Sample records for specific adaptive responses

  1. Stimulus change detection in phasic auditory units in the frog midbrain: frequency and ear specific adaptation.

    PubMed

    Ponnath, Abhilash; Hoke, Kim L; Farris, Hamilton E

    2013-04-01

    Neural adaptation, a reduction in the response to a maintained stimulus, is an important mechanism for detecting stimulus change. Contributing to change detection is the fact that adaptation is often stimulus specific: adaptation to a particular stimulus reduces excitability to a specific subset of stimuli, while the ability to respond to other stimuli is unaffected. Phasic cells (e.g., cells responding to stimulus onset) are good candidates for detecting the most rapid changes in natural auditory scenes, as they exhibit fast and complete adaptation to an initial stimulus presentation. We made recordings of single phasic auditory units in the frog midbrain to determine if adaptation was specific to stimulus frequency and ear of input. In response to an instantaneous frequency step in a tone, 28% of phasic cells exhibited frequency specific adaptation based on a relative frequency change (delta-f=±16%). Frequency specific adaptation was not limited to frequency steps, however, as adaptation was also overcome during continuous frequency modulated stimuli and in response to spectral transients interrupting tones. The results suggest that adaptation is separated for peripheral (e.g., frequency) channels. This was tested directly using dichotic stimuli. In 45% of binaural phasic units, adaptation was ear specific: adaptation to stimulation of one ear did not affect responses to stimulation of the other ear. Thus, adaptation exhibited specificity for stimulus frequency and lateralization at the level of the midbrain. This mechanism could be employed to detect rapid stimulus change within and between sound sources in complex acoustic environments.

  2. Stimulus change detection in phasic auditory units in the frog midbrain: frequency and ear specific adaptation

    PubMed Central

    Ponnath, Abhilash; Hoke, Kim L.

    2013-01-01

    Neural adaptation, a reduction in the response to a maintained stimulus, is an important mechanism for detecting stimulus change. Contributing to change detection is the fact that adaptation is often stimulus specific: adaptation to a particular stimulus reduces excitability to a specific subset of stimuli, while the ability to respond to other stimuli is unaffected. Phasic cells (e.g., cells responding to stimulus onset) are good candidates for detecting the most rapid changes in natural auditory scenes, as they exhibit fast and complete adaptation to an initial stimulus presentation. We made recordings of single phasic auditory units in the frog midbrain to determine if adaptation was specific to stimulus frequency and ear of input. In response to an instantaneous frequency step in a tone, 28 % of phasic cells exhibited frequency specific adaptation based on a relative frequency change (delta-f = ±16 %). Frequency specific adaptation was not limited to frequency steps, however, as adaptation was also overcome during continuous frequency modulated stimuli and in response to spectral transients interrupting tones. The results suggest that adaptation is separated for peripheral (e.g., frequency) channels. This was tested directly using dichotic stimuli. In 45 % of binaural phasic units, adaptation was ear specific: adaptation to stimulation of one ear did not affect responses to stimulation of the other ear. Thus, adaptation exhibited specificity for stimulus frequency and lateralization at the level of the midbrain. This mechanism could be employed to detect rapid stimulus change within and between sound sources in complex acoustic environments. PMID:23344947

  3. Statistical context shapes stimulus-specific adaptation in human auditory cortex

    PubMed Central

    Henry, Molly J.; Fromboluti, Elisa Kim; McAuley, J. Devin

    2015-01-01

    Stimulus-specific adaptation is the phenomenon whereby neural response magnitude decreases with repeated stimulation. Inconsistencies between recent nonhuman animal recordings and computational modeling suggest dynamic influences on stimulus-specific adaptation. The present human electroencephalography (EEG) study investigates the potential role of statistical context in dynamically modulating stimulus-specific adaptation by examining the auditory cortex-generated N1 and P2 components. As in previous studies of stimulus-specific adaptation, listeners were presented with oddball sequences in which the presentation of a repeated tone was infrequently interrupted by rare spectral changes taking on three different magnitudes. Critically, the statistical context varied with respect to the probability of small versus large spectral changes within oddball sequences (half of the time a small change was most probable; in the other half a large change was most probable). We observed larger N1 and P2 amplitudes (i.e., release from adaptation) for all spectral changes in the small-change compared with the large-change statistical context. The increase in response magnitude also held for responses to tones presented with high probability, indicating that statistical adaptation can overrule stimulus probability per se in its influence on neural responses. Computational modeling showed that the degree of coadaptation in auditory cortex changed depending on the statistical context, which in turn affected stimulus-specific adaptation. Thus the present data demonstrate that stimulus-specific adaptation in human auditory cortex critically depends on statistical context. Finally, the present results challenge the implicit assumption of stationarity of neural response magnitudes that governs the practice of isolating established deviant-detection responses such as the mismatch negativity. PMID:25652920

  4. Statistical context shapes stimulus-specific adaptation in human auditory cortex.

    PubMed

    Herrmann, Björn; Henry, Molly J; Fromboluti, Elisa Kim; McAuley, J Devin; Obleser, Jonas

    2015-04-01

    Stimulus-specific adaptation is the phenomenon whereby neural response magnitude decreases with repeated stimulation. Inconsistencies between recent nonhuman animal recordings and computational modeling suggest dynamic influences on stimulus-specific adaptation. The present human electroencephalography (EEG) study investigates the potential role of statistical context in dynamically modulating stimulus-specific adaptation by examining the auditory cortex-generated N1 and P2 components. As in previous studies of stimulus-specific adaptation, listeners were presented with oddball sequences in which the presentation of a repeated tone was infrequently interrupted by rare spectral changes taking on three different magnitudes. Critically, the statistical context varied with respect to the probability of small versus large spectral changes within oddball sequences (half of the time a small change was most probable; in the other half a large change was most probable). We observed larger N1 and P2 amplitudes (i.e., release from adaptation) for all spectral changes in the small-change compared with the large-change statistical context. The increase in response magnitude also held for responses to tones presented with high probability, indicating that statistical adaptation can overrule stimulus probability per se in its influence on neural responses. Computational modeling showed that the degree of coadaptation in auditory cortex changed depending on the statistical context, which in turn affected stimulus-specific adaptation. Thus the present data demonstrate that stimulus-specific adaptation in human auditory cortex critically depends on statistical context. Finally, the present results challenge the implicit assumption of stationarity of neural response magnitudes that governs the practice of isolating established deviant-detection responses such as the mismatch negativity. Copyright © 2015 the American Physiological Society.

  5. The specificity of stimulus-specific adaptation in human auditory cortex increases with repeated exposure to the adapting stimulus.

    PubMed

    Briley, Paul M; Krumbholz, Katrin

    2013-12-01

    The neural response to a sensory stimulus tends to be more strongly reduced when the stimulus is preceded by the same, rather than a different, stimulus. This stimulus-specific adaptation (SSA) is ubiquitous across the senses. In hearing, SSA has been suggested to play a role in change detection as indexed by the mismatch negativity. This study sought to test whether SSA, measured in human auditory cortex, is caused by neural fatigue (reduction in neural responsiveness) or by sharpening of neural tuning to the adapting stimulus. For that, we measured event-related cortical potentials to pairs of pure tones with varying frequency separation and stimulus onset asynchrony (SOA). This enabled us to examine the relationship between the degree of specificity of adaptation as a function of frequency separation and the rate of decay of adaptation with increasing SOA. Using simulations of tonotopic neuron populations, we demonstrate that the fatigue model predicts independence of adaptation specificity and decay rate, whereas the sharpening model predicts interdependence. The data showed independence and thus supported the fatigue model. In a second experiment, we measured adaptation specificity after multiple presentations of the adapting stimulus. The multiple adapters produced more adaptation overall, but the effect was more specific to the adapting frequency. Within the context of the fatigue model, the observed increase in adaptation specificity could be explained by assuming a 2.5-fold increase in neural frequency selectivity. We discuss possible bottom-up and top-down mechanisms of this effect.

  6. Polymicrobial sepsis and non-specific immunization induce adaptive immunosuppression to a similar degree.

    PubMed

    Schmoeckel, Katrin; Mrochen, Daniel M; Hühn, Jochen; Pötschke, Christian; Bröker, Barbara M

    2018-01-01

    Sepsis is frequently complicated by a state of profound immunosuppression, in its extreme form known as immunoparalysis. We have studied the role of the adaptive immune system in the murine acute peritonitis model. To read out adaptive immunosuppression, we primed post-septic and control animals by immunization with the model antigen TNP-ovalbumin in alum, and measured the specific antibody-responses via ELISA and ELISpot assay as well as T-cell responses in a proliferation assay after restimulation. Specific antibody titers, antibody affinity and plasma cell counts in the bone marrow were reduced in post-septic animals. The antigen-induced splenic proliferation was also impaired. The adaptive immunosuppression was positively correlated with an overwhelming general antibody response to the septic insult. Remarkably, antigen "overload" by non-specific immunization induced a similar degree of adaptive immunosuppression in the absence of sepsis. In both settings, depletion of regulatory T cells before priming reversed some parameters of the immunosuppression. In conclusion, our data show that adaptive immunosuppression occurs independent of profound systemic inflammation and life-threatening illness.

  7. Polymicrobial sepsis and non-specific immunization induce adaptive immunosuppression to a similar degree

    PubMed Central

    Hühn, Jochen; Pötschke, Christian

    2018-01-01

    Sepsis is frequently complicated by a state of profound immunosuppression, in its extreme form known as immunoparalysis. We have studied the role of the adaptive immune system in the murine acute peritonitis model. To read out adaptive immunosuppression, we primed post-septic and control animals by immunization with the model antigen TNP-ovalbumin in alum, and measured the specific antibody-responses via ELISA and ELISpot assay as well as T-cell responses in a proliferation assay after restimulation. Specific antibody titers, antibody affinity and plasma cell counts in the bone marrow were reduced in post-septic animals. The antigen-induced splenic proliferation was also impaired. The adaptive immunosuppression was positively correlated with an overwhelming general antibody response to the septic insult. Remarkably, antigen “overload” by non-specific immunization induced a similar degree of adaptive immunosuppression in the absence of sepsis. In both settings, depletion of regulatory T cells before priming reversed some parameters of the immunosuppression. In conclusion, our data show that adaptive immunosuppression occurs independent of profound systemic inflammation and life-threatening illness. PMID:29415028

  8. Statistical Physics of T-Cell Development and Pathogen Specificity

    NASA Astrophysics Data System (ADS)

    Košmrlj, Andrej; Kardar, Mehran; Chakraborty, Arup K.

    2013-04-01

    In addition to an innate immune system that battles pathogens in a nonspecific fashion, higher organisms, such as humans, possess an adaptive immune system to combat diverse (and evolving) microbial pathogens. Remarkably, the adaptive immune system mounts pathogen-specific responses, which can be recalled upon reinfection with the same pathogen. It is difficult to see how the adaptive immune system can be preprogrammed to respond specifically to a vast and unknown set of pathogens. Although major advances have been made in understanding pertinent molecular and cellular phenomena, the precise principles that govern many aspects of an immune response are largely unknown. We discuss complementary approaches from statistical mechanics and cell biology that can shed light on how key components of the adaptive immune system, T cells, develop to enable pathogen-specific responses against many diverse pathogens. The mechanistic understanding that emerges has implications for how host genetics may influence the development of T cells with differing responses to the human immunodeficiency virus (HIV) infection.

  9. Face adaptation aftereffects reveal anterior medial temporal cortex role in high level category representation.

    PubMed

    Furl, N; van Rijsbergen, N J; Treves, A; Dolan, R J

    2007-08-01

    Previous studies have shown reductions of the functional magnetic resonance imaging (fMRI) signal in response to repetition of specific visual stimuli. We examined how adaptation affects the neural responses associated with categorization behavior, using face adaptation aftereffects. Adaptation to a given facial category biases categorization towards non-adapted facial categories in response to presentation of ambiguous morphs. We explored a hypothesis, posed by recent psychophysical studies, that these adaptation-induced categorizations are mediated by activity in relatively advanced stages within the occipitotemporal visual processing stream. Replicating these studies, we find that adaptation to a facial expression heightens perception of non-adapted expressions. Using comparable behavioral methods, we also show that adaptation to a specific identity heightens perception of a second identity in morph faces. We show both expression and identity effects to be associated with heightened anterior medial temporal lobe activity, specifically when perceiving the non-adapted category. These regions, incorporating bilateral anterior ventral rhinal cortices, perirhinal cortex and left anterior hippocampus are regions previously implicated in high-level visual perception. These categorization effects were not evident in fusiform or occipital gyri, although activity in these regions was reduced to repeated faces. The findings suggest that adaptation-induced perception is mediated by activity in regions downstream to those showing reductions due to stimulus repetition.

  10. The influence of surround suppression on adaptation effects in primary visual cortex

    PubMed Central

    Wissig, Stephanie C.

    2012-01-01

    Adaptation, the prolonged presentation of stimuli, has been used to probe mechanisms of visual processing in physiological, imaging, and perceptual studies. Previous neurophysiological studies have measured adaptation effects by using stimuli tailored to evoke robust responses in individual neurons. This approach provides an incomplete view of how an adapter alters the representation of sensory stimuli by a population of neurons with diverse functional properties. We implanted microelectrode arrays in primary visual cortex (V1) of macaque monkeys and measured orientation tuning and contrast sensitivity in populations of neurons before and after prolonged adaptation. Whereas previous studies in V1 have reported that adaptation causes stimulus-specific suppression of responsivity and repulsive shifts in tuning preference, we have found that adaptation can also lead to response facilitation and shifts in tuning toward the adapter. To explain this range of effects, we have proposed and tested a simple model that employs stimulus-specific suppression in both the receptive field and the spatial surround. The predicted effects on tuning depend on the relative drive provided by the adapter to these two receptive field components. Our data reveal that adaptation can have a much richer repertoire of effects on neuronal responsivity and tuning than previously considered and suggest an intimate mechanistic relationship between spatial and temporal contextual effects. PMID:22423001

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

    NASA Technical Reports Server (NTRS)

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

    1999-01-01

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

  12. Memory and Specificity in the Insect Immune System: Current Perspectives and Future Challenges.

    PubMed

    Cooper, Dustin; Eleftherianos, Ioannis

    2017-01-01

    The immune response of a host to a pathogen is typically described as either innate or adaptive. The innate form of the immune response is conserved across all organisms, including insects. Previous and recent research has focused on the nature of the insect immune system and the results imply that the innate immune response of insects is more robust and specific than previously thought. Priming of the insect innate immune system involves the exposure of insects to dead or a sublethal dose of microbes in order to elicit an initial response. Comparing subsequent infections in primed insects to non-primed individuals indicates that the insect innate immune response may possess some of the qualities of an adaptive immune system. Although some studies demonstrate that the protective effects of priming are due to a "loitering" innate immune response, others have presented more convincing elements of adaptivity. While an immune mechanism capable of producing the same degree of recognition specificity as seen in vertebrates has yet to be discovered in insects, a few interesting cases have been identified and discussed.

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

    PubMed Central

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

    2017-01-01

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

  14. Concurrent exercise training: do opposites distract?

    PubMed

    Coffey, Vernon G; Hawley, John A

    2017-05-01

    Specificity is a core principle of exercise training to promote the desired adaptations for maximising athletic performance. The principle of specificity of adaptation is underpinned by the volume, intensity, frequency and mode of contractile activity and is most evident when contrasting the divergent phenotypes that result after undertaking either prolonged endurance or resistance training. The molecular profiles that generate the adaptive response to different exercise modes have undergone intense scientific scrutiny. Given divergent exercise induces similar signalling and gene expression profiles in skeletal muscle of untrained or recreationally active individuals, what is currently unclear is how the specificity of the molecular response is modified by prior training history. The time course of adaptation and when 'phenotype specificity' occurs has important implications for exercise prescription. This context is essential when attempting to concomitantly develop resistance to fatigue (through endurance-based exercise) and increased muscle mass (through resistance-based exercise), typically termed 'concurrent training'. Chronic training studies provide robust evidence that endurance exercise can attenuate muscle hypertrophy and strength but the mechanistic underpinning of this 'interference' effect with concurrent training is unknown. Moreover, despite the potential for several key regulators of muscle metabolism to explain an incompatibility in adaptation between endurance and resistance exercise, it now seems likely that multiple integrated, rather than isolated, effectors or processes generate the interference effect. Here we review studies of the molecular responses in skeletal muscle and evidence for the interference effect with concurrent training within the context of the specificity of training adaptation. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

  15. A maturational model for the study of airway smooth muscle adaptation to mechanical oscillation.

    PubMed

    Wang, Lu; Chitano, Pasquale; Murphy, Thomas M

    2005-10-01

    It has been shown that mechanical stretches imposed on airway smooth muscle (ASM) by deep inspiration reduce the subsequent contractile response of the ASM. This passive maneuver of lengthening and retraction of the muscle is beneficial in normal subjects to counteract bronchospasm. However, it is detrimental to hyperresponsive airways because it triggers further bronchoconstriction. Although the exact mechanisms for this contrary response by normal and hyperresponsive airways are unclear, it has been suggested that the phenomenon is related to changes in ASM adaptability to mechanical oscillation. Healthy immature airways of both human and animal exhibit hyperresponsiveness, but whether the adaptative properties of hyperresponsive airway differ from normal is still unknown. In this article, we review the phenomenon of ASM adaptation to mechanical oscillation and its relevance and implication to airway hyperresponsiveness. We demonstrate that the age-specific expression of ASM adaptation is prominent using an established maturational animal model developed in our laboratory. Our data on immature ASM showed potentiated contractile force shortly after a length oscillation compared with the maximum force generated before oscillation. Several potential mechanisms such as myogenic response, changes in actin polymerization, or changes in the quantity of the cytoskeletal regulatory proteins plectin and vimentin, which may underlie this age-specific force potentiation, are discussed. We suggest a working model of the structure of smooth muscle associated with force transmission, which may help to elucidate the mechanisms responsible for the age-specific expression of smooth muscle adaptation. It is important to study the maturational profile of ASM adaptation as it could contribute to juvenile hyperresponsiveness.

  16. Concurrent exercise training: do opposites distract?

    PubMed Central

    Coffey, Vernon G.

    2016-01-01

    Abstract Specificity is a core principle of exercise training to promote the desired adaptations for maximising athletic performance. The principle of specificity of adaptation is underpinned by the volume, intensity, frequency and mode of contractile activity and is most evident when contrasting the divergent phenotypes that result after undertaking either prolonged endurance or resistance training. The molecular profiles that generate the adaptive response to different exercise modes have undergone intense scientific scrutiny. Given divergent exercise induces similar signalling and gene expression profiles in skeletal muscle of untrained or recreationally active individuals, what is currently unclear is how the specificity of the molecular response is modified by prior training history. The time course of adaptation and when ‘phenotype specificity’ occurs has important implications for exercise prescription. This context is essential when attempting to concomitantly develop resistance to fatigue (through endurance‐based exercise) and increased muscle mass (through resistance‐based exercise), typically termed ‘concurrent training’. Chronic training studies provide robust evidence that endurance exercise can attenuate muscle hypertrophy and strength but the mechanistic underpinning of this ‘interference’ effect with concurrent training is unknown. Moreover, despite the potential for several key regulators of muscle metabolism to explain an incompatibility in adaptation between endurance and resistance exercise, it now seems likely that multiple integrated, rather than isolated, effectors or processes generate the interference effect. Here we review studies of the molecular responses in skeletal muscle and evidence for the interference effect with concurrent training within the context of the specificity of training adaptation. PMID:27506998

  17. A review: Development of a microdose model for analysis of adaptive response and bystander dose response behavior.

    PubMed

    Leonard, Bobby E

    2008-02-27

    Prior work has provided incremental phases to a microdosimetry modeling program to describe the dose response behavior of the radio-protective adaptive response effect. We have here consolidated these prior works (Leonard 2000, 2005, 2007a, 2007b, 2007c) to provide a composite, comprehensive Microdose Model that is also herein modified to include the bystander effect. The nomenclature for the model is also standardized for the benefit of the experimental cellular radio-biologist. It extends the prior work to explicitly encompass separately the analysis of experimental data that is 1.) only dose dependent and reflecting only adaptive response radio-protection, 2.) both dose and dose-rate dependent data and reflecting only adaptive response radio-protection for spontaneous and challenge dose damage, 3.) only dose dependent data and reflecting both bystander deleterious damage and adaptive response radio-protection (AR-BE model). The Appendix cites the various applications of the model. Here we have used the Microdose Model to analyze the, much more human risk significant, Elmore et al (2006) data for the dose and dose rate influence on the adaptive response radio-protective behavior of HeLa x Skin cells for naturally occurring, spontaneous chromosome damage from a Brachytherapy type (125)I photon radiation source. We have also applied the AR-BE Microdose Model to the Chromosome inversion data of Hooker et al (2004) reflecting both low LET bystander and adaptive response effects. The micro-beam facility data of Miller et al (1999), Nagasawa and Little (1999) and Zhou et al (2003) is also examined. For the Zhou et al (2003) data, we use the AR-BE model to estimate the threshold for adaptive response reduction of the bystander effect. The mammogram and diagnostic X-ray induction of AR and protective BE are observed. We show that bystander damage is reduced in the similar manner as spontaneous and challenge dose damage as shown by the Azzam et al (1996) data. We cite primary unresolved questions regarding adaptive response behavior and bystander behavior. The five features of major significance provided by the Microdose Model so far are 1. Single Specific Energy Hits initiate Adaptive Response. 2. Mammogram and diagnostic X-rays induce a protective Bystander Effect as well as Adaptive Response radio-protection. 3. For mammogram X-rays the Adaptive Response protection is retained at high primer dose levels. 4. The dose range of the AR protection depends on the value of the Specific Energy per Hit, 1 >. 5. Alpha particle induced deleterious Bystander damage is modulated by low LET radiation.

  18. HIV-1 adaptation to antigen processing results in population-level immune evasion and affects subtype diversification.

    PubMed

    Tenzer, Stefan; Crawford, Hayley; Pymm, Phillip; Gifford, Robert; Sreenu, Vattipally B; Weimershaus, Mirjana; de Oliveira, Tulio; Burgevin, Anne; Gerstoft, Jan; Akkad, Nadja; Lunn, Daniel; Fugger, Lars; Bell, John; Schild, Hansjörg; van Endert, Peter; Iversen, Astrid K N

    2014-04-24

    The recent HIV-1 vaccine failures highlight the need to better understand virus-host interactions. One key question is why CD8(+) T cell responses to two HIV-Gag regions are uniquely associated with delayed disease progression only in patients expressing a few rare HLA class I variants when these regions encode epitopes presented by ~30 more common HLA variants. By combining epitope processing and computational analyses of the two HIV subtypes responsible for ~60% of worldwide infections, we identified a hitherto unrecognized adaptation to the antigen-processing machinery through substitutions at subtype-specific motifs. Multiple HLA variants presenting epitopes situated next to a given subtype-specific motif drive selection at this subtype-specific position, and epitope abundances correlate inversely with the HLA frequency distribution in affected populations. This adaptation reflects the sum of intrapatient adaptations, is predictable, facilitates viral subtype diversification, and increases global HIV diversity. Because low epitope abundance is associated with infrequent and weak T cell responses, this most likely results in both population-level immune evasion and inadequate responses in most people vaccinated with natural HIV-1 sequence constructs. Our results suggest that artificial sequence modifications at subtype-specific positions in vitro could refocus and reverse the poor immunogenicity of HIV proteins. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

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

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    David A. Boothman

    1999-08-11

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

  20. Direction-Specific Adaptation in Neuronal and Behavioral Responses of an Insect Mechanosensory System.

    PubMed

    Ogawa, Hiroto; Oka, Kotaro

    2015-08-19

    Stimulus-specific adaptation (SSA) is considered to be the neural underpinning of habituation to frequent stimuli and novelty detection. However, neither the cellular mechanism underlying SSA nor the link between SSA-like neuronal plasticity and behavioral modulation is well understood. The wind-detection system in crickets is one of the best models for investigating the neural basis of SSA. We found that crickets exhibit stimulus-direction-specific adaptation in wind-elicited avoidance behavior. Repetitive air currents inducing this behavioral adaptation reduced firings to the stimulus and the amplitude of excitatory synaptic potentials in wind-sensitive giant interneurons (GIs) related to the avoidance behavior. Injection of a Ca(2+) chelator into GIs diminished both the attenuation of firings and the synaptic depression induced by the repetitive stimulation, suggesting that adaptation of GIs induced by this stimulation results in Ca(2+)-mediated modulation of postsynaptic responses, including postsynaptic short-term depression. Some types of GIs showed specific adaptation to the direction of repetitive stimuli, resulting in an alteration of their directional tuning curves. The types of GIs for which directional tuning was altered displayed heterogeneous direction selectivity in their Ca(2+) dynamics that was restricted to a specific area of dendrites. In contrast, other types of GIs with constant directionality exhibited direction-independent global Ca(2+) elevation throughout the dendritic arbor. These results suggest that depression induced by local Ca(2+) accumulation at repetitively activated synapses of key neurons underlies direction-specific behavioral adaptation. This input-selective depression mediated by heterogeneous Ca(2+) dynamics could confer the ability to detect novelty at the earliest stages of sensory processing in crickets. Stimulus-specific adaptation (SSA) is considered to be the neural underpinning of habituation and novelty detection. We found that crickets exhibit stimulus-direction-specific adaptation in wind-elicited avoidance behavior. Repetitive air currents inducing this behavioral adaptation altered the directional selectivity of wind-sensitive giant interneurons (GIs) via direction-specific adaptation mediated by dendritic Ca(2+) elevation. The GIs for which directional tuning was altered displayed heterogeneous direction selectivity in their Ca(2+) dynamics and the transient increase in Ca(2+) evoked by the repeated puffs was restricted to a specific area of dendrites. These results suggest that depression induced by local Ca(2+) accumulation at repetitively activated synapses of key neurons underlies direction-specific behavioral adaptation. Our findings elucidate the subcellular mechanism underlying SSA-like neuronal plasticity related to behavioral adaptation. Copyright © 2015 the authors 0270-6474/15/3511644-12$15.00/0.

  1. Adaptive Automation Design and Implementation

    DTIC Science & Technology

    2015-09-17

    Study : Space Navigator This section demonstrates the player modeling paradigm, focusing specifically on the response generation section of the player ...human-machine system, a real-time player modeling framework for imitating a specific person’s task performance, and the Adaptive Automation System...Model . . . . . . . . . . . . . . . . . . . . . . . 13 Clustering-Based Real-Time Player Modeling . . . . . . . . . . . . . . . . . . . . . . 15 An

  2. Cell type-specific responses to salinity - the epidermal bladder cell transcriptome of Mesembryanthemum crystallinum.

    PubMed

    Oh, Dong-Ha; Barkla, Bronwyn J; Vera-Estrella, Rosario; Pantoja, Omar; Lee, Sang-Yeol; Bohnert, Hans J; Dassanayake, Maheshi

    2015-08-01

    Mesembryanthemum crystallinum (ice plant) exhibits extreme tolerance to salt. Epidermal bladder cells (EBCs), developing on the surface of aerial tissues and specialized in sodium sequestration and other protective functions, are critical for the plant's stress adaptation. We present the first transcriptome analysis of EBCs isolated from intact plants, to investigate cell type-specific responses during plant salt adaptation. We developed a de novo assembled, nonredundant EBC reference transcriptome. Using RNAseq, we compared the expression patterns of the EBC-specific transcriptome between control and salt-treated plants. The EBC reference transcriptome consists of 37 341 transcript-contigs, of which 7% showed significantly different expression between salt-treated and control samples. We identified significant changes in ion transport, metabolism related to energy generation and osmolyte accumulation, stress signalling, and organelle functions, as well as a number of lineage-specific genes of unknown function, in response to salt treatment. The salinity-induced EBC transcriptome includes active transcript clusters, refuting the view of EBCs as passive storage compartments in the whole-plant stress response. EBC transcriptomes, differing from those of whole plants or leaf tissue, exemplify the importance of cell type-specific resolution in understanding stress adaptive mechanisms. No claim to original US government works. New Phytologist © 2015 New Phytologist Trust.

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

    PubMed Central

    Leonard, Bobby E.

