Sample records for adaptive response induced

  1. Oxidized DNA induces an adaptive response in human fibroblasts

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    Kostyuk, Svetlana V., E-mail: [Research Centre for Medical Genetics, Russian Academy of Medical Sciences, Moscow (Russian Federation); Tabakov, Viacheslav J.; Chestkov, Valerij V.; Konkova, Marina S.; Glebova, Kristina V.; Baydakova, Galina V.; Ershova, Elizaveta S.; Izhevskaya, Vera L. [Research Centre for Medical Genetics, Russian Academy of Medical Sciences, Moscow (Russian Federation); Baranova, Ancha, E-mail: [Research Centre for Medical Genetics, Russian Academy of Medical Sciences, Moscow (Russian Federation); Center for the Study of Chronic Metabolic Diseases, School of System Biology, George Mason University, Fairfax, VA 22030 (United States); Veiko, Natalia N. [Research Centre for Medical Genetics, Russian Academy of Medical Sciences, Moscow (Russian Federation)


    Highlights: • We describe the effects of gDNAOX on human fibroblasts cultivated in serum withdrawal conditions. • gDNAOX evokes an adaptive response in human fibroblasts. • gDNAOX increases the survival rates in serum starving cell populations. • gDNAOX enhances the survival rates in cell populations irradiated at 1.2 Gy dose. • gDNAOX up-regulates NRF2 and inhibits NF-kappaB-signaling. - Abstract: Cell-free DNA (cfDNA) released from dying cells contains a substantial proportion of oxidized nucleotides, thus, forming cfDNA{sup OX}. The levels of cfDNA{sup OX} are increased in the serum of patients with chronic diseases. Oxidation of DNA turns it into a stress signal. The samples of genomic DNA (gDNA) oxidized by H{sub 2}O{sub 2}in vitro (gDNA{sup OX}) induce effects similar to that of DNA released from damaged cells. Here we describe the effects of gDNA{sup OX} on human fibroblasts cultivated in the stressful conditions of serum withdrawal. In these cells, gDNA{sup OX} evokes an adaptive response that leads to an increase in the rates of survival in serum starving cell populations as well as in populations irradiated at the dose of 1.2 Gy. These effects are not seen in control populations of fibroblasts treated with non-modified gDNA. In particular, the exposure to gDNA{sup OX} leads to a decrease in the expression of the proliferation marker Ki-67 and an increase in levels of PSNA, a decrease in the proportion of subG1- and G2/M cells, a decrease in proportion of cells with double strand breaks (DSBs). Both gDNA{sup OX} and gDNA suppress the expression of DNA sensors TLR9 and AIM2 and up-regulate nuclear factor-erythroid 2 p45-related factor 2 (NRF2), while only gDNA{sup OX} inhibits NF-κB signaling. gDNA{sup OX} is a model for oxidized cfDNA{sup OX} that is released from the dying tumor cells and being carried to the distant organs. The systemic effects of oxidized DNA have to be taken into account when treating tumors. In particular, the damaged DNA

  2. PD-1 blockade induces responses by inhibiting adaptive immune resistance (United States)

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


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

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

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    Zhongrong Liu


    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.

  4. Radio-adaptive Response in Myocardial Perfusion Imaging Induced by Technetium-99m (United States)

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


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

  5. Bioanalytical evidence that chemicals in tattoo ink can induce adaptive stress responses. (United States)

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


    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.

  6. Effects of Adrenergic Blockade on Postpartum Adaptive Responses Induced by Labor Contractions (United States)

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


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

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

    KAUST Repository

    Turek, Ilona


    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.

  8. The acid adaptive tolerance response in Campylobacter jejuni induces a global response, as suggested by proteomics and microarrays. (United States)

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


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

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

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    Miyata, Ryohei; Eeden, Stephan F. van, E-mail:


    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.

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

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    Ying Yang


    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.

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

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    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.

  12. Adaptive response of the heart to long-term anemia induced by iron deficiency. (United States)

    Naito, Yoshiro; Tsujino, Takeshi; Matsumoto, Mika; Sakoda, Tsuyoshi; Ohyanagi, Mitsumasa; Masuyama, Tohru


    Anemia is common in patients with chronic heart failure and an independent predictor of poor prognosis. Chronic anemia leads to left ventricular (LV) hypertrophy and heart failure, but its molecular mechanisms remain largely unknown. We investigated the mechanisms, including the molecular signaling pathway, of cardiac remodeling induced by iron deficiency anemia (IDA). Weanling Sprague-Dawley rats were fed an iron-deficient diet for 20 wk to induce IDA, and the molecular mechanisms of cardiac remodeling were evaluated. The iron-deficient diet initially induced severe anemia, which resulted in LV hypertrophy and dilation with preserved systolic function associated with increased serum erythropoietin (Epo) concentration. Cardiac STAT3 phosphorylation and VEGF gene expression increased by 12 wk of IDA, causing angiogenesis in the heart. Thereafter, sustained IDA induced upregulation of cardiac hypoxia inducible factor-1alpha gene expression and maintained upregulation of cardiac VEGF gene expression and cardiac angiogenesis; however, sustained IDA promoted cardiac fibrosis and lung congestion, with decreased serum Epo concentration and cardiac STAT3 phosphorylation after 20 wk of IDA compared with 12 wk. Upregulation of serum Epo concentration and cardiac STAT3 phosphorylation is associated with a beneficial adaptive mechanism of anemia-induced cardiac hypertrophy, and later decreased levels of these molecules may be critical for the transition from adaptive cardiac hypertrophy to cardiac dysfunction in long-term anemia. Understanding the mechanism of cardiac maladaptation to anemia may lead to a new strategy for treatment of chronic heart failure with anemia.

  13. Radiation-induced bystander effects and adaptive responses--the Yin and Yang of low dose radiobiology?

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    Mothersill, Carmel [Medical Physics and Applied Radiation Sciences Unit, McMaster University, Hamilton, Ont., L8S 4K1 (Canada)]. E-mail:; Seymour, Colin [Medical Physics and Applied Radiation Sciences Unit, McMaster University, Hamilton, Ont., L8S 4K1 (Canada)]. E-mail:


    Our current knowledge of the mechanisms underlying the induction of bystander effects by low doses of high or low LET ionizing radiation is reviewed. The question of what actually constitutes a protective effect is discussed in the context of adaptive (often referred to as hormetic or protective) responses. Finally the review considers critically, how bystander effects may be related to observed adaptive responses or other seemingly protective effects of low doses exposures. Bystander effects induce responses at the tissue level, which are similar to generalized stress responses. Most of the work involving low LET radiation exposure discussed in the existing literature measures a death response. Since many cell populations carry damaged cells without being exposed to radiation (so-called 'background damage'), it is possible that low doses exposures cause removal of cells carrying potentially problematic lesions, prior to exposure to radiation. This mechanism could lead to the production of 'U-shaped' or hormetic dose-response curves. The level of adverse, adaptive or apparently beneficial response will be related to the background damage carried by the original cell population, the level of organization at which damage or harm are scored and the precise definition of 'harm'. This model may be important when attempting to predict the consequences of mixed exposures involving low doses of radiation and other environmental stressors.

  14. Adaptive stress response pathways induced by environmental mixtures of bioaccumulative chemicals in dugongs. (United States)

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


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

  15. Metabolic and adaptive immune responses induced in mice infected with tissue-dwelling nematode Trichinella zimbabwensis (United States)

    Onkoba, N.; Chimbari, M.J.; Kamau, J.M.; Mukaratirwa, S.


    Tissue-dwelling helminths are known to induce intestinal and systemic inflammation accompanied with host compensatory mechanisms to counter balance nutritional and metabolic deficiencies. The metabolic and immune responses of the host depend on parasite species and tissues affected by the parasite. 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 randomly assigned into T. zimbabwensis-infected and control groups. Levels of Th1 (interferon-γ) and Th17 (interleukin-17) cytokines, insulin and blood glucose were determined as well as measurements of body weight, food and water intake. Results showed that during the enteric phase of infection, insulin and IFN-γ levels were significantly higher in the Trichinella infected group accompanied with a reduction in the trends of food intake and weight loss compared with the control group. During systemic larval migration, trends in food and water intake were significantly altered and this was attributed to compensatory feeding resulting in weight gain, reduced insulin levels and increased IL-17 levels. Larval migration also induced a Th1/Th17 derived inflammatory response. It was concluded that T. zimbabwensis alters metabolic parameters by instigating host compensatory feeding. Furthermore, we showed for the first time that non-encapsulated T. zimbabwensis parasite plays a role in immunomodulating host Th1/Th17 type responses during chronic infection. PMID:27882304

  16. Adaptive response of the mutagenicity of the somatic and germ cells in mice induced by in vivo 147Pm radiation

    Institute of Scientific and Technical Information of China (English)

    YANGZhanxhan; ZHUShoupeng; 等


    Effects of pretreatment of mouse with low doses of internally deposited 147Pm on the mutagenicity of both the bone marrow lymphocytes and the spermatoblasts induced by subsequent high dose of internally deposited 147Pm were studied.Kunming male mice were injected from the tail vein with low doses of 147Pm(NO3)3 of 0.37,3.7 and 37Bq/g body weight.Three days later the mice were injected with a high dose of 147Pm(NO3)3 of 18.5kBq/g body weight.The animals were sacrificed at 24h after the high dose injection.The results show that the bone marrow lymplhocytes and the spermatoblasts pre-exposed in vivo to low doses of 147Pm can produce an adaptive response.The radioadapted cells had a resistance to the mutagenicity induced by the subsequent high dose of 147Pm,that is,the proportion of both the bone marrow lymphocytes containing micronuclei and the sperm shape abnormalities was significantly lower than those for the pure high dose group(P<0.01),In addition,the induction of the adaptive response of the cells possesses the different dose ranges for the different biological aprameters.The 147Pm dose ranges of the adaptive response are 0.37-3.7and 0.37-37Bq/g body weight for the frequency of micronucleated bone marrow lymphocytes and abnormal sperms,respectively.

  17. Cyclic variations in incubation conditions induce adaptive responses to later heat exposure in chickens: a review. (United States)

    Loyau, T; Bedrani, L; Berri, C; Métayer-Coustard, S; Praud, C; Coustham, V; Mignon-Grasteau, S; Duclos, M J; Tesseraud, S; Rideau, N; Hennequet-Antier, C; Everaert, N; Yahav, S; Collin, A


    Selection programs have enabled broiler chickens to gain muscle mass without similar enlargement of the cardiovascular and respiratory systems that are essential for thermoregulatory efficiency. Meat-type chickens cope with high ambient temperature by reducing feed intake and growth during chronic and moderate heat exposure. In case of acute heat exposure, a dramatic increase in morbidity and mortality can occur. In order to alleviate heat stress in the long term, research has recently focused on early thermal manipulation. Aimed at stimulation of long-term thermotolerance, the thermal manipulation of embryos is a method based on fine tuning of incubation conditions, taking into account the level and duration of increases in temperature and relative humidity during a critical period of embryogenesis. The consequences of thermal manipulation on the performance and meat quality of broiler chickens have been explored to ensure the potential application of this strategy. The physiological basis of the method is the induction of epigenetic and metabolic mechanisms that control body temperature in the long term. Early thermal manipulation can enhance poultry resistance to environmental changes without much effect on growth performance. This review presents the main strategies of early heat exposure and the physiological concepts on which these methods were based. The cellular mechanisms potentially underlying the adaptive response are discussed as well as the potential interest of thermal manipulation of embryos for poultry production.

  18. Nitric oxide induces stomatal closure and enhances the adaptive plant responses against drought stress. (United States)

    García-Mata, C; García Mata, C; Lamattina, L


    Nitric oxide (NO) is a very active molecule involved in many and diverse biological pathways where it has proved to be protective against damages provoked by oxidative stress conditions. In this work, we studied the effect of two NO donors, sodium nitroprusside (SNP) and S-nitroso-N-acetylpenicillamine SNP-treated on the response of wheat (Triticum aestivum) to water stress conditions. After 2 and 3 h of drought, detached wheat leaves pretreated with 150 microM SNP retained up to 15% more water than those pretreated with water or NO(2)(-)/NO(3)(-). The effect of SNP treatment on water retention was also found in wheat seedlings after 7 d of drought. These results were consistent with a 20% decrease in the transpiration rate of SNP-treated detached wheat leaves for the same analyzed time. In parallel experiments, NO was also able to induce a 35%, 30%, and 65% of stomatal closure in three different species, Tradescantia sp. (monocotyledonous) and two dicotyledonous, Salpichroa organifolia and fava bean (Vicia faba), respectively. In SNP-treated leaves of Tradescantia sp., the stomatal closure was correlated with a 10% increase on RWC. Ion leakage, a cell injury index, was 25% lower in SNP-treated wheat leaves compared with control ones after the recovery period. Carboxy-PTIO (2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide), a specific NO scavenger, reverted SNP action by restoring the transpiration rate, stomatal aperture, and the ion leakage to the level found in untreated leaves. Northern-blot analysis showed that SNP-treated wheat leaves display a 2-fold accumulation of a group three late embryogenesis abundant transcript with respect to control leaves both after 2 and 4 h of drought periods. All together, these results suggest that the exogenous application of NO donors might confer an increased tolerance to severe drought stress conditions in plants.

  19. PGC-1alpha is not mandatory for exercise- and training-induced adaptive gene responses in mouse skeletal muscle

    DEFF Research Database (Denmark)

    Leick, Lotte; Wojtaszewski, Jørgen F P; Johansen, Sune T.;


    The aim of the present study was to test the hypothesis that peroxisome proliferator activated receptor-gamma coactivator (PGC) 1alpha is required for exercise-induced adaptive gene responses in skeletal muscle. Whole body PGC-1alpha knockout (KO) and littermate wild-type (WT) mice performed...... a single treadmill-running exercise bout. Soleus and white gastrocnemius (WG) were obtained immediately, 2 h, or 6 h after exercise. Another group of PGC-1alpha KO and WT mice performed 5-wk exercise training. Soleus, WG, and quadriceps were obtained approximately 37 h after the last training session....... Resting muscles of the PGC-1alpha KO mice had lower ( approximately 20%) cytochrome c (cyt c), cytochrome oxidase (COX) I, and aminolevulinate synthase (ALAS) 1 mRNA and protein levels than WT, but similar levels of AMP-activated protein kinase (AMPK) alpha1, AMPKalpha2, and hexokinase (HK) II compared...

  20. Brugia malayi microfilariae induce a regulatory monocyte/macrophage phenotype that suppresses innate and adaptive immune responses.

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    Noëlle Louise O'Regan


    Full Text Available Monocytes and macrophages contribute to the dysfunction of immune responses in human filariasis. During patent infection monocytes encounter microfilariae in the blood, an event that occurs in asymptomatically infected filariasis patients that are immunologically hyporeactive.To determine whether blood microfilariae directly act on blood monocytes and in vitro generated macrophages to induce a regulatory phenotype that interferes with innate and adaptive responses.Monocytes and in vitro generated macrophages from filaria non-endemic normal donors were stimulated in vitro with Brugia malayi microfilarial (Mf lysate. We could show that monocytes stimulated with Mf lysate develop a defined regulatory phenotype, characterised by expression of the immunoregulatory markers IL-10 and PD-L1. Significantly, this regulatory phenotype was recapitulated in monocytes from Wuchereria bancrofti asymptomatically infected patients but not patients with pathology or endemic normals. Monocytes from non-endemic donors stimulated with Mf lysate directly inhibited CD4+ T cell proliferation and cytokine production (IFN-γ, IL-13 and IL-10. IFN-γ responses were restored by neutralising IL-10 or PD-1. Furthermore, macrophages stimulated with Mf lysate expressed high levels of IL-10 and had suppressed phagocytic abilities. Finally Mf lysate applied during the differentiation of macrophages in vitro interfered with macrophage abilities to respond to subsequent LPS stimulation in a selective manner.Conclusively, our study demonstrates that Mf lysate stimulation of monocytes from healthy donors in vitro induces a regulatory phenotype, characterized by expression of PD-L1 and IL-10. This phenotype is directly reflected in monocytes from filarial patients with asymptomatic infection but not patients with pathology or endemic normals. We suggest that suppression of T cell functions typically seen in lymphatic filariasis is caused by microfilaria-modulated monocytes in an IL

  1. Brugia malayi Microfilariae Induce a Regulatory Monocyte/Macrophage Phenotype That Suppresses Innate and Adaptive Immune Responses (United States)

    Venugopal, Gopinath; Rao, Gopala B.; Lucius, Richard; Srikantam, Aparna; Hartmann, Susanne


    Background Monocytes and macrophages contribute to the dysfunction of immune responses in human filariasis. During patent infection monocytes encounter microfilariae in the blood, an event that occurs in asymptomatically infected filariasis patients that are immunologically hyporeactive. Aim To determine whether blood microfilariae directly act on blood monocytes and in vitro generated macrophages to induce a regulatory phenotype that interferes with innate and adaptive responses. Methodology and principal findings Monocytes and in vitro generated macrophages from filaria non-endemic normal donors were stimulated in vitro with Brugia malayi microfilarial (Mf) lysate. We could show that monocytes stimulated with Mf lysate develop a defined regulatory phenotype, characterised by expression of the immunoregulatory markers IL-10 and PD-L1. Significantly, this regulatory phenotype was recapitulated in monocytes from Wuchereria bancrofti asymptomatically infected patients but not patients with pathology or endemic normals. Monocytes from non-endemic donors stimulated with Mf lysate directly inhibited CD4+ T cell proliferation and cytokine production (IFN-γ, IL-13 and IL-10). IFN-γ responses were restored by neutralising IL-10 or PD-1. Furthermore, macrophages stimulated with Mf lysate expressed high levels of IL-10 and had suppressed phagocytic abilities. Finally Mf lysate applied during the differentiation of macrophages in vitro interfered with macrophage abilities to respond to subsequent LPS stimulation in a selective manner. Conclusions and significance Conclusively, our study demonstrates that Mf lysate stimulation of monocytes from healthy donors in vitro induces a regulatory phenotype, characterized by expression of PD-L1 and IL-10. This phenotype is directly reflected in monocytes from filarial patients with asymptomatic infection but not patients with pathology or endemic normals. We suggest that suppression of T cell functions typically seen in lymphatic

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

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


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

  3. Inducible colony formation within the Scenedesmaceae: adaptive responses to infochemicals from two different herbivore taxa

    NARCIS (Netherlands)

    Verschoor, A.M.; Van der Stap, I.; Helmsing, N.R.; Lürling, M.; Van Donk, E.


    We studied the occurrence of colony formation within 40 different strains of Scenedesmaceae (Chlorococcales, Chlorophyta) in response to grazing-released infochemicals from the herbivorous zooplankters Brachionus calyciflorus Pallas (Rotifera) and Daphnia magna Strauss (Cladocera). With the exceptio

  4. Inducible colony formation within the Scenedesmaceae: Adaptive responses to infochemicals from two different herbivore taxa

    NARCIS (Netherlands)

    Verschoor, A.M.; Stap, I.; Helmsing, N.R.; Lürling, M.F.L.L.W.; Donk, van E.


    We studied the occurrence of colony formation within 40 different strains of Scenedesmaceae (Chlorococcales, Chlorophyta) in response to grazing-released infochemicals from the herbivorous zooplankters Brachionus calyciflorus Pallas (Rotifera) and Daphnia magna Strauss (Cladocera). With the exceptio

  5. Vanguards of Paradigm Shift in Radiation Biology: Radiation-Induced Adaptive and Bystander Responses


    MATSUMOTO, Hideki; Hamada, Nobuyuki; Takahashi, Akihisa; Kobayashi, Yasuhiko; Ohnishi, Takeo


    The risks of exposure to low dose ionizing radiation (below 100 mSv) are estimated by extrapolating from data obtained after exposure to high dose radiation, using a linear no-threshold model (LNT model). However, the validity of using this dose-response model is controversial because evidence accumulated over the past decade has indicated that living organisms, including humans, respond differently to low dose/low dose-rate radiation than they do to high dose/high dose-rate radiation. In oth...

  6. Alarm signal transduction and DNA repair in the adaptive response induced by X-rays in human lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Wojewodzka, M.; Kruszewski, M.; Szumiel, I.; Wojcik, A. [Institute of Nuclear Chemistry and Technology, Warsaw (Poland); Staffer, C. [Universitatklinikum, Essen (Germany); Gasinska, A. [Radiotherapy Clinic Oncology Center, Cracow (Poland)


    Irradiation of human lymphocytes (1 cGy, 37 deg C) evoked a 30% decrease in the frequency of micronuclei upon subsequent X-irradiation (1.5 Gy). The response was reflected both by a reduction in the formation of micronuclei frequency and in an increase in the DNA repair rate measured by the comet assay directly after the challenge dose. The calcium antagonist, TMB-8, and staurosporine, an inhibitor of protein kinases, prevented the development of the adaptive response measured by the appearance of micronuclei. Psi-tectorigenin, an inhibitor of phosphatidylinositol turnover, did not modify the adaptive response. The induction of adaptation as not accompanied by altered progression through the cell cycle, or changes in chromatin condensation as determined by flow cytometry (DNA content and 90 deg side scatter, respectively). (author). 24 refs, 8 figs.

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

    Energy Technology Data Exchange (ETDEWEB)

    Ishii, Keiichiro; Hoshi, Yuko; Iwasaki, Toshiyasu [Central Research Inst. of Electric Power Industry, Komae, Tokyo (Japan). Komae Research Lab.; Watanabe, Masami


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

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

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


    Existence of adaptive response (AR) was previously demonstrated in C57BL/6J mice. Irradiations were performed by delivering a priming low dose of X-rays (0.50 Gy) in combination with a challenge high dose of accelerated carbon or neon ion particles. AR was characterized by significantly decreased mortality in the 30-day survival test. This mouse AR model ('Yonezawa Effect') was originally established by using X-rays as both the priming and challenge irradiations. The underlying mechanism was due to radio-resistance occurring in blood-forming tissues. In this study, we verified the existence of AR and further investigated residual damage in the hematopoietic system in surviving animals. Results showed that the priming low dose of X-rays could relieve the detrimental effects on the hematopoietic system. We observed both an improvement in the blood platelet count and the ratio of polychromatic erythrocytes (PCEs) to the sum of PCEs and normochromatic erythrocytes (NCEs) and a marked reduction of the incidences of micronucleated PCEs and micronucleated NCEs. These findings suggest that the priming low dose of low linear energy transfer (LET) X-rays induced a protective effect on the hematopoietic system, which may play an important role in both rescue from acute lethal damage (mouse killing) and prevention of late detrimental consequences (residual anhematopoiesis and delayed genotoxic effects) caused by exposure to a high challenge dose from low-LET (X-ray) or high-LET (carbon and neon ion) irradiations. These findings provide new knowledge of the characterization of the Yonezawa Effect by providing new insight into the mechanistic study of AR in vivo.

  9. Berberine is a dopamine D1- and D2-like receptor antagonist and ameliorates experimentally induced colitis by suppressing innate and adaptive immune responses. (United States)

    Kawano, Masaaki; Takagi, Rie; Kaneko, Atsushi; Matsushita, Sho


    Berberine is an herbal alkaloid with various biological activities, including anti-inflammatory and antidepressant effects. Here, we examined the effects of berberine on dopamine receptors and the ensuing anti-inflammatory responses. Berberine was found to be an antagonist at both dopamine D1- and D2-like receptors and ameliorates the development of experimentally induced colitis in mice. In lipopolysaccharide-stimulated immune cells, berberine treatment modified cytokine levels, consistent with the effects of the dopamine receptor specific antagonists SCH23390 and L750667. Our findings indicate that dopamine receptor antagonists suppress innate and adaptive immune responses, providing a foundation for their use in combatting inflammatory diseases.

  10. Satellite cell activation induced by aerobic muscle adaptation in response to endurance exercise in humans and rodents. (United States)

    Abreu, Phablo; Mendes, Sávio Victor Diógenes; Ceccatto, Vânia Marilande; Hirabara, Sandro Massao


    Although the requirement of satellite cells activation and expansion following injury, mechanical load or growth stimulus provoked by resistance exercise has been well established, their function in response to aerobic exercise adaptation remains unclear. A clear relationship between satellite cell expansion in fiber-type specific myosin heavy chain and aerobic performance has been related, independent of myonuclear accretion or muscle growth. However, the trigger for this activation process is not fully understood yet and it seems to be a multi-faceted and well-orchestrated process. Emerging in vitro studies suggest a role for metabolic pathways and oxygen availability for satellite cell activation, modulating the self-renewal potential and cell fate control. The goal of this review is to describe and discuss the current knowledge about the satellite cell activation and expansion in response to aerobic exercise adaptation in human and rodent models. Additionally, findings about the in vitro metabolic control, which seems be involved in the satellite cell activation and cell fate control, are presented and discussed.

  11. Intranasal organic dust exposure-induced airway adaptation response marked by persistent lung inflammation and pathology in mice


    Poole, Jill A.; Wyatt, Todd A; Oldenburg, Peter J.; Elliott, Margaret K.; West, William W.; Sisson, Joseph H.; Von Essen, Susanna G.; Romberger, Debra J.


    Organic dust exposure in agricultural environments results in an inflammatory response that attenuates over time, but repetitive exposures can result in chronic respiratory disease. Animal models to study these mechanisms are limited. This study investigated the effects of single vs. repetitive dust-induced airway inflammation in mice by intranasal exposure method. Mice were exposed to swine facility dust extract (DE) or saline once and once daily for 1 and 2 wk. Dust exposure resulted in inc...

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

    Energy Technology Data Exchange (ETDEWEB)

    J. Leslie Redpath, Ph.D.


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

  13. 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


    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.

  14. Inducible competitors and adaptive diversification

    Institute of Scientific and Technical Information of China (English)



    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.

  15. Inducible competitors and adaptive diversification

    Directory of Open Access Journals (Sweden)

    Beren W. ROBINSON, David W. PFENNIG


    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].

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

    Institute of Scientific and Technical Information of China (English)


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

  17. 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)


    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)

  18. 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

    Directory of Open Access Journals (Sweden)

    Vanz Ana Leticia


    Full Text Available Abstract 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

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

    Energy Technology Data Exchange (ETDEWEB)


    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.

  20. 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


    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

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


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


    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% Na...

  2. Radio-Adaptive Responses of Mouse Myocardiocytes (United States)

    Seawright, John W.; Westby, Christian M.


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

  3. 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; Kristensen, Caroline Maag;


    -induced increases in exercise capacity and expression of metabolic proteins, as well as acute exercise-induced gene regulation, would be compromised in muscle-specific AMPKα1 and -α2 double-knockout (mdKO) mice. An acute bout of exercise increased skeletal muscle mRNA content of cytochrome c oxidase subunit I...

  4. Mechanical ventilation induces a Toll/interleukin-1 receptor domain-containing adapter-inducing interferon beta-dependent inflammatory response in healthy mice.

    NARCIS (Netherlands)

    Vaneker, M.; Heunks, L.M.A.; Joosten, L.A.B.; Hees, J. van; Snijdelaar, D.G.; Halbertsma, F.J.; Egmond, J. van; Netea, M.G.; Hoeven, J.G. van der; Scheffer, G.J.


    BACKGROUND: Mechanical ventilation (MV) can induce lung injury. Proinflammatory cytokines have been shown to play an important role in the development of ventilator-induced lung injury. Previously, the authors have shown a role for Toll-like receptor 4 signaling. The current study aims to investigat

  5. Response-Adaptive Allocation for Circular Data. (United States)

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


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

  6. Monitoring adaptive genetic responses to environmental change

    DEFF Research Database (Denmark)

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


    Widespread environmental changes including climate change, selective harvesting and landscape alterations now greatly affect selection regimes for most organisms. How animals and plants can adapt to these altered environments via contemporary evolution is thus of strong interest. We discuss how...... for selection and establishing clear links between genetic and environmental change. We then review a few exemplary studies that explore adaptive responses to climate change in Drosophila, selective responses to hunting and fishing, and contemporary evolution in Daphnia using resurrected resting eggs. We...

  7. Salient Distractors Can Induce Saccade Adaptation

    Directory of Open Access Journals (Sweden)

    Afsheen Khan


    Full Text Available When saccadic eye movements consistently fail to land on their intended target, saccade accuracy is maintained by gradually adapting the movement size of successive saccades. The proposed error signal for saccade adaptation has been based on the distance between where the eye lands and the visual target (retinal error. We studied whether the error signal could alternatively be based on the distance between the predicted and actual locus of attention after the saccade. Unlike conventional adaptation experiments that surreptitiously displace the target once a saccade is initiated towards it, we instead attempted to draw attention away from the target by briefly presenting salient distractor images on one side of the target after the saccade. To test whether less salient, more predictable distractors would induce less adaptation, we separately used fixed random noise distractors. We found that both visual attention distractors were able to induce a small degree of downward saccade adaptation but significantly more to the more salient distractors. As in conventional adaptation experiments, upward adaptation was less effective and salient distractors did not significantly increase amplitudes. We conclude that the locus of attention after the saccade can act as an error signal for saccade adaptation.

  8. 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 regardi

  9. Adaptive Modeling for Security Infrastructure Fault Response

    Institute of Scientific and Technical Information of China (English)

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


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

  10. FDG-PET response-adapted therapy

    DEFF Research Database (Denmark)

    Hutchings, Martin


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

  11. 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)


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

  12. Incorporating adaptive responses into future projections of coral bleaching. (United States)

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


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

  13. Adaptive immune responses to Candida albicans infection. (United States)

    Richardson, Jonathan P; Moyes, David L


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

  14. Adaptive Response Surface Techniques in Reliability Estimation

    DEFF Research Database (Denmark)

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


    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 deter...

  15. Meditation-induced cognitive-control states regulate response-conflict adaptation: Evidence from trial-to-trial adjustments in the Simon task. (United States)

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


    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.

  16. Target Response Adaptation for Correlation Filter Tracking

    KAUST Repository

    Bibi, Adel Aamer


    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.

  17. The relative magnitude of transgene-specific adaptive immune responses induced by human and chimpanzee adenovirus vectors differs between laboratory animals and a target species. (United States)

    Dicks, Matthew D J; Guzman, Efrain; Spencer, Alexandra J; Gilbert, Sarah C; Charleston, Bryan; Hill, Adrian V S; Cottingham, Matthew G


    Adenovirus vaccine vectors generated from new viral serotypes are routinely screened in pre-clinical laboratory animal models to identify the most immunogenic and efficacious candidates for further evaluation in clinical human and veterinary settings. Here, we show that studies in a laboratory species do not necessarily predict the hierarchy of vector performance in other mammals. In mice, after intramuscular immunization, HAdV-5 (Human adenovirus C) based vectors elicited cellular and humoral adaptive responses of higher magnitudes compared to the chimpanzee adenovirus vectors ChAdOx1 and AdC68 from species Human adenovirus E. After HAdV-5 vaccination, transgene specific IFN-γ(+) CD8(+) T cell responses reached peak magnitude later than after ChAdOx1 and AdC68 vaccination, and exhibited a slower contraction to a memory phenotype. In cattle, cellular and humoral immune responses were at least equivalent, if not higher, in magnitude after ChAdOx1 vaccination compared to HAdV-5. Though we have not tested protective efficacy in a disease model, these findings have important implications for the selection of candidate vectors for further evaluation. We propose that vaccines based on ChAdOx1 or other Human adenovirus E serotypes could be at least as immunogenic as current licensed bovine vaccines based on HAdV-5.

  18. Pentavalent outer membrane vesicles of Vibrio cholerae induce adaptive immune response and protective efficacy in both adult and passive suckling mice models. (United States)

    Sinha, Ritam; Koley, Hemanta; Nag, Dhrubajyoti; Mitra, Soma; Mukhopadhyay, Asish K; Chattopadhyay, Brajadulal


    Recently, we demonstrated oral immunizations with single serotype outer membrane vesicles of Vibrio cholerae induced serogroup specific protective immunity in the RITARD model. In our present study, we advanced our research by formulating multi-serotype outer membrane vesicles, mixing the OMVs of five virulent V. cholerae strains. Four doses of oral immunization with cholera pentavalent outer membrane vesicles (CPMVs) induced V. cholerae specific B and T cell responses. CPMVs-immunized mice generated long lasting serum IgG, IgA, IgM as well as mucosal sIgA and also elicited a higher percentage of CD4+ T cell distribution in spleen. Our study revealed that in vitro CPMVs-activated dendritic cells were secreting T cell polarizing cytokines, IL-12p40, IL-4, IL-6 and IL-1β. Moreover, purified splenic CD4+ T cells of immunized mice also secreted IL-4, IL-13 and IL-17 cytokines, indicating the initiation of Th2 and Th17 cell mediated immune responses. CPMVs immunized adult female mice and their offspring were significantly protected from heterologous challenge with wild type V. cholerae. CPMVs could be exploited for the development of a novel non-living vaccine against circulating cholera in near future.

