ward, P.J.

    2015-01-01

    Jakarta, as the capital of the Republic of Indonesia, has long been known to be at risk from flood hazard. It is increasingly recognized that community responses and adaptation strategies are essential for planning future mitigation action. In order to investigate the community responses and

  17. Thermotolerant yeasts selected by adaptive evolution express heat stress response at 30ºC

    DEFF Research Database (Denmark)

    Caspeta, Luis; Chen, Yun; Nielsen, Jens

    2016-01-01

    to grow at increased temperature, activated a constitutive heat stress response when grown at the optimal ancestral temperature, and that this is associated with a reduced growth rate. This preventive response was perfected by additional transcriptional changes activated when the cultivation temperature...... temperatures, but this also causes a trade-off in the growth rate at the optimal ancestral temperature.......Exposure to long-term environmental changes across >100s of generations results in adapted phenotypes, but little is known about how metabolic and transcriptional responses are optimized in these processes. Here, we show that thermotolerant yeast strains selected by adaptive laboratory evolution...

  18. Adaptation

    International Development Research Centre (IDRC) Digital Library (Canada)

    Nairobi, Kenya. 28 Adapting Fishing Policy to Climate Change with the Aid of Scientific and Endogenous Knowledge. Cap Verde, Gambia,. Guinea, Guinea Bissau,. Mauritania and Senegal. Environment and Development in the Third World. (ENDA-TM). Dakar, Senegal. 29 Integrating Indigenous Knowledge in Climate Risk ...

  19. Rapid adaptive evolution of photoperiodic response during invasion and range expansion across a climatic gradient.

    Science.gov (United States)

    Urbanski, Jennifer; Mogi, Motoyoshi; O'Donnell, Deborah; DeCotiis, Mark; Toma, Takako; Armbruster, Peter

    2012-04-01

    Abstract Understanding the mechanisms of adaptation to spatiotemporal environmental variation is a fundamental goal of evolutionary biology. This issue also has important implications for anticipating biological responses to contemporary climate warming and determining the processes by which invasive species are able to spread rapidly across broad geographic ranges. Here, we compare data from a historical study of latitudinal variation in photoperiodic response among Japanese and U.S. populations of the invasive Asian tiger mosquito Aedes albopictus with contemporary data obtained using comparable methods. Our results demonstrated rapid adaptive evolution of the photoperiodic response during invasion and range expansion across ∼15° of latitude in the United States. In contrast to the photoperiodic response, size-based morphological traits implicated in climatic adaptation in a wide range of other insects did not show evidence of adaptive variation in Ae. albopictus across either the U.S. (invasive) or Japanese (native) range. These results show that photoperiodism has been an important adaptation to climatic variation across the U.S. range of Ae. albopictus and, in conjunction with previous studies, strongly implicate the photoperiodic control of seasonal development as a critical evolutionary response to ongoing contemporary climate change. These results also emphasize that photoperiodism warrants increased attention in studies of the evolution of invasive species.

  20. The Adaptive Response, Genetic Haplo-Insufficiency and Genomic Instability

    Energy Technology Data Exchange (ETDEWEB)

    Geard, Charles R. [Columbia Univ., New York, NY (United States). Center for Radiological Research

    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.

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

    DEFF Research Database (Denmark)

    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 ...

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

    Directory of Open Access Journals (Sweden)

    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.

  3. Hepatitis C Virus Evasion of Adaptive Immune Responses- A Model for Viral Persistence

    OpenAIRE

    Burke, Kelly P.; Cox, Andrea L.

    2010-01-01

    Hepatitis C virus (HCV) infects over 170 million people worldwide and is a leading cause of cirrhosis and hepatocellular carcinoma. Approximately 20% of those acutely infected clear the infection, whereas the remaining 80% progress to chronic infection. Hepatitis C thus provides a model in which successful and unsuccessful responses can be compared to better understand the human response to viral infection. Our laboratory studies the strategies by which HCV evades the adaptive immune response...

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

    International Nuclear Information System (INIS)

    Nicolardi, Valentina; Cai, Giampiero; Parrotta, Luigi; Puglia, Michele; Bianchi, Laura; Bini, Luca; Gaggi, Carlo

    2012-01-01

    Lichens are an excellent model to study the bioaccumulation of heavy metals but limited information is available on the molecular mechanisms occurring during bioaccumulation. We investigated the changes of the lichen proteome during exposure to constant concentrations of mercury. We found that most of changes involves proteins of the photosynthetic pathway, such as the chloroplastic photosystem I reaction center subunit II, the oxygen-evolving protein and the chloroplastic ATP synthase β-subunit. This suggests that photosynthesis is a target of the toxic effects of mercury. These findings are also supported by changes in the content of photosynthetic pigments (chlorophyll a and b, and β-carotene). Alterations to the photosynthetic machinery also reflect on the structure of thylakoid membranes of algal cells. Response of lichens to mercury also involves stress-related proteins (such as Hsp70) but not cytoskeletal proteins. Results suggest that lichens adapt to mercury exposure by changing the metabolic production of energy. - 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.

  5. Bacillus subtilis mutants deficient in the adaptive response to simple alkylating agents

    Energy Technology Data Exchange (ETDEWEB)

    Morohoshi, F.; Munakata, N.

    1985-03-01

    Three mutant strains exhibiting hyper-sensitivity to N-methyl-N'-nitro-N-nitrosoguanidine, but not to methyl methanesulfonate, were selected by a replica method from mutagenized spores of Bacillus subtilis. All three were totally deficient in the adaptive response to N-methyl-N'-nitro-N-nitrosoguanidine with regard to both lethality and mutagenesis. The activity to destroy O/sup 6/-methylguanine residues in the methylated DNA was not elevated in the mutant cells by the pretreatment with sublethal concentrations of N-methyl-N-nitro-N-nitrosoguanidine. This deficiency corresponded to the persistance of O/sup 6/-methylguanine residues in the DNA of both control and pretreated mutant cells challenged with the drug. The lethal and mutagenic sensitivity of the mutant strains were observed only for methyl- or ethyl-nitroso compounds that are thought to be active as inducers and are also active in O-alkylation. Except for the insensitivity to methyl methanesulfonate, the phenotypes of these mutants look very similar to those of ada mutants isolated previously in Escherichia coli.

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

    Science.gov (United States)

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

    2013-09-01

    Local adaptation and species interactions have been shown to affect geographic ranges; therefore, we need models of climate impact that include both factors. To identify possible dynamics of species when including these factors, we ran simulations of two competing species using an individual-based, coupled map-lattice model using a linear climatic gradient that varies across latitude and is warmed over time. Reproductive success is governed by an individual's adaptation to local climate as well as its location relative to global constraints. In exploratory experiments varying the strength of adaptation and competition, competition reduces genetic diversity and slows range change, although the two species can coexist in the absence of climate change and shift in the absence of competitors. We also found that one species can drive the other to extinction, sometimes long after climate change ends. Weak selection on local adaptation and poor dispersal ability also caused surfing of cooler-adapted phenotypes from the expanding margin backwards, causing loss of warmer-adapted phenotypes. Finally, geographic ranges can become disjointed, losing centrally-adapted genotypes. These initial results suggest that the interplay between local adaptation and interspecific competition can significantly influence species' responses to climate change, in a way that demands future research. © 2013 New York Academy of Sciences.

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

    Science.gov (United States)

    van Loon, Luc J C; Tipton, Kevin D

    2013-01-01

    Nutrition plays a key role in allowing the numerous training hours to be translated into useful adaptive responses of various tissues in the individual athlete. Research over the last decade has shown many examples of the impact of dietary interventions to modulate the skeletal muscle adaptive response to prolonged exercise training. Proper nutritional coaching should be applied throughout both training and competition, each with their specific requirements regarding nutrient provision. Such dietary support will improve exercise training efficiency and, as such, further increase performance capacity. Here, we provide an overview on the properties of various nutritional interventions that may be useful to support the adaptive response to exercise training and competition and, as such, to augment exercise training efficiency. Copyright © 2013 Nestec Ltd., Vevey/S. Karger AG, Basel.

  8. Acute response and chronic stimulus for cardiac structural and functional adaptation in a professional boxer.

    Science.gov (United States)

    Oxborough, David; George, Keith; Utomi, Victor; Lord, Rachel; Morton, James; Jones, Nigel; Somauroo, John

    2014-06-01

    The individual response to acute and chronic changes in cardiac structure and function to intense exercise training is not fully understood and therefore evidence in this setting may help to improve the timing and interpretation of pre-participation cardiac screening. The following case report highlights an acute increase in right ventricular (RV) size and a reduction in left ventricular (LV) basal radial function with concomitant increase at the mid-level in response to a week's increase in training volume in a professional boxer. These adaptations settle by the second week; however, chronic physiological adaptation occurs over a 12-week period. Electrocardiographic findings demonstrate an acute lateral T-wave inversion at 1 week, which revert to baseline for the duration of training. It appears that a change in training intensity and volume generates an acute response within the RV that acts as a stimulus for chronic adaptation in this professional boxer.

  9. Radiation Induced Immune Response in Prostate Cancer

    Science.gov (United States)

    2014-12-01

    dependent cell- mediated phagocytosis ( ADCP ). This research will allow us to characterize antigens and antibodies intended for clinical trials in patients...Moreover, TIP1 is inducible in nearly all mouse models of cancer resulting in opsonization and activation of ADCC and ADCP . Antibodies that we...antibody-dependent cell-mediated phagocytosis ( ADCP ). ScFv antibodies Overall Project Summary Subtask 1.1 Binding of antibodies to irradiated

  10. Stress-Induced Eating Dampens Physiological and Behavioral Stress Responses

    OpenAIRE

    Finch, LE; Tomiyama, AJ

    2014-01-01

    Both psychological and physical stressors induce the secretion of glucocorticoids and insulin, which increase the consumption of palatable high-fat, high-sugar "comfort foods." Chronic engagement in stress-induced eating behavior leads to visceral fat accumulation, which in turn dampens hypothalamic-pituitary-adrenal axis activity. The joint role of stress-induced eating and abdominal fat stores in attenuating physiological stress responses has been well characterized in nonhuman animal model...

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

    Science.gov (United States)

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

    2017-02-13

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

  12. Evolution of plasticity and adaptive responses to climate change along climate gradients.

    Science.gov (United States)

    Kingsolver, Joel G; Buckley, Lauren B

    2017-08-16

    The relative contributions of phenotypic plasticity and adaptive evolution to the responses of species to recent and future climate change are poorly understood. We combine recent (1960-2010) climate and phenotypic data with microclimate, heat balance, demographic and evolutionary models to address this issue for a montane butterfly, Colias eriphyle , along an elevational gradient. Our focal phenotype, wing solar absorptivity, responds plastically to developmental (pupal) temperatures and plays a central role in thermoregulatory adaptation in adults. Here, we show that both the phenotypic and adaptive consequences of plasticity vary with elevation. Seasonal changes in weather generate seasonal variation in phenotypic selection on mean and plasticity of absorptivity, especially at lower elevations. In response to climate change in the past 60 years, our models predict evolutionary declines in mean absorptivity (but little change in plasticity) at high elevations, and evolutionary increases in plasticity (but little change in mean) at low elevation. The importance of plasticity depends on the magnitude of seasonal variation in climate relative to interannual variation. Our results suggest that selection and evolution of both trait means and plasticity can contribute to adaptive response to climate change in this system. They also illustrate how plasticity can facilitate rather than retard adaptive evolutionary responses to directional climate change in seasonal environments. © 2017 The Author(s).

  13. Electrical field stimulation-induced excitatory responses of ...

    African Journals Online (AJOL)

    effect of the endothelium on electrical field stimulation (EFS)-induced excitatory responses of pulmonary artery segments from pulmonary hypertensive rats. Methods: Pulmonary hypertension was induced in rats with a single dose of monocrotaline (60 mg/kg) and 21 days later, arterial rings were set up for isometric tension ...

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

    International Nuclear Information System (INIS)

    Steel, Christina D.; Hahto, Suzanne M.; Ciavarra, Richard P.

    2009-01-01

    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 (CD45 high CD11b + ) 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.

  15. Increased sensitivity of DNA damage response-deficient cells to stimulated microgravity-induced DNA lesions.

    Directory of Open Access Journals (Sweden)

    Nan Li

    Full Text Available Microgravity is a major stress factor that astronauts have to face in space. In the past, the effects of microgravity on genomic DNA damage were studied, and it seems that the effect on genomic DNA depends on cell types and the length of exposure time to microgravity or simulated microgravity (SMG. In this study we used mouse embryonic stem (MES and mouse embryonic fibroblast (MEF cells to assess the effects of SMG on DNA lesions. To acquire the insight into potential mechanisms by which cells resist and/or adapt to SMG, we also included Rad9-deleted MES and Mdc1-deleted MEF cells in addition to wild type cells in this study. We observed significant SMG-induced DNA double strand breaks (DSBs in Rad9-/- MES and Mdc1-/- MEF cells but not in their corresponding wild type cells. A similar pattern of DNA single strand break or modifications was also observed in Rad9-/- MES. As the exposure to SMG was prolonged, Rad9-/- MES cells adapted to the SMG disturbance by reducing the induced DNA lesions. The induced DNA lesions in Rad9-/- MES were due to SMG-induced reactive oxygen species (ROS. Interestingly, Mdc1-/- MEF cells were only partially adapted to the SMG disturbance. That is, the induced DNA lesions were reduced over time, but did not return to the control level while ROS returned to a control level. In addition, ROS was only partially responsible for the induced DNA lesions in Mdc1-/- MEF cells. Taken together, these data suggest that SMG is a weak genomic DNA stress and can aggravate genomic instability in cells with DNA damage response (DDR defects.

  16. Sensing and adaptation to low pH mediated by inducible amino acid decarboxylases in Salmonella.

    Directory of Open Access Journals (Sweden)

    Julie P M Viala

    Full Text Available During the course of infection, Salmonella enterica serovar Typhimurium must successively survive the harsh acid stress of the stomach and multiply into a mild acidic compartment within macrophages. Inducible amino acid decarboxylases are known to promote adaptation to acidic environments. Three low pH inducible amino acid decarboxylases were annotated in the genome of S. Typhimurium, AdiA, CadA and SpeF, which are specific for arginine, lysine and ornithine, respectively. In this study, we characterized and compared the contributions of those enzymes in response to acidic challenges. Individual mutants as well as a strain deleted for the three genes were tested for their ability (i to survive an extreme acid shock, (ii to grow at mild acidic pH and (iii to infect the mouse animal model. We showed that the lysine decarboxylase CadA had the broadest range of activity since it both had the capacity to promote survival at pH 2.3 and growth at pH 4.5. The arginine decarboxylase AdiA was the most performant in protecting S. Typhimurium from a shock at pH 2.3 and the ornithine decarboxylase SpeF conferred the best growth advantage under anaerobiosis conditions at pH 4.5. We developed a GFP-based gene reporter to monitor the pH of the environment as perceived by S. Typhimurium. Results showed that activities of the lysine and ornithine decarboxylases at mild acidic pH did modify the local surrounding of S. Typhimurium both in culture medium and in macrophages. Finally, we tested the contribution of decarboxylases to virulence and found that these enzymes were dispensable for S. Typhimurium virulence during systemic infection. In the light of this result, we examined the genomes of Salmonella spp. normally responsible of systemic infection and observed that the genes encoding these enzymes were not well conserved, supporting the idea that these enzymes may be not required during systemic infection.

  17. Reproductive stimulation by low doses of xenoestrogens contrasts with the view of hormesis as an adaptive response.

    Science.gov (United States)

    Weltje, Lennart; vom Saal, Frederick S; Oehlmann, Jörg

    2005-09-01

    We discuss the similarities and differences of two types of effects that occur at low but not high doses of chemicals: hormesis and stimulation by oestrogenic endocrine-disrupting chemicals or xenoestrogens. While hormesis is a general phenomenon evoked by many compounds, oestrogenic stimulation occurs for specific chemicals that disrupt actions of endogenous oestrogen. Both types of phenomena can induce an inverted-U dose-response curve, resulting from low-dose stimulation of response, and thus challenge current methods of risk assessment. Hormesis is generally thought to be caused by an over-reaction of detoxification mechanisms, which is considered an adaptive response that should protect an organism from subsequent stress. One view of the hormetic low-dose stimulatory response, i.e., increased performance, is that it is beneficial. In contrast, we propose that for manmade xenoestrogens this is never the case. This is demonstrated with examples for low doses of the oestrogenic environmental chemicals bisphenol A and octylphenol, and the oestrogenic drug diethylstilbestrol. Adverse low-dose effects include oviduct rupture, an enlarged prostate, feminization of males and reduced sperm quality. These adverse stimulatory effects divert energy needed for other processes, resulting in reduced fitness. In conclusion, while there are similarities (inverted-U dose-response), there are also differences, adaptive response for hormesis versus adverse stimulatory response for low doses of manmade xenoestrogens, that have been almost totally ignored in discussions of hormesis. We propose that the risk posed by low doses of manmade xenoestrogens that show inverted-U dose-response curves is underestimated by the current threshold model used in risk assessment, and this is likely to apply to other endocrine-disrupting chemicals.