    2008-01-01

    Prior work has provided incremental phases to a microdosimetry modeling program to describe the dose response behavior of the radio-protective adaptive response effect. We have here consolidated these prior works (Leonard 2000, 2005, 2007a, 2007b, 2007c) to provide a composite, comprehensive Microdose Model that is also herein modified to include the bystander effect. The nomenclature for the model is also standardized for the benefit of the experimental cellular radio-biologist. It extends the prior work to explicitly encompass separately the analysis of experimental data that is 1.) only dose dependent and reflecting only adaptive response radio-protection, 2.) both dose and dose-rate dependent data and reflecting only adaptive response radio-protection for spontaneous and challenge dose damage, 3.) only dose dependent data and reflecting both bystander deleterious damage and adaptive response radio-protection (AR-BE model). The Appendix cites the various applications of the model. Here we have used the Microdose Model to analyze the, much more human risk significant, Elmore et al (2006) data for the dose and dose rate influence on the adaptive response radio-protective behavior of HeLa x Skin cells for naturally occurring, spontaneous chromosome damage from a Brachytherapy type 125I photon radiation source. We have also applied the AR-BE Microdose Model to the Chromosome inversion data of Hooker et al (2004) reflecting both low LET bystander and adaptive response effects. The micro-beam facility data of Miller et al (1999), Nagasawa and Little (1999) and Zhou et al (2003) is also examined. For the Zhou et al (2003) data, we use the AR-BE model to estimate the threshold for adaptive response reduction of the bystander effect. The mammogram and diagnostic X-ray induction of AR and protective BE are observed. We show that bystander damage is reduced in the similar manner as spontaneous and challenge dose damage as shown by the Azzam et al (1996) data. We cite primary unresolved questions regarding adaptive response behavior and bystander behavior. The five features of major significance provided by the Microdose Model so far are 1.) Single Specific Energy Hits initiate Adaptive Response, 2.) Mammogram and diagnostic X-rays induce a protective Bystander Effect as well as Adaptive Response radio-protection. 3.) For mammogram X-rays the Adaptive Response protection is retained at high primer dose levels. 4.) The dose range of the AR protection depends on the value of the Specific Energy per Hit, . 5.) Alpha particle induced deleterious Bystander damage is modulated by low LET radiation. PMID:18648579

  4. Kruppel-like factor 15 is required for the cardiac adaptive response to fasting.

    PubMed

    Sugi, Keiki; Hsieh, Paishiun N; Ilkayeva, Olga; Shelkay, Shamanthika; Moroney, Bridget; Baadh, Palvir; Haynes, Browning; Pophal, Megan; Fan, Liyan; Newgard, Christopher B; Prosdocimo, Domenick A; Jain, Mukesh K

    2018-01-01

    Cardiac metabolism is highly adaptive in response to changes in substrate availability, as occur during fasting. This metabolic flexibility is essential to the maintenance of contractile function and is under the control of a group of select transcriptional regulators, notably the nuclear receptor family of factors member PPARα. However, the diversity of physiologic and pathologic states through which the heart must sustain function suggests the possible existence of additional transcriptional regulators that play a role in matching cardiac metabolism to energetic demand. Here we show that cardiac KLF15 is required for the normal cardiac response to fasting. Specifically, we find that cardiac function is impaired upon fasting in systemic and cardiac specific Klf15-null mice. Further, cardiac specific Klf15-null mice display a fasting-dependent accumulation of long chain acylcarnitine species along with a decrease in expression of the carnitine translocase Slc25a20. Treatment with a diet high in short chain fatty acids relieves the KLF15-dependent long chain acylcarnitine accumulation and impaired cardiac function in response to fasting. Our observations establish KLF15 as a critical mediator of the cardiac adaptive response to fasting through its regulation of myocardial lipid utilization.

  5. Different Adjuvants Induce Common Innate Pathways That Are Associated with Enhanced Adaptive Responses against a Model Antigen in Humans

    PubMed Central

    Burny, Wivine; Callegaro, Andrea; Bechtold, Viviane; Clement, Frédéric; Delhaye, Sophie; Fissette, Laurence; Janssens, Michel; Leroux-Roels, Geert; Marchant, Arnaud; van den Berg, Robert A.; Garçon, Nathalie; van der Most, Robbert; Didierlaurent, Arnaud M.; Bechtold, Viviane

    2017-01-01

    To elucidate the role of innate responses in vaccine immunogenicity, we compared early responses to hepatitis B virus (HBV) surface antigen (HBsAg) combined with different Adjuvant Systems (AS) in healthy HBV-naïve adults, and included these parameters in multi-parametric models of adaptive responses. A total of 291 participants aged 18–45 years were randomized 1:1:1:1:1 to receive HBsAg with AS01B, AS01E, AS03, AS04, or Alum/Al(OH)3 at days 0 and 30 (ClinicalTrials.gov: NCT00805389). Blood protein, cellular, and mRNA innate responses were assessed at early time-points and up to 7 days after vaccination, and used with reactogenicity symptoms in linear regression analyses evaluating their correlation with HBs-specific CD4+ T-cell and antibody responses at day 44. All AS induced transient innate responses, including interleukin (IL)-6 and C-reactive protein (CRP), mostly peaking at 24 h post-vaccination and subsiding to baseline within 1–3 days. After the second but not the first injection, median interferon (IFN)-γ levels were increased in the AS01B group, and IFN-γ-inducible protein-10 levels and IFN-inducible genes upregulated in the AS01 and AS03 groups. No distinct marker or signature was specific to one particular AS. Innate profiles were comparable between AS01B, AS01E, and AS03 groups, and between AS04 and Alum groups. AS group rankings within adaptive and innate response levels and reactogenicity prevalence were similar (AS01B ≥ AS01E > AS03 > AS04 > Alum), suggesting an association between magnitudes of inflammatory and vaccine responses. Modeling revealed associations between adaptive responses and specific traits of the innate response post-dose 2 (activation of the IFN-signaling pathway, CRP and IL-6 responses). In conclusion, the ability of AS01 and AS03 to enhance adaptive responses to co-administered HBsAg is likely linked to their capacity to activate innate immunity, particularly the IFN-signaling pathway. PMID:28855902

  6. Poliovirus intrahost evolution is required to overcome tissue-specific innate immune responses.

    PubMed

    Xiao, Yinghong; Dolan, Patrick Timothy; Goldstein, Elizabeth Faul; Li, Min; Farkov, Mikhail; Brodsky, Leonid; Andino, Raul

    2017-08-29

    RNA viruses, such as poliovirus, have a great evolutionary capacity, allowing them to quickly adapt and overcome challenges encountered during infection. Here we show that poliovirus infection in immune-competent mice requires adaptation to tissue-specific innate immune microenvironments. The ability of the virus to establish robust infection and virulence correlates with its evolutionary capacity. We further identify a region in the multi-functional poliovirus protein 2B as a hotspot for the accumulation of minor alleles that facilitate a more effective suppression of the interferon response. We propose that population genetic dynamics enables poliovirus spread between tissues through optimization of the genetic composition of low frequency variants, which together cooperate to circumvent tissue-specific challenges. Thus, intrahost virus evolution determines pathogenesis, allowing a dynamic regulation of viral functions required to overcome barriers to infection.RNA viruses, such as polioviruses, have a great evolutionary capacity and can adapt quickly during infection. Here, the authors show that poliovirus infection in mice requires adaptation to innate immune microenvironments encountered in different tissues.

  7. Resilience of Adapting Networks: Results from a Stylized Infrastructure Model.

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Beyeler, Walter E.; Vugrin, Eric D.; Forden, Geoffrey Ethan

    2015-01-01

    Adaptation is believed to be a source of resilience in systems. It has been difficult to measure the contribution of adaptation to resilience, unlike other resilience mechanisms such as restoration and recovery. One difficulty comes from treating adaptation as a deus ex machina that is interjected after a disruption. This provides no basis for bounding possible adaptive responses. We can bracket the possible effects of adaptation when we recognize that it occurs continuously, and is in part responsible for the current system’s properties. In this way the dynamics of the system’s pre-disruption structure provides information about post-disruption adaptive reaction. Seenmore » as an ongoing process, adaptation has been argued to produce “robust-yet-fragile” systems. Such systems perform well under historical stresses but become committed to specific features of those stresses in a way that makes them vulnerable to system-level collapse when those features change. In effect adaptation lessens the cost of disruptions within a certain historical range, at the expense of increased cost from disruptions outside that range. Historical adaptive responses leave a signature in the structure of the system. Studies of ecological networks have suggested structural metrics that pick out systemic resilience in the underlying ecosystems. If these metrics are generally reliable indicators of resilience they provide another strategy for gaging adaptive resilience. To progress in understanding how the process of adaptation and the property of resilience interrelate in infrastructure systems, we pose some specific questions: Does adaptation confer resilience?; Does it confer resilience to novel shocks as well, or does it tune the system to fragility?; Can structural features predict resilience to novel shocks?; Are there policies or constraints on the adaptive process that improve resilience?.« less

  8. Focused cognitive control in dishonesty: Evidence for predominantly transient conflict adaptation.

    PubMed

    Foerster, Anna; Pfister, Roland; Schmidts, Constantin; Dignath, David; Wirth, Robert; Kunde, Wilfried

    2018-04-01

    Giving a dishonest response to a question entails cognitive conflict due to an initial activation of the truthful response. Following conflict monitoring theory, dishonest responding could therefore elicit transient and sustained control adaptation processes to mitigate such conflict, and the current experiments take on the scope and specificity of such conflict adaptation in dishonesty. Transient adaptation reduces differences between honest and dishonest responding following a recent dishonest response. Sustained adaptation has a similar behavioral signature but is driven by the overall frequency of dishonest responding. Both types of adaptation to recent and frequent dishonest responses have been separately documented, leaving open whether control processes in dishonest responding can flexibly adapt to transient and sustained conflict signals of dishonest and other actions. This was the goal of the present experiments which studied (dis)honest responding to autobiographical yes/no questions. Experiment 1 showed robust transient adaptation to recent dishonest responses whereas sustained control adaptation failed to exert an influence on behavior. It further revealed that transient effects may create a spurious impression of sustained adaptation in typical experimental settings. Experiments 2 and 3 examined whether dishonest responding can profit from transient and sustained adaption processes triggered by other behavioral conflicts. This was clearly not the case: Dishonest responding adapted markedly to recent (dis)honest responses but not to any context of other conflicts. These findings indicate that control adaptation in dishonest responding is strong but surprisingly focused and they point to a potential trade-off between transient and sustained adaptation. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

  9. MITA/STING and Its Alternative Splicing Isoform MRP Restrict Hepatitis B Virus Replication

    PubMed Central

    Liu, Shuhui; Zhao, Kaitao; Su, Xi; Lu, Lu; Zhao, He; Zhang, Xianwen; Wang, Yun; Wu, Chunchen; Chen, Jizheng; Zhou, Yuan; Hu, Xue; Wang, Yanyi; Lu, Mengji; Chen, Xinwen; Pei, Rongjuan

    2017-01-01

    An efficient clearance of hepatitis B virus (HBV) requires the coordinated work of both the innate and adaptive immune responses. MITA/STING, an adapter protein of the innate immune signaling pathways, plays a key role in regulating innate and adaptive immune responses to DNA virus infection. Previously, we identified an alternatively spliced isoform of MITA/STING, called MITA-related protein (MRP), and found that MRP could specifically block MITA-mediated interferon (IFN) induction while retaining the ability to activate NF-κB. Here, we asked whether MITA/STING and MRP were able to control the HBV replication. Both MITA/STING and MRP significantly inhibited HBV replication in vitro. MITA overexpression stimulated IRF3-IFN pathway; while MRP overexpression activated NF-κB pathway, suggesting these two isoforms may inhibit HBV replication through different ways. Using a hydrodynamic injection (HI) mouse model, we found that HBV replication was reduced following MITA/STING and MRP expression vectors in mice and was enhanced by the knockout of MITA/STING (MITA/STING-/-). The HBV specific humoral and CD8+ T cell responses were impaired in MITA/STING deficient mice, suggesting the participation of MITA/STING in the initiation of host adaptive immune responses. In summary, our data suggest that MITA/STING and MRP contribute to HBV control via modulation of the innate and adaptive responses. PMID:28056087

  10. MITA/STING and Its Alternative Splicing Isoform MRP Restrict Hepatitis B Virus Replication.

    PubMed

    Liu, Shuhui; Zhao, Kaitao; Su, Xi; Lu, Lu; Zhao, He; Zhang, Xianwen; Wang, Yun; Wu, Chunchen; Chen, Jizheng; Zhou, Yuan; Hu, Xue; Wang, Yanyi; Lu, Mengji; Chen, Xinwen; Pei, Rongjuan

    2017-01-01

    An efficient clearance of hepatitis B virus (HBV) requires the coordinated work of both the innate and adaptive immune responses. MITA/STING, an adapter protein of the innate immune signaling pathways, plays a key role in regulating innate and adaptive immune responses to DNA virus infection. Previously, we identified an alternatively spliced isoform of MITA/STING, called MITA-related protein (MRP), and found that MRP could specifically block MITA-mediated interferon (IFN) induction while retaining the ability to activate NF-κB. Here, we asked whether MITA/STING and MRP were able to control the HBV replication. Both MITA/STING and MRP significantly inhibited HBV replication in vitro. MITA overexpression stimulated IRF3-IFN pathway; while MRP overexpression activated NF-κB pathway, suggesting these two isoforms may inhibit HBV replication through different ways. Using a hydrodynamic injection (HI) mouse model, we found that HBV replication was reduced following MITA/STING and MRP expression vectors in mice and was enhanced by the knockout of MITA/STING (MITA/STING-/-). The HBV specific humoral and CD8+ T cell responses were impaired in MITA/STING deficient mice, suggesting the participation of MITA/STING in the initiation of host adaptive immune responses. In summary, our data suggest that MITA/STING and MRP contribute to HBV control via modulation of the innate and adaptive responses.

  11. A correlate of HIV-1 control consisting of both innate and adaptive immune parameters best predicts viral load by multivariable analysis in HIV-1 infected viremic controllers and chronically-infected non-controllers.

    PubMed

    Tomescu, Costin; Liu, Qin; Ross, Brian N; Yin, Xiangfan; Lynn, Kenneth; Mounzer, Karam C; Kostman, Jay R; Montaner, Luis J

    2014-01-01

    HIV-1 infected viremic controllers maintain durable viral suppression below 2000 copies viral RNA/ml without anti-retroviral therapy (ART), and the immunological factor(s) associated with host control in presence of low but detectable viral replication are of considerable interest. Here, we utilized a multivariable analysis to identify which innate and adaptive immune parameters best correlated with viral control utilizing a cohort of viremic controllers (median 704 viral RNA/ml) and non-controllers (median 21,932 viral RNA/ml) that were matched for similar CD4+ T cell counts in the absence of ART. We observed that HIV-1 Gag-specific CD8+ T cell responses were preferentially targeted over Pol-specific responses in viremic controllers (p = 0.0137), while Pol-specific responses were positively associated with viral load (rho = 0.7753, p = 0.0001, n = 23). Viremic controllers exhibited significantly higher NK and plasmacytoid dendritic cells (pDC) frequency as well as retained expression of the NK CD16 receptor and strong target cell-induced NK cell IFN-gamma production compared to non-controllers (p<0.05). Despite differences in innate and adaptive immune function however, both viremic controllers (p<0.05) and non-controller subjects (p<0.001) exhibited significantly increased CD8+ T cell activation and spontaneous NK cell degranulation compared to uninfected donors. Overall, we identified that a combination of innate (pDC frequency) and adaptive (Pol-specific CD8+ T cell responses) immune parameters best predicted viral load (R2 = 0.5864, p = 0.0021, n = 17) by a multivariable analysis. Together, this data indicates that preferential Gag-specific over Pol-specific CD8+ T cell responses along with a retention of functional innate subsets best predict host control over viral replication in HIV-1 infected viremic controllers compared to chronically-infected non-controllers.

  12. Adapting to wildfire: Rebuilding after home loss

    Treesearch

    Miranda H. Mockrin; Susan I. Stewart; Volker C. Radeloff; Roger B. Hammer; Patricia M. Alexandre

    2015-01-01

    Wildfire management now emphasizes fire-adapted communities that coexist with wildfires, although it is unclear how communities will progress to this goal. Hazards research suggests that response to wildfire - specifically, rebuilding after fire - may be a crucial opportunity for homeowner and community adaptation. We explore rebuilding after the 2010 Fourmile Canyon...

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

    PubMed

    van Loon, Luc J C; Tipton, Kevin D

    2013-01-01

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

  14. Switching between pitch surfaces: practical applications and future perspectives for soccer training.

    PubMed

    Rago, Vincenzo; Silva, João R; Brito, João; Barreira, Daniel; Mohr, Magni; Krustrup, Peter; Rebelo, António N

    2018-04-04

    Soccer training and completion is conventionally practiced on natural grass (NG) or artificial turf (AT). Recently, AT pitches for training / competition, and of unstable surfaces for injury prevention training has increased. Therefore, soccer players are frequently exposed to variations in pitch surface during either training or competition. These ground changes may impact physical and physiological responses, adaptations as well as the injury. The aim of this review was to summarize the acute physical and physiological responses, chronic adaptations, and injury risk associated with exercising on different pitch surfaces in soccer. Eligible studies were published in English, had pitch surface as an independent variable, and had physical, physiological or epidemiological information as outcome variables. Specific data extracted from the articles included the training response, training adaptations or injury outcomes according to different pitch surfaces. A total of 224 studies were retrieved from a literature search. Twenty articles met the inclusion criteria: 9 for acute physical and physiological responses, 2 for training adaptations and 9 for injury assessment. The literature lacks consistent evidence regarding the effects of pitch surface on performance and health outcomes in soccer players. However, it seems that occasionally switching training surfaces seems a valuable strategy for focusing on specific musculoskeletal queries and enhancing players' fitness. For instance, sand training may be occasionally proposed as complementary training strategy, given the recruitment of additional musculature probably not involved on firmer surfaces, but the possible training-induced adaptations of non-conventional soccer surfaces (e.g., sand) might potentially result into a negative transfer on AT or NG. Since the specific physical demands of soccer can differ between surfaces, coaches should resort to the use of non-traditional surfaces with parsimony, emphasizing the specific surface-related motor tasks, normally observed on natural grass or artificial turf. Further studies are required to better understand the physiological effects induced by systematic surface-specific training, or switching between pitch surfaces.

  15. Extract of medicinal mushroom Agaricus blazei Murill enhances the non-specific and adaptive immune activities in BALB/c mice.

    PubMed

    Ni, Wei-Ya; Wu, Ming-Fanf; Liao, Nien-Chieh; Yeh, Ming-Yang; Lu, Hsu-Feng; Hsueh, Shu-Ching; Liu, Jia-You; Huang, Yi-Ping; Chang, Chuan-Hsun; Chung, Jing-Gung

    2013-01-01

    Agaricus blazei Murill (AbM) is traditionally used against a wide range of conditions such as ulcerative colitis, Crohn's disease, foot-and-mouth disease and chronic hepatitis C infection. In this study, we evaluated the immunomodulatory effects of AbM. For the non-specific immune response experiments, a total of 40 female BALB/c mice were divided into control (group 1) and experimental (groups 2-4) groups of 10 animals each. Groups 2, 3 and 4 were orally-administered high (819 mg/kg), medium (273 mg/kg) and low (136.5 mg/kg) doses of AbM daily for six weeks and then six parameters related to non-specific immune response were detected. For the adaptive immune response experiments, 40 female mice were similarly divided into four groups. After six weeks of treatment, animals were immunized with the OVA immunogen. Two weeks later, splenocytes and sera were collected. Four parameters related to adaptive immune response were evaluated. We found that feeding mice with AbM extract increased the IgG level in serum, promoted phagocytosis of peritoneal macrophages and elevated the activity of Natural killer cells. We also found that the highest dose of AbM increased interleukin-2 (IL-2) levels in splenocytes and that a medium dose increased interferon-γ. The levels of interleukin-4 (IL-4) were reduced or unchanged. T-helper type 1 cytokine levels were increased. AbM increased the humoral immune response and also affected the cellular immune response. These results provide evidence that AbM can modulate innate and adaptive immunity.

  16. Lack of broad functional differences in immunity in fully vaccinated vs. unvaccinated children.

    PubMed

    Sherrid, Ashley M; Ruck, Candice E; Sutherland, Darren; Cai, Bing; Kollmann, Tobias R

    2017-04-01

    Concerns have been raised that with an increase in the number of vaccines administered early in life, immune development could be altered, leading to either increased or decreased immune reactivity. We investigated the impact of vaccination on immune status, contrasting the immune response to general, nonantigen-specific stimuli in a cohort of entirely unvaccinated vs. fully vaccinated children at 3-5 y of age. Innate immunity was assessed by quantifying bulk and cell-type-specific cytokine production in response to stimulation with pathogen associated microbial patterns. Adaptive immune status was characterized by assessing lymphocyte proliferation and cytokine production in response to generic T cell stimuli. Our investigations failed to reveal a broadly evident alteration of either innate or adaptive immunity in vaccinated children. Equivalently robust innate and adaptive responses to pathogen associated microbial patterns and generic T cell stimulants were observed in both groups. Although our sample size was small, our data suggest that standard childhood vaccinations do not lead to long-lasting gross alterations of the immune system.

  17. A Functional Toll-Interacting Protein Variant Is Associated with Bacillus Calmette-Guérin-Specific Immune Responses and Tuberculosis.

    PubMed

    Shah, Javeed A; Musvosvi, Munyaradzi; Shey, Muki; Horne, David J; Wells, Richard D; Peterson, Glenna J; Cox, Jeffery S; Daya, Michelle; Hoal, Eileen G; Lin, Lin; Gottardo, Raphael; Hanekom, Willem A; Scriba, Thomas J; Hatherill, Mark; Hawn, Thomas R

    2017-08-15

    The molecular mechanisms that regulate tuberculosis susceptibility and bacillus Calmette-Guérin (BCG)-induced immunity are mostly unknown. However, induction of the adaptive immune response is a critical step in host control of Mycobacterium tuberculosis. Toll-interacting protein (TOLLIP) is a ubiquitin-binding protein that regulates innate immune responses, including Toll-like receptor signaling, which initiate adaptive immunity. TOLLIP variation is associated with susceptibility to tuberculosis, but the mechanism by which it regulates tuberculosis immunity is poorly understood. To identify functional TOLLIP variants and evaluate the role of TOLLIP variation on innate and adaptive immune responses to mycobacteria and susceptibility to tuberculosis. We used human cellular immunology approaches to characterize the role of a functional TOLLIP variant on monocyte mRNA expression and M. tuberculosis-induced monocyte immune functions. We also examined the association of TOLLIP variation with BCG-induced T-cell responses and susceptibility to latent tuberculosis infection. We identified a functional TOLLIP promoter region single-nucleotide polymorphism, rs5743854, which was associated with decreased TOLLIP mRNA expression in infant monocytes. After M. tuberculosis infection, TOLLIP-deficient monocytes demonstrated increased IL-6, increased nitrite, and decreased bacterial replication. The TOLLIP-deficiency G/G genotype was associated with decreased BCG-specific IL-2 + CD4 + T-cell frequency and proliferation. This genotype was also associated with increased susceptibility to latent tuberculosis infection. TOLLIP deficiency is associated with decreased BCG-specific T-cell responses and increased susceptibility to tuberculosis. We hypothesize that the heightened antibacterial monocyte responses after vaccination of TOLLIP-deficient infants are responsible for decreased BCG-specific T-cell responses. Activating TOLLIP may provide a novel adjuvant strategy for BCG vaccination.

  18. Extreme Terrestrial Environments: Life in Thermal Stress and Hypoxia. A Narrative Review.

    PubMed

    Burtscher, Martin; Gatterer, Hannes; Burtscher, Johannes; Mairbäurl, Heimo

    2018-01-01

    Living, working and exercising in extreme terrestrial environments are challenging tasks even for healthy humans of the modern new age. The issue is not just survival in remote environments but rather the achievement of optimal performance in everyday life, occupation, and sports. Various adaptive biological processes can take place to cope with the specific stressors of extreme terrestrial environments like cold, heat, and hypoxia (high altitude). This review provides an overview of the physiological and morphological aspects of adaptive responses in these environmental stressors at the level of organs, tissues, and cells. Furthermore, adjustments existing in native people living in such extreme conditions on the earth as well as acute adaptive responses in newcomers are discussed. These insights into general adaptability of humans are complemented by outcomes of specific acclimatization/acclimation studies adding important information how to cope appropriately with extreme environmental temperatures and hypoxia.

  19. Extreme Terrestrial Environments: Life in Thermal Stress and Hypoxia. A Narrative Review

    PubMed Central

    Burtscher, Martin; Gatterer, Hannes; Burtscher, Johannes; Mairbäurl, Heimo

    2018-01-01

    Living, working and exercising in extreme terrestrial environments are challenging tasks even for healthy humans of the modern new age. The issue is not just survival in remote environments but rather the achievement of optimal performance in everyday life, occupation, and sports. Various adaptive biological processes can take place to cope with the specific stressors of extreme terrestrial environments like cold, heat, and hypoxia (high altitude). This review provides an overview of the physiological and morphological aspects of adaptive responses in these environmental stressors at the level of organs, tissues, and cells. Furthermore, adjustments existing in native people living in such extreme conditions on the earth as well as acute adaptive responses in newcomers are discussed. These insights into general adaptability of humans are complemented by outcomes of specific acclimatization/acclimation studies adding important information how to cope appropriately with extreme environmental temperatures and hypoxia. PMID:29867589

  20. Herbaceous plant species invading natural areas tend to have stronger adaptive root foraging than other naturalized species

    PubMed Central

    Keser, Lidewij H.; Visser, Eric J. W.; Dawson, Wayne; Song, Yao-Bin; Yu, Fei-Hai; Fischer, Markus; Dong, Ming; van Kleunen, Mark

    2015-01-01

    Although plastic root-foraging responses are thought to be adaptive, as they may optimize nutrient capture of plants, this has rarely been tested. We investigated whether nutrient-foraging responses are adaptive, and whether they pre-adapt alien species to become natural-area invaders. We grew 12 pairs of congeneric species (i.e., 24 species) native to Europe in heterogeneous and homogeneous nutrient environments, and compared their foraging responses and performance. One species in each pair is a USA natural-area invader, and the other one is not. Within species, individuals with strong foraging responses, measured as plasticity in root diameter and specific root length, had a higher biomass. Among species, the ones with strong foraging responses, measured as plasticity in root length and root biomass, had a higher biomass. Our results therefore suggest that root foraging is an adaptive trait. Invasive species showed significantly stronger root-foraging responses than non-invasive species when measured as root diameter. Biomass accumulation was decreased in the heterogeneous vs. the homogeneous environment. In aboveground, but not belowground and total biomass, this decrease was smaller in invasive than in non-invasive species. Our results show that strong plastic root-foraging responses are adaptive, and suggest that it might aid in pre-adapting species to becoming natural-area invaders. PMID:25964790

  1. Effective Combination Adjuvants Engage Both TLR and Inflammasome Pathways To Promote Potent Adaptive Immune Responses.

    PubMed

    Seydoux, Emilie; Liang, Hong; Dubois Cauwelaert, Natasha; Archer, Michelle; Rintala, Nicholas D; Kramer, Ryan; Carter, Darrick; Fox, Christopher B; Orr, Mark T

    2018-05-16

    The involvement of innate receptors that recognize pathogen- and danger-associated molecular patterns is critical to programming an effective adaptive immune response to vaccination. The synthetic TLR4 agonist glucopyranosyl lipid adjuvant (GLA) synergizes with the squalene oil-in-water emulsion (SE) formulation to induce strong adaptive responses. Although TLR4 signaling through MyD88 and TIR domain-containing adapter inducing IFN-β are essential for GLA-SE activity, the mechanisms underlying the synergistic activity of GLA and SE are not fully understood. In this article, we demonstrate that the inflammasome activation and the subsequent release of IL-1β are central effectors of the action of GLA-SE, as infiltration of innate cells into the draining lymph nodes and production of IFN-γ are reduced in ASC -/- animals. Importantly, the early proliferation of Ag-specific CD4 + T cells was completely ablated after immunization in ASC -/- animals. Moreover, numbers of Ag-specific CD4 + T and B cells as well as production of IFN-γ, TNF-α, and IL-2 and Ab titers were considerably reduced in ASC -/- , NLRP3 -/- , and IL-1R -/- mice compared with wild-type mice and were completely ablated in TLR4 -/- animals. Also, extracellular ATP, a known trigger of the inflammasome, augments Ag-specific CD4 + T cell responses, as hydrolyzing it with apyrase diminished adaptive responses induced by GLA-SE. These data thus demonstrate that GLA-SE adjuvanticity acts through TLR4 signaling and NLRP3 inflammasome activation to promote robust Th1 and B cell responses to vaccine Ags. The findings suggest that engagement of both TLR and inflammasome activators may be a general paradigm for induction of robust CD4 T cell immunity with combination adjuvants such as GLA-SE. Copyright © 2018 by The American Association of Immunologists, Inc.

  2. The Immunology of Posttransplant CMV Infection: Potential Effect of CMV Immunoglobulins on Distinct Components of the Immune Response to CMV

    PubMed Central

    Carbone, Javier

    2016-01-01

    Abstract The immune response to cytomegalovirus (CMV) infection is highly complex, including humoral, cellular, innate, and adaptive immune responses. Detection of CMV by the innate immune system triggers production of type I IFNs and inflammatory cytokines which initiate cellular and humoral responses that are critical during the early viremic phase of CMV infection. Sustained control of CMV infection is largely accounted for by cellular immunity, involving various T-cell and B-cell subsets. In solid organ transplant patients, global suppression of innate and adaptive immunities by immunosuppressive agents limits immunological defense, including inhibition of natural killer cell activity with ongoing lowering of Ig levels and CMV-specific antibody titers. This is coupled with a short-term suppression of CMV-specific T cells, the extent and duration of which can predict risk of progression to CMV viremia. CMV immunoglobulin (CMVIG) preparations have the potential to exert immunomodulatory effects as well as providing passive immunization. Specific CMVIG antibodies and virus neutralization might be enhanced by modulation of dendritic cell activity and by a decrease in T-cell activation, effects which are of importance during the initial phase of infection. In summary, the role of CMVIG in reconstituting specific anti-CMV antibodies may be enhanced by some degree of modulation of the innate and adaptive immune responses, which could help to control some of the direct and indirect effects of CMV infection. PMID:26900990

  3. The Immunology of Posttransplant CMV Infection: Potential Effect of CMV Immunoglobulins on Distinct Components of the Immune Response to CMV.