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

    Directory of Open Access Journals (Sweden)

    Shumikhina Svetlana


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

  20. Innate and adaptive immune responses in HCV infections. (United States)

    Heim, Markus H; Thimme, Robert


    Hepatitis C virus has been identified a quarter of a decade ago as a leading cause of chronic viral hepatitis that can lead to cirrhosis and hepatocellular carcinoma. Only a minority of patients can clear the virus spontaneously during acute infection. Elimination of HCV during acute infection correlates with a rapid induction of innate, especially interferon (IFN) induced genes, and a delayed induction of adaptive immune responses. However, the majority of patients is unable to clear the virus and develops viral persistence in face of an ongoing innate and adaptive immune response. The virus has developed several strategies to escape these immune responses. For example, to escape innate immunity, the HCV NS3/4A protease can efficiently cleave and inactivate two important signalling molecules in the sensory pathways that react to HCV pathogen-associated molecular patterns (PAMPs) to induce IFNs, i.e., the mitochondrial anti-viral signalling protein (MAVS) and the Toll-IL-1 receptor-domain-containing adaptor-inducing IFN-β (TRIF). Despite these escape mechanisms, IFN-stimulated genes (ISGs) are induced in a large proportion of patients with chronic infection. Of note, chronically HCV infected patients with constitutive IFN-stimulated gene (ISG) expression have a poor response to treatment with pegylated IFN-α (PegIFN-α) and ribavirin. The mechanisms that protect HCV from IFN-mediated innate immune reactions are not entirely understood, but might involve blockade of ISG protein translation at the ribosome, localization of viral replication to cell compartments that are not accessible to anti-viral IFN-stimulated effector systems, or direct antagonism of effector systems by viral proteins. Escape from adaptive immune responses can be achieved by emergence of viral escape mutations that avoid recognition by antibodies and T cells. In addition, chronic infection is characterized by the presence of functionally and phenotypically altered NK and T cell responses that

  1. Eccentric Contraction-Induced Muscle Fibre Adaptation

    Directory of Open Access Journals (Sweden)

    Arabadzhiev T. I.


    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.

  2. Plant Responses to Salt Stress: Adaptive Mechanisms

    Directory of Open Access Journals (Sweden)

    Jose Ramón Acosta-Motos


    Full Text Available This review deals with the adaptive mechanisms that plants can implement to cope with the challenge of salt stress. Plants tolerant to NaCl implement a series of adaptations to acclimate to salinity, including morphological, physiological and biochemical changes. These changes include increases in the root/canopy ratio and in the chlorophyll content in addition to changes in the leaf anatomy that ultimately lead to preventing leaf ion toxicity, thus maintaining the water status in order to limit water loss and protect the photosynthesis process. Furthermore, we deal with the effect of salt stress on photosynthesis and chlorophyll fluorescence and some of the mechanisms thought to protect the photosynthetic machinery, including the xanthophyll cycle, photorespiration pathway, and water-water cycle. Finally, we also provide an updated discussion on salt-induced oxidative stress at the subcellular level and its effect on the antioxidant machinery in both salt-tolerant and salt-sensitive plants. The aim is to extend our understanding of how salinity may affect the physiological characteristics of plants.

  3. Oxidative stress as a significant factor for development of an adaptive response in irradiated and nonirradiated human lymphocytes after inducing the bystander effect by low-dose X-radiation

    Energy Technology Data Exchange (ETDEWEB)

    Ermakov, Aleksei V., E-mail: [Research Centre for Medical Genetics, Russian Academy of Medical Science, ul. Moskvorechye, 1, Moscow 115478 (Russian Federation); Konkova, Marina S.; Kostyuk, Svetlana V.; Egolina, Natalya A.; Efremova, Liudmila V.; Veiko, Natalya N. [Research Centre for Medical Genetics, Russian Academy of Medical Science, ul. Moskvorechye, 1, Moscow 115478 (Russian Federation)


    X-radiation (10 cGy) was shown to induce in human lymphocytes transposition of homologous chromosomes loci from the membrane towards the centre of the nucleus and activation of the chromosomal nucleolus-forming regions (NFRs). These effects are transmitted by means of extracellular DNA (ecDNA) fragments to nonirradiated cells (the so-called bystander effect, BE). We demonstrated that in the development of the BE an important role is played by oxidative stress (which is brought about by low radiation doses and ecDNA fragments of the culture medium of the irradiated cells), by an enzyme of apoptosis called caspase-3, and by DNA-binding receptors of the bystander cells, presumably TLR9. Proposed herein is a scheme of the development of an adaptive response and the BE on exposure to radiation. Ionizing radiation induces apoptosis of the radiosensitive fraction of cells due to the development of the 'primary' oxidative stress (OS). DNA fragments of apoptotic cells are released into the intercellular space and interact with the DNA-binding receptors of the bystander cells. This interaction activates in lymphocytes signalling pathways associated with synthesis of the reactive oxygen species and nitrogen species, i.e., induces secondary oxidative stress accompanied by apoptosis of part of the cells, etc. Hence, single exposure to radiation may be followed by relatively long-lasting in the cellular population oxidative stress contributing to the development of an adaptive response. We thus believe that ecDNA of irradiated apoptotic lymphocytes is a significant factor of stress-signalling.

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

  5. Adaptive immune response during hepatitis C virus infection. (United States)

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


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

  6. 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.


    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.

  7. Adaptive translation as a mechanism of stress response and adaptation


    Pan, Tao


    The composition of the cellular proteome is commonly thought to strictly adhere to the genetic code. However, accumulating evidence indicates that cells also regulate the synthesis of mutant protein molecules that deviate from the genetic code. Production of mutant proteins varies in amounts and specificity and generally occurs when cells are stressed or undergo environmental adaptation. The deliberate synthesis of protein mutants suggests that some of these proteins can be useful in cellular...

  8. Training induced adaptation in horse skeletal muscle

    NARCIS (Netherlands)

    Dam, K.G. van


    It appears that the physiological and biochemical adaptation of skeletal muscle to training in equine species shows a lot of similarities with human and rodent physiological adaptation. On the other hand it is becoming increasingly clear that intra-cellular mechanisms of adaptation (substrate transp

  9. Innate and adaptive immune responses to in utero infection with bovine viral diarrhea virus (United States)

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

  10. "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


    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

  11. How Language Supports Adaptive Teaching through a Responsive Learning Culture (United States)

    Johnston, Peter; Dozier, Cheryl; Smit, Julie


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

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

    Directory of Open Access Journals (Sweden)

    Lan Li


    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.

  13. Aneuploidy as a mechanism for stress-induced liver adaptation. (United States)

    Duncan, Andrew W; Hanlon Newell, Amy E; Bi, Weimin; Finegold, Milton J; Olson, Susan B; Beaudet, Arthur L; Grompe, Markus


    Over half of the mature hepatocytes in mice and humans are aneuploid and yet retain full ability to undergo mitosis. This observation has raised the question of whether this unusual somatic genetic variation evolved as an adaptive mechanism in response to hepatic injury. According to this model, hepatotoxic insults select for hepatocytes with specific numerical chromosome abnormalities, rendering them differentially resistant to injury. To test this hypothesis, we utilized a strain of mice heterozygous for a mutation in the homogentisic acid dioxygenase (Hgd) gene located on chromosome 16. Loss of the remaining Hgd allele protects from fumarylacetoacetate hydrolase (Fah) deficiency, a genetic liver disease model. When adult mice heterozygous for Hgd and lacking Fah were exposed to chronic liver damage, injury-resistant nodules consisting of Hgd-null hepatocytes rapidly emerged. To determine whether aneuploidy played a role in this phenomenon, array comparative genomic hybridization (aCGH) and metaphase karyotyping were performed. Strikingly, loss of chromosome 16 was dramatically enriched in all mice that became completely resistant to tyrosinemia-induced hepatic injury. The frequency of chromosome 16-specific aneuploidy was approximately 50%. This result indicates that selection of a specific aneuploid karyotype can result in the adaptation of hepatocytes to chronic liver injury. The extent to which aneuploidy promotes hepatic adaptation in humans remains under investigation.

  14. Adaptive Filtering for Aeroservoelastic Response Suppression Project (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...

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

    Directory of Open Access Journals (Sweden)

    T. Bruder-Nascimento


    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.

  16. Temporal and spatial adaptation of transient responses to local features

    Directory of Open Access Journals (Sweden)

    David C O'Carroll


    Full Text Available Interpreting visual motion within the natural environment is a challenging task, particularly considering that natural scenes vary enormously in brightness, contrast and spatial structure. Current models for the detection of self-generated optic flow depend heavily on these very parameters, but despite this, animals manage to successfully navigate within a broad range of scenes. Within global scenes local areas with more salient features are common. Recent work has highlighted the influence that local, salient features have on the encoding of optic flow, but it has been difficult to quantify how local transient responses affect responses to subsequent features and thus contribute to the global neural response. To investigate this in more detail we used experimenter-designed stimuli and recorded intracellularly from motion-sensitive neurons. We limited the stimulus to a small vertically elongated strip, to investigate local and global neural responses to pairs of local ‘doublet’ features that were designed to interact with each other in the temporal and spatial domain. We show that the passage of a high contrast doublet feature produces a complex transient response from local motion detectors consistent with predictions of a simple computational model. In the neuron, the passage of a high-contrast feature induces a local reduction in responses to subsequent low contrast features. However, this neural contrast gain reduction appears to be recruited only when features stretch vertically (i.e. orthogonal to the direction of motion across at least several aligned neighbouring ommatidia. Horizontal displacement of the components of elongated features abolishes the local adaptation effect. It is thus likely that features in natural scenes with vertically aligned edges, such as tree trunks, would be expected to recruit the greatest amount of response suppression, which could emphasize the local responses to such features vs those in nearby texture

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

    Institute of Scientific and Technical Information of China (English)

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


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

  18. Alternative scenarios of starvation-induced adaptation in Pectobacterium atrosepticum. (United States)

    Petrova, Olga; Gorshkov, Vladimir; Sergeeva, Iuliia; Daminova, Amina; Ageeva, Marina; Gogolev, Yuri


    Bacteria have high adaptive potential that ensures their survival during various environmental challenges. To adapt, bacteria activate a physiological program of stress response that makes them able to persist under adverse conditions. The present study sought to examine the ability of a particular bacterial species to induce a stress response in alternative scenarios. Cells of the phytopathogenic microorganism Pectobacterium atrosepticum were taken as a model. The cells were exposed to starvation in different physiological states (actively growing exponential phase and stationary phase cells), and the resulting starving cultures were monitored using CFU counting, quantitative PCR and electron microscopy. When exponential phase cells were subjected to starvation, the nucleoids of the cells became condensed and their DNA was detected by qPCR less effectively than that of cells growing in nutrient-rich medium, or stationary phase cells after starvation. Exponential phase cells subjected to starvation showed increased expression of genes encoding DNA binding histone-like proteins, whereas, in cultures inoculated by stationary phase cells, cell-wall-deficient forms that were inefficient at colony forming and that had a non-culturable phenotype were formed. The cell-wall-deficient forms displayed reduced expression of genes encoding synthases of cell wall components.

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

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


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

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

    DEFF Research Database (Denmark)

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


    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 deadlock freedom and liveness in the SPIN model checker by utilizing a mapping from DCR Graphs to PROMELA code. We exemplify the approach by a small workflow extracted from a field study at a danish hospital....

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

    NARCIS (Netherlands)

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


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

  2. Responsibility for private sector adaptation to climate change

    Directory of Open Access Journals (Sweden)

    Tina Schneider


    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

  3. Using response times for item selection in adaptive testing

    NARCIS (Netherlands)

    Linden, van der Wim J.


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

  4. Adaptive workflow simulation of emergency response

    NARCIS (Netherlands)

    Bruinsma, Guido Wybe Jan


    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

  5. T Cell Adaptive Immunity Proceeds through Environment-Induced Adaptation from the Exposure of Cryptic Genetic Variation (United States)

    Whitacre, James M.; Lin, Joseph; Harding, Angus


    Evolution is often characterized as a process involving incremental genetic changes that are slowly discovered and fixed in a population through genetic drift and selection. However, a growing body of evidence is finding that changes in the environment frequently induce adaptations that are much too rapid to occur by an incremental genetic search process. Rapid evolution is hypothesized to be facilitated by mutations present within the population that are silent or “cryptic” within the first environment but are co-opted or “exapted” to the new environment, providing a selective advantage once revealed. Although cryptic mutations have recently been shown to facilitate evolution in RNA enzymes, their role in the evolution of complex phenotypes has not been proven. In support of this wider role, this paper describes an unambiguous relationship between cryptic genetic variation and complex phenotypic responses within the immune system. By reviewing the biology of the adaptive immune system through the lens of evolution, we show that T cell adaptive immunity constitutes an exemplary model system where cryptic alleles drive rapid adaptation of complex traits. In naive T cells, normally cryptic differences in T cell receptor reveal diversity in activation responses when the cellular population is presented with a novel environment during infection. We summarize how the adaptive immune response presents a well studied and appropriate experimental system that can be used to confirm and expand upon theoretical evolutionary models describing how seemingly small and innocuous mutations can drive rapid cellular evolution. PMID:22363338

  6. Transcriptome analysis of adaptive heat shock response of Streptococcus thermophilus.

    Directory of Open Access Journals (Sweden)

    Jin-song Li

    Full Text Available Streptococcus thermophilus, a gram-positive facultative anaerobe, is one of the most important lactic acid bacteria widely used in the dairy fermentation industry. In this study, we have analyzed the global transcriptional profiling of S. thermophilus upon temperature change. During a temperature shift from 42°C to 50°C, it is found that 196 (10.4% genes show differential expression with 102 up-regulated and 94 down-regulated at 50°C. In particular, 1 Heat shock genes, such as DnaK, GroESL and clpL, are identified to be elevated at 50°C; 2 Transcriptional regulators, such as HrcA, CtsR, Fur, MarR and MerR family, are differentially expressed, indicating the complex molecular mechanisms of S. thermophilus adapting to heat shock; 3 Genes associated with signal transduction, cell wall genes, iron homeostasis, ABC transporters and restriction-modification system were induced; 4 A large number of the differentially expressed genes are hypothetical genes of unknown function, indicating that much remains to be investigated about the heat shock response of S. thermophilus. Experimental investigation of selected heat shock gene ClpL shows that it plays an important role in the physiology of S. thermophilus at high temperature and meanwhile we confirmed ClpL as a member of the CtsR regulon. Overall, this study has contributed to the underlying adaptive molecular mechanisms of S. thermophilus upon temperature change and provides a basis for future in-depth functional studies.

  7. Influence of stimulus and oral adaptation temperature on gustatory responses in central taste-sensitive neurons. (United States)

    Li, Jinrong; Lemon, Christian H


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

  8. Genetic erosion impedes adaptive responses to stressful environments

    NARCIS (Netherlands)

    Bijlsma, R.; Loeschcke, Volker


    Biodiversity is increasingly subjected to human-induced changes of the environment. To persist, populations continually have to adapt to these often stressful changes including pollution and climate change. Genetic erosion in small populations, owing to fragmentation of natural habitats, is expected

  9. Readapting the adaptive immune response - therapeutic strategies for atherosclerosis. (United States)

    Sage, Andrew P; Mallat, Ziad


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


    Directory of Open Access Journals (Sweden)

    Deborah eSuchecki


    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.

  11. Adaptation responses of crops to climate change

    Energy Technology Data Exchange (ETDEWEB)

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


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

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

    Directory of Open Access Journals (Sweden)

    Yi Cao


    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.

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

    Indian Academy of Sciences (India)

    Ashu Bhan Tiku; R K Kale


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

  14. Adaptation responses in C4 photosynthesis of maize under salinity. (United States)

    Omoto, Eiji; Taniguchi, Mitsutaka; Miyake, Hiroshi


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

  15. Adaptation responses to climate change differ between global megacities (United States)

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


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

  16. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Wilbanks, Thomas J [ORNL; Kates, Dr. Robert W. [Independent Scholar, Bangor, Maine


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

  18. A Framework to Formulate Adaptivity for Adaptive e-Learning System Using User Response Theory

    Directory of Open Access Journals (Sweden)

    Maria Dominic


    Full Text Available These days different e-learning architecture provide different kinds of e-learning experiences due to “one size fits for all” concept. This is no way better than the traditional learning and does not exploit the technological advances. Thus the e-learning system began to evolve to adaptable e-learning systems which adapts or personalizes the learning experience of the learners. Systems infer the characteristics of the learners and identify the preferences of the learners and automatically generate personalized learning path and customize learning contents to the individuals needs. This process is known as adaptation and systems which adapt are known are adaptive systems. So the main objective of this research was to provide an adaptive e-learning system framework which personalizes the learning experience in an efficient way. In this paper a framework for adaptive e-learning system using user response theory is proposed to meet the research objectives identified in section 1.D.

  19. Adaptive Patterns of Stress Responsivity: A Preliminary Investigation (United States)

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


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

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

    NARCIS (Netherlands)

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


    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 hyporesponsiv

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

    Directory of Open Access Journals (Sweden)

    Alexandra Avloniti


    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.

  2. De novo cholesterol synthesis at the crossroads of adaptive response to extracellular stress through SREBP. (United States)

    Robichon, Céline; Dugail, Isabelle


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

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

    NARCIS (Netherlands)

    Keijzer, C.


    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

  4. Prism adaptation magnitude has differential influences on perceptual versus manual responses. (United States)

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


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

  5. 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.


    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.

  6. [Adaptive immune response of people living near chemically hazardous object]. (United States)

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


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

  7. Frequency Response Adaptive Control of a Refrigeration Cycle

    Directory of Open Access Journals (Sweden)

    Jens G. Balchen


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

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

    Energy Technology Data Exchange (ETDEWEB)

    Smith, Mark William; Wick, David Victor


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

  9. The adaptive response of jaw muscles to varying functional demands. (United States)

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


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

  10. Adaptive thermoregulation in endotherms may alter responses to climate change. (United States)

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


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

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

    DEFF Research Database (Denmark)

    Jørgensen, Stine Ringholm

    and interferes with the exercise-induced adaptive response in human skeletal muscle. Study II demonstrates that mouse liver glucose-6-phosphatase (G6Pase) mRNA content increased in recovery from acute exercise in both wildtype (WT) and PGC-1α knockout (KO) mice, while phosphoenolpyruvate carboxykinase (PEPCK...... content in WT, but not in PGC-1α KO mice. This shows that exercise training increases UCP1, COXIV and CD31 protein in mouse iWAT, likely as a cumulative effect of transient increases in mRNA expression after each exercise bout, and that PGC-1α is required for these adaptations. Study IV demonstrates...

  12. Landowner response to wildfire risk: Adaptation, mitigation or doing nothing. (United States)

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


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

  13. Sequential monitoring of response-adaptive randomized clinical trials

    CERN Document Server

    Zhu, Hongjian; 10.1214/10-AOS796


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

  14. HLA alleles associated with the adaptive immune response to smallpox vaccine: a replication study. (United States)

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


    We previously reported HLA allelic associations with vaccinia virus (VACV)-induced adaptive immune responses in a cohort of healthy individuals (n = 1,071 subjects) after a single dose of the licensed smallpox (Dryvax) vaccine. This study demonstrated that specific HLA alleles were significantly associated with VACV-induced neutralizing antibody (NA) titers (HLA-B*13:02, *38:02, *44:03, *48:01, and HLA-DQB1*03:02, *06:04) and cytokine (HLA-DRB1*01:03, *03:01, *10:01, *13:01, *15:01) immune responses. We undertook an independent study of 1,053 healthy individuals and examined associations between HLA alleles and measures of adaptive immunity after a single dose of Dryvax-derived ACAM2000 vaccine to evaluate previously discovered HLA allelic associations from the Dryvax study and determine if these associations are replicated with ACAM2000. Females had significantly higher NA titers than male subjects in both study cohorts [median ID50 discovery cohort 159 (93, 256) vs. 125 (75, 186), p smallpox vaccine-induced adaptive immune responses are significantly influenced by HLA gene polymorphisms. These data provide information for functional studies and design of novel candidate smallpox vaccines.

  15. The Role of Exercise-Induced Cardiovascular Adaptation in Brain Health. (United States)

    Tarumi, Takashi; Zhang, Rong


    Regular aerobic exercise improves brain health; however, a potential dose-response relationship and the underling physiological mechanisms remain unclear. Existing data support the following hypotheses: 1) exercise-induced cardiovascular adaptation plays an important role in improving brain perfusion, structure, and function, and 2) a hormetic relation seems to exist between the intensity of exercise and brain health, which needs to be further elucidated.

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

    Directory of Open Access Journals (Sweden)

    Debra Heilpern


    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.

  17. Bayesian response-adaptive designs for basket trials. (United States)

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


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


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

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


    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.

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


    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. PMID:21631497

  1. Principles of exercise physiology: responses to acute exercise and long-term adaptations to training. (United States)

    Rivera-Brown, Anita M; Frontera, Walter R


    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.

  2. Imbalanced adaptive responses associated with microsatellite instability in cholangiocarcinoma (United States)

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


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

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

    Directory of Open Access Journals (Sweden)

    Kosuke Yamamoto

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

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

    DEFF Research Database (Denmark)

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


    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...

  5. Genome-wide transcriptional responses to a lipid hydroperoxide: adaptation occurs without induction of oxidant defenses. (United States)

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


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

  6. Lactate as a Signaling Molecule That Regulates Exercise-Induced Adaptations

    Directory of Open Access Journals (Sweden)

    Minas Nalbandian


    Full Text Available Lactate (or its protonated form: lactic acid has been studied by many exercise scientists. The lactate paradigm has been in constant change since lactate was first discovered in 1780. For many years, it was unfairly seen as primarily responsible for muscular fatigue during exercise and a waste product of glycolysis. The status of lactate has slowly changed to an energy source, and in the last two decades new evidence suggests that lactate may play a much bigger role than was previously believed: many adaptations to exercise may be mediated in some way by lactate. The mechanisms behind these adaptations are yet to be understood. The aim of this review is to present the state of lactate science, focusing on how this molecule may mediate exercise-induced adaptations.

  7. Plant adaptation to low atmospheric pressures: potential molecular responses (United States)

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


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

  8. Aeroelastic Response of the Adaptive Compliant Trailing Edge Transtition Section (United States)

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


    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.

  9. Innate and adaptive immune responses in allergic contact dermatitis and autoimmune skin diseases. (United States)

    Edele, Fanny; Esser, Philipp R; Lass, Christian; Laszczyk, Melanie N; Oswald, Eva; Strüh, Christian M; Rensing-Ehl, Anne; Martin, Stefan F


    Allergic contact dermatitis is induced by chemicals or metal ions. A hallmark of this T cell mediated skin disease is the activation of the innate immune system by contact allergens. This immune response results in inflammation and is a prerequisite for the activation of the adaptive immune system with tissue-specific migration of effector and regulatory T cells. Recent studies have begun to address in detail the innate immune cells as well as the innate receptors on these cells and the associated signaling pathways which lead to skin inflammation. We review here recent findings regarding innate and adaptive immune responses and immune regulation of contact dermatitis and other skin diseases as well as recent developments towards an in vitro assessment of the allergenic potential of chemicals. The elucidation of the innate inflammatory pathways, cellular components and mediators will help to identify new drug targets for more efficient treatment of allergic contact dermatitis and hopefully also for its prevention.

  10. 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: [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)


    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.

  11. Biological and Theoretical Studies of Adaptive Networks: The Conditioned Response. (United States)


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

  12. Studies of adaptive response and mutation induction in MCF-10A cells following exposure to chronic or acute ionizing radiation. (United States)

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


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

  13. Adaptation-Induced Compression of Event Time Occurs Only for Translational Motion. (United States)

    Fornaciai, Michele; Arrighi, Roberto; Burr, David C


    Adaptation to fast motion reduces the perceived duration of stimuli displayed at the same location as the adapting stimuli. Here we show that the adaptation-induced compression of time is specific for translational motion. Adaptation to complex motion, either circular or radial, did not affect perceived duration of subsequently viewed stimuli. Adaptation with multiple patches of translating motion caused compression of duration only when the motion of all patches was in the same direction. These results show that adaptation-induced compression of event-time occurs only for uni-directional translational motion, ruling out the possibility that the neural mechanisms of the adaptation occur at early levels of visual processing.

  14. Climate Change and Infectious Disease Risk in Western Europe: A Survey of Dutch Expert Opinion on Adaptation Responses and Actors (United States)

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


    There is growing evidence of climate change affecting infectious disease risk in Western Europe. The call for effective adaptation to this challenge becomes increasingly stronger. This paper presents the results of a survey exploring Dutch expert perspectives on adaptation responses to climate change impacts on infectious disease risk in Western Europe. Additionally, the survey explores the expert sample’s prioritization of mitigation and adaptation, and expert views on the willingness and capacity of relevant actors to respond to climate change. An integrated view on the causation of infectious disease risk is employed, including multiple (climatic and non-climatic) factors. The results show that the experts consider some adaptation responses as relatively more cost-effective, like fostering interagency and community partnerships, or beneficial to health, such as outbreak investigation and response. Expert opinions converge and diverge for different adaptation responses. Regarding the prioritization of mitigation and adaptation responses expert perspectives converge towards a 50/50 budgetary allocation. The experts consider the national government/health authority as the most capable actor to respond to climate change-induced infectious disease risk. Divergence and consensus among expert opinions can influence adaptation policy processes. Further research is necessary to uncover prevailing expert perspectives and their roots, and compare these. PMID:26295247

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

    Directory of Open Access Journals (Sweden)

    Su-Mia Akin


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

  16. Climate Change and Infectious Disease Risk in Western Europe: A Survey of Dutch Expert Opinion on Adaptation Responses and Actors. (United States)

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


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

  17. GH3-mediated auxin homeostasis links growth regulation with stress adaptation response in Arabidopsis. (United States)

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


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

  18. 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


    Fishing may induce neutral and adaptive evolution affecting life-history traits, and molecular evidence has shown that neutral genetic diversity has declined in some exploited populations. Here, we theoretically study the interplay between neutral and adaptive evolution caused by fishing. An indi...

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

    Directory of Open Access Journals (Sweden)

    Kosuke Yamamoto


    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.

  20. Response of pulmonary rapidly adapting receptors during lung inflation. (United States)

    Pack, A I; DeLaney, R G


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

  1. Naturalistic Stress and Cortisol Response to Awakening: Adaptation to Seafaring (United States)

    Liberzon, Jonathan; Abelson, James L.; King, Anthony; Liberzon, Israel


    Study of the hypothalmic-pituitary adrenal (HPA) axis has been critical to advancing our understanding of human adaptation to stress. The cortisol response to awakening (CRA) is a potentially useful measure for understanding group and individual differences in HPA axis regulation. In this study, the CRA was examined in the context of a naturalistic stressor – a six-week voyage of work and study aboard an oceangoing ship, including both experienced and novice sailors. Thirty-one subjects provided weekday and weekend baseline CRA data onshore prior to boarding, followed by three CRAs at sea and one shore leave CRA. Subjective measures of sleep, stress and control were also collected. Results suggest that novice sailors' cortisol response to awakening was elevated at sea relative to both a shoreside weekend and a shore leave during the voyage, but the most striking elevation was found during a workday onshore. Inexperienced students' profiles changed differently over the course of the voyage from those of professional crew. CRAs were not affected by sleep variables and were not predicted by subjective ratings. These data support the value of the cortisol response to awakening as a neuroendocrine marker of HPA regulatory responses to a naturalistic stressor, influenced by changes in work and living environment, and perhaps prior experience with the stressor. PMID:18657911

  2. Do responses of galliform birds vary adaptively with predator size? (United States)

    Palleroni, Alberto; Hauser, Marc; Marler, Peter


    Past studies of galliform anti-predator behavior show that they discriminate between aerial and ground predators, producing distinctive, functionally referential vocalizations to each class. Within the category of aerial predators, however, studies using overhead models, video images and observations of natural encounters with birds of prey report little evidence that galliforms discriminate between different raptor species. This pattern suggests that the aerial alarm response may be triggered by general features of objects moving in the air. To test whether these birds are also sensitive to more detailed differences between raptor species, adult chickens with young were presented with variously sized trained raptors (small, intermediate, large) under controlled conditions. In response to the small hawk, there was a decline in anti-predator aggression and in aerial alarm calling as the young grew older and less vulnerable to attack by a hawk of this size. During the same developmental period, responses to the largest hawk, which posed the smallest threat to the young at all stages, did not change; there were intermediate changes at this time in response to the middle-sized hawk. Thus the anti-predator behavior of the adult birds varied in an adaptive fashion, changing as a function of both chick age and risk. We discuss these results in light of current issues concerning the cognitive mechanisms underlying alarm calling behavior in animals.

  3. Radiation-induced gene responses

    Energy Technology Data Exchange (ETDEWEB)

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


    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.

  4. Multiple-objective response-adaptive repeated measurement designs in clinical trials for binary responses. (United States)

    Liang, Yuanyuan; Li, Yin; Wang, Jing; Carriere, Keumhee C


    A multiple-objective allocation strategy was recently proposed for constructing response-adaptive repeated measurement designs for continuous responses. We extend the allocation strategy to constructing response-adaptive repeated measurement designs for binary responses. The approach with binary responses is quite different from the continuous case, as the information matrix is a function of responses, and it involves nonlinear modeling. To deal with these problems, we first build the design on the basis of success probabilities. Then we illustrate how various models can accommodate carryover effects on the basis of logits of response profiles as well as any correlation structure. Through computer simulations, we find that the allocation strategy developed for continuous responses also works well for binary responses. As expected, design efficiency in terms of mean squared error drops sharply, as more emphasis is placed on increasing treatment benefit than estimation precision. However, we find that it can successfully allocate more patients to better treatment sequences without sacrificing much estimation precision.

  5. Biological stress response terminology: Integrating the concepts of adaptive response and preconditioning stress within a hormetic dose-response framework. (United States)

    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


    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.

  6. Development and Standardization of the Diagnostic Adaptive Behavior Scale: Application of Item Response Theory to the Assessment of Adaptive Behavior (United States)

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


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

  7. Vitamin E supplementation modifies adaptive responses to training in rat skeletal muscle. (United States)

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


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

  8. Variability: The common factor linking low dose-induced genomic instability, adaptation and bystander effects

    Energy Technology Data Exchange (ETDEWEB)

    Schwartz, Jeffrey L. [Department of Radiation Oncology, University of Washington Medical Center, 1959 NE Pacific, Box 356069, Seattle, WA 98195-6069 (United States)]. E-mail:


    The characteristics of low dose radiation-induced genomic instability, adaptive responses, and bystander effects were compared in order to probe possible underlying mechanisms, and develop models for predicting response to in vivo low dose radiation exposures. While there are some features that are common to all three (e.g., absence of a true dose-response, the multiple endpoints affected by each), other characteristics appear to distinguish one from the other (e.g., TP53 involvement, LET response, influence of DNA repair). Each of the responses is also highly variable; not all cell and tissue models show the same response and there is much interindividual variation in response. Most of these studies have employed in vitro cell culture or tissue explant models, and understanding underlying mechanisms and the biological significance of these low dose-responses will require study of tissue-specific in vivo endpoints. The in vitro studies strongly suggest that modeling low dose radiation effects will be a complex process, and will likely require separate study of each of these low dose phenomena. Knowledge of instability responses, for example, may not aid in predicting other low dose effects in the same tissue.

  9. Aberrant Pregnancy Adaptations in the Peripheral Immune Response in Type 1 Diabetes: A Rat Model.

    Directory of Open Access Journals (Sweden)

    Bart Groen

    Full Text Available Despite tight glycemic control, pregnancy complication rate in type 1 diabetes patients is higher than in normal pregnancy. Other etiological factors may be responsible for the development of adverse pregnancy outcome. Acceptance of the semi-allogeneic fetus is accompanied by adaptations in the maternal immune-response. Maladaptations of the immune-response has been shown to contribute to pregnancy complications. We hypothesized that type 1 diabetes, as an autoimmune disease, may be associated with maladaptations of the immune-response to pregnancy, possibly resulting in pregnancy complications.We studied pregnancy outcome and pregnancy-induced immunological adaptations in a normoglycemic rat-model of type 1 diabetes, i.e. biobreeding diabetes-prone rats (BBDP; 5 non-pregnant rats, 7 pregnant day 10 rats and 6 pregnant day 18 rats , versus non-diabetic control rats (i.e. congenic non-diabetic biobreeding diabetes-resistant (BBDR; 6 non-pregnant rats, 6 pregnant day 10 rats and 6 pregnant day 18 rats and Wistar-rats (6 non-pregnant, 6 pregnant day 10 rats and 5 pregnant day 18 rats.We observed reduced litter size, lower fetal weight of viable fetuses and increased numbers of resorptions versus control rats. These complications are accompanied by various differences in the immune-response between BBDP and control rats in both pregnant and non-pregnant animals. The immune-response in non-pregnant BBDP-rats was characterized by decreased percentages of lymphocytes, increased percentages of effector T-cells, regulatory T-cells and natural killer cells, an increased Th1/Th2-ratio and activated monocytes versus Wistar and BBDR-rats. Furthermore, pregnancy-induced adaptations in BBDP-rats coincided with an increased Th1/Th2-ratio, a decreased mean fluorescence intensity CD161a/NKR-P1b ratio and no further activation of monocytes versus non-diabetic control rats.This study suggests that even in the face of strict normoglycemia, pregnancy complications

  10. Control of the adaptive immune response by tumor vasculature

    Directory of Open Access Journals (Sweden)

    Laetitia eMauge


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

  11. The microglial "activation" continuum: from innate to adaptive responses

    Directory of Open Access Journals (Sweden)

    Nikolic Veljko


    Full Text Available Abstract Microglia are innate immune cells of myeloid origin that take up residence in the central nervous system (CNS during embryogenesis. While classically regarded as macrophage-like cells, it is becoming increasingly clear that reactive microglia play more diverse roles in the CNS. Microglial "activation" is often used to refer to a single phenotype; however, in this review we consider that a continuum of microglial activation exists, with phagocytic response (innate activation at one end and antigen presenting cell function (adaptive activation at the other. Where activated microglia fall in this spectrum seems to be highly dependent on the type of stimulation provided. We begin by addressing the classical roles of peripheral innate immune cells including macrophages and dendritic cells, which seem to define the edges of this continuum. We then discuss various types of microglial stimulation, including Toll-like receptor engagement by pathogen-associated molecular patterns, microglial challenge with myelin epitopes or Alzheimer's β-amyloid in the presence or absence of CD40L co-stimulation, and Alzheimer disease "immunotherapy". Based on the wide spectrum of stimulus-specific microglial responses, we interpret these cells as immune cells that demonstrate remarkable plasticity following activation. This interpretation has relevance for neurodegenerative/neuroinflammatory diseases where reactive microglia play an etiological role; in particular viral/bacterial encephalitis, multiple sclerosis and Alzheimer disease.