  18. A biological-based model that links genomic instability, bystander effects, and adaptive response

    International Nuclear Information System (INIS)

    Scott, B.R.

    2004-01-01

    This paper links genomic instability, bystander effects, and adaptive response in mammalian cell communities via a novel biological-based, dose-response model called NEOTRANS 3 . The model is an extension of the NEOTRANS 2 model that addressed stochastic effects (genomic instability, mutations, and neoplastic transformation) associated with brief exposure to low radiation doses. With both models, ionizing radiation produces DNA damage in cells that can be associated with varying degrees of genomic instability. Cells with persistent problematic instability (PPI) are mutants that arise via misrepair of DNA damage. Progeny of PPI cells also have PPI and can undergo spontaneous neoplastic transformation. Unlike NEOTRANS 2 , with NEOTRANS 3 newly induced mutant PPI cells and their neoplastically transformed progeny can be suppressed via our previously introduced protective apoptosis-mediated (PAM) process, which can be activated by low linear energy transfer (LET) radiation. However, with NEOTRANS 3 (which like NEOTRANS 2 involves cross-talk between nongenomically compromised [e.g., nontransformed, nonmutants] and genomically compromised [e.g., mutants, transformants, etc.] cells), it is assumed that PAM is only activated over a relatively narrow, dose-rate-dependent interval (D PAM ,D off ); where D PAM is a small stochastic activation threshold, and D off is the stochastic dose above which PAM does not occur. PAM cooperates with activated normal DNA repair and with activated normal apoptosis in guarding against genomic instability. Normal repair involves both error-free repair and misrepair components. Normal apoptosis and the error-free component of normal repair protect mammals by preventing the occurrence of mutant cells. PAM selectively removes mutant cells arising via the misrepair component of normal repair, selectively removes existing neoplastically transformed cells, and probably selectively removes other genomically compromised cells when it is activated

  19. Cardiac Response to Chronic Intermittent Hypoxia with a Transition from Adaptation to Maladaptation: The Role of Hydrogen Peroxide

    Directory of Open Access Journals (Sweden)

    Xia Yin

    2012-01-01

    Full Text Available Obstructive sleep apnea (OSA is a highly prevalent respiratory disorder of sleep, and associated with chronic intermittent hypoxia (CIH. Experimental evidence indicates that CIH is a unique physiological state with potentially “adaptive” and “maladaptive” consequences for cardio-respiratory homeostasis. CIH is also a critical element accounting for most of cardiovascular complications of OSA. Cardiac response to CIH is time-dependent, showing a transition from cardiac compensative (such as hypertrophy to decompensating changes (such as failure. CIH-provoked mild and transient oxidative stress can induce adaptation, but severe and persistent oxidative stress may provoke maladaptation. Hydrogen peroxide as one of major reactive oxygen species plays an important role in the transition of adaptive to maladaptive response to OSA-associated CIH. This may account for the fact that although oxidative stress has been recognized as a driver of cardiac disease progression, clinical interventions with antioxidants have had little or no impact on heart disease and progression. Here we focus on the role of hydrogen peroxide in CIH and OSA, trying to outline the potential of antioxidative therapy in preventing CIH-induced cardiac damage.

  20. The zebrafish miR-125c is induced under hypoxic stress via hypoxia-inducible factor 1α and functions in cellular adaptations and embryogenesis.

    Science.gov (United States)

    He, Yan; Huang, Chun-Xiao; Chen, Nan; Wu, Meng; Huang, Yan; Liu, Hong; Tang, Rong; Wang, Wei-Min; Wang, Huan-Ling

    2017-09-26

    Hypoxia is a unique environmental stress. Hypoxia inducible factor-lα (HIF-lα) is a major transcriptional regulator of cellular adaptations to hypoxic stress. MicroRNAs (miRNAs) as posttranscriptional gene expression regulators occupy a crucial role in cell survival under low-oxygen environment. Previous evidences suggested that miR-125c is involved in hypoxia adaptation, but its precise biological roles and the regulatory mechanism underlying hypoxic responses remain unknown. The present study showed that zebrafish miR-125c is upregulated by hypoxia in a Hif-lα-mediated manner in vitro and in vivo . Dual-luciferase assay revealed that cdc25a is a novel target of miR-125c. An inverse correlation between miR-125c and cdc25a was further confirmed in vivo , suggesting miR-125c as a crucial physiological inhibitor of cdc25a which responds to cellular hypoxia. Overexpression of miR-125c suppressed cell proliferation, led to cell cycle arrest at the G1 phase in ZF4 cells and induced apoptotic responses during embryo development. More importantly, miR-125c overexpression resulted in severe malformation and reduction of motility during zebrafish embryonic development. Taken together, we conclude that miR-125c plays a pivotal role in cellular adaptations to hypoxic stress at least in part through the Hif-1α/miR-125c/cdc25a signaling and has great impact on zebrafish early embryonic development.

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

    Science.gov (United States)

    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

  2. Enhancement of the production of L-glutaminase, an anticancer enzyme, from Aeromonas veronii by adaptive and induced mutation techniques.

    Directory of Open Access Journals (Sweden)

    S Aravinth Vijay Jesuraj

    Full Text Available Microbial anti-cancer enzymes have been proven to be effective and economical agents for cancer treatment. Aeromonas veronii has been identified as a microorganism with the potential to produce L-glutaminase, an anticancer agent effective against acute lymphocytic leukaemia. In this study, a selective medium of Aeromonas veronii was used to culture the microorganism. Strain improvement was done by adaptive and induced mutational techniques. A selective minimal agar media was incorporated for the growth of the strain which further supports adaptive mutation. Strains were also UV-irradiated and successively treated with N-methyl-N'-nitro-N-nitrosoguanidine to find a resilient strain capable of producing L-glutaminase efficiently. The Plackett-Burman design and central composite designs were used to screen and optimize additional carbon and nitrogen sources. Adaptive mutation resulted in promising yield improvements compared to native strain (P<0.001. The mean yield of 30 treated colonies from the induced mutation was significantly increased compared to the non-induced strain (P< 0.001. The economically feasible statistical designs were found to reinforce each other in order to maximize the yield of the enzyme. The interactions of nutrient factors were understood from the 3D response surface plots. The model was found to be a perfect fit in terms of maximizing enzyme yield, with the productivity improving at every stage to a fourfold output of enzyme (591.11 ±7.97 IU/mL compared to the native strain (135±3.51 IU/mL.

  3. ATR controls cellular adaptation to hypoxia through positive regulation of hypoxia-inducible factor 1 (HIF-1) expression.

    Science.gov (United States)

    Fallone, F; Britton, S; Nieto, L; Salles, B; Muller, C

    2013-09-12

    Tumor cells adaptation to severe oxygen deprivation (hypoxia) plays a major role in tumor progression. The transcription factor HIF-1 (hypoxia-inducible factor 1), whose α-subunit is stabilized under hypoxic conditions is a key component of this process. Recent studies showed that two members of the phosphoinositide 3-kinase-related kinases (PIKKs) family, ATM (ataxia telangiectasia mutated) and DNA-PK (DNA-dependent protein kinase), regulate the hypoxic-dependent accumulation of HIF-1. These proteins initiate cellular stress responses when DNA damage occurs. In addition, it has been demonstrated that extreme hypoxia induces a replicative stress resulting in regions of single-stranded DNA at stalled replication forks and the activation of ATR (ataxia telangiectasia and Rad3 related protein), another member of the PIKKs family. Here, we show that even less severe hypoxia (0.1% O2) also induces activation of ATR through replicative stress. Importantly, in using either transiently silenced ATR cells, cells expressing an inactive form of ATR or cells exposed to an ATR inhibitor (CGK733), we demonstrate that hypoxic ATR activation positively regulates the key transcription factor HIF-1 independently of the checkpoint kinase Chk1. We show that ATR kinase activity regulates HIF-1α at the translational level and we find that the elements necessary for the regulation of HIF-1α translation are located within the coding region of HIF-1α mRNA. Finally, by using three independent cellular models, we clearly show that the loss of ATR expression and/or kinase activity results in the decrease of HIF-1 DNA binding under hypoxia and consequently affects protein expression levels of two HIF-1 target genes, GLUT-1 and CAIX. Taken together, our data show a new function for ATR in cellular adaptation to hypoxia through regulation of HIF-1α translation. Our work offers new prospect for cancer therapy using ATR inhibitors with the potential to decrease cellular adaptation in hypoxic

  4. 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

    International Nuclear Information System (INIS)

    Boreham, D.R.; Bahen, M.E.; Dolling, J-A.

    1997-01-01

    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

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

    International Nuclear Information System (INIS)

    Conolly, Rory B.; Gaylor, David W.; Lutz, Werner K.

    2005-01-01

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

  6. Occurrence of long-term depression in the cerebellar flocculus during adaptation of optokinetic response.

    Science.gov (United States)

    Inoshita, Takuma; Hirano, Tomoo

    2018-03-27

    Long-term depression (LTD) at parallel fiber (PF) to Purkinje cell (PC) synapses has been considered as a main cellular mechanism for motor learning. However, the necessity of LTD for motor learning was challenged by demonstration of normal motor learning in the LTD-defective animals. Here, we addressed possible involvement of LTD in motor learning by examining whether LTD occurs during motor learning in the wild-type mice. As a model of motor learning, adaptation of optokinetic response (OKR) was used. OKR is a type of reflex eye movement to suppress blur of visual image during animal motion. OKR shows adaptive change during continuous optokinetic stimulation, which is regulated by the cerebellar flocculus. After OKR adaptation, amplitudes of quantal excitatory postsynaptic currents at PF-PC synapses were decreased, and induction of LTD was suppressed in the flocculus. These results suggest that LTD occurs at PF-PC synapses during OKR adaptation. © 2018, Inoshita et al.

  7. Acid resistance and response to pH-induced stress in two Lactobacillus plantarum strains with probiotic potential.

    Science.gov (United States)

    Šeme, H; Gjuračić, K; Kos, B; Fujs, Š; Štempelj, M; Petković, H; Šušković, J; Bogovič Matijašić, B; Kosec, G

    2015-01-01

    Two new Lactobacillus plantarum strains, KR6-DSM 28780 and M5 isolated from sour turnip and traditional dried fresh cheese, respectively, were evaluated for species identity, antibiotic susceptibility, resistance to gastrointestinal conditions and adaptive response to low pH. Resistance mechanisms involved in the adaptation to acid-induced stress in these two strains were investigated by quantitative PCR of the atpA, cfa1, mleS and hisD genes. In addition to absence of antibiotic resistance, the two L. plantarum strains showed excellent survival rates at pH values as low as 2.4. Adaptive response to low pH was clearly observed in both strains; strain KR6 was superior to M5, as demonstrated by its ability to survive during 3 h incubation at pH 2.0 upon adaptation to moderately acidic conditions. In contrast, acid adaptation did not significantly affect the survival rate during simulated passage through the gastrointestinal tract. In both strains, induction of histidine biosynthesis (hisD) was upregulated during the acid adaptation response. In addition, significant upregulation of the cfa1 gene, involved in modulation of membrane fatty acid composition, was observed during the adaptation phase in strain KR6 but not in strain M5. Cells adapted to moderately acidic conditions also showed a significantly increased viability after the lyophilisation procedure, a cross-protection phenomenon providing additional advantage in probiotic application.

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

    Science.gov (United States)

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

    2014-09-01

    Gene expression varies widely in natural populations, yet the proximate and ultimate causes of this variation are poorly known. Understanding how variation in gene expression affects abiotic stress tolerance, fitness, and adaptation is central to the field of evolutionary genetics. We tested the hypothesis that genes with natural genetic variation in their expression responses to abiotic stress are likely to be involved in local adaptation to climate in Arabidopsis thaliana. Specifically, we compared genes with consistent expression responses to environmental stress (expression stress responsive, "eSR") to genes with genetically variable responses to abiotic stress (expression genotype-by-environment interaction, "eGEI"). We found that on average genes that exhibited eGEI in response to drought or cold had greater polymorphism in promoter regions and stronger associations with climate than those of eSR genes or genomic controls. We also found that transcription factor binding sites known to respond to environmental stressors, especially abscisic acid responsive elements, showed significantly higher polymorphism in drought eGEI genes in comparison to eSR genes. By contrast, eSR genes tended to exhibit relatively greater pairwise haplotype sharing, lower promoter diversity, and fewer nonsynonymous polymorphisms, suggesting purifying selection or selective sweeps. Our results indicate that cis-regulatory evolution and genetic variation in stress responsive gene expression may be important mechanisms of local adaptation to climatic selective gradients. © The Author 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  9. Intermittent and continuous high-intensity exercise training induce similar acute but different chronic muscle adaptations.

    Science.gov (United States)

    Cochran, Andrew J R; Percival, Michael E; Tricarico, Steven; Little, Jonathan P; Cermak, Naomi; Gillen, Jenna B; Tarnopolsky, Mark A; Gibala, Martin J

    2014-05-01

    High-intensity interval training (HIIT) performed in an 'all-out' manner (e.g. repeated Wingate tests) is a time-efficient strategy to induce skeletal muscle remodelling towards a more oxidative phenotype. A fundamental question that remains unclear, however, is whether the intermittent or 'pulsed' nature of the stimulus is critical to the adaptive response. In study 1, we examined whether the activation of signalling cascades linked to mitochondrial biogenesis was dependent on the manner in which an acute high-intensity exercise stimulus was applied. Subjects performed either four 30 s Wingate tests interspersed with 4 min of rest (INT) or a bout of continuous exercise (CONT) that was matched for total work (67 ± 7 kJ) and which required ∼4 min to complete as fast as possible. Both protocols elicited similar increases in markers of adenosine monophosphate-activated protein kinase (AMPK) and p38 mitogen-activated protein kinase activation, as well as Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) mRNA expression (main effects for time, P ≤ 0.05). In study 2, we determined whether 6 weeks of the CONT protocol (3 days per week) would increase skeletal muscle mitochondrial content to a similar extent to what we have previously reported after 6 weeks of INT. Despite similar acute signalling responses to the CONT and INT protocols, training with CONT did not increase the maximal activity or protein content of a range of mitochondrial markers. However, peak oxygen uptake was higher after CONT training (from 45.7 ± 5.4 to 48.3 ± 6.5 ml kg(-1) min(-1); P < 0.05) and 250 kJ time trial performance was improved (from 26:32 ± 4:48 to 23:55 ± 4:16 min:s; P < 0.001) in our recreationally active participants. We conclude that the intermittent nature of the stimulus is important for maximizing skeletal muscle adaptations to low-volume, all-out HIIT. Despite the lack of skeletal muscle mitochondrial adaptations

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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

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

    KAUST Repository

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    DEFF Research Database (Denmark)

    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...... to be an adaptive response. Despite almost a century of studies on phenotypic plasticity, the relation between plasticity and evolution is still not clear and theoretical prediction are often not met by empirical data. In my PhD I have investigated if and when plasticity can evolve. I selected Drosophila simulans......Phenotypic plasticity is the ability of a genotype to modify its phenotype in response to environmental changes as a consequence of an interaction between genes and environment (Bradshaw, 1965). Plasticity contributes to the vast phenotypic variation observed in natural populations. Many examples...

  15. The zebrafish miR-462/miR-731 cluster is induced under hypoxic stress via hypoxia-inducible factor 1α and functions in cellular adaptations.

    Science.gov (United States)

    Huang, Chun-Xiao; Chen, Nan; Wu, Xin-Jie; Huang, Cui-Hong; He, Yan; Tang, Rong; Wang, Wei-Min; Wang, Huan-Ling

    2015-12-01

    Hypoxia, a unique and essential environmental stress, evokes highly coordinated cellular responses, and hypoxia-inducible factor (HIF) 1 in the hypoxia signaling pathway, an evolutionarily conserved cellular signaling pathway, acts as a master regulator of the transcriptional response to hypoxic stress. MicroRNAs (miRNAs), a major class of posttranscriptional gene expression regulators, also play pivotal roles in orchestrating hypoxia-mediated cellular adaptations. Here, global miRNA expression profiling and quantitative real-time PCR indicated that the up-regulation of the miR-462/miR-731 cluster in zebrafish larvae is induced by hypoxia. It was further validated that miR-462 and miR-731 are up-regulated in a Hif-1α-mediated manner under hypoxia and specifically target ddx5 and ppm1da, respectively. Overexpression of miR-462 and miR-731 represses cell proliferation through blocking cell cycle progress of DNA replication, and induces apoptosis. In situ detection revealed that the miR-462/miR-731 cluster is highly expressed in a consistent and ubiquitous manner throughout the early developmental stages. Additionally, the transcripts become restricted to the notochord, pharyngeal arch, liver, and gut regions from postfertilization d 3 to 5. These data highlight a previously unidentified role of the miR-462/miR-731 cluster as a crucial signaling mediator for hypoxia-mediated cellular adaptations and provide some insights into the potential function of the cluster during embryonic development. © FASEB.

  16. Once more on adaptation: A response to Seweryna Wysłouch

    Directory of Open Access Journals (Sweden)

    Marek Hendrykowski

    2015-11-01

    Full Text Available Marek Hendrykowski’s paper provides certain remarks and necessary explanations in response to Seweryna Wysłouch’s polemic (“A film adaptation – a translation or montage?”, published in Przestrzenie Teorii no. 22, 2014.