    PubMed

    Carbone, Javier

    2016-03-01

    The immune response to cytomegalovirus (CMV) infection is highly complex, including humoral, cellular, innate, and adaptive immune responses. Detection of CMV by the innate immune system triggers production of type I IFNs and inflammatory cytokines which initiate cellular and humoral responses that are critical during the early viremic phase of CMV infection. Sustained control of CMV infection is largely accounted for by cellular immunity, involving various T-cell and B-cell subsets. In solid organ transplant patients, global suppression of innate and adaptive immunities by immunosuppressive agents limits immunological defense, including inhibition of natural killer cell activity with ongoing lowering of Ig levels and CMV-specific antibody titers. This is coupled with a short-term suppression of CMV-specific T cells, the extent and duration of which can predict risk of progression to CMV viremia. CMV immunoglobulin (CMVIG) preparations have the potential to exert immunomodulatory effects as well as providing passive immunization. Specific CMVIG antibodies and virus neutralization might be enhanced by modulation of dendritic cell activity and by a decrease in T-cell activation, effects which are of importance during the initial phase of infection. In summary, the role of CMVIG in reconstituting specific anti-CMV antibodies may be enhanced by some degree of modulation of the innate and adaptive immune responses, which could help to control some of the direct and indirect effects of CMV infection.

  4. Noncoding RNA danger motifs bridge innate and adaptive immunity and are potent adjuvants for vaccination

    PubMed Central

    Wang, Lilin; Smith, Dan; Bot, Simona; Dellamary, Luis; Bloom, Amy; Bot, Adrian

    2002-01-01

    The adaptive immune response is triggered by recognition of T and B cell epitopes and is influenced by “danger” motifs that act via innate immune receptors. This study shows that motifs associated with noncoding RNA are essential features in the immune response reminiscent of viral infection, mediating rapid induction of proinflammatory chemokine expression, recruitment and activation of antigen-presenting cells, modulation of regulatory cytokines, subsequent differentiation of Th1 cells, isotype switching, and stimulation of cross-priming. The heterogeneity of RNA-associated motifs results in differential binding to cellular receptors, and specifically impacts the immune profile. Naturally occurring double-stranded RNA (dsRNA) triggered activation of dendritic cells and enhancement of specific immunity, similar to selected synthetic dsRNA motifs. Based on the ability of specific RNA motifs to block tolerance induction and effectively organize the immune defense during viral infection, we conclude that such RNA species are potent danger motifs. We also demonstrate the feasibility of using selected RNA motifs as adjuvants in the context of novel aerosol carriers for optimizing the immune response to subunit vaccines. In conclusion, RNA-associated motifs produced during viral infection bridge the early response with the late adaptive phase, regulating the activation and differentiation of antigen-specific B and T cells, in addition to a short-term impact on innate immunity. PMID:12393853

  5. Predation risk modifies behaviour by shaping the response of identified brain neurons.

    PubMed

    Magani, Fiorella; Luppi, Tomas; Nuñez, Jesus; Tomsic, Daniel

    2016-04-15

    Interpopulation comparisons in species that show behavioural variations associated with particular ecological disparities offer good opportunities for assessing how environmental factors may foster specific functional adaptations in the brain. Yet, studies on the neural substrate that can account for interpopulation behavioural adaptations are scarce. Predation is one of the strongest driving forces for behavioural evolvability and, consequently, for shaping structural and functional brain adaptations. We analysed the escape response of crabs ITALIC! Neohelice granulatafrom two isolated populations exposed to different risks of avian predation. Individuals from the high-risk area proved to be more reactive to visual danger stimuli (VDS) than those from an area where predators are rare. Control experiments indicate that the response difference was specific for impending visual threats. Subsequently, we analysed the response to VDS of a group of giant brain neurons that are thought to play a main role in the visually guided escape response of the crab. Neurons from animals of the population with the stronger escape response were more responsive to VDS than neurons from animals of the less reactive population. Our results suggest a robust linkage between the pressure imposed by the predation risk, the response of identified neurons and the behavioural outcome. © 2016. Published by The Company of Biologists Ltd.

  6. Peptide-specific recognition of human cytomegalovirus strains controls adaptive natural killer cells.

    PubMed

    Hammer, Quirin; Rückert, Timo; Borst, Eva Maria; Dunst, Josefine; Haubner, André; Durek, Pawel; Heinrich, Frederik; Gasparoni, Gilles; Babic, Marina; Tomic, Adriana; Pietra, Gabriella; Nienen, Mikalai; Blau, Igor Wolfgang; Hofmann, Jörg; Na, Il-Kang; Prinz, Immo; Koenecke, Christian; Hemmati, Philipp; Babel, Nina; Arnold, Renate; Walter, Jörn; Thurley, Kevin; Mashreghi, Mir-Farzin; Messerle, Martin; Romagnani, Chiara

    2018-05-01

    Natural killer (NK) cells are innate lymphocytes that lack antigen-specific rearranged receptors, a hallmark of adaptive lymphocytes. In some people infected with human cytomegalovirus (HCMV), an NK cell subset expressing the activating receptor NKG2C undergoes clonal-like expansion that partially resembles anti-viral adaptive responses. However, the viral ligand that drives the activation and differentiation of adaptive NKG2C + NK cells has remained unclear. Here we found that adaptive NKG2C + NK cells differentially recognized distinct HCMV strains encoding variable UL40 peptides that, in combination with pro-inflammatory signals, controlled the population expansion and differentiation of adaptive NKG2C + NK cells. Thus, we propose that polymorphic HCMV peptides contribute to shaping of the heterogeneity of adaptive NKG2C + NK cell populations among HCMV-seropositive people.

  7. Adaptive responses induced by 24S-hydroxycholesterol through liver X receptor pathway reduce 7-ketocholesterol-caused neuronal cell death☆

    PubMed Central

    Okabe, Akishi; Urano, Yasuomi; Itoh, Sayoko; Suda, Naoto; Kotani, Rina; Nishimura, Yuki; Saito, Yoshiro; Noguchi, Noriko

    2013-01-01

    Lipid peroxidation products have been known to induce cellular adaptive responses and enhance tolerance against subsequent oxidative stress through up-regulation of antioxidant compounds and enzymes. 24S-hydroxycholesterol (24SOHC) which is endogenously produced oxysterol in the brain plays an important role in maintaining brain cholesterol homeostasis. In this study, we evaluated adaptive responses induced by brain-specific oxysterol 24SOHC in human neuroblastoma SH-SY5Y cells. Cells treated with 24SOHC at sub-lethal concentrations showed significant reduction in cell death induced by subsequent treatment with 7-ketocholesterol (7KC) in both undifferentiated and retinoic acid-differentiated SH-SY5Y cells. These adaptive responses were also induced by other oxysterols such as 25-hydroxycholesterol and 27-hydroxycholesterol which are known to be ligands of liver X receptor (LXR). Co-treatment of 24SOHC with 9-cis retinoic acid, a retinoid X receptor ligand, enhanced the adaptive responses. Knockdown of LXRβ by siRNA diminished the adaptive responses induced by 24SOHC almost completely. The treatment with 24SOHC induced the expression of LXR target genes, such as ATP-binding cassette transporter A1 (ABCA1) and G1 (ABCG1). The 24SOHC-induced adaptive responses were significantly attenuated by siRNA for ABCG1 but not by siRNA for ABCA1. Taken together, these results strongly suggest that 24SOHC at sub-lethal concentrations induces adaptive responses via transcriptional activation of LXR signaling pathway, thereby protecting neuronal cells from subsequent 7KC-induced cytotoxicity. PMID:24371802

  8. Climate change and health effects in Northwest Alaska.

    PubMed

    Brubaker, Michael; Berner, James; Chavan, Raj; Warren, John

    2011-01-01

    This article provides examples of adverse health effects, including weather-related injury, food insecurity, mental health issues, and water infrastructure damage, and the responses to these effects that are currently being applied in two Northwest Alaska communities. In Northwest Alaska, warming is resulting in a broad range of unusual weather and environmental conditions, including delayed freeze-up, earlier breakup, storm surge, coastal erosion, and thawing permafrost. These are just some of the climate impacts that are driving concerns about weather-related injury, the spread of disease, mental health issues, infrastructure damage, and food and water security. Local leaders are challenged to identify appropriate adaptation strategies to address climate impacts and related health effects. IMPLEMENTATION PROCESS: The tribal health system is combining local observations, traditional knowledge, and western science to perform community-specific climate change health impact assessments. Local leaders are applying this information to develop adaptation responses. The Alaska Native Tribal Health Consortium will describe relationships between climate impacts and health effects and provide examples of community-scaled adaptation actions currently being applied in Northwest Alaska. Climate change is increasing vulnerability to injury, disease, mental stress, food insecurity, and water insecurity. Northwest communities are applying adaptation approaches that are both specific and appropriate. The health impact assessment process is effective in raising awareness, encouraging discussion, engaging partners, and implementing adaptation planning. With community-specific information, local leaders are applying health protective adaptation measures.

  9. Climate change and health effects in Northwest Alaska

    PubMed Central

    Brubaker, Michael; Berner, James; Chavan, Raj; Warren, John

    2011-01-01

    This article provides examples of adverse health effects, including weather-related injury, food insecurity, mental health issues, and water infrastructure damage, and the responses to these effects that are currently being applied in two Northwest Alaska communities. Background In Northwest Alaska, warming is resulting in a broad range of unusual weather and environmental conditions, including delayed freeze-up, earlier breakup, storm surge, coastal erosion, and thawing permafrost. These are just some of the climate impacts that are driving concerns about weather-related injury, the spread of disease, mental health issues, infrastructure damage, and food and water security. Local leaders are challenged to identify appropriate adaptation strategies to address climate impacts and related health effects. Implementation process The tribal health system is combining local observations, traditional knowledge, and western science to perform community-specific climate change health impact assessments. Local leaders are applying this information to develop adaptation responses. Objective The Alaska Native Tribal Health Consortium will describe relationships between climate impacts and health effects and provide examples of community-scaled adaptation actions currently being applied in Northwest Alaska. Findings Climate change is increasing vulnerability to injury, disease, mental stress, food insecurity, and water insecurity. Northwest communities are applying adaptation approaches that are both specific and appropriate. Conclusion The health impact assessment process is effective in raising awareness, encouraging discussion, engaging partners, and implementing adaptation planning. With community-specific information, local leaders are applying health protective adaptation measures. PMID:22022304

  10. Opinion: Interactions of innate and adaptive lymphocytes

    PubMed Central

    Gasteiger, Georg; Rudensky, Alexander Y.

    2015-01-01

    Innate lymphocytes, including natural killer (NK) cells and the recently discovered innate lymphoid cells (ILCs) have crucial roles during infection, tissue injury and inflammation. Innate signals regulate the activation and homeostasis of innate lymphocytes. Less well understood is the contribution of the adaptive immune system to the orchestration of innate lymphocyte responses. We review our current understanding of the interactions between adaptive and innate lymphocytes, and propose a model in which adaptive T cells function as antigen-specific sensors for the activation of innate lymphocytes to amplify and instruct local immune responses. We highlight the potential role of regulatory and helper T cells in these processes and discuss major questions in the emerging area of crosstalk between adaptive and innate lymphocytes. PMID:25132095

  11. Frequency-specific adaptation and its underlying circuit model in the auditory midbrain.

    PubMed

    Shen, Li; Zhao, Lingyun; Hong, Bo

    2015-01-01

    Receptive fields of sensory neurons are considered to be dynamic and depend on the stimulus history. In the auditory system, evidence of dynamic frequency-receptive fields has been found following stimulus-specific adaptation (SSA). However, the underlying mechanism and circuitry of SSA have not been fully elucidated. Here, we studied how frequency-receptive fields of neurons in rat inferior colliculus (IC) changed when exposed to a biased tone sequence. Pure tone with one specific frequency (adaptor) was presented markedly more often than others. The adapted tuning was compared with the original tuning measured with an unbiased sequence. We found inhomogeneous changes in frequency tuning in IC, exhibiting a center-surround pattern with respect to the neuron's best frequency. Central adaptors elicited strong suppressive and repulsive changes while flank adaptors induced facilitative and attractive changes. Moreover, we proposed a two-layer model of the underlying network, which not only reproduced the adaptive changes in the receptive fields but also predicted novelty responses to oddball sequences. These results suggest that frequency-specific adaptation in auditory midbrain can be accounted for by an adapted frequency channel and its lateral spreading of adaptation, which shed light on the organization of the underlying circuitry.

  12. Frequency-specific adaptation and its underlying circuit model in the auditory midbrain

    PubMed Central

    Shen, Li; Zhao, Lingyun; Hong, Bo

    2015-01-01

    Receptive fields of sensory neurons are considered to be dynamic and depend on the stimulus history. In the auditory system, evidence of dynamic frequency-receptive fields has been found following stimulus-specific adaptation (SSA). However, the underlying mechanism and circuitry of SSA have not been fully elucidated. Here, we studied how frequency-receptive fields of neurons in rat inferior colliculus (IC) changed when exposed to a biased tone sequence. Pure tone with one specific frequency (adaptor) was presented markedly more often than others. The adapted tuning was compared with the original tuning measured with an unbiased sequence. We found inhomogeneous changes in frequency tuning in IC, exhibiting a center-surround pattern with respect to the neuron's best frequency. Central adaptors elicited strong suppressive and repulsive changes while flank adaptors induced facilitative and attractive changes. Moreover, we proposed a two-layer model of the underlying network, which not only reproduced the adaptive changes in the receptive fields but also predicted novelty responses to oddball sequences. These results suggest that frequency-specific adaptation in auditory midbrain can be accounted for by an adapted frequency channel and its lateral spreading of adaptation, which shed light on the organization of the underlying circuitry. PMID:26483641

  13. Neural responses in songbird forebrain reflect learning rates, acquired salience, and stimulus novelty after auditory discrimination training.

    PubMed

    Bell, Brittany A; Phan, Mimi L; Vicario, David S

    2015-03-01

    How do social interactions form and modulate the neural representations of specific complex signals? This question can be addressed in the songbird auditory system. Like humans, songbirds learn to vocalize by imitating tutors heard during development. These learned vocalizations are important in reproductive and social interactions and in individual recognition. As a model for the social reinforcement of particular songs, male zebra finches were trained to peck for a food reward in response to one song stimulus (GO) and to withhold responding for another (NoGO). After performance reached criterion, single and multiunit neural responses to both trained and novel stimuli were obtained from multiple electrodes inserted bilaterally into two songbird auditory processing areas [caudomedial mesopallium (CMM) and caudomedial nidopallium (NCM)] of awake, restrained birds. Neurons in these areas undergo stimulus-specific adaptation to repeated song stimuli, and responses to familiar stimuli adapt more slowly than to novel stimuli. The results show that auditory responses differed in NCM and CMM for trained (GO and NoGO) stimuli vs. novel song stimuli. When subjects were grouped by the number of training days required to reach criterion, fast learners showed larger neural responses and faster stimulus-specific adaptation to all stimuli than slow learners in both areas. Furthermore, responses in NCM of fast learners were more strongly left-lateralized than in slow learners. Thus auditory responses in these sensory areas not only encode stimulus familiarity, but also reflect behavioral reinforcement in our paradigm, and can potentially be modulated by social interactions. Copyright © 2015 the American Physiological Society.

  14. Tissue-Restricted Adaptive Type 2 Immunity Is Orchestrated by Expression of the Costimulatory Molecule OX40L on Group 2 Innate Lymphoid Cells.

    PubMed

    Halim, Timotheus Y F; Rana, Batika M J; Walker, Jennifer A; Kerscher, Bernhard; Knolle, Martin D; Jolin, Helen E; Serrao, Eva M; Haim-Vilmovsky, Liora; Teichmann, Sarah A; Rodewald, Hans-Reimer; Botto, Marina; Vyse, Timothy J; Fallon, Padraic G; Li, Zhi; Withers, David R; McKenzie, Andrew N J

    2018-06-19

    The local regulation of type 2 immunity relies on dialog between the epithelium and the innate and adaptive immune cells. Here we found that alarmin-induced expression of the co-stimulatory molecule OX40L on group 2 innate lymphoid cells (ILC2s) provided tissue-restricted T cell co-stimulation that was indispensable for Th2 and regulatory T (Treg) cell responses in the lung and adipose tissue. Interleukin (IL)-33 administration resulted in organ-specific surface expression of OX40L on ILC2s and the concomitant expansion of Th2 and Treg cells, which was abolished upon deletion of OX40L on ILC2s (Il7ra Cre/+ Tnfsf4 fl/fl mice). Moreover, Il7ra Cre/+ Tnfsf4 fl/fl mice failed to mount effective Th2 and Treg cell responses and corresponding adaptive type 2 pulmonary inflammation arising from Nippostrongylus brasiliensis infection or allergen exposure. Thus, the increased expression of OX40L in response to IL-33 acts as a licensing signal in the orchestration of tissue-specific adaptive type 2 immunity, without which this response fails to establish. Copyright © 2018 MRC Laboratory of Molecular Biology. Published by Elsevier Inc. All rights reserved.

  15. Color-specific conditioning effects due to both orange and blue stimuli are observed in a Halobacterium salinarum strain devoid of putative methylatable sites on HtrI.

    PubMed

    Lucia, S; Cercignani, G; Frediani, A; Petracchi, D

    2003-01-01

    Behavioral responses of Halobacterium salinarum appear as changes in the frequency of motion reversals. Turning on orange light decreases the reversal frequency, whereas blue light induces reversals. Light pulses normally induce the same response as step-up stimuli. However, anomalous behavioral reactions, including inverse responses, are seen when stimuli are applied in sequence. The occurrence of a prior stimulus is conditioning for successive stimulation on a time scale of the same order of adaptational processes. These prolonged conditioning effects are color-specific. The only adaptation process identified so far is methylation of the transducers, and this could be somehow color-specific. Therefore we tested for the behavioral anomalies in a mutant in which all methylation sites on the transducer have been eliminated. The results show that behavioral anomalies are unaffected by the absence of methylation processes on the transducer.

  16. Transactional Associations Between Youths’ Responses to Peer Stress and Depression: The Moderating Roles of Sex and Stress Exposure

    PubMed Central

    Agoston, Anna Monica; Rudolph, Karen D.

    2011-01-01

    This study examined transactional associations between responses to peer stress and depression in youth. Specifically, it tested the hypotheses that (a) depression would predict fewer effortful responses and more involuntary, dysregulated responses to peer stress over time; and (b) fewer adaptive and more maladaptive responses would predict subsequent depression. Youth (M age = 12.41; SD = 1.19; 86 girls, 81 boys) and their maternal caregivers completed semi-structured interviews and questionnaires at three annual waves. Multi-group comparison path analyses were conducted to examine sex and stress-level differences in the proposed reciprocal-influence model. In girls and in youth exposed to high levels of peer stress, maladaptive stress responses predicted more depressive symptoms and adaptive stress responses predicted fewer depressive symptoms at each wave. These findings suggest the utility of preventive interventions for depression designed to enhance the quality of girls’ stress responses. In boys, depression predicted less adaptive and more maladaptive stress responses, but only at the second wave. These findings suggest that interventions designed to reduce boys’ depressive symptoms may help them develop more adaptive stress responses. PMID:20852929

  17. Allele specific expression analysis identifies regulatory variation associated with stress-related genes in the Mexican highland maize landrace Palomero Toluqueño

    PubMed Central

    González-Segovia, Eric; Ross-Ibarra, Jeffrey; Simpson, June K.

    2017-01-01

    Background Gene regulatory variation has been proposed to play an important role in the adaptation of plants to environmental stress. In the central highlands of Mexico, farmer selection has generated a unique group of maize landraces adapted to the challenges of the highland niche. In this study, gene expression in Mexican highland maize and a reference maize breeding line were compared to identify evidence of regulatory variation in stress-related genes. It was hypothesised that local adaptation in Mexican highland maize would be associated with a transcriptional signature observable even under benign conditions. Methods Allele specific expression analysis was performed using the seedling-leaf transcriptome of an F1 individual generated from the cross between the highland adapted Mexican landrace Palomero Toluqueño and the reference line B73, grown under benign conditions. Results were compared with a published dataset describing the transcriptional response of B73 seedlings to cold, heat, salt and UV treatments. Results A total of 2,386 genes were identified to show allele specific expression. Of these, 277 showed an expression difference between Palomero Toluqueño and B73 alleles under benign conditions that anticipated the response of B73 cold, heat, salt and/or UV treatments, and, as such, were considered to display a prior stress response. Prior stress response candidates included genes associated with plant hormone signaling and a number of transcription factors. Construction of a gene co-expression network revealed further signaling and stress-related genes to be among the potential targets of the transcription factors candidates. Discussion Prior activation of responses may represent the best strategy when stresses are severe but predictable. Expression differences observed here between Palomero Toluqueño and B73 alleles indicate the presence of cis-acting regulatory variation linked to stress-related genes in Palomero Toluqueño. Considered alongside gene annotation and population data, allele specific expression analysis of plants grown under benign conditions provides an attractive strategy to identify functional variation potentially linked to local adaptation. PMID:28852597

  18. The wake-promoting drug modafinil stimulates specific hypothalamic circuits to promote adaptive stress responses in an animal model of PTSD

    PubMed Central

    Cohen, S; Ifergane, G; Vainer, E; Matar, M A; Kaplan, Z; Zohar, J; Mathé, A A; Cohen, H

    2016-01-01

    Pharmacotherapeutic intervention during traumatic memory consolidation has been suggested to alleviate or even prevent the development of posttraumatic stress disorder (PTSD). We recently reported that, in a controlled, prospective animal model, depriving rats of sleep following stress exposure prevents the development of a PTSD-like phenotype. Here, we report that administering the wake-promoting drug modafinil to rats in the aftermath of a stressogenic experience has a similar prophylactic effect, as it significantly reduces the prevalence of PTSD-like phenotype. Moreover, we show that the therapeutic value of modafinil appears to stem from its ability to stimulate a specific circuit within the hypothalamus, which ties together the neuropeptide Y, the orexin system and the HPA axis, to promote adaptive stress responses. The study not only confirms the value of sleep prevention and identifies the mechanism of action of a potential prophylactic treatment after traumatic exposure, but also contributes to understanding mechanisms underlying the shift towards adaptive behavioral response. PMID:27727245

  19. Let’s Tie the Knot: Marriage of Complement and Adaptive Immunity in Pathogen Evasion, for Better or Worse

    PubMed Central

    Bennett, Kaila M.; Rooijakkers, Suzan H. M.; Gorham, Ronald D.

    2017-01-01

    The complement system is typically regarded as an effector arm of innate immunity, leading to recognition and killing of microbial invaders in body fluids. Consequently, pathogens have engaged in an arms race, evolving molecules that can interfere with proper complement responses. However, complement is no longer viewed as an isolated system, and links with other immune mechanisms are continually being discovered. Complement forms an important bridge between innate and adaptive immunity. While its roles in innate immunity are well-documented, its function in adaptive immunity is less characterized. Therefore, it is no surprise that the field of pathogenic complement evasion has focused on blockade of innate effector functions, while potential inhibition of adaptive immune responses (via complement) has been overlooked to a certain extent. In this review, we highlight past and recent developments on the involvement of complement in the adaptive immune response. We discuss the mechanisms by which complement aids in lymphocyte stimulation and regulation, as well as in antigen presentation. In addition, we discuss microbial complement evasion strategies, and highlight specific examples in the context of adaptive immune responses. These emerging ties between complement and adaptive immunity provide a catalyst for future discovery in not only the field of adaptive immune evasion but in elucidating new roles of complement. PMID:28197139

  20. Let's Tie the Knot: Marriage of Complement and Adaptive Immunity in Pathogen Evasion, for Better or Worse.

    PubMed

    Bennett, Kaila M; Rooijakkers, Suzan H M; Gorham, Ronald D

    2017-01-01

    The complement system is typically regarded as an effector arm of innate immunity, leading to recognition and killing of microbial invaders in body fluids. Consequently, pathogens have engaged in an arms race, evolving molecules that can interfere with proper complement responses. However, complement is no longer viewed as an isolated system, and links with other immune mechanisms are continually being discovered. Complement forms an important bridge between innate and adaptive immunity. While its roles in innate immunity are well-documented, its function in adaptive immunity is less characterized. Therefore, it is no surprise that the field of pathogenic complement evasion has focused on blockade of innate effector functions, while potential inhibition of adaptive immune responses (via complement) has been overlooked to a certain extent. In this review, we highlight past and recent developments on the involvement of complement in the adaptive immune response. We discuss the mechanisms by which complement aids in lymphocyte stimulation and regulation, as well as in antigen presentation. In addition, we discuss microbial complement evasion strategies, and highlight specific examples in the context of adaptive immune responses. These emerging ties between complement and adaptive immunity provide a catalyst for future discovery in not only the field of adaptive immune evasion but in elucidating new roles of complement.

  1. Identification and characterization of insect-specific proteins by genome data analysis

    PubMed Central

    Zhang, Guojie; Wang, Hongsheng; Shi, Junjie; Wang, Xiaoling; Zheng, Hongkun; Wong, Gane Ka-Shu; Clark, Terry; Wang, Wen; Wang, Jun; Kang, Le

    2007-01-01

    Background Insects constitute the vast majority of known species with their importance including biodiversity, agricultural, and human health concerns. It is likely that the successful adaptation of the Insecta clade depends on specific components in its proteome that give rise to specialized features. However, proteome determination is an intensive undertaking. Here we present results from a computational method that uses genome analysis to characterize insect and eukaryote proteomes as an approximation complementary to experimental approaches. Results Homologs in common to Drosophila melanogaster, Anopheles gambiae, Bombyx mori, Tribolium castaneum, and Apis mellifera were compared to the complete genomes of three non-insect eukaryotes (opisthokonts) Homo sapiens, Caenorhabditis elegans and Saccharomyces cerevisiae. This operation yielded 154 groups of orthologous proteins in Drosophila to be insect-specific homologs; 466 groups were determined to be common to eukaryotes (represented by three opisthokonts). ESTs from the hemimetabolous insect Locust migratoria were also considered in order to approximate their corresponding genes in the insect-specific homologs. Stress and stimulus response proteins were found to constitute a higher fraction in the insect-specific homologs than in the homologs common to eukaryotes. Conclusion The significant representation of stress response and stimulus response proteins in proteins determined to be insect-specific, along with specific cuticle and pheromone/odorant binding proteins, suggest that communication and adaptation to environments may distinguish insect evolution relative to other eukaryotes. The tendency for low Ka/Ks ratios in the insect-specific protein set suggests purifying selection pressure. The generally larger number of paralogs in the insect-specific proteins may indicate adaptation to environment changes. Instances in our insect-specific protein set have been arrived at through experiments reported in the literature, supporting the accuracy of our approach. PMID:17407609

  2. A Conceptual Model of Childhood Adaptation to Type 1 Diabetes

    PubMed Central

    Whittemore, Robin; Jaser, Sarah; Guo, Jia; Grey, Margaret

    2010-01-01

    The Childhood Adaptation Model to Chronic Illness: Diabetes Mellitus was developed to identify factors that influence childhood adaptation to type 1 diabetes (T1D). Since this model was proposed, considerable research has been completed. The purpose of this paper is to update the model on childhood adaptation to T1D using research conducted since the original model was proposed. The framework suggests that individual and family characteristics, such as age, socioeconomic status, and in children with T1D, treatment modality (pump vs. injections), psychosocial responses (depressive symptoms and anxiety), and individual and family responses (self-management, coping, self-efficacy, family functioning, social competence) influence the level of adaptation. Adaptation has both physiologic (metabolic control) and psychosocial (QOL) components. This revised model provides greater specificity to the factors that influence adaptation to chronic illness in children. Research and clinical implications are discussed. PMID:20934079

  3. Adaptive control and noise suppression by a variable-gain gradient algorithm

    NASA Technical Reports Server (NTRS)

    Merhav, S. J.; Mehta, R. S.

    1987-01-01

    An adaptive control system based on normalized LMS filters is investigated. The finite impulse response of the nonparametric controller is adaptively estimated using a given reference model. Specifically, the following issues are addressed: The stability of the closed loop system is analyzed and heuristically established. Next, the adaptation process is studied for piecewise constant plant parameters. It is shown that by introducing a variable-gain in the gradient algorithm, a substantial reduction in the LMS adaptation rate can be achieved. Finally, process noise at the plant output generally causes a biased estimate of the controller. By introducing a noise suppression scheme, this bias can be substantially reduced and the response of the adapted system becomes very close to that of the reference model. Extensive computer simulations validate these and demonstrate assertions that the system can rapidly adapt to random jumps in plant parameters.