  12. Explosive type of moderate-resistance training induces functional, cardiovascular, and molecular adaptations in the elderly

    DEFF Research Database (Denmark)

    Beltran Valls, Maria Reyes; Dimauro, Ivan; Brunelli, Andrea


    , inflammatory, and damage parameters. Moreover, trained elderly subjects showed an adaptive response at both systemic and cellular levels by modulation of antioxidant and stress-induced markers such as myeloperoxidase (MPO), heat shock protein 70 (Hsp70) and 27 (Hsp27), and thioredoxin reductase 1 (TrxR1).......Current recommendations aimed at reducing neuromuscular and functional loss in aged muscle have identified muscle power as a key target for intervention trials, although little is known about the biological and cardiovascular systemic response in the elderly. This study investigated the effects...... of 12 weeks of low-frequency, moderate-intensity, explosive-type resistance training (EMRT) on muscle strength and power in old community-dwelling people (70-75 years), monitoring functional performance linked to daily living activities (ADL) and cardiovascular response, as well as biomarkers of muscle...

  13. Can the adaptive response to ionizing radiation detect by the cytokinesis-blocked micronuclei assay?

    Energy Technology Data Exchange (ETDEWEB)

    Kwon, Hee-Kyung; Lee, Hye-Jin; Park, Mi-Young [Korea institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)] (and others)


    Many studies have been performed to assess the development and application of potentially useful biodosimetry. At present, although chromosome dicentric assay is a sensitive method for dose estimation, it is laborious and requires enough experience for estimation. Therefore, we need an alternative cytogenetic dosimetry to estimate the absorbed dose of victims after low dose exposure such as radiation accidents in hospital workers and workers of radiation related facilities1. An alternative and simple cytogenetic technique is the measurement of the micronucleus frequency in cultured human lymphocytes. The reliability of conventional micronucleus (MN) assays is diminished owing to the inclusion of non-dividing cells in the estimate, but this problem has been overcome by the development of the cytokinesis-blocked (CB) MN assay. The reliable and ease assays of the cytokinesis blocked-approach are obvious advantages in biological monitoring, but there are no developed recognizable and reliable techniques for biological dosimetry of a low dose exposure until recently. Adaptive response is important in determining the biological responses at low doses of radiation and has the potential to impact the shape of the dose-response relationship. We analyzed the frequency of both spontaneous and in vitro {sup 137}Cs {gamma}-rays-induced MNs in the low dose radiation-exposed workers to estimate the cytokinesisblocked (CB) MN assay is proper assay or not as a screening the adaptive response.


    Directory of Open Access Journals (Sweden)

    Panagiotis Karagounis


    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

  15. Transcriptomic analysis reveals adaptive responses of an Enterobacteriaceae strain LSJC7 to arsenic exposure

    Directory of Open Access Journals (Sweden)

    Yingjiao eZhang


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

  16. Transcriptomic Analysis Reveals Adaptive Responses of an Enterobacteriaceae Strain LSJC7 to Arsenic Exposure. (United States)

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


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

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

    Directory of Open Access Journals (Sweden)

    Millet Grégoire P


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

  18. Suppression of the GLUT4 adaptive response to exercise in fructose-fed rats. (United States)

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


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

  19. Physiological responses induced by pleasant stimuli. (United States)

    Watanuki, Shigeki; Kim, Yeon-Kyu


    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.

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

    Directory of Open Access Journals (Sweden)

    Shumikhina Svetlana


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

  1. Detrimental effects for colonocytes of an increased exposure to luminal hydrogen sulfide: The adaptive response. (United States)

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


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

  2. 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


    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)

  3. Predator-induced phenotypic plasticity in metabolism and rate of growth: rapid adaptation to a novel environment. (United States)

    Handelsman, Corey A; Broder, E Dale; Dalton, Christopher M; Ruell, Emily W; Myrick, Christopher A; Reznick, David N; Ghalambor, Cameron K


    Novel environments often impose directional selection for a new phenotypic optimum. Novel environments, however, can also change the distribution of phenotypes exposed to selection by inducing phenotypic plasticity. Plasticity can produce phenotypes that either align with or oppose the direction of selection. When plasticity and selection are parallel, plasticity is considered adaptive because it provides a better pairing between the phenotype and the environment. If the plastic response is incomplete and falls short of producing the optimum phenotype, synergistic selection can lead to genetic divergence and bring the phenotype closer to the optimum. In contrast, non-adaptive plasticity should increase the strength of selection, because phenotypes will be further from the local optimum, requiring antagonistic selection to overcome the phenotype-environment mismatch and facilitate adaptive divergence. We test these ideas by documenting predator-induced plasticity for resting metabolic rate and growth rate in populations of the Trinidadian guppy (Poecilia reticulata) adapted to high and low predation. We find reduced metabolic rates and growth rates when cues from a predator are present during development, a pattern suggestive of adaptive and non-adaptive plasticity, respectively. When we compared populations recently transplanted from a high-predation environment into four streams lacking predators, we found evidence for rapid adaptive evolution both in metabolism and growth rate. We discuss the implications for predicting how traits will respond to selection, depending on the type of plasticity they exhibit.

  4. Distributed adaptive diagnosis of sensor faults using structural response data (United States)

    Dragos, Kosmas; Smarsly, Kay


    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.

  5. Distributed reinforcement learning for adaptive and robust network intrusion response (United States)

    Malialis, Kleanthis; Devlin, Sam; Kudenko, Daniel


    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.

  6. Epigenetic memory for stress response and adaptation in plants. (United States)

    Kinoshita, Tetsu; Seki, Motoaki


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

  7. Optimization of biguanide derivatives as selective antitumor agents blocking adaptive stress responses in the tumor microenvironment. (United States)

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


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

  8. 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.

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

    CERN Document Server

    Kaluza, Pablo


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


    Institute of Scientific and Technical Information of China (English)



    A multistage adaptive higher-order nonlinear finite impulse response (MAHONFIR) filter is proposed to predict chaotic time series. Using this approach, we may readily derive the decoupled parallel algorithm for the adaptation of the coefficients of the MAHONFIR filter, to guarantee a more rapid convergence of the adaptive weights to their optimal values. Numerical simulation results show that the MAHONFIR filters proposed here illustrate a very good performance for making an adaptive prediction of chaotic time series.

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

    Directory of Open Access Journals (Sweden)

    Robin Bronen


    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.

  12. Transcriptomic Analysis of Laribacter hongkongensis Reveals Adaptive Response Coupled with Temperature (United States)

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


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

  13. Somatic-evoked brain responses as indicators of adaptation to nitrogen narcosis. (United States)

    Langley, T D; Hamilton, R W


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

  14. In Vitro Cytotoxicity and Adaptive Stress Responses to Selected Haloacetic Acid and Halobenzoquinone Water Disinfection Byproducts. (United States)

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


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

  15. Innate and adaptive immune responses to in utero infection with bovine viral diarrhea virus. (United States)

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


    Infection of pregnant cows with noncytopathic (ncp) bovine viral diarrhea virus (BVDV) induces rapid innate and adaptive immune responses, resulting in clearance of the virus in less than 3 weeks. Seven to 14 days after inoculation of the cow, ncpBVDV crosses the placenta and induces a fetal viremia. Establishment of persistent infection with ncpBVDV in the fetus has been attributed to the inability to mount an immune response before 90-150 days of gestational age. The result is 'immune tolerance', persistent viral replication and shedding of ncpBVDV. In contrast, we describe the chronic upregulation of fetal Type I interferon (IFN) pathway genes and the induction of IFN-γ pathways in fetuses of cows infected on day 75 of gestation. Persistently infected (PI) fetal IFN-γ concentrations also increased at day 97 at the peak of fetal viremia and IFN-γ mRNA was significantly elevated in fetal thymus, liver and spleen 14-22 days post maternal inoculation. PI fetuses respond to ncpBVDV infection through induction of Type I IFN and IFN-γ activated genes leading to a reduction in ncpBVDV titer. We hypothesize that fetal infection with BVDV persists because of impaired induction of IFN-γ in the face of activated Type I IFN responses. Clarification of the mechanisms involved in the IFN-associated pathways during BVDV fetal infection may lead to better detection methods, antiviral compounds and selection of genetically resistant breeding animals.

  16. Transgenerational epimutations induced by multi-generation drought imposition mediate rice plant’s adaptation to drought condition (United States)

    Zheng, Xiaoguo; Chen, Liang; Xia, Hui; Wei, Haibin; Lou, Qiaojun; Li, Mingshou; Li, Tiemei; Luo, Lijun


    Epigenetic mechanisms are crucial mediators of appropriate plant reactions to adverse environments, but their involvement in long-term adaptation is less clear. Here, we established two rice epimutation accumulation lines by applying drought conditions to 11 successive generations of two rice varieties. We took advantage of recent technical advances to examine the role of DNA methylation variations on rice adaptation to drought stress. We found that multi-generational drought improved the drought adaptability of offspring in upland fields. At single-base resolution, we discovered non-random appearance of drought-induced epimutations. Moreover, we found that a high proportion of drought-induced epimutations maintained their altered DNA methylation status in advanced generations. In addition, genes related to transgenerational epimutations directly participated in stress-responsive pathways. Analysis based on a cluster of drought-responsive genes revealed that their DNA methylation patterns were affected by multi-generational drought. These results suggested that epigenetic mechanisms play important roles in rice adaptations to upland growth conditions. Epigenetic variations have morphological, physiological and ecological consequences and are heritable across generations, suggesting that epigenetics can be considered an important regulatory mechanism in plant long-term adaptation and evolution under adverse environments. PMID:28051176

  17. Induction of a Radio-Adaptive Response by Low-dose Gamma Irradiation in Mouse Cardiomyocytes (United States)

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


    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 p53-mediated apoptosis genes Casp3, Casp9, Trp53, and Myc exhibited down-regulation but did not achieve a notable level of significance 4hr after H. 24hr after H, genetic down-regulation was no longer present compared to 24hr control. These data suggest a general reduction in genetic expression 4hrs after a high dose of gamma radiation. However, pre-exposure to 5cGy gamma radiation appears to facilitate a radio-adaptive response that mitigates the reduction in genetic expression associated

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

    NARCIS (Netherlands)

    Mees, Heleen


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

  19. 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.

  20. Dynamic Condition Response Graphs for Trustworthy Adaptive Case Management

    DEFF Research Database (Denmark)

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


    By trustworthy adaptive case management we mean that it should be possible to adapt processes and goals at runtime while guaranteeing that no deadlocks and livelocks are introduced. We propose to support this by applying a formal declarative process model, DCR Graphs, and exemplify its operational...... specified either as linear time logic (LTL) or DCR Graphs, extend the language with time and data and offer extended support for cross-organizational case management systems....

  1. 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


    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.

  2. Physiological responses to food deprivation in the house sparrow, a species not adapted to prolonged fasting. (United States)

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


    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.

  3. Adaptative nitric oxide overproduction in perivascular adipose tissue during early diet-induced obesity. (United States)

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


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

  4. 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

    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

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

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


    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.

  6. Using Randomization Tests to Preserve Type I Error With Response-Adaptive and Covariate-Adaptive Randomization. (United States)

    Simon, Richard; Simon, Noah Robin


    We demonstrate that clinical trials using response adaptive randomized treatment assignment rules are subject to substantial bias if there are time trends in unknown prognostic factors and standard methods of analysis are used. We develop a general class of randomization tests based on generating the null distribution of a general test statistic by repeating the adaptive randomized treatment assignment rule holding fixed the sequence of outcome values and covariate vectors actually observed in the trial. We develop broad conditions on the adaptive randomization method and the stochastic mechanism by which outcomes and covariate vectors are sampled that ensure that the type I error is controlled at the level of the randomization test. These conditions ensure that the use of the randomization test protects the type I error against time trends that are independent of the treatment assignments. Under some conditions in which the prognosis of future patients is determined by knowledge of the current randomization weights, the type I error is not strictly protected. We show that response-adaptive randomization can result in substantial reduction in statistical power when the type I error is preserved. Our results also ensure that type I error is controlled at the level of the randomization test for adaptive stratification designs used for balancing covariates.

  7. Delayed adaptive immunity is related to higher MMR vaccine-induced antibody titers in children. (United States)

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


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

  8. Interactions between aboveground and belowground induced responses against phytophages

    NARCIS (Netherlands)

    Dam, van N.M.; Harvey, J.A.; Waeckers, F.L.; Bezemer, T.M.; Putten, van der W.H.; Vet, L.E.M.


    Since their discovery about thirty years ago, induced plant responses have mainly been studied in interactions of plants with aboveground (AG) pathogens, herbivores and their natural enemies. Many induced responses, however, are known to be systemic and thus it is likely that responses induced by AG

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

    DEFF Research Database (Denmark)

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

    were obtained with flies held for several generations in a laboratory common garden setting, therefore we suggest that exposure to and avoidance of high temperatures under natural conditions has been an important selective agent causing the suggested adaptive differentiation between the populations.......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...

  10. A Comparison of the Adaptive Immune Response between Recovered Anthrax Patients and Individuals Receiving Three Different Anthrax Vaccines. (United States)

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


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

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

    Directory of Open Access Journals (Sweden)

    Thomas R Laws

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

  12. R-citalopram prevents the neuronal adaptive changes induced by escitalopram. (United States)

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


    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.

  13. 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.


    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

  14. A review of adaptive mechanisms in cell responses towards oxidative stress caused by dental resin monomers. (United States)

    Krifka, Stephanie; Spagnuolo, Gianrico; Schmalz, Gottfried; Schweikl, Helmut


    Dental composite resins are biomaterials commonly used to aesthetically restore the structure and function of teeth impaired by caries, erosion, or fracture. Residual monomers released from resin restorations as a result of incomplete polymerization processes interact with living oral tissues. Monomers like triethylene glycol dimethacrylate (TEGDMA) or 2-hydroxylethyl methacrylate (HEMA) are cytotoxic via apoptosis, induce genotoxic effects, and delay the cell cycle. Monomers also influence the response of cells of the innate immune system, inhibit specific odontoblast cell functions, or delay the odontogenic differentiation and mineralization processes in pulp-derived cells including stem cells. These observations indicate that resin monomers act as environmental stressors which inevitably disturb regulatory cellular networks through interference with signal transduction pathways. We hypothesize that an understanding of the cellular mechanisms underlying these phenomena will provide a better estimation of the consequences associated with dental therapy using composite materials, and lead to innovative therapeutic strategies and improved materials being used at tissue interfaces within the oral cavity. Current findings strongly suggest that monomers enhance the formation of reactive oxygen species (ROS), which is most likely the cause of biological reactions activated by dental composites and resin monomers. The aim of the present review manuscript is to discuss adaptive cell responses to oxidative stress caused by monomers. The particular significance of a tightly controlled network of non-enzymatic as well as enzymatic antioxidants for the regulation of cellular redox homeostasis and antioxidant defense in monomer-exposed cells will be addressed. The expression of ROS-metabolizing antioxidant enzymes like superoxide dismutase (SOD1), glutathione peroxidase (GPx1/2), and catalase in cells exposed to monomers will be discussed with particular emphasis on the role

  15. The role of the innate and adaptive immune responses in Acanthamoeba keratitis. (United States)

    Niederkorn, Jerry Y


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

  16. The biology of developmental plasticity and the Predictive Adaptive Response hypothesis. (United States)

    Bateson, Patrick; Gluckman, Peter; Hanson, Mark


    Many forms of developmental plasticity have been observed and these are usually beneficial to the organism. The Predictive Adaptive Response (PAR) hypothesis refers to a form of developmental plasticity in which cues received in early life influence the development of a phenotype that is normally adapted to the environmental conditions of later life. When the predicted and actual environments differ, the mismatch between the individual's phenotype and the conditions in which it finds itself can have adverse consequences for Darwinian fitness and, later, for health. Numerous examples exist of the long-term effects of cues indicating a threatening environment affecting the subsequent phenotype of the individual organism. Other examples consist of the long-term effects of variations in environment within a normal range, particularly in the individual's nutritional environment. In mammals the cues to developing offspring are often provided by the mother's plane of nutrition, her body composition or stress levels. This hypothetical effect in humans is thought to be important by some scientists and controversial by others. In resolving the conflict, distinctions should be drawn between PARs induced by normative variations in the developmental environment and the ill effects on development of extremes in environment such as a very poor or very rich nutritional environment. Tests to distinguish between different developmental processes impacting on adult characteristics are proposed. Many of the mechanisms underlying developmental plasticity involve molecular epigenetic processes, and their elucidation in the context of PARs and more widely has implications for the revision of classical evolutionary theory.

  17. Clinal adaptation and adaptive plasticity in Artemisia californica: implications for the response of a foundation species to predicted climate change. (United States)

    Pratt, Jessica D; Mooney, Kailen A


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

  18. 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)


    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) =.


    Directory of Open Access Journals (Sweden)

    N. V. Krylova


    Full Text Available The review examines in a comparative perspective the key moments of formation of innate and adaptive immune responses to different types of current flavivirus vaccines: live attenuated against yellow fever virus and inactivated whole virus against tick-borne encephalitis virus. Particular attention is paid to the ability of these different vaccines, containing exogenous pathogen-associated molecular structures, to stimulate innate immunity. Live attenuated vaccine by infecting several subtypes of dendritic cells activates them through various pattern-recognition receptors, such as Tolland RIG-I-like receptors, which leads to significant production of proinflammatory cytokines, including interferon-α primary mediator of innate antiviral immunity. By simulating natural viral infection, this vaccine quickly spreads over the vascular network, and the dendritic cells, activated by it, migrate to the draining lymph nodes and trigger multiple foci of Tand B-cell activation. Inactivated vaccine stimulates the innate immunity predominantly at the injection site, and for the sufficient activation requires the presence in its composition of an adjuvant (aluminum hydroxide, which effects the formation and activation of inflammasomes, ensuring the formation and secretion of IL-1β and IL-18 that, in turn, trigger a cascade of cellular and humoral innate immune responses. We demonstrated the possibility of involvement in the induction of innate immunity, mediated by the inactivated vaccine, endogenous pathogenassociated molecular patterns (uric acid and host cell DNA, forming at the vaccine injection site. We discuss the triggering of Band T-cell responses by flavivirus vaccines that determine various duration of protection against various pathogens. A single injection of the live vaccine against yellow fever virus induces polyvalent adaptive immune response, including the production of cytotoxic T-lymphocytes, Th1and Th2-cells and neutralizing antibodies

  20. 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


    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

  1. Stability of sublethal acid stress adaptation and induced cross protection against lauric arginate in Listeria monocytogenes. (United States)

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


    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.

  2. Environmental Stress Response and Adaptation Mechanisms in Rhizobia

    Directory of Open Access Journals (Sweden)

    Sanja Kajić


    Full Text Available Rhizobia are bacteria that can fixate atmospheric nitrogen in association within the root or the stem nodules of legume plants and transform atmospheric nitrogen to ammonia. Soil environmental conditions are critical factors for the persistence and survival of rhizobia in the soil. The changes in the rhizosphere environment can affect both growth and saprophytic competence, which will influence competitiveness and persistence. Environmental stress imposes a major threat to symbiotic nitrogen fixation and agriculture that can be limited by soil and climatic factors such as salinity, drought, temperature, acidity/alkalinity and heavy metals. In this review we present several different mechanisms in rhizobia adaptation under stress factors.

  3. Length adaptation of smooth muscle contractile filaments in response to sustained activation. (United States)

    Stålhand, Jonas; Holzapfel, Gerhard A


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

  4. Inherited adaptation of genome-rewired cells in response to a challenging environment (United States)

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


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

  5. A new family of covariate-adjusted response adaptive designs and their properties

    Institute of Scientific and Technical Information of China (English)

    ZHANG Li-Xin; HU Fei-fang


    It is often important to incorporate covariate information in the design of clinical trials. In literature there are many designs of using stratification and covariate-adaptive randomization to balance certain known covaxiate. Recently, some covariate-adjusted response-adaptive (CARA) designs have been proposed and their asymptotic properties have been studied (Ann.Statist. 2007). However, these CARA designs usually have high variabilities. In this paper, a new family of covariate-adjusted response-adaptive (CARA) designs is presented. It is shown that the new designs have less variables and therefore are more efficient.

  6. Smart plants, smart models? On adaptive responses in vegetation-soil systems (United States)

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


    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

  7. 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


    administration for 3 days (P TNF-alpha, IFN-gamma, and IL-6 responses to TT were enhanced after 8 and 14 days (P responses increased significantly within 3 days (P ... below baseline levels after 14 days (P responses to both CA and TT (P responses were observed. Upon addition to normal mononuclear cells in vitro, Immulina elicited strong TNF-alpha, IL-1......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....

  8. Biological and Theoretical Studies of Adaptive Networks: The Conditioned Response (United States)


    stimulation of the red nucleus produces EPSPs in contralateral AAN neurons at mono- synaptic latencies 26 Holstege and Tan "’ report that with...Consistent with these anatomical data. intermediate facial nucleus neurons respond with EPSPs at monosynaptic latencies to red nucleus stimulation...responses. SpoV cells could project to red nucleus intrinsic inhibitory intemneurons. If these interneurons fired in 276 response to movement

  9. Identification of heat stress-responsive genes in heat-adapted thermal Agrostis scabra by suppression subtractive hybridization. (United States)

    Tian, Jiang; Belanger, Faith C; Huang, Bingru


    To gain insights into molecular mechanisms of grass tolerance to heat stress, we constructed a suppression subtractive cDNA library to identify heat-responsive genes for a C(3) grass species, thermal Agrostis scabra adapted to heat stress in geothermal areas in Yellowstone National Park. Plants were exposed to 20 degrees C (control) or 35 degrees C for 12d. The SSH analysis was performed with control samples as the driver and heat-stressed samples as the tester. Differentially expressed cDNA fragments were cloned to screen the heat up-regulated library. The SSH analysis identified 120 non-redundant putative heat-responsive cDNAs out of 1180 clones. Genes with homology to known proteins were categorized into six functional groups, with the largest group of genes involved in stress/defense, followed by the group of genes related to protein metabolism. Immunoblot analysis confirmed increases in transcripts of selected genes under heat stress. Transcripts of seven and eight genes were strongly enhanced or induced in shoots and roots, respectively, while two genes were only induced in roots under heat stress. The heat up-regulated genes in thermal A. scabra adapted to long-term heat stress are potential candidate genes for engineering stress-tolerant grasses and for revealing molecular mechanisms of grass adaptation to heat stress.

  10. Adaptive peripheral immune response increases proliferation of neural precursor cells in the adult hippocampus. (United States)

    Wolf, Susanne A; Steiner, Barbara; Wengner, Antje; Lipp, Martin; Kammertoens, Thomas; Kempermann, Gerd


    To understand the link between peripheral immune activation and neuronal precursor biology, we investigated the effect of T-cell activation on adult hippocampal neurogenesis in female C57Bl/6 mice. A peripheral adaptive immune response triggered by adjuvant-induced rheumatoid arthritis (2 microg/microl methylated BSA) or staphylococcus enterotoxin B (EC(50) of 0.25 microg/ml per 20 g body weight) was associated with a transient increase in hippocampal precursor cell proliferation and neurogenesis as assessed by immunohistochemistry and confocal microscopy. Both treatments were paralleled by an increase in corticosterone levels in the hippocampus 1- to 2-fold over the physiological amount measured by quantitative radioimmunoassay. In contrast, intraperitoneal administration of the innate immune response activator lipopolysaccaride (EC(50) of 0.5 microg/ml per 20 g body weight) led to a chronic 5-fold increase of hippocampal glucocorticoid levels and a decrease of adult neurogenesis. In vitro exposure of murine neuronal progenitor cells to corticosterone triggered either cell death at high (1.5 nM) or proliferation at low (0.25 nM) concentrations. This effect could be blocked using a viral vector system expressing a transdomain of the glucocorticoid receptor. We suggest an evolutionary relevant communication route for the brain to respond to environmental stressors like inflammation mediated by glucocorticoid levels in the hippocampus.

  11. Skeletal muscle adaptation in response to exercise(Ⅱ)

    Institute of Scientific and Technical Information of China (English)

    Ping Li; Zhen Yan


    @@ MITOCHONDRIAL BIOGENESIS AND SLOW MUSCLE GENE EXPRESSION Recent findings in proxisome proliferators-activated recep tor γ (PPARγ) coactivator-1α (PGC-1α) gene regulation and function have led to the consideration of PGC-1α as a key regulator in regulating important features of skeletal muscle adaptation.PGC-1α is a transcriptional coactivator cloned originally by a yeast-two-hybrid screen from a differentiated brown fat cell line using PPARγ as bait[80]. PGC-1α mRNA and protein are highly expressed in slow,oxidative fibers compared to the fast, glycolytic fibers[81-82],consistent with the function of a gene involved in fiber type specialization. The functional importance of PGC-1α in striated muscles has been suggested by several different models [83-84].

  12. Exercise-induced metacarpophalangeal joint adaptation in the Thoroughbred racehorse. (United States)

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


    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

  13. Spider mites adaptively learn recognizing mycorrhiza-induced changes in host plant volatiles. (United States)

    Patiño-Ruiz, J David; Schausberger, Peter


    Symbiotic root micro-organisms such as arbuscular mycorrhizal fungi commonly change morphological, physiological and biochemical traits of their host plants and may thus influence the interaction of aboveground plant parts with herbivores and their natural enemies. While quite a few studies tested the effects of mycorrhiza on life history traits, such as growth, development and reproduction, of aboveground herbivores, information on possible effects of mycorrhiza on host plant choice of herbivores via constitutive and/or induced plant volatiles is lacking. Here we assessed whether symbiosis of the mycorrhizal fungus Glomus mosseae with common bean plants Phaseolus vulgaris influences the response of the two-spotted spider mite Tetranychus urticae to volatiles of plants that were clean or infested with spider mites. Mycorrhiza-naïve and -experienced spider mites, reared on mycorrhizal or non-mycorrhizal bean plants for several days before the experiments, were subjected to Y-tube olfactometer choice tests. Experienced but not naïve spider mites distinguished between constitutive volatiles of clean non-mycorrhizal and mycorrhizal plants, preferring the latter. Neither naïve nor experienced spider mites distinguished between spider mite-induced volatiles of mycorrhizal and non-mycorrhizal plants. Learning the odor of clean mycorrhizal plants, resulting in a subsequent preference for these odors, is adaptive because mycorrhizal plants are more favorable host plants for fitness of the spider mites than are non-mycorrhizal plants.

  14. 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


    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 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.

  15. Induced mutations in yeast cell populations adapting to an unforeseen challenge. (United States)

    Moore, Lindsay S; Wei, Wu; Stolovicki, Elad; Benbenishty, Tamar; Wilkening, Stefan; Steinmetz, Lars M; Braun, Erez; David, Lior


    The modern evolutionary synthesis assumes that mutations occur at random, independently of the environment in which they confer an advantage. However, there are indications that cells facing challenging conditions can adapt rapidly, utilizing processes beyond selection of pre-existing genetic variation. Here, we show that a strong regulatory challenge can induce mutations in many independent yeast cells, in the absence of general mutagenesis. Whole genome sequencing of cell lineages reveals a repertoire of independent mutations within a single lineage that arose only after the cells were exposed to the challenging environment, while other cells in the same lineage adapted without any mutation in their genomes. Thus, our experiments uncovered multiple alternative routes for heritable adaptation that were all induced in the same lineage during a short time period. Our results demonstrate the existence of adaptation mechanisms beyond random mutation, suggesting a tight connection between physiological and genetic processes.

  16. Direct Adaptive Rejection of Vortex-Induced Disturbances for a Powered SPAR Platform (United States)

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


    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.

  17. Design of artificial genetic regulatory networks with multiple delayed adaptive responses* (United States)

    Kaluza, Pablo; Inoue, Masayo


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

  18. Minimization of biosynthetic costs in adaptive gene expression responses of yeast to environmental changes.

    Directory of Open Access Journals (Sweden)

    Ester Vilaprinyo


    Full Text Available Yeast successfully adapts to an environmental stress by altering physiology and fine-tuning metabolism. This fine-tuning is achieved through regulation of both gene expression and protein activity, and it is shaped by various physiological requirements. Such requirements impose a sustained evolutionary pressure that ultimately selects a specific gene expression profile, generating a suitable adaptive response to each environmental change. Although some of the requirements are stress specific, it is likely that others are common to various situations. We hypothesize that an evolutionary pressure for minimizing biosynthetic costs might have left signatures in the physicochemical properties of proteins whose gene expression is fine-tuned during adaptive responses. To test this hypothesis we analyze existing yeast transcriptomic data for such responses and investigate how several properties of proteins correlate to changes in gene expression. Our results reveal signatures that are consistent with a selective pressure for economy in protein synthesis during adaptive response of yeast to various types of stress. These signatures differentiate two groups of adaptive responses with respect to how cells manage expenditure in protein biosynthesis. In one group, significant trends towards downregulation of large proteins and upregulation of small ones are observed. In the other group we find no such trends. These results are consistent with resource limitation being important in the evolution of the first group of stress responses.

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

    DEFF Research Database (Denmark)

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


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

  1. The innate and adaptive immune response to avian influenza virus infections and vaccines (United States)

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

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

  3. Understanding How Space Travel Affects Blood Vessels: Arterial Remodeling and Functional Adaptations Induced by Microgravity (United States)

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


    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

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

    DEFF Research Database (Denmark)

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


    and adenocarcinoma of the esophagogastric junction, in order to investigate whether the use of PET-guided treatment individualization results in a survival benefit. In Hodgkin lymphoma and aggressive non-Hodgkin lymphoma, several trials are ongoing. Some studies aim to investigate the use of PET in early...... 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...... realized in adenocarcinoma of the esophagogastric junction. These trials showed that patients with an early metabolic response to neoadjuvant chemotherapy benefit from this treatment, whereas metabolic non-responders should switch early to surgery, thus reducing the risk of tumor progression during...

  5. Chemical Tools To Monitor and Manipulate Adaptive Immune Responses. (United States)

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


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

  6. Gender differences in farmers' responses to climate change adaptation in Yongqiao District, China. (United States)

    Jin, Jianjun; Wang, Xiaomin; Gao, Yiwei


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

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


    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 muscle adaptations to low-volume, all-out HIIT. Despite the lack of skeletal muscle mitochondrial adaptations, our data show that a training programme based on a brief bout of high-intensity exercise, which lasted <10 min per session including warm-up, and performed three times per week for 6 weeks, improved peak oxygen uptake in young healthy subjects.

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

    Directory of Open Access Journals (Sweden)

    Ashley S P Boggs

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

  9. Adaptive responses to dasatinib-treated lung squamous cell cancer cells harboring DDR2 mutations. (United States)

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


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

  10. Pancreatic β- and α-cell adaptation in response to metabolic changes


    Ellenbroek, Johanne Hendrike (Rianne)


    Insulin-producing pancreatic β-cells are essential to maintain blood glucose levels within a narrow range. β-cells can adapt to an increased insulin demand by enhancing insulin secretion via increased β-cell function and/or increased β-cell mass. Inadequate β-cell adaptation leads to hyperglycemia and eventually diabetes mellitus. Therefore, it is critical to understand how the β-cell mass is regulated. We investigated β- and α-cell adaptation in response to different metabolic changes. We fo...

  11. 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;


    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 species (maize (Zea mays), sorghum (Sorghum bicolor), and rice (Oryza sativa)) and five temperate Pooideae...... of positive selection were significantly stronger in LTI trees after the rice and Pooideae split but before the Brachypodium divergence (P ... 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...

  12. Quantifying rates of evolutionary adaptation in response to ocean acidification. (United States)

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


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

  13. In vivo imaging of C. elegans ASH neurons: cellular response and adaptation to chemical repellents


    Hilliard, Massimo A.; Apicella, Alfonso J.; Kerr, Rex; Suzuki, Hiroshi; Bazzicalupo, Paolo; Schafer, William R


    ASH sensory neurons are required in Caenorhabditis elegans for a wide range of avoidance behaviors in response to chemical repellents, high osmotic solutions and nose touch. The ASH neurons are therefore hypothesized to be polymodal nociceptive neurons. To understand the nature of polymodal sensory response and adaptation at the cellular level, we expressed the calcium indicator protein cameleon in ASH and analyzed intracellular Ca2+ responses following stimulation with chemical repellents, o...