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

    Indian Academy of Sciences (India)

    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 ...

  18. Lipopolysaccharide (LPS)-Induced Autophagy Is Responsible for Enhanced Osteoclastogenesis.

    Science.gov (United States)

    Sul, Ok-Joo; Park, Hyun-Jung; Son, Ho-Jung; Choi, Hye-Seon

    2017-11-30

    We hypothesized that inflammation affects number and activity of osteoclasts (OCs) via enhancing autophagy. Lipopolysaccharide (LPS) induced autophagy, osteoclastogenesis, and cytoplasmic reactive oxygen species (ROS) in bone marrow-derived macrophages that were pre-stimulated with receptor activator of nuclear factor-κB ligand. An autophagy inhibitor, 3-methyladenine (3-MA) decreased LPS-induced OC formation and bone resorption, indicating that autophagy is responsible for increasing number and activity of OCs upon LPS stimulus. Knockdown of autophagy-related protein 7 attenuated the effect of LPS on OC-specific genes, supporting a role of LPS as an autophagy inducer in OC. Removal of ROS decreased LPS-induced OC formation as well as autophagy. However, 3-MA did not affect LPS-induced ROS levels, suggesting that ROS act upstream of phosphatidylinositol-4,5-bisphosphate 3-kinase in LPS-induced autophagy. Our results suggest the possible use of autophagy inhibitors targeting OCs to reduce inflammatory bone loss.

  19. Effects of exogenous glucagon-like peptide-2 and distal bowel resection on intestinal and systemic adaptive responses in rats

    Science.gov (United States)

    de Heuvel, Elaine; Wallace, Laurie E.; Hartmann, Bolette; Holst, Jens J.; Brindle, Mary E.; Chelikani, Prasanth K.; Sigalet, David L.

    2017-01-01

    Objective To determine the effects of exogenous glucagon-like peptide-2 (GLP-2), with or without massive distal bowel resection, on adaptation of jejunal mucosa, enteric neurons, gut hormones and tissue reserves in rats. Background GLP-2 is a gut hormone known to be trophic for small bowel mucosa, and to mimic intestinal adaptation in short bowel syndrome (SBS). However, the effects of exogenous GLP-2 and SBS on enteric neurons are unclear. Methods Sprague Dawley rats were randomized to four treatments: Transected Bowel (TB) (n = 8), TB + GLP-2 (2.5 nmol/kg/h, n = 8), SBS (n = 5), or SBS + GLP-2 (2.5 nmol/kg/h, n = 9). SBS groups underwent a 60% jejunoileal resection with cecectomy and jejunocolic anastomosis. All rats were maintained on parenteral nutrition for 7 d. Parameters measured included gut morphometry, qPCR for hexose transporter (SGLT-1, GLUT-2, GLUT-5) and GLP-2 receptor mRNA, whole mount immunohistochemistry for neurons (HuC/D, VIP, nNOS), plasma glucose, gut hormones, and body composition. Results Resection increased the proportion of nNOS immunopositive myenteric neurons, intestinal muscularis propria thickness and crypt cell proliferation, which were not recapitulated by GLP-2 therapy. Exogenous GLP-2 increased jejunal mucosal surface area without affecting enteric VIP or nNOS neuronal immunopositivity, attenuated resection-induced reductions in jejunal hexose transporter abundance (SGLT-1, GLUT-2), increased plasma amylin and decreased peptide YY concentrations. Exogenous GLP-2 attenuated resection-induced increases in blood glucose and body fat loss. Conclusions Exogenous GLP-2 stimulates jejunal adaptation independent of enteric neuronal VIP or nNOS changes, and has divergent effects on plasma amylin and peptide YY concentrations. The novel ability of exogenous GLP-2 to modulate resection-induced changes in peripheral glucose and lipid reserves may be important in understanding the whole-body response following intestinal resection, and is worthy

  20. Effects of exogenous glucagon-like peptide-2 and distal bowel resection on intestinal and systemic adaptive responses in rats.

    Directory of Open Access Journals (Sweden)

    Sarah W Lai

    Full Text Available To determine the effects of exogenous glucagon-like peptide-2 (GLP-2, with or without massive distal bowel resection, on adaptation of jejunal mucosa, enteric neurons, gut hormones and tissue reserves in rats.GLP-2 is a gut hormone known to be trophic for small bowel mucosa, and to mimic intestinal adaptation in short bowel syndrome (SBS. However, the effects of exogenous GLP-2 and SBS on enteric neurons are unclear.Sprague Dawley rats were randomized to four treatments: Transected Bowel (TB (n = 8, TB + GLP-2 (2.5 nmol/kg/h, n = 8, SBS (n = 5, or SBS + GLP-2 (2.5 nmol/kg/h, n = 9. SBS groups underwent a 60% jejunoileal resection with cecectomy and jejunocolic anastomosis. All rats were maintained on parenteral nutrition for 7 d. Parameters measured included gut morphometry, qPCR for hexose transporter (SGLT-1, GLUT-2, GLUT-5 and GLP-2 receptor mRNA, whole mount immunohistochemistry for neurons (HuC/D, VIP, nNOS, plasma glucose, gut hormones, and body composition.Resection increased the proportion of nNOS immunopositive myenteric neurons, intestinal muscularis propria thickness and crypt cell proliferation, which were not recapitulated by GLP-2 therapy. Exogenous GLP-2 increased jejunal mucosal surface area without affecting enteric VIP or nNOS neuronal immunopositivity, attenuated resection-induced reductions in jejunal hexose transporter abundance (SGLT-1, GLUT-2, increased plasma amylin and decreased peptide YY concentrations. Exogenous GLP-2 attenuated resection-induced increases in blood glucose and body fat loss.Exogenous GLP-2 stimulates jejunal adaptation independent of enteric neuronal VIP or nNOS changes, and has divergent effects on plasma amylin and peptide YY concentrations. The novel ability of exogenous GLP-2 to modulate resection-induced changes in peripheral glucose and lipid reserves may be important in understanding the whole-body response following intestinal resection, and is worthy of further study.

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

    Directory of Open Access Journals (Sweden)

    Jonathan J Hansen

    Full Text Available 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.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.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.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 the identification of novel microbial targets

  2. Transcriptional Analysis of The Adaptive Digestive System of The Migratory Locust in Response to Plant Defensive Protease Inhibitors

    Science.gov (United States)

    Spit, Jornt; Holtof, Michiel; Badisco, Liesbet; Vergauwen, Lucia; Vogel, Elise; Knapen, Dries; vanden Broeck, Jozef

    2016-09-01

    Herbivorous insects evolved adaptive mechanisms to compensate for the presence of plant defensive protease inhibitors (PI) in their food. The underlying regulatory mechanisms of these compensatory responses remain largely elusive. In the current study, we investigated the initiation of this adaptive response in the migratory locust, Locusta migratoria, via microarray analysis of gut tissues. Four hours after dietary uptake of PIs, 114 and 150 transcripts were respectively found up- or downregulated. The results suggest a quick trade-off between compensating for potential loss of digestive activity on the one hand, and stress tolerance, defense, and structural integrity of the gut on the other hand. We additionally addressed the role of a group of related upregulated hexamerin-like proteins in the PI-induced response. Simultaneous knockdown of corresponding transcripts by means of RNA interference resulted in a reduced capacity of the locust nymphs to cope with the effects of PI. Moreover, since insect hexamerins have been shown to bind Juvenile Hormone (JH), we also investigated the effect of JH on the proteolytic digestion in L. migratoria. Our results indicate that JH has a stimulatory effect on the expression of three homologous chymotrypsin genes, while knocking down the JH receptor (methoprene tolerant) led to opposite effects.

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

    Science.gov (United States)

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

    2013-01-01

    Pathogenic New World hantaviruses cause severe disease in humans characterized by a vascular leak syndrome, leading to pulmonary oedema and respiratory distress with case fatality rates approaching 40%. Hantaviruses infect microvascular endothelial cells without conspicuous cytopathic effects, indicating that destruction of the endothelium is not a mechanism of disease. In humans, high levels of inflammatory cytokines are present in the lungs of patients that succumb to infection. This, along with other observations, suggests that disease has an immunopathogenic component. Currently the only animal model available to study hantavirus disease is the Syrian hamster, where infection with Andes virus (ANDV), the primary agent of disease in South America, results in disease that closely mimics that seen in humans. Conversely, inoculation of hamsters with a passaged Sin Nombre virus (SNV), the virus responsible for most cases of disease in North America, results in persistent infection with high levels of viral replication. We found that ANDV elicited a stronger innate immune response, whereas SNV elicited a more robust adaptive response in the lung. Additionally, ANDV infection resulted in significant changes in the blood lymphocyte populations. To determine whether the adaptive immune response influences infection outcome, we depleted hamsters of CD4+ and CD8+ T cells before infection with hantaviruses. Depletion resulted in inhibition of virus-specific antibody responses, although the pathogenesis and replication of these viruses were unaltered. These data show that neither hantavirus replication, nor pathogenesis caused by these viruses, is influenced by the adaptive immune response in the Syrian hamster. PMID:23600567

  4. Neonicotinoid insecticides induce salicylate-associated plant defense responses

    Science.gov (United States)

    Ford, Kevin A.; Casida, John E.; Chandran, Divya; Gulevich, Alexander G.; Okrent, Rachel A.; Durkin, Kathleen A.; Sarpong, Richmond; Bunnelle, Eric M.; Wildermuth, Mary C.

    2010-01-01

    Neonicotinoid insecticides control crop pests based on their action as agonists at the insect nicotinic acetylcholine receptor, which accepts chloropyridinyl- and chlorothiazolyl-analogs almost equally well. In some cases, these compounds have also been reported to enhance plant vigor and (a)biotic stress tolerance, independent of their insecticidal function. However, this mode of action has not been defined. Using Arabidopsis thaliana, we show that the neonicotinoid compounds, imidacloprid (IMI) and clothianidin (CLO), via their 6-chloropyridinyl-3-carboxylic acid and 2-chlorothiazolyl-5-carboxylic acid metabolites, respectively, induce salicylic acid (SA)-associated plant responses. SA is a phytohormone best known for its role in plant defense against pathogens and as an inducer of systemic acquired resistance; however, it can also modulate abiotic stress responses. These neonicotinoids effect a similar global transcriptional response to that of SA, including genes involved in (a)biotic stress response. Furthermore, similar to SA, IMI and CLO induce systemic acquired resistance, resulting in reduced growth of a powdery mildew pathogen. The action of CLO induces the endogenous synthesis of SA via the SA biosynthetic enzyme ICS1, with ICS1 required for CLO-induced accumulation of SA, expression of the SA marker PR1, and fully enhanced resistance to powdery mildew. In contrast, the action of IMI does not induce endogenous synthesis of SA. Instead, IMI is further bioactivated to 6-chloro-2-hydroxypyridinyl-3-carboxylic acid, which is shown here to be a potent inducer of PR1 and inhibitor of SA-sensitive enzymes. Thus, via different mechanisms, these chloropyridinyl- and chlorothiazolyl-neonicotinoids induce SA responses associated with enhanced stress tolerance. PMID:20876120

  5. Toll‐Like Receptor‐2 Mediates Adaptive Cardiac Hypertrophy in Response to Pressure Overload Through Interleukin‐1β Upregulation via Nuclear Factor κB Activation

    Science.gov (United States)

    Higashikuni, Yasutomi; Tanaka, Kimie; Kato, Megumi; Nureki, Osamu; Hirata, Yasunobu; Nagai, Ryozo; Komuro, Issei; Sata, Masataka

    2013-01-01

    Background Inflammation is induced in the heart during the development of cardiac hypertrophy. The initiating mechanisms and the role of inflammation in cardiac hypertrophy, however, remain unclear. Toll‐like receptor‐2 (TLR2) recognizes endogenous molecules that induce noninfectious inflammation. Here, we examined the role of TLR2‐mediated inflammation in cardiac hypertrophy. Methods and Results At 2 weeks after transverse aortic constriction, Tlr2−/− mice showed reduced cardiac hypertrophy and fibrosis with greater left ventricular dilatation and impaired systolic function compared with wild‐type mice, which indicated impaired cardiac adaptation in Tlr2−/− mice. Bone marrow transplantation experiment revealed that TLR2 expressed in the heart, but not in bone marrow–derived cells, is important for cardiac adaptive response to pressure overload. In vitro experiments demonstrated that TLR2 signaling can induce cardiomyocyte hypertrophy and fibroblast and vascular endothelial cell proliferation through nuclear factor–κB activation and interleukin‐1β upregulation. Systemic administration of a nuclear factor–κB inhibitor or anti–interleukin‐1β antibodies to wild‐type mice resulted in impaired adaptive cardiac hypertrophy after transverse aortic constriction. We also found that heat shock protein 70, which was increased in murine plasma after transverse aortic constriction, can activate TLR2 signaling in vitro and in vivo. Systemic administration of anti–heat shock protein 70 antibodies to wild‐type mice impaired adaptive cardiac hypertrophy after transverse aortic constriction. Conclusions Our results demonstrate that TLR2‐mediated inflammation induced by extracellularly released heat shock protein 70 is essential for adaptive cardiac hypertrophy in response to pressure overload. Thus, modulation of TLR2 signaling in the heart may provide a novel strategy for treating heart failure due to inadequate adaptation to hemodynamic

  6. Compensatory regulation of HDAC5 in muscle maintains metabolic adaptive responses and metabolism in response to energetic stress.

    Science.gov (United States)

    McGee, Sean L; Swinton, Courtney; Morrison, Shona; Gaur, Vidhi; Campbell, Duncan E; Jorgensen, Sebastian B; Kemp, Bruce E; Baar, Keith; Steinberg, Gregory R; Hargreaves, M

    2014-08-01

    Some gene deletions or mutations have little effect on metabolism and metabolic adaptation because of redundancy and/or compensation in metabolic pathways. The mechanisms for redundancy and/or compensation in metabolic adaptation in mammalian cells are unidentified. Here, we show that in mouse muscle and myogenic cells, compensatory regulation of the histone deacetylase (HDAC5) transcriptional repressor maintains metabolic integrity. HDAC5 phosphorylation regulated the expression of diverse metabolic genes and glucose metabolism in mouse C2C12 myogenic cells. However, loss of AMP-activated protein kinase (AMPK), a HDAC5 kinase, in muscle did not affect HDAC5 phosphorylation in mouse skeletal muscle during exercise, but resulted in a compensatory increase (32.6%) in the activation of protein kinase D (PKD), an alternate HDAC5 kinase. Constitutive PKD activation in mouse C2C12 myogenic cells regulated metabolic genes and glucose metabolism. Although aspects of this response were HDAC5 phosphorylation dependent, blocking HDAC5 phosphorylation when PKD was active engaged an alternative compensatory adaptive mechanism, which involved post-transcriptional reductions in HDAC5 mRNA (-93.1%) and protein. This enhanced the expression of a specific subset of metabolic genes and mitochondrial metabolism. These data show that compensatory regulation of HDAC5 maintains metabolic integrity in mammalian cells and reinforces the importance of preserving the cellular metabolic adaptive response. © FASEB.

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

    Energy Technology Data Exchange (ETDEWEB)

    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)

  8. Characterization of capsaicin induced responses in mice vas deferens

    DEFF Research Database (Denmark)

    Sheykhzade, Majid; Gupta, Saurabh; Sørensen, Tinne

    2011-01-01

    -depth in 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......CGRP>amylin (AMY). These responses were disinhibited by the CGRP receptor antagonists and TRPV1 antagonists. The addition of CGRP receptor antagonists caused a transient potentiation of the twitch response and this potentiation was blocked by pretreatment with capsaicin and enhanced by incubation with exogenous...

  9. Micromanaging the gut: unravelling the regulatory pathways that mediate the intestinal adaptive response.

    Science.gov (United States)

    Balakrishnan, A

    2018-03-01

    Short bowel syndrome occurs following the loss of a large portion of functional intestine and is associated with high morbidity and mortality. The intestine exhibits pronounced diurnal rhythms in glucose absorption and mounts a profound proliferative response following massive small bowel resection. Understanding the molecular pathways that underpin this could yield novel treatment options. Two in vivo models were employed using the nocturnally active Sprague Dawley® rat, namely daytime feeding and massive small bowel resection. Glucose absorption exhibited a 24-hour periodicity in the gut and peaked during maximal nutrient delivery, mediated by rhythms in the glucose transporter sodium glucose co-transporter 1 (SGLT1). Feeding during the day shifted the peak in the circadian clock gene PER1 and SGLT1. RNA interference and luciferase assays demonstrated that PER1 transcriptionally regulates SGLT1, linking for the first time clock genes and intestinal glucose absorption. Intestinal proliferation also exhibited diurnal rhythmicity, with peak absorptive surface area occurring during maximal nutrient availability. mir-16 is diurnally expressed in intestinal crypts, exhibiting minimal expression during maximal nutritional availability. mir-16 overexpression increased apoptosis and arrested proliferation in vitro. mir-125a was upregulated in intestinal crypts following 80% small bowel resection, and induced apoptosis and growth arrest upon overexpression in vitro. This work provides novel insights into the role of circadian clock genes, intestinal transporters and microRNAs in regulating intestinal absorption and proliferation and is the first demonstration of a role for microRNAs in these adaptive phenomena. Modulation of these pathways may represent a new therapeutic option for the management of short bowel syndrome.