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

    PubMed

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

    2017-07-01

    Primary HIV-1 infection induces a virus-specific adaptive/cytolytic immune response that impacts the plasma viral load set point and the rate of progression to AIDS. Combination antiretroviral therapy (cART) suppresses plasma viremia to undetectable levels that rebound upon cART treatment interruption. Following cART withdrawal, the memory component of the virus-specific adaptive immune response may improve viral control compared to primary infection. Here, using primary infection and treatment interruption data from macaques infected with simian/human immunodeficiency virus (SHIV), we observe a lower peak viral load but an unchanged viral set point during viral rebound. The addition of an autologous stem cell transplant before cART withdrawal alters viral dynamics: we found a higher rebound set point but similar peak viral loads compared to the primary infection. Mathematical modeling of the data that accounts for fundamental immune parameters achieves excellent fit to heterogeneous viral loads. Analysis of model output suggests that the rapid memory immune response following treatment interruption does not ultimately lead to better viral containment. Transplantation decreases the durability of the adaptive immune response following cART withdrawal and viral rebound. Our model's results highlight the impact of the endogenous adaptive immune response during primary SHIV infection. Moreover, because we capture adaptive immune memory and the impact of transplantation, this model will provide insight into further studies of cure strategies inspired by the Berlin patient. IMPORTANCE HIV patients who interrupt combination antiretroviral therapy (cART) eventually experience viral rebound, the return of viral loads to pretreatment levels. However, the "Berlin patient" remained free of HIV rebound over a decade after stopping cART. His cure is attributed to leukemia treatment that included an HIV-resistant stem cell transplant. Inspired by this case, we studied the impact of stem cell transplantation in a macaque simian/HIV (SHIV) system. Using a mechanistic mathematical model, we found that while primary infection generates an adaptive immune memory response, stem cell transplantation disrupts this learned immunity. The results have implications for HIV cure regimens based on stem cell transplantation. Copyright © 2017 American Society for Microbiology.

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

    PubMed Central

    Peterson, Christopher W.; Kiem, Hans-Peter

    2017-01-01

    ABSTRACT Primary HIV-1 infection induces a virus-specific adaptive/cytolytic immune response that impacts the plasma viral load set point and the rate of progression to AIDS. Combination antiretroviral therapy (cART) suppresses plasma viremia to undetectable levels that rebound upon cART treatment interruption. Following cART withdrawal, the memory component of the virus-specific adaptive immune response may improve viral control compared to primary infection. Here, using primary infection and treatment interruption data from macaques infected with simian/human immunodeficiency virus (SHIV), we observe a lower peak viral load but an unchanged viral set point during viral rebound. The addition of an autologous stem cell transplant before cART withdrawal alters viral dynamics: we found a higher rebound set point but similar peak viral loads compared to the primary infection. Mathematical modeling of the data that accounts for fundamental immune parameters achieves excellent fit to heterogeneous viral loads. Analysis of model output suggests that the rapid memory immune response following treatment interruption does not ultimately lead to better viral containment. Transplantation decreases the durability of the adaptive immune response following cART withdrawal and viral rebound. Our model's results highlight the impact of the endogenous adaptive immune response during primary SHIV infection. Moreover, because we capture adaptive immune memory and the impact of transplantation, this model will provide insight into further studies of cure strategies inspired by the Berlin patient. IMPORTANCE HIV patients who interrupt combination antiretroviral therapy (cART) eventually experience viral rebound, the return of viral loads to pretreatment levels. However, the “Berlin patient” remained free of HIV rebound over a decade after stopping cART. His cure is attributed to leukemia treatment that included an HIV-resistant stem cell transplant. Inspired by this case, we studied the impact of stem cell transplantation in a macaque simian/HIV (SHIV) system. Using a mechanistic mathematical model, we found that while primary infection generates an adaptive immune memory response, stem cell transplantation disrupts this learned immunity. The results have implications for HIV cure regimens based on stem cell transplantation. PMID:28404854

  6. Adaptive tuning of mutation rates allows fast response to lethal stress in Escherichia coli

    PubMed Central

    Swings, Toon; Van den Bergh, Bram; Wuyts, Sander; Oeyen, Eline; Voordeckers, Karin; Verstrepen, Kevin J; Fauvart, Maarten; Verstraeten, Natalie; Michiels, Jan

    2017-01-01

    While specific mutations allow organisms to adapt to stressful environments, most changes in an organism's DNA negatively impact fitness. The mutation rate is therefore strictly regulated and often considered a slowly-evolving parameter. In contrast, we demonstrate an unexpected flexibility in cellular mutation rates as a response to changes in selective pressure. We show that hypermutation independently evolves when different Escherichia coli cultures adapt to high ethanol stress. Furthermore, hypermutator states are transitory and repeatedly alternate with decreases in mutation rate. Specifically, population mutation rates rise when cells experience higher stress and decline again once cells are adapted. Interestingly, we identified cellular mortality as the major force driving the quick evolution of mutation rates. Together, these findings show how organisms balance robustness and evolvability and help explain the prevalence of hypermutation in various settings, ranging from emergence of antibiotic resistance in microbes to cancer relapses upon chemotherapy. DOI: http://dx.doi.org/10.7554/eLife.22939.001 PMID:28460660

  7. Host-Specific Response to HCV Infection in the Chimeric SCID-beige/Alb-uPA Mouse Model: Role of the Innate Antiviral Immune Response

    PubMed Central

    Thompson, Jill C; Smith, Maria W; Yeh, Matthew M; Proll, Sean; Zhu, Lin-Fu; Gao, T. J; Kneteman, Norman M; Tyrrell, D. Lorne; Katze, Michael G

    2006-01-01

    The severe combined immunodeficiency disorder (SCID)-beige/albumin (Alb)-urokinase plasminogen activator (uPA) mouse containing a human-mouse chimeric liver is currently the only small animal model capable of supporting hepatitis C virus (HCV) infection. This model was utilized to characterize the host transcriptional response to HCV infection. The purpose of these studies was to investigate the genetic component of the host response to HCV infection and also to distinguish virus-induced gene expression changes from adaptive HCV-specific immune-mediated effects. Gene expression profiles from HCV-infected mice were also compared to those from HCV-infected patients. Analyses of the gene expression data demonstrate that host factors regulate the response to HCV infection, including the nature of the innate antiviral immune response. They also indicate that HCV mediates gene expression changes, including regulation of lipid metabolism genes, which have the potential to be directly cytopathic, indicating that liver pathology may not be exclusively mediated by HCV-specific adaptive immune responses. This effect appears to be inversely related to the activation of the innate antiviral immune response. In summary, the nature of the initial interferon response to HCV infection may determine the extent of viral-mediated effects on host gene expression. PMID:16789836

  8. Context-specific adaptation of the gain of the oculomotor response to lateral translation using roll and pitch head tilts as contexts

    NASA Technical Reports Server (NTRS)

    Shelhamer, Mark; Peng, Grace C Y.; Ramat, Stefano; Patel, Vivek

    2002-01-01

    Previous studies established that vestibular and oculomotor behaviors can have two adapted states (e.g., gain) simultaneously, and that a context cue (e.g., vertical eye position) can switch between the two states. The present study examined this phenomenon of context-specific adaptation for the oculomotor response to interaural translation (which we term "linear vestibulo-ocular reflex" or LVOR even though it may have extravestibular components). Subjects sat upright on a linear sled and were translated at 0.7 Hz and 0.3 gpeak acceleration while a visual-vestibular mismatch paradigm was used to adaptively increase (x2) or decrease (x0) the gain of the LVOR. In each experimental session, gain increase was asked for in one context, and gain decrease in another context. Testing in darkness with steps and sines before and after adaptation, in each context, assessed the extent to which the context itself could recall the gain state that was imposed in that context during adaptation. Two different contexts were used: head pitch (26 degrees forward and backward) and head roll (26 degrees or 45 degrees, right and left). Head roll tilt worked well as a context cue: with the head rolled to the right the LVOR could be made to have a higher gain than with the head rolled to the left. Head pitch tilt was less effective as a context cue. This suggests that the more closely related a context cue is to the response being adapted, the more effective it is.

  9. Domain-specific conflict adaptation without feature repetitions.

    PubMed

    Akçay, Çağlar; Hazeltine, Eliot

    2011-06-01

    An influential account of how cognitive control deals with conflicting sources of information holds that conflict is monitored by a module that automatically recruits attention to resolve the conflict. This leads to reduced effects of conflict on the subsequent trial, a phenomenon termed conflict adaptation. A prominent question is whether control processes are domain specific--that is, recruited only by the particular type of conflict they resolve. Previous studies that have examined this question used two-choice tasks in which feature repetition effects could be responsible for domain-specific adaptation effects. We report two experiments using four-choice (Experiment 1) and five-choice (Experiment 2) tasks that contain two types of irrelevant sources of potentially conflicting information: stimulus location (Simon conflict) and distractors (flanker conflict). In both experiments, we found within-type conflict adaptation for both types of conflict after eliminating trials on which stimulus features were repeated from one trial to the next. Across-type conflict adaptation, however, was not significant. Thus, conflict adaptation was due to domain-specific recruitment of cognitive control. Our results add converging evidence to the idea that multiple independent control processes are involved in reactive cognitive control, although whether control is always local remains to be determined.

  10. A conceptual model of childhood adaptation to type 1 diabetes.

    PubMed

    Whittemore, Robin; Jaser, Sarah; Guo, Jia; Grey, Margaret

    2010-01-01

    The Childhood Adaptation Model to Chronic Illness: Diabetes Mellitus was developed to identify factors that influence childhood adaptation to type 1 diabetes (T1D). Since this model was proposed, considerable research has been completed. The purpose of this article is to update the model on childhood adaptation to T1D using research conducted since the original model was proposed. The framework suggests that, in individuals and families, characteristics such as age and socioeconomic status as well as the individuals' and families' responses (self-management, coping, self-efficacy, family functioning, social competence) influence the level of adaptation; in children with T1D, characteristics such as treatment modality (pump vs injections) and psychosocial responses (depressive symptoms and anxiety) also influence the level of adaptation. Adaptation has both physiologic (metabolic control) and psychosocial (Quality of Life [QOL]) components. This revised model provides greater specificity to the factors that influence adaptation to chronic illness in children. Research and clinical implications are discussed. Copyright © 2010 Mosby, Inc. All rights reserved.

  11. Adaptive Filtering to Enhance Noise Immunity of Impedance and Admittance Spectroscopy: Comparison with Fourier Transformation

    NASA Astrophysics Data System (ADS)

    Stupin, Daniil D.; Koniakhin, Sergei V.; Verlov, Nikolay A.; Dubina, Michael V.

    2017-05-01

    The time-domain technique for impedance spectroscopy consists of computing the excitation voltage and current response Fourier images by fast or discrete Fourier transformation and calculating their relation. Here we propose an alternative method for excitation voltage and current response processing for deriving a system impedance spectrum based on a fast and flexible adaptive filtering method. We show the equivalence between the problem of adaptive filter learning and deriving the system impedance spectrum. To be specific, we express the impedance via the adaptive filter weight coefficients. The noise-canceling property of adaptive filtering is also justified. Using the RLC circuit as a model system, we experimentally show that adaptive filtering yields correct admittance spectra and elements ratings in the high-noise conditions when the Fourier-transform technique fails. Providing the additional sensitivity of impedance spectroscopy, adaptive filtering can be applied to otherwise impossible-to-interpret time-domain impedance data. The advantages of adaptive filtering are justified with practical living-cell impedance measurements.

  12. Proteomic analysis of the intestinal adaptation response reveals altered expression of fatty acid binding proteins following massive small bowel resection.

    PubMed

    Stephens, Andrew N; Pereira-Fantini, Prue M; Wilson, Guineva; Taylor, Russell G; Rainczuk, Adam; Meehan, Katie L; Sourial, Magdy; Fuller, Peter J; Stanton, Peter G; Robertson, David M; Bines, Julie E

    2010-03-05

    Intestinal adaptation in response to the loss of the small intestine is essential to restore enteral autonomy in patients who have undergone massive small bowel resection (MSBR). In a proportion of patients, intestinal function is not restored, resulting in chronic intestinal failure (IF). Early referral of such patients for transplant provides the best prognosis; however, the molecular mechanisms underlying intestinal adaptation remain elusive and there is currently no convenient marker to predict whether patients will develop IF. We have investigated the adaptation response in a well-characterized porcine model of intestinal adaptation. 2D DIGE analysis of ileal epithelium from piglets recovering from massive small bowel resection (MSBR) identified over 60 proteins that changed specifically in MSBR animals relative to nonoperational or sham-operated controls. Three fatty acid binding proteins (L-FABP, FABP-6, and I-FABP) showed changes in MSBR animals. The expression changes and localization of each FABP were validated by immunoblotting and immunohistochemical analysis. FABP expression changes in MSBR animals occurred concurrently with altered triglyceride and bile acid metabolism as well as weight gain. The observed FABP expression changes in the ileal epithelium occur as part of the intestinal adaptation response and could provide a clinically useful marker to evaluate adaptation following MSBR.

  13. Development of a Bayesian response-adaptive trial design for the Dexamethasone for Excessive Menstruation study.

    PubMed

    Holm Hansen, Christian; Warner, Pamela; Parker, Richard A; Walker, Brian R; Critchley, Hilary Od; Weir, Christopher J

    2017-12-01

    It is often unclear what specific adaptive trial design features lead to an efficient design which is also feasible to implement. This article describes the preparatory simulation study for a Bayesian response-adaptive dose-finding trial design. Dexamethasone for Excessive Menstruation aims to assess the efficacy of Dexamethasone in reducing excessive menstrual bleeding and to determine the best dose for further study. To maximise learning about the dose response, patients receive placebo or an active dose with randomisation probabilities adapting based on evidence from patients already recruited. The dose-response relationship is estimated using a flexible Bayesian Normal Dynamic Linear Model. Several competing design options were considered including: number of doses, proportion assigned to placebo, adaptation criterion, and number and timing of adaptations. We performed a fractional factorial study using SAS software to simulate virtual trial data for candidate adaptive designs under a variety of scenarios and to invoke WinBUGS for Bayesian model estimation. We analysed the simulated trial results using Normal linear models to estimate the effects of each design feature on empirical type I error and statistical power. Our readily-implemented approach using widely available statistical software identified a final design which performed robustly across a range of potential trial scenarios.

  14. Final Report - Epigenetics of low dose radiation effects in an animal model

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kovalchuk, Olga

    This project sought mechanistic understanding of the epigenetic response of tissues as well as the consequences of those responses, when induced by low dose irradiation in a well-established model system (mouse). Based on solid and extensive preliminary data we investigated the molecular epigenetic mechanisms of in vivo radiation responses, particularly – effects of low, occupationally relevant radiation exposures on the genome stability and adaptive response in mammalian tissues and organisms. We accumulated evidence that low dose irradiation altered epigenetic profiles and impacted radiation target organs of the exposed animals. The main long-term goal was to dissect the epigenetic basis ofmore » induction of the low dose radiation-induced genome instability and adaptive response and the specific fundamental roles of epigenetic changes (i.e. DNA methylation, histone modifications and miRNAs) in their generation. We hypothesized that changes in global and regional DNA methylation, global histone modifications and regulatory microRNAs played pivotal roles in the generation and maintenance low-dose radiation-induced genome instability and adaptive response. We predicted that epigenetic changes influenced the levels of genetic rearrangements (transposone reactivation). We hypothesized that epigenetic responses from low dose irradiation were dependent on exposure regimes, and would be greatest when organisms are exposed in a protracted/fractionated manner: fractionated exposures > acute exposures. We anticipated that the epigenetic responses were correlated with the gene expression levels. Our immediate objectives were: • To investigate the exact nature of the global and locus-specific DNA methylation changes in the LDR exposed cells and tissues and dissect their roles in adaptive response • To investigate the roles of histone modifications in the low dose radiation effects and adaptive response • To dissect the roles of regulatory microRNAs and their targets in low dose radiation effects and adaptive response • To correlate the levels of epigenetic changes with genetic rearrangement levels and gene expression patterns. In sum, we determined the precise global and locus-specific DNA methylation patterns in the LDR-exposed cells and tissues of mice, and to correlated DNA methylation changes with the gene expression patterns and manifestations of genome instability. We also determined the alterations of global histone modification pattern in the LDR exposed tissues. Additionally, we established the nature of microRNAome changes in the LDR exposed tissue. In this study we for the first time found that LDR exposure caused profound tissue-specific epigenetic changes in the exposed tissues. We established that LDR exposure affect methylation of repetitive elements in the murine genome, causes changes in histone methylation, acetylation and phosphorylation. Importantly, we found that LDR causes profound and persistent effects on small RNA profiles and gene expression, and that miRNAs are excellent biomarkers of LDR exposure. Furthermore, we extended our analysis and studied LDR effects in rat tissues and human tissues and cell lines. There we also analyzed LDR-induced gene expression, DNA methylation and miRNA changes. Our datasets laid foundation for several new research projects aimed to understand molecular underpinnings of low dose radiation responses, and biological repercussions of low dose radiation effects and radiation carcinogenesis.« less

  15. An application of adaption-innovation theory to bioremediation

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Guerin, L.J.; Guerin, T.F.

    1995-12-31

    This paper provides a discussion of the potential application of the Kirton Adaption-Innovation Inventory (KAI) for assessing the adaptive-innovative cognitive style of individuals and organizations within the bioremediation industry. Human-resource and line managers, or other individuals responsible for staff evaluation, selection, and project planning, should consider using the KAI to assist them in selecting individuals for specific roles requiring either an innovative or adaptive style. The KAI, a measure for assessing adaption-innovation at the individual employee level, is introduced and its potential value in the bioremediation industry is discussed.

  16. Early indices of deviance detection in humans and animal models.

    PubMed

    Grimm, Sabine; Escera, Carles; Nelken, Israel

    2016-04-01

    Detecting unexpected stimuli in the environment is a critical function of the auditory system. Responses to unexpected "deviant" sounds are enhanced compared to responses to expected stimuli. At the human scalp, deviance detection is reflected in the mismatch negativity (MMN) and in an enhancement of the middle-latency response (MLR). Single neurons often respond more strongly to a stimulus when rare than when common, a phenomenon termed stimulus-specific adaptation (SSA). Here we compare stimulus-specific adaptation with scalp-recorded deviance-related responses. We conclude that early markers of deviance detection in the time range of the MLR could be a direct correlate of cortical SSA. Both occur at an early level of cortical activation, both are robust findings with low-probability stimuli, and both show properties of genuine deviance detection. Their causal relation with the later scalp-recorded MMN is a key question in this field. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Stressor specificity of central neuroendocrine responses: implications for stress-related disorders.

    PubMed

    Pacák, K; Palkovits, M

    2001-08-01

    Despite the fact that many research articles have been written about stress and stress-related diseases, no scientifically accepted definition of stress exists. Selye introduced and popularized stress as a medical and scientific idea. He did not deny the existence of stressor-specific response patterns; however, he emphasized that such responses did not constitute stress, only the shared nonspecific component. In this review we focus mainly on the similarities and differences between the neuroendocrine responses (especially the sympathoadrenal and the sympathoneuronal systems and the hypothalamo-pituitary-adrenocortical axis) among various stressors and a strategy for testing Selye's doctrine of nonspecificity. In our experiments, we used five different stressors: immobilization, hemorrhage, cold exposure, pain, or hypoglycemia. With the exception of immobilization stress, these stressors also differed in their intensities. Our results showed marked heterogeneity of neuroendocrine responses to various stressors and that each stressor has a neurochemical "signature." By examining changes of Fos immunoreactivity in various brain regions upon exposure to different stressors, we also attempted to map central stressor-specific neuroendocrine pathways. We believe the existence of stressor-specific pathways and circuits is a clear step forward in the study of the pathogenesis of stress-related disorders and their proper treatment. Finally, we define stress as a state of threatened homeostasis (physical or perceived treat to homeostasis). During stress, an adaptive compensatory specific response of the organism is activated to sustain homeostasis. The adaptive response reflects the activation of specific central circuits and is genetically and constitutionally programmed and constantly modulated by environmental factors.

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

    PubMed

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

    2017-03-20

    From an ecological point of view, it is generally suggested that the main goal of vision in rats and mice is navigation and (aerial) predator evasion [1-3]. The latter requires fast and accurate detection of a change in the visual environment. An outstanding question is whether there are mechanisms in the rodent visual system that would support and facilitate visual change detection. An experimental protocol frequently used to investigate change detection in humans is the oddball paradigm, in which a rare, unexpected stimulus is presented in a train of stimulus repetitions [4]. A popular "predictive coding" theory of cortical responses states that neural responses should decrease for expected sensory input and increase for unexpected input [5, 6]. Despite evidence for response suppression and enhancement in noninvasive scalp recordings in humans with this paradigm [7, 8], it has proven challenging to observe both phenomena in invasive action potential recordings in other animals [9-11]. During a visual oddball experiment, we recorded multi-unit spiking activity in rat primary visual cortex (V1) and latero-intermediate area (LI), which is a higher area of the rodent ventral visual stream. In rat V1, there was only evidence for response suppression related to stimulus-specific adaptation, and not for response enhancement. However, higher up in area LI, spiking activity showed clear surprise-based response enhancement in addition to stimulus-specific adaptation. These results show that neural responses along the rat ventral visual stream become increasingly sensitive to changes in the visual environment, suggesting a system specialized in the detection of unexpected events. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Multispectral imaging method and apparatus

    DOEpatents

    Sandison, D.R.; Platzbecker, M.R.; Vargo, T.D.; Lockhart, R.R.; Descour, M.R.; Richards-Kortum, R.

    1999-07-06

    A multispectral imaging method and apparatus are described which are adapted for use in determining material properties, especially properties characteristic of abnormal non-dermal cells. A target is illuminated with a narrow band light beam. The target expresses light in response to the excitation. The expressed light is collected and the target's response at specific response wavelengths to specific excitation wavelengths is measured. From the measured multispectral response the target's properties can be determined. A sealed, remote probe and robust components can be used for cervical imaging. 5 figs.

  20. Multispectral imaging method and apparatus

    DOEpatents

    Sandison, David R.; Platzbecker, Mark R.; Vargo, Timothy D.; Lockhart, Randal R.; Descour, Michael R.; Richards-Kortum, Rebecca

    1999-01-01

    A multispectral imaging method and apparatus adapted for use in determining material properties, especially properties characteristic of abnormal non-dermal cells. A target is illuminated with a narrow band light beam. The target expresses light in response to the excitation. The expressed light is collected and the target's response at specific response wavelengths to specific excitation wavelengths is measured. From the measured multispectral response the target's properties can be determined. A sealed, remote probe and robust components can be used for cervical imaging

  1. Failing Tests: Commentary on "Adapting Educational Measurement to the Demands of Test-Based Accountability"

    ERIC Educational Resources Information Center

    Thissen, David

    2015-01-01

    In "Adapting Educational Measurement to the Demands of Test-Based Accountability" Koretz takes the time-honored engineering approach to educational measurement, identifying specific problems with current practice and proposing minimal modifications of the system to alleviate those problems. In response to that article, David Thissen…

  2. Adaptations in rod outer segment disc membranes in response to environmental lighting conditions.

    PubMed

    Rakshit, Tatini; Senapati, Subhadip; Parmar, Vipul M; Sahu, Bhubanananda; Maeda, Akiko; Park, Paul S-H

    2017-10-01

    The light-sensing rod photoreceptor cell exhibits several adaptations in response to the lighting environment. While adaptations to short-term changes in lighting conditions have been examined in depth, adaptations to long-term changes in lighting conditions are less understood. Atomic force microscopy was used to characterize the structure of rod outer segment disc membranes, the site of photon absorption by the pigment rhodopsin, to better understand how photoreceptor cells respond to long-term lighting changes. Structural properties of the disc membrane changed in response to housing mice in constant dark or light conditions and these adaptive changes required output from the phototransduction cascade initiated by rhodopsin. Among these were changes in the packing density of rhodopsin in the membrane, which was independent of rhodopsin synthesis and specifically affected scotopic visual function as assessed by electroretinography. Studies here support the concept of photostasis, which maintains optimal photoreceptor cell function with implications in retinal degenerations. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Exposure to Stressful Environments: Strategy of Adaptive Responses

    NASA Technical Reports Server (NTRS)

    Farhi, Leon E.

    1991-01-01

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

  4. Transactional Associations between Youths' Responses to Peer Stress and Depression: The Moderating Roles of Sex and Stress Exposure

    ERIC Educational Resources Information Center

    Agoston, Anna M.; Rudolph, Karen D.

    2011-01-01

    This study examined transactional associations between responses to peer stress and depression in youth. Specifically, it tested the hypotheses that (a) depression would predict fewer effortful responses and more involuntary, dysregulated responses to peer stress over time; and (b) fewer adaptive and more maladaptive responses would predict…

  5. Convergence in probiotic Lactobacillus gut-adaptive responses in humans and mice.

    PubMed

    Marco, Maria L; de Vries, Maaike C; Wels, Michiel; Molenaar, Douwe; Mangell, Peter; Ahrne, Siv; de Vos, Willem M; Vaughan, Elaine E; Kleerebezem, Michiel

    2010-11-01

    Probiotic bacteria provide unique opportunities to study the global responses and molecular mechanisms underlying the effects of gut-associated microorganisms in the human digestive tract. In this study, we show by comparative transcriptome analysis using DNA microarrays that the established probiotic Lactobacillus plantarum 299v specifically adapts its metabolic capacity in the human intestine for carbohydrate acquisition and expression of exopolysaccharide and proteinaceous cell surface compounds. This report constitutes the first application of global gene expression profiling of a commensal microorganism in the human gut. A core L. plantarum transcriptome expressed in the mammalian intestine was also determined through comparisons of L. plantarum 299v activities in humans to those found for L. plantarum WCFS1 in germ-free mice. These results identify the niche-specific adaptations of a dietary microorganism to the intestinal ecosystem and provide novel targets for molecular analysis of microbial-host interactions which affect human health.

  6. The AdaptiSPECT Imaging Aperture

    PubMed Central

    Chaix, Cécile; Moore, Jared W.; Van Holen, Roel; Barrett, Harrison H.; Furenlid, Lars R.

    2015-01-01

    In this paper, we present the imaging aperture of an adaptive SPECT imaging system being developed at the Center for Gamma Ray Imaging (AdaptiSPECT). AdaptiSPECT is designed to automatically change its configuration in response to preliminary data, in order to improve image quality for a particular task. In a traditional pinhole SPECT imaging system, the characteristics (magnification, resolution, field of view) are set by the geometry of the system, and any modification can be accomplished only by manually changing the collimator and the distance of the detector to the center of the field of view. Optimization of the imaging system for a specific task on a specific individual is therefore difficult. In an adaptive SPECT imaging system, on the other hand, the configuration can be conveniently changed under computer control. A key component of an adaptive SPECT system is its aperture. In this paper, we present the design, specifications, and fabrication of the adaptive pinhole aperture that will be used for AdaptiSPECT, as well as the controls that enable autonomous adaptation. PMID:27019577

  7. Local auxin production underlies a spatially restricted neighbor-detection response in Arabidopsis

    PubMed Central

    Michaud, Olivier

    2017-01-01

    Competition for light triggers numerous developmental adaptations known as the “shade-avoidance syndrome” (SAS). Important molecular events underlying specific SAS responses have been identified. However, in natural environments light is often heterogeneous, and it is currently unknown how shading affecting part of a plant leads to local responses. To study this question, we analyzed upwards leaf movement (hyponasty), a rapid adaptation to neighbor proximity, in Arabidopsis. We show that manipulation of the light environment at the leaf tip triggers a hyponastic response that is restricted to the treated leaf. This response is mediated by auxin synthesized in the blade and transported to the petiole. Our results suggest that a strong auxin response in the vasculature of the treated leaf and auxin signaling in the epidermis mediate leaf elevation. Moreover, the analysis of an auxin-signaling mutant reveals signaling bifurcation in the control of petiole elongation versus hyponasty. Our work identifies a mechanism for a local shade response that may pertain to other plant adaptations to heterogeneous environments. PMID:28652343

  8. Increased susceptibility to fungal disease accompanies adaptation to drought in Brassica rapa.

    PubMed

    O'Hara, Niamh B; Rest, Joshua S; Franks, Steven J

    2016-01-01

    Recent studies have demonstrated adaptive evolutionary responses to climate change, but little is known about how these responses may influence ecological interactions with other organisms, including natural enemies. We used a resurrection experiment in the greenhouse to examine the effect of evolutionary responses to drought on the susceptibility of Brassica rapa plants to a fungal pathogen, Alternaria brassicae. In agreement with previous studies in this population, we found an evolutionary shift to earlier flowering postdrought, which was previously shown to be adaptive. Here, we report the novel finding that postdrought descendant plants were also more susceptible to disease, indicating a rapid evolutionary shift to increased susceptibility. This was accompanied by an evolutionary shift to increased specific leaf area (thinner leaves) following drought. We found that flowering time and disease susceptibility displayed plastic responses to experimental drought treatments, but that this plasticity did not match the direction of evolution, indicating that plastic and evolutionary responses to changes in climate can be opposed. The observed evolutionary shift to increased disease susceptibility accompanying adaptation to drought provides evidence that even if populations can rapidly adapt in response to climate change, evolution in other traits may have ecological effects that could make species more vulnerable. © 2015 The Author(s). Evolution © 2015 The Society for the Study of Evolution.