  14. Effects of local adaptation and interspecific competition on species' responses to climate change. (United States)

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


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

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

    Directory of Open Access Journals (Sweden)

    Milašinović Ljubomir


    Full Text Available Introduction Pregnancy is an intriguing immunologic phenomenon. In spite of genetic differences, maternal and fetal cells are in close contact over the whole course of pregnancy with no evidence of either humoral and/or cellular immunologic response of mother to fetus as an allotransplant. The general opinion is that the fundamental protective mechanism must be located locally at the contact-plate, between the maternal and fetal tissues. Immunologic investigations proved the presence of specific systems which block the function of antipaternal maternal antibodies, as well as formation of cytotoxic maternal T-cells to paternal antigens. The system preventing rejection of graft during pregnancy is functioning at the level of maternal and fetal tissues. The protective mechanisms are coded by genes of MCH region, locus HLA-G. Protective mechanisms in the placenta The placenta protects itself against antibody-mediated damage. A high level of complement-regulatory proteins (CD46, CD55 and CD59, being the response to the synthesis of complement-fixing maternal antibodies to paternal antigens and regulation of the placental HLA expression as a preventive reaction of the feto-placental unit to the influence of maternal CTL, are the most important protective mechanisms of placenta. Protective mechanisms shared by the placenta and uterus Protective mechanisms common both for placenta and uterus are as follows: expressions of Fas ligand prevention of infiltration of activated immune cells, regulation of immunosuppression which prevents proliferation of immune cells and high natural immunity (Na cells and macrophages of the decidua.

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

    Directory of Open Access Journals (Sweden)

    Devon eChandler-Brown


    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.

  17. Sorbitol treatment extends lifespan and induces the osmotic stress response in Caenorhabditis elegans. (United States)

    Chandler-Brown, Devon; Choi, Haeri; Park, Shirley; Ocampo, Billie R; Chen, Shiwen; Le, Anna; Sutphin, George L; Shamieh, Lara S; Smith, Erica D; Kaeberlein, Matt


    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.


    Directory of Open Access Journals (Sweden)

    Rishav Kumar


    Full Text Available The Present paper deals with the herbicide Butachlor (5,10 ,20,40 and 80ppm-induced changes in physiological and biochemical parameters related to photosynthesis and defense systems in paddy field cyanobacterium Plectonema boryanum grown under laboratory conditions. Growth and photosynthetic pigments, i.e., chlorophyll a and carotenoids were adversely affected by Butachlor treatment and the inhibition was found to be dose dependent. The toxic effect of Butachlor was more pronounced protein; however, a considerable reduction in chlorophyll a, and carotenoids was also noticed. Furthermore, Butachlor with increasing doses accelerated the formation of active oxygen species, i.e., O2- and H2O2, in cells progressively. As a consequence of active oxygen species (AOS generation in Butachlor -treated cells, the activity of superoxide dismutase (SOD and peroxidase (POD was enhanced considerably. Besides the accelerated action of enzymatic defense systems, Protein damage also showed an increasing trend with the rising concentration of Butachlor (5, 10, 20, 40 and 80 ppm.

  19. 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


    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 ...

  20. Plasticity and genetic adaptation mediate amphibian and reptile responses to climate change. (United States)

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


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

  1. Exercise-induced ROS in heat shock proteins response. (United States)

    Dimauro, Ivan; Mercatelli, Neri; Caporossi, Daniela


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

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


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

  3. Different types of exercise induce differential effects on neuronal adaptations and memory performance. (United States)

    Lin, Tzu-Wei; Chen, Shean-Jen; Huang, Tung-Yi; Chang, Chia-Yuan; Chuang, Jih-Ing; Wu, Fong-Sen; Kuo, Yu-Min; Jen, Chauying J


    Different exercise paradigms show differential effects on various forms of memory. We hypothesize that the differential effects of exercises on memory performance are caused by different neuroplasticity changes in relevant brain regions in response to different exercise trainings. We examined the effects of treadmill running (TR) and wheel running (WR) on the Pavlovian fear conditioning task that assesses learning and memory performance associated with the amygdala (cued conditioning) and both the amygdala and hippocampus (contextual conditioning). The skeletal muscle citrate synthase activity, an indicator of aerobic capacity, was elevated in rats received 4 w of TR, but not WR. While both TR and WR elevated the contextual conditional response, only TR facilitated the cued conditional response. Using a single-neuron labeling technique, we found that while both TR and MR enlarged the dendritic field and increased the spine density in hippocampal CA3 neurons, only TR showed these effects in basolateral amygdalar neurons. Moreover, both types of exercise upregulated synaptic proteins (i.e., TrkB and SNAP-25) in the hippocampus; however only TR showed similar effects in the amygdala. Injection of K252a, a TrkB kinase inhibitor, in the dorsal hippocampus or basolateral amygdala abolished the exercise-facilitated contextual or cued fear learning and memory performance, respectively, regardless of the types of exercise. In summary, our results supported that different types of exercise affect the performance of learning and memory via BDNF-TrkB signaling and neuroplasticity in specific brain regions. The brain region-specific neuronal adaptations are possibly induced by various levels of intensity/stress elicited by different types of exercise.

  4. Adaptive and Pathogenic Responses to Stress by Stem Cells during Development

    Directory of Open Access Journals (Sweden)

    Daniel A. Rappolee


    Full Text Available Cellular stress is the basis of a dose-dependent continuum of responses leading to adaptive health or pathogenesis. For all cells, stress leads to reduction in macromolecular synthesis by shared pathways and tissue and stress-specific homeostatic mechanisms. For stem cells during embryonic, fetal, and placental development, higher exposures of stress lead to decreased anabolism, macromolecular synthesis and cell proliferation. Coupled with diminished stem cell proliferation is a stress-induced differentiation which generates minimal necessary function by producing more differentiated product/cell. This compensatory differentiation is accompanied by a second strategy to insure organismal survival as multipotent and pluripotent stem cells differentiate into the lineages in their repertoire. During stressed differentiation, the first lineage in the repertoire is increased and later lineages are suppressed, thus prioritized differentiation occurs. Compensatory and prioritized differentiation is regulated by at least two types of stress enzymes. AMP-activated protein kinase (AMPK which mediates loss of nuclear potency factors and stress-activated protein kinase (SAPK that does not. SAPK mediates an increase in the first essential lineage and decreases in later lineages in placental stem cells. The clinical significance of compensatory and prioritized differentiation is that stem cell pools are depleted and imbalanced differentiation leads to gestational diseases and long term postnatal pathologies.

  5. Adaptive and Pathogenic Responses to Stress by Stem Cells during Development. (United States)

    Mansouri, Ladan; Xie, Yufen; Rappolee, Daniel A


    Cellular stress is the basis of a dose-dependent continuum of responses leading to adaptive health or pathogenesis. For all cells, stress leads to reduction in macromolecular synthesis by shared pathways and tissue and stress-specific homeostatic mechanisms. For stem cells during embryonic, fetal, and placental development, higher exposures of stress lead to decreased anabolism, macromolecular synthesis and cell proliferation. Coupled with diminished stem cell proliferation is a stress-induced differentiation which generates minimal necessary function by producing more differentiated product/cell. This compensatory differentiation is accompanied by a second strategy to insure organismal survival as multipotent and pluripotent stem cells differentiate into the lineages in their repertoire. During stressed differentiation, the first lineage in the repertoire is increased and later lineages are suppressed, thus prioritized differentiation occurs. Compensatory and prioritized differentiation is regulated by at least two types of stress enzymes. AMP-activated protein kinase (AMPK) which mediates loss of nuclear potency factors and stress-activated protein kinase (SAPK) that does not. SAPK mediates an increase in the first essential lineage and decreases in later lineages in placental stem cells. The clinical significance of compensatory and prioritized differentiation is that stem cell pools are depleted and imbalanced differentiation leads to gestational diseases and long term postnatal pathologies.

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

    Directory of Open Access Journals (Sweden)

    Maddalena Pennacchia


    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.

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

    Directory of Open Access Journals (Sweden)

    Richard A Goldstein


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

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

    DEFF Research Database (Denmark)

    Caspeta, Luis; Chen, Yun; Nielsen, Jens


    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....... This demonstrates robustness of the yeast transcriptional program when exposed to heat, and that the thermotolerant strains streamlined their path to rapidly and optimally reach post-stress transcriptional and metabolic levels. Thus, long-term adaptation to heat improved yeasts ability to rapidly adapt to increased...

  9. Differential molecular responses of rapeseed cotyledons to light and dark reveal metabolic adaptations towards autotrophy establishment

    Directory of Open Access Journals (Sweden)

    Dongli He


    Full Text Available Photosynthesis competent autotrophy should be established during the postgerminative stage of plant growth. Among the multiple factors, light plays a decisive role in the switch from heterotrophic to autotrophic growth. Under dark condition, the rapeseed hypocotyl extends quickly with an apical hook, and the cotyledon is yellow and folded, and maintains high level of the isocitrate lyase (ICL. By contrast, in the light, the hypocotyl extends slowly, the cotyledon unfolds and turns green, the ICL content changes in parallel with the cotyledon greening. To reveal metabolic adaptations during the establishment of postgerminative autotrophy in rapeseed, we conducted comparative proteomic and metabolomic analyses of the cotyledons of seedlings grown under light versus dark conditions. Under both conditions, the increase of the protease, fatty acids β-oxidation and glyoxylate-cycle related proteins was accompanied with rapid degradation of the stored proteins and lipids with an accumulation of the amino acids, while light condition partially retarded these conversions. Light significantly induced the expression of chlorophyll-binding and photorespiration related proteins, resulting in an increase of the reducing-sugar. However, the levels of some chlide conversion, Calvin-cycle and photorespiration related proteins also accumulated in dark grown cotyledons, implying that the transition from heterotrophy to autotrophy is programmed in the seed rather than induced by light. Various anti-stress systems, e.g., redox related proteins, salicylic acid, proline and chaperones, were employed to release the oxidative stress, which was mainly derived from lipid oxidation or photorespiration, under both conditions. This study provides a comprehensive understanding of the differential molecular responses of rapeseed cotyledons to light and dark conditions, which will facilitate further study on the complex mechanism underlying the transition from heterotrophy to

  10. The role of ER stress response on ionizing radiation-induced apoptosis in intestinal epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Eun Sang; Kim, Kwang Seok; Woo, Sang Keun; Lee, Yong Jin; Jeong, Jae Hoon; Lee, Yoon Jin; Kang, Seong Man; Lim, Young Bin [Laboratory of Radiation Effect, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)


    Apoptosis in the intestinal epithelium is the primary pathologic factor that initiates radiation-induced intestinal injury. However, mechanism involved in ionizing radiation (IR)-induced apoptosis in the intestinal epithelium is not clearly understood. The endoplasmic reticulum (ER) stress is triggered by perturbation of the ER functions, leading to the activation of the unfolded protein response (UPR), an adaptive signaling cascade aimed at restoring ER homeostasis by facilitating the degradation of misfolded proteins and expanding the protein folding capacity of the cell. Recently, IR has also been shown to induce ER stress, thereby activating the UPR signaling pathway in intestinal epithelial cells. In this study, we report the role of ER stress responses in IR-induced intestinal epithelial cell death. We show that chemical ER stress inducers, such as tunicamycin or thapsigargin, enhance IR-induced caspase3 activation. Knockdown of xbp1 or atf6 with siRNA leads to inhibition of IR-induced caspase3 activation. Taken together, our results suggest a pro-apoptotic role of ER stress in IR-exposed intestinal epithelial cells. Our findings could contribute to the development of new strategies based on modulating ER stress responses to prevent IR-induced intestinal injury.

  11. Adaptive responses reveal contemporary and future ecotypes in a desert shrub. (United States)

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


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

  12. Modeling light adaptation in circadian clock: prediction of the response that stabilizes entrainment. (United States)

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


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

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

    Directory of Open Access Journals (Sweden)

    Kunichika Tsumoto

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

  14. 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


    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.

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


    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.

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

    KAUST Repository

    Bryant, C. M.


    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.

  17. 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.


    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.

  18. Integrating human responses to climate change into conservation vulnerability assessments and adaptation planning. (United States)

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


    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.

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


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


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

  20. Rhetorical Dissent as an Adaptive Response to Classroom Problems: A Test of Protection Motivation Theory (United States)

    Bolkan, San; Goodboy, Alan K.


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

  1. Determining adaptive and adverse oxidative stress responses in human bronical epithelial cells exposed to zinc (United States)

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

  2. Adapting a Multigenre-Response Model for College Readers of American Literature (United States)

    Hsu, Jeng-yih Tim


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

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

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

  4. Developing adaptive mobile support for crisis response in synthetic task environments

    NARCIS (Netherlands)

    Brake, G.M. te; Smets, N.J.J.M.


    This paper presents an experimental platform for the development and evaluation of mobile decision support for crisis response operations. Using a game-engine, synthetic task environments can be created in which coordination support and the usability of adaptive user interfaces for first responders

  5. Adaptations to exercise training and contraction-induced muscle injury in animal models of muscular dystrophy. (United States)

    Carter, Gregory T; Abresch, R Ted; Fowler, William M


    This article reviews the current status of exercise training and contraction-induced muscle-injury investigations in animal models of muscular dystrophy. Most exercise-training studies have compared the adaptations of normal and dystrophic muscles with exercise. Adaptation of diseased muscle to exercise occurs at many levels, starting with the extracellular matrix, but also involves cytoskeletal architecture, muscle contractility, repair mechanisms, and gene regulation. The majority of exercise-injury investigations have attempted to determine the susceptibility of dystrophin-deficient muscles to contraction-induced injury. There is some evidence in animal models that diseased muscle can adapt and respond to mechanical stress. However, exercise-injury studies show that dystrophic muscles have an increased susceptibility to high mechanical forces. Most of the studies involving exercise training have shown that muscle adaptations in dystrophic animals were qualitatively similar to the adaptations observed in control muscle. Deleterious effects of the dystrophy usually occur only in older animals with advanced muscle fiber degeneration or after high-resistive eccentric training. The main limitations in applying these conclusions to humans are the differences in phenotypic expression between humans and genetically homologous animal models and in the significant biomechanical differences between humans and these animal models.

  6. Hypoxia Inducible Factor Pathway and Physiological Adaptation: A Cell Survival Pathway? (United States)

    Kumar, Hemant; Choi, Dong-Kug


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

  7. The adaptive immune response does not influence hantavirus disease or persistence in the Syrian hamster. (United States)

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


    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.

  8. Genetic mapping of ada and adc mutations affecting the adaptive response of Escherichia coli to alkylating agents. (United States)

    Sedgwick, B


    The adaptive response to alkylating agents is an inducible repair system which protects Escherichia coli against the mutagenicity and toxicity of these agents. Four mutations, ada-3, ada-5, ada-6, and adc-1, which confer differing phenotypes as regards this response, were shown to be cotransducible with gyrA, and were located at 47 min on the E. coli genetic map. A mutation already shown on the map at 47 min as tag (B. J. Bachmann and K. B. Low, Microbiol. Rev. 44:1--56, 1980; Karran et al., J. Mol. Biol. 140:101--127, 1980) is now known to be an ada mutation (G. Evensen and E. Seeberg, personal communication).

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

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    Willis Cynthia R


    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

  10. Secretome analysis revealed adaptive and non-adaptive responses of the Staphylococcus carnosus femB mutant. (United States)

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


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

  11. Adaptive immune response in JAM-C-deficient mice: normal initiation but reduced IgG memory. (United States)

    Zimmerli, Claudia; Lee, Boris P L; Palmer, Gaby; Gabay, Cem; Adams, Ralf; Aurrand-Lions, Michel; Imhof, Beat A


    We have recently shown that junctional adhesion molecule (JAM)-C-deficient mice have leukocytic pulmonary infiltrates, disturbed neutrophil homeostasis, and increased postnatal mortality. This phenotype was partially rescued when mice were housed in ventilated isolators, suggesting an inability to cope with opportunistic infections. In the present study, we further examined the adaptive immune responses in JAM-C(-/-) mice. We found that murine conventional dendritic cells express in addition to Mac-1 and CD11c also JAM-B as ligand for JAM-C. By in vitro adhesion assay, we show that murine DCs can interact with recombinant JAM-C via Mac-1. However, this interaction does not seem to be necessary for dendritic cell migration and function in vivo, even though JAM-C is highly expressed by lymphatic sinuses of lymph nodes. Nevertheless, upon immunization and boosting with a protein Ag, JAM-C-deficient mice showed decreased persistence of specific circulating Abs although the initial response was normal. Such a phenotype has also been observed in a model of Ag-induced arthritis, showing that specific IgG2a Ab titers are reduced in the serum of JAM-C(-/-) compared with wild-type mice. Taken together, these data suggest that JAM-C deficiency affects the adaptive humoral immune response against pathogens, in addition to the innate immune system.

  12. Distinctive adaptive response to repeated exposure to hydrogen peroxide associated with upregulation of DNA repair genes and cell cycle arrest

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    Gloria A. Santa-Gonzalez


    Full Text Available Many environmental and physiological stresses are chronic. Thus, cells are constantly exposed to diverse types of genotoxic insults that challenge genome stability, including those that induce oxidative DNA damage. However, most in vitro studies that model cellular response to oxidative stressors employ short exposures and/or acute stress models. In this study, we tested the hypothesis that chronic and repeated exposure to a micromolar concentration of hydrogen peroxide (H2O2 could activate DNA damage responses, resulting in cellular adaptations. For this purpose, we developed an in vitro model in which we incubated mouse myoblast cells with a steady concentration of ~50 μM H2O2 for one hour daily for seven days, followed by a final challenge of a 10 or 20X higher dose of H2O2 (0.5 or 1 mM. We report that intermittent long-term exposure to this oxidative stimulus nearly eliminated cell toxicity and significantly decreased genotoxicity (in particular, a >5-fold decreased in double-strand breaks resulting from subsequent acute exposure to oxidative stress. This protection was associated with cell cycle arrest in G2/M and induction of expression of nine DNA repair genes. Together, this evidence supports an adaptive response to chronic, low-level oxidative stress that results in genomic protection and up-regulated maintenance of cellular homeostasis.

  13. Transcriptional Analysis of The Adaptive Digestive System of The Migratory Locust in Response to Plant Defensive Protease Inhibitors (United States)

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


    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.

  14. Sliding mode control of wind-induced vibrations using fuzzy sliding surface and gain adaptation (United States)

    Thenozhi, Suresh; Yu, Wen


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

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

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    Jonathan J Hansen

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

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

    Wang, Y.; Pan, Y.


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

  17. Acid resistance and response to pH-induced stress in two Lactobacillus plantarum strains with probiotic potential. (United States)

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


    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.

  18. Rate and adaptation effects on the auditory evoked brainstem response in human newborns and adults. (United States)

    Lasky, R E


    Auditory evoked brainstem response (ABR) latencies increased and amplitudes decreased with increasing stimulus repetition rate for human newborns and adults. The wave V latency increases were larger for newborns than adults. The wave V amplitude decreases were smaller for newborns than adults. These differences could not be explained by developmental differences in frequency responsivity. The transition from the unadapted to the fully adapted response was less rapid in newborns than adults at short (= 10 ms) inter stimulus intervals (ISIs). At longer ISIs (= 20 ms) there were no developmental differences in the transition to the fully adapted response. The newborn transition occurred in a two stage process. The rapid initial stage observed in adults and newborns was complete by about 40 ms. A second slower stage was observed only in newborns although it has been observed in adults in other studies (Weatherby and Hecox, 1982; Lightfoot, 1991; Lasky et al., 1996). These effects were replicated at different stimulus intensities. After the termination of stimulation the return to the wave V unadapted response took nearly 500 ms in newborns. Neither the newborn nor the adult data can be explained by forward masking of one click on the next click. These results indicate human developmental differences in adaptation to repetitive auditory stimulation at the level of the brainstem.

  19. 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.

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

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    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.

  1. A cascade reaction network mimicking the basic functional steps of adaptive immune response (United States)

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


    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Davis, L.C., E-mail: [10244 Normandy Dr., Plymouth, MI 48170 (United States)


    The region of string stability of a platoon of adaptive cruise control vehicles, taking into account the delay and response of the vehicle powertrain, is found. An upper bound on the explicit delay time as a function the first-order powertrain response time constant is determined. The system is characterized by a headway time constant, a sensitivity parameter, relative (to the vehicle immediately in front) velocity control, and delayed-velocity feedback or acceleration feedback. -- Highlights: ► I find the region of stability for a realistic adaptive cruise control system. ► Vehicle response time and explicit delay are included in the analysis. ► Delayed-feedback enlarges the parameter space that gives string stability.

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

    Energy Technology Data Exchange (ETDEWEB)

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


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

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


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


    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 levo...

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

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


    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

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

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


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

  7. Noise-induced interspike interval correlations and spike train regularization in spike-triggered adapting neurons (United States)

    Urdapilleta, Eugenio


    Spike generation in neurons produces a temporal point process, whose statistics is governed by intrinsic phenomena and the external incoming inputs to be coded. In particular, spike-evoked adaptation currents support a slow temporal process that conditions spiking probability at the present time according to past activity. In this work, we study the statistics of interspike interval correlations arising in such non-renewal spike trains, for a neuron model that reproduces different spike modes in a small adaptation scenario. We found that correlations are stronger as the neuron fires at a particular firing rate, which is defined by the adaptation process. When set in a subthreshold regime, the neuron may sustain this particular firing rate, and thus induce correlations, by noise. Given that, in this regime, interspike intervals are negatively correlated at any lag, this effect surprisingly implies a reduction in the variability of the spike count statistics at a finite noise intensity.

  8. Noise-induced interspike interval correlations and spike train regularization in spike-triggered adapting neurons

    CERN Document Server

    Urdapilleta, Eugenio


    Spike generation in neurons produces a temporal point process, whose statistics is governed by intrinsic phenomena and the external incoming inputs to be coded. In particular, spike-evoked adaptation currents support a slow temporal process that conditions spiking probability at the present time according to past activity. In this work, we study the statistics of interspike interval correlations arising in such non-renewal spike trains, for a neuron model that reproduces different spike modes in a small adaptation scenario. We found that correlations are stronger as the neuron fires at a particular firing rate, which is defined by the adaptation process. When set in a subthreshold regime, the neuron may sustain this particular firing rate, and thus induce correlations, by noise. Given that, in this regime, interspike intervals are negatively correlated at any lag, this effect surprisingly implies a reduction in the variability of the spike count statistics at a finite noise intensity.

  9. Androgen deprivation modulates the inflammatory response induced by irradiation

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    Lin Paul-Yang


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

  10. 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


    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

  11. Adaptive response to chronic mild ethanol stress involves ROS, sirtuins and changes in chromosome dosage in wine yeasts. (United States)

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


    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.

  12. Mutagenic adaptive response to high-LET radiation in human lymphoblastoid cells exposed to X-rays. (United States)

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


    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.

  13. Non-homologous end joining dependency of {gamma}-irradiation-induced adaptive frameshift mutation formation in cell cycle-arrested yeast cells

    Energy Technology Data Exchange (ETDEWEB)

    Heidenreich, Erich [Institute of Cancer Research, Division of Molecular Genetics, Medical University of Vienna, Borschkegasse 8a, A-1090 Vienna (Austria)]. E-mail:; Eisler, Herfried [Institute of Cancer Research, Division of Molecular Genetics, Medical University of Vienna, Borschkegasse 8a, A-1090 Vienna (Austria)


    There is a strong selective pressure favoring adaptive mutations which relieve proliferation-limiting adverse living conditions. Due to their importance for evolution and pathogenesis, we are interested in the mechanisms responsible for the formation of such adaptive, gain-of-fitness mutations in stationary-phase cells. During previous studies on the occurrence of spontaneous reversions of an auxotrophy-causing frameshift allele in the yeast Saccharomyces cerevisiae, we noticed that about 50% of the adaptive reversions depended on a functional non-homologous end joining (NHEJ) pathway of DNA double-strand break (DSB) repair. Here, we show that the occasional NHEJ component Pol4, which is the yeast ortholog of mammalian DNA polymerase lambda, is not required for adaptive mutagenesis. An artificially imposed excess of DSBs by {gamma}-irradiation resulted in a dramatic increase in the incidence of adaptive, cell cycle arrest-releasing frameshift reversions. By the use of DNA ligase IV-deficient strains we detected that the majority of the {gamma}-induced adaptive mutations were also dependent on a functional NHEJ pathway. This suggests that the same mutagenic NHEJ mechanism acts on spontaneously arising as well as on ionizing radiation-induced DSBs. Inaccuracy of the NHEJ repair pathway may extensively contribute to the incidence of frameshift mutations in resting (non-dividing) eukaryotic cells, and thus act as a driving force in tumor development.

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

    Institute of Scientific and Technical Information of China (English)



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

  15. Adaptive response to GSH depletion and resistance to L-buthionine-(S,R)-sulfoximine: involvement of Nrf2 activation. (United States)

    Lee, Hyang-Rim; Cho, Jeong-Min; Shin, Dong-ha; Yong, Chul Soon; Choi, Han-Gon; Wakabayashi, Nobunao; Kwak, Mi-Kyoung


    Pharmacological depletion of L-gamma-glutamyl-L-cysteinyl-glycine (GSH) has been implicated in the sensitization of cancer cells to alkylating agents and apoptosis. However, some types of cells do not induce apoptotic response following chemical depletion of GSH. In the present study, we report that murine embryonic fibroblasts (MEFs) can survive in the presence of GSH inhibitor L-buthionine-(S,R)-sulfoximine (BSO), even though most intracellular GSH was depleted. As a cellular adaptive mechanism, BSO treatment effectively activated the NF-E2-related factor 2 (Nrf2) pathway, which led to up-regulation of antioxidant enzymes in these cells through the extracellular signal-regulated kinase cascade. While nrf2-deficient MEFs lost the inducibility of antioxidant genes, which resulted in higher levels of reactive oxygen species accumulation, caspase-3 activation, and cell death than wild-type cells. Finally, nrf2-deficient cells can be more sensitized to doxorubicin-induced cell death by BSO pre-incubation, while wild-type cells were not. In addition, BSO-mediated cell death was facilitated by administering Nrf2 siRNA to chemoresistant human ovarian cancer cells. These results indicate that Nrf2 is the primary factor inducing the cell survival system under GSH depletion and that the effect of BSO as a chemosensitizer might be enhanced by inhibition of Nrf2.

  16. β-Cell adaptation in a mouse model of glucocorticoid-induced metabolic syndrome. (United States)

    Fransson, Liselotte; Franzén, Stephanie; Rosengren, Victoria; Wolbert, Petra; Sjöholm, Åke; Ortsäter, Henrik


    Glucocorticoids (GCs) are stress hormones primarily responsible for mobilizing glucose to the circulation. Due to this effect, insulin resistance and glucose intolerance are concerns in patients with endogenous overproduction of GCs and in patients prescribed GC-based therapy. In addition, hypercortisolemic conditions share many characteristics with the metabolic syndrome. This study reports on a thorough characterization, in terms of glucose control and lipid handling, of a mouse model where corticosterone is given via the drinking water. C57BL/6J mice were treated with corticosterone (100 or 25 μg/ml) or vehicle in their drinking water for 5 weeks after which they were subjected to insulin or glucose tolerance tests. GC-treated mice displayed increased food intake, body weight gain, and central fat deposit accumulations. In addition, the GC treatment led to dyslipidemia as well as accumulation of ectopic fat in the liver and skeletal muscle, having a substantial negative effect on insulin sensitivity. Also glucose intolerance and hypertension, both part of the metabolic syndrome, were evident in the GC-treated mice. However, the observed effects of corticosterone were reversed after drug removal. Furthermore, this study reveals insights into β-cell adaptation to the GC-induced insulin resistance. Increased pancreatic islet volume due to cell proliferation, increased insulin secretion capacity, and increased islet chaperone expression were found in GC-treated animals. This model mimics the human metabolic syndrome. It could be a valuable model for studying the complex mechanisms behind the development of the metabolic syndrome and type 2 diabetes, as well as the multifaceted relations between GC excess and disease.

  17. Classification of osteosarcoma T-ray responses using adaptive and rational wavelets for feature extraction (United States)

    Ng, Desmond; Wong, Fu Tian; Withayachumnankul, Withawat; Findlay, David; Ferguson, Bradley; Abbott, Derek


    In this work we investigate new feature extraction algorithms on the T-ray response of normal human bone cells and human osteosarcoma cells. One of the most promising feature extraction methods is the Discrete Wavelet Transform (DWT). However, the classification accuracy is dependant on the specific wavelet base chosen. Adaptive wavelets circumvent this problem by gradually adapting to the signal to retain optimum discriminatory information, while removing redundant information. Using adaptive wavelets, classification accuracy, using a quadratic Bayesian classifier, of 96.88% is obtained based on 25 features. In addition, the potential of using rational wavelets rather than the standard dyadic wavelets in classification is explored. The advantage it has over dyadic wavelets is that it allows a better adaptation of the scale factor according to the signal. An accuracy of 91.15% is obtained through rational wavelets with 12 coefficients using a Support Vector Machine (SVM) as the classifier. These results highlight adaptive and rational wavelets as an efficient feature extraction method and the enormous potential of T-rays in cancer detection.

  18. The human milk oligosaccharide 2'-fucosyllactose augments the adaptive response to extensive intestinal. (United States)

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


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

  19. Biophysical adaptation of the theory of photo-induced phase transition: model of cooperative gating of cardiac ryanodine receptors

    Energy Technology Data Exchange (ETDEWEB)

    Moskvin, A S [Ural State University, Ekaterinburg, 620083 (Russian Federation); Philipiev, M P [Ural State University, Ekaterinburg, 620083 (Russian Federation); Solovyova, O E [Ural State University, Ekaterinburg, 620083 (Russian Federation); Markhasin, V S [Institute of Immunology and Physiology, Ekaterinburg, 620219 (Russian Federation)


    Theory of photo-induced phase transitions has been adapted to describe the cooperative dynamics of the lattice of ryanodine receptors/channels (RyR) in cardiac muscle which regulate the release of the intracellular activator calcium from calcium stores in the sarcoplasmic reticulum (SR) by a process of Ca{sup 2+}-induced Ca{sup 2+} release (CICR). We introduce two main degrees of freedom for RyR channel, fast electronic and slow conformational ones. The RyR lattice response to the L-type channel triggering evolves due to a nucleation process with a step-by-step domino-like opening of RyR channels. Typical mode of RyR lattice functioning in a CICR process implies the fractional release with a robust termination due to the depletion of SR with a respective change in effective conformational strain. The SR overload leads to an unconventional auto-oscillation regime with a spontaneous calcium release. The model is believed to consistently describe the main features of CICR, that is its gradedness, coupled gating, irreversibility, inactivation/adaptation, and spark termination.

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

    Directory of Open Access Journals (Sweden)

    Artur Summerfield


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

  1. Vagal afferents are essential for maximal resection-induced intestinal adaptive growth in orally fed rats. (United States)

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


    Small bowel resection stimulates intestinal adaptive growth by a neuroendocrine process thought to involve both sympathetic and parasympathetic innervation and enterotrophic hormones such as glucagon-like peptide-2 (GLP-2). We investigated whether capsaicin-sensitive vagal afferent neurons are essential for maximal resection-induced intestinal growth. Rats received systemic or perivagal capsaicin or ganglionectomy before 70% midjejunoileal resection or transection and were fed orally or by total parenteral nutrition (TPN) for 7 days after surgery. Growth of residual bowel was assessed by changes in mucosal mass, protein, DNA, and histology. Both systemic and perivagal capsaicin significantly attenuated by 48-100% resection-induced increases in ileal mucosal mass, protein, and DNA in rats fed orally. Villus height was significantly reduced in resected rats given capsaicin compared with vehicle. Sucrase specific activity in jejunal mucosa was not significantly different; ileal mucosal sucrase specific activity was significantly increased by resection in capsaicin-treated rats. Capsaicin did not alter the 57% increase in ileal proglucagon mRNA or the 150% increase in plasma concentration of bioactive GLP-2 resulting from resection in orally fed rats. Ablation of spinal/splanchnic innervation by ganglionectomy failed to attenuate resection-induced adaptive growth. In TPN rats, capsaicin did not attenuate resection-induced mucosal growth. We conclude that vagal afferents are not essential for GLP-2 secretion when the ileum has direct contact with luminal nutrients after resection. In summary, vagal afferent neurons are essential for maximal resection-induced intestinal adaptation through a mechanism that appears to involve stimulation by luminal nutrients.

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


    Omueti, Modupe Omogbohun


    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...

  3. Pre-Sleep Protein Ingestion to Improve the Skeletal Muscle Adaptive Response to Exercise Training. (United States)

    Trommelen, Jorn; van Loon, Luc J C


    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.

  4. Transport induced inflammatory responses in horses. (United States)

    Wessely-Szponder, J; Bełkot, Z; Bobowiec, R; Kosior-Korzecka, U; Wójcik, M


    Deleterious response to road transport is an important problem in equine practice. It determines different physiological, immunological and metabolic changes which lead to increased susceptibility to several disorders such as pneumonia, diarrhea, colics, laminitis, injuries and rhabdomyolisis. The aim of our study was to look for possible relationships between transportation of female young and older horses over a long and short distance and an inflammatory state reflected by an increase of acute phase protein concentration, oxidative stress and muscle injury. The study was conducted on 24 cold-blooded female horses divided into four groups. Six fillies aged 6-18 months and six mares aged 10-12 years were transported over the distance of about 550 km, six fillies aged 6-18 months and six mares aged 10-12 years were transported over the distance of about 50 km. Plasma and serum were obtained from blood samples taken before transportation (T0), immediately after transportation (T1) and at an abattoir during slaughter (T2). In these samples fibrinogen, MDA, AST and CK were assessed. Fibrinogen increased in all studied groups especially in fillies after long distance transportation, where it reached 205±7.07 mg/dl before transportation, 625±35.35 mg/dl after transportation, and 790±14.14 mg/dl during slaughter. MDA concentrations rose after transportation and reached the maximal level during slaughter. CK activity was more elevated after short transportation in younger horses, whereas initial activity of AST was higher in older horses. We estimated that intensified responses from acute phase, oxidative stress and muscle injury parameters indicated an inflammatory state.