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

    Science.gov (United States)

    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

  11. Lithocholic acid controls adaptive immune responses by inhibition of Th1 activation through the Vitamin D receptor.

    Science.gov (United States)

    Pols, Thijs W H; Puchner, Teresa; Korkmaz, H Inci; Vos, Mariska; Soeters, Maarten R; de Vries, Carlie J M

    2017-01-01

    Bile acids are established signaling molecules next to their role in the intestinal emulsification and uptake of lipids. We here aimed to identify a potential interaction between bile acids and CD4+ Th cells, which are central in adaptive immune responses. We screened distinct bile acid species for their potency to affect T cell function. Primary human and mouse CD4+ Th cells as well as Jurkat T cells were used to gain insight into the mechanism underlying these effects. We found that unconjugated lithocholic acid (LCA) impedes Th1 activation as measured by i) decreased production of the Th1 cytokines IFNγ and TNFαα, ii) decreased expression of the Th1 genes T-box protein expressed in T cells (T-bet), Stat-1 and Stat4, and iii) decreased STAT1α/β phosphorylation. Importantly, we observed that LCA impairs Th1 activation at physiological relevant concentrations. Profiling of MAPK signaling pathways in Jurkat T cells uncovered an inhibition of ERK-1/2 phosphorylation upon LCA exposure, which could provide an explanation for the impaired Th1 activation. LCA induces these effects via Vitamin D receptor (VDR) signaling since VDR RNA silencing abrogated these effects. These data reveal for the first time that LCA controls adaptive immunity via inhibition of Th1 activation. Many factors influence LCA levels, including bile acid-based drugs and gut microbiota. Our data may suggest that these factors also impact on adaptive immunity via a yet unrecognized LCA-Th cell axis.

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

    Science.gov (United States)

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

    2016-01-01

    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

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

    Science.gov (United States)

    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. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

  14. Role of MicroRNAs in Obesity-Induced Metabolic Disorder and Immune Response

    Directory of Open Access Journals (Sweden)

    Hong Zhong

    2018-01-01

    Full Text Available In all living organisms, metabolic homeostasis and the immune system are the most fundamental requirements for survival. Recently, obesity has become a global public health issue, which is the cardinal risk factor for metabolic disorder. Many diseases emanating from obesity-induced metabolic dysfunction are responsible for the activated immune system, including innate and adaptive responses. Of note, inflammation is the manifest accountant signal. Deeply studied microRNAs (miRNAs have participated in many pathways involved in metabolism and immune responses to protect cells from multiple harmful stimulants, and they play an important role in determining the progress through targeting different inflammatory pathways. Thus, immune response and metabolic regulation are highly integrated with miRNAs. Collectively, miRNAs are the new targets for therapy in immune dysfunction.

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

    Science.gov (United States)

    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.

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

    International Nuclear Information System (INIS)

    Dutilleul, M.

    2013-01-01

    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

  17. Global immune disregulation in multiple sclerosis: from the adaptive response to the innate immunity.

    Science.gov (United States)

    Ristori, G; Montesperelli, C; Perna, A; Cannoni, S; Battistini, L; Borsellino, G; Riccio, P; Pesole, G; Chersi, A; Pozzilli, C; Buttinelli, C; Salvetti, M

    2000-07-24

    Increasing evidences show a global immune disregulation in multiple sclerosis (MS). The possible involvement of myelin and non-myelin (auto-)antigens in the autoaggressive process as well as the disregulation of both adaptive and innate immunity challenge the concept of specific immunotherapy. T cells at the boundary between innate and adaptive immunity, whose immunoregulatory role is becoming increasingly clear, have recently been shown to bear relevance for MS pathogenesis. Global immune interventions (and type I interferons may be considered as such) aimed at interfering with both innate and acquired immune responses seem to be a most promising therapeutic option in MS.

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

    OpenAIRE

    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...

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

    Energy Technology Data Exchange (ETDEWEB)

    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

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

    International Nuclear Information System (INIS)

    Lavoie Jose; Dolling Jo-Anna; Mitchel Ron E J; Boreham Douglas R

    2004-01-01

    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

  1. NURSING CARE APPROCH MODEL (NCAM–PAKAR ON THE INCREASING OF COGNITIF AND BIOLOGICAL ADAPTATION RESPONSES PATIENT WITH HIV INFECTION

    Directory of Open Access Journals (Sweden)

    Nursalam Nursalam

    2017-04-01

    Full Text Available Introduction: PAKAR model that focused on coping strategy and social support (nurse, family and patients lead to positive coping mechanism through the learning process. The purpose of the study was to examine the effect of PAKAR toward adaptive response on PWH infection. PNI and nursing sciences from Roy paradigm were used in this study. Method: Quasy-experimental pre-post-test non randomized control group design is used in this study. Forty (40 PWH infections in Intermediate Department Care for Infection Disease (UPIPI Dr. Soetomo hospital in Surabaya were selected and non-randomized assignment divided into 2 groups of 20, experiment and control group. In vitro- test were used to measure biological response change: cortical, CD4, IFNγ, and Anti-HIV. Psychological, social, and spiritual response were measured and observed by using questionnaires, in depth interview and Focus Group Discussion. A Multivariate analysis was used to evaluate the data of biological response and non-parametric test: Wilcoxon and Mann Whitney were used to measure cognitive response. Result: Result showed that there were significantly differences on cognitive response between PAKAR and Standard, namely; spiritual response on be patient, social response on emotional stable, and acceptance response on anger and bargaining. In addition, biological response were significantly differences between the groups with F = 0.497 and p = 0.000. The cortical and Anti-HIV variables were the pattern contribution between the groups, with 77.5%. The increase the number of CD4 was found to be the dominance factor that was correlated toward the positive of cognitive response caused by PAKAR. Discussion: PAKAR model that focused on coping strategy and utilizing social support lead to treat cognitive response PWH infection. The model is based on nursing science theory (Roy and Hall combined with psychoneuroimmunology paradigm that is able to induce immune response modulation, especially the

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

    Science.gov (United States)

    Varès, Guillaume; Wang, Bing; Tanaka, Kaoru; Kakimoto, Ayana; Eguchi-Kasai, Kyomi; Nenoi, Mitsuru

    2011-01-10

    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 0.02-0.1Gy X-rays, followed 6h later by challenging 1Gy heavy-ion radiation (carbon-ion: 20 and 40keV/μm, neon-ion: 150keV/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. Copyright © 2010 Elsevier B.V. All rights reserved.

  3. Adaptive response to chronic mild ethanol stress involves ROS, sirtuins and changes in chromosome dosage in wine yeasts.

    Science.gov (United States)

    Adamczyk, Jagoda; Deregowska, Anna; Skoneczny, Marek; Skoneczna, Adrianna; Kwiatkowska, Aleksandra; Potocki, Leszek; Rawska, Ewa; Pabian, Sylwia; Kaplan, Jakub; Lewinska, Anna; Wnuk, Maciej

    2016-05-24

    Industrial yeast strains of economic importance used in winemaking and beer production are genomically diverse and subjected to harsh environmental conditions during fermentation. In the present study, we investigated wine yeast adaptation to chronic mild alcohol stress when cells were cultured for 100 generations in the presence of non-cytotoxic ethanol concentration. Ethanol-induced reactive oxygen species (ROS) and superoxide signals promoted growth rate during passages that was accompanied by increased expression of sirtuin proteins, Sir1, Sir2 and Sir3, and DNA-binding transcription regulator Rap1. Genome-wide array-CGH analysis revealed that yeast genome was shaped during passages. The gains of chromosomes I, III and VI and significant changes in the gene copy number in nine functional gene categories involved in metabolic processes and stress responses were observed. Ethanol-mediated gains of YRF1 and CUP1 genes were the most accented. Ethanol also induced nucleolus fragmentation that confirms that nucleolus is a stress sensor in yeasts. Taken together, we postulate that wine yeasts of different origin may adapt to mild alcohol stress by shifts in intracellular redox state promoting growth capacity, upregulation of key regulators of longevity, namely sirtuins and changes in the dosage of genes involved in the telomere maintenance and ion detoxification.

  4. Adaptive responses to salinity stress across multiple life stages in anuran amphibians.

    Science.gov (United States)

    Albecker, Molly A; McCoy, Michael W

    2017-01-01

    In many regions, freshwater wetlands are increasing in salinity at rates exceeding historic levels. Some freshwater organisms, like amphibians, may be able to adapt and persist in salt-contaminated wetlands by developing salt tolerance. Yet adaptive responses may be more challenging for organisms with complex life histories, because the same environmental stressor can require responses across different ontogenetic stages. Here we investigated responses to salinity in anuran amphibians: a common, freshwater taxon with a complex life cycle. We conducted a meta-analysis to define how the lethality of saltwater exposure changes across multiple life stages, surveyed wetlands in a coastal region experiencing progressive salinization for the presence of anurans, and used common garden experiments to investigate whether chronic salt exposure alters responses in three sequential life stages (reproductive, egg, and tadpole life stages) in Hyla cinerea , a species repeatedly observed in saline wetlands. Meta-analysis revealed differential vulnerability to salt stress across life stages with the egg stage as the most salt-sensitive. Field surveys revealed that 25% of the species known to occur in the focal region were detected in salt-intruded habitats. Remarkably, Hyla cinerea was found in large abundances in multiple wetlands with salinity concentrations 450% higher than the tadpole-stage LC 50 . Common garden experiments showed that coastal (chronically salt exposed) populations of H. cinerea lay more eggs, have higher hatching success, and greater tadpole survival in higher salinities compared to inland (salt naïve) populations. Collectively, our data suggest that some species of anuran amphibians have divergent and adaptive responses to salt exposure across populations and across different life stages. We propose that anuran amphibians may be a novel and amenable natural model system for empirical explorations of adaptive responses to environmental change.

  5. Distinct DC subsets regulate adaptive Th1 and 2 responses during Trichuris muris infection

    DEFF Research Database (Denmark)

    Demiri, M.; Müller-Luda, K.; Agace, William Winston

    2017-01-01

    Low- and high-dose infections with the murine large intestinal nematode Trichuris muris are associated with induction of adaptive Th1 and Th2 responses, respectively, in mesenteric lymph nodes (MLN). Classical dendritic cells (cDC) accumulate in the large intestinal mucosa and MLN upon T. muris...... a high-dose infection and displayed impaired Th2 responses. Conversely, mice lacking IRF8-dependent cDC cleared a low-dose infection and displayed an impaired Th1 response while increased production of Th2 cytokines. Finally, mice lacking both IRF4- and IRF8-dependent cDC were able to generate a Th2...

  6. Cellular Responses to Cisplatin-Induced DNA Damage

    Directory of Open Access Journals (Sweden)

    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.

  7. The host response to lesions induced by human papillomavirus.

    Science.gov (United States)

    Stanley, M; Coleman, N; Chambers, M

    1994-01-01

    Human papillomaviruses (HPVs) are strictly intraepithelial pathogens: in the natural productive infection they induce benign epithelial proliferations of mucocutaneous surfaces, some of which may progress to malignancy. Benign HPV-induced lesions are chronic persistent growths; high levels of viral antigen are expressed in the apparent absence of a host immune response suggesting that these viruses have evolved efficient mechanisms of immune evasion. Cell-mediated responses are central in the pathogenesis of HPV and regression of both cutaneous and genital warts histologically resembles a delayed-type hypersensitivity response (DTH). The antigen(s) in the wart against which this response is initiated are not known but in an experimental murine model DTH responses to the E6 and E7 proteins of HPV-16 can be elicited when viral antigen is presented via the epithelial route. Priming with low levels of viral antigen in this model induces non-responsiveness and the loss of DTH. In HPV-associated cancers the E6/E7 genes are expressed and an antibody response to the proteins is found in at least 50% of cases indicating that these oncoproteins are potential targets for immunotherapy.

  8. Cocaine-Induced Adaptations in Cellular Redox Balance Contributes to Enduring Behavioral Plasticity

    OpenAIRE

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

    2011-01-01

    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 det...

  9. Mobilisation, politics, investment and constant adaptation: lessons from the Australian health-promotion response to HIV.

    Science.gov (United States)

    Brown, Graham; O'Donnell, Daryl; Crooks, Levinia; Lake, Rob

    2014-04-01

    The Australian response to HIV oversaw one of the most rapid and sustained changes in community behaviour in Australia's health-promotion history. The combined action of communities of gay men, sex workers, people who inject drugs, people living with HIV and clinicians working in partnership with government, public health and research has been recognised for many years as highly successful in minimising the HIV epidemic. This article will show how the Australian HIV partnership response moved from a crisis response to a constant and continuously adapting response, with challenges in sustaining the partnership. Drawing on key themes, lessons for broader health promotion are identified. The Australian HIV response has shown that a partnership that is engaged, politically active, adaptive and resourced to work across multiple social, structural, behavioural and health-service levels can reduce the transmission and impact of HIV. The experience of the response to HIV, including its successes and failures, has lessons applicable across health promotion. This includes the need to harness community mobilisation and action; sustain participation, investment and leadership across the partnership; commit to social, political and structural approaches; and build and use evidence from multiple sources to continuously adapt and evolve. So what? The Australian HIV response was one of the first health issues to have the Ottawa Charter embedded from the beginning, and has many lessons to offer broader health promotion and common challenges. As a profession and a movement, health promotion needs to engage with the interactions and synergies across the promotion of health, learn from our evidence, and resist the siloing of our responses.

  10. Allergen-induced changes in airway responsiveness are related to baseline airway responsiveness

    NARCIS (Netherlands)

    deBruinWeller, MS; Weller, FR; RijssenbeekNouwens, LHM; Jansen, HM; deMonchy, JGR

    In the literature, bronchial allergen challenge is usually reported to result in an increase in histamine-induced airway responsiveness (AR). The present study investigated the relation between baseline AR and allergen-induced changes in AR. The effect of allergen challenge on AR was investigated in

  11. A lower dose threshold for the in vivo protective adaptive response to radiation. Tumorigenesis in chronically exposed normal and Trp53 heterozygous C57BL/6 mice

    International Nuclear Information System (INIS)

    Mitchel, R.E.J.; Burchart, P.; Wyatt, H.

    2008-01-01

    Low doses of ionizing radiation to cells and animals may induce adaptive responses that reduce the risk of cancer. However, there are upper dose thresholds above which these protective adaptive responses do not occur. We have now tested the hypothesis that there are similar lower dose thresholds that must be exceeded in order to induce protective effects in vivo. We examined the effects of low dose/low dose rate fractionated exposures on cancer formation in Trp53 normal or cancer-prone Trp53 heterozygous female C57BL/6 mice. Beginning at 6 weeks of age, mice were exposed 5 days/week to single daily doses (0.33 mGy, 0.7 mGy/h) totaling 48, 97 or 146 mGy over 30, 60 or 90 weeks. The exposures for shorter times (up to 60 weeks) appeared to be below the level necessary to induce overall protective adaptive responses in Trp53 normal mice, and detrimental effects (shortened lifespan, increased frequency) evident for only specific tumor types (B- and T-cell lymphomas), were produced. Only when the exposures were continued for 90 weeks did the dose become sufficient to induce protective adaptive responses, balancing the detrimental effects for these specific cancers, and reducing the risk level back to that of the unexposed animals. Detrimental effects were not seen for other tumor types, and a protective effect was seen for sarcomas after 60 weeks of exposure, which was then lost when the exposure continued for 90 weeks. As previously shown for the upper dose threshold for protection by low doses, the lower dose boundary between protection and harm was influenced by Trp53 functionality. Neither protection nor harm was observed in exposed Trp53 heterozygous mice, indicating that reduced Trp53 function raises the lower dose/dose rate threshold for both detrimental and protective tumorigenic effects. (author)

  12. Adaptive Surrogate Modeling for Response Surface Approximations with Application to Bayesian Inference

    KAUST Repository

    Prudhomme, Serge

    2015-01-07

    The need for surrogate models and adaptive methods can be best appreciated if one is interested in parameter estimation using a Bayesian calibration procedure for validation purposes. We extend here our latest work on error decomposition and adaptive refinement for response surfaces to the development of surrogate models that can be substituted for the full models to estimate the parameters of Reynolds-averaged Navier-Stokes models. The error estimates and adaptive schemes are driven here by a quantity of interest and are thus based on the approximation of an adjoint problem. We will focus in particular to the accurate estimation of evidences to facilitate model selection. The methodology will be illustrated on the Spalart-Allmaras RANS model for turbulence simulation.

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

    Science.gov (United States)

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

    2015-01-01

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

  14. Acetobacter pasteurianus metabolic change induced by initial acetic acid to adapt to acetic acid fermentation conditions.