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

    PubMed

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

    2016-01-01

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

  10. Antitumor immune responses mediated by dendritic cells

    PubMed Central

    Spel, Lotte; Boelens, Jaap-Jan; Nierkens, Stefan; Boes, Marianne

    2013-01-01

    Dendritic cells (DCs) are essential for the induction of adaptive immune responses against malignant cells by virtue of their capacity to effectively cross-present exogenous antigens to T lymphocytes. Dying cancer cells are indeed a rich source of antigens that may be harnessed for the development of DC-based vaccines. In particular, malignant cells succumbing to apoptosis, rather than necrosis, appear to release antigens in a manner that allows for the elicitation of adaptive immune responses. In this review, we describe the processes that mediate the cross-presentation of antigens released by apoptotic cancer cells to CD8+ T lymphocytes, resulting in the activation of protective tumor-specific immune responses. PMID:24482744

  11. Postural perturbations: new insights for treatment of balance disorders

    NASA Technical Reports Server (NTRS)

    Horak, F. B.; Henry, S. M.; Shumway-Cook, A.; Peterson, B. W. (Principal Investigator)

    1997-01-01

    This article reviews the neural control of posture as understood through studies of automatic responses to mechanical perturbations. Recent studies of responses to postural perturbations have provided a new view of how postural stability is controlled, and this view has profound implications for physical therapy practice. We discuss the implications for rehabilitation of balance disorders and demonstrate how an understanding of the specific systems underlying postural control can help to focus and enrich our therapeutic approaches. By understanding the basic systems underlying control of balance, such as strategy selection, rapid latencies, coordinated temporal spatial patterns, force control, and context-specific adaptations, therapists can focus their treatment on each patient's specific impairments. Research on postural responses to surface translations has shown that balance is not based on a fixed set of equilibrium reflexes but on a flexible, functional motor skill that can adapt with training and experience. More research is needed to determine the extent to which quantification of automatic postural responses has practical implications for predicting falls in patients with constraints in their postural control system.

  12. Adaptation and perceptual norms

    NASA Astrophysics Data System (ADS)

    Webster, Michael A.; Yasuda, Maiko; Haber, Sara; Leonard, Deanne; Ballardini, Nicole

    2007-02-01

    We used adaptation to examine the relationship between perceptual norms--the stimuli observers describe as psychologically neutral, and response norms--the stimulus levels that leave visual sensitivity in a neutral or balanced state. Adapting to stimuli on opposite sides of a neutral point (e.g. redder or greener than white) biases appearance in opposite ways. Thus the adapting stimulus can be titrated to find the unique adapting level that does not bias appearance. We compared these response norms to subjectively defined neutral points both within the same observer (at different retinal eccentricities) and between observers. These comparisons were made for visual judgments of color, image focus, and human faces, stimuli that are very different and may depend on very different levels of processing, yet which share the property that for each there is a well defined and perceptually salient norm. In each case the adaptation aftereffects were consistent with an underlying sensitivity basis for the perceptual norm. Specifically, response norms were similar to and thus covaried with the perceptual norm, and under common adaptation differences between subjectively defined norms were reduced. These results are consistent with models of norm-based codes and suggest that these codes underlie an important link between visual coding and visual experience.

  13. CHRONIC ALCOHOL NEUROADAPTATION AND STRESS CONTRIBUTE TO SUSCEPTIBILITY FOR ALCOHOL CRAVING AND RELAPSE

    PubMed Central

    BREESE, GEORGE R.; SINHA, RAJITA; HEILIG, MARKUS

    2010-01-01

    Alcoholism is a chronic relapsing disorder. Major characteristics observed in alcoholics during an initial period of alcohol abstinence are altered physiological functions and a negative emotional state. Evidence suggests that a persistent, cumulative adaptation involving a kindling/allostasis-like process occurs during the course of repeated chronic alcohol exposures that is critical for the negative symptoms observed during alcohol withdrawal. Basic studies have provided evidence for specific neurotransmitters within identified brain sites being responsible for the negative emotion induced by the persistent cumulative adaptation following intermittent-alcohol exposures. After an extended period of abstinence, the cumulative alcohol adaptation increases susceptibility to stress- and alcohol cue-induced negative symptoms and alcohol seeking, both of which can facilitate excessive ingestion of alcohol. In the alcoholic, stressful imagery and alcohol cues alter physiological responses, enhance negative emotion, and induce craving. Brain fMRI imaging following stress and alcohol cues has documented neural changes in specific brain regions of alcoholics not observed in social drinkers. Such altered activity in brain of abstinent alcoholics to stress and alcohol cues is consistent with a continuing ethanol adaptation being responsible. Therapies in alcoholics found to block responses to stress and alcohol cues would presumably be potential treatments by which susceptibility for continued alcohol abuse can be reduced. By continuing to define the neurobiological basis of the sustained alcohol adaptation critical for the increased susceptibility of alcoholics to stress and alcohol cues that facilitate craving, a new era is expected to evolve in which the high rate of relapse in alcoholism is minimized. 250 PMID:20951730

  14. Correlation of proteome-wide changes with social immunity behaviors provides insight into resistance to the parasitic mite, Varroa destructor, in the honey bee (Apis mellifera)

    PubMed Central

    2012-01-01

    Background Disease is a major factor driving the evolution of many organisms. In honey bees, selection for social behavioral responses is the primary adaptive process facilitating disease resistance. One such process, hygienic behavior, enables bees to resist multiple diseases, including the damaging parasitic mite Varroa destructor. The genetic elements and biochemical factors that drive the expression of these adaptations are currently unknown. Proteomics provides a tool to identify proteins that control behavioral processes, and these proteins can be used as biomarkers to aid identification of disease tolerant colonies. Results We sampled a large cohort of commercial queen lineages, recording overall mite infestation, hygiene, and the specific hygienic response to V. destructor. We performed proteome-wide correlation analyses in larval integument and adult antennae, identifying several proteins highly predictive of behavior and reduced hive infestation. In the larva, response to wounding was identified as a key adaptive process leading to reduced infestation, and chitin biosynthesis and immune responses appear to represent important disease resistant adaptations. The speed of hygienic behavior may be underpinned by changes in the antenna proteome, and chemosensory and neurological processes could also provide specificity for detection of V. destructor in antennae. Conclusions Our results provide, for the first time, some insight into how complex behavioural adaptations manifest in the proteome of honey bees. The most important biochemical correlations provide clues as to the underlying molecular mechanisms of social and innate immunity of honey bees. Such changes are indicative of potential divergence in processes controlling the hive-worker maturation. PMID:23021491

  15. Correlation of proteome-wide changes with social immunity behaviors provides insight into resistance to the parasitic mite, Varroa destructor, in the honey bee (Apis mellifera).

    PubMed

    Parker, Robert; Guarna, M Marta; Melathopoulos, Andony P; Moon, Kyung-Mee; White, Rick; Huxter, Elizabeth; Pernal, Stephen F; Foster, Leonard J

    2012-06-29

    Disease is a major factor driving the evolution of many organisms. In honey bees, selection for social behavioral responses is the primary adaptive process facilitating disease resistance. One such process, hygienic behavior, enables bees to resist multiple diseases, including the damaging parasitic mite Varroa destructor. The genetic elements and biochemical factors that drive the expression of these adaptations are currently unknown. Proteomics provides a tool to identify proteins that control behavioral processes, and these proteins can be used as biomarkers to aid identification of disease tolerant colonies. We sampled a large cohort of commercial queen lineages, recording overall mite infestation, hygiene, and the specific hygienic response to V. destructor. We performed proteome-wide correlation analyses in larval integument and adult antennae, identifying several proteins highly predictive of behavior and reduced hive infestation. In the larva, response to wounding was identified as a key adaptive process leading to reduced infestation, and chitin biosynthesis and immune responses appear to represent important disease resistant adaptations. The speed of hygienic behavior may be underpinned by changes in the antenna proteome, and chemosensory and neurological processes could also provide specificity for detection of V. destructor in antennae. Our results provide, for the first time, some insight into how complex behavioural adaptations manifest in the proteome of honey bees. The most important biochemical correlations provide clues as to the underlying molecular mechanisms of social and innate immunity of honey bees. Such changes are indicative of potential divergence in processes controlling the hive-worker maturation.

  16. A surgeons' guide to renal transplant immunopathology, immunology, and immunosuppression.

    PubMed

    Gaber, Lillian W; Knight, Richard J; Patel, Samir J

    2013-12-01

    The response to allografting involves adaptive and innate immune mechanisms. In the adaptive system, activated T cells differentiate to cytotoxic effectors that attack the graft and trigger B cells to differentiation to plasma cells that produce anti-HLA antibodies. The innate immune system recognizes antigens in a non-specific manner and recruits immune cells to the graft through the productions of chemotactic factors, and activation of cytokines and the complement cascade. In the kidney the tubules and the endothelium are the targets of the rejection response. Immune suppression is effective in modulating the adaptive immune system effect on graft histology. Copyright © 2013 Elsevier Inc. All rights reserved.

  17. Tactile Speech Indicator: Adaptive Telephone Device for Deaf-Blind Clients.

    ERIC Educational Resources Information Center

    Lynch, M. R.

    1990-01-01

    This article describes basic applications of an adaptive telephone device for deaf-blind persons with speaking voices. The deaf-blind caller poses questions requiring one-word answers, and the device vibrates in response to touch-tone pulses from the other party. Specific suggestions for such uses as making appointments and emergency calls are…

  18. Reactive oxygen species mediate growth and death in submerged plants

    PubMed Central

    Steffens, Bianka; Steffen-Heins, Anja; Sauter, Margret

    2013-01-01

    Aquatic and semi-aquatic plants are well adapted to survive partial or complete submergence which is commonly accompanied by oxygen deprivation. The gaseous hormone ethylene controls a number of adaptive responses to submergence including adventitious root growth and aerenchyma formation. Reactive oxygen species (ROS) act as signaling intermediates in ethylene-controlled submergence adaptation and possibly also independent of ethylene. ROS levels are controlled by synthesis, enzymatic metabolism, and non-enzymatic scavenging. While the actors are by and large known, we still have to learn about altered ROS at the subcellular level and how they are brought about, and the signaling cascades that trigger a specific response. This review briefly summarizes our knowledge on the contribution of ROS to submergence adaptation and describes spectrophotometrical, histochemical, and live cell imaging detection methods that have been used to study changes in ROS abundance. Electron paramagnetic resonance (EPR) spectroscopy is introduced as a method that allows identification and quantification of specific ROS in cell compartments. The use of advanced technologies such as EPR spectroscopy will be necessary to untangle the intricate and partially interwoven signaling networks of ethylene and ROS. PMID:23761805

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

    PubMed Central

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

    2016-01-01

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

  20. Analysis of the microRNA signature driving adaptive right ventricular hypertrophy in an ovine model of congenital heart disease.

    PubMed

    Kameny, Rebecca Johnson; He, Youping; Zhu, Terry; Gong, Wenhui; Raff, Gary W; Chapin, Cheryl J; Datar, Sanjeev A; Boehme, Jason; Hata, Akiko; Fineman, Jeffrey R

    2018-06-15

    The right ventricular (RV) response to pulmonary arterial hypertension (PAH) is heterogeneous. Most patients have maladaptive changes with RV dilation and failure while some-especially patients with PAH secondary to congenital heart disease (CHD)-have an adaptive response with hypertrophy and preserved systolic function. Mechanisms for RV adaptation to PAH are unknown despite RV function being a primary determinant of mortality. In our CHD ovine model with fetally-implanted aortopulmonary shunt (shunt lambs), we previously demonstrated an adaptive physiologic RV response to increased afterload with hypertrophy. In this study, we examined small noncoding microRNA (miRNA) expression in shunt RV and characterized downstream effects of a key miRNA. RV tissue was harvested from 4-week-old shunt and control lambs (n=5) and miRNA, mRNA, and proteins were quantitated. We found differential expression of 40 cardiovascular-specific miRNA in shunt RV. Interestingly, this miRNA signature is distinct from models of RV failure, suggesting that miRNAs might contribute to adaptive RV hypertrophy. Among RV miRNAs, miR-199b is decreased in RV with eventual downregulation of nuclear factor of activated T-cells (NFAT)/calcineurin signaling. Furthermore, anti-fibrotic miR-29a is increased in shunt RV with reduction of miR-29 targets Collagen A1 and 3A1 and decreased fibrosis. Thus, we conclude that the miRNA signature specific to shunt lambs is distinct from RV failure and drives gene expression required for adaptive RV hypertrophy. We propose that the adaptive RV miRNA signature may serve as a prognostic and therapeutic tool in patients with PAH to attenuate or prevent progression of RV failure and premature death.

  1. Obstacle avoidance locomotor tasks: adaptation, memory and skill transfer.

    PubMed

    Kloter, Evelyne; Dietz, Volker

    2012-05-01

    The aim of this study was to explore the neural basis of adaptation, memory and skill transfer during human stepping over obstacles. Whilst walking on a treadmill, subjects had to perform uni- and bilateral obstacle steps. Acoustic feedback information about foot clearance was provided. Non-noxious electrical stimuli were applied to the right tibial nerve during the mid-stance phase of the right leg, i.e. 'prior' to the right or 'during' the left leg swing over the obstacle. The electromyogram (EMG) responses evoked by these stimuli in arm and leg muscles are known to reflect the neural coordination during normal and obstacle steps. The leading and trailing legs rapidly adapted foot clearance during obstacle steps with small further changes when the same obstacle condition was repeated. This adaptation was associated with a corresponding decrease in arm and leg muscle reflex EMG responses. Arm (but not leg) muscle EMG responses were greater when the stimulus was applied 'during' obstacle crossing by the left leg leading compared with stimulation 'prior' to right leg swing over the obstacle. A corresponding difference existed in arm muscle background EMG. The results indicate that, firstly, the somatosensory information gained by the performance and adaptation of uni- and bilateral obstacle stepping becomes transferred to the trailing leg in a context-specific manner. Secondly, EMG activity in arm and leg muscles parallels biomechanical adaptation of foot clearance. Thirdly, a consistently high EMG activity in the arm muscles during swing over the obstacle is required for equilibrium control. Thus, such a precision locomotor task is achieved by a context-specific, coordinated activation of arm and leg muscles for performance and equilibrium control that includes adaptation, memory and skill transfer. © 2012 The Authors. European Journal of Neuroscience © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

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

    PubMed

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

    2005-01-01

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

  3. Does Cultural Adaptation Have a Role in Substance Abuse Treatment?

    PubMed Central

    Burlew, A. Kathleen; Copeland, Valire Carr; Ahuama-Jonas, Chizara; Calsyn, Donald A.

    2013-01-01

    The changing ethnic composition of the nation and increasing requirements to use evidence-based treatments (EBTs) challenge mental health professionals to adapt treatments and interventions to be appropriate for their clients. This article applies the available information on cultural adaptation to substance abuse. The authors’ review suggests that the most common approaches for adapting substance use interventions include some combination of either community involvement in the adaptation, existing research and literature, and/or consultation from experts to adapt EBTs. The challenges facing the development of culturally adapted interventions include the need for additional research to determine which specific EBTs warrant adaptation, the responsibility of maintaining the balance between fidelity and adaptation, and the challenge of intragroup diversity. PMID:23731430

  4. Interactive Book Reading to Accelerate Word Learning by Kindergarten Children with Specific Language Impairment: Identifying an Adequate Intensity and Variation in Treatment Response

    ERIC Educational Resources Information Center

    Storkel, Holly L.; Voelmle, Krista; Fierro, Veronica; Flake, Kelsey; Fleming, Kandace K.; Romine, Rebecca Swinburne

    2017-01-01

    Purpose: This study sought to identify an adequate intensity of interactive book reading for new word learning by children with specific language impairment (SLI) and to examine variability in treatment response. Method: An escalation design adapted from nontoxic drug trials (Hunsberger, Rubinstein, Dancey, & Korn, 2005) was used in this Phase…

  5. Enhancement of infectious disease vaccines through TLR9-dependent recognition of CpG DNA.

    PubMed

    McCluskie, M J; Krieg, A M

    2006-01-01

    The adaptive immune system-with its remarkable ability to generate antigen-specific antibodies and T lymphocytes against pathogens never before "seen" by an organism-is one of the marvels of evolution. However, to generate these responses, the adaptive immune system requires activation by the innate immune system. Toll-like receptors (TLRs) are perhaps the best-understood family of innate immune receptors for detecting infections and stimulating adaptive immune responses. TLR9 appears to have evolved to recognize infections by a subtle structural difference between eukaryotic and prokaryotic/viral DNA; only the former frequently methylates CpG dinucleotides. Used as vaccine adjuvants, synthetic oligodeoxynucleotide (ODN) ligands for TLR9--CpG ODN--greatly enhance the speed and strength of the immune responses to vaccination.

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

    NASA Astrophysics Data System (ADS)

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

    2015-10-01

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

  7. A model of anuran auditory periphery reveals frequency-dependent adaptation to be a contributing mechanism for two-tone suppression and amplitude modulation coding.

    PubMed

    Wotton, J M; Ferragamo, M J

    2011-10-01

    Anuran auditory nerve fibers (ANF) tuned to low frequencies display unusual frequency-dependent adaptation which results in a more phasic response to signals above best frequency (BF) and a more tonic response to signals below. A network model of the first two layers of the anuran auditory system was used to test the contribution of this dynamic peripheral adaptation on two-tone suppression and amplitude modulation (AM) tuning. The model included a peripheral sandwich component, leaky-integrate-and-fire cells and adaptation was implemented by means of a non-linear increase in threshold weighted by the signal frequency. The results of simulations showed that frequency-dependent adaptation was both necessary and sufficient to produce high-frequency-side two-tone suppression for the ANF and cells of the dorsal medullary nucleus (DMN). It seems likely that both suppression and this dynamic adaptation share a common mechanism. The response of ANFs to AM signals was influenced by adaptation and carrier frequency. Vector strength synchronization to an AM signal improved with increased adaptation. The spike rate response to a carrier at BF was the expected flat function with AM rate. However, for non-BF carrier frequencies the response showed a weak band-pass pattern due to the influence of signal sidebands and adaptation. The DMN received inputs from three ANFs and when the frequency tuning of inputs was near the carrier, then the rate response was a low-pass or all-pass shape. When most of the inputs were biased above or below the carrier, then band-pass responses were observed. Frequency-dependent adaptation enhanced the band-pass tuning for AM rate, particularly when the response of the inputs was predominantly phasic for a given carrier. Different combinations of inputs can therefore bias a DMN cell to be especially well suited to detect specific ranges of AM rates for a particular carrier frequency. Such selection of inputs would clearly be advantageous to the frog in recognizing distinct spectral and temporal parameters in communication calls. Copyright © 2011 Elsevier B.V. All rights reserved.

  8. The Escherichia coli Cpx envelope stress response regulates genes of diverse function that impact antibiotic resistance and membrane integrity.

    PubMed

    Raivio, Tracy L; Leblanc, Shannon K D; Price, Nancy L

    2013-06-01

    The Cpx envelope stress response mediates adaptation to stresses that cause envelope protein misfolding. Adaptation is partly conferred through increased expression of protein folding and degradation factors. The Cpx response also plays a conserved role in the regulation of virulence determinant expression and impacts antibiotic resistance. We sought to identify adaptive mechanisms that may be involved in these important functions by characterizing changes in the transcriptome of two different Escherichia coli strains when the Cpx response is induced. We show that, while there is considerable strain- and condition-specific variability in the Cpx response, the regulon is enriched for proteins and functions that are inner membrane associated under all conditions. Genes that were changed by Cpx pathway induction under all conditions were involved in a number of cellular functions and included several intergenic regions, suggesting that posttranscriptional regulation is important during Cpx-mediated adaptation. Some Cpx-regulated genes are centrally involved in energetics and play a role in antibiotic resistance. We show that a number of small, uncharacterized envelope proteins are Cpx regulated and at least two of these affect phenotypes associated with membrane integrity. Altogether, our work suggests new mechanisms of Cpx-mediated envelope stress adaptation and antibiotic resistance.

  9. Muscle redox signalling pathways in exercise. Role of antioxidants.

    PubMed

    Mason, Shaun A; Morrison, Dale; McConell, Glenn K; Wadley, Glenn D

    2016-09-01

    Recent research highlights the importance of redox signalling pathway activation by contraction-induced reactive oxygen species (ROS) and nitric oxide (NO) in normal exercise-related cellular and molecular adaptations in skeletal muscle. In this review, we discuss some potentially important redox signalling pathways in skeletal muscle that are involved in acute and chronic responses to contraction and exercise. Specifically, we discuss redox signalling implicated in skeletal muscle contraction force, mitochondrial biogenesis and antioxidant enzyme induction, glucose uptake and muscle hypertrophy. Furthermore, we review evidence investigating the impact of major exogenous antioxidants on these acute and chronic responses to exercise. Redox signalling pathways involved in adaptive responses in skeletal muscle to exercise are not clearly elucidated at present, and further research is required to better define important signalling pathways involved. Evidence of beneficial or detrimental effects of specific antioxidant compounds on exercise adaptations in muscle is similarly limited, particularly in human subjects. Future research is required to not only investigate effects of specific antioxidant compounds on skeletal muscle exercise adaptations, but also to better establish mechanisms of action of specific antioxidants in vivo. Although we feel it remains somewhat premature to make clear recommendations in relation to application of specific antioxidant compounds in different exercise settings, a bulk of evidence suggests that N-acetylcysteine (NAC) is ergogenic through its effects on maintenance of muscle force production during sustained fatiguing events. Nevertheless, a current lack of evidence from studies using performance tests representative of athletic competition and a potential for adverse effects with high doses (>70mg/kg body mass) warrants caution in its use for performance enhancement. In addition, evidence implicates high dose vitamin C (1g/day) and E (≥260 IU/day) supplementation in impairments to some skeletal muscle cellular adaptations to chronic exercise training. Thus, determining the utility of antioxidant supplementation in athletes likely requires a consideration of training and competition periodization cycles of athletes in addition to type, dose and duration of antioxidant supplementation. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Accounting for sequential trial effects in the flanker task: conflict adaptation or associative priming?

    PubMed

    Nieuwenhuis, Sander; Stins, John F; Posthuma, Danielle; Polderman, Tinca J C; Boomsma, Dorret I; de Geus, Eco J

    2006-09-01

    The conflict-control loop theory proposes that the detection of conflict in information processing triggers an increase in cognitive control, resulting in improved performance on the subsequent trial. This theory seems consistent with the robust finding that conflict susceptibility is reduced following correct trials associated with high conflict: the conflict adaptation effect. However, despite providing favorable conditions for eliciting and detecting conflict-triggered performance adjustments, none of the five experiments reported here provide unequivocal evidence of such adjustments. Instead, the results corroborate and extend earlier findings by demonstrating that the conflict adaptation effect, at least in the flanker task, is only present for a specific subset of trial sequences that is characterized by a response repetition. This pattern of results provides strong evidence that the conflict adaptation effect reflects associative stimulus-response priming instead of conflict-driven adaptations in cognitive control.

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

    PubMed

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

    2017-07-23

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

  12. Molecular and physiological evidence of genetic assimilation to high CO2 in the marine nitrogen fixer Trichodesmium.

    PubMed

    Walworth, Nathan G; Lee, Michael D; Fu, Fei-Xue; Hutchins, David A; Webb, Eric A

    2016-11-22

    Most investigations of biogeochemically important microbes have focused on plastic (short-term) phenotypic responses in the absence of genetic change, whereas few have investigated adaptive (long-term) responses. However, no studies to date have investigated the molecular progression underlying the transition from plasticity to adaptation under elevated CO 2 for a marine nitrogen-fixer. To address this gap, we cultured the globally important cyanobacterium Trichodesmium at both low and high CO 2 for 4.5 y, followed by reciprocal transplantation experiments to test for adaptation. Intriguingly, fitness actually increased in all high-CO 2 adapted cell lines in the ancestral environment upon reciprocal transplantation. By leveraging coordinated phenotypic and transcriptomic profiles, we identified expression changes and pathway enrichments that rapidly responded to elevated CO 2 and were maintained upon adaptation, providing strong evidence for genetic assimilation. These candidate genes and pathways included those involved in photosystems, transcriptional regulation, cell signaling, carbon/nitrogen storage, and energy metabolism. Conversely, significant changes in specific sigma factor expression were only observed upon adaptation. These data reveal genetic assimilation as a potentially adaptive response of Trichodesmium and importantly elucidate underlying metabolic pathways paralleling the fixation of the plastic phenotype upon adaptation, thereby contributing to the few available data demonstrating genetic assimilation in microbial photoautotrophs. These molecular insights are thus critical for identifying pathways under selection as drivers in plasticity and adaptation.

  13. Cross-cultural adaptation and validation of the Korean version of the EQ-5D in patients with rheumatic diseases.

    PubMed

    Kim, Myoung-Hee; Cho, Young-Shin; Uhm, Wan-Sik; Kim, Sehyun; Bae, Sang-Cheol

    2005-06-01

    This study aimed to determine the cross-cultural adaptation and validation of the Korean version of the EQ-5D in rheumatic conditions. Translation, back-translation and cognitive debriefing were performed according to the EuroQol group's guidelines. For validity, 508 patients were recruited and administered the EQ-5D, Short-Form 36 and condition-specific measures. Construct validity and sensitivity were evaluated by testing a-priori hypotheses. For reliability, another 57 patients repeated the EQ-5D at 1-week interval, and intra-class correlations (ICC) and kappa statistics were estimated. For responsiveness, another 60 patients repeated it at 12-week interval within the context of clinical trial, and standardized response mean(SRM) were calculated. The cross-cultural adaptation produced no major modifications in the scale. The associations of the EQ-5D with the generic- and condition-specific measures were observed as expected in hypotheses: the higher EQ-5Dindex and EQ-5D(VAS) scores, the better health status by generic- or condition-specific measures, and the better functional class. The ICCs were 0.751 and 0.767, respectively, and kappa ranged from 0.455 to 0.772. The SRM were 0.649 and 0.410, respectively. The Korean EQ-5D exhibits good validity and sensitivity in various rheumatic conditions. Although its reliability and responsiveness were not excellent, it seems acceptable if condition-specific measures are applied together.

  14. Evaluating within-population variability in behavior and demography for the adaptive potential of a dispersal-limited species to climate change

    USGS Publications Warehouse

    Muñoz, David J.; Miller Hesed, Kyle; Grant, Evan H. Campbell; Miller, David A.W.

    2016-01-01

    Multiple pathways exist for species to respond to changing climates. However, responses of dispersal-limited species will be more strongly tied to ability to adapt within existing populations as rates of environmental change will likely exceed movement rates. Here, we assess adaptive capacity in Plethodon cinereus, a dispersal-limited woodland salamander. We quantify plasticity in behavior and variation in demography to observed variation in environmental variables over a 5-year period. We found strong evidence that temperature and rainfall influence P. cinereus surface presence, indicating changes in climate are likely to affect seasonal activity patterns. We also found that warmer summer temperatures reduced individual growth rates into the autumn, which is likely to have negative demographic consequences. Reduced growth rates may delay reproductive maturity and lead to reductions in size-specific fecundity, potentially reducing population-level persistence. To better understand within-population variability in responses, we examined differences between two common color morphs. Previous evidence suggests that the color polymorphism may be linked to physiological differences in heat and moisture tolerance. We found only moderate support for morph-specific differences for the relationship between individual growth and temperature. Measuring environmental sensitivity to climatic variability is the first step in predicting species' responses to climate change. Our results suggest phenological shifts and changes in growth rates are likely responses under scenarios where further warming occurs, and we discuss possible adaptive strategies for resulting selective pressures.