  5. Correlation between the adaptive response and individual sensitivity to monoepoxybutene in in vitro experiments on human lymphocytes. (United States)

    Sasiadek, M; Paprocka-Borowicz, M


    Individual variations in the susceptibility to mutagenic/carcinogenic chemicals depend on the activity of xenobiotic metabolizing enzymes and on DNA- and chromosome-damage repair systems. Monoepoxybutene (MEB) is a genotoxic metabolite of 1,3-butadiene (BD), which has been classified as a probable carcinogen in humans. The purpose of the present study was to investigate by in vitro experiments on human whole blood lymphocytes (WBL), whether an individual sensitivity to MEB correlates with the adaptive response to the tested agent. In the analyzed group, 8.3% of blood donors were relatively sensitive to MEB. The comparison of SCE induction in cultures pretreated and not pretreated with an adaptive dose (AD) of MEB showed, that there was an adaptive response to MEB. The adaptive response in the group of relatively sensitive donors was similar to that of the relatively resistant ones. This result suggests that individual sensitivity to the tested agent and adaptive response depend on different biological mechanisms.

  6. Sex-related adaptive responses to interaction of drought and salinity in Populus yunnanensis. (United States)

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


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

  7. Distinct immune response induced by peptidoglycan derived from Lactobacillus sp

    Institute of Scientific and Technical Information of China (English)

    Jin Sun; Yong-Hui Shi; Guo-Wei Le; Xi-Yi Ma


    AIM: To analyze the distinct immune responses induced by Lactobacillus peptidoglycan (PG).METHODS: BALB/c mice were intraperitoneally injected with PG once a day for three consecutive days. Peritoneal macrophage and splenocyte mRNA was extracted and the gene expression profile was studied using high-density oligonucleotide microarrays. Inhibitory effects of Lactobacillus PG on colon tumor tissue were studied in vitro and in vivo.RESULTS: The gene expression profiles revealed that the TLR-NF-κB and Jak-STAT signaling pathways were highly activated. An inflammatory phenotype was induced when peritoneal macrophages were initially exposed to Lactobacillus PG and switched to a more complex phenotype when BALB/c mice were treated with three doses of Lactobacillus PG. A protective physiological inflammatory response was induced after three consecutive days of PG treatment. It was tending toward Th1 dominant immune response. Lactobacillus PG also appeared to induce a significantin vivo anti-colon tumor effect.CONCLUSION: Lactobacillus PG is responsible for certain immune responses induced by Lactobacilli. Anti-tumor effects of Lactobacilli are likely to attribute to the activation of macrophages by PG expressed on the bacterial cell surface.

  8. Adaptation response surfaces from an ensemble of wheat projections under climate change in Europe (United States)

    Ruiz-Ramos, Margarita; Ferrise, Roberto


    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. Nanomaterial Induced Immune Responses and Cytotoxicity. (United States)

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


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

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


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


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

  11. Ozone-Induced Hypertussive Responses in Rabbits and Guinea Pigs. (United States)

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


    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.

  12. TIR Domain-Containing Adapter-Inducing Beta Interferon (TRIF) Mediates Immunological Memory against Bacterial Pathogens. (United States)

    Kanagavelu, Saravana; Flores, Claudia; Termini, J M; Romero, Laura; Riveron, Reldy; Ruiz, Jose; Arditi, Moshe; Schesser, Kurt; Fukata, Masayuki


    Induction of adaptive immunity leads to the establishment of immunological memory; however, how innate immunity regulates memory T cell function remains obscure. Here we show a previously undefined mechanism in which innate and adaptive immunity are linked by TIR domain-containing adapter-inducing beta interferon (TRIF) during establishment and reactivation of memory T cells against Gram-negative enteropathogens. Absence of TRIF in macrophages (Mϕs) but not dendritic cells led to a predominant generation of CD4(+) central memory T cells that express IL-17 during enteric bacterial infection in mice. TRIF-dependent type I interferon (IFN) signaling in T cells was essential to Th1 lineage differentiation and reactivation of memory T cells. TRIF activated memory T cells to facilitate local neutrophil influx and enhance bacterial elimination. These results highlight the importance of TRIF as a mediator of the innate and adaptive immune interactions in achieving the protective properties of memory immunity against Gram-negative bacteria and suggest TRIF as a potential therapeutic target.

  13. Lipolytic response of adipose tissue and metabolic adaptations to long periods of fasting in red tilapia (Oreochromis sp., Teleostei: Cichlidae

    Directory of Open Access Journals (Sweden)



    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.

  14. Fibrocyte-like cells recruited to the spleen support innate and adaptive immune responses to acute injury or infection. (United States)

    Kisseleva, Tatiana; von Köckritz-Blickwede, Maren; Reichart, Donna; McGillvray, Shauna M; Wingender, Gerhard; Kronenberg, Mitchell; Glass, Christopher K; Nizet, Victor; Brenner, David A


    Bone marrow (BM)-derived fibrocytes are a population of CD45(+) and collagen Type I-expressing cells that migrate to the spleen and to target injured organs, such as skin, lungs, kidneys, and liver. While CD45(+)Col(+) fibrocytes contribute to collagen deposition at the site of injury, the role of CD45(+)Col(+) cells in spleen has not been elucidated. Here, we demonstrate that hepatotoxic injury (CCl(4)), TGF-β1, lipopolysaccharide, or infection with Listeria monocytogenes induce rapid recruitment of CD45(+)Col(+) fibrocyte-like cells to the spleen. These cells have a gene expression pattern that includes antimicrobial factors (myleoperoxidase, cathelicidin, and defensins) and MHC II at higher levels than found on quiescent or activated macrophages. The immune functions of these splenic CD45(+)Col(+) fibrocyte-like cells include entrapment of bacteria into extracellular DNA-based structures containing cathelicidin and presentation of antigens to naïve CD8(+) T cells to induce their proliferation. Stimulation of these splenic fibrocyte-like cells with granulocyte macrophage-colony stimulating factor or macrophage-colony stimulating factor induces downregulation of collagen expression and terminal differentiation into the dendritic cells or macrophage. Thus, splenic CD45(+)Col(+) cells are a population of rapidly mobilized BM-derived fibrocyte-like cells that respond to inflammation or infection to participate in innate and adaptive immune responses.

  15. 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

  16. 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


    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.

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

    Directory of Open Access Journals (Sweden)

    Pierre Olivier Lang


    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.

  18. The influence of Mineral Trioxide Aggregate (MTA) on adaptive immune responses to endodontic pathogens in mice (United States)

    Rezende, Taia Maria Berto; Vieira, Leda Quercia; Sobrinho, Antônio Paulino Ribeiro; Oliveira, Ricardo Reis; Taubman, Martin A.; Kawai, Toshihisa


    This study assessed the influence of mineral trioxide aggregate (MTA) on adaptive immune responses. BALB/c mice were immunized with heat-killed Fusobacterium nucleatum (Fn) in MTA or other control adjuvants, and serum IgG responses to Fn were measured. Either Fn- or Peptostreptococcus anaerobius (Pa)-reactive memory T cells (Tm) were pre-incubated in vitro with/without MTA and restimulated with Fn or Pa. Tm proliferation and cytokine production were assessed. Compared to control groups, IgG-antibody responses were upregulated in mice immunized with Fn in MTA in a similar manner to animals immunized with Fn in Freund's adjuvant or aluminum hydroxide adjuvant. While MTA did not affect the upregulated expression of IL-10, TNF-α or RANKL by Tm, it suppressed the proliferation of Pa- or Fn-Tm and inhibited their production of Th1- or Th2-signature cytokines. MTA upregulated the adaptive humoral immune responses, but had little or no effect on pro- or anti-inflammatory cytokine production by Tm. PMID:18718367

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

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


    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.

  20. Dark Adaptation at High Altitude: An Unexpected Pupillary Response to Chronic Hypoxia in Andean Highlanders. (United States)

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


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

  1. Recent Visual Experience Shapes Visual Processing in Rats through Stimulus-Specific Adaptation and Response Enhancement. (United States)

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


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

  2. The physiological effects of IGF-1 (class 1:Ea transgene) over-expression on exercise-induced damage and adaptation in dystrophic muscles of mdx mice. (United States)

    Ridgley, James A; Pinniger, Gavin J; Hamer, Peter W; Grounds, Miranda D


    Duchenne muscular dystrophy (DMD) is a genetic disorder in which muscle weakness and fragility contribute to ongoing muscle degeneration. Although exercise-induced muscle damage is associated with adaptation that protects normal muscle from further damage, exploiting this process to protect dystrophic muscle has been avoided for fear of inducing excessive muscle degeneration. However, muscle-specific over-expression of the class 1:Ea isoform of insulin-like growth factor-1 (IGF-1) reduces myofibre necrosis in dystrophic mdx mice (a model for DMD) and, therefore, may enhance the adaptation process in response to eccentric exercise. To test this hypothesis, we evaluated the effect of transgenic class 1:Ea IGF-1 over-expression on the susceptibility to muscle damage and subsequent adaptation in 12-week-old dystrophic mdx and non-dystrophic control mice. Experiments were conducted in vivo using a custom-built isokinetic mouse dynamometer to measure the deficit in joint torque (indicating muscle damage) after 20 maximal lengthening (eccentric) contractions. Adaptation to this damaging exercise was evaluated by repeating the protocol 7 days after the initial exercise. The over-expression of IGF-1 significantly increased the normalised joint torque in non-dystrophic mice and appeared to ameliorate the muscle weakness in dystrophic mice. All mice displayed a marked reduction in the susceptibility to muscle damage on day 7; however, this adaptation was unaffected by IGF-1, showing that IGF-1 does not protect the dystrophic muscles of adult mdx mice against damage resulting from maximal lengthening contractions.

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


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


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

  4. 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.

  5. Cellular Responses to Cisplatin-Induced DNA Damage

    Directory of Open Access Journals (Sweden)

    Alakananda Basu


    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.

  6. Imaging of non-Hodgkin lymphomas: diagnosis and response-adapted strategies. (United States)

    El-Galaly, Tarec Christoffer; Hutchings, Martin


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

  7. Effect of simulated microgravity on endocrine response to insulin-induced hypoglycemia in physically fit men. (United States)

    Ksinantova, L; Koska, J; Kvetnansky, R; Marko, M; Hamar, D; Vigas, M


    Adaptation to microgravity is associated with alteration in some endocrine functions. In the present longitudinal study, the counterregulatory hormonal response to insulin-induced hypoglycemia (ITT, 0.1 IU/kg short acting insulin i. v.) was evaluated under simulated microgravity conditions in 15 physically fit subjects. ITT was performed at the beginning of the investigation, and again after completion of 6 weeks of endurance training and after a subsequent period of 4 days of head-down bed rest at a backward tilt of 6 degrees from the horizontal. Endurance training showed a significant increase in maximal aerobic capacity in previously well-trained subjects (increase by 12 %), as well as on attenuation of counterregulatory response of epinephrine to hypoglycemia. After 4 days of bed rest, basal concentrations of plasma norepinephrine was diminished (p < 0.002) and plasma renin activity was enhanced (p < 0.02). After bed rest, decreased responses of the two catecholamines (norepinephrine, p < 0.001; epinephrine, p < 0.001), growth hormone (p < 0.001), and cortisol (p < 0.05) were observed. Response of plasma renin activity after bed rest was increased (p < 0.01). This longitudinal study indicated that 4 days of bed rest in endurance-trained subjects induced increased response of PRA to hypoglycemia and attenuation of other counterregulatory neuroendocrine responses.

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

    CERN Document Server

    Goel, Pranay


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

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

    CERN Document Server

    Moses, Melanie


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

  10. Evidence of local adaptation in the demographic response of American ginseng to interannual temperature variation. (United States)

    Souther, Sara; McGraw, James B


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

  11. The Dynamic cerebral autoregulatory adaptive response to noradrenaline is attenuated during systemic inflammation in humans

    DEFF Research Database (Denmark)

    Berg, Ronan M G; Plovsing, Ronni R; Bailey, Damian M;


    CA following lipopolysaccharide (LPS) infusion, a human-experimental model of the systemic inflammatory response during early sepsis. The dCA in eight healthy males was examined prior to and during an intended noradrenaline-induced MAP increase of approximately 30 mmHg. This was performed at baseline...... neuroprotective effect by enhancing dCA in patients with early sepsis....

  12. Responses of leaf traits to climatic gradients: adaptive variation versus compositional shifts (United States)

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


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

  13. Block-Sparsity-Induced Adaptive Filter for Multi-Clustering System Identification (United States)

    Jiang, Shuyang; Gu, Yuantao


    In order to improve the performance of least mean square (LMS)-based adaptive filtering for identifying block-sparse systems, a new adaptive algorithm called block-sparse LMS (BS-LMS) is proposed in this paper. The basis of the proposed algorithm is to insert a penalty of block-sparsity, which is a mixed \\$l_{2, 0}\\$ norm of adaptive tap-weights with equal group partition sizes, into the cost function of traditional LMS algorithm. To describe a block-sparse system response, we first propose a Markov-Gaussian model, which can generate a kind of system responses of arbitrary average sparsity and arbitrary average block length using given parameters. Then we present theoretical expressions of the steady-state misadjustment and transient convergence behavior of BS-LMS with an appropriate group partition size for white Gaussian input data. Based on the above results, we theoretically demonstrate that BS-LMS has much better convergence behavior than \\$l_0\\$-LMS with the same small level of misadjustment. Finally, numerical experiments verify that all of the theoretical analysis agrees well with simulation results in a large range of parameters.

  14. A Dual-Responsive Nanocomposite toward Climate-Adaptable Solar Modulation for Energy-Saving Smart Windows. (United States)

    Lee, Heng Yeong; Cai, Yufeng; Bi, Shuguang; Liang, Yen Nan; Song, Yujie; Hu, Xiao Matthew


    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. Reduction of skin stretch induced motion artifacts in electrocardiogram monitoring using adaptive filtering. (United States)

    Liu, Yan; Pecht, Michael G


    The effectiveness of electrocardiogram (ECG) monitors can be significantly impaired by motion artifacts which can cause misdiagnoses, lead to inappropriate treatment decisions, and trigger false alarms. Skin stretch associated with patient motion is a significant source of motion artifacts in current ECG monitoring. In this study, motion artifacts are adaptively filtered by using skin strain as the reference variable. Skin strain is measured non-invasively using a light emitting diode (LED) and an optical sensor incorporated in an ECG electrode. The results demonstrate that this device and method can significantly reduce skin strain induced ECG artifacts.

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

    Directory of Open Access Journals (Sweden)

    Jörn E Schmitz


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

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

    Directory of Open Access Journals (Sweden)

    Gianluca CORNO


    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

  18. 获得性免疫反应与海人藻酸引起的C57BL/6小鼠海马损伤的关系%Adaptive immune response is involved in kainic acid-induced hippocampal injury in C57BL/6 mice

    Institute of Scientific and Technical Information of China (English)

    祝威; 崔香艳; 祝捷


    BACKGROUND: Kainic acid (KA)-induced hippocampal injury in rodents is a good model for studying human neurodegenerative diseases. Although many studies have evidenced that inflammatory molecules and responses participate in and accelerated the process of disease, it is still unclear whether adaptive immune response, especially immune competent cells, such as T and B cells, is involved in the pathogenesis of neurodegenerative diseases.OBJECTIVE: To observe the roles of B and T cell subsets in KA-induced hippocampal neurodegeneration.DESIGN: Randomized controlled animal trial.5ETTING: Department of Otolaryngology and Head, and Department of Neurology, First Hospital, Jilin University; Division of Geriatrics, Department of Neurotec, Huddinge Hospital, Karolinska Institute.MATERrALS: This trial was conducted in the Department of Neurotec, Huddinge Hospital, Karolinska Institute during June to September 2000. Twenty male C57 BL/6 mice (wide-type), and knockout mice CD4(-/-) (n =17), CD8(-/-)(n =19), CD4/CD8(-/-) (n =15) and Igh-6(-/-) (n =14) of C57BL/6 background were involved in this trial. They were aged 5 to 6 weeks,weighing 18 to 20 g. Three age- and body mass-matched C57BL/6 mice received water as controls. Reagent and instruments: KA (Sigma, USA). Bicolor flow cytometer and CellQuest (Becton Dickinson, CA, USA).METHODS: ① Eighty-five anesthetized mice were slowly administrated with 7.69 g/L KA by micropipette which was connected to nose of mouse at the dose of 48 mg/kg. Three control C57BL/6 mice received the same amount of water intranasally. ②Clinical symptoms of mice were monitored. Seizures were graded using a 6-point scale, 0: normal; 6: death.③After 4 to 5 hours of administration of KA, surface immunofluorescence staining of spleen cells was measured with flow cytometer. ④After 7 days of administration of KA, all the mice were anesthetized, and their brains were harvested,then fixed and embedded. For assessment of the severity and extent of

  19. Improving the response of accelerometers for automotive applications by using LMS adaptive filters. (United States)

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


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

  20. Different protein of Echinococcus granulosus stimulates dendritic induced immune response. (United States)

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


    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.

  1. 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


    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.

  2. Response and adaptability of mangrove habitats from the Indian subcontinent to changing climate

    Digital Repository Service at National Institute of Oceanography (India)

    Jagtap, T.G.; Nagle, V.L.

    stream_size 37402 stream_content_type text/plain stream_name Ambio_36_328.pdf.txt stream_source_info Ambio_36_328.pdf.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 Response and adaptability...) are prominent in the Indian subcontinent. The deltaic regions show alluvial deposits of 3.4 m thick and composed of fine clay and silt and clay looms. Lakshdweep group of island in the Arabian sea are emerging type distinguished by coral reefs and lagoons...

  3. 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.)


    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)

  4. 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

  5. Evidence of fast serotonin transmission in frog slowly adapting type 1 responses. (United States)

    Press, Daniel; Mutlu, Sevinç; Güçlü, Burak


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

  6. Adaptation to delayed auditory feedback induces the temporal recalibration effect in both speech perception and production. (United States)

    Yamamoto, Kosuke; Kawabata, Hideaki


    We ordinarily speak fluently, even though our perceptions of our own voices are disrupted by various environmental acoustic properties. The underlying mechanism of speech is supposed to monitor the temporal relationship between speech production and the perception of auditory feedback, as suggested by a reduction in speech fluency when the speaker is exposed to delayed auditory feedback (DAF). While many studies have reported that DAF influences speech motor processing, its relationship to the temporal tuning effect on multimodal integration, or temporal recalibration, remains unclear. We investigated whether the temporal aspects of both speech perception and production change due to adaptation to the delay between the motor sensation and the auditory feedback. This is a well-used method of inducing temporal recalibration. Participants continually read texts with specific DAF times in order to adapt to the delay. Then, they judged the simultaneity between the motor sensation and the vocal feedback. We measured the rates of speech with which participants read the texts in both the exposure and re-exposure phases. We found that exposure to DAF changed both the rate of speech and the simultaneity judgment, that is, participants' speech gained fluency. Although we also found that a delay of 200 ms appeared to be most effective in decreasing the rates of speech and shifting the distribution on the simultaneity judgment, there was no correlation between these measurements. These findings suggest that both speech motor production and multimodal perception are adaptive to temporal lag but are processed in distinct ways.

  7. Adaptive radiation of gall-inducing insects within a single host-plant species. (United States)

    Joy, Jeffrey B; Crespi, Bernard J


    Speciation of plant-feeding insects is typically associated with host-plant shifts, with subsequent divergent selection and adaptation to the ecological conditions associated with the new plant. However, a few insect groups have apparently undergone speciation while remaining on the same host-plant species, and such radiations may provide novel insights into the causes of adaptive radiation. We used mitochondrial and nuclear DNA to infer a phylogeny for 14 species of gall-inducing Asphondylia flies (Diptera: Cecidomyiidae) found on Larrea tridentata (creosote bush), which have been considered to be monophyletic based on morphological evidence. Our phylogenetic analyses provide strong support for extensive within-host plant speciation in this group, and it demonstrates that diversification has involved numerous shifts between different plant organs (leaves, buds, flowers, and stems) of the same host-plant species. Within-plant speciation of Asphondylia is thus apparently facilitated by the opportunity to partition the plant ecologically. One clade exhibits temporal isolation among species, which may have facilitated divergence via allochronic shifts. Using a novel method based on Bayesian reconstruction, we show that the rate of change in an ecomorphological trait, ovipositor length, was significantly higher along branches with inferred shifts between host-plant organs than along branches without such shifts. This finding suggests that Larrea gall midges exhibit close morphological adaptation to specific host-plant parts, which may mediate ecological transitions via disruptive selection.

  8. Characterization of capsaicin induced responses in mice vas deferens

    DEFF Research Database (Denmark)

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


    Calcitonin gene-related peptide (CGRP) is extensively distributed in primary afferent sensory nerves, including those innervating the genitourinary tract. Capsaicin can stimulate the release of CGRP from intracellular stores of these nerves, but this phenomenon has not been investigated in......-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...

  9. Governmental responses and smallholders' adaptations to climatic variability in southeastern Mexico (United States)

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


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

  10. Priority of repetitive adaptation to mismatch response following undiscriminable auditory stimulation: a magnetoencephalographic study. (United States)

    Hoshiyama, Minoru; Okamoto, Hidehiko; Kakigi, Ryusuke


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

  11. Anthrax lethal toxin-mediated killing of human and murine dendritic cells impairs the adaptive immune response.

    Directory of Open Access Journals (Sweden)

    Abdelkrim Alileche


    Full Text Available Many pathogens have acquired strategies to combat the immune response. Bacillus anthracis interferes with host defenses by releasing anthrax lethal toxin (LT, which inactivates mitogen-activated protein kinase pathways, rendering dendritic cells (DCs and T lymphocytes nonresponsive to immune stimulation. However, these cell types are considered resistant to killing by LT. Here we show that LT kills primary human DCs in vitro, and murine DCs in vitro and in vivo. Kinetics of LT-mediated killing of murine DCs, as well as cell death pathways induced, were dependent upon genetic background: LT triggered rapid necrosis in BALB/c-derived DCs, and slow apoptosis in C57BL/6-derived DCs. This is consistent with rapid and slow killing of LT-injected BALB/c and C57BL/6 mice, respectively. We present evidence that anthrax LT impairs adaptive immunity by specifically targeting DCs. This may represent an immune-evasion strategy of the bacterium, and contribute to anthrax disease progression. We also established that genetic background determines whether apoptosis or necrosis is induced by LT. Finally, killing of C57BL/6-derived DCs by LT mirrors that of human DCs, suggesting that C57BL/6 DCs represent a better model system for human anthrax than the prototypical BALB/c macrophages.

  12. 5-Lipoxygenase deficiency impairs innate and adaptive immune responses during fungal infection.

    Directory of Open Access Journals (Sweden)

    Adriana Secatto

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

  13. On optimal allocation in binary response trials; is adaptive design really necessary?

    CERN Document Server

    Azriel, David; Rinott, Yosef


    We consider the classical problem of selecting the best of two treatments in clinical trials with binary response. The target is to find the design that maximizes the power of the relevant test. Many papers use a normal approximation to the power function and claim that \\textit{Neyman allocation} that assigns subjects to treatment groups according to the ratio of the responses' standard deviations, should be used. As the standard deviations are unknown, an adaptive design is often recommended. The asymptotic justification of this approach is arguable, since it uses the normal approximation in tails where the error in the approximation is larger than the estimated quantity. We consider two different approaches for optimality of designs that are related to Pitman and Bahadur definitions of relative efficiency of tests. We prove that the optimal allocation according to the Pitman criterion is the balanced allocation and that the optimal allocation according to the Bahadur approach depends on the unknown paramete...

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

    Directory of Open Access Journals (Sweden)

    Sergio eGiannattasio


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

  15. Neuroticism and responsiveness to error feedback: adaptive self-regulation versus affective reactivity. (United States)

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


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

  16. The role of seasonal flowering responses in adaptation of grasses to temperate climates (United States)

    Fjellheim, Siri; Boden, Scott; Trevaskis, Ben


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

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

    Directory of Open Access Journals (Sweden)

    Siri eFjellheim


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

  18. Adaptive Response of Wild and Mutant Type Synechococcus cedrorum to a Polychlorinated Pesticied—Endosulfan

    Institute of Scientific and Technical Information of China (English)

    P.S.BISEN; SharutiMATHUR


    The effect of endosulfan,a hexachlorinated pesticide,on growth,inorganic nitrogenous nutrient uptake(NO3-,NO2-AD NH4+),change in pigmentation and glycogen content on wild type and chemically mutagenised cells of Synechococcus cedrorum was investigated.The pattern of response to pesticide stress in wild and mutant type was the same.Growth reappeared in both after a period of initial lag in presence of endosulfan.The duration of lag increased with increasing doses of pesticide.Paradoxically,however,the rate of uptake of NO3-,NO2-and NH4+,pigment and glycogen content progressively increased with increasing oses.The difference in the adaptation response between wild and mutant types was observed only in the concentration of pesticide that could be tolerated;with the mutant tolerating2.5fold more.

  19. Cyclone preparedness and response: an analysis of lessons identified using an adapted military planning framework. (United States)

    Tatham, Peter; Oloruntoba, Richard; Spens, Karen


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

  20. Responses of leaf traits to climatic gradients: adaptive variation vs. compositional shifts

    Directory of Open Access Journals (Sweden)

    T.-T. Meng


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

  1. Adaptation of the inflammatory immune response across pregnancy and postpartum in Black and White women. (United States)

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


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

  2. Adaptive responses to cool climate promotes persistence of a non-native lizard. (United States)

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


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

  3. Adaptation responses of individuals to environmental changes in the ciliate Euplotes crassus (United States)

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


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

  4. Adaptations of writing posture in response to task demands for left- and right-handers. (United States)

    Szeligo, Frank; Brazier, Bette; Houston, Joël


    Handedness and writing posture are visible manifestations of differences between left- and right-handers. Although an inverted posture is witnessed in both groups, there is a much higher proportion of left-handers who invert. This study is framed within the adaptation hypothesis of writing posture, which states that invertedness in left-handers develops in response to the demands of cursive writing. Participants (N = 57) comprising left-handed inverters, left-handed standard writers, and right-handed standard writers engaged in tasks that required them to form letters and pen strokes at extreme angles. In addition participants were questioned about attempts to change writing posture. We hypothesised that letter angle controls posture in both left- and right-handers and that inverted posture would be a target of intervention. The results of the study showed some support for these hypotheses in that left- and right-handers adapted their posture in response to the constraints placed upon them and inverters reported more intervention.

  5. Polysaccharides isolated from Acai fruit induce innate immune responses.

    Directory of Open Access Journals (Sweden)

    Jeff Holderness

    Full Text Available The Açaí (Acai fruit is a popular nutritional supplement that purportedly enhances immune system function. These anecdotal claims are supported by limited studies describing immune responses to the Acai polyphenol fraction. Previously, we characterized γδ T cell responses to both polyphenol and polysaccharide fractions from several plant-derived nutritional supplements. Similar polyphenol and polysaccharide fractions are found in Acai fruit. Thus, we hypothesized that one or both of these fractions could activate γδ T cells. Contrary to previous reports, we did not identify agonist activity in the polyphenol fraction; however, the Acai polysaccharide fraction induced robust γδ T cell stimulatory activity in human, mouse, and bovine PBMC cultures. To characterize the immune response to Acai polysaccharides, we fractionated the crude polysaccharide preparation and tested these fractions for activity in human PBMC cultures. The largest Acai polysaccharides were the most active in vitro as indicated by activation of myeloid and γδ T cells. When delivered in vivo, Acai polysaccharide induced myeloid cell recruitment and IL-12 production. These results define innate immune responses induced by the polysaccharide component of Acai and have implications for the treatment of asthma and infectious disease.

  6. Chronic N(G)-nitro-L-arginine methyl ester-induced hypertension : novel molecular adaptation to systolic load in absence of hypertrophy (United States)

    Bartunek, J.; Weinberg, E. O.; Tajima, M.; Rohrbach, S.; Katz, S. E.; Douglas, P. S.; Lorell, B. H.; Schneider, M. (Principal Investigator)


    BACKGROUND: Chronic N(G)-nitro-L-arginine methyl ester (L-NAME), which inhibits nitric oxide synthesis, causes hypertension and would therefore be expected to induce robust cardiac hypertrophy. However, L-NAME has negative metabolic effects on protein synthesis that suppress the increase in left ventricular (LV) mass in response to sustained pressure overload. In the present study, we used L-NAME-induced hypertension to test the hypothesis that adaptation to pressure overload occurs even when hypertrophy is suppressed. METHODS AND RESULTS: Male rats received L-NAME (50 mg. kg(-1). d(-1)) or no drug for 6 weeks. Rats with L-NAME-induced hypertension had levels of systolic wall stress similar to those of rats with aortic stenosis (85+/-19 versus 92+/-16 kdyne/cm). Rats with aortic stenosis developed a nearly 2-fold increase in LV mass compared with controls. In contrast, in the L-NAME rats, no increase in LV mass (1. 00+/-0.03 versus 1.04+/-0.04 g) or hypertrophy of isolated myocytes occurred (3586+/-129 versus 3756+/-135 microm(2)) compared with controls. Nevertheless, chronic pressure overload was not accompanied by the development of heart failure. LV systolic performance was maintained by mechanisms of concentric remodeling (decrease of in vivo LV chamber dimension relative to wall thickness) and augmented myocardial calcium-dependent contractile reserve associated with preserved expression of alpha- and beta-myosin heavy chain isoforms and sarcoplasmic reticulum Ca(2+) ATPase (SERCA-2). CONCLUSIONS: When the expected compensatory hypertrophic response is suppressed during L-NAME-induced hypertension, severe chronic pressure overload is associated with a successful adaptation to maintain systolic performance; this adaptation depends on both LV remodeling and enhanced contractility in response to calcium.

  7. Localizing evoked and induced responses to faces using magnetoencephalography. (United States)

    Perry, Gavin; Singh, Krish D


    A rich pattern of responses in frequency, time and space are known to be generated in the visual cortex in response to faces. Recently, a number of studies have used magnetoencephalography (MEG) to try to record these responses non-invasively - in many cases using source analysis techniques based on the beamforming method. Here we sought both to characterize best practice for measuring face-specific responses using MEG beamforming, and to determine whether the results produced by the beamformer match evidence from other modalities. We measured activity to visual presentation of face stimuli and phase-scrambled control stimuli, and performed source analyses of both induced and evoked responses using Synthetic Aperture Magnetometry. We localized the gamma-band response to bilateral lateral occipital cortex, and both the gamma-band response and the M170-evoked response to the right fusiform gyrus. Differences in the gamma-band response between faces and scrambled stimuli were confined to the frequency range 50-90 Hz; gamma-band activity at higher frequencies did not differ between the two stimulus categories. We additionally identified a component of the M220-evoked response - localized to the parieto-occipital sulcus - which was enhanced for scrambled vs. unscrambled faces. These findings help to establish that MEG beamforming can localize face-specific responses in time, frequency and space with good accuracy (when validated against established findings from functional magnetic resonance imaging and intracranial recordings), as well as contributing to the establishment of best methodological practice for the use of the beamformer method to measure face-specific responses.