    Science.gov (United States)

    Zheng, Yu; Zhang, Renkuan; Yin, Haisong; Bai, Xiaolei; Chang, Yangang; Xia, Menglei; Wang, Min

    2017-09-01

    Initial acetic acid can improve the ethanol oxidation rate of acetic acid bacteria for acetic acid fermentation. In this work, Acetobacter pasteurianus was cultured in ethanol-free medium, and energy production was found to increase by 150% through glucose consumption induced by initial acetic acid. However, oxidation of ethanol, instead of glucose, became the main energy production pathway when upon culturing ethanol containing medium. Proteome assay was used to analyze the metabolism change induced by initial acetic acid, which provided insight into carbon metabolic and energy regulation of A. pasteurianus to adapt to acetic acid fermentation conditions. Results were further confirmed by quantitative real-time PCR. In summary, decreased intracellular ATP as a result of initial acetic acid inhibition improved the energy metabolism to produce more energy and thus adapt to the acetic acid fermentation conditions. A. pasteurianus upregulated the expression of enzymes related to TCA and ethanol oxidation to improve the energy metabolism pathway upon the addition of initial acetic acid. However, enzymes involved in the pentose phosphate pathway, the main pathway of glucose metabolism, were downregulated to induce a change in carbon metabolism. Additionally, the enhancement of alcohol dehydrogenase expression promoted ethanol oxidation and strengthened the acetification rate, thereby producing a strong proton motive force that was necessary for energy production and cell tolerance to acetic acid.

  15. Hypobaric intermittent hypoxia attenuates hypoxia-induced depressor response.

    Directory of Open Access Journals (Sweden)

    Fang Cui

    Full Text Available Hypobaric intermittent hypoxia (HIH produces many favorable effects in the cardiovascular system such as anti-hypertensive effect. In this study, we showed that HIH significantly attenuated a depressor response induced by acute hypoxia.Sprague-Dawley rats received HIH in a hypobaric chamber simulating an altitude of 5000 m. The artery blood pressure (ABP, heart rate (HR and renal sympathetic nerve activity (RSNA were recorded in anesthetized control rats and rats received HIH. The baseline ABP, HR and RSNA were not different between HIH and control rats. Acute hypoxia-induced decrease in ABP was significantly attenuated in HIH rat compared with control rats. However, acute hypoxia-induced increases in HR and RSNA were greater in HIH rat than in control rats. After removal of bilateral ascending depressor nerves, acute hypoxia-induced depressor and sympathoexcitatory responses were comparable in control and HIH rats. Furthermore, acute hypoxia-induced depressor and sympathoexcitatory responses did not differ between control and HIH groups after blocking ATP-dependent K(+ channels by glibenclamide. The baroreflex function evaluated by intravenous injection of phenylephrine and sodium nitroprusside was markedly augmented in HIH rats compared with control rats. The pressor and sympathoexcitatory responses evoked by intravenous injection of cyanide potassium were also significantly greater in HIH rats than in control rats.Our findings suggest that HIH suppresses acute hypoxia-induced depressor response through enhancement of baroreflex and chemoreflex function, which involves activation of ATP-dependent K(+ channels. This study provides new information and underlying mechanism on the beneficiary effect of HIH on maintaining cardiovascular homeostasis.

  16. Creative tensions: mutual responsiveness adapted to private sector research and development.

    Science.gov (United States)

    Sonck, Matti; Asveld, Lotte; Landeweerd, Laurens; Osseweijer, Patricia

    2017-09-07

    The concept of mutual responsiveness is currently based on little empirical data in the literature of Responsible Research and Innovation (RRI). This paper explores RRI's idea of mutual responsiveness in the light of recent RRI case studies on private sector research and development (R&D). In RRI, responsible innovation is understood as a joint endeavour of innovators and societal stakeholders, who become mutually responsive to each other in defining the 'right impacts' of the innovation in society, and in steering the innovation towards realising those impacts. Yet, the case studies identified several reasons for why the idea of mutual responsiveness does not always appear feasible or desirable in actual R&D situations. Inspired by the discrepancies between theory and practice, we suggest three further elaborations for the concept of responsiveness in RRI. Process-responsiveness is suggested for identifying situations that require stakeholder involvement specifically during R&D. Product-responsiveness is suggested for mobilising the potential of innovation products to be adaptable according to diverse stakeholder needs. Presponsiveness is suggested as responsiveness towards stakeholders that are not (yet) reachable at a given time of R&D. Our aim is to contribute to a more tangible understanding of responsiveness in RRI, and suggest directions for further analysis in upcoming RRI case studies.

  17. SU-D-BRB-05: Quantum Learning for Knowledge-Based Response-Adaptive Radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    El Naqa, I; Ten, R [Haken University of Michigan, Ann Arbor, MI (United States)

    2016-06-15

    Purpose: There is tremendous excitement in radiotherapy about applying data-driven methods to develop personalized clinical decisions for real-time response-based adaptation. However, classical statistical learning methods lack in terms of efficiency and ability to predict outcomes under conditions of uncertainty and incomplete information. Therefore, we are investigating physics-inspired machine learning approaches by utilizing quantum principles for developing a robust framework to dynamically adapt treatments to individual patient’s characteristics and optimize outcomes. Methods: We studied 88 liver SBRT patients with 35 on non-adaptive and 53 on adaptive protocols. Adaptation was based on liver function using a split-course of 3+2 fractions with a month break. The radiotherapy environment was modeled as a Markov decision process (MDP) of baseline and one month into treatment states. The patient environment was modeled by a 5-variable state represented by patient’s clinical and dosimetric covariates. For comparison of classical and quantum learning methods, decision-making to adapt at one month was considered. The MDP objective was defined by the complication-free tumor control (P{sup +}=TCPx(1-NTCP)). A simple regression model represented state-action mapping. Single bit in classical MDP and a qubit of 2-superimposed states in quantum MDP represented the decision actions. Classical decision selection was done using reinforcement Q-learning and quantum searching was performed using Grover’s algorithm, which applies uniform superposition over possible states and yields quadratic speed-up. Results: Classical/quantum MDPs suggested adaptation (probability amplitude ≥0.5) 79% of the time for splitcourses and 100% for continuous-courses. However, the classical MDP had an average adaptation probability of 0.5±0.22 while the quantum algorithm reached 0.76±0.28. In cases where adaptation failed, classical MDP yielded 0.31±0.26 average amplitude while the

  18. SU-D-BRB-05: Quantum Learning for Knowledge-Based Response-Adaptive Radiotherapy

    International Nuclear Information System (INIS)

    El Naqa, I; Ten, R

    2016-01-01

    Purpose: There is tremendous excitement in radiotherapy about applying data-driven methods to develop personalized clinical decisions for real-time response-based adaptation. However, classical statistical learning methods lack in terms of efficiency and ability to predict outcomes under conditions of uncertainty and incomplete information. Therefore, we are investigating physics-inspired machine learning approaches by utilizing quantum principles for developing a robust framework to dynamically adapt treatments to individual patient’s characteristics and optimize outcomes. Methods: We studied 88 liver SBRT patients with 35 on non-adaptive and 53 on adaptive protocols. Adaptation was based on liver function using a split-course of 3+2 fractions with a month break. The radiotherapy environment was modeled as a Markov decision process (MDP) of baseline and one month into treatment states. The patient environment was modeled by a 5-variable state represented by patient’s clinical and dosimetric covariates. For comparison of classical and quantum learning methods, decision-making to adapt at one month was considered. The MDP objective was defined by the complication-free tumor control (P + =TCPx(1-NTCP)). A simple regression model represented state-action mapping. Single bit in classical MDP and a qubit of 2-superimposed states in quantum MDP represented the decision actions. Classical decision selection was done using reinforcement Q-learning and quantum searching was performed using Grover’s algorithm, which applies uniform superposition over possible states and yields quadratic speed-up. Results: Classical/quantum MDPs suggested adaptation (probability amplitude ≥0.5) 79% of the time for splitcourses and 100% for continuous-courses. However, the classical MDP had an average adaptation probability of 0.5±0.22 while the quantum algorithm reached 0.76±0.28. In cases where adaptation failed, classical MDP yielded 0.31±0.26 average amplitude while the quantum

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

    Science.gov (United States)

    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. © 2015 Society for Risk Analysis.

  20. Cytotoxic amounts of cisplatin induce either checkpoint adaptation or apoptosis in a concentration-dependent manner in cancer cells.

    Science.gov (United States)

    Swift, Lucy H; Golsteyn, Roy M

    2016-05-01

    Checkpoint adaptation (entry into mitosis with damaged DNA) is a process that links arrest at the G2/M cell cycle checkpoint and cell death in cancer cells. It is not known, however, whether cells treated with the genotoxic agent, cisplatin, undergo checkpoint adaptation or if checkpoint adaptation is a major pathway leading to cell death or not. Therefore, we investigated the relationship between treatment with cisplatin and cytotoxicity in cancer cells. Treatment of HT-29 human colorectal adenocarcinoma cells with cisplatin can induce cell death by one of two different mechanisms. Cells treated with a cytotoxic 30 μM amount of cisplatin died after undergoing checkpoint adaptation. Before dying, however, almost all treated cells were positive for histone γH2AX staining and contained high levels of cyclin B1. Rounded cells appeared that were positive for phospho-Ser10 histone H3, with low levels of phospho-Tyr15 cyclin-dependent kinase 1, high levels of cyclin-dependent kinase 1 activity, and checkpoint kinase 1 that was not phosphorylated on Ser345. These cells were in mitosis with damaged DNA. Strikingly, with 30 μM cisplatin, 81% of cells had entered mitosis before dying. By contrast, after treatment with 100 μM cisplatin, nearly all cells died but only 7% of cells had entered mitosis. Instead, these cells died by apoptosis; they were positive for annexin-V staining, contained cleaved caspase 3, cleaved caspase 9 and cleaved PARP and did not contain Mcl-1. Our data demonstrate that cancer cells treated with cisplatin can undergo one of two modes of cell death depending upon concentration used. These findings suggest that checkpoint adaptation is likely a primary pathway in genotoxic cell death at pharmacological concentrations of cisplatin. Checkpoint adaptation might be a common biochemical pathway taken by human cancer cells in response to pharmacologically relevant, cytotoxic amounts of damaged DNA. © 2016 Société Française des Microscopies and Soci

  1. Different protein of Echinococcus granulosus stimulates dendritic induced immune response.

    Science.gov (United States)

    Wang, Yana; Wang, Qiang; Lv, Shiyu; Zhang, Shengxiang

    2015-06-01

    Cystic echinococcosis is a chronic infectious disease that results from a host/parasite interaction. Vaccination with ferritin derived from Echinococcus granulosus is a potential preventative treatment. To understand whether ferritin is capable of inducing a host immune response, we investigated the response of dendritic cells (DCs) to both recombinant ferritin protein and the hydatid fluid (HF) of E. granulosus. We evaluated the immunomodulatory potential of these antigens by performing, immunocytochemistry, electron microscopy and in vivo imaging of monocyte-derived murine DCs. During antigen stimulation of DCs, ferritin cause DCs maturation and induced higher levels of surface marker expression and activated T-cell proliferation and migration. On contrary, HF failed to induce surface marker expression and to stimulate T-cell proliferation. In response to HF, DCs produced interleukin-6 (IL-6), but no IL-12 and IL-10. DCs stimulated with ferritin produced high levels of cytokines. Overall, HF appears to induce host immunosuppression in order to ensure parasite survival via inhibits DC maturation and promotes Th2-dependent secretion of cytokines. Although ferritin also promoted DC maturation and cytokine release, it also activates CD4+T-cell proliferation, but regard of the mechanism of the Eg.ferritin induce host to eradicate E. granulosus were not clear.

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

    Science.gov (United States)

    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.

  3. Persistence of the immune response induced by BCG vaccination

    Directory of Open Access Journals (Sweden)

    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

  4. Cardiovascular and autonomic response induced by a 20-week ...

    African Journals Online (AJOL)

    DOI:10.7196/SAJSM.564. Cardiovascular and autonomic response induced by a 20-week military training programme in young healthy South African males ... processed foods) and rural urbanisation in sub-Saharan Africa has seen a shift in the underlying population distribution of risk factors for cardiovascular disease.

  5. Cyclooxygenase inhibitors and the exercise-induced stress response

    African Journals Online (AJOL)

    steroidal anti-inflammatory drug (NSAID) naproxen, and of the coxib, rofecoxib, on the exercise-induced stress response. Design. Eight subjects (age 20.9 ± 1.1 years, weight 70.4 ± 3.9 kg, height 170.9 ± 6.7 cm, body surface area 1.82 ± 0.09 m2, ...

  6. Effects of vitamin C supplement on vascular responses induced by ...

    African Journals Online (AJOL)

    Effects of vitamin C supplement on vascular responses induced by warmth or cold stimulation in normal Nigerians. SI Jaja, SI Aisuodionwe, S Gbenebitse, MO Kehinde. Abstract. No abstract. Nigerian Quarterly Journal of Hospital Medicine Vol. 13(1-2): 61-64. Full Text: EMAIL FULL TEXT EMAIL FULL TEXT · DOWNLOAD ...

  7. The response of Cyclamen hederifolium to water stress induced by ...

    African Journals Online (AJOL)

    STORAGESEVER

    The response of Cyclamen hederifolium to water stress induced by different irrigation levels. Murat Yıldırım1*, Arda ... stress can affect the stomatal closure and reduce photo- synthesis of New Guinea Impatients and limit total flower- ... MATERIALS AND METHODS. The experiment was carried out in a controlled chamber (4 ...

  8. Radiation-induced augmentation of the immune response

    International Nuclear Information System (INIS)

    Anderson, R.E.; Lefkovits, I.; Troup, G.M.

    1980-01-01

    Radiation-induced augmentation of the immune response has been shown to occur both in vivo and in vitro. Evidence is presented to implicate injury to an extremely radiosensitive T cell in the expression of this phenomenon. Experiments are outlined which could be employed to support or reflect this hypothesis

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

    OpenAIRE

    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...

  10. Growth, uniformity, local responsiveness, and system-wide adaptation in multiunit franchising

    OpenAIRE

    Boulay, Jacques; Caemmerer, Barbara; Evanschitzky, Heiner; Duniach, Krista

    2016-01-01

    Using the resource-based view framework, we investigate the link between multiunit franchising (MUF) and performance on four key challenges in franchise chain management: growth, uniformity, local responsiveness, and system-wide adaptation. Our findings support the assertion that system growth is positively related to MUF rate within a system, in particular in relation to geographic expansion. Interestingly, while uniformity does not seem to be related to MUF rate, we find marginal support fo...

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

    OpenAIRE

    Schmolke, Mirco; García-Sastre, Adolfo

    2010-01-01

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

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

    Directory of Open Access Journals (Sweden)

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    Trommelen, Jorn; van Loon, Luc J C

    2016-11-28

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Jorn Trommelen

    2016-11-01

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

  17. Adaptation of exercise-induced stress in well-trained healthy young men

    NARCIS (Netherlands)

    Janssen Duijghuijsen, L.M.; Keijer, J.; Mensink, M.R.; Lenaerts, Kaatje; Ridder, L.O.; Nierkens, Stefan; Kartaram, Shirley; Verschuren, Martie C.M.; Pieters, Raymond; Bas, Richard; Witkamp, R.F.; Wichers, H.J.; Norren, van K.

    2017-01-01

    Strenuous exercise induces different stress-related physiological changes, potentially including changes in intestinal barrier function. In the Protégé Study (ISRCTN14236739; www.isrctn.com) we determined the test-retest repeatability in responses to exercise in well-trained individuals.
    Eleven

  18. Adaptation of exercise-induced stress in well-trained healthy young men

    NARCIS (Netherlands)

    JanssenDuijghuijsen, Lonneke M; Keijer, Jaap; Mensink, Marco; Lenaerts, Kaatje; Ridder, Lars; Nierkens, Stefan; Kartaram, Shirley W; Verschuren, Martie C M; Pieters, Raymond H H; Bas, Richard; Witkamp, Renger F; Wichers, Harry J; van Norren, Klaske

    2017-01-01

    Strenuous exercise induces different stress-related physiological changes, potentially including changes in intestinal barrier function. In the Protégé Study (ISRCTN14236739; www.isrctn.com) we determined the test-retest repeatability in responses to exercise in well-trained individuals. Eleven

  19. Endogenous pleiotrophin and midkine regulate LPS-induced glial responses.

    Science.gov (United States)

    Fernández-Calle, Rosalía; Vicente-Rodríguez, Marta; Gramage, Esther; de la Torre-Ortiz, Carlos; Pérez-García, Carmen; Ramos, María P; Herradón, Gonzalo

    2018-01-01

    Pleiotrophin (PTN) and Midkine (MK) are two growth factors that modulate neuroinflammation. PTN overexpression in the brain prevents LPS-induced astrocytosis in mice but potentiates microglial activation. The modest astrocytic response caused by a low dose of LPS (0.5mg/kg) is blocked in the striatum of MK-/- mice whereas microglial response is unaffected. We have now tested the effects of an intermediate dose of LPS (7.5mg/kg) in glial response in PTN-/- and MK-/- mice. We found that LPS-induced astrocytosis is prevented in prefrontal cortex and striatum of both PTN-/- and MK-/- mice. Some of the morphological changes of microglia induced by LPS tended to increase in both genotypes, particularly in PTN-/- mice. Since we previously showed that PTN potentiates LPS-induced activation of BV2 microglial cells, we tested the activation of FYN kinase, a substrate of the PTN receptor RPTPβ/ζ, and the subsequent ERK1/2 phosphorylation on LPS and PTN-treated BV2 cells. LPS effects on BV2 cells were not affected by the addition of PTN, suggesting that PTN does not recruit the FYN-MAP kinase signaling pathway in order to modulate LPS effects on microglial cells. Taking together, evidences demonstrate that regulation of astroglial responses to LPS administration are highly dependent on the levels of expression of PTN and MK. Further studies are needed to clarify the possible roles of endogenous expression of PTN and MK in LPS-induced microglial responses. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Rapid flow-induced responses in endothelial cells

    Science.gov (United States)

    Stamatas, G. N.; McIntire, L. V.