  15. Glycosylation at Asn91 of H1N1 haemagglutinin affects binding to glycan receptors

    PubMed Central

    Jayaraman, Akila; Koh, Xiaoying; Li, Jing; Raman, Rahul; Viswanathan, Karthik; Shriver, Zachary; Sasisekharan, Ram

    2012-01-01

    The glycoprotein HA (haemagglutinin) on the surface of influenza A virus plays a central role in recognition and binding to specific host cell-surface glycan receptors and in fusion of viral membrane to the host nuclear membrane during viral replication. Given the abundance of HA on the viral surface, this protein is also the primary target for host innate and adaptive immune responses. Although addition of glycosylation sites on HA are a part of viral evolution to evade the host immune responses, there are specific glycosylation sites that are conserved during most of the evolution of the virus. In the present study, it was demonstrated that one such conserved glycosylation site at Asn91 in H1N1 HA critically governs the glycan receptor-binding specificity and hence would potentially impinge on the host adaptation of the virus. PMID:22642577

  16. Glycosylation at Asn91 of H1N1 haemagglutinin affects binding to glycan receptors.

    PubMed

    Jayaraman, Akila; Koh, Xiaoying; Li, Jing; Raman, Rahul; Viswanathan, Karthik; Shriver, Zachary; Sasisekharan, Ram

    2012-06-15

    The glycoprotein HA (haemagglutinin) on the surface of influenza A virus plays a central role in recognition and binding to specific host cell-surface glycan receptors and in fusion of viral membrane to the host nuclear membrane during viral replication. Given the abundance of HA on the viral surface, this protein is also the primary target for host innate and adaptive immune responses. Although addition of glycosylation sites on HA are a part of viral evolution to evade the host immune responses, there are specific glycosylation sites that are conserved during most of the evolution of the virus. In the present study, it was demonstrated that one such conserved glycosylation site at Asn(91) in H1N1 HA critically governs the glycan receptor-binding specificity and hence would potentially impinge on the host adaptation of the virus.

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

    PubMed Central

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

    2016-01-01

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

  18. The specificity of neural responses to music and their relation to voice processing: an fMRI-adaptation study.

    PubMed

    Armony, Jorge L; Aubé, William; Angulo-Perkins, Arafat; Peretz, Isabelle; Concha, Luis

    2015-04-23

    Several studies have identified, using functional magnetic resonance imaging (fMRI), a region within the superior temporal gyrus that preferentially responds to musical stimuli. However, in most cases, significant responses to other complex stimuli, particularly human voice, were also observed. Thus, it remains unknown if the same neurons respond to both stimulus types, albeit with different strengths, or whether the responses observed with fMRI are generated by distinct, overlapping neural populations. To address this question, we conducted an fMRI experiment in which short music excerpts and human vocalizations were presented in a pseudo-random order. Critically, we performed an adaptation-based analysis in which responses to the stimuli were analyzed taking into account the category of the preceding stimulus. Our results confirm the presence of a region in the anterior STG that responds more strongly to music than voice. Moreover, we found a music-specific adaptation effect in this area, consistent with the existence of music-preferred neurons. Lack of differences between musicians and non-musicians argues against an expertise effect. These findings provide further support for neural separability between music and speech within the temporal lobe. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  19. Induction of adaptive response in human blood lymphocytes exposed to radiofrequency radiation.

    PubMed

    Sannino, Anna; Sarti, Maurizio; Reddy, Siddharth B; Prihoda, Thomas J; Vijayalaxmi; Scarfì, Maria Rosaria

    2009-06-01

    The incidence of micronuclei was evaluated to assess the induction of an adaptive response to non-ionizing radiofrequency (RF) radiation in peripheral blood lymphocytes collected from five different human volunteers. After stimulation with phytohemagglutinin for 24 h, the cells were exposed to an adaptive dose of 900 MHz RF radiation used for mobile communications (at a peak specific absorption rate of 10 W/kg) for 20 h and then challenged with a single genotoxic dose of mitomycin C (100 ng/ml) at 48 h. Lymphocytes were collected at 72 h to examine the frequency of micronuclei in cytokinesis-blocked binucleated cells. Cells collected from four donors exhibited the induction of adaptive response (i.e., responders). Lymphocytes that were pre-exposed to 900 MHz RF radiation had a significantly decreased incidence of micronuclei induced by the challenge dose of mitomycin C compared to those that were not pre-exposed to 900 MHz RF radiation. These preliminary results suggested that the adaptive response can be induced in cells exposed to non-ionizing radiation. A similar phenomenon has been reported in cells as well as in animals exposed to ionizing radiation in several earlier studies. However, induction of adaptive response was not observed in the remaining donor (i.e., non-responder). The incidence of micronuclei induced by the challenge dose of mitomycin C was not significantly different between the cells that were pre-exposed and unexposed to 900 MHz RF radiation. Thus the overall data indicated the existence of heterogeneity in the induction of an adaptive response between individuals exposed to RF radiation and showed that the less time-consuming micronucleus assay can be used to determine whether an individual is a responder or non-responder.

  20. Tissue adaptation to physical stress: a proposed "Physical Stress Theory" to guide physical therapist practice, education, and research.

    PubMed

    Mueller, Michael J; Maluf, Katrina S

    2002-04-01

    The purpose of this perspective is to present a general theory--the Physical Stress Theory (PST). The basic premise of the PST is that changes in the relative level of physical stress cause a predictable adaptive response in all biological tissue. Specific thresholds define the upper and lower stress levels for each characteristic tissue response. Qualitatively, the 5 tissue responses to physical stress are decreased stress tolerance (eg, atrophy), maintenance, increased stress tolerance (eg, hypertrophy), injury, and death. Fundamental principles of tissue adaptation to physical stress are described that, in the authors' opinion, can be used to help guide physical therapy practice, education, and research. The description of fundamental principles is followed by a review of selected literature describing adaptation to physical stress for each of the 4 main organ systems described in the Guide to Physical Therapist Practice (ie, cardiovascular/pulmonary, integumentary, musculoskeletal, neuromuscular). Limitations and implications of the PST for practice, research, and education are presented.

  1. What Works for You? Using Teacher Feedback to Inform Adaptations of Pivotal Response Training for Classroom Use

    PubMed Central

    Stahmer, Aubyn C.; Suhrheinrich, Jessica; Reed, Sarah; Schreibman, Laura

    2012-01-01

    Several evidence-based practices (EBPs) have been identified as efficacious for the education of students with autism spectrum disorders (ASD). However, effectiveness research has rarely been conducted in schools and teachers express skepticism about the clinical utility of EBPs for the classroom. Innovative methods are needed to optimally adapt EBPs for community use. This study utilizes qualitative methods to identify perceived benefits and barriers of classroom implementation of a specific EBP for ASD, Pivotal Response Training (PRT). Teachers' perspectives on the components of PRT, use of PRT as a classroom intervention strategy, and barriers to the use of PRT were identified through guided discussion. Teachers found PRT valuable; however, they also found some components challenging. Specific teacher recommendations for adaptation and resource development are discussed. This process of obtaining qualitative feedback from frontline practitioners provides a generalizable model for researchers to collaborate with teachers to optimally promote EBPs for classroom use. PMID:23209896

  2. What works for you? Using teacher feedback to inform adaptations of pivotal response training for classroom use.

    PubMed

    Stahmer, Aubyn C; Suhrheinrich, Jessica; Reed, Sarah; Schreibman, Laura

    2012-01-01

    Several evidence-based practices (EBPs) have been identified as efficacious for the education of students with autism spectrum disorders (ASD). However, effectiveness research has rarely been conducted in schools and teachers express skepticism about the clinical utility of EBPs for the classroom. Innovative methods are needed to optimally adapt EBPs for community use. This study utilizes qualitative methods to identify perceived benefits and barriers of classroom implementation of a specific EBP for ASD, Pivotal Response Training (PRT). Teachers' perspectives on the components of PRT, use of PRT as a classroom intervention strategy, and barriers to the use of PRT were identified through guided discussion. Teachers found PRT valuable; however, they also found some components challenging. Specific teacher recommendations for adaptation and resource development are discussed. This process of obtaining qualitative feedback from frontline practitioners provides a generalizable model for researchers to collaborate with teachers to optimally promote EBPs for classroom use.

  3. Reconstructing meaning through occupation after the death of a family member: accommodation, assimilation, and continuing bonds.

    PubMed

    Hoppes, Steve; Segal, Ruth

    2010-01-01

    Reactions to death have been studied extensively from psychological, behavioral, and physiological perspectives. Occupational adaptation to loss has received scant attention. Qualitative research was undertaken to identify and describe occupational responses in bereavement. The constant comparative approach was used to analyze and interpret the occupational responses. Adaptive strategies of occupational accommodation and assimilation were used after the death of a family member. Desire to sustain bonds with the deceased motivated specific occupational engagements. These occupational responses served to reconstruct meaning after the death of a family member. These findings contribute to understanding adaptation after death by adding an occupational perspective to previous theories. Occupational therapists' abilities to support clients after loss can be enhanced through appreciation of occupational accommodation and assimilation and the role of continuing occupational bonds after the death of a loved one.

  4. Adaptation to seasonality and the winter freeze

    PubMed Central

    Preston, Jill C.; Sandve, Simen R.

    2013-01-01

    Flowering plants initially diversified during the Mesozoic era at least 140 million years ago in regions of the world where temperate seasonal environments were not encountered. Since then several cooling events resulted in the contraction of warm and wet environments and the establishment of novel temperate zones in both hemispheres. In response, less than half of modern angiosperm families have members that evolved specific adaptations to cold seasonal climates, including cold acclimation, freezing tolerance, endodormancy, and vernalization responsiveness. Despite compelling evidence for multiple independent origins, the level of genetic constraint on the evolution of adaptations to seasonal cold is not well understood. However, the recent increase in molecular genetic studies examining the response of model and crop species to seasonal cold offers new insight into the evolutionary lability of these traits. This insight has major implications for our understanding of complex trait evolution, and the potential role of local adaptation in response to past and future climate change. In this review, we discuss the biochemical, morphological, and developmental basis of adaptations to seasonal cold, and synthesize recent literature on the genetic basis of these traits in a phylogenomic context. We find evidence for multiple genetic links between distinct physiological responses to cold, possibly reinforcing the coordinated expression of these traits. Furthermore, repeated recruitment of the same or similar ancestral pathways suggests that land plants might be somewhat pre-adapted to dealing with temperature stress, perhaps making inducible cold traits relatively easy to evolve. PMID:23761798

  5. Origins of adaptive immunity.

    PubMed

    Liongue, Clifford; John, Liza B; Ward, Alister

    2011-01-01

    Adaptive immunity, involving distinctive antibody- and cell-mediated responses to specific antigens based on "memory" of previous exposure, is a hallmark of higher vertebrates. It has been argued that adaptive immunity arose rapidly, as articulated in the "big bang theory" surrounding its origins, which stresses the importance of coincident whole-genome duplications. Through a close examination of the key molecules and molecular processes underpinning adaptive immunity, this review suggests a less-extreme model, in which adaptive immunity emerged as part of longer evolutionary journey. Clearly, whole-genome duplications provided additional raw genetic materials that were vital to the emergence of adaptive immunity, but a variety of other genetic events were also required to generate some of the key molecules, whereas others were preexisting and simply co-opted into adaptive immunity.

  6. Modeling rate sensitivity of exercise transient responses to limb motion.

    PubMed

    Yamashiro, Stanley M; Kato, Takahide

    2014-10-01

    Transient responses of ventilation (V̇e) to limb motion can exhibit predictive characteristics. In response to a change in limb motion, a rapid change in V̇e is commonly observed with characteristics different than during a change in workload. This rapid change has been attributed to a feed-forward or adaptive response. Rate sensitivity was explored as a specific hypothesis to explain predictive V̇e responses to limb motion. A simple model assuming an additive feed-forward summation of V̇e proportional to the rate of change of limb motion was studied. This model was able to successfully account for the adaptive phase correction observed during human sinusoidal changes in limb motion. Adaptation of rate sensitivity might also explain the reduction of the fast component of V̇e responses previously reported following sudden exercise termination. Adaptation of the fast component of V̇e response could occur by reduction of rate sensitivity. Rate sensitivity of limb motion was predicted by the model to reduce the phase delay between limb motion and V̇e response without changing the steady-state response to exercise load. In this way, V̇e can respond more quickly to an exercise change without interfering with overall feedback control. The asymmetry between responses to an incremental and decremental ramp change in exercise can also be accounted for by the proposed model. Rate sensitivity leads to predicted behavior, which resembles responses observed in exercise tied to expiratory reserve volume. Copyright © 2014 the American Physiological Society.

  7. Complex Visual Adaptations in Squid for Specific Tasks in Different Environments

    PubMed Central

    Chung, Wen-Sung; Marshall, N. Justin

    2017-01-01

    In common with their major competitors, the fish, squid are fast moving visual predators that live over a great range of depths in the ocean. Both squid and fish show a variety of adaptations with respect to optical properties, receptors and their underlying neural circuits, and these adaptations are often linked to the light conditions of their specific niche. In contrast to the extensive investigations of adaptive strategies in fish, vision in response to the varying quantity and quality of available light, our knowledge of visual adaptations in squid remains sparse. This study therefore undertook a comparative study of visual adaptations and capabilities in a number of squid species collected between 0 and 1,200 m. Histology, magnetic resonance imagery (MRI), and depth distributions were used to compare brains, eyes, and visual capabilities, revealing that the squid eye designs reflect the lifestyle and the versatility of neural architecture in its visual system. Tubular eyes and two types of regional retinal deformation were identified and these eye modifications are strongly associated with specific directional visual tasks. In addition, a combination of conventional and immuno-histology demonstrated a new form of a complex retina possessing two inner segment layers in two mid-water squid species which they rhythmically move across a broad range of depths (50–1,000 m). In contrast to their relatives with the regular single-layered inner segment retina live in the upper mesopelagic layer (50–400 m), the new form of retinal interneuronal layers suggests that the visual sensitivity of these two long distance vertical migrants may increase in response to dimmer environments. PMID:28286484

  8. Adaptation to vestibular disorientation. XI, The influence of specific and nonspecific gravi-receptors on nystagmic responses to angular acceleration.

    DOT National Transportation Integrated Search

    1969-10-01

    Data from several recent experiments indicate that the otoliths (detectors of linear acceleration) may exert regulatory effects on responses of the semicircular canals (detectors of angular acceleration). This study was designed to explore further th...

  9. Comparative quantitative proteomics analysis of the ABA response of roots of drought-sensitive and drought-tolerant wheat varieties identifies proteomic signatures of drought adaptability.

    PubMed

    Alvarez, Sophie; Roy Choudhury, Swarup; Pandey, Sona

    2014-03-07

    Wheat is one of the most highly cultivated cereals in the world. Like other cultivated crops, wheat production is significantly affected by abiotic stresses such as drought. Multiple wheat varieties suitable for different geographical regions of the world have been developed that are adapted to different environmental conditions; however, the molecular basis of such adaptations remains unknown in most cases. We have compared the quantitative proteomics profile of the roots of two different wheat varieties, Nesser (drought-tolerant) and Opata (drought-sensitive), in the absence and presence of abscisic acid (ABA, as a proxy for drought). A labeling LC-based quantitative proteomics approach using iTRAQ was applied to elucidate the changes in protein abundance levels. Quantitative differences in protein levels were analyzed for the evaluation of inherent differences between the two varieties as well as the overall and variety-specific effect of ABA on the root proteome. This study reveals the most elaborate ABA-responsive root proteome identified to date in wheat. A large number of proteins exhibited inherently different expression levels between Nesser and Opata. Additionally, significantly higher numbers of proteins were ABA-responsive in Nesser roots compared with Opata roots. Furthermore, several proteins showed variety-specific regulation by ABA, suggesting their role in drought adaptation.

  10. Species-specific responses to ocean acidification should account for local adaptation and adaptive plasticity.

    PubMed

    Vargas, Cristian A; Lagos, Nelson A; Lardies, Marco A; Duarte, Cristian; Manríquez, Patricio H; Aguilera, Victor M; Broitman, Bernardo; Widdicombe, Steve; Dupont, Sam

    2017-03-13

    Global stressors, such as ocean acidification, constitute a rapidly emerging and significant problem for marine organisms, ecosystem functioning and services. The coastal ecosystems of the Humboldt Current System (HCS) off Chile harbour a broad physical-chemical latitudinal and temporal gradient with considerable patchiness in local oceanographic conditions. This heterogeneity may, in turn, modulate the specific tolerances of organisms to climate stress in species with populations distributed along this environmental gradient. Negative response ratios are observed in species models (mussels, gastropods and planktonic copepods) exposed to changes in the partial pressure of CO 2 (pCO2) far from the average and extreme pCO2 levels experienced in their native habitats. This variability in response between populations reveals the potential role of local adaptation and/or adaptive phenotypic plasticity in increasing resilience of species to environmental change. The growing use of standard ocean acidification scenarios and treatment levels in experimental protocols brings with it a danger that inter-population differences are confounded by the varying environmental conditions naturally experienced by different populations. Here, we propose the use of a simple index taking into account the natural pCO2 variability, for a better interpretation of the potential consequences of ocean acidification on species inhabiting variable coastal ecosystems. Using scenarios that take into account the natural variability will allow understanding of the limits to plasticity across organismal traits, populations and species.

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

    PubMed

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

    2017-02-06

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

  12. The role of extracellular vesicles when innate meets adaptive.

    PubMed

    Groot Kormelink, Tom; Mol, Sanne; de Jong, Esther C; Wauben, Marca H M

    2018-04-03

    Innate immune cells are recognized for their rapid and critical contribution to the body's first line of defense against invading pathogens and harmful agents. These actions can be further amplified by specific adaptive immune responses adapted to the activating stimulus. Recently, the awareness has grown that virtually all innate immune cells, i.e., mast cells, neutrophils, macrophages, eosinophils, basophils, and NK cells, are able to communicate with dendritic cells (DCs) and/or T and B cells, and thereby significantly contribute to the orchestration of adaptive immune responses. The means of communication that are thus far primarily associated with this function are cell-cell contacts and the release of a broad range of soluble mediators. Moreover, the possible contribution of innate immune cell-derived extracellular vesicles (EVs) to the modulation of adaptive immunity will be outlined in this review. EVs are submicron particles composed of a lipid bilayer, proteins, and nucleic acids released by cells in a regulated fashion. EVs are involved in intercellular communication between multiple cell types, including those of the immune system. A good understanding of the mechanisms by which innate immune cell-derived EVs influence adaptive immune responses, or vice versa, may reveal novel insights in the regulation of the immune system and can open up new possibilities for EVs (or their components) in controlling immune responses, either as a therapy, target, or as an adjuvant in future immune modulating treatments.

  13. Social influences on adaptive criterion learning.

    PubMed

    Cassidy, Brittany S; Dubé, Chad; Gutchess, Angela H

    2015-07-01

    People adaptively shift decision criteria when given biased feedback encouraging specific types of errors. Given that work on this topic has been conducted in nonsocial contexts, we extended the literature by examining adaptive criterion learning in both social and nonsocial contexts. Specifically, we compared potential differences in criterion shifting given performance feedback from social sources varying in reliability and from a nonsocial source. Participants became lax when given false positive feedback for false alarms, and became conservative when given false positive feedback for misses, replicating prior work. In terms of a social influence on adaptive criterion learning, people became more lax in response style over time if feedback was provided by a nonsocial source or by a social source meant to be perceived as unreliable and low-achieving. In contrast, people adopted a more conservative response style over time if performance feedback came from a high-achieving and reliable source. Awareness that a reliable and high-achieving person had not provided their feedback reduced the tendency to become more conservative, relative to those unaware of the source manipulation. Because teaching and learning often occur in a social context, these findings may have important implications for many scenarios in which people fine-tune their behaviors, given cues from others.

  14. On the frequency response of a Wenglor particle-counting system for aeolian transport measurements

    NASA Astrophysics Data System (ADS)

    Bauer, Bernard O.; Davidson-Arnott, Robin G. D.; Hilton, Michael J.; Fraser, Douglas

    2018-06-01

    A commonly deployed particle-counting system for aeolian saltation flux, consisting of a Wenglor fork sensor and an Onset Hobo Pulse Input Adapter linked to an Onset Hobo Energy Logger Pro data logger, was tested for frequency response. The Wenglor fork sensor is an optical gate device that has very fast switching capacity that can accommodate the time of flight of saltating sand particles through the sensing volume with the exception of very fine sand or silt and very quickly moving particles. The Pulse Input Adapter, in contrast, imposes limitations on the frequency response of the system. The manufacturer of the pulse adapter specifies an upper limit of 120 Hz, although bench tests with an electronic pulse generator indicate that the frequency response of the Pulse Input Adapter, in isolation, is excellent up to 3000 Hz, with only small error (less than 1.6%) due to under-counting during data transfer intervals. A mechanical test of the integrated system (fork sensor, pulse input adapter, and data logger) demonstrates excellent performance up to about 700 Hz (less than 2% error), but significant under-counting above 1000 Hz for unknown reasons. This specific particle-counting system therefore has a frequency response that is well suited for investigation of the dynamics of aeolian saltation as typically encountered in most field conditions on coastal beaches with the exception of extreme wind events and very small particle sizes.

  15. Shared internal models for feedforward and feedback control.

    PubMed

    Wagner, Mark J; Smith, Maurice A

    2008-10-15

    A child often learns to ride a bicycle in the driveway, free of unforeseen obstacles. Yet when she first rides in the street, we hope that if a car suddenly pulls out in front of her, she will combine her innate goal of avoiding an accident with her learned knowledge of the bicycle, and steer away or brake. In general, when we train to perform a new motor task, our learning is most robust if it updates the rules of online error correction to reflect the rules and goals of the new task. Here we provide direct evidence that, after a new feedforward motor adaptation, motor feedback responses to unanticipated errors become precisely task appropriate, even when such errors were never experienced during training. To study this ability, we asked how, if at all, do online responses to occasional, unanticipated force pulses during reaching arm movements change after adapting to altered arm dynamics? Specifically, do they change in a task-appropriate manner? In our task, subjects learned novel velocity-dependent dynamics. However, occasional force-pulse perturbations produced unanticipated changes in velocity. Therefore, after adaptation, task-appropriate responses to unanticipated pulses should compensate corresponding changes in velocity-dependent dynamics. We found that after adaptation, pulse responses precisely compensated these changes, although they were never trained to do so. These results provide evidence for a smart feedback controller which automatically produces responses specific to the learned dynamics of the current task. To accomplish this, the neural processes underlying feedback control must (1) be capable of accurate real-time state prediction for velocity via a forward model and (2) have access to recently learned changes in internal models of limb dynamics.

  16. Influenza vaccine response profiles are affected by vaccine preparation and preexisting immunity, but not HIV infection.

    PubMed

    Berger, Christoph T; Greiff, Victor; Mehling, Matthias; Fritz, Stefanie; Meier, Marc A; Hoenger, Gideon; Conen, Anna; Recher, Mike; Battegay, Manuel; Reddy, Sai T; Hess, Christoph

    2015-01-01

    Vaccines dramatically reduce infection-related morbidity and mortality. Determining factors that modulate the host response is key to rational vaccine design and demands unsupervised analysis. To longitudinally resolve influenza-specific humoral immune response dynamics we constructed vaccine response profiles of influenza A- and B-specific IgM and IgG levels from 42 healthy and 31 HIV infected influenza-vaccinated individuals. Pre-vaccination antibody levels and levels at 3 predefined time points after vaccination were included in each profile. We performed hierarchical clustering on these profiles to study the extent to which HIV infection associated immune dysfunction, adaptive immune factors (pre-existing influenza-specific antibodies, T cell responses), an innate immune factor (Mannose Binding Lectin, MBL), demographic characteristics (gender, age), or the vaccine preparation (split vs. virosomal) impacted the immune response to influenza vaccination. Hierarchical clustering associated vaccine preparation and pre-existing IgG levels with the profiles of healthy individuals. In contrast to previous in vitro and animal data, MBL levels had no impact on the adaptive vaccine response. Importantly, while HIV infected subjects with low CD4 T cell counts showed a reduced magnitude of their vaccine response, their response profiles were indistinguishable from those of healthy controls, suggesting quantitative but not qualitative deficits. Unsupervised profile-based analysis ranks factors impacting the vaccine-response by relative importance, with substantial implications for comparing, designing and improving vaccine preparations and strategies. Profile similarity between HIV infected and HIV negative individuals suggests merely quantitative differences in the vaccine response in these individuals, offering a rationale for boosting strategies in the HIV infected population.

  17. Specialized Proresolving Mediators in Innate and Adaptive Immune Responses in Airway Diseases.

    PubMed

    Krishnamoorthy, Nandini; Abdulnour, Raja-Elie E; Walker, Katherine H; Engstrom, Braden D; Levy, Bruce D

    2018-07-01

    Airborne pathogens and environmental stimuli evoke immune responses in the lung. It is critical to health that these responses be controlled to prevent tissue damage and the compromise of organ function. Resolution of inflammation is a dynamic process that is coordinated by biochemical and cellular mechanisms. Recently, specialized proresolving mediators (SPMs) have been identified in resolution exudates. These molecules orchestrate anti-inflammatory and proresolving actions that are cell type specific. In this review, we highlight SPM biosynthesis, the influence of SPMs on the innate and adaptive immune responses in the lung, as well as recent insights from SPMs on inflammatory disease pathophysiology. Uncovering these mediators and cellular mechanisms for resolution is providing new windows into physiology and disease pathogenesis.

  18. Divergent and convergent evolution in metastases suggest treatment strategies based on specific metastatic sites

    PubMed Central

    Cunningham, Jessica J.; Brown, Joel S.; Vincent, Thomas L.

    2015-01-01

    Background and objective: Systemic therapy for metastatic cancer is currently determined exclusively by the site of tumor origin. Yet, there is increasing evidence that the molecular characteristics of metastases significantly differ from the primary tumor. We define the evolutionary dynamics of metastases that govern this molecular divergence and examine their potential contribution to variations in response to targeted therapies. Methodology: Darwinian interactions of transformed cells with the tissue microenvironments at primary and metastatic sites are analyzed using evolutionary game theory. Computational models simulate responses to targeted therapies in different organs within the same patient. Results: Tumor cells, although maximally fit at their primary site, typically have lower fitness on the adaptive landscapes offered by the metastatic sites due to organ-specific variations in mesenchymal properties and signaling pathways. Clinically evident metastases usually exhibit time-dependent divergence from the phenotypic mean of the primary population as the tumor cells evolve and adapt to their new circumstances. In contrast, tumors from different primary sites evolving on identical metastatic adaptive landscapes exhibit phenotypic convergence. Thus, metastases in the liver from different primary tumors and even in different hosts will evolve toward similar adaptive phenotypes. The combination of evolutionary divergence from the primary cancer phenotype and convergence towards similar adaptive strategies in the same tissue cause significant variations in treatment responses particularly for highly targeted therapies. Conclusion and implications: The results suggest that optimal therapies for disseminated cancer must take into account the site(s) of metastatic growth as well as the primary organ. PMID:25794501

  19. Immunological tools for the assessment of both humoral and cellular immune responses in Foxes (Vulpes vulpes) using ovalbumin and cholera toxin B as an antigenic model.

    PubMed

    Rolland-Turner, Magali; Farre, Guillaume; Muller, Delphine; Rouet, Nelly; Boue, Franck

    2004-10-22

    The immune response in the fox (Vulpes vulpes), despite the success of the oral rabies vaccine is not well characterized, and specific immunological tools are needed. To investigate both the humoral and cellular immune response, we used ovalbumin (OVA) and cholera toxin B (CTB) as an antigenic model to set-up ELISA and ELISPOT antibodies secreting cells (ASC) assays in the fox model. Identification of antibodies that cross-react with fox immunoglobulin was performed by Western blot, and their use was adapted for both the ELISA and ELISPOT ASC assay. The humoral and cellular specific immune responses were assessed after intra-muscular or intra-nasal immunization. Intra-muscular immunization resulted in the development of both cellular and humoral anti-OVA and anti-CTB responses in peripheral blood mononuclear cells (PBMCs). Immunization via the intra-nasal route resulted in the development of a cellular and humoral response against CTB in PBMCs. This immune response was confirmed using splenocytes from immunized animals by ELISPOT assay at euthanasia. Females immunized via the intra-nasal route developed specific anti-CTB IgM, IgA and IgG in vaginal fluids after the initial boost (day 26) showing that mucosal immunization produces a vaginal immune response in foxes. These immunological tools developed here are now available to be adapted to other antigenic models to facilitate further immune studies in foxes.