  8. Staphylococcus aureus isolates from chronic osteomyelitis are characterized by high host cell invasion and intracellular adaptation, but still induce inflammation. (United States)

    Kalinka, Julia; Hachmeister, Marie; Geraci, Jennifer; Sordelli, Daniel; Hansen, Uwe; Niemann, Silke; Oetermann, Sylvia; Peters, Georg; Löffler, Bettina; Tuchscherr, Lorena


    Osteomyelitis is a severe inflammatory disease of the bone that is mainly caused by Staphylococcus aureus. Particularly, bone infections are difficult to treat and can develop into a chronic course with a high relapsing rate despite of antimicrobial treatments. The complex interaction of staphylococci with osseous tissue and the bacterial ability to invade host cells are thought to determine the severity of infection. Yet, defined bacterial virulence factors responsible for the pathogenesis of osteomyelitis have not been clearly identified. The aim of this study was to detect S. aureus virulence factors that are associated with osteomyelitis and contribute to a chronic course of infection. To this purpose, we collected 41 S. aureus isolates, each 11 from acute osteomyelitis (infection period less than 2 months), 10 from chronic osteomyelitis (infection period more than 12 months), 10 from sepsis and 10 from nasal colonization. All isolates were analyzed for gene expression and in functional in-vitro systems. Adhesion assays to bone matrix revealed that all isolates equally bound to matrix structures, but invasion assays in human osteoblasts showed a high invasive capacity of chronic osteomyelitis isolates. The high invasion rate could not be explained by defined adhesins, as all infecting strains expressed a multitude of adhesins that act together and determine the level of adhesion. Following host cell invasion isolates from chronic osteomyelitis induced less cytotoxicity than all other isolates and a higher percentage of Small-colony-variant (SCV)-formation, which represents an adaptation mechanism during long-term persistence. Isolates from acute and chronic osteomyelitis strongly produced biofilm and highly expressed agr and sarA that regulate secreted virulence factors and induced an inflammatory response in osteoblasts. In conclusion, chronic osteomyelitis isolates were characterized by a high host cell invasion rate, low cytotoxicity and the ability to

  9. Differential Adaptive Response and Survival of Salmonella enterica Serovar Enteritidis Planktonic and Biofilm Cells Exposed to Benzalkonium Chloride▿ (United States)

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


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

  10. Rhesus monkeys (Macaca mulatta) adaptively adjust information seeking in response to information accumulated. (United States)

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


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

  11. Whether Plant Responses to Microgravity are Adaptive in Full or in Part. (United States)

    Kordyum, Elizabeth

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

  12. Adaptation mechanisms of bacteria during the degradation of polychlorinated biphenyls in the presence of natural and synthetic terpenes as potential degradation inducers. (United States)

    Zorádová-Murínová, Slavomíra; Dudášová, Hana; Lukáčová, Lucia; Certík, Milan; Silharová, Katarína; Vrana, Branislav; Dercová, Katarína


    In this study, we examined the effect of polychlorinated biphenyls (PCBs) in the presence of natural and synthetic terpenes and biphenyl on biomass production, lipid accumulation, and membrane adaptation mechanisms of two PCB-degrading bacterial strains Pseudomonas stutzeri and Burkholderia xenovorans LB400. According to the results obtained, it could be concluded that natural terpenes, mainly those contained in ivy leaves and pine needles, decreased adaptation responses induced by PCBs in these strains. The adaptation processes under investigation included growth inhibition, lipid accumulation, composition of fatty acids, cis/trans isomerization, and membrane saturation. Growth inhibition effect decreased upon addition of these natural compounds to the medium. The amount of unsaturated fatty acids that can lead to elevated membrane fluidity increased in both strains after the addition of the two natural terpene sources. The cells adaptation changes were more prominent in the presence of carvone, limonene, and biphenyl than in the presence of natural terpenes, as indicated by growth inhibition, lipid accumulation, and cis/trans isomerization. Addition of biphenyl and carvone simultaneously with PCBs increased the trans/cis ratio of fatty acids in membrane fractions probably as a result of fluidizing effects of PCBs. This stimulation is more pronounced in the presence of PCBs as a sole carbon source. This suggests that PCBs alone have a stronger effect on bacterial membrane adaptation mechanisms than when added together with biphenyl or natural or synthetic terpenes.

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

    Energy Technology Data Exchange (ETDEWEB)

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


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

  14. Genome and low-iron response of an oceanic diatom adapted to chronic iron limitation (United States)


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

  15. The adaptive endoplasmic reticulum stress response to lipotoxicity in progressive human nonalcoholic fatty liver disease. (United States)

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


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

  16. The exercise-induced stress response of skeletal muscle, with specific emphasis on humans. (United States)

    Morton, James P; Kayani, Anna C; McArdle, Anne; Drust, Barry


    Skeletal muscle adapts to the stress of contractile activity via changes in gene expression to yield an increased content of a family of highly conserved cytoprotective proteins known as heat shock proteins (HSPs). These proteins function to maintain homeostasis, facilitate repair from injury and provide protection against future insults. The study of the exercise-induced production of HSPs in skeletal muscle is important for the exercise scientist as it may provide a valuable insight into the molecular mechanisms by which regular exercise can provide increased protection against related and non-related stressors. As molecular chaperones, HSPs are also fundamental in facilitating the cellular remodelling processes inherent to the training response. Whilst the exercise-induced stress response of rodent skeletal muscle is relatively well characterized, data from humans are more infrequent and less insightful. Data indicate that acute endurance- and resistance-type exercise protocols increase the muscle content of ubiquitin, alphaB-crystallin, HSP27, HSP60, HSC70 and HSP70. Although increased HSP transcription occurs during exercise, immediately post-exercise or several hours following exercise, time-course studies using western blotting techniques have typically demonstrated a significant increase in protein content is only detectable within 1-2 days following the exercise stress. However, comparison amongst studies is complicated by variations in exercise protocol (mode, intensity, duration, damaging, non-damaging), muscle group examined, predominant HSP measured and, perhaps most importantly, differences in subject characteristics both within and between studies (training status, recent activity levels, nutritional status, age, sex, etc.). Following 'non-damaging' endurance-type activities (exercise that induces no overt structural and functional damage to the muscle), the stress response is thought to be mediated by redox signalling (transient and reversible

  17. Lithium treatment induces a hypersensitive-like response in tobacco. (United States)

    Naranjo, Miguel A; Romero, Carlos; Bellés, José M; Montesinos, Consuelo; Vicente, Oscar; Serrano, Ramón


    Treatment of tobacco ( Nicotiana tabacum L.) plants with lithium induces the formation of necrotic lesions and leaf curling as in the case of incompatible pathogen interactions. Further similarities at the molecular level include accumulation of ethylene and of salicylic and gentisic acids, and induced expression of pathogenesis-related PR-P, PR5 and PR1 genes. With the exception of PR1 induction, lithium produced the same effects in transgenic tobacco plants that do not accumulate salicylate because of overexpression of the bacterial hydroxylase gene nahG. On the other hand, inhibition of ethylene biosynthesis with aminoethoxyvinylglycine prevented lithium-induced cell death and PR5 expression. These results suggest that lithium triggers a hypersensitive-like response where ethylene signalling is essential.

  18. An adaptive and generalizable closed-loop system for control of medically induced coma and other states of anesthesia (United States)

    Yang, Yuxiao; Shanechi, Maryam M.


    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

  19. IL-12 induces T helper 1-directed antitumor response. (United States)

    Tsung, K; Meko, J B; Peplinski, G R; Tsung, Y L; Norton, J A


    Although IL-12 possesses the most potent single-cytokine antitumor efficacy, the mechanism by which IL-12 exerts its antitumor activities remains unclear. Using a complete tumor regression model induced by IL-12 treatment, we demonstrate that the antitumor response induced by IL-12 is mediated by a Th1 cell-directed process, with the macrophage as the effector cell and nitric oxide produced by the activated macrophage as the effector molecule. The induction of the Th1 response by IL-12 depends on the existence of a host T cell response to the tumor before IL-12 administration. IL-12 treatment causes the complete regression of 10-day established s.c. tumors (4-8 mm). Associated with the induction of tumor necrosis, activated macrophages expressing high levels of inducible nitric oxide synthase were found surrounding the tumor. The importance of nitric oxide as the effector molecule was further confirmed by the delay and loss of tumor regression in the presence of a nitric oxide synthase inhibitor in vivo. Examination of tumor-associated T cells indicates that IL-12 induces production of the Th1 cytokine IFN-gamma and suppresses production of IL-2, IL-4, and IL-10 at the tumor site, where these are found to be the predominant cytokines produced by tumor-associated T cells before IL-12 treatment. These findings demonstrate that IL-12 plays an essential role in the induction of an effective Th1 type of cell-mediated immune response against established tumors.

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

    DEFF Research Database (Denmark)

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


    Aim: The aim of this study was to test the hypothesis that IL-6 regulates exercise-induced gene responses in subcutaneous adipose tissue in mice. Methods: Four months old male IL-6 whole body knockout (KO) mice and C57B wild-type (WT) mice performed 1h of treadmill exercise, where subcutaneous...... adipose tissue (AT) was removed either immediately after, 4h or 10h after exercise as well as from mice not running acutely. Moreover, AT was sampled at resting conditions after 5 weeks of exercise training. Results: AT leptin mRNA decreased immediately after a single running exercise bout in both...... in regulating exercise and training-induced leptin and PPAR¿ expression in adipose tissue. In addition, while IL-6 is required for TNF-a mRNA reduction in response to acute exercise, IL-6 does not appear to be mandatory for anti-inflammatory effects of exercise training in adipose tissue....

  1. 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.

  2. Does individual responsibility increase the adaptive capacity of society? The case of local water management in the Netherlands

    NARCIS (Netherlands)

    Bergsma, E.; Gupta, J.; Jong, P.


    In different parts of the world, neo-liberal politics is shifting responsibilities from the nation state to other governmental and non-governmental actors. This is also evident in the governance of adaptation to the impacts of climate change, where the responsibility of the individual is increasingl

  3. 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


    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.

  4. Thiol dependent NF-κB suppression and inhibition of T-cell mediated adaptive immune responses by a naturally occurring steroidal lactone Withaferin A. (United States)

    Gambhir, Lokesh; Checker, Rahul; Sharma, Deepak; Thoh, M; Patil, Anand; Degani, M; Gota, Vikram; Sandur, Santosh K


    Withaferin A (WA), a steroidal lactone isolated from ayurvedic medicinal plant Withania somnifera, was shown to inhibit tumor growth by inducing oxidative stress and suppressing NF-κB pathway. However, its effect on T-cell mediated adaptive immune responses and the underlying mechanism has not been investigated. Since both T-cell responses and NF-κB pathway are known to be redox sensitive, the present study was undertaken to elucidate the effect of WA on adaptive immune responses in vitro and in vivo. WA inhibited mitogen induced T-cell and B-cell proliferation in vitro without inducing any cell death. It inhibited upregulation of T-cell (CD25, CD69, CD71 and CD54) and B-cell (CD80, CD86 and MHC-II) activation markers and secretion of Th1 and Th2 cytokines. WA induced oxidative stress by increasing the basal ROS levels and the immunosuppressive effects of WA were abrogated only by thiol anti-oxidants. The redox modulatory effects of WA in T-cells were attributed to its ability to directly interact with free thiols. WA inhibited NF-κB nuclear translocation in lymphocytes and prevented the direct binding of nuclear NF-κB to its consensus sequence. MALDI-TOF analysis using a synthetic NF-κB-p50 peptide containing Cys-62 residue suggested that WA can modify the cysteine residue of NF-κB. The pharmacokinetic studies for WA were also carried out and in vivo efficacy of WA was studied using mouse model of Graft-versus-host disease. In conclusion, WA is a potent inhibitor of T-cell responses and acts via a novel thiol dependent mechanism and inhibition of NF-κB pathway.

  5. Adaptive reorganization of 2D molecular nanoporous network induced by coadsorbed guest molecule. (United States)

    Zheng, Qing-Na; Wang, Lei; Zhong, Yu-Wu; Liu, Xuan-He; Chen, Ting; Yan, Hui-Juan; Wang, Dong; Yao, Jian-Nian; Wan, Li-Jun


    The ordered array of nanovoids in nanoporous networks, such as honeycomb, Kagome, and square, provides a molecular template for the accommodation of "guest molecules". Compared with the commonly studied guest molecules featuring high symmetry evenly incorporated into the template, guest molecules featuring lower symmetry are rare to report. Herein, we report the formation of a distinct patterned superlattice of guest molecules by selective trapping of guest molecules into the honeycomb network of trimesic acid (TMA). Two distinct surface patterns have been achieved by the guest inclusion induced adaptive reconstruction of a 2D molecular nanoporous network. The honeycomb networks can synergetically tune the arrangement upon inclusion of the guest molecules with different core size but similar peripherals groups, resulting in a trihexagonal Kagome or triangular patterns.

  6. Autophagy is required for exercise training-induced skeletal muscle adaptation and improvement of physical performance. (United States)

    Lira, Vitor A; Okutsu, Mitsuharu; Zhang, Mei; Greene, Nicholas P; Laker, Rhianna C; Breen, David S; Hoehn, Kyle L; Yan, Zhen


    Pathological and physiological stimuli, including acute exercise, activate autophagy; however, it is unknown whether exercise training alters basal levels of autophagy and whether autophagy is required for skeletal muscle adaptation to training. We observed greater autophagy flux (i.e., a combination of increased LC3-II/LC3-I ratio and LC3-II levels and reduced p62 protein content indicating a higher rate of initiation and resolution of autophagic events), autophagy protein expression (i.e., Atg6/Beclin1, Atg7, and Atg8/LC3) and mitophagy protein Bnip3 expression in tonic, oxidative muscle compared to muscles of either mixed fiber types or of predominant glycolytic fibers in mice. Long-term voluntary running (4 wk) resulted in increased basal autophagy flux and expression of autophagy proteins and Bnip3 in parallel to mitochondrial biogenesis in plantaris muscle with mixed fiber types. Conversely, exercise training promoted autophagy protein expression with no significant increases of autophagy flux and mitochondrial biogenesis in the oxidative soleus muscle. We also observed increased basal autophagy flux and Bnip3 content without increases in autophagy protein expression in the plantaris muscle of sedentary muscle-specific Pgc-1α transgenic mice, a genetic model of augmented mitochondrial biogenesis. These findings reveal that endurance exercise training-induced increases in basal autophagy, including mitophagy, only take place if an enhanced oxidative phenotype is achieved. However, autophagy protein expression is mainly dictated by contractile activity independently of enhancements in oxidative phenotype. Exercise-trained mice heterozygous for the critical autophagy protein Atg6 showed attenuated increases of basal autophagy flux, mitochondrial content, and angiogenesis in skeletal muscle, along with impaired improvement of endurance capacity. These results demonstrate that increased basal autophagy is required for endurance exercise training-induced skeletal

  7. Skeletal nutrient vascular adaptation induced by external oscillatory intramedullary fluid pressure intervention

    Directory of Open Access Journals (Sweden)

    Qin Yi-Xian


    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.

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

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


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

  9. Managing urban water crises: adaptive policy responses to drought and flood in Southeast Queensland, Australia

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    Brian W. Head


    Full Text Available In this case study, I examine the quality of decision-making under conditions of rapidly evolving urban water crises, and the adaptive policy challenges of building regional resilience in response to both drought and flood. Like other regions of Australia, Southeast Queensland has been subject to substantial cycles of drought and flood. I draw on resilience literature concerning sustainability, together with governance literature on policy change, to explain the changing awareness of urban water crises and the strategic options available for addressing these crises in this case study. The problem of resilience thinking opens up a number of important questions about the efficacy and adaptability of the policy system. The case provides insights into the interplay between the ways in which problems are framed, the knowledge bases required for planning and decision-making, the collaborative governance processes required for managing complex and rapidly evolving issues, and the overall capacity for policy learning over time. Regional resilience was proclaimed as a policy goal by government, but the practices remained largely anchored in traditional technical frameworks. Centralized investment decisions and governance restructures provoked conflict between levels of government, undermining the capacity of stakeholders to create more consensual approaches to problem-solving and limiting the collective learning that could have emerged.

  10. Electricity for groundwater use: constraints and opportunities for adaptive response to climate change (United States)

    Scott, Christopher A.


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

  11. Compensatory structural adaptive modifications of vagina in response to functional demand in goat. (United States)

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


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

  12. Dose response of micronuclei induced by combination radiation of α-particles and γ-rays in human lymphoblast cells

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    Ren, Ruiping; He, Mingyuan; Dong, Chen; Xie, Yuexia; Ye, Shuang; Yuan, Dexiao [Institute of Radiation Medicine, Fudan University, No. 2094 Xie-Tu Road, Shanghai 200032 (China); Shao, Chunlin, E-mail: [Institute of Radiation Medicine, Fudan University, No. 2094 Xie-Tu Road, Shanghai 200032 (China)


    Highlights: ► α-Particle induced MN had a biphasic dose–response followed by a bystander model. ► MN dose–response of α- and γ-combination IR was similar to that of α-particle. ► α-Particles followed by γ-rays yielded a synergistic effect on MN induction. ► Low dose γ-rays triggered antagonistic and adaptive responses against α-particle. - Abstract: Combination radiation is a real situation of both nuclear accident exposure and space radiation environment, but its biological dosimetry is still not established. This study investigated the dose–response of micronuclei (MN) induction in lymphocyte by irradiating HMy2.CIR lymphoblast cells with α-particles, γ-rays, and their combinations. Results showed that the dose–response of MN induced by γ-rays was well-fitted with the linear-quadratic model. But for α-particle irradiation, the MN induction had a biphasic phenomenon containing a low dose hypersensitivity characteristic and its dose response could be well-stimulated with a state vector model where radiation-induced bystander effect (RIBE) was involved. For the combination exposure, the dose response of MN was similar to that of α-irradiation. However, the yield of MN was closely related to the sequence of irradiations. When the cells were irradiated with α-particles at first and then γ-rays, a synergistic effect of MN induction was observed. But when the cells were irradiated with γ-rays followed by α-particles, an antagonistic effect of MN was observed in the low dose range although this combination radiation also yielded a synergistic effect at high doses. When the interval between two irradiations was extended to 4 h, a cross-adaptive response against the other irradiation was induced by a low dose of γ-rays but not α-particles.

  13. Clearance of low levels of HCV viremia in the absence of a strong adaptive immune response

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    Manns Michael P


    Full Text Available Abstract Spontaneous clearance of hepatitis C virus (HCV has frequently been associated with the presence of HCV-specific cellular immunity. However, there had been also reports in chimpanzees demonstrating clearance of HCV-viremia in the absence of significant levels of detectable HCV-specific cellular immune responses. We here report seven asymptomatic acute hepatitis C cases with peak HCV-RNA levels between 300 and 100.000 copies/ml who all cleared HCV-RNA spontaneously. Patients were identified by a systematic screening of 1176 consecutive new incoming offenders in a German young offender institution. Four of the seven patients never developed anti-HCV antibodies and had normal ALT levels throughout follow-up. Transient weak HCV-specific CD4+ T cell responses were detectable in five individuals which did not differ in strength and breadth from age- and sex-matched patients with chronic hepatitis C and long-term recovered patients. In contrast, HCV-specific MHC-class-I-tetramer-positive cells were found in 3 of 4 HLA-A2-positive patients. Thus, these cases highlight that clearance of low levels of HCV viremia is possible in the absence of a strong adaptive immune response which might explain the low seroconversion rate after occupational exposure to HCV.

  14. In vivo adaptive response of the peripheral conduit artery in patients with borderline systolic hypertension

    Institute of Scientific and Technical Information of China (English)

    陶军; 靳亚非; 王礼春; 唐安丽; 廖新学; 杨震; 马虹


    Objective To investigate elastic changes of the radial artery, a medium-sized muscular peripheral conduit artery, in patients with borderline systolic hypertension. Methods Using a non-invasive high-resolution echo-tracking device coupled to a photoplethysmography (Finapres system) allowing simultaneous arterial diameter and finger blood pressure monitoring, we measured radial artery elastic parameters of 20 patients with borderline systolic hypertension and 20 normal subjects according to Langewouters model.Results The diameter of the radial artery of control subjects and those with borderline systolic hypertension at the isobaric level of 100 mmHg and mean arterial pressure was similar, but the compliance and distensibility at similar conditions in patients with borderline systolic hypertension did not further reduced and even increased. Conclusion In patients with borderline systolic hypertension, the adaptive responses of the radial artery compliance and distensibility to increased pressure were directed to maintain its elasticity, contributing to the homeostasis of the cardiovascular system.

  15. Age aspect of adaptive response of the central nervous system in the state of emotional pain

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    Demchenko Ye.M.


    Full Text Available The formation of higher adaptive response in the postoperative period was investigated in experiments on rats of two age groups. It was found inhibition of the orientation-motor and emotional activity in young (5-6 months and old rats (20-24 months with the greatear effect in animals of the first age group. In young rats the inhibition of spatial memory was observed – number of food-getting depleted reactions decreased by 28%. Cognitive deficit was accompanied by opposite changes in the content of free unsaturated fatty acids (C18: 2.3, respectively to age features: decreased by 46% in the cortex of young rats and increased by 2.5-fold in the hippocampus of old animals.

  16. Statistical inference for response adaptive randomization procedures with adjusted optimal allocation proportions. (United States)

    Zhu, Hongjian


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

  17. Impacts of climate change on tourism in the Mediterranean. Adaptive responses

    Energy Technology Data Exchange (ETDEWEB)

    Perry, A. [University of Wales Swansea, Swansea, Wales (United Kingdom)


    Key sensitivities to Mediterranean tourism include drought and heat waves, both of which are likely to increase with projected greenhouse warming. Adaptive responses must include lengthening of the present season and particularly taking care to cater for the increasing number of older people in the population of Northern European countries who will demand high environmental and accommodation standards and look for more bespoke holidays than the mass market tourist. Climate change in Northern Europe may affect the push-pull factors which currently favour a summer peak of tourists in many Mediterranean destinations. Infra structure and beaches may well be at risk from sea level rise and there are likely to be increased problems from forest fires, water supplies and hygiene.

  18. Plant Heat Adaptation: priming in response to heat stress [version 1; referees: 2 approved

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    Isabel Bäurle


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

  19. The adaptive response of lichens to mercury exposure involves changes in the photosynthetic machinery. (United States)

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


    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.

  20. Graded-threshold parametric response maps: towards a strategy for adaptive dose painting (United States)

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


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

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

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    Niraj K Nirala


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

  2. Leptin contributes to the adaptive responses of mice to high-fat diet intake through suppressing the lipogenic pathway.

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    Lei Jiang

    Full Text Available BACKGROUND: Leptin is an adipocyte-derived hormone that plays a critical role in energy homeostasis and lipid metabolism. Overnutrition-associated obesity is known to be accompanied by hyperleptinemia. However, the physiological actions of leptin in the metabolic responses to high-fat diet (HFD intake remain to be completely elucidated. Here we characterized the metabolic features of mice fed high-fat diets and investigated the impact of leptin upon the lipogenic program which was found to be suppressed by HFD feeding through a proteomics approach. RESULTS: When maintained on two types of high-fat diets for up to 16 weeks, mice with a higher fat intake exhibited increased body fat accumulation at a greater pace, developing more severely impaired glucose tolerance. Notably, HFD feeding at 4 weeks elicited the onset of marked hyperleptinemia, prior to the occurrence of apparent insulin resistance and hyperinsulinemia. Proteomic analysis revealed dramatically decreased expression of lipogenic enzymes in the white adipose tissue (WAT from HFD-fed mice, including ATP-citrate lyase (ACL and fatty acid synthase (FAS. The expression of ACL and FAS in the liver was similarly suppressed in response to HFD feeding. By contrast, HFD-induced downregulation of hepatic ACL and FAS was significantly attenuated in leptin receptor-deficient db/db mice. Furthermore, in the liver and WAT of wild type animals, intraperitoneal leptin administration was able to directly suppress the expression of these two lipogenic enzymes, accompanied by reduced triglyceride levels both in the liver and serum. CONCLUSIONS: These results suggest that leptin contributes to the metabolic responses in adaptation to overnutrition through suppressing the expression of lipogenic enzymes, and that the lipogenic pathway represents a key targeted peripheral component in exerting leptin's liporegulatory actions.

  3. Inducible defenses in Olympia oysters in response to an invasive predator. (United States)

    Bible, Jillian M; Griffith, Kaylee R; Sanford, Eric


    The prey naiveté hypothesis suggests that native prey may be vulnerable to introduced predators because they have not evolved appropriate defenses. However, recent evidence suggests that native prey sometimes exhibit induced defenses to introduced predators, as a result of rapid evolution or other processes. We examined whether Olympia oysters (Ostrea lurida) display inducible defenses in the presence of an invasive predator, the Atlantic oyster drill (Urosalpinx cinerea), and whether these responses vary among oyster populations from estuaries with and without this predator. We spawned oysters from six populations distributed among three estuaries in northern California, USA, and raised their offspring through two generations under common conditions to minimize effects of environmental history. We exposed second-generation oysters to cue treatments: drills eating oysters, drills eating barnacles, or control seawater. Oysters from all populations grew smaller shells when exposed to drill cues, and grew thicker and harder shells when those drills were eating oysters. Oysters exposed to drills eating other oysters were subsequently preyed upon at a slower rate. Although all oyster populations exhibited inducible defenses, oysters from the estuary with the greatest exposure to drills grew the smallest shells suggesting that oyster populations have evolved adaptive differences in the strength of their responses to predators. Our findings add to a growing body of literature that suggests that marine prey may be less likely to exhibit naiveté in the face of invasive predators than prey in communities that are more isolated from native predators, such as many freshwater and terrestrial island ecosystems.

  4. Stress Induces a Shift Towards Striatum-Dependent Stimulus-Response Learning via the Mineralocorticoid Receptor. (United States)

    Vogel, Susanne; Klumpers, Floris; Schröder, Tobias Navarro; Oplaat, Krista T; Krugers, Harm J; Oitzl, Melly S; Joëls, Marian; Doeller, Christian F; Fernández, Guillén


    Stress is assumed to cause a shift from flexible 'cognitive' memory to more rigid 'habit' memory. In the spatial memory domain, stress impairs place learning depending on the hippocampus whereas stimulus-response learning based on the striatum appears to be improved. While the neural basis of this shift is still unclear, previous evidence in rodents points towards cortisol interacting with the mineralocorticoid receptor (MR) to affect amygdala functioning. The amygdala is in turn assumed to orchestrate the stress-induced shift in memory processing. However, an integrative study testing these mechanisms in humans is lacking. Therefore, we combined functional neuroimaging of a spatial memory task, stress-induction, and administration of an MR-antagonist in a full-factorial, randomized, placebo-controlled between-subjects design in 101 healthy males. We demonstrate that stress-induced increases in cortisol lead to enhanced stimulus-response learning, accompanied by increased amygdala activity and connectivity to the striatum. Importantly, this shift was prevented by an acute administration of the MR-antagonist spironolactone. Our findings support a model in which the MR and the amygdala play an important role in the stress-induced shift towards habit memory systems, revealing a fundamental mechanism of adaptively allocating neural resources that may have implications for stress-related mental disorders.Neuropsychopharmacology advance online publication, 21 December 2016; doi:10.1038/npp.2016.262.

  5. Monte Carlo-based adaptive EPID dose kernel accounting for different field size responses of imagers. (United States)

    Wang, Song; Gardner, Joseph K; Gordon, John J; Li, Weidong; Clews, Luke; Greer, Peter B; Siebers, Jeffrey V


    The aim of this study is to present an efficient method to generate imager-specific Monte Carlo (MC)-based dose kernels for amorphous silicon-based electronic portal image device dose prediction and determine the effective backscattering thicknesses for such imagers. EPID field size-dependent responses were measured for five matched Varian accelerators from three institutions with 6 MV beams at the source to detector distance (SDD) of 105 cm. For two imagers, measurements were made with and without the imager mounted on the robotic supporting arm. Monoenergetic energy deposition kernels with 0-2.5 cm of water backscattering thicknesses were simultaneously computed by MC to a high precision. For each imager, the backscattering thickness required to match measured field size responses was determined. The monoenergetic kernel method was validated by comparing measured and predicted field size responses at 150 cm SDD, 10 x 10 cm2 multileaf collimator (MLC) sliding window fields created with 5, 10, 20, and 50 mm gaps, and a head-and-neck (H&N) intensity modulated radiation therapy (IMRT) patient field. Field size responses for the five different imagers deviated by up to 1.3%. When imagers were removed from the robotic arms, response deviations were reduced to 0.2%. All imager field size responses were captured by using between 1.0 and 1.6 cm backscatter. The predicted field size responses by the imager-specific kernels matched measurements for all involved imagers with the maximal deviation of 0.34%. The maximal deviation between the predicted and measured field size responses at 150 cm SDD is 0.39%. The maximal deviation between the predicted and measured MLC sliding window fields is 0.39%. For the patient field, gamma analysis yielded that 99.0% of the pixels have gamma < 1 by the 2%, 2 mm criteria with a 3% dose threshold. Tunable imager-specific kernels can be generated rapidly and accurately in a single MC simulation. The resultant kernels are imager position

  6. Enhanced oxidative stress is responsible for TRPV4-induced neurotoxicity

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    Zhiwen Hong


    Full Text Available Transient receptor potential vanilloid 4 (TRPV4 has been reported to be responsible for neuronal injury in pathological conditions. Excessive oxidative stress can lead to neuronal damage, and activation of TRPV4 increases the production of reactive oxygen species and nitric oxide (NO in many types of cells. The present study explored whether TRPV4-induced neuronal injury is mediated through enhancing oxidative stress. We found that intracerebroventricular injection of the TRPV4 agonist GSK1016790A increased the content of methane dicarboxylic aldehyde (MDA and NO in the hippocampus, which was blocked by administration of the TRPV4 specific antagonist HC-067047. The activities of catalase (CAT and glutathione peroxidase (GSH-Px were decreased by GSK1016790A, whereas the activity of superoxide dismutase remained unchanged. Moreover, the protein level and activity of neuronal nitric oxide synthase (nNOS were increased by GSK1016790A, and the GSK1016790A-induced increase in NO content was blocked by an nNOS specific antagonist ARL-17477. The GSK1016790A-induced modulations of CAT, GSH-Px and nNOS activities and the protein level of nNOS were significantly inhibited by HC-067047. Finally, GSK1016790A-induced neuronal death and apoptosis in the hippocampal CA1 area were markedly attenuated by administration of a reactive oxygen species scavenger Trolox or ARL-17477. We conclude that activation of TRPV4 enhances oxidative stress by inhibiting CAT and GSH-Px and increasing nNOS, which is responsible, at least in part, for TRPV4-induced neurotoxicity.

  7. Characterization of homologous and heterologous adaptive immune responses in porcine reproductive and respiratory syndrome virus infection

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    Díaz Ivan


    Full Text Available Abstract The present study characterized the homologous and heterologous immune response in type-I porcine reproductive and respiratory syndrome virus (PRRSV infection. Two experiments were conducted: in experiment 1, eight pigs were inoculated with PRRSV strain 3262 and 84 days post-inoculation (dpi they were challenged with either strain 3262 or strain 3267 and followed for the next 14 days (98 dpi. In experiment 2, eight pigs were inoculated with strain 3267 and challenged at 84 dpi as above. Clinical course, viremia, humoral response (neutralizing and non-neutralizing antibodies, NA and virus-specific IFN-γ responses (ELISPOT were evaluated all throughout the study. Serum levels of IL-1, IL-6, IL-8, TNF-α and TGF-β were determined (ELISA after the second challenge. In experiment 1 primo-inoculation with strain 3262 induced viremia of ≤ 28 days, low titres of homologous NA but strong IFN-γ responses. In contrast, strain 3267 induced longer viremias (up to 56 days, higher NA titres (≤ 6 log2 and lower IFN-γ responses. Inoculation with 3267 produced higher serum IL-8 levels. After the re-challenge at 84 dpi, pigs in experiment 1 developed mostly a one week viremia regardless of the strain used. In experiment 2, neither the homologous nor the heterologous challenge resulted in detectable viremia although PRRSV was present in tonsils of some animals. Homologous re-inoculation with 3267 produced elevated TGF-β levels in serum for 7–14 days but this did not occur with the heterologous re-inoculation. In conclusion, inoculation with different PRRSV strains result in different virological and immunological outcomes and in different degrees of homologous and heterologous protection.

  8. A Drosophila immune response against Ras-induced overgrowth

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    Thomas Hauling


    Full Text Available Our goal is to characterize the innate immune response against the early stage of tumor development. For this, animal models where genetic changes in specific cells and tissues can be performed in a controlled way have become increasingly important, including the fruitfly Drosophila melanogaster. Many tumor mutants in Drosophila affect the germline and, as a consequence, also the immune system itself, making it difficult to ascribe their phenotype to a specific tissue. Only during the past decade, mutations have been induced systematically in somatic cells to study the control of tumorous growth by neighboring cells and by immune cells. Here we show that upon ectopic expression of a dominant-active form of the Ras oncogene (RasV12, both imaginal discs and salivary glands are affected. Particularly, the glands increase in size, express metalloproteinases and display apoptotic markers. This leads to a strong cellular response, which has many hallmarks of the granuloma-like encapsulation reaction, usually mounted by the insect against larger foreign objects. RNA sequencing of the fat body reveals a characteristic humoral immune response. In addition we also identify genes that are specifically induced upon expression of RasV12. As a proof-of-principle, we show that one of the induced genes (santa-maria, which encodes a scavenger receptor, modulates damage to the salivary glands. The list of genes we have identified provides a rich source for further functional characterization. Our hope is that this will lead to a better understanding of the earliest stage of innate immune responses against tumors with implications for mammalian immunity.

  9. MALT1 induced immune response is governed by miR-2909 RNomics. (United States)

    Kaul, Deepak; Arora, M; Garg, A; Sharma, S


    The paracaspase mucosa-associated lymphoid tissue 1 (MALT1) has been widely recognized to play crucial role in lymphocyte activation, development and the generation of lymphomas through the modulation of innate and adaptive immune responses. Our results reported here provide evidence for the first time to support the view that MALT1 exerts its effect upon immune response involving genes coding for retinoic acid-inducible gene 1 (RIG1); interferon-β (IFN-β); apo-lipoprotein B mRNA-editing, enzyme-catalytic, polypeptide-like 3G (APOBEC3G); IFN-γ; chemokine (C-C motif) ligand 5 (CCL5) and interleukin-17 (IL-17) through the initiation of cellular miR-2909 RNomics. This ensures sustained expression of specificity protein 1 (SP1)-dependent regulation of genes that in-turn governs MALT1 induced immune response. Based upon these results, a mechanistic-pathway is proposed that links the epigenomic-interplay between MALT1 and miR-2909.