    2001-01-01

    Endothelial cells alter their morphology, growth rate, and metabolism in response to fluid shear stress. To study rapid flow-induced responses in the 3D endothelial cell morphology and calcium distribution, coupled fluorescence microscopy with optical sectioning, digital imaging, and numerical deconvolution techniques have been utilized. Results demonstrate that within the first minutes of flow application nuclear calcium is increasing. In the same time frame whole cell height and nuclear height are reduced by about 1 microm. Whole cell height changes may facilitate reduction of shear stress gradients on the luminal surface, whereas nuclear structural changes may be important for modulating endothelial growth rate and metabolism. To study the role of the cytoskeleton in these responses, endothelial cells have been treated with specific disrupters (acrylamide, cytochalasin D, and colchicine) of each of the cytoskeleton elements (intermediate filaments, microfilaments, and microtubules, respectively). None of these compounds had any effect on the shear-induced calcium response. Cytochalasin D and acrylamide did not affect the shear-induced nuclear morphology changes. Colchicine, however, completely abrogated the response, indicating that microtubules may be implicated in force transmission from the plasma membrane to the nucleus. A pedagogical model based on tensegrity theory principles is presented that is consistent with the results on the 3D endothelial morphology.

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

    DEFF Research Database (Denmark)

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

    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...... differentially activate multiple signaling pathways within the mast cells required for the generation and/or release of inflammatory mediators. Thus, the composition of the suite of mediators released and the physiologic ramifications of these responses are dependent on the stimuli and the microenvironment...

  2. Successive annual influenza vaccination induces a recurrent oligoclonotypic memory response in circulating T follicular helper cells

    Science.gov (United States)

    Herati, Ramin Sedaghat; Muselman, Alexander; Vella, Laura; Bengsch, Bertram; Parkhouse, Kaela; Del Alcazar, Daniel; Kotzin, Jonathan; Doyle, Susan A.; Tebas, Pablo; Hensley, Scott E.; Su, Laura F.; Schmader, Kenneth E.; Wherry, E. John

    2017-01-01

    T follicular helper (Tfh) CD4 cells are crucial providers of B cell help during adaptive immune responses. A circulating population of CD4 T cells, termed cTfh, have similarity to lymphoid Tfh, can provide B cell help, and responded to influenza vaccination. However, it is unclear whether human vaccination-induced cTfh respond in an antigen-specific manner and whether they form long-lasting memory. Here, we identified a cTfh population that expressed multiple T cell activation markers and could be readily identified by coexpression of ICOS and CD38. This subset expressed more Bcl-6, c-Maf, and IL-21 than other blood CD4 subsets. Influenza vaccination induced a strong response in the ICOS+CD38+ cTfh at day 7, and this population included hemagglutinin-specific cells by tetramer staining and antigen-stimulated Activation Induced Marker (AIM) expression. Moreover, TCRB sequencing identified a clonal response in ICOS+CD38+ cTfh that correlated strongly with the increased circulating ICOS+CD38+ cTfh frequency and the circulating plasmablast response. In subjects who received successive annual vaccinations, a recurrent oligoclonal response was identified in the ICOS+CD38+ cTfh subset at 7 days after every vaccination. These oligoclonal responses in ICOS+CD38+ cTfh after vaccination persisted in the ICOS−CD38− cTfh repertoire in subsequent years, suggesting clonal maintenance in a memory reservoir in the more-stable ICOS−CD38− cTfh subset. These data highlight the antigen-specificity, lineage relationships and memory properties of human cTfh responses to vaccination, providing new avenues for tracking and monitoring cTfh responses during infection and vaccination in humans. PMID:28620653

  3. A simulation study for comparing testing statistics in response-adaptive randomization.

    Science.gov (United States)

    Gu, Xuemin; Lee, J Jack

    2010-06-05

    Response-adaptive randomizations are able to assign more patients in a comparative clinical trial to the tentatively better treatment. However, due to the adaptation in patient allocation, the samples to be compared are no longer independent. At large sample sizes, many asymptotic properties of test statistics derived for independent sample comparison are still applicable in adaptive randomization provided that the patient allocation ratio converges to an appropriate target asymptotically. However, the small sample properties of commonly used test statistics in response-adaptive randomization are not fully studied. Simulations are systematically conducted to characterize the statistical properties of eight test statistics in six response-adaptive randomization methods at six allocation targets with sample sizes ranging from 20 to 200. Since adaptive randomization is usually not recommended for sample size less than 30, the present paper focuses on the case with a sample of 30 to give general recommendations with regard to test statistics for contingency tables in response-adaptive randomization at small sample sizes. Among all asymptotic test statistics, the Cook's correction to chi-square test (TMC) is the best in attaining the nominal size of hypothesis test. The William's correction to log-likelihood ratio test (TML) gives slightly inflated type I error and higher power as compared with TMC, but it is more robust against the unbalance in patient allocation. TMC and TML are usually the two test statistics with the highest power in different simulation scenarios. When focusing on TMC and TML, the generalized drop-the-loser urn (GDL) and sequential estimation-adjusted urn (SEU) have the best ability to attain the correct size of hypothesis test respectively. Among all sequential methods that can target different allocation ratios, GDL has the lowest variation and the highest overall power at all allocation ratios. The performance of different adaptive randomization

  4. Redox stress proteins are involved in adaptation response of the hyperthermoacidophilic archaeon Sulfolobus solfataricus to nickel challenge

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    Scaloni Andrea

    2007-08-01

    Full Text Available Abstract Background Exposure to nickel (Ni and its chemical derivatives has been associated with severe health effects in human. On the contrary, poor knowledge has been acquired on target physiological processes or molecular mechanisms of this metal in model organisms, including Bacteria and Archaea. In this study, we describe an analysis focused at identifying proteins involved in the recovery of the archaeon Sulfolobus solfataricus strain MT4 from Ni-induced stress. Results To this purpose, Sulfolobus solfataricus was grown in the presence of the highest nickel sulphate concentration still allowing cells to survive; crude extracts from treated and untreated cells were compared at the proteome level by using a bi-dimensional chromatography approach. We identified several proteins specifically repressed or induced as result of Ni treatment. Observed up-regulated proteins were largely endowed with the ability to trigger recovery from oxidative and osmotic stress in other biological systems. It is noteworthy that most of the proteins induced following Ni treatment perform similar functions and a few have eukaryal homologue counterparts. Conclusion These findings suggest a series of preferential gene expression pathways activated in adaptation response to metal challenge.

  5. Lipolytic response of adipose tissue and metabolic adaptations to long periods of fasting in red tilapia (Oreochromis sp., Teleostei: Cichlidae

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    WALTER DIAS JUNIOR

    2016-01-01

    Full Text Available ABSTRACT Adaptive changes of carbohydrate and lipid metabolism induced by 7, 15, 30, 60, 90, 150 and 200 days of fasting were investigated in red tilapia (Oreochromis sp.. Plasma glucose, lactate and free fatty acids (FFA levels, liver and muscle glycogen and total lipid contents and rates of FFA release from mesenteric adipose tissue (MAT were measured. Plasma glucose levels showed significant differences only after 90 days of fasting, when glycemia was 34% lower (50±5mg.dL-1 than fed fish values (74±1mg.dL-1, remaining relatively constant until 200 days of fasting. The content of liver glycogen ("15% in fed tilapia fell 40% in 7 days of food deprivation. In 60, 90 and 150 days of fasting, plasma FFA levels increased 49%, 64% and 90%, respectively, compared to fed fish values. In agreement with the increase in plasma FFA, fasting induced a clear increase in lipolytic activity of MAT incubated in vitro. Addition of isobutylmethylxanthine (cAMP-phosphodiesterase inhibitor and isoproterenol (non selective beta adrenergic agonist to the incubation medium induced a reduction of lipolysis in fasted fish, differently to what was observed in mammal adipose tissue. This study allowed a physiological assessment of red tilapia response to starvation.

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

    Science.gov (United States)

    Pareek, Ashwani; Singla-Pareek, Sneh Lata

    2016-01-01

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

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

    Science.gov (United States)

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

    1996-05-01

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

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

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    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

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

    Science.gov (United States)

    Burke, Kelly P; Cox, Andrea L

    2010-07-01

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

  10. Winter-swimming as a building-up body resistance factor inducing adaptive changes in the oxidant/antioxidant status.

    Science.gov (United States)

    Lubkowska, Anna; Dołęgowska, Barbara; Szyguła, Zbigniew; Bryczkowska, Iwona; Stańczyk-Dunaj, Małgorzata; Sałata, Daria; Budkowska, Marta

    2013-01-01

    The aim of our research was to examine whether winter-swimming for five consecutive months results in adaptational changes improving tolerance to stress induced by exposure to cryogenic temperatures during whole-body cryostimulation (WBC). The research involved 15 healthy men, with normal bodyweight, who had never been subjected to either WBC or cold water immersion. During the experiment, the participants were twice subjected to WBC (3 min/- 130°C), namely before the winter-swimming season and after the season. Blood was taken seven times: In the morning before each cryostimulation, 30 min after each cryostimulation and the next morning. Additionally, control blood was collected in the middle of the winter season, in February. Our analysis concerned changes in hematological parameters as well as in reduced glutathione and oxidized glutathione, total oxidant status, total antioxidant status and in components of the antioxidant system: Superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione S-transferase and 8-Isoprostanes as a sensitive indicator of oxidative stress. We found significant changes in hemoglobin concentration, the number of red blood cells, the hematocrit index and mean corpuscular volume of red blood cell and the percentage of monocytes and granulocytes after the winter swimming season. The response to cryogenic temperatures was milder after five months of winter-swimming. The obtained results may indicate positive adaptive changes in the antioxidant system of healthy winter-swimmers. These changes seem to increase the readiness of the human body to stress factors.

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

    Directory of Open Access Journals (Sweden)

    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

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

    International Nuclear Information System (INIS)

    Maldonado, Solvey; Findeisen, Rolf

    2010-01-01

    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.

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

    Science.gov (United States)

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

    2016-01-01

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

  14. Cardiovascular Responses Induced by Obstructive Apnea Are Enhanced in Hypertensive Rats Due to Enhanced Chemoreceptor Responsivity

    Science.gov (United States)

    Angheben, Juliana M. M.; Schoorlemmer, Guus H. M.; Rossi, Marcio V.; Silva, Thiago A.; Cravo, Sergio L.

    2014-01-01

    Spontaneously hypertensive rats (SHR), like patients with sleep apnea, have hypertension, increased sympathetic activity, and increased chemoreceptor drive. We investigated the role of carotid chemoreceptors in cardiovascular responses induced by obstructive apnea in awake SHR. A tracheal balloon and vascular cannulas were implanted, and a week later, apneas of 15 s each were induced. The effects of apnea were more pronounced in SHR than in control rats (Wistar Kyoto; WKY). Blood pressure increased by 57±3 mmHg during apnea in SHR and by 28±3 mmHg in WKY (papneas were induced two days later. The inactivation of chemoreceptors reduced the responses to apnea and abolished the difference between SHR and controls. The apnea-induced hypertension was 11±4 mmHg in SHR and 8±4 mmHg in WKY. The respiratory effort was 15±2 mmHg in SHR and 15±2 mmHg in WKY. The heart rate fell 63±18 bpm in SHR and 52±14 bpm in WKY. Similarly, when the chemoreceptors were unloaded by the administration of 100% oxygen, the responses to apnea were reduced. In conclusion, arterial chemoreceptors contribute to the responses induced by apnea in both strains, but they are more important in SHR and account for the exaggerated responses of this strain to apnea. PMID:24466272

  15. Cytomegalovirus: pathophysiological mechanisms of the cytomegalovirus-induced cellular responses

    International Nuclear Information System (INIS)

    Nokta, M.A.

    1986-01-01

    Cytomegalovirus (CMV) infection of fibroblasts of human origin is associated with a cascade of morphologic cellular responses which in other systems have been associated with regulation of intracellular free (IF) [Ca ++ ]. In the present study, the relationship of specific ion fluxes (Ca ++ , Na + ) to the development of cytomegalovirus (CMV)-induced morphologic cellular responses was investigated. An influx of Ca ++ was observed by the first hour after CMV infection (PI), and total calcium sequestered by infected cells was enhanced by 5 hr Pl. A gradual rise in intracellular free (IF) [Ca ++ ] was observed that continued through 48 hour postinfection (hr Pl). The IF [Ca ++ ] response to CMV infection was shown to be multiplicity dependent, require viable virus, and occur under conditions consistent with the expression of immediate early CMV genes. Development and progression of cytomegaly was found to be independent of CMV DNA synthesis and appeared to be dependent on the IF [Ca ++ ] response. Ca ++ influx blockers (e.g. verapamil) and cyclic nucleotide modulators (e.g. papaverine) inhibited both Ca ++ responses and cytomegaly. Quabain-sensitive 86 Rb uptake and sequestering of Ca ++ increased in parallel with development of cytomegaly. There may be a relationship between Ca ++ influx, IF [Ca ++ ], activation of the Na + /H + exchanger, induction of Na + , Cl - , HCO 3 cotransport, Na + entry, Na + /K + ATPase activity and development of CMV-induced morphologic cellular responses including cytomegaly

  16. Low-Dose Ionizing Radiation Affects Mesenchymal Stem Cells via Extracellular Oxidized Cell-Free DNA: A Possible Mediator of Bystander Effect and Adaptive Response

    Directory of Open Access Journals (Sweden)

    V. A. Sergeeva

    2017-01-01

    Full Text Available We have hypothesized that the adaptive response to low doses of ionizing radiation (IR is mediated by oxidized cell-free DNA (cfDNA fragments. Here, we summarize our experimental evidence for this model. Studies involving measurements of ROS, expression of the NOX (superoxide radical production, induction of apoptosis and DNA double-strand breaks, antiapoptotic gene expression and cell cycle inhibition confirm this hypothesis. We have demonstrated that treatment of mesenchymal stem cells (MSCs with low doses of IR (10 cGy leads to cell death of part of cell population and release of oxidized cfDNA. cfDNA has the ability to penetrate into the cytoplasm of other cells. Oxidized cfDNA, like low doses of IR, induces oxidative stress, ROS production, ROS-induced oxidative modifications of nuclear DNA, DNA breaks, arrest of the cell cycle, activation of DNA reparation and antioxidant response, and inhibition of apoptosis. The MSCs pretreated with low dose of irradiation or oxidized cfDNA were equally effective in induction of adaptive response to challenge further dose of radiation. Our studies suggest that oxidized cfDNA is a signaling molecule in the stress signaling that mediates radiation-induced bystander effects and that it is an important component of the development of radioadaptive responses to low doses of IR.

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

    International Nuclear Information System (INIS)

    Ma, Jie; Nossa, Carlos W.; Xiu, Zongming; Rixey, William G.; Alvarez, Pedro J.J.

    2013-01-01

    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

  18. Evolutionary adaptation to environmental stressors: a common response at the proteomic level.

    Science.gov (United States)

    Sørensen, Jesper G; Schou, Mads F; Loeschcke, Volker

    2017-06-01

    Mechanistic trade-offs between traits under selection can shape and constrain evolutionary adaptation to environmental stressors. However, our knowledge of the quantitative and qualitative overlap in the molecular machinery among stress tolerance traits is highly restricted by the challenges of comparing and interpreting data between separate studies and laboratories, as well as to extrapolating between different levels of biological organization. We investigated the expression of the constitutive proteome (833 proteins) of 35 Drosophila melanogaster replicate populations artificially selected for increased resistance to six different environmental stressors. The evolved proteomes were significantly differentiated from replicated control lines. A targeted analysis of the constitutive proteomes revealed a regime-specific selection response among heat-shock proteins, which provides evidence that selection also adjusts the constitutive expression of these molecular chaperones. Although the selection response in some proteins was regime specific, the results were dominated by evidence for a "common stress response." With the exception of high temperature survival, we found no evidence for negative correlations between environmental stress resistance traits, meaning that evolutionary adaptation is not constrained by mechanistic trade-offs in regulation of functional important proteins. Instead, standing genetic variation and genetic trade-offs outside regulatory domains likely constrain the evolutionary responses in natural populations. © 2017 The Author(s). Evolution © 2017 The Society for the Study of Evolution.

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

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    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.