  20. Evolution of adaptation mechanisms: Adaptation energy, stress, and oscillating death.

    PubMed

    Gorban, Alexander N; Tyukina, Tatiana A; Smirnova, Elena V; Pokidysheva, Lyudmila I

    2016-09-21

    In 1938, Selye proposed the notion of adaptation energy and published 'Experimental evidence supporting the conception of adaptation energy.' Adaptation of an animal to different factors appears as the spending of one resource. Adaptation energy is a hypothetical extensive quantity spent for adaptation. This term causes much debate when one takes it literally, as a physical quantity, i.e. a sort of energy. The controversial points of view impede the systematic use of the notion of adaptation energy despite experimental evidence. Nevertheless, the response to many harmful factors often has general non-specific form and we suggest that the mechanisms of physiological adaptation admit a very general and nonspecific description. We aim to demonstrate that Selye׳s adaptation energy is the cornerstone of the top-down approach to modelling of non-specific adaptation processes. We analyze Selye׳s axioms of adaptation energy together with Goldstone׳s modifications and propose a series of models for interpretation of these axioms. Adaptation energy is considered as an internal coordinate on the 'dominant path' in the model of adaptation. The phenomena of 'oscillating death' and 'oscillating remission' are predicted on the base of the dynamical models of adaptation. Natural selection plays a key role in the evolution of mechanisms of physiological adaptation. We use the fitness optimization approach to study of the distribution of resources for neutralization of harmful factors, during adaptation to a multifactor environment, and analyze the optimal strategies for different systems of factors. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Complexities of gene expression patterns in natural populations of an extremophile fish (Poecilia mexicana, Poeciliidae)

    PubMed Central

    Passow, Courtney N.; Brown, Anthony P.; Arias-Rodriguez, Lenin; Yee, Muh-Ching; Sockell, Alexandra; Schartl, Manfred; Warren, Wesley C.; Bustamante, Carlos; Kelley, Joanna L.; Tobler, Michael

    2017-01-01

    Variation in gene expression can provide insights into organismal responses to environmental stress and physiological mechanisms mediating adaptation to habitats with contrasting environmental conditions. We performed an RNA-sequencing experiment to quantify gene expression patterns in fish adapted to habitats with different combinations of environmental stressors, including the presence of toxic hydrogen sulphide (H2S) and the absence of light in caves. We specifically asked how gene expression varies among populations living in different habitats, whether population differences were consistent among organs, and whether there is evidence for shared expression responses in populations exposed to the same stressors. We analysed organ-specific transcriptome-wide data from four ecotypes of Poecilia mexicana (nonsulphidic surface, sulphidic surface, nonsulphidic cave and sulphidic cave). The majority of variation in gene expression was correlated with organ type, and the presence of specific environmental stressors elicited unique expression differences among organs. Shared patterns of gene expression between populations exposed to the same environmental stressors increased with levels of organismal organization (from transcript to gene to physiological pathway). In addition, shared patterns of gene expression were more common between populations from sulphidic than populations from cave habitats, potentially indicating that physiochemical stressors with clear biochemical consequences can constrain the diversity of adaptive solutions that mitigate their adverse effects. Overall, our analyses provided insights into transcriptional variation in a unique system, in which adaptation to H2S and darkness coincide. Functional annotations of differentially expressed genes provide a springboard for investigating physiological mechanisms putatively underlying adaptation to extreme environments. PMID:28598519

  2. A Systems Approach to the Estimation of Ecosystem and Human Health Stressors in Air, Land and Water

    EPA Science Inventory

    A model linkage paradigm, based on the nitrogen cascade, is introduced. This general paradigm is then adapted to specific multi-media nitrogen issues and specific models to be linked. An example linked modeling system addressing potential nitrogen responses to biofuel-driven co...

  3. Impacts of Near-Term Climate Change on Irrigation Demands and Crop Yields in the Columbia River Basin

    NASA Astrophysics Data System (ADS)

    Rajagopalan, K.; Chinnayakanahalli, K. J.; Stockle, C. O.; Nelson, R. L.; Kruger, C. E.; Brady, M. P.; Malek, K.; Dinesh, S. T.; Barber, M. E.; Hamlet, A. F.; Yorgey, G. G.; Adam, J. C.

    2018-03-01

    Adaptation to a changing climate is critical to address future global food and water security challenges. While these challenges are global, successful adaptation strategies are often generated at regional scales; therefore, regional-scale studies are critical to inform adaptation decision making. While climate change affects both water supply and demand, water demand is relatively understudied, especially at regional scales. The goal of this work is to address this gap, and characterize the direct impacts of near-term (for the 2030s) climate change and elevated CO2 levels on regional-scale crop yields and irrigation demands for the Columbia River basin (CRB). This question is addressed through a coupled crop-hydrology model that accounts for site-specific and crop-specific characteristics that control regional-scale response to climate change. The overall near-term outlook for agricultural production in the CRB is largely positive, with yield increases for most crops and small overall increases in irrigation demand. However, there are crop-specific and location-specific negative impacts as well, and the aggregate regional response of irrigation demands to climate change is highly sensitive to the spatial crop mix. Low-value pasture/hay varieties of crops—typically not considered in climate change assessments—play a significant role in determining the regional response of irrigation demands to climate change, and thus cannot be overlooked. While, the overall near-term outlook for agriculture in the region is largely positive, there may be potential for a negative outlook further into the future, and it is important to consider this in long-term planning.

  4. The maternal social environment shapes offspring growth, physiology, and behavioural phenotype in guinea pigs.

    PubMed

    von Engelhardt, Nikolaus; Kowalski, Gabriele J; Guenther, Anja

    2015-01-01

    Prenatal conditions influence offspring development in many species. In mammals, the effects of social density have traditionally been considered a detrimental form of maternal stress. Now their potential adaptive significance is receiving greater attention.Sex-specific effects of maternal social instability on offspring in guinea pigs (Cavia aperea f. porcellus) have been interpreted as adaptations to high social densities, while the effects of low social density are unknown. Hence, we compared morphological, behavioural and physiological development between offspring born to mothers housed either individually or in groups during the second half of pregnancy. Females housed individually and females housed in groups gave birth to litters of similar size and sex-ratios, and there were no differences in birth weight. Sons of individually-housed mothers grew faster than their sisters, whereas daughters ofgroup-housed females grew faster than their brothers, primarily due to an effect on growth of daughters. There were few effects on offspring behaviour. Baseline cortisol levels in saliva of pups on day 1 and day 7 were not affected, but we saw a blunted cortisol response to social separation on day 7 in sons of individually-housed females and daughters of group-housed females. The effects were consistent across two replicate experiments. The observed effects only partially support the adaptive hypothesis. Increased growth of daughters may be adaptive under high densities due to increasedfemale competition, but it is unclear why growth of sons is not increased under low social densities when males face less competition from older, dominant males. The differences in growth may be causally linked to sex-specific effects on cortisol response, although individual cortisol response and growth were not correlated, and various other mechanisms are possible. The observed sex-specific effects on early development are intriguing, yet the potential adaptive benefits and physiological mechanisms require further study.

  5. Molecular Mechanisms Underlying Cardiac Adaptation to Exercise

    PubMed Central

    Vega, Rick B.; Konhilas, John P.; Kelly, Daniel P.; Leinwand, Leslie A.

    2017-01-01

    Exercise elicits coordinated multi-organ responses including skeletal muscle, vasculature, heart and lung. In the short term, the output of the heart increases to meet the demand of strenuous exercise. Long term exercise instigates remodeling of the heart including growth and adaptive molecular and cellular re-programming. Signaling pathways such as the insulin-like growth factor 1/PI3K/Akt pathway mediate many of these responses. Exercise-induced, or physiologic, cardiac growth contrasts with growth elicited by pathological stimuli such as hypertension. Comparing the molecular and cellular underpinnings of physiologic and pathologic cardiac growth has unveiled phenotype-specific signaling pathways and transcriptional regulatory programs. Studies suggest that exercise pathways likely antagonize pathological pathways, and exercise training is often recommended for patients with chronic stable heart failure or following myocardial infarction. Herein, we summarize the current understanding of the structural and functional cardiac responses to exercise as well as signaling pathways and downstream effector molecules responsible for these adaptations. PMID:28467921

  6. Transcriptomic analysis of Escherichia coli O157:H7 and K-12 cultures exposed to inorganic and organic acids in stationary phase reveals acidulant- and strain-specific acid tolerance responses.

    PubMed

    King, Thea; Lucchini, Sacha; Hinton, Jay C D; Gobius, Kari

    2010-10-01

    The food-borne pathogen Escherichia coli O157:H7 is commonly exposed to organic acid in processed and preserved foods, allowing adaptation and the development of tolerance to pH levels otherwise lethal. Since little is known about the molecular basis of adaptation of E. coli to organic acids, we studied K-12 MG1655 and O157:H7 Sakai during exposure to acetic, lactic, and hydrochloric acid at pH 5.5. This is the first analysis of the pH-dependent transcriptomic response of stationary-phase E. coli. Thirty-four genes and three intergenic regions were upregulated by both strains during exposure to all acids. This universal acid response included genes involved in oxidative, envelope, and cold stress resistance and iron and manganese uptake, as well as 10 genes of unknown function. Acidulant- and strain-specific responses were also revealed. The acidulant-specific response reflects differences in the modes of microbial inactivation, even between weak organic acids. The two strains exhibited similar responses to lactic and hydrochloric acid, while the response to acetic acid was distinct. Acidulant-dependent differences between the strains involved induction of genes involved in the heat shock response, osmoregulation, inorganic ion and nucleotide transport and metabolism, translation, and energy production. E. coli O157:H7-specific acid-inducible genes were identified, suggesting that the enterohemorrhagic E. coli strain possesses additional molecular mechanisms contributing to acid resistance that are absent in K-12. While E. coli K-12 was most resistant to lactic and hydrochloric acid, O157:H7 may have a greater ability to survive in more complex acidic environments, such as those encountered in the host and during food processing.

  7. The impact of eicosanoids on the crosstalk between innate and adaptive immunity: the key roles of dendritic cells.

    PubMed

    Harizi, H; Gualde, N

    2005-06-01

    The innate immune response is essentially the first line of defense against an invading pathogen. Through specialized receptors, known as pattern recognition receptors, especially Toll-like receptors, specialized cells of myeloid origin, including macrophages and dendritic cells (DCs) are able to phagocytose microorganisms and induce an innate inflammatory response. Although B and T lymphocytes recognize tissue antigens with high specificity, they are unable to initiate immune responses. The decision to activate an appropriate immune response is made by unique DC, the most professional antigen-presenting cells (APCs) which control the responses of several types of lymphocytes and play central role in the transition between innate and adaptive immunity. Increased secretion of inflammatory endogenous mediators such as cytokines and arachidonic acid-derived lipid mediators, also termed eicosanoids, can activate APC, particularly DC, which in turn induce an adaptive immune response. There is an increasing evidence that eicosanoids play an important role in connecting innate and adaptive immunity by acting on cells of both systems. Prostanoids, a major class of eicosanoids, have a great impact on inflammatory and immune responses. PGE(2) is one of the best known and most well-characterized prostanoids in terms of immunomodulation. Although cytokines are known as key regulators of immunity, eicosanoids, including PGE(2), PGD(2), LTB(4), and LTC(4), may also affect cells of immune system by modulating cytokine release, cell differentiation, survival, migration, antigen presentation, and apoptosis. By acting on various aspects of immune and inflammatory reactions, these lipid mediators emerge as key regulators of the crosstalk between innate and adaptive immunity.

  8. The Multirole of Liposomes in Therapy and Prevention of Infectious Diseases

    PubMed Central

    Nisini, Roberto; Poerio, Noemi; Mariotti, Sabrina; De Santis, Federica; Fraziano, Maurizio

    2018-01-01

    Liposomes are closed bilayer structures spontaneously formed by hydrated phospholipids that are widely used as efficient delivery systems for drugs or antigens, due to their capability to encapsulate bioactive hydrophilic, amphipathic, and lipophilic molecules into inner water phase or within lipid leaflets. The efficacy of liposomes as drug or antigen carriers has been improved in the last years to ameliorate pharmacokinetics and capacity to release their cargo in selected target organs or cells. Moreover, different formulations and variations in liposome composition have been often proposed to include immunostimulatory molecules, ligands for specific receptors, or stimuli responsive compounds. Intriguingly, independent research has unveiled the capacity of several phospholipids to play critical roles as intracellular messengers in modulating both innate and adaptive immune responses through various mechanisms, including (i) activation of different antimicrobial enzymatic pathways, (ii) driving the fusion–fission events between endosomes with direct consequences to phagosome maturation and/or to antigen presentation pathway, and (iii) modulation of the inflammatory response. These features can be exploited by including selected bioactive phospholipids in the bilayer scaffold of liposomes. This would represent an important step forward since drug or antigen carrying liposomes could be engineered to simultaneously activate different signal transduction pathways and target specific cells or tissues to induce antigen-specific T and/or B cell response. This lipid-based host-directed strategy can provide a focused antimicrobial innate and adaptive immune response against specific pathogens and offer a novel prophylactic or therapeutic option against chronic, recurrent, or drug-resistant infections. PMID:29459867

  9. The IL-1R/TLR signaling pathway is essential for efficient CD8+ T-cell responses against hepatitis B virus in the hydrodynamic injection mouse model.

    PubMed

    Ma, Zhiyong; Liu, Jia; Wu, Weimin; Zhang, Ejuan; Zhang, Xiaoyong; Li, Qian; Zelinskyy, Gennadiy; Buer, Jan; Dittmer, Ulf; Kirschning, Carsten J; Lu, Mengji

    2017-12-01

    The outcome of hepatitis B viral (HBV) infection is determined by the complex interactions between replicating HBV and the immune system. While the role of the adaptive immune system in the resolution of HBV infection has been studied extensively, the contribution of innate immune mechanisms remains to be defined. Here we examined the role of the interleukin-1 receptor/Toll-like receptor (IL-1R/TLR) signaling pathway in adaptive immune responses and viral clearance by exploring the HBV mouse model. Hydrodynamic injection with a replication-competent HBV genome was performed in wild-type mice (WT) and a panel of mouse strains lacking specific innate immunity component expression. We found higher levels of HBV protein production and replication in Tlr2 -/- , Tlr23479 -/- , 3d/Tlr24 -/- , Myd88/Trif -/- and Irak4 -/- mice, which was associated with reduced HBV-specific CD8 + T-cell responses in these mice. Importantly, HBV clearance was delayed for more than 2 weeks in 3d/Tlr24 -/- , Myd88/Trif -/- and Irak4 -/- mice compared to WT mice. HBV-specific CD8 + T-cell responses were functionally impaired for producing the cytokines IFN-γ, TNF-α and IL-2 in TLR signaling-deficient mice compared to WT mice. In conclusion, the IL-1R/TLR signaling pathway might contribute to controlling HBV infection by augmenting HBV-specific CD8 + T-cell responses.

  10. A novel comparative pattern count analysis reveals a chronic ethanol-induced dynamic shift in immediate early NF-κB genome-wide promoter binding during liver regeneration.

    PubMed

    Kuttippurathu, Lakshmi; Patra, Biswanath; Hoek, Jan B; Vadigepalli, Rajanikanth

    2016-03-01

    Liver regeneration after partial hepatectomy is a clinically important process that is impaired by adaptation to chronic alcohol intake. We focused on the initial time points following partial hepatectomy (PHx) to analyze the genome-wide binding activity of NF-κB, a key immediate early regulator. We investigated the effect of chronic alcohol intake on immediate early NF-κB genome-wide localization, in the adapted state as well as in response to partial hepatectomy, using chromatin immunoprecipitation followed by promoter microarray analysis. We found many ethanol-specific NF-κB binding target promoters in the ethanol-adapted state, corresponding to the regulation of biosynthetic processes, oxidation-reduction and apoptosis. Partial hepatectomy induced a diet-independent shift in NF-κB binding loci relative to the transcription start sites. We employed a novel pattern count analysis to exhaustively enumerate and compare the number of promoters corresponding to the temporal binding patterns in ethanol and pair-fed control groups. The highest pattern count corresponded to promoters with NF-κB binding exclusively in the ethanol group at 1 h post PHx. This set was associated with the regulation of cell death, response to oxidative stress, histone modification, mitochondrial function, and metabolic processes. Integration with the global gene expression profiles to identify putative transcriptional consequences of NF-κB binding patterns revealed that several of ethanol-specific 1 h binding targets showed ethanol-specific differential expression through 6 h post PHx. Motif analysis yielded co-incident binding loci for STAT3, AP-1, CREB, C/EBP-β, PPAR-γ and C/EBP-α, likely participating in co-regulatory modules with NF-κB in shaping the immediate early response to PHx. We conclude that adaptation to chronic ethanol intake disrupts the NF-κB promoter binding landscape with consequences for the immediate early gene regulatory response to the acute challenge of PHx.

  11. Linking population, fertility, and family planning with adaptation to climate change: perspectives from Ethiopia.

    PubMed

    Rovin, Kimberly; Hardee, Karen; Kidanu, Aklilu

    2013-09-01

    Global climate change is felt disproportionately in the world's most economically disadvantaged countries. As adaption to an evolving climate becomes increasingly salient on national and global scales, it is important to assess how people at the local-level are already coping with changes. Understanding local responses to climate change is essential for helping countries to construct strategies to bolster resilience to current and future effects. This qualitative research investigated responses to climate change in Ethiopia; specifically, how communities react to and cope with climate variation, which groups are most vulnerable, and the role of family planning in increasing resilience. Participants were highly aware of changing climate effects, impacts of rapid population growth, and the need for increased access to voluntary family planning. Identification of family planning as an important adaptation strategy supports the inclusion of rights-based voluntary family planning and reproductive health into local and national climate change adaptation plans.

  12. FMRI-adaptation to highly-rendered color photographs of animals and manipulable artifacts during a classification task.

    PubMed

    Chouinard, Philippe A; Goodale, Melvyn A

    2012-02-01

    We used fMRI to identify brain areas that adapted to either animals or manipulable artifacts while participants classified highly-rendered color photographs into subcategories. Several key brain areas adapted more strongly to one class of objects compared to the other. Namely, we observed stronger adaptation for animals in the lingual gyrus bilaterally, which are known to analyze the color of objects, and in the right frontal operculum and in the anterior insular cortex bilaterally, which are known to process emotional content. In contrast, the left anterior intraparietal sulcus, which is important for configuring the hand to match the three-dimensional structure of objects during grasping, adapted more strongly to manipulable artifacts. Contrary to what a previous study has found using gray-scale photographs, we did not replicate categorical-specific adaptation in the lateral fusiform gyrus for animals and categorical-specific adaptation in the medial fusiform gyrus for manipulable artifacts. Both categories of objects adapted strongly in the fusiform gyrus without any clear preference in location along its medial-lateral axis. We think that this is because the fusiform gyrus has an important role to play in color processing and hence its responsiveness to color stimuli could be very different than its responsiveness to gray-scale photographs. Nevertheless, on the basis of what we found, we propose that the recognition and subsequent classification of animals may depend primarily on perceptual properties, such as their color, and on their emotional content whereas other factors, such as their function, may play a greater role for classifying manipulable artifacts. Copyright © 2011 Elsevier Inc. All rights reserved.

  13. Comparative proteomics of two life cycle stages of stable isotope-labeled Trypanosoma brucei reveals novel components of the parasite's host adaptation machinery.

    PubMed

    Butter, Falk; Bucerius, Ferdinand; Michel, Margaux; Cicova, Zdenka; Mann, Matthias; Janzen, Christian J

    2013-01-01

    Trypanosoma brucei developed a sophisticated life cycle to adapt to different host environments. Although developmental differentiation of T. brucei has been the topic of intensive research for decades, the mechanisms responsible for adaptation to different host environments are not well understood. We developed stable isotope labeling by amino acids in cell culture in trypanosomes to compare the proteomes of two different life cycle stages. Quantitative comparison of 4364 protein groups identified many proteins previously not known to be stage-specifically expressed. The identification of stage-specific proteins helps to understand how parasites adapt to different hosts and provides new insights into differences in metabolism, gene regulation, and cell architecture. A DEAD-box RNA helicase, which is highly up-regulated in the bloodstream form of this parasite and which is essential for viability and proper cell cycle progression in this stage is described as an example.

  14. Phenotypic variation and differentiated gene expression of Australian plants in response to declining rainfall

    PubMed Central

    Fowler, William; Lim, Sim Lin; Enright, Neal; He, Tianhua

    2016-01-01

    Declining rainfall is projected to have negative impacts on the demographic performance of plant species. Little is known about the adaptive capacity of species to respond to drying climates, and whether adaptation can keep pace with climate change. In fire-prone ecosystems, episodic recruitment of perennial plant species in the first year post-fire imposes a specific selection environment, offering a unique opportunity to quantify the scope for adaptive response to climate change. We examined the growth of seedlings of four fire-killed species under control and drought conditions for seeds from populations established in years following fire receiving average-to-above-average winter rainfall, or well-below-average winter rainfall. We show that offspring of plants that had established under drought had more efficient water uptake, and/or stored more water per unit biomass, or developed denser leaves, and all maintained higher survival in simulated drought than did offspring of plants established in average annual rainfall years. Adaptive phenotypic responses were not consistent across all traits and species, while plants that had established under severe drought or established in years with average-to-above-average rainfall had an overall different physiological response when growing either with or without water constraints. Seedlings descended from plants established under severe drought also had elevated gene expression in key pathways relating to stress response. Our results demonstrate the capacity for rapid adaptation to climate change through phenotypic variation and regulation of gene expression. However, effective and rapid adaptation to climate change may vary among species depending on their capacity to maintain robust populations under multiple stresses. PMID:28018654

  15. Phenotypic variation and differentiated gene expression of Australian plants in response to declining rainfall.

    PubMed

    D'Agui, Haylee; Fowler, William; Lim, Sim Lin; Enright, Neal; He, Tianhua

    2016-11-01

    Declining rainfall is projected to have negative impacts on the demographic performance of plant species. Little is known about the adaptive capacity of species to respond to drying climates, and whether adaptation can keep pace with climate change. In fire-prone ecosystems, episodic recruitment of perennial plant species in the first year post-fire imposes a specific selection environment, offering a unique opportunity to quantify the scope for adaptive response to climate change. We examined the growth of seedlings of four fire-killed species under control and drought conditions for seeds from populations established in years following fire receiving average-to-above-average winter rainfall, or well-below-average winter rainfall. We show that offspring of plants that had established under drought had more efficient water uptake, and/or stored more water per unit biomass, or developed denser leaves, and all maintained higher survival in simulated drought than did offspring of plants established in average annual rainfall years. Adaptive phenotypic responses were not consistent across all traits and species, while plants that had established under severe drought or established in years with average-to-above-average rainfall had an overall different physiological response when growing either with or without water constraints. Seedlings descended from plants established under severe drought also had elevated gene expression in key pathways relating to stress response. Our results demonstrate the capacity for rapid adaptation to climate change through phenotypic variation and regulation of gene expression. However, effective and rapid adaptation to climate change may vary among species depending on their capacity to maintain robust populations under multiple stresses.

  16. Natural variation in germination responses of Arabidopsis to seasonal cues and their associated physiological mechanisms

    PubMed Central

    Barua, Deepak; Butler, Colleen; Tisdale, Tracy E.; Donohue, Kathleen

    2012-01-01

    Background and Aims Despite the intense interest in phenological adaptation to environmental change, the fundamental character of natural variation in germination is almost entirely unknown. Specifically, it is not known whether different genotypes within a species are germination specialists to particular conditions, nor is it known what physiological mechanisms of germination regulation vary in natural populations and how they are associated with responses to particular environmental factors. Methods We used a set of recombinant inbred genotypes of Arabidopsis thaliana, in which linkage disequilibrium has been disrupted over seven generations, to test for genetic variation and covariation in germination responses to distinct environmental factors. We then examined physiological mechanisms associated with those responses, including seed-coat permeability and sensitivity to the phytohormones gibberellic acid (GA) and abscisic acid (ABA). Key Results Genetic variation for germination was environment-dependent, but no evidence for specialization of germination to different conditions was found. Hormonal sensitivities also exhibited significant genetic variation, but seed-coat properties did not. GA sensitivity was associated with germination responses to multiple environmental factors, but seed-coat permeability and ABA sensitivity were associated with specific germination responses, suggesting that an evolutionary change in GA sensitivity could affect germination in multiple environments, but that of ABA sensitivity may affect germination under more restricted conditions. Conclusions The physiological mechanisms of germination responses to specific environmental factors therefore can influence the ability to adapt to diverse seasonal environments encountered during colonization of new habitats or with future predicted climate change. PMID:22012958

  17. Neurons in the inferior colliculus of the rat show stimulus-specific adaptation for frequency, but not for intensity

    PubMed Central

    Duque, Daniel; Wang, Xin; Nieto-Diego, Javier; Krumbholz, Katrin; Malmierca, Manuel S.

    2016-01-01

    Electrophysiological and psychophysical responses to a low-intensity probe sound tend to be suppressed by a preceding high-intensity adaptor sound. Nevertheless, rare low-intensity deviant sounds presented among frequent high-intensity standard sounds in an intensity oddball paradigm can elicit an electroencephalographic mismatch negativity (MMN) response. This has been taken to suggest that the MMN is a correlate of true change or “deviance” detection. A key question is where in the ascending auditory pathway true deviance sensitivity first emerges. Here, we addressed this question by measuring low-intensity deviant responses from single units in the inferior colliculus (IC) of anesthetized rats. If the IC exhibits true deviance sensitivity to intensity, IC neurons should show enhanced responses to low-intensity deviant sounds presented among high-intensity standards. Contrary to this prediction, deviant responses were only enhanced when the standards and deviants differed in frequency. The results could be explained with a model assuming that IC neurons integrate over multiple frequency-tuned channels and that adaptation occurs within each channel independently. We used an adaptation paradigm with multiple repeated adaptors to measure the tuning widths of these adaption channels in relation to the neurons’ overall tuning widths. PMID:27066835

  18. Anger and Sadness in Response to an Emotionally-Neutral Film: Evidence for Age-Specific Associations with Well-Being

    PubMed Central

    Haase, Claudia M.; Seider, Benjamin H.; Shiota, Michelle N.; Levenson, Robert W.

    2011-01-01

    When the association between emotion and well-being is being considered, positive emotions usually come to mind. However, negative emotions serve important adaptive functions and particular negative emotions may be especially adaptive at different stages of adult development. We examined the associations between self-reported negative emotions in response to an emotionally-neutral, thematically-ambiguous film and subjective well-being among 76 young (age 20–29), 73 middle-aged (age 40–49), and 73 older (age 60–69) adults. Results indicated that higher self-reported anger in response to the film was associated with higher well-being for middle-aged adults, but not for young and older adults. Higher self-reported sadness in response to the film was associated with higher well-being for older adults, but not for young and middle-aged adults. These findings were stronger for cognitive well-being (i.e., satisfaction with life) than for affective well-being (i.e., ratio of positive to negative affect) and were specific to these emotions (not found for self-reported disgust or fear) and to the emotionally-neutral film (not found for sad or disgusting films). Results are discussed in terms of the functions that anger and sadness are thought to serve and the control opportunities afforded in midlife and late life that render these functions differentially adaptive. PMID:21843005

  19. Acclimation of Saccharomyces cerevisiae to low temperature: a chemostat-based transcriptome analysis.

    PubMed

    Tai, Siew Leng; Daran-Lapujade, Pascale; Walsh, Michael C; Pronk, Jack T; Daran, Jean-Marc

    2007-12-01

    Effects of suboptimal temperatures on transcriptional regulation in yeast have been extensively studied in batch cultures. To eliminate indirect effects of specific growth rates that are inherent to batch-cultivation studies, genome-wide transcriptional responses to low temperatures were analyzed in steady-state chemostats, grown at a fixed specific growth rate (0.03 h(-1)). Although in vivo metabolic fluxes were essentially the same in cultures grown at 12 and at 30 degrees C, concentrations of the growth-limiting nutrients (glucose or ammonia) were higher at 12 degrees C. This difference was reflected by transcript levels of genes that encode transporters for the growth-limiting nutrients. Several transcriptional responses to low temperature occurred under both nutrient-limitation regimes. Increased transcription of ribosome-biogenesis genes emphasized the importance of adapting protein-synthesis capacity to low temperature. In contrast to observations in cold-shock and batch-culture studies, transcript levels of environmental stress response genes were reduced at 12 degrees C. Transcription of trehalose-biosynthesis genes and intracellular trehalose levels indicated that, in contrast to its role in cold-shock adaptation, trehalose is not involved in steady-state low-temperature adaptation. Comparison of the chemostat-based transcriptome data with literature data revealed large differences between transcriptional reprogramming during long-term low-temperature acclimation and the transcriptional responses to a rapid transition to low temperature.

  20. Evasion of adaptive and innate immune response mechanisms by γ-herpesviruses

    PubMed Central

    Feng, Pinghui; Moses, Ashlee; Früh, Klaus

    2015-01-01

    γ-Herpesviral immune evasion mechanisms are optimized to support the acute, lytic and the longterm, latent phase of infection. During acute infection, specific immune modulatory proteins limit, but also exploit, the antiviral activities of cell intrinsic innate immune responses as well as those of innate and adaptive immune cells. During latent infection, a restricted gene expression program limits immune targeting and cis-acting mechanisms to reduce the antigen presentation as well as antigenicity of latency-associated proteins. Here, we will review recent progress in our understanding of γ-herpesviral immune evasion strategies. PMID:23735334

  1. Guiding climate change adaptation within vulnerable natural resource management systems.

    PubMed

    Bardsley, Douglas K; Sweeney, Susan M

    2010-05-01

    Climate change has the potential to compromise the sustainability of natural resources in Mediterranean climatic systems, such that short-term reactive responses will increasingly be insufficient to ensure effective management. There is a simultaneous need for both the clear articulation of the vulnerabilities of specific management systems to climate risk, and the development of appropriate short- and long-term strategic planning responses that anticipate environmental change or allow for sustainable adaptive management in response to trends in resource condition. Governments are developing climate change adaptation policy frameworks, but without the recognition of the importance of responding strategically, regional stakeholders will struggle to manage future climate risk. In a partnership between the South Australian Government, the Adelaide and Mt Lofty Ranges Natural Resource Management Board and the regional community, a range of available research approaches to support regional climate change adaptation decision-making, were applied and critically examined, including: scenario modelling; applied and participatory Geographical Information Systems modelling; environmental risk analysis; and participatory action learning. As managers apply ideas for adaptation within their own biophysical and socio-cultural contexts, there would be both successes and failures, but a learning orientation to societal change will enable improvements over time. A base-line target for regional responses to climate change is the ownership of the issue by stakeholders, which leads to an acceptance that effective actions to adapt are now both possible and vitally important. Beyond such baseline knowledge, the research suggests that there is a range of tools from the social and physical sciences available to guide adaptation decision-making.