  10. Impaired Hepatic Adaptation to Chronic Cholestasis induced by Primary Sclerosing Cholangitis (United States)

    Milkiewicz, Malgorzata; Klak, Marta; Kempinska-Podhorodecka, Agnieszka; Wiechowska-Kozlowska, Anna; Urasinska, Elzbieta; Blatkiewicz, Malgorzata; Wunsch, Ewa; Elias, Elwyn; Milkiewicz, Piotr


    Pathogenesis of primary sclerosing cholangitis (PSC) may involve impaired bile acid (BA) homeostasis. We analyzed expressions of factors mediating enterohepatic circulation of BA using ileal and colonic (ascending and sigmoid) biopsies obtained from patients with PSC with and without ulcerative colitis (UC) and explanted PSC livers. Two-fold increase of BA-activated farnesoid X receptor (FXR) protein levels were seen in ascending and sigmoid colon of PSC patients with correspondingly decreased apical sodium-dependent BA transporter (ASBT) gene expression. This was associated with increased OSTβ protein levels in each part of analyzed gut. An intestinal fibroblast growth factor (FGF19) protein expression was significantly enhanced in ascending colon. Despite increased hepatic nuclear receptors (FXR, CAR, SHP), and FGF19, neither CYP7A1 suppression nor CYP3A4 induction were observed. The lack of negative regulation of BA synthesis may be accountable for lower levels of cholesterol observed in PSC in comparison to primary biliary cholangitis (PBC). In conclusion, chronic cholestasis in PSC induces adaptive changes in expression of BA transporters and FXR in the intestine. However hepatic impairment of expected in chronic cholestasis downregulation of CYP7A1 and upregulation of CYP3A4 may promote BA-induced liver injury in PSC. PMID:28008998

  11. Noninvasive Monitoring of Training Induced Muscle Adaptation with -MRS: Fibre Type Shifts Correlate with Metabolic Changes

    Directory of Open Access Journals (Sweden)

    Eike Hoff


    Full Text Available Purpose. To evaluate training induced metabolic changes noninvasively with magnetic resonance spectroscopy (-MRS for measuring muscle fibre type adaptation. Methods. Eleven volunteers underwent a 24-week training, consisting of speed-strength, endurance, and detraining (each 8 weeks. Prior to and following each training period, needle biopsies and -MRS of the resting gastrocnemius muscle were performed. Fibre type distribution was analyzed histologically and tested for correlation with the ratios of high energy phosphates ([PCr]/[], [PCr]/[βATP] and [PCr + ]/[βATP]. The correlation between the changes of the -MRS parameters during training and the resulting changes in fibre composition were also analysed. Results. We observed an increased type-II-fibre proportion after speed-strength and detraining. After endurance training the percentage of fast-twitch fibres was reduced. The progression of the [PCr]/[]-ratio was similar to that of the fast-twitch fibres during the training. We found a correlation between the type-II-fibre proportion and [PCr]/[] (, or [PCr]/[βATP] (, ; the correlations between its changes (delta and the fibre-shift were significant as well (delta[PCr]/[] , delta[PCr]/[βATP] , . Conclusion. Shifts in fibre type composition and high energy phosphate metabolite content covary in human gastrocnemius muscle. Therefore -MRS might be a feasible method for noninvasive monitoring of exercise-induced fibre type transformation.

  12. Allele-specific down-regulation of RPTOR expression induced by retinoids contributes to climate adaptations.

    Directory of Open Access Journals (Sweden)

    Chang Sun


    Full Text Available The mechanistic target of rapamycin (MTOR pathway regulates cell growth, energy homeostasis, apoptosis, and immune response. The regulatory associated protein of MTOR encoded by the RPTOR gene is a key component of this pathway. A previous survey of candidate genes found that RPTOR contains multiple SNPs with strong correlations between allele frequencies and climate variables, consistent with the action of selective pressures that vary across environments. Using data from a recent genome scan for selection signals, we honed in on a SNP (rs11868112 26 kb upstream to the transcription start site of RPTOR that exhibits the strongest association with temperature variables. Transcription factor motif scanning and mining of recently mapped transcription factor binding sites identified a binding site for POU class 2 homeobox 1 (POU2F1 spanning the SNP and an adjacent retinoid acid receptor (RAR binding site. Using expression quantification, chromatin immunoprecipitation (ChIP, and reporter gene assays, we demonstrate that POU2F1 and RARA do bind upstream of the RPTOR gene to regulate its expression in response to retinoids; this regulation is affected by the allele status at rs11868112 with the derived allele resulting in lower expression levels. We propose a model in which the derived allele influences thermogenesis or immune response by altering MTOR pathway activity and thereby increasing fitness in colder climates. Our results show that signatures of genetic adaptations can identify variants with functional effects, consistent with the idea that selection signals may be used for SNP annotation.

  13. Excess copper induced oxidative stress and response of antioxidants in rice. (United States)

    Thounaojam, Thorny Chanu; Panda, Piyalee; Panda, P; Mazumdar, Purabi; Mazumdar, P; Kumar, Devanand; Sharma, Gauri Dutta; Sharma, G D; Sahoo, Lingaraj; Sahoo, L; Panda, Sanjib Kumar; Panda, S K


    To investigate the effects of copper (Cu), rice plant (Oryza sativa. L. var. MSE-9) was treated with different Cu concentrations (0, 10, 50 and 100 μM) for 5 days in hydroponic condition. Gradual decrease in shoot and root growth was observed with the increase of Cu concentration and duration of treatment where maximum inhibition was recorded in root growth. Cu was readily absorbed by the plant though the maximum accumulation was found in root than shoot. Hydrogen peroxide (H(2)O(2)) production and lipid peroxidation were found increased with the elevated Cu concentration indicating excess Cu induced oxidative stress. Antioxidant enzymes superoxide dismutase (SOD), guaiacol peroxidase (GPX) and ascorbate peroxidase (APX) and glutathione reductase (GR) were effectively generated at the elevated concentrations of Cu though catalase (CAT) did not show significant variation with respect to control. Ascorbate (ASH), glutathione (GSH) and proline contents were also increased in all the Cu treated plants compared with the control. SOD isoenzyme was greatly affected by higher concentration of Cu and it was consistent with the changes of the activity assayed in solution. The present study confirmed that excess Cu inhibits growth, induced oxidative stress by inducing ROS formation while the stimulated antioxidative system appears adaptive response of rice plant against Cu induced oxidative stress. Moreover proline accumulation in Cu stress plant seems to provide additional defense against the oxidative stress.

  14. Cholic acid induces a Cftr dependent biliary secretion and liver growth response in mice.

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    Frank A J A Bodewes

    Full Text Available The cause of Cystic fibrosis liver disease (CFLD, is unknown. It is well recognized that hepatic exposure to hydrophobic bile salts is associated with the development of liver disease. For this reason, we hypothesize that, CFTR dependent variations, in the hepatic handling of hydrophobic bile salts, are related to the development CFLD. To test our hypothesis we studied, in Cftr-/- and control mice, bile production, bile composition and liver pathology, in normal feeding condition and during cholate exposure, either acute (intravenous or chronic (three weeks via the diet. In Cftr-/- and control mice the basal bile production was comparable. Intravenous taurocholate increased bile production to the same extent in Cftr-/- and control mice. However, chronic cholate exposure increased the bile flow significantly less in Cftr-/- mice than in controls, together with significantly higher biliary bile salt concentration in Cftr-/- mice. Prolonged cholate exposure, however, did not induce CFLD like pathology in Cftr-/- mice. Chronic cholate exposure did induce a significant increase in liver mass in controls that was absent in Cftr-/- mice. Chronic cholate administration induces a cystic fibrosis-specific hepatobiliary phenotype, including changes in bile composition. These changes could not be associated with CFLD like pathological changes in CF mouse livers. However, chronic cholate administration induces liver growth in controls that is absent in Cftr-/- mice. Our findings point to an impaired adaptive homeotrophic liver response to prolonged hydrophobic bile salt exposure in CF conditions.

  15. Natural and Induced Humoral Responses to MUC1

    Directory of Open Access Journals (Sweden)

    Silvia Von Mensdorff-Pouilly


    Full Text Available MUC1 is a membrane-tethered mucin expressed on the ductal cell surface of glandular epithelial cells. Loss of polarization, overexpression and aberrant glycosylation of MUC1 in mucosal inflammation and in adenocarcinomas induces humoral immune responses to the mucin. MUC1 IgG responses have been associated with a benefit in survival in patients with breast, lung, pancreatic, ovarian and gastric carcinomas. Antibodies bound to the mucin may curb tumor progression by restoring cell-cell interactions altered by tumor-associated MUC1, thus preventing metastatic dissemination, as well as counteracting the immune suppression exerted by the molecule. Furthermore, anti-MUC1 antibodies are capable of effecting tumor cell killing by antibody-dependent cell-mediated cytotoxicity. Although cytotoxic T cells are indispensable to achieve anti-tumor responses in advanced disease, abs to tumor-associated antigens are ideally suited to address minimal residual disease and may be sufficient to exert adequate immune surveillance in an adjuvant setting, destroying tumor cells as they arise or maintaining occult disease in an equilibrium state. Initial evaluation of MUC1 peptide/glycopeptide mono and polyvalent vaccines has shown them to be immunogenic and safe; anti-tumor responses are scarce. Progress in carbohydrate synthesis has yielded a number of sophisticated substrates that include MUC1 glycopeptide epitopes that are at present in preclinical testing. Adjuvant vaccination with MUC1 glycopeptide polyvalent vaccines that induce strong humoral responses may prevent recurrence of disease in patients with early stage carcinomas. Furthermore, prophylactic immunotherapy targeting MUC1 may be a strategy to strengthen immune surveillance and prevent disease in subjects at hereditary high risk of breast, ovarian and colon cancer.

  16. Trypanosomiasis-induced Th17-like immune responses in carp.

    Directory of Open Access Journals (Sweden)

    Carla M S Ribeiro

    Full Text Available BACKGROUND: In mammalian vertebrates, the cytokine interleukin (IL-12 consists of a heterodimer between p35 and p40 subunits whereas interleukin-23 is formed by a heterodimer between p19 and p40 subunits. During an immune response, the balance between IL-12 and IL-23 can depend on the nature of the pathogen associated molecular pattern (PAMP recognized by, for example TLR2, leading to a preferential production of IL-23. IL-23 production promotes a Th17-mediated immune response characterized by the production of IL-17A/F and several chemokines, important for neutrophil recruitment and activation. For the cold blooded vertebrate common carp, only the IL-12 subunits have been described so far. METHODOLOGY/PRINCIPAL FINDINGS: Common carp is the natural host of two protozoan parasites: Trypanoplasma borreli and Trypanosoma carassii. We found that these parasites negatively affect p35 and p40a gene expression in carp. Transfection studies of HEK293 and carp macrophages show that T. carassii-derived PAMPs are agonists of carp TLR2, promoting p19 and p40c gene expression. The two protozoan parasites induce different immune responses as assessed by gene expression and histological studies. During T. carassii infections, in particular, we observed a propensity to induce p19 and p40c gene expression, suggestive of the formation of IL-23. Infections with T. borreli and T. carassii lead to an increase of IFN-γ2 gene expression whereas IL-17A/F2 gene expression was only observed during T. carasssii infections. The moderate increase in the number of splenic macrophages during T. borreli infection contrasts the marked increase in the number of splenic neutrophilic granulocytes during T. carassii infection, along with an increased gene expression of metalloproteinase-9 and chemokines. CONCLUSION/SIGNIFICANCE: This is the first study that provides evidence for a Th17-like immune response in fish in response to infection with a protozoan parasite.

  17. Natural and Induced Humoral Responses to MUC1

    Energy Technology Data Exchange (ETDEWEB)

    Mensdorff-Pouilly, Silvia von, E-mail:; Moreno, Maria [Department of Obstetrics and Gynecology, VU University Medical Center, De Boelelaan 1117, Amsterdam 1081 HV (Netherlands); Verheijen, René H. M. [Department of Woman & Baby, Division of Surgical & Oncological Gynaecology, University Medical Center Utrecht, Heidelberglaan 100, Utrecht 3508 GA (Netherlands)


    MUC1 is a membrane-tethered mucin expressed on the ductal cell surface of glandular epithelial cells. Loss of polarization, overexpression and aberrant glycosylation of MUC1 in mucosal inflammation and in adenocarcinomas induces humoral immune responses to the mucin. MUC1 IgG responses have been associated with a benefit in survival in patients with breast, lung, pancreatic, ovarian and gastric carcinomas. Antibodies bound to the mucin may curb tumor progression by restoring cell-cell interactions altered by tumor-associated MUC1, thus preventing metastatic dissemination, as well as counteracting the immune suppression exerted by the molecule. Furthermore, anti-MUC1 antibodies are capable of effecting tumor cell killing by antibody-dependent cell-mediated cytotoxicity. Although cytotoxic T cells are indispensable to achieve anti-tumor responses in advanced disease, abs to tumor-associated antigens are ideally suited to address minimal residual disease and may be sufficient to exert adequate immune surveillance in an adjuvant setting, destroying tumor cells as they arise or maintaining occult disease in an equilibrium state. Initial evaluation of MUC1 peptide/glycopeptide mono and polyvalent vaccines has shown them to be immunogenic and safe; anti-tumor responses are scarce. Progress in carbohydrate synthesis has yielded a number of sophisticated substrates that include MUC1 glycopeptide epitopes that are at present in preclinical testing. Adjuvant vaccination with MUC1 glycopeptide polyvalent vaccines that induce strong humoral responses may prevent recurrence of disease in patients with early stage carcinomas. Furthermore, prophylactic immunotherapy targeting MUC1 may be a strategy to strengthen immune surveillance and prevent disease in subjects at hereditary high risk of breast, ovarian and colon cancer.

  18. Platelets protect lung from injury induced by systemic inflammatory response (United States)

    Luo, Shuhua; Wang, Yabo; An, Qi; Chen, Hao; Zhao, Junfei; Zhang, Jie; Meng, Wentong; Du, Lei


    Systemic inflammatory responses can severely injure lungs, prompting efforts to explore how to attenuate such injury. Here we explored whether platelets can help attenuate lung injury in mice resulting from extracorporeal circulation (ECC)-induced systemic inflammatory responses. Mice were subjected to ECC for 30 min, then treated with phosphate-buffered saline, platelets, the GPIIb/IIIa inhibitor Tirofiban, or the combination of platelets and Tirofiban. Blood and lung tissues were harvested 60 min later, and lung injury and inflammatory status were assessed. As expected, ECC caused systemic inflammation and pulmonary dysfunction, and platelet transfusion resulted in significantly milder lung injury and higher lung function. It also led to greater numbers of circulating platelet-leukocyte aggregates and greater platelet accumulation in the lung. Platelet transfusion was associated with higher production of transforming growth factor-β and as well as lower levels of tumour necrosis factor-α and neutrophil elastase in plasma and lung. None of these platelet effects was observed in the presence of Tirofiban. Our results suggest that, at least under certain conditions, platelets can protect lung from injury induced by systemic inflammatory responses. PMID:28155889

  19. Immunological aspects of the immune response induced by mosquito allergens. (United States)

    Cantillo, José Fernando; Fernández-Caldas, Enrique; Puerta, Leonardo


    Allergies caused by mosquito bites may produce local or systemic reactions. The inhalation of mosquito allergens may also cause asthma and/or allergic rhinoconjunctivitis in sensitized individuals. The mechanisms implicated in the development of these immune responses involve IgE antibodies, different subtypes of IgG and proinflammatory cytokines as well as basophils, eosinophils and mast cells. Several allergenic components have been identified in the saliva and bodies of mosquitoes and some of these are present in different mosquito species. The most common species implicated in allergic reactions belong to the genera Aedes, Culex and Anopheles. Several Aedes aegypti allergens have been cloned and sequenced. The recombinant molecules show IgE reactivity similar to that of the native allergens, making them good candidates for the diagnosis of mosquito allergies. Allergen-specific immunotherapy with mosquito extracts induces a protective response characterized by a decreased production of IgE antibodies, increased IgG levels, a reduction in the severity of cutaneous and respiratory symptoms and the need for medication. The aims of this review are to summarize the progress made in the characterization of mosquito allergens and discuss the types of immune responses induced by mosquito bites and the inhalation of mosquito allergens in atopic individuals.

  20. Muscle Plasticity and β2-Adrenergic Receptors: Adaptive Responses of β2-Adrenergic Receptor Expression to Muscle Hypertrophy and Atrophy

    Directory of Open Access Journals (Sweden)

    Shogo Sato


    Full Text Available We discuss the functional roles of β2-adrenergic receptors in skeletal muscle hypertrophy and atrophy as well as the adaptive responses of β2-adrenergic receptor expression to anabolic and catabolic conditions. β2-Adrenergic receptor stimulation using anabolic drugs increases muscle mass by promoting muscle protein synthesis and/or attenuating protein degradation. These effects are prevented by the downregulation of the receptor. Endurance training improves oxidative performance partly by increasing β2-adrenergic receptor density in exercise-recruited slow-twitch muscles. However, excessive stimulation of β2-adrenergic receptors negates their beneficial effects. Although the preventive effects of β2-adrenergic receptor stimulation on atrophy induced by muscle disuse and catabolic hormones or drugs are observed, these catabolic conditions decrease β2-adrenergic receptor expression in slow-twitch muscles. These findings present evidence against the use of β2-adrenergic agonists in therapy for muscle wasting and weakness. Thus, β2-adrenergic receptors in the skeletal muscles play an important physiological role in the regulation of protein and energy balance.

  1. Decrease in membrane phospholipid unsaturation induces unfolded protein response. (United States)

    Ariyama, Hiroyuki; Kono, Nozomu; Matsuda, Shinji; Inoue, Takao; Arai, Hiroyuki


    Various kinds of fatty acids are distributed in membrane phospholipids in mammalian cells and tissues. The degree of fatty acid unsaturation in membrane phospholipids affects many membrane-associated functions and can be influenced by diet and by altered activities of lipid-metabolizing enzymes such as fatty acid desaturases. However, little is known about how mammalian cells respond to changes in phospholipid fatty acid composition. In this study we showed that stearoyl-CoA desaturase 1 (SCD1) knockdown increased the amount of saturated fatty acids and decreased that of monounsaturated fatty acids in phospholipids without affecting the amount or the composition of free fatty acid and induced unfolded protein response (UPR), evidenced by increased expression of C/EBP homologous protein (CHOP) and glucose-regulated protein 78 (GRP78) mRNAs and splicing of Xbox-binding protein 1 (XBP1) mRNA. SCD1 knockdown-induced UPR was rescued by various unsaturated fatty acids and was enhanced by saturated fatty acid. Lysophosphatidylcholine acyltransferase 3 (LPCAT3), which incorporates preferentially polyunsaturated fatty acids into phosphatidylcholine, was up-regulated in SCD1 knockdown cells. Knockdown of LPCAT3 synergistically enhanced UPR with SCD1 knockdown. Finally we showed that palmitic acid-induced UPR was significantly enhanced by LPCAT3 knockdown as well as SCD1 knockdown. These results suggest that a decrease in membrane phospholipid unsaturation induces UPR.

  2. Discovering the role of mitochondria in the iron deficiency-induced metabolic responses of plants. (United States)

    Vigani, Gianpiero


    In plants, iron (Fe) deficiency-induced chlorosis is a major problem, affecting both yield and quality of crops. Plants have evolved multifaceted strategies, such as reductase activity, proton extrusion, and specialised storage proteins, to mobilise Fe from the environment and distribute it within the plant. Because of its fundamental role in plant productivity, several issues concerning Fe homeostasis in plants are currently intensively studied. The activation of Fe uptake reactions requires an overall adaptation of the primary metabolism because these activities need the constant supply of energetic substrates (i.e., NADPH and ATP). Several studies concerning the metabolism of Fe-deficient plants have been conducted, but research focused on mitochondrial implications in adaptive responses to nutritional stress has only begun in recent years. Mitochondria are the energetic centre of the root cell, and they are strongly affected by Fe deficiency. Nevertheless, they display a high level of functional flexibility, which allows them to maintain the viability of the cell. Mitochondria represent a crucial target of studies on plant homeostasis, and it might be of interest to concentrate future research on understanding how mitochondria orchestrate the reprogramming of root cell metabolism under Fe deficiency. In this review, I summarise what it is known about the effect of Fe deficiency on mitochondrial metabolism and morphology. Moreover, I present a detailed view of the possible roles of mitochondria in the development of plant responses to Fe deficiency, integrating old findings with new and discussing new hypotheses for future investigations.

  3. In Vivo Synthesis of Cyclic-di-GMP Using a Recombinant Adenovirus Preferentially Improves Adaptive Immune Responses against Extracellular Antigens. (United States)

    Alyaqoub, Fadel S; Aldhamen, Yasser A; Koestler, Benjamin J; Bruger, Eric L; Seregin, Sergey S; Pereira-Hicks, Cristiane; Godbehere, Sarah; Waters, Christopher M; Amalfitano, Andrea


    There is a compelling need for more effective vaccine adjuvants to augment induction of Ag-specific adaptive immune responses. Recent reports suggested the bacterial second messenger bis-(3'-5')-cyclic-dimeric-guanosine monophosphate (c-di-GMP) acts as an innate immune system modulator. We recently incorporated a Vibrio cholerae diguanylate cyclase into an adenovirus vaccine, fostering production of c-di-GMP as well as proinflammatory responses in mice. In this study, we recombined a more potent diguanylate cyclase gene, VCA0848, into a nonreplicating adenovirus serotype 5 (AdVCA0848) that produces elevated amounts of c-di-GMP when expressed in mammalian cells in vivo. This novel platform further improved induction of type I IFN-β and activation of innate and adaptive immune cells early after administration into mice as compared with control vectors. Coadministration of the extracellular protein OVA and the AdVCA0848 adjuvant significantly improved OVA-specific T cell responses as detected by IFN-γ and IL-2 ELISPOT, while also improving OVA-specific humoral B cell adaptive responses. In addition, we found that coadministration of AdVCA0848 with another adenovirus serotype 5 vector expressing the HIV-1-derived Gag Ag or the Clostridium difficile-derived toxin B resulted in significant inhibitory effects on the induction of Gag and toxin B-specific adaptive immune responses. As a proof of principle, these data confirm that in vivo synthesis of c-di-GMP stimulates strong innate immune responses that correlate with enhanced adaptive immune responses to concomitantly administered extracellular Ag, which can be used as an adjuvant to heighten effective immune responses for protein-based vaccine platforms against microbial infections and cancers.

  4. Radioadaptive response for protection against radiation-induced teratogenesis. (United States)

    Okazaki, Ryuji; Ootsuyama, Akira; Norimura, Toshiyuki


    To clarify the characteristics of the radioadaptive response in mice, we compared the incidence of radiation-induced malformations in ICR mice. Pregnant ICR mice were exposed to a priming dose of 2 cGy (667 muGy/min) on day 9.5 of gestation and to a challenging dose of 2 Gy (1.04 Gy/min) 4 h later and were killed on day 18.5 of gestation. The incidence of malformations and prenatal death and fetal body weights were studied. The incidence of external malformations was significantly lower (by approximately 10%) in the primed (2 cGy + 2 Gy) mice compared to the unprimed (2 Gy alone) mice. However, there were no differences in the incidence of prenatal death or the skeletal malformations or the body weights between primed and unprimed mice. These results suggest that primary conditioning with low doses of radiation suppresses radiation-induced teratogenesis.

  5. SOS response induces persistence to fluoroquinolones in Escherichia coli.

    Directory of Open Access Journals (Sweden)

    Tobias Dörr


    Full Text Available Bacteria can survive antibiotic treatment without acquiring heritable antibiotic resistance. We investigated persistence to the fluoroquinolone ciprofloxacin in Escherichia coli. Our data show that a majority of persisters to ciprofloxacin were formed upon exposure to the antibiotic, in a manner dependent on the SOS gene network. These findings reveal an active and inducible mechanism of persister formation mediated by the SOS response, challenging the prevailing view that persisters are pre-existing and formed purely by stochastic means. SOS-induced persistence is a novel mechanism by which cells can counteract DNA damage and promote survival to fluoroquinolones. This unique survival mechanism may be an important factor influencing the outcome of antibiotic therapy in vivo.

  6. Ribosome biogenesis adaptation in resistance training-induced human skeletal muscle hypertrophy. (United States)

    Figueiredo, Vandre C; Caldow, Marissa K; Massie, Vivien; Markworth, James F; Cameron-Smith, David; Blazevich, Anthony J


    Resistance training (RT) has the capacity to increase skeletal muscle mass, which is due in part to transient increases in the rate of muscle protein synthesis during postexercise recovery. The role of ribosome biogenesis in supporting the increased muscle protein synthetic demands is not known. This study examined the effect of both a single acute bout of resistance exercise (RE) and a chronic RT program on the muscle ribosome biogenesis response. Fourteen healthy young men performed a single bout of RE both before and after 8 wk of chronic RT. Muscle cross-sectional area was increased by 6 ± 4.5% in response to 8 wk of RT. Acute RE-induced activation of the ERK and mTOR pathways were similar before and after RT, as assessed by phosphorylation of ERK, MNK1, p70S6K, and S6 ribosomal protein 1 h postexercise. Phosphorylation of TIF-IA was also similarly elevated following both RE sessions. Cyclin D1 protein levels, which appeared to be regulated at the translational rather than transcriptional level, were acutely increased after RE. UBF was the only protein found to be highly phosphorylated at rest after 8 wk of training. Also, muscle levels of the rRNAs, including the precursor 45S and the mature transcripts (28S, 18S, and 5.8S), were increased in response to RT. We propose that ribosome biogenesis is an important yet overlooked event in RE-induced muscle hypertrophy that warrants further investigation.

  7. Adaptation to climate change and climate variability in European agriculture: The importance of farm level responses

    NARCIS (Netherlands)

    Reidsma, P.; Ewert, F.; Oude Lansink, A.G.J.M.; Leemans, R.


    Climatic conditions and hence climate change influence agriculture. Most studies that addressed the vulnerability of agriculture to climate change have focused on potential impacts without considering adaptation. When adaptation strategies are considered, socio-economic conditions and farm managemen

  8. Responses of the autonomic nervous system in altitude adapted and high altitude pulmonary oedema subjects (United States)

    Mathew, Lazar; Purkayastha, S. S.; Jayashankar, A.; Radhakrishnan, U.; Sen Gupta, J.; Nayar, H. S.


    Studies were carried out to ascertain the role of sympatho-parasympathetic responses in the process of adaptation to altitude. The assessment of status of autonomic balance was carried out in a group of 20 young male subjects by recording their resting heart rate, blood pressure, oral temperature, mean skin temperature, extremity temperatures, pupillary diameter, cold pressor response, oxygen consumption, cardioacceleration during orthostasis and urinary excretion of catecholamines; in a thermoneutral laboratory. The same parameters were repeated on day 3 and at weekly intervals for a period of 3 weeks, after exposing them to 3,500 m; and also after return to sea level. At altitude, similar studies were carried out in a group of 10 acclimatized lowlanders, 10 high altitude natives and 6 patients who had recently recovered from high altitude pulmonary oedema. In another phase, similar studies were done in two groups of subjects, one representing 15 subjects who had stayed at altitude (3,500 4,000 m) without any ill effects and the other comprising of 10 subjects who had either suffered from high altitude pulmonary oedema (HAPO) or acute mountain sickness (AMS). The results revealed sympathetic overactivity on acute induction to altitude which showed gradual recovery on prolonged stay, the high altitude natives had preponderance to parasympathetic system. Sympathetic preponderance may not be an essential etiological factor for the causation of maladaptation syndromes.

  9. Perceptions of wellness to monitor adaptive responses to training and competition in elite Australian football. (United States)

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


    Perceptions of wellness are often used by athletes and coaches to assess adaptive responses to training. The purpose of this research was to describe how players were coping with the demands of elite level Australian football over a competitive season using subjective ratings of physical and psychological wellness and to assess the ecological validity of such a monitoring approach. Twenty-seven players completed ratings for 9 items (fatigue, general muscle, hamstring, quadriceps, pain/stiffness, power, sleep quality, stress, well-being). Players subjectively rated each item as they arrived at the training or competition venue on a 1-5 visual analog scale, with 1 representing the positive end of the continuum. A total of 2,583 questionnaires were analyzed from completions on 183 days throughout the season (92 ± 24 per player, 103 ± 20 per week; mean ± SD). Descriptive statistics and multilevel modelling were used to understand how player ratings of wellness varied over the season and during the week leading into game day and whether selected player characteristics moderated these relationships. Results indicated that subjective ratings of physical and psychological wellness were sensitive to weekly training manipulations (i.e., improve steadily throughout the week to a game day low, p wellness provide a useful tool for coaches and practitioners to monitor player responses to the rigorous demands of training, competition, and life as a professional athlete.

  10. The adaptation and implementation of guidelines for responsible media reporting on suicide in Slovenia (United States)

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


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

  11. Silver nanoparticles induce endoplasmatic reticulum stress response in zebrafish

    Energy Technology Data Exchange (ETDEWEB)

    Christen, Verena [University of Applied Sciences and Arts Northwestern Switzerland, School of Life Sciences, Gründenstrasse 40, CH-4132 Muttenz (Switzerland); Capelle, Martinus [Crucell, P.O. Box 2048, NL-2301 Leiden (Netherlands); Fent, Karl, E-mail: [University of Applied Sciences and Arts Northwestern Switzerland, School of Life Sciences, Gründenstrasse 40, CH-4132 Muttenz (Switzerland); Swiss Federal Institute of Technology Zürich, Department of Environmental Systems Science, CH-8092 Zürich (Switzerland)


    Silver nanoparticles (AgNPs) find increasing applications, and therefore humans and the environment are increasingly exposed to them. However, potential toxicological implications are not sufficiently known. Here we investigate effects of AgNPs (average size 120 nm) on zebrafish in vitro and in vivo, and compare them to human hepatoma cells (Huh7). AgNPs are incorporated in zebrafish liver cells (ZFL) and Huh7, and in zebrafish embryos. In ZFL cells AgNPs lead to induction of reactive oxygen species (ROS), endoplasmatic reticulum (ER) stress response, and TNF-α. Transcriptional alterations also occur in pro-apoptotic genes p53 and Bax. The transcriptional profile differed in ZFL and Huh7 cells. In ZFL cells, the ER stress marker BiP is induced, concomitant with the ER stress marker ATF-6 and spliced XBP-1 after 6 h and 24 h exposure to 0.5 g/L and 0.05 g/L AgNPs, respectively. This indicates the induction of different pathways of the ER stress response. Moreover, AgNPs induce TNF-α. In zebrafish embryos exposed to 0.01, 0.1, 1 and 5 mg/L AgNPs hatching was affected and morphological defects occurred at high concentrations. ER stress related gene transcripts BiP and Synv are significantly up-regulated after 24 h at 0.1 and 5 mg/L AgNPs. Furthermore, transcriptional alterations occurred in the pro-apoptotic genes Noxa and p21. The ER stress response was strong in ZFL cells and occurred in zebrafish embryos as well. Our data demonstrate for the first time that AgNPs lead to induction of ER stress in zebrafish. The induction of ER stress can have several consequences including the activation of apoptotic and inflammatory pathways. - Highlights: • Effects of silver nanoparticles (120 nm AgNPs) are investigated in zebrafish. • AgNPs induce all ER stress reponses in vitro in zebrafish liver cells. • AgNPs induce weak ER stress in zebrafish embryos. • AgNPs induce oxidative stress and transcripts of pro-apoptosis genes.

  12. Synchronization transitions induced by the fluctuation of adaptive coupling strength in delayed Newman-Watts neuronal networks. (United States)

    Wang, Qi; Gong, Yubing; Wu, Yanan


    Introducing adaptive coupling in delayed neuronal networks and regulating the dissipative parameter (DP) of adaptive coupling by noise, we study the effect of fluctuations of the changing rate of adaptive coupling on the synchronization of the neuronal networks. It is found that time delay can induce synchronization transitions for intermediate DP values, and the synchronization transitions become strongest when DP is optimal. As the intensity of DP noise is varied, the neurons can also exhibit synchronization transitions, and the phenomenon is delay-dependent and is enhanced for certain time delays. Moreover, the synchronization transitions change with the change of DP and become strongest when DP is optimal. These results show that randomly changing adaptive coupling can considerably change the synchronization of the neuronal networks, and hence could play a crucial role in the information processing and transmission in neural systems.

  13. Efficient Spike-Coding with Multiplicative Adaptation in a Spike Response Model

    NARCIS (Netherlands)

    Bohte, S.M.


    Neural adaptation underlies the ability of neurons to maximize encoded informa- tion over a wide dynamic range of input stimuli. While adaptation is an intrinsic feature of neuronal models like the Hodgkin-Huxley model, the challenge is to in- tegrate adaptation in models of neural computation. Rece

  14. Early adaptive response of the retina to a pro-diabetogenic diet: Impairment of cone response and gene expression changes in high-fructose fed rats. (United States)

    Thierry, Magalie; Pasquis, Bruno; Buteau, Bénédicte; Fourgeux, Cynthia; Dembele, Doulaye; Leclere, Laurent; Gambert-Nicot, Ségolène; Acar, Niyazi; Bron, Alain M; Creuzot-Garcher, Catherine P; Bretillon, Lionel


    The lack of plasticity of neurons to respond to dietary changes, such as high fat and high fructose diets, by modulating gene and protein expression has been associated with functional and behavioral impairments that can have detrimental consequences. The inhibition of high fat-induced rewiring of hypothalamic neurons induced obesity. Feeding rodents with high fructose is a recognized and widely used model to trigger obesity and metabolic syndrome. However the adaptive response of the retina to short term feeding with high fructose is poorly documented. We therefore aimed to characterize both the functional and gene expression changes in the neurosensory retina of Brown Norway rats fed during 3 and 8 days with a 60%-rich fructose diet (n = 16 per diet and per time point). Glucose, insulin, leptin, triacylglycerols, total cholesterol, HDL-cholesterol, LDL-cholesterol and fructosamine were quantified in plasma (n = 8 in each group). Functionality of the inner retina was studied using scotopic single flash electroretinography (n = 8 in each group) and the individual response of rod and cone photoreceptors was determined using 8.02 Hz Flicker electroretinography (n = 8 in each group). Analysis of gene expression in the neurosensory retina was performed by Affymetrix genechips, and confirmed by RT-qPCR (n = 6 in each group). Elevated glycemia (+13%), insulinemia (+83%), and leptinemia (+172%) was observed after 8 days of fructose feeding. The cone photoreceptor response was altered at day 8 in high fructose fed rats (Δ = 0.5 log unit of light stimulus intensity). Affymetrix analysis of gene expression highlighted significant modulation of the pathways of eIF2 signaling and endoplasmic reticulum stress, regulation of eIF4 and p70S6K signaling, as well as mTOR signaling and mitochondrial dysfunction. RT-qPCR analysis confirmed the down regulation of Crystallins, Npy, Nid1 and Optc genes after 3 days of fructose feeding, and up regulation of End2. Meanwhile, a trend

  15. Fibre-specific responses to endurance and low volume high intensity interval training: striking similarities in acute and chronic adaptation.