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

    Science.gov (United States)

    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. © 2015 New York Academy of Sciences.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  2. Dataset of red light induced pupil constriction superimposed on post-illumination pupil response

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    Shaobo Lei

    2016-09-01

    Full Text Available We collected and analyzed pupil diameter data from of 7 visually normal participants to compare the maximum pupil constriction (MPC induced by “Red Only” vs. “Blue+Red” visual stimulation conditions.The “Red Only” condition consisted of red light (640±10 nm stimuli of variable intensity and duration presented to dark-adapted eyes with pupils at resting state. This condition stimulates the cone-driven activity of the intrinsically photosensitive retinal ganglion cells (ipRGC. The “Blue+Red” condition consisted of the same red light stimulus presented during ongoing blue (470±17 nm light-induced post-illumination pupil response (PIPR, representing the cone-driven ipRGC activity superimposed on the melanopsin-driven intrinsic activity of the ipRGCs (“The Absence of Attenuating Effect of Red light Exposure on Pre-existing Melanopsin-Driven Post-illumination Pupil Response” Lei et al. (2016 [1].MPC induced by the “Red Only” condition was compared with the MPC induced by the “Blue+Red” condition by multiple paired sample t-tests with Bonferroni correction. Keywords: Pupil light reflex, Chromatic pupillometry, Melanopsin, Post-illumination pupil response

  3. Mitigation of Temperature Induced Single Event Crosstalk Noise by Applying Adaptive Forward Body Bias

    Science.gov (United States)

    Bhowmik, Pankaj

    Soft Errors due to Single Event (SE) Transients is one of the important reliability issues, which is becoming very prominent in advanced technology and in space applications. Increasing coupling effects among interconnects, on the other hand, can cause SE Transients to contaminate electronically unrelated circuit paths, which in turn can increase circuit sensitivity to radiation. Coupling capacitance increases due to reducing distances between interconnect lines making crosstalk noise more important. On the other hand, chips now experience higher temperatures due to environmental factors and high performance of chips. High-performance VLSI circuits consume more power and hence experience higher temperature due to high utilization factor. The increased temperature affects both interconnect resistance and driving strength of interconnect buffers. This work shows that thermal effects increase the amount of crosstalk noise observed on the victim line at nominal supply voltages. With thermally induced crosstalk contribution, total crosstalk noise may exceed the noise margin of the subsequent gate causing a wrong value to be propagated. The crosstalk prevention measures taken such as victim driver sizing may not be sufficient if thermal effects are not properly considered. This work aims to provide a mitigation method for thermally induced crosstalk noise using adaptive forward body bias. At high temperature, drain current reduces, and adaptive body biasing makes the CMOS recover the lost the drain current. A temperature sensor is proposed here to generate a necessary voltage at the CMOS body. A good temperature sensitivity is achieved with the tiny sensors that keep constant driving strength. Interconnect is modeled in using 10-pi modeling and 45nm technology was use for this simulation. Our proposed method mitigates 90% of temperature induced crosstalk contribution.

  4. Overexpression of mitochondrial uncoupling protein 1 (UCP1) induces a hypoxic response in Nicotiana tabacum leaves.

    Science.gov (United States)

    Barreto, Pedro; Okura, Vagner; Pena, Izabella A; Maia, Renato; Maia, Ivan G; Arruda, Paulo

    2016-01-01

    Mitochondrial uncoupling protein 1 (UCP1) decreases reactive oxygen species production under stress conditions by uncoupling the electrochemical gradient from ATP synthesis. This study combined transcriptome profiling with experimentally induced hypoxia to mechanistically dissect the impact of Arabidopsis thaliana UCP1 (AtUCP1) overexpression in tobacco. Transcriptomic analysis of AtUCP1-overexpressing (P07) and wild-type (WT) plants was carried out using RNA sequencing. Metabolite and carbohydrate profiling of hypoxia-treated plants was performed using (1)H-nuclear magnetic resonance spectroscopy and high-performance anion-exchange chromatography with pulsed amperometric detection. The transcriptome of P07 plants revealed a broad induction of stress-responsive genes that were not strictly related to the mitochondrial antioxidant machinery, suggesting that overexpression of AtUCP1 imposes a strong stress response within the cell. In addition, transcripts that mapped into carbon fixation and energy expenditure pathways were broadly altered. It was found that metabolite markers of hypoxic adaptation, such as alanine and tricarboxylic acid intermediates, accumulated in P07 plants under control conditions at similar rates to WT plants under hypoxia. These findings indicate that constitutive overexpression of AtUCP1 induces a hypoxic response. The metabolites that accumulated in P07 plants are believed to be important in signalling for an improvement in carbon assimilation and induction of a hypoxic response. Under these conditions, mitochondrial ATP production is less necessary and fermentative glycolysis becomes critical to meet cell energy demands. In this scenario, the more flexible energy metabolism along with an intrinsically activated hypoxic response make these plants better adapted to face several biotic and abiotic stresses. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  5. Overexpression of mitochondrial uncoupling protein 1 (UCP1) induces a hypoxic response in Nicotiana tabacum leaves

    Science.gov (United States)

    Barreto, Pedro; Okura, Vagner; Pena, Izabella A.; Maia, Renato; Maia, Ivan G.; Arruda, Paulo

    2016-01-01

    Mitochondrial uncoupling protein 1 (UCP1) decreases reactive oxygen species production under stress conditions by uncoupling the electrochemical gradient from ATP synthesis. This study combined transcriptome profiling with experimentally induced hypoxia to mechanistically dissect the impact of Arabidopsis thaliana UCP1 (AtUCP1) overexpression in tobacco. Transcriptomic analysis of AtUCP1-overexpressing (P07) and wild-type (WT) plants was carried out using RNA sequencing. Metabolite and carbohydrate profiling of hypoxia-treated plants was performed using 1H-nuclear magnetic resonance spectroscopy and high-performance anion-exchange chromatography with pulsed amperometric detection. The transcriptome of P07 plants revealed a broad induction of stress-responsive genes that were not strictly related to the mitochondrial antioxidant machinery, suggesting that overexpression of AtUCP1 imposes a strong stress response within the cell. In addition, transcripts that mapped into carbon fixation and energy expenditure pathways were broadly altered. It was found that metabolite markers of hypoxic adaptation, such as alanine and tricarboxylic acid intermediates, accumulated in P07 plants under control conditions at similar rates to WT plants under hypoxia. These findings indicate that constitutive overexpression of AtUCP1 induces a hypoxic response. The metabolites that accumulated in P07 plants are believed to be important in signalling for an improvement in carbon assimilation and induction of a hypoxic response. Under these conditions, mitochondrial ATP production is less necessary and fermentative glycolysis becomes critical to meet cell energy demands. In this scenario, the more flexible energy metabolism along with an intrinsically activated hypoxic response make these plants better adapted to face several biotic and abiotic stresses. PMID:26494730

  6. MiR-155-regulated molecular network orchestrates cell fate in the innate and adaptive immune response to Mycobacterium tuberculosis.

    Science.gov (United States)

    Rothchild, Alissa C; Sissons, James R; Shafiani, Shahin; Plaisier, Christopher; Min, Deborah; Mai, Dat; Gilchrist, Mark; Peschon, Jacques; Larson, Ryan P; Bergthaler, Andreas; Baliga, Nitin S; Urdahl, Kevin B; Aderem, Alan

    2016-10-11

    The regulation of host-pathogen interactions during Mycobacterium tuberculosis (Mtb) infection remains unresolved. MicroRNAs (miRNAs) are important regulators of the immune system, and so we used a systems biology approach to construct an miRNA regulatory network activated in macrophages during Mtb infection. Our network comprises 77 putative miRNAs that are associated with temporal gene expression signatures in macrophages early after Mtb infection. In this study, we demonstrate a dual role for one of these regulators, miR-155. On the one hand, miR-155 maintains the survival of Mtb-infected macrophages, thereby providing a niche favoring bacterial replication; on the other hand, miR-155 promotes the survival and function of Mtb-specific T cells, enabling an effective adaptive immune response. MiR-155-induced cell survival is mediated through the SH2 domain-containing inositol 5-phosphatase 1 (SHIP1)/protein kinase B (Akt) pathway. Thus, dual regulation of the same cell survival pathway in innate and adaptive immune cells leads to vastly different outcomes with respect to bacterial containment.

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

    Directory of Open Access Journals (Sweden)

    Melissa E Slocumb

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

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

    Science.gov (United States)

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

    2015-08-01

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

  9. The health policy implications of individual adaptive behavior responses to smog pollution in urban China.

    Science.gov (United States)

    Ban, Jie; Zhou, Lian; Zhang, Yi; Brooke Anderson, G; Li, Tiantian

    2017-09-01

    Smog pollution is a serious public health issue in urban China, where it is associated with public health through a range of respiratory and cardiovascular illnesses. Despite the negative health impacts of smog pollution, individual adaptive behaviors are poorly understood. This knowledge gap hinders the development of effective public policy to support and encourage the adoption of individual adaptive and mitigating behaviors to smog pollution. A questionnaire survey of 1141 randomly sampled individuals in a typical PM 2.5 -polluted Chinese city was designed to establish smog concerns and behavior changes during smog events. The results demonstrate a variety of behavior responses associated with risk perception, experience of smog, age, and gender of respondents. An understanding of these variations is critical to the development of effective public policy and ultimately to the improvement of public health in cities affected by smog. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    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. Adaptive response to acetic acid in the highly resistant yeast species Zygosaccharomyces bailii revealed by quantitative proteomics.

    Science.gov (United States)

    Guerreiro, Joana F; Mira, Nuno P; Sá-Correia, Isabel

    2012-08-01

    Zygosaccharomyces bailii is the most tolerant yeast species to acetic acid-induced toxicity, being able to grow in the presence of concentrations of this food preservative close to the legal limits. For this reason, Z. bailii is the most important microbial contaminant of acidic food products but the mechanisms behind this intrinsic resistance to acetic acid are very poorly characterized. To gain insights into the adaptive response and tolerance to acetic acid in Z. bailii, we explored an expression proteomics approach, based on quantitative 2DE, to identify alterations occurring in the protein content in response to sudden exposure or balanced growth in the presence of an inhibitory but nonlethal concentration of this weak acid. A coordinate increase in the content of proteins involved in cellular metabolism, in particular, in carbohydrate metabolism (Mdh1p, Aco1p, Cit1p, Idh2p, and Lpd1p) and energy generation (Atp1p and Atp2p), as well as in general and oxidative stress response (Sod2p, Dak2p, Omp2p) was registered. Results reinforce the concept that glucose and acetic acid are coconsumed in Z. bailii, with acetate being channeled into the tricarboxylic acid cycle. When acetic acid is the sole carbon source, results suggest the activation of gluconeogenic and pentose phosphate pathways, based on the increased content of several proteins of these pathways after glucose exhaustion. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Recent advances in understanding the adaptive immune response to Zika virus and the effect of previous flavivirus exposure.

    Science.gov (United States)

    Andrade, Daniela V; Harris, Eva

    2017-06-26

    Zika virus (ZIKV) caused explosive epidemics across the Americas, starting in Brazil in 2015, and has been associated with severe manifestations such as microcephaly in babies born to infected mothers and Guillain-Barré syndrome in adults. As the underlying mechanisms of pathogenesis remain largely unknown, diverse investigations have focused on a potential role for flavivirus cross-reactive antibodies in enhancing ZIKV infection. Antibody-dependent enhancement is especially concerning due to structural similarities between ZIKV and other flaviviruses, especially dengue virus (DENV), that co-circulate in areas affected by ZIKV. Conversely, investigating cross-neutralizing antibodies is important for understanding protection among flaviviruses, including ZIKV. In this review, we discuss the latest findings regarding ZIKV-induced adaptive immunity, such as monoclonal and polyclonal antibody responses, structural immunology, and T cell-mediated responses. Much progress has been made in a short amount of time, but many questions remain. Fully understanding the specificity, magnitude, and kinetics of B cell/antibody and T cell responses in ZIKV-infected individuals with or without prior exposure to flaviviruses is of great relevance for diagnostics and vaccine development. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. FGF21 as a mediator of adaptive responses to stress and metabolic benefits of anti-diabetic drugs.

    Science.gov (United States)

    Kim, Kook Hwan; Lee, Myung-Shik

    2015-07-01

    Most hormones secreted from specific organs of the body in response to diverse stimuli contribute to the homeostasis of the whole organism. Fibroblast growth factor 21 (FGF21), a hormone induced by a variety of environmental or metabolic stimuli, plays a crucial role in the adaptive response to these stressful conditions. In addition to its role as a stress hormone, FGF21 appears to function as a mediator of the therapeutic effects of currently available drugs and those under development for treatment of metabolic diseases. In this review, we highlight molecular mechanisms and the functional importance of FGF21 induction in response to diverse stress conditions such as changes of nutritional status, cold exposure, and exercise. In addition, we describe recent findings regarding the role of FGF21 in the pathogenesis and treatment of diabetes associated with obesity, liver diseases, pancreatitis, muscle atrophy, atherosclerosis, cardiac hypertrophy, and diabetic nephropathy. Finally, we discuss the current understanding of the actions of FGF21 as a crucial regulator mediating beneficial metabolic effects of therapeutic agents such as metformin, glucagon/glucagon-like peptide 1 analogues, thiazolidinedione, sirtuin 1 activators, and lipoic acid. © 2015 Society for Endocrinology.

  14. A Dual-Responsive Nanocomposite toward Climate-Adaptable Solar Modulation for Energy-Saving Smart Windows.

    Science.gov (United States)

    Lee, Heng Yeong; Cai, Yufeng; Bi, Shuguang; Liang, Yen Nan; Song, Yujie; Hu, Xiao Matthew

    2017-02-22

    In this work, a novel fully autonomous photothermotropic material made by hybridization of the poly(N-isopropylacrylamide) (PNIPAM) hydrogel and antimony-tin oxide (ATO) is presented. In this photothermotropic system, the near-infrared (NIR)-absorbing ATO acts as nanoheater to induce the optical switching of the hydrogel. Such a new passive smart window is characterized by excellent NIR shielding, a photothermally activated switching mechanism, enhanced response speed, and solar modulation ability. Systems with 0, 5, 10, and 15 atom % Sb-doped ATO in PNIPAM were investigated, and it was found that a PNIPAM/ATO nanocomposite is able to be photothermally activated. The 10 atom % Sb-doped PNIPAM/ATO exhibits the best response speed and solar modulation ability. Different film thicknesses and ATO contents will affect the response rate and solar modulation ability. Structural stability tests at 15 cycles under continuous exposure to solar irradiation at 1 sun intensity demonstrated the performance stability of such a photothermotropic system. We conclude that such a novel photothermotropic hybrid can be used as a new generation of autonomous passive smart windows for climate-adaptable solar modulation.

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

    Science.gov (United States)

    Kasten, Kevin R; Goetzman, Holly S; Reid, Maria R; Rasper, Alison M; Adediran, Samuel G; Robinson, Chad T; Cave, Cindy M; Solomkin, Joseph S; Lentsch, Alex B; Johannigman, Jay A; Caldwell, Charles C

    2010-01-25

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

    Directory of Open Access Journals (Sweden)

    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.

  17. Streptococcus pneumoniae and Pseudomonas aeruginosa pneumonia induce distinct host responses.

    Science.gov (United States)

    McConnell, Kevin W; McDunn, Jonathan E; Clark, Andrew T; Dunne, W Michael; Dixon, David J; Turnbull, Isaiah R; Dipasco, Peter J; Osberghaus, William F; Sherman, Benjamin; Martin, James R; Walter, Michael J; Cobb, J Perren; Buchman, Timothy G; Hotchkiss, Richard S; Coopersmith, Craig M

    2010-01-01

    Pathogens that cause pneumonia may be treated in a targeted fashion by antibiotics, but if this therapy fails, then treatment involves only nonspecific supportive measures, independent of the inciting infection. The purpose of this study was to determine whether host response is similar after disparate infections with similar mortalities. Prospective, randomized controlled study. Animal laboratory in a university medical center. Pneumonia was induced in FVB/N mice by either Streptococcus pneumoniae or two different concentrations of Pseudomonas aeruginosa. Plasma and bronchoalveolar lavage fluid from septic animals was assayed by a microarray immunoassay measuring 18 inflammatory mediators at multiple time points. The host response was dependent on the causative organism as well as kinetics of mortality, but the pro-inflammatory and anti-inflammatory responses were independent of inoculum concentration or degree of bacteremia. Pneumonia caused by different concentrations of the same bacteria, Pseudomonas aeruginosa, also yielded distinct inflammatory responses; however, inflammatory mediator expression did not directly track the severity of infection. For all infections, the host response was compartmentalized, with markedly different concentrations of inflammatory mediators in the systemic circulation and the lungs. Hierarchical clustering analysis resulted in the identification of five distinct clusters of the host response to bacterial infection. Principal components analysis correlated pulmonary macrophage inflammatory peptide-2 and interleukin-10 with progression of infection, whereas elevated plasma tumor necrosis factor sr2 and macrophage chemotactic peptide-1 were indicative of fulminant disease with >90% mortality within 48 hrs. Septic mice have distinct local and systemic responses to Streptococcus pneumoniae and Pseudomonas aeruginosa pneumonia. Targeting specific host inflammatory responses induced by distinct bacterial infections could represent a

  18. Wave-induced Hydroelastic response of fast monohull ships

    DEFF Research Database (Denmark)

    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 insensitive...... 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...