    Directory of Open Access Journals (Sweden)

    Trisha D Scribbans

    Full Text Available The current study involved the completion of two distinct experiments. Experiment 1 compared fibre specific and whole muscle responses to acute bouts of either low-volume high-intensity interval training (LV-HIT or moderate-intensity continuous endurance exercise (END in a randomized crossover design. Experiment 2 examined the impact of a six-week training intervention (END or LV-HIT; 4 days/week, on whole body and skeletal muscle fibre specific markers of aerobic and anaerobic capacity. Six recreationally active men (Age: 20.7 ± 3.8 yrs; VO2peak: 51.9 ± 5.1 mL/kg/min reported to the lab on two separate occasions for experiment 1. Following a muscle biopsy taken in a fasted state, participants completed an acute bout of each exercise protocol (LV-HIT: 8, 20-second intervals at ∼ 170% of VO2peak separated by 10 seconds of rest; END: 30 minutes at ∼ 65% of VO2peak, immediately followed by a muscle biopsy. Glycogen content of type I and IIA fibres was significantly (p<0.05 reduced, while p-ACC was significantly increased (p<0.05 following both protocols. Nineteen recreationally active males (n = 16 and females (n = 3 were VO2peak-matched and assigned to either the LV-HIT (n = 10; 21 ± 2 yrs or END (n = 9; 20.7 ± 3.8 yrs group for experiment 2. After 6 weeks, both training protocols induced comparable increases in aerobic capacity (END: Pre: 48.3 ± 6.0, Mid: 51.8 ± 6.0, Post: 55.0 ± 6.3 mL/kg/min LV-HIT: Pre: 47.9 ± 8.1, Mid: 50.4 ± 7.4, Post: 54.7 ± 7.6 mL/kg/min, fibre-type specific oxidative and glycolytic capacity, glycogen and IMTG stores, and whole-muscle capillary density. Interestingly, only LV-HIT induced greater improvements in anaerobic performance and estimated whole-muscle glycolytic capacity. These results suggest that 30 minutes of END exercise at ∼ 65% VO2peak or 4 minutes of LV-HIT at ∼ 170% VO2peak induce comparable changes in the intra-myocellular environment (glycogen content and signaling activation

  16. The presence of alpha interferon at the time of infection alters the innate and adaptive immune responses to porcine reproductive and respiratory syndrome virus. (United States)

    Brockmeier, Susan L; Loving, Crystal L; Nelson, Eric A; Miller, Laura C; Nicholson, Tracy L; Register, Karen B; Grubman, Marvin J; Brough, Douglas E; Kehrli, Marcus E


    Porcine reproductive and respiratory syndrome (PRRS) is one of the most devastating and costly diseases to the swine industry worldwide. Overall, the adaptive immune response to PRRS virus (PRRSV) is weak, which results in delayed elimination of virus from the host and inferior vaccine protection. PRRSV has been shown to induce a meager alpha interferon (IFN-α) response, and we hypothesized that elevated IFN-α levels early in infection would shorten the induction time and increase elements of the adaptive immune response. To test this, we measured both antibody and cell-mediated immunity in pigs after the administration of a nonreplicating human adenovirus type 5 vector expressing porcine IFN-α (Ad5-pIFN-α) at the time of PRRSV infection and compared the results to those for pigs infected with PRRSV alone. Viremia was delayed, and there was a decrease in viral load in the sera of pigs administered the Ad5-pIFN-α. Although seroconversion was slightly delayed in pigs receiving Ad5-pIFN-α, probably due to the early reduction in viral replication, little difference in the overall or neutralizing antibody response was seen. However, there was an increase in the number of virus-specific IFN-γ-secreting cells detected in the pigs receiving Ad5-pIFN-α, as well as an altered cytokine profile in the lung at 14 days postinfection, indicating that the presence of IFN-α at the time of infection can alter innate and adaptive immune responses to PRRSV.

  17. Progesterone-based contraceptives reduce adaptive immune responses and protection against sequential influenza A virus infections. (United States)

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


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

  18. Titin isoform switching is a major cardiac adaptive response in hibernating grizzly bears. (United States)

    Nelson, O Lynne; Robbins, Charles T; Wu, Yiming; Granzier, Henk


    The hibernation phenomenon captures biological as well as clinical interests to understand how organs adapt. Here we studied how hibernating grizzly bears (Ursus arctos horribilis) tolerate extremely low heart rates without developing cardiac chamber dilation. We evaluated cardiac filling function in unanesthetized grizzly bears by echocardiography during the active and hibernating period. Because both collagen and titin are involved in altering diastolic function, we investigated both in the myocardium of active and hibernating grizzly bears. Heart rates were reduced from 84 beats/min in active bears to 19 beats/min in hibernating bears. Diastolic volume, stroke volume, and left ventricular ejection fraction were not different. However, left ventricular muscle mass was significantly lower (300 +/- 12 compared with 402 +/- 14 g; P = 0.003) in the hibernating bears, and as a result the diastolic volume-to-left ventricular muscle mass ratio was significantly greater. Early ventricular filling deceleration times (106.4 +/- 14 compared with 143.2 +/- 20 ms; P = 0.002) were shorter during hibernation, suggesting increased ventricular stiffness. Restrictive pulmonary venous flow patterns supported this conclusion. Collagen type I and III comparisons did not reveal differences between the two groups of bears. In contrast, the expression of titin was altered by a significant upregulation of the stiffer N2B isoform at the expense of the more compliant N2BA isoform. The mean ratio of N2BA to N2B titin was 0.73 +/- 0.07 in the active bears and decreased to 0.42 +/- 0.03 (P = 0.006) in the hibernating bears. The upregulation of stiff N2B cardiac titin is a likely explanation for the increased ventricular stiffness that was revealed by echocardiography, and we propose that it plays a role in preventing chamber dilation in hibernating grizzly bears. Thus our work identified changes in the alternative splicing of cardiac titin as a major adaptive response in hibernating grizzly

  19. Adaptive growth of tree root systems in response to wind action and site conditions. (United States)

    Nicoll, Bruce C.; Ray, Duncan


    Soil-root plate dimensions and structural root architecture were examined on 46-year-old Sitka spruce (Picea sitchensis (Bong.) Carr.) trees that had been mechanically uprooted. Rooting depth was restricted by a water table, and root system morphology had adapted to resist the wind movement associated with shallow rooting. The spread of the root system and the ratio of root mass to shoot mass (root/shoot ratio) were both negatively related to soil-root plate depth. Root systems had more structural root mass on the leeward side than the windward side of the tree relative to the prevailing wind direction. Cross sections of structural roots were obtained at distances of 0.5, 0.75, 1.0, and 1.25 m from the tree center. Buttressed parts of roots had greater lateral and vertical secondary thickening above rather than below the biological center. This uneven growth, which produced a shape similar in cross section to a T-beam, was greater on the leeward side of the tree, and was greatest at 0.5 m from the tree center of shallow rooted trees. Further from the tree, particularly on the windward side, many roots developed eccentric cross-sectional shapes comparable to I-beams, which would efficiently resist vertical flexing. Roots became more ovoid in shape with increasing distance from the tree, especially on deep rooted trees where lateral roots tapered rapidly to a small diameter. We conclude that these forms of adaptive growth in response to wind movement improve the rigidity of the soil-root plate and counteract the increasing vulnerability to windthrow as the tree grows.

  20. Adaptive responses of energy storage and fish life histories to climatic gradients. (United States)

    Giacomini, Henrique C; Shuter, Brian J


    Energy storage is a common adaptation of fish living in seasonal environments. For some species, the energy accumulated during the growing season, and stored primarily as lipids, is crucial to preventing starvation mortality over winter. Thus, in order to understand the adaptive responses of fish life history to climate, it is important to determine how energy should be allocated to storage and how it trades off with the other body components that contribute to fitness. In this paper, we extend previous life history theory to include an explicit representation of how the seasonal allocation of energy to storage acts as a constraint on fish growth. We show that a strategy that privileges allocation to structural mass in the first part of the growing season and switches to storage allocation later on, as observed empirically in several fish species, is the strategy that maximizes growth efficiency and hence is expected to be favored by natural selection. Stochastic simulations within this theoretical framework demonstrate that the relative performance of this switching strategy is robust to a wide range of fluctuations in growing season length, and to moderate short-term (i.e., daily) fluctuations in energy intake and/or expenditure within the growing season. We then integrate this switching strategy with a biphasic growth modeling framework to predict typical growth rates of walleye Sander vitreus, a cool water species, and lake trout Salvelinus namaycush, a cold water specialist, across a climatic gradient in North America. As predicted, growth rates increased linearly with the duration of the growing season. Regression line intercepts were negative, indicating that growth can only occur when growing season length exceeds a threshold necessary to produce storage for winter survival. The model also reveals important differences between species, showing that observed growth rates of lake trout are systematically higher than those of walleye in relatively colder lakes

  1. Hurricane Sandy: Caught in the eye of the storm and a city's adaptation response (United States)

    Orton, P. M.; Horton, R. M.; Blumberg, A. F.; Rosenzweig, C.; Solecki, W.; Bader, D.


    The NOAA RISA program has funded the seven-institution Consortium for Climate Risk in the Urban Northeast (CCRUN) for the past five years to serve stakeholder needs in assessing and managing risks from climate variability and change. When Hurricane Sandy struck, we were in an ideal position, making flood forecasts and communicating NOAA forecasts to the public with dozens of media placements, translating the poorly understood flood forecasts into human dimensions. In 2013 and 2015, by request of New York City (NYC), we worked through the NYC Panel on Climate Change to deliver updated climate risk assessment reports, to be used in the post-Sandy rebuilding and resiliency efforts. These utilized innovative methodologies for probabilistic local and regional sea level change projections, and contrasted methods of dynamic versus (the more common) static flood mapping. We participated in a federal-academic partnership that developed a Sea Level Tool for Sandy Recovery that integrates CCRUN sea level rise projections with policy-relevant FEMA flood maps, and now several updated flood maps and coastal flood mapping tools (NOAA, FEMA, and USACE) incorporate our projections. For the adaptation response, we helped develop NYC's $20 billion flood adaptation plan, and we were on a winning team under the Housing and Urban Development Rebuild By Design (RBD) competition, a few of the many opportunities that arose with negligible additional funding and which CCRUN funds supported. Our work at times disrupted standard lines of thinking, but NYC showed an openness to altering course. In one case we showed that an NYC plan of wetland restoration in Jamaica Bay would provide no reduction in flooding unless deep-dredged channels circumventing them were shallowed or narrowed. In another, the lead author's RBD team challenged the notion at one location that levees were the solution to accelerating sea level rise, developing a plan to use ecological breakwaters and layered components of

  2. Adaptation of the Agrobacterium tumefaciens VirG response regulator to activate transcription in plants. (United States)

    Czarnecka-Verner, Eva; Salem, Tarek A; Gurley, William B


    The Agrobacterium tumefaciens VirG response regulator of the VirA/VirG two-component system was adapted to function in tobacco protoplasts. The subcellular localization of VirG and VirA proteins transiently expressed in onion cells was determined using GFP fusions. Preliminary studies using Gal4DBD-VP16 fusions with VirG and Escherichia coli UhpA, and NarL response regulators indicated compatibility of these bacterial proteins with the eukaryotic transcriptional apparatus. A strong transcriptional activator based on tandem activation domains from the Drosophila fushi tarazu and Herpes simplex VP16 was created. Selected configurations of the two-site Gal4-vir box GUS reporters were activated by chimeric effectors dependent on either the yeast Gal4 DNA-binding domain or that of VirG. Transcriptional induction of the GUS reporter was highest for the VirE19-element promoter with both constitutive and wild-type VirG-tandem activation domain effectors. Multiple VirE19 elements increased the reporter activity proportionately, indicating that the VirG DNA binding domain was functional in plants. The VirG constitutive-Q-VP16 effector was more active than the VirG wild-type. In both the constitutive and wild-type forms of VirG, Q-VP16 activated transcription of the GUS reporter best when located at the C-terminus, i.e. juxtaposed to the VirG DNA binding domain. These results demonstrate the possibility of using DNA binding domains from bacterial response regulators and their cognate binding elements in the engineering of plant gene expression.

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

    Directory of Open Access Journals (Sweden)

    W. R.J. Dean


    Full Text Available Human adaptation and response to drought is primarily through evasion or endurance. A review of historical agricultural practices in southern Africa demonstrates evidence of drought evasion response strategies in well-established transhumance routes, where herders move livestock on a seasonal basis in order to exploit resources subject to different climatic regimes. European settlers to the arid regions of South Africa quickly recognised the necessity of these evasion options to survive drought, and adopted the transhumance practices of indigenous farmers. Areas of geographically diverse resource bases became hotly contested by settlers and indigenous farmers. The success of evasion systems are shown to hinge on good social and institutional support structures. When movement is not an option, drought endurance is pursued by attempting to limit the damage to the natural resource base. This is through a number of means such as forage conservation, varying livestock types and numbers, water and soil conservation and taking up alternative livelihood options. State responses to drought over the last century reflect the general South African pattern of racially divided and unjust policies relating to resource access. Historically the state provided considerable support to white commercial farmers. This support was frequently contradictory in its aims and generally was inadequate to enable farmers to cope with drought. Since the advent of democracy in 1994, the state has intervened less, with some support extended to previously disadvantaged and poor communal farmers. Climate change predictions suggest an increase in drought, suggesting that the adoption of mitigating strategies should be a matter of urgency. To do this South Africa needs to build social and institutional capacity, strive for better economic and environmental sustainability, embed drought-coping mechanisms into land restitution policy to ensure the success of this programme, and

  4. Early-phase muscular adaptations in response to slow-speed versus traditional resistance-training regimens. (United States)

    Schuenke, Mark D; Herman, Jennifer R; Gliders, Roger M; Hagerman, Fredrick C; Hikida, Robert S; Rana, Sharon R; Ragg, Kerry E; Staron, Robert S


    Thirty-four untrained women participated in a 6-week program to investigate slow-speed versus "normal" speed resistance-training protocols. Subjects were divided into: slow-speed (SS), normal-speed/traditional-strength (TS), normal-speed/traditional muscular endurance (TE), and non-exercising control (C) groups. Leg press, squats, and knee extensions were performed 2 days/week for the first week and 3 days/week for the remaining 5 weeks (~2 min rest). The SS group performed 6-10 repetitions maximum (6-10RM) for each set with 10 s concentric (con) and 4 s eccentric (ecc) contractions. The TS and TE groups performed sets of 6-10RM and 20-30RM, respectively, at "normal" speed (1-2 s/con and ecc contractions). TE and SS trained at the same relative intensity (~40-60% 1RM), whereas TS trained at ~80-85% 1RM. Pre- and post-training muscle biopsies were analyzed for fiber-type composition, cross-sectional area (CSA), and myosin heavy chain (MHC) content. The percentage of type IIX fibers decreased and IIAX increased in all three training groups. However, only TS showed an increase in percentage of type IIA fibers. CSA of fiber types I, IIA, and IIX increased in TS. In SS, only the CSA of IIA and IIX fibers increased. These changes were supported by MHC data. No significant changes for any parameters were found for the C group. In conclusion, slow-speed strength training induced a greater adaptive response compared to training with a similar resistance at "normal" speed. However, training with a higher intensity at "normal" speed resulted in the greatest overall muscle fiber response in each of the variables assessed.

  5. Sphingolipid biosynthesis upregulation by TOR complex 2-Ypk1 signaling during yeast adaptive response to acetic acid stress. (United States)

    Guerreiro, Joana F; Muir, Alexander; Ramachandran, Subramaniam; Thorner, Jeremy; Sá-Correia, Isabel


    Acetic acid-induced inhibition of yeast growth and metabolism limits the productivity of industrial fermentation processes, especially when lignocellulosic hydrolysates are used as feedstock in industrial biotechnology. Tolerance to acetic acid of food spoilage yeasts is also a problem in the preservation of acidic foods and beverages. Thus understanding the molecular mechanisms underlying adaptation and tolerance to acetic acid stress is increasingly important in industrial biotechnology and the food industry. Prior genetic screens for Saccharomyces cerevisiae mutants with increased sensitivity to acetic acid identified loss-of-function mutations in the YPK1 gene, which encodes a protein kinase activated by the target of rapamycin (TOR) complex 2 (TORC2). We show in the present study by several independent criteria that TORC2-Ypk1 signaling is stimulated in response to acetic acid stress. Moreover, we demonstrate that TORC2-mediated Ypk1 phosphorylation and activation is necessary for acetic acid tolerance, and occurs independently of Hrk1, a protein kinase previously implicated in the cellular response to acetic acid. In addition, we show that TORC2-Ypk1-mediated activation of l-serine:palmitoyl-CoA acyltransferase, the enzyme complex that catalyzes the first committed step of sphingolipid biosynthesis, is required for acetic acid tolerance. Furthermore, analysis of the sphingolipid pathway using inhibitors and mutants indicates that it is production of certain complex sphingolipids that contributes to conferring acetic acid tolerance. Consistent with that conclusion, promoting sphingolipid synthesis by adding exogenous long-chain base precursor phytosphingosine to the growth medium enhanced acetic acid tolerance. Thus appropriate modulation of the TORC2-Ypk1-sphingolipid axis in industrial yeast strains may have utility in improving fermentations of acetic acid-containing feedstocks.

  6. Complex adaptive responses during antagonistic coevolution between Tribolium castaneum and its natural parasite Nosema whitei revealed by multiple fitness components

    Directory of Open Access Journals (Sweden)

    Bérénos Camillo


    Full Text Available Abstract Background Host-parasite coevolution can lead to local adaptation of either parasite or host if there is specificity (GxG interactions and asymmetric evolutionary potential between host and parasite. This has been demonstrated both experimentally and in field studies, but a substantial proportion of studies fail to detect such clear-cut patterns. One explanation for this is that adaptation can be masked by counter-adaptation by the antagonist. Additionally, genetic architecture underlying the interaction is often highly complex thus preventing specific adaptive responses. Here, we have employed a reciprocal cross-infection experiment to unravel the adaptive responses of two components of fitness affecting both parties with different complexities of the underlying genetic architecture (i.e. mortality and spore load. Furthermore, our experimental coevolution of hosts (Tribolium castaneum and parasites (Nosema whitei included paired replicates of naive hosts from identical genetic backgrounds to allow separation between host- and parasite-specific responses. Results In hosts, coevolution led to higher resistance and altered resistance profiles compared to paired control lines. Host genotype × parasite genotype interactions (GH × GP were observed for spore load (the trait of lower genetic complexity, but not for mortality. Overall parasite performance correlated with resistance of its matching host coevolution background reflecting a directional and unspecific response to strength of selection during coevolution. Despite high selective pressures exerted by the obligatory killing parasite, and host- and parasite-specific mortality profiles, no general pattern of local adaptation was observed, but one case of parasite maladaptation was consistently observed on both coevolved and control host populations. In addition, the use of replicate control host populations in the assay revealed one case of host maladaptation and one case of parasite

  7. Natural background radiation induces cytogenetic radioadaptive response more effectively than occupational exposure in human peripheral blood lymphocytes (United States)

    Monfared, A. Shabestani; Mozdarani, H.; Amiri, M.


    Ramsar, a city in the northern Iran, has the highest level of natural background radiation in the world. It has been clearly shown that low doses of ionising radiation can induce resistance to subsequent higher exposures. This phenomenon is termed radioadaptive response. We have compared induction of cytogenetic radioadaptive response by High Natural Background Radiation (HNBR) in Ramsar and X-ray occupational exposure as conditioning doses in human peripheral blood lymphocytes. 30 healthy control individuals, living in Ramsar but in normal background radiation areas, 15 healthy individuals from Talesh Mahalleh, a region with extraordinary high level of background radiation, and 7 X-ray radiographers working in Ramsar hospital located in normal natural background ionising radiation area were evaluated. Peripheral blood samples were prepared and exposed to challenge dose of 0 and 2 Gy. Lymphocytes were scored using analysis of metaphase, for the presence of chromosomal aberrations. An adaptive response was observed in HNBR and radiation workers groups in comparison with sham controls. A significant increase in adaptive response was observed in the HNBR group if compared with the occupationally exposed group. These findings indicate that both natural background radiation and occupational exposure could induce cytogenetic radioadaptive response and it is more significant regarding to natural background ionising radiation.

  8. Sublingual vaccination induces mucosal and systemic adaptive immunity for protection against lung tumor challenge. (United States)

    Singh, Shailbala; Yang, Guojun; Schluns, Kimberly S; Anthony, Scott M; Sastry, K Jagannadha


    Sublingual route offers a safer and more practical approach for delivering vaccines relative to other systemic and mucosal immunization strategies. Here we present evidence demonstrating protection against ovalbumin expressing B16 (B16-OVA) metastatic melanoma lung tumor formation by sublingual vaccination with the model tumor antigen OVA plus synthetic glycolipid alpha-galactosylceramide (aGalCer) for harnessing the adjuvant potential of natural killer T (NKT) cells, which effectively bridge innate and adaptive arms of the immune system. The protective efficacy of immunization with OVA plus aGalCer was antigen-specific as immunized mice challenged with parental B16 tumors lacking OVA expression were not protected. Multiple sublingual immunizations in the presence, but not in the absence of aGalCer, resulted in repeated activation of NKT cells in the draining lymph nodes, spleens, and lungs of immunized animals concurrent with progressively increasing OVA-specific CD8+ T cell responses as well as serum IgG and vaginal IgA levels. Furthermore, sublingual administration of the antigen only in the presence of the aGalCer adjuvant effectively boosted the OVA-specific immune responses. These results support potential clinical utility of sublingual route of vaccination with aGalCer-for prevention of pulmonary metastases.

  9. Sublingual vaccination induces mucosal and systemic adaptive immunity for protection against lung tumor challenge.

    Directory of Open Access Journals (Sweden)

    Shailbala Singh

    Full Text Available Sublingual route offers a safer and more practical approach for delivering vaccines relative to other systemic and mucosal immunization strategies. Here we present evidence demonstrating protection against ovalbumin expressing B16 (B16-OVA metastatic melanoma lung tumor formation by sublingual vaccination with the model tumor antigen OVA plus synthetic glycolipid alpha-galactosylceramide (aGalCer for harnessing the adjuvant potential of natural killer T (NKT cells, which effectively bridge innate and adaptive arms of the immune system. The protective efficacy of immunization with OVA plus aGalCer was antigen-specific as immunized mice challenged with parental B16 tumors lacking OVA expression were not protected. Multiple sublingual immunizations in the presence, but not in the absence of aGalCer, resulted in repeated activation of NKT cells in the draining lymph nodes, spleens, and lungs of immunized animals concurrent with progressively increasing OVA-specific CD8+ T cell responses as well as serum IgG and vaginal IgA levels. Furthermore, sublingual administration of the antigen only in the presence of the aGalCer adjuvant effectively boosted the OVA-specific immune responses. These results support potential clinical utility of sublingual route of vaccination with aGalCer-for prevention of pulmonary metastases.

  10. Local adaptation and the potential effects of a contaminant on predator avoidance and antipredator responses under global warming: a space-for-time substitution approach. (United States)

    Janssens, Lizanne; Dinh Van, Khuong; Debecker, Sara; Bervoets, Lieven; Stoks, Robby


    The ability to deal with temperature-induced changes in interactions with contaminants and predators under global warming is one of the outstanding, applied evolutionary questions. For this, it is crucial to understand how contaminants will affect activity levels, predator avoidance and antipredator responses under global warming and to what extent gradual thermal evolution may mitigate these effects. Using a space-for-time substitution approach, we assessed the potential for gradual thermal evolution shaping activity (mobility and foraging), predator avoidance and antipredator responses when Ischnura elegans damselfly larvae were exposed to zinc in a common-garden warming experiment at the mean summer water temperatures of shallow water bodies at southern and northern latitudes (24 and 20°C, respectively). Zinc reduced mobility and foraging, predator avoidance and escape swimming speed. Importantly, high-latitude populations showed stronger zinc-induced reductions in escape swimming speed at both temperatures, and in activity levels at the high temperature. The latter indicates that local thermal adaptation may strongly change the ecological impact of contaminants under global warming. Our study underscores the critical importance of considering local adaptation along natural gradients when integrating biotic interactions in ecological risk assessment, and the potential of gradual thermal evolution mitigating the effects of warming on the vulnerability to contaminants.

  11. Daily rhythmicity of the thermoregulatory responses of locally adapted Brazilian sheep in a semiarid environment (United States)

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


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

  12. Prolonged inorganic arsenite exposure suppresses insulin-stimulated AKT S473 phosphorylation and glucose uptake in 3T3-L1 adipocytes: Involvement of the adaptive antioxidant response

    Energy Technology Data Exchange (ETDEWEB)

    Xue, Peng [The Hamner Institutes for Health Sciences, Research Triangle Park, NC 27709 (United States); School of Public Health, China Medical University, Shenyang 110001 (China); Hou, Yongyong; Zhang, Qiang; Woods, Courtney G.; Yarborough, Kathy; Liu, Huiyu [The Hamner Institutes for Health Sciences, Research Triangle Park, NC 27709 (United States); Sun, Guifan [School of Public Health, China Medical University, Shenyang 110001 (China); Andersen, Melvin E. [The Hamner Institutes for Health Sciences, Research Triangle Park, NC 27709 (United States); Pi, Jingbo, E-mail: [The Hamner Institutes for Health Sciences, Research Triangle Park, NC 27709 (United States)


    Highlights: {yields} In 3T3-L1 adipocytes iAs{sup 3+} decreases insulin-stimulated glucose uptake. {yields} iAs{sup 3+} attenuates insulin-induced phosphorylation of AKT S473. {yields} iAs{sup 3+} activates the cellular adaptive oxidative stress response. {yields} iAs{sup 3+} impairs insulin-stimulated ROS signaling. {yields} iAs{sup 3+} decreases expression of adipogenic genes and GLUT4. -- Abstract: There is growing evidence that chronic exposure of humans to inorganic arsenic, a potent environmental oxidative stressor, is associated with the incidence of type 2 diabetes (T2D). One critical feature of T2D is insulin resistance in peripheral tissues, especially in mature adipocytes, the hallmark of which is decreased insulin-stimulated glucose uptake (ISGU). Despite the deleterious effects of reactive oxygen species (ROS), they have been recognized as a second messenger serving an intracellular signaling role for insulin action. Nuclear factor erythroid 2-related factor 2 (NRF2) is a central transcription factor regulating cellular adaptive response to oxidative stress. This study proposes that in response to arsenic exposure, the NRF2-mediated adaptive induction of endogenous antioxidant enzymes blunts insulin-stimulated ROS signaling and thus impairs ISGU. Exposure of differentiated 3T3-L1 cells to low-level (up to 2 {mu}M) inorganic arsenite (iAs{sup 3+}) led to decreased ISGU in a dose- and time-dependent manner. Concomitant to the impairment of ISGU, iAs{sup 3+} exposure significantly attenuated insulin-stimulated intracellular ROS accumulation and AKT S473 phosphorylation, which could be attributed to the activation of NRF2 and induction of a battery of endogenous antioxidant enzymes. In addition, prolonged iAs{sup 3+} exposure of 3T3-L1 adipocytes resulted in significant induction of inflammatory response genes and decreased expression of adipogenic genes and glucose transporter type 4 (GLUT4), suggesting chronic inflammation and reduction in GLUT4

  13. Deep-sea pennatulaceans (sea pens) - recent discoveries, morphological adaptations, and responses to benthic oceanographic parameters (United States)

    Williams, G. C.


    Pennatulaceans are sessile, benthic marine organisms that are bathymetrically wide-ranging, from the intertidal to approximately 6300 m in depth, and are conspicuous constituents of deep-sea environments. The vast majority of species are adapted for anchoring in soft sediments by the cylindrical peduncle - a muscular hydrostatic skeleton. However, in the past decade a few species ("Rockpens") have been discovered and described that can attach to hard substratum such as exposed rocky outcrops at depths between 669 and 1969 m, by a plunger-like adaptation of the base of the peduncle. Of the thirty-six known genera, eleven (or 30%) have been recorded from depths greater than 1000 m. The pennatulacean depth record holders are an unidentified species of Umbellula from 6260 m in the Peru-Chile Trench and a recently-discovered and described genus and species, Porcupinella profunda, from 5300 m the Porcupine Abyssal Plain of the northeastern Atlantic. A morphologically-differentiated type of polyp (acrozooid) have recently been discovered and described in two genera of shallow-water coral reef sea pens. Acrozooids apparently represent asexual buds and presumably can detach from the adult to start clonal colonies through asexual budding. Acrozooids are to be expected in deep-sea pennatulaceans, but so far have not been observed below 24 m in depth. Morphological responses at depths greater than 1000 m in deep-sea pennatulaceas include: fewer polyps, larger polyps, elongated stalks, and clustering of polyps along the rachis. Responses to deep-ocean physical parameters and anthropogenic changes that could affect the abundance and distribution of deep-sea pennatulaceans include changes in bottom current flow and food availability, changes in seawater temperature and pH, habitat destruction by fish trawling, and sunken refuse pollution. No evidence of the effects of ocean acidification or other effects of anthropogenic climate change in sea pens of the deep-sea has been

  14. OH* imager response to turbulence-induced temperature fluctuations (United States)

    Gardner, Chester S.; Vargas, Fabio A.


    The layer of the excited state hydroxyl radical (OH*) is formed in the mesopause region by the reaction of ozone (O3) and atomic hydrogen (H). We derive the theoretical expressions for the OH* brightness and rotational temperature (T*) responses to high-frequency atmospheric temperature perturbations. The theory is used to calculate the 1-D and 2-D horizontal wave number spectra of the OH* and T* image fluctuations induced by atmospheric turbulence. By applying the theory to images of a breaking gravity wave packet, acquired by the Utah State University Advanced Mesospheric Temperature Mapper, we show that existing infrared OH* imager technology can observe the evolution of gravity wave breakdown and characterize the resulting turbulent eddies in the source region and in the inertial subrange of the turbulence spectrum. For the example presented here, the RMS OH* brightness fluctuations induced by the gravity wave packet was 2.90% and by the associated turbulence was 1.07%. Unfortunately, the T* fluctuations induced by turbulence are usually too small to be observed in the OH* rotational temperature maps.

  15. Tourniquet-induced systemic inflammatory response in extremity surgery.

    LENUS (Irish Health Repository)

    Wakai, A


    BACKGROUND: Tourniquet-induced reperfusion injury in animals produces significant systemic inflammatory effects. This study investigated whether a biologic response occurs in a clinically relevant model of tourniquet-induced reperfusion injury. METHODS: Patients undergoing elective knee arthroscopy were prospectively randomized into controls (no tourniquet) and subjects (tourniquet-controlled). The effects of tourniquet-induced reperfusion on monocyte activation state, neutrophil activation state, and transendothelial migration (TEM) were studied. Changes in the cytokines implicated in reperfusion injury, tumor necrosis factor-alpha, interleukin (IL)-1beta, and IL-10 were also determined. RESULTS: After 15 minutes of reperfusion, neutrophil and monocyte activation were significantly increased. Pretreatment of neutrophils with pooled subject (ischemia-primed) plasma significantly increased TEM. In contrast, TEM was not significantly altered by ischemia-primed plasma pretreatment of the endothelial monolayer. Significant elevation of tumor necrosis factor-alpha and IL-1beta were observed in subjects compared with controls after 15 minutes of reperfusion. There was no significant difference in serum IL-10 levels between the groups at all the time points studied. CONCLUSION: These results indicate a transient neutrophil and monocyte activation after tourniquet-ischemia that translates into enhanced neutrophil transendothelial migration with potential for tissue injury.

  16. Global Megacities Differing Adaptation Responses to Climate Change: an Analysis of Annual Spend of Ten Major cities on the adaptation economy (United States)

    Maslin, M. A.; Georgeson, L.


    Urban areas are increasingly at risk from climate change with negative impacts predicted for human health, the economy and ecosystems. These risks require responses from cities, to improve the resilience of their infrastructure, economy and environment to climate change. Policymakers need to understand what is already being spent on adaptation so that they can make more effective and comprehensive adaptation plans. Through the measurement of spend in the newly defined 'Adaptation Economy' we analysis the current efforts of 10 global megacities in adapting to climate change. These cities were chosen based on their size, geographical location and their developmental status. The cities are London, Paris, New York, Mexico City, Sao Paulo, Beijing, Mumbai, Jakarta, Lagos and Addis Ababa. It is important to study a range of cities in different regions of the world, with different climates and at different states of socio-economic development. While in economic terms, disaster losses from weather, climate and geophysical events