  19. Fetal responses to induced maternal relaxation during pregnancy

    OpenAIRE

    DiPietro, Janet A.; Costigan, Kathleen A.; Nelson, Priscilla; Gurewitsch, Edith D.; Laudenslager, Mark L.

    2007-01-01

    Fetal responses to induced maternal relaxation during the 32nd week of pregnancy were recorded in 100 maternal-fetal pairs using a digitized data collection system. The 18-minute guided imagery relaxation manipulation generated significant changes in maternal heart rate, skin conductance, respiration period, and respiratory sinus arrhythmia. Significant alterations in fetal neurobehavior were observed, including decreased fetal heart rate (FHR), increased FHR variability, suppression of fetal...

  20. Thyroid transcriptome analysis reveals different adaptive responses to cold environmental conditions between two chicken breeds.

    Science.gov (United States)

    Xie, Shanshan; Yang, Xukai; Wang, Dehe; Zhu, Feng; Yang, Ning; Hou, Zhuocheng; Ning, Zhonghua

    2018-01-01

    Selection for cold tolerance in chickens is important for improving production performance and animal welfare. The identification of chicken breeds with higher cold tolerance and production performance will help to target candidates for the selection. The thyroid gland plays important roles in thermal adaptation, and its function is influenced by breed differences and transcriptional plasticity, both of which remain largely unknown in the chicken thyroid transcriptome. In this study, we subjected Bashang Long-tail (BS) and Rhode Island Red (RIR) chickens to either cold or warm environments for 21 weeks and investigated egg production performance, body weight changes, serum thyroid hormone concentrations, and thyroid gland transcriptome profiles. RIR chickens had higher egg production than BS chickens under warm conditions, but BS chickens produced more eggs than RIRs under cold conditions. Furthermore, BS chickens showed stable body weight gain under cold conditions while RIRs did not. These results suggested that BS breed is a preferable candidate for cold-tolerance selection and that the cold adaptability of RIRs should be improved in the future. BS chickens had higher serum thyroid hormone concentrations than RIRs under both environments. RNA-Seq generated 344.3 million paired-end reads from 16 sequencing libraries, and about 90% of the processed reads were concordantly mapped to the chicken reference genome. Differential expression analysis identified 46-1,211 genes in the respective comparisons. With regard to breed differences in the thyroid transcriptome, BS chickens showed higher cell replication and development, and immune response-related activity, while RIR chickens showed higher carbohydrate and protein metabolism activity. The cold environment reduced breed differences in the thyroid transcriptome compared with the warm environment. Transcriptional plasticity analysis revealed different adaptive responses in BS and RIR chickens to cope with the cold

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

    DEFF Research Database (Denmark)

    Jørgensen, Stine Ringholm

    (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....... Furthermore the physical inactivity abolished the exercise-induced mRNA response of PGC-1α and vascular endothelial growth factor (VEGF) in skeletal muscle that was present before bed rest. This indicates that just 7 days of physical inactivity reduces the metabolic capacity of human skeletal muscle...... that citrate synthase (CS) activity and mtDNA/nDNA content decreased with age in skeletal muscle of WT mice. CS activity, mtDNA/nDNA content, pyruvate dehydrogenase-E1α and VEGF protein content increased with lifelong exercise training in WT mice but not in PGC-1α KO mice. In contrast, lifelong resveratrol...

  2. Improving the Response of Accelerometers for Automotive Applications by Using LMS Adaptive Filters

    Directory of Open Access Journals (Sweden)

    Wilmar Hernandez

    2009-12-01

    Full Text Available In this paper, the least-mean-squares (LMS algorithm was used to eliminate noise corrupting the important information coming from a piezoresisitive accelerometer for automotive applications. This kind of accelerometer is designed to be easily mounted in hard to reach places on vehicles under test, and they usually feature ranges from 50 to 2,000 g (where is the gravitational acceleration, 9.81 m/s2 and frequency responses to 3,000 Hz or higher, with DC response, durable cables, reliable performance and relatively low cost. However, here we show that the response of the sensor under test had a lot of noise and we carried out the signal processing stage by using both conventional and optimal adaptive filtering. Usually, designers have to build their specific analog and digital signal processing circuits, and this fact increases considerably the cost of the entire sensor system and the results are not always satisfactory, because the relevant signal is sometimes buried in a broad-band noise background where the unwanted information and the relevant signal sometimes share a very similar frequency band. Thus, in order to deal with this problem, here we used the LMS adaptive filtering algorithm and compare it with others based on the kind of filters that are typically used for automotive applications. The experimental results are satisfactory.

  3. RAGE Expression in Human T Cells: A Link between Environmental Factors and Adaptive Immune Responses

    Science.gov (United States)

    Akirav, Eitan M.; Preston-Hurlburt, Paula; Garyu, Justin; Henegariu, Octavian; Clynes, Raphael; Schmidt, Ann Marie; Herold, Kevan C.

    2012-01-01

    The Receptor for Advanced Glycation Endproducts (RAGE) is a scavenger ligand that binds glycated endproducts as well as molecules released during cell death such as S100b and HMGB1. RAGE is expressed on antigen presenting cells where it may participate in activation of innate immune responses but its role in adaptive human immune responses has not been described. We have found that RAGE is expressed intracellularly in human T cells following TCR activation but constitutively on T cells from patients with diabetes. The levels of RAGE on T cells from patients with diabetes are not related to the level of glucose control. It co-localizes to the endosomes. Its expression increases in activated T cells from healthy control subjects but bystander cells also express RAGE after stimulation of the antigen specific T cells. RAGE ligands enhance RAGE expression. In patients with T1D, the level of RAGE expression decreases with T cell activation. RAGE+ T cells express higher levels of IL-17A, CD107a, and IL-5 than RAGE− cells from the same individual with T1D. Our studies have identified the expression of RAGE on adaptive immune cells and a role for this receptor and its ligands in modulating human immune responses. PMID:22509345

  4. Molecular mechanisms of adaptive life-history changes in Daphnia magna induced by predator kairomones

    OpenAIRE

    Effertz, Christoph

    2014-01-01

    Planktonic crustaceans of the genus Daphnia play an important role as keystone species in almost all standing freshwater ecosystems. As unselective filter feeders, Daphnia are typically the major herbivorous grazers of phytoplankton and are major prey for predators at higher trophic levels. Daphnia magna has become a textbook example for inducible defences in response to chemical signals released by predators. Daphnia as important prey organism for both invertebrate predators a...

  5. Peptide fragments induce a more rapid immune response than intact proteins in earthworms.

    Science.gov (United States)

    Hanusová, R; Tucková, L; Halada, P; Bezouska, K; Bilej, M

    1999-01-01

    The effect of in vivo proteolytic processing of protein antigen was studied in Eisenia foetida earthworms. Parenteral administration of the protein antigen induces elevated levels of an antigen-binding protein (ABP) which recognizes the protein used for stimulation. When the protein antigen is administered simultaneously with nontoxic serine proteinase inhibitor, ABP levels remain close to background. On the other hand, the in vivo adaptive response of earthworms to peptide fragments obtained by coelomic fluid digestion of the foreign antigen occurs even in the presence of proteinase inhibitor and, moreover, is significantly faster as compared to the response to intact antigen. These findings confirm the role of proteolytic processing in earthworms. MALDI mass spectrometric analysis of the fragments after coelomic fluid digestion has revealed the presence of the peptide fragments with molecular weights in the mass range 700-1100 Da.

  6. CsBAFF, a Teleost B Cell Activating Factor, Promotes Pathogen-Induced Innate Immunity and Vaccine-Induced Adaptive Immunity.

    Directory of Open Access Journals (Sweden)

    Yun Sun

    Full Text Available B cell activating factor (BAFF is a member of the tumor necrosis factor family that is known to play an important role in B cell activation, proliferation, and differentiation in mammals. However, studies of BAFF in teleosts are very limited and its function, in particular that under in vivo conditions, is essentially unknown. In this study, we conducted in vivo as well as in vitro functional analyses of a BAFF homologue (CsBAFF from the teleost fish tongue sole (Cynoglossus semilaevis. CsBAFF is composed of 261 residues and shares moderate sequence identities with known BAFFs of other teleosts. CsBAFF expression was most abundant in immune organs and was upregulated during bacterial infection. Purified recombinant CsBAFF (rCsBAFF bound to tongue sole lymphocytes and promoted cellular proliferation and survival. The results of an in vivo study showed that CsBAFF overexpression in tongue sole significantly enhanced macrophage activation and reduced bacterial infection in fish tissues, whereas knockdown of CsBAFF expression resulted in increased bacterial dissemination and colonization in fish tissues. Furthermore, vaccination studies showed that CsBAFF enhanced the immunoprotection of a DNA vaccine and augmented the production of specific serum antibodies. Taken together, these results provide the first in vivo evidence to indicate that teleost BAFF is an immunostimulator that significantly contributes to the innate antibacterial immune response and vaccine-induced adaptive immune response.

  7. An adaptive and generalizable closed-loop system for control of medically induced coma and other states of anesthesia

    Science.gov (United States)

    Yang, Yuxiao; Shanechi, Maryam M.

    2016-12-01

    Objective. Design of closed-loop anesthetic delivery (CLAD) systems is an important topic, particularly for medically induced coma, which needs to be maintained for long periods. Current CLADs for medically induced coma require a separate offline experiment for model parameter estimation, which causes interruption in treatment and is difficult to perform. Also, CLADs may exhibit bias due to inherent time-variation and non-stationarity, and may have large infusion rate variations at steady state. Finally, current CLADs lack theoretical performance guarantees. We develop the first adaptive CLAD for medically induced coma, which addresses these limitations. Further, we extend our adaptive system to be generalizable to other states of anesthesia. Approach. We designed general parametric pharmacodynamic, pharmacokinetic and neural observation models with associated guidelines, and derived a novel adaptive controller. We further penalized large steady-state drug infusion rate variations in the controller. We derived theoretical guarantees that the adaptive system has zero steady-state bias. Using simulations that resembled real time-varying and noisy environments, we tested the closed-loop system for control of two different anesthetic states, burst suppression in medically induced coma and unconsciousness in general anesthesia. Main results. In 1200 simulations, the adaptive system achieved precise control of both anesthetic states despite non-stationarity, time-variation, noise, and no initial parameter knowledge. In both cases, the adaptive system performed close to a baseline system that knew the parameters exactly. In contrast, a non-adaptive system resulted in large steady-state bias and error. The adaptive system also resulted in significantly smaller steady-state infusion rate variations compared to prior systems. Significance. These results have significant implications for clinically viable CLAD design for a wide range of anesthetic states, with potential cost

  8. Evasion of adaptive and innate immune response mechanisms by γ-herpesviruses

    Science.gov (United States)

    Feng, Pinghui; Moses, Ashlee; Früh, Klaus

    2015-01-01

    γ-Herpesviral immune evasion mechanisms are optimized to support the acute, lytic and the longterm, latent phase of infection. During acute infection, specific immune modulatory proteins limit, but also exploit, the antiviral activities of cell intrinsic innate immune responses as well as those of innate and adaptive immune cells. During latent infection, a restricted gene expression program limits immune targeting and cis-acting mechanisms to reduce the antigen presentation as well as antigenicity of latency-associated proteins. Here, we will review recent progress in our understanding of γ-herpesviral immune evasion strategies. PMID:23735334

  9. Distinct clpP Genes Control Specific Adaptive Responses in Bacillus thuringiensis

    OpenAIRE

    Fedhila, Sinda; Msadek, Tarek; Nel, Patricia; Lereclus, Didier

    2002-01-01

    ClpP and ClpC are subunits of the Clp ATP-dependent protease, which is ubiquitous among prokaryotic and eukaryotic organisms. The role of these proteins in stress tolerance, stationary-phase adaptive responses, and virulence in many bacterial species has been demonstrated. Based on the amino acid sequences of the Bacillus subtilis clpC and clpP genes, we identified one clpC gene and two clpP genes (designated clpP1 and clpP2) in Bacillus thuringiensis. Predicted proteins ClpP1 and ClpP2 have ...

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

    Science.gov (United States)

    Schmolke, Mirco; García-Sastre, Adolfo

    2010-07-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    Directory of Open Access Journals (Sweden)

    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

  13. Skeletal nutrient vascular adaptation induced by external oscillatory intramedullary fluid pressure intervention

    Directory of Open Access Journals (Sweden)

    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.

  14. Myosin heavy chain and physiological adaptation of the rat diaphragm in elastase-induced emphysema

    Directory of Open Access Journals (Sweden)

    Stedman Hansell H

    2003-02-01

    Full Text Available Abstract Background Several physiological adaptations occur in the respiratory muscles in rodent models of elastase-induced emphysema. Although the contractile properties of the diaphragm are altered in a way that suggests expression of slower isoforms of myosin heavy chain (MHC, it has been difficult to demonstrate a shift in MHCs in an animal model that corresponds to the shift toward slower MHCs seen in human emphysema. Methods We sought to identify MHC and corresponding physiological changes in the diaphragms of rats with elastase-induced emphysema. Nine rats with emphysema and 11 control rats were studied 10 months after instillation with elastase. MHC isoform composition was determined by both reverse transcriptase polymerase chain reaction (RT-PCR and immunocytochemistry by using specific probes able to identify all known adult isoforms. Physiological adaptation was studied on diaphragm strips stimulated in vitro. Results In addition to confirming that emphysematous diaphragm has a decreased fatigability, we identified a significantly longer time-to-peak-tension (63.9 ± 2.7 ms versus 53.9 ± 2.4 ms. At both the RNA (RT-PCR and protein (immunocytochemistry levels, we found a significant decrease in the fastest, MHC isoform (IIb in emphysema. Conclusion This is the first demonstration of MHC shifts and corresponding physiological changes in the diaphragm in an animal model of emphysema. It is established that rodent emphysema, like human emphysema, does result in a physiologically significant shift toward slower diaphragmatic MHC isoforms. In the rat, this occurs at the faster end of the MHC spectrum than in humans.

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

    Energy Technology Data Exchange (ETDEWEB)

    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)

  16. Fetal responses to induced maternal relaxation during pregnancy.

    Science.gov (United States)

    DiPietro, Janet A; Costigan, Kathleen A; Nelson, Priscilla; Gurewitsch, Edith D; Laudenslager, Mark L

    2008-01-01

    Fetal responses to induced maternal relaxation during the 32nd week of pregnancy were recorded in 100 maternal-fetal pairs using a digitized data collection system. The 18-min guided imagery relaxation manipulation generated significant changes in maternal heart rate, skin conductance, respiration period, and respiratory sinus arrhythmia. Significant alterations in fetal neurobehavior were observed, including decreased fetal heart rate (FHR), increased FHR variability, suppression of fetal motor activity (FM), and increased FM-FHR coupling. Attribution of the two fetal cardiac responses to the guided imagery procedure itself, as opposed to simple rest or recumbency, is tempered by the observed pattern of response. Evaluation of correspondence between changes within individual maternal-fetal pairs revealed significant associations between maternal autonomic measures and fetal cardiac patterns, lower umbilical and uterine artery resistance and increased FHR variability, and declining salivary cortisol and FM activity. Potential mechanisms that may mediate the observed results are discussed.

  17. Changes of brain response induced by simulated weightlessness

    Science.gov (United States)

    Wei, Jinhe; Yan, Gongdong; Guan, Zhiqiang

    The characteristics change of brain response was studied during 15° head-down tilt (HDT) comparing with 45° head-up tilt (HUT). The brain responses evaluated included the EEG power spectra change at rest and during mental arithmetic, and the event-related potentials (ERPs) of somatosensory, selective attention and mental arithmetic activities. The prominent feature of brain response change during HDT revealed that the brain function was inhibited to some extent. Such inhibition included that the significant increment of "40Hz" activity during HUT arithmetic almost disappeared during HDT arithmetic, and that the positive-potential effect induced by HDT presented in all kinds of ERPs measured, but the slow negative wave reflecting mental arithmetic and memory process was elongated. These data suggest that the brain function be affected profoundly by the simulated weightlessness, therefore, the brain function change during space flight should be studied systematically.

  18. Enhancement of human adaptive immune responses by administration of a high-molecular-weight polysaccharide extract from the cyanobacterium Arthrospira platensisTumor necrosis factor-alpha binding capacity and anti-infliximab antibodies measured by fluid-phase radioimmunoassays as predictors

    DEFF Research Database (Denmark)

    Lobner, M.; Walsted, A.; Larsen, R.

    2008-01-01

    The effect of consumption of Immulina, a high-molecular-weight polysaccharide extract from the cyanobacterium Arthrospira platensis, on adaptive immune responses was investigated by evaluation of changes in leukocyte responsiveness to two foreign recall antigens, Candida albicans (CA) and tetanus......-alpha, IL-1beta, and IL-6 responses, indicating that it acts by inducing a pro-inflammatory state. Taken together, the data suggest that Immulina causes an age-dependent, temporary enhancement of adaptive immune responses Udgivelsesdato: 2008/6...

  19. Adaptive immunity alters distinct host feeding pathways during nematode induced inflammation, a novel mechanism in parasite expulsion.

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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