  2. Genome Resequencing Identifies Unique Adaptations of Tibetan Chickens to Hypoxia and High-Dose Ultraviolet Radiation in High-Altitude Environments

    PubMed Central

    Zhang, Qian; Gou, Wenyu; Wang, Xiaotong; Zhang, Yawen; Ma, Jun; Zhang, Hongliang; Zhang, Ying; Zhang, Hao

    2016-01-01

    Tibetan chicken, unlike their lowland counterparts, exhibit specific adaptations to high-altitude conditions. The genetic mechanisms of such adaptations in highland chickens were determined by resequencing the genomes of four highland (Tibetan and Lhasa White) and four lowland (White Leghorn, Lindian, and Chahua) chicken populations. Our results showed an evident genetic admixture in Tibetan chickens, suggesting a history of introgression from lowland gene pools. Genes showing positive selection in highland populations were related to cardiovascular and respiratory system development, DNA repair, response to radiation, inflammation, and immune responses, indicating a strong adaptation to oxygen scarcity and high-intensity solar radiation. The distribution of allele frequencies of nonsynonymous single nucleotide polymorphisms between highland and lowland populations was analyzed using chi-square test, which showed that several differentially distributed genes with missense mutations were enriched in several functional categories, especially in blood vessel development and adaptations to hypoxia and intense radiation. RNA sequencing revealed that several differentially expressed genes were enriched in gene ontology terms related to blood vessel and respiratory system development. Several candidate genes involved in the development of cardiorespiratory system (FGFR1, CTGF, ADAM9, JPH2, SATB1, BMP4, LOX, LPR, ANGPTL4, and HYAL1), inflammation and immune responses (AIRE, MYO1F, ZAP70, DDX60, CCL19, CD47, JSC, and FAS), DNA repair, and responses to radiation (VCP, ASH2L, and FANCG) were identified to play key roles in the adaptation to high-altitude conditions. Our data provide new insights into the unique adaptations of highland animals to extreme environments. PMID:26907498

  3. Guiding Climate Change Adaptation Within Vulnerable Natural Resource Management Systems

    NASA Astrophysics Data System (ADS)

    Bardsley, Douglas K.; Sweeney, Susan M.

    2010-05-01

    Climate change has the potential to compromise the sustainability of natural resources in Mediterranean climatic systems, such that short-term reactive responses will increasingly be insufficient to ensure effective management. There is a simultaneous need for both the clear articulation of the vulnerabilities of specific management systems to climate risk, and the development of appropriate short- and long-term strategic planning responses that anticipate environmental change or allow for sustainable adaptive management in response to trends in resource condition. Governments are developing climate change adaptation policy frameworks, but without the recognition of the importance of responding strategically, regional stakeholders will struggle to manage future climate risk. In a partnership between the South Australian Government, the Adelaide and Mt Lofty Ranges Natural Resource Management Board and the regional community, a range of available research approaches to support regional climate change adaptation decision-making, were applied and critically examined, including: scenario modelling; applied and participatory Geographical Information Systems modelling; environmental risk analysis; and participatory action learning. As managers apply ideas for adaptation within their own biophysical and socio-cultural contexts, there would be both successes and failures, but a learning orientation to societal change will enable improvements over time. A base-line target for regional responses to climate change is the ownership of the issue by stakeholders, which leads to an acceptance that effective actions to adapt are now both possible and vitally important. Beyond such baseline knowledge, the research suggests that there is a range of tools from the social and physical sciences available to guide adaptation decision-making.

  4. Identifying Stress Transcription Factors Using Gene Expression and TF-Gene Association Data

    PubMed Central

    Wu, Wei-Sheng; Chen, Bor-Sen

    2007-01-01

    Unicellular organisms such as yeasts have evolved to survive environmental stresses by rapidly reorganizing the genomic expression program to meet the challenges of harsh environments. The complex adaptation mechanisms to stress remain to be elucidated. In this study, we developed Stress Transcription Factor Identification Algorithm (STFIA), which integrates gene expression and TF-gene association data to identify the stress transcription factors (TFs) of six kinds of stresses. We identified some general stress TFs that are in response to various stresses, and some specific stress TFs that are in response to one specific stress. The biological significance of our findings is validated by the literature. We found that a small number of TFs may be sufficient to control a wide variety of expression patterns in yeast under different stresses. Two implications can be inferred from this observation. First, the adaptation mechanisms to different stresses may have a bow-tie structure. Second, there may exist extensive regulatory cross-talk among different stress responses. In conclusion, this study proposes a network of the regulators of stress responses and their mechanism of action. PMID:20066130

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

    NASA Technical Reports Server (NTRS)

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

    2002-01-01

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

  6. Monitoring and Correcting Autonomic Function Aboard Mir: NASA Technology Used in Space and on Earth to Facilitate Adaptation

    NASA Technical Reports Server (NTRS)

    Cowings, P.; Toscano, W.; Taylor, B.; DeRoshia, C.; Kornilova, L.; Koslovskaya, I.; Miller, N.

    1999-01-01

    The broad objective of the research was to study individual characteristics of human adaptation to long duration spaceflight and possibilities of their correction using autonomic conditioning. The changes in autonomic state during adaptation to microgravity can have profound effects on the operational efficiency of crewmembers and may result in debilitating biomedical symptoms. Ground-based and inflight experiment results showed that certain responses of autonomic nervous system were correlated with, or consistently preceded, reports of performance decrements or the symptoms. Autogenic-Feedback-Training Exercise (AFTE) is a physiological conditioning method that has been used to train people to voluntary control several of their own physiological responses. The specific objectives were: 1) To study human autonomic nervous system (ANS) responses to sustained exposure to microgravity; 2) To study human behavior/performance changes related to physiology; 3) To evaluate the effectiveness of preflight autonomic conditioning (AFTE) for facilitating adaptation to space and readaptation to Earth; and 4) To archive these data for the NASA Life Sciences Data Archive and thereby make this information available to the international scientific community.

  7. Metabolomics of cereals under biotic stress: current knowledge and techniques

    PubMed Central

    Balmer, Dirk; Flors, Victor; Glauser, Gaetan; Mauch-Mani, Brigitte

    2013-01-01

    Prone to attacks by pathogens and pests, plants employ intricate chemical defense mechanisms consisting of metabolic adaptations. However, many plant attackers are manipulating the host metabolism to counteract defense responses and to induce favorable nutritional conditions. Advances in analytical chemistry have allowed the generation of extensive metabolic profiles during plant-pathogen and pest interactions. Thereby, metabolic processes were found to be highly specific for given tissues, species, and plant-pathogen/pest interactions. The clusters of identified compounds not only serve as base in the quest of novel defense compounds, but also as markers for the characterization of the plants' defensive state. The latter is especially useful in agronomic applications where meaningful markers are essential for crop protection. Cereals such as maize make use of their metabolic arsenal during both local and systemic defense responses, and the chemical response is highly adapted to specific attackers. Here, we summarize highlights and recent findings of metabolic patterns of cereals under pathogen and pest attack. PMID:23630531

  8. Skeletal muscle plasticity: cellular and molecular responses to altered physical activity paradigms

    NASA Technical Reports Server (NTRS)

    Baldwin, Kenneth M.; Haddad, Fadia

    2002-01-01

    The goal of this article is to examine our current understanding of the chain of events known to be involved in the adaptive process whereby specific genes and their protein products undergo altered expression; specifically, skeletal muscle adaptation in response to altered loading states will be discussed, with a special focus on the regulation of the contractile protein, myosin heavy chain gene expression. This protein, which is both an important structural and regulatory protein comprising the contractile apparatus, can be expressed as different isoforms, thereby having an impact on the functional diversity of the muscle. Because the regulation of the myosin gene family is under the control of a complex set of processes including, but not limited to, activity, hormonal, and metabolic factors, this protein will serve as a cellular "marker" for studies of muscle plasticity in response to various mechanical perturbations in which the quantity and type of myosin isoform, along with other important cellular proteins, are altered in expression.

  9. Age-associated loss of selectivity in human olfactory sensory neurons

    PubMed Central

    Rawson, Nancy E.; Gomez, George; Cowart, Beverly J.; Kriete, Andres; Pribitkin, Edmund; Restrepo, Diego

    2011-01-01

    We report a cross-sectional study of olfactory impairment with age based on both odorant-stimulated responses of human olfactory sensory neurons (OSNs) and tests of olfactory threshold sensitivity. A total of 621 OSNs from 440 subjects in two age groups of younger ( 45 years) and older (≥60 years) subjects were investigated using fluorescence intensity ratio fura-2 imaging. OSNs were tested for responses to two odorant mixtures, as well as to subsets of and individual odors in those mixtures. Whereas cells from younger donors were highly selective in the odorants to which they responded, cells from older donors were more likely to respond to multiple odor stimuli, despite a loss in these subjects’ absolute olfactory sensitivity, suggesting a loss of specificity. This degradation in peripheral cellular specificity may impact odor discrimination and olfactory adaptation in the elderly. It is also possible that chronic adaptation as a result of reduced specificity contributes to observed declines in absolute sensitivity. PMID:22074806

  10. Good decision-making is associated with an adaptive cardiovascular response to social competitive stress.

    PubMed

    Alacreu-Crespo, Adrián; Costa, Raquel; Abad-Tortosa, Diana; Salvador, Alicia; Serrano, Miguel Ángel

    2018-06-22

    Competition elicits different psychological and cardiovascular responses depending on a person's skills. Decision-making has been considered a distal factor that influences competition, but there are no studies analyzing this relationship. Our objective was to analyze whether decision-making affects the response to competition. Specifically, we aimed to test whether good performers on a decision-making test, the Iowa Gambling Task (IGT), showed an adaptive cardiovascular response to competition. In all, 116 participants (44 women) performed the IGT and were classified into Good or Poor decision-makers. Subsequently, they were exposed to a stress task in two different conditions: a face-to-face competition (winners/losers) or a control condition, while an electrocardiogram was recorded. In the competition group, good decision-makers increased their high-frequency respect to the total heart rate variability (HF/HRV) levels during the task, compared to Poor decision-makers. Again, competition group good decision-makers, showed lower LF and higher HF/HRV reactivity than the control group, which represents lower HRV stress pattern. Moreover, in the group of losers, good decision-makers had a decline in low frequency (LF) during the task and faster recovery than poor decision-makers. In conclusion, good decision-makers have a more adaptive stress response and higher levels of mental effort, based on total HRV interpretation. Decision-making skills could be a factor in a more adaptive cardiovascular response to competition.

  11. Interferon alpha inhibits replication of a live-attenuated porcine reproductive and respiratory syndrome virus vaccine preventing development of an adaptive immune response in swine.

    PubMed

    Brockmeier, Susan L; Loving, Crystal L; Eberle, Kirsten C; Hau, Samantha J; Buckley, Alexandra; Van Geelen, Albert; Montiel, Nestor A; Nicholson, Tracy; Lager, Kelly M

    2017-12-01

    Type I interferons, such as interferon alpha (IFN-α), contribute to innate antiviral immunity by promoting production of antiviral mediators and are also involved in promoting an adaptive immune response. Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most devastating and costly viruses to the swine industry world-wide and has been shown to induce a meager IFN-α response. Previously we administered porcine IFN-α using a replication-defective adenovirus vector (Ad5-IFN-α) at the time of challenge with virulent PRRSV and demonstrated an increase in the number of virus-specific IFNγ secreting cells, indicating that the presence of IFN-α at the time of infection can alter the adaptive immune responses to PRRSV. In the current experiment, we explored the use of IFN-α as an adjuvant administered with live-attenuated PRRSV vaccine as a method to enhance immune response to the vaccine. Unlike the previous studies with fully virulent virus, one injection of the Ad5-IFN-α abolished replication of the vaccine virus and as a result there was no detectible adaptive immune response. Although IFN-α did not have the desired adjuvant effect, the results further highlight the use of IFN-α as a treatment for PRRSV infection. Published by Elsevier B.V.

  12. Root Type-Specific Reprogramming of Maize Pericycle Transcriptomes by Local High Nitrate Results in Disparate Lateral Root Branching Patterns1[OPEN

    PubMed Central

    Lithio, Andrew

    2016-01-01

    The adaptability of root system architecture to unevenly distributed mineral nutrients in soil is a key determinant of plant performance. The molecular mechanisms underlying nitrate dependent plasticity of lateral root branching across the different root types of maize are only poorly understood. In this study, detailed morphological and anatomical analyses together with cell type-specific transcriptome profiling experiments combining laser capture microdissection with RNA-seq were performed to unravel the molecular signatures of lateral root formation in primary, seminal, crown, and brace roots of maize (Zea mays) upon local high nitrate stimulation. The four maize root types displayed divergent branching patterns of lateral roots upon local high nitrate stimulation. In particular, brace roots displayed an exceptional architectural plasticity compared to other root types. Transcriptome profiling revealed root type-specific transcriptomic reprogramming of pericycle cells upon local high nitrate stimulation. The alteration of the transcriptomic landscape of brace root pericycle cells in response to local high nitrate stimulation was most significant. Root type-specific transcriptome diversity in response to local high nitrate highlighted differences in the functional adaptability and systemic shoot nitrogen starvation response during development. Integration of morphological, anatomical, and transcriptomic data resulted in a framework underscoring similarity and diversity among root types grown in heterogeneous nitrate environments. PMID:26811190

  13. Modulation of alloimmune response by commensal gut microbiota and potential new avenues to influence the outcome of allogeneic transplantation by modification of the 'gut culture'.

    PubMed

    Kanangat, S

    2017-02-01

    Host defence response against microbial infections was the foundation for the Science of Immunology. Now, we know the mechanisms of such host defence which include innate immune responses that is generally nonspecific but effective in many cases and lead to more specific responses called adaptive immune response. The gene loci of class I, II and III of the major histocompatibility complex (MHC) play a major role in directing the adaptive immune responses by presenting processed antigens to T and B cells to induce appropriate antigen-specific cellular and or humoral immune responses. In humans, these are commonly referred to as human leucocyte antigens class I/II-HLA I/II). The class III region, the gamma region in the MHC complex, is mostly associated with regulation of immune responses along with genes associated with complement activation. The adaptive immune responses are orchestrated by T and B cells that are tuned to respond to antigens that are normally foreign to the body, because these cells are educated to avoid self-antigens by a process of thymic education and selection of the T cells that are mostly non-self-reactive which also helps the B cells in eliciting specific immune responses to non-self-antigens. A by-product of this is the ability of the T and B cells to elicit strong immune responses to foreign HLA/MHC (alloimmune response), which developed into the field of histocompatibility testing for allogeneic transplantation of stem cells and organs. Now, we are beginning to learn that such alloimmune responses can be influenced by the microbiota that symbiotically live in our body especially on the mucosal surfaces and on the skin. This review deals with new and emerging data on how the commensal mucosal and skin microbiota influence the immune homeostasis, and how manipulating the commensal microbiota of the mucosa and skin could influence the survival and long-term functions of the allografts. Also, alterations of the microbiota by the inevitable immunosuppression prior to and following allogeneic transplantation could contribute towards the outcome of the allografts by alloimmune responses generated due to microbial antigen vs HLA cross-reactivity. © 2017 John Wiley & Sons Ltd.

  14. Enhanced retinal responses in Huntington's disease patients.

    PubMed

    Pearl, Jocelynn R; Heath, Laura M; Bergey, Dani E; Kelly, John P; Smith, Corrie; Laurino, Mercy Y; Weiss, Avery; Price, Nathan D; LaSpada, Albert; Bird, Thomas D; Jayadev, Suman

    2017-01-01

    Huntington's disease (HD) is a fatal progressive neurodegenerative disease characterized by chorea, cognitive impairment and psychiatric symptoms. Retinal examination of HD patients as well as in HD animal models have shown evidence of retinal dysfunction. However, a detailed retinal study employing clinically available measurement tools has not been reported to date in HD. The goal of this study was to assess retinal responses measured by electroretinogram (ERG) between HD patients and controls and evaluate any correlation between ERG measurements and stage of disease. Eighteen patients and 10 controls with inclusion criteria of ages 18-70 years (average age HD subjects: 52.1 yrs and control subjects: 51.9 yrs) were recruited for the study. Subjects with previous history of retinal or ophthalmologic disease were excluded. Retinal function was examined by full-field ERG in both eyes of each subject. Amplitudes and latencies to increasing flash intensities in both light- and dark-adaptation were measured in all subjects. Statistical analyses employed generalized estimating equations, which account for repeated measures per subject. We analyzed the b-wave amplitudes of ERG response in all flash intensities and with 30 Hz flicker stimulation. We found statistically significant increased amplitudes in HD patients compared to controls at light-adapted (photopic) 24.2 and 60.9 cd.sec/m2 intensities, dark-adapted (scotopic, red flash) 0.22 cd.sec/m2 intensity, and a trend toward significance at light-adapted 30 Hz flicker. Furthermore, we found a significant increase in light-adapted ERG response from female compared to male HD patients, but no significant difference between gender amongst controls. We also noted a positive association between number of CAG repeats and ERG response at the smallest light adapted intensity (3.1 cd.sec/m2). ERG studies revealed significantly altered retinal responses at multiple flash intensities in subjects with an HD expansion allele compared to controls. Significant differences were observed with either light-adapted tests or the dark-adapted red flash which suggests that the enhanced responses in HD patients is specific to the cone photoreceptor pathway.

  15. Ants and antlions: The impact of ecology, coevolution and learning on an insect predator-prey relationship.

    PubMed

    Hollis, Karen L

    2017-06-01

    A behavioural ecological approach to the relationship between pit-digging larval antlions and their common prey, ants, provides yet another example of how the specific ecological niche that species inhabit imposes selection pressures leading to unique behavioural adaptations. Antlions rely on multiple strategies to capture prey with a minimal expenditure of energy and extraordinary efficiency while ants employ several different strategies for avoiding capture, including rescue of trapped nestmates. Importantly, both ants and antlions rely heavily on their capacity for learning, a tool that sometimes is overlooked in predator-prey relationships, leading to the implicit assumption that behavioural adaptations are the result of fixed, hard-wired responses. Nonetheless, like hard-wired responses, learned behaviour, too, is uniquely adapted to the ecological niche, a reminder that the expression of associative learning is species-specific. Beyond the study of ants and antlions, per se, this particular predator-prey relationship reveals the important role that the capacity to learn plays in coevolutionary arms races. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Hepatic IRE1α regulates fasting-induced metabolic adaptive programs through the XBP1s-PPARα axis signalling.

    PubMed

    Shao, Mengle; Shan, Bo; Liu, Yang; Deng, Yiping; Yan, Cheng; Wu, Ying; Mao, Ting; Qiu, Yifu; Zhou, Yubo; Jiang, Shan; Jia, Weiping; Li, Jingya; Li, Jia; Rui, Liangyou; Yang, Liu; Liu, Yong

    2014-03-27

    Although the mammalian IRE1α-XBP1 branch of the cellular unfolded protein response has been implicated in glucose and lipid metabolism, the exact metabolic role of IRE1α signalling in vivo remains poorly understood. Here we show that hepatic IRE1α functions as a nutrient sensor that regulates the metabolic adaptation to fasting. We find that prolonged deprivation of food or consumption of a ketogenic diet activates the IRE1α-XBP1 pathway in mouse livers. Hepatocyte-specific abrogation of Ire1α results in impairment of fatty acid β-oxidation and ketogenesis in the liver under chronic fasting or ketogenic conditions, leading to hepatosteatosis; liver-specific restoration of XBP1s reverses the defects in IRE1α null mice. XBP1s directly binds to and activates the promoter of PPARα, the master regulator of starvation responses. Hence, our results demonstrate that hepatic IRE1α promotes the adaptive shift of fuel utilization during starvation by stimulating mitochondrial β-oxidation and ketogenesis through the XBP1s-PPARα axis.

  17. The simultaneous ex vivo detection of low-frequency antigen-specific CD4+ and CD8+ T-cell responses using overlapping peptide pools.

    PubMed

    Singh, Satwinder Kaur; Meyering, Maaike; Ramwadhdoebe, Tamara H; Stynenbosch, Linda F M; Redeker, Anke; Kuppen, Peter J K; Melief, Cornelis J M; Welters, Marij J P; van der Burg, Sjoerd H

    2012-11-01

    The ability to measure antigen-specific T cells at the single-cell level by intracellular cytokine staining (ICS) is a promising immunomonitoring tool and is extensively applied in the evaluation of immunotherapy of cancer. The protocols used to detect antigen-specific CD8+ T-cell responses generally work for the detection of antigen-specific T cells in samples that have undergone at least one round of in vitro pre-stimulation. Application of a common protocol but now using long peptides as antigens was not suitable to simultaneously detect antigen-specific CD8+ and CD4+ T cells directly ex vivo in cryopreserved samples. CD8 T-cell reactivity to monocytes pulsed with long peptides as antigens ranged between 5 and 25 % of that observed against monocytes pulsed with a direct HLA class I fitting minimal CTL peptide epitope. Therefore, we adapted our ICS protocol and show that the use of tenfold higher concentration of long peptides to load APC, the use of IFN-α and poly(I:C) to promote antigen processing and improve T-cell stimulation, does allow for the ex vivo detection of low-frequency antigen-specific CD8+ and CD4+ T cells in an HLA-independent setting. While most of the improvements were related to increasing the ability to measure CD8+ T-cell reactivity following stimulation with long peptides to at least 50 % of the response detected when using a minimal peptide epitope, the final analysis of blood samples from vaccinated patients successfully showed that the adapted ICS protocol also increases the ability to ex vivo detect low-frequency p53-specific CD4+ T-cell responses in cryopreserved PBMC samples.

  18. Bartonella quintana Deploys Host and Vector Temperature-Specific Transcriptomes

    PubMed Central

    Previte, Domenic; Yoon, Kyong S.; Clark, J. Marshall; DeRisi, Joseph L.; Koehler, Jane E.

    2013-01-01

    The bacterial pathogen Bartonella quintana is passed between humans by body lice. B. quintana has adapted to both the human host and body louse vector niches, producing persistent infection with high titer bacterial loads in both the host (up to 105 colony-forming units [CFU]/ml) and vector (more than 108 CFU/ml). Using a novel custom microarray platform, we analyzed bacterial transcription at temperatures corresponding to the host (37°C) and vector (28°C), to probe for temperature-specific and growth phase-specific transcriptomes. We observed that transcription of 7% (93 genes) of the B. quintana genome is modified in response to change in growth phase, and that 5% (68 genes) of the genome is temperature-responsive. Among these transcriptional changes in response to temperature shift and growth phase was the induction of known B. quintana virulence genes and several previously unannotated genes. Hemin binding proteins, secretion systems, response regulators, and genes for invasion and cell attachment were prominent among the differentially-regulated B. quintana genes. This study represents the first analysis of global transcriptional responses by B. quintana. In addition, the in vivo experiments provide novel insight into the B. quintana transcriptional program within the body louse environment. These data and approaches will facilitate study of the adaptation mechanisms employed by Bartonella during the transition between human host and arthropod vector. PMID:23554923

  19. Ambiguous Tilt and Translation Motion Cues in Astronauts After Space Flight (ZAG)

    NASA Astrophysics Data System (ADS)

    Clement, Guilles; Harm, Deborah; Rupert, Angus; Beaton, Kara; Wood, Scott

    2008-06-01

    Adaptive changes during space flight in how the brain integrates vestibular cues with visual, proprioceptive, and somatosensory information can lead to impaired movement coordination, vertigo, spatial disorientation, and perceptual illusions following transitions between gravity levels. This joint ESA-NASA pre- and post-flight experiment is designed to examine both the physiological basis and operational implications for disorientation and tilt-translation disturbances in astronauts following short-duration space flights. Specifically, this study addresses three questions: (1) What adaptive changes occur in eye movements and motion perception in response to different combinations of tilt and translation motion? (2) Do adaptive changes in tilt-translation responses impair ability to manually control vehicle orientation? (3) Can sensory substitution aids (e.g., tactile) mitigate risks associated with manual control of vehicle orientation?

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

    PubMed

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

    2013-01-01

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

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

    PubMed Central

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

    2013-01-01

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

  2. Cardiac-specific overexpression of aldehyde dehydrogenase 2 exacerbates cardiac remodeling in response to pressure overload.

    PubMed

    Dassanayaka, Sujith; Zheng, Yuting; Gibb, Andrew A; Cummins, Timothy D; McNally, Lindsey A; Brittian, Kenneth R; Jagatheesan, Ganapathy; Audam, Timothy N; Long, Bethany W; Brainard, Robert E; Jones, Steven P; Hill, Bradford G

    2018-06-01

    Pathological cardiac remodeling during heart failure is associated with higher levels of lipid peroxidation products and lower abundance of several aldehyde detoxification enzymes, including aldehyde dehydrogenase 2 (ALDH2). An emerging idea that could explain these findings concerns the role of electrophilic species in redox signaling, which may be important for adaptive responses to stress or injury. The purpose of this study was to determine whether genetically increasing ALDH2 activity affects pressure overload-induced cardiac dysfunction. Mice subjected to transverse aortic constriction (TAC) for 12 weeks developed myocardial hypertrophy and cardiac dysfunction, which were associated with diminished ALDH2 expression and activity. Cardiac-specific expression of the human ALDH2 gene in mice augmented myocardial ALDH2 activity but did not improve cardiac function in response to pressure overload. After 12 weeks of TAC, ALDH2 transgenic mice had larger hearts than their wild-type littermates and lower capillary density. These findings show that overexpression of ALDH2 augments the hypertrophic response to pressure overload and imply that downregulation of ALDH2 may be an adaptive response to certain forms of cardiac pathology. Copyright © 2018. Published by Elsevier B.V.

  3. Helper T Cell Responses to Respiratory Viruses in the Lung: Development, Virus Suppression, and Pathogenesis.

    PubMed

    Miyauchi, Kosuke

    The lung is an important line of defense that is exposed to respiratory infectious pathogens, including viruses. Lung epithelial cells and/or alveolar macrophages are initially targeted by respiratory viruses. Once respiratory viruses invade the cells of the lung, innate immunity is activated to inhibit viral replication. Innate immune signaling also activates virus-specific adaptive immune responses. The helper T cells play pivotal roles in the humoral and cellular adaptive immune responses. Helper T cells are categorized into several distinct subsets (e.g., T H 1, T H 2, T FH , T H 17, and Treg), differentiated by their corresponding signature cytokine production profiles. Helper T cells migrate into the airways and the lung after respiratory virus infections. The behavior of the helper T cells differs with each respiratory virus-in some cases, the response is beneficial; in other cases, it is harmful. Here, the general mechanisms underlying helper T cell responses to viral infections are summarized, and functions and reactions of the helper T cells against some respiratory viral infections are discussed. In influenza virus infections, T H 1 cells, which regulate the cytotoxic T lymphocytes and IgG2 responses, are efficiently activated. T FH cells required for highly specific and memory humoral responses are also activated on influenza infections. In infections with respiratory syncytial virus and rhinovirus, T H 2 cells develop in the lung and contribute to pathogenesis. In many cases, Treg cells inhibit excessive virus-specific T cell responses that can contribute to viral pathogenicity.

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

    USGS Publications Warehouse

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

    2014-01-01

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

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

    PubMed

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

    2014-03-01

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

  6. Lineage-specific evolution of bitter taste receptor genes in the giant and red pandas implies dietary adaptation.

    PubMed

    Shan, Lei; Wu, Qi; Wang, Le; Zhang, Lei; Wei, Fuwen

    2018-03-01

    Taste 2 receptors (TAS2R) mediate bitterness perception in mammals, thus are called bitter taste receptors. It is believed that these genes evolved in response to species-specific diets. The giant panda (Ailuropoda melanoleuca) and red panda (Ailurus fulgens styani) in the order Carnivora are specialized herbivores with an almost exclusive bamboo diet (>90% bamboo). Because bamboo is full of bitter tasting compounds, we hypothesized that adaptive evolution has occurred at TAS2R genes in giant and red pandas throughout the course of their dietary shift. Here, we characterized 195 TAS2R genes in 9 Carnivora species and examined selective pressures on these genes. We found that both pandas harbor more putative functional TAS2R genes than other carnivores, and pseudogenized TAS2R genes in the giant panda are different from the red panda. The purifying selection on TAS2R1, TAS2R9 and TAS2R38 in the giant panda, and TAS2R62 in the red panda, has been strengthened throughout the course of adaptation to bamboo diet, while selective constraint on TAS2R4 and TAS2R38 in the red panda is relaxed. Remarkably, a few positively selected sites on TAS2R42 have been specifically detected in the giant panda. These results suggest an adaptive response in both pandas to a dietary shift from carnivory to herbivory, and TAS2R genes evolved independently in the 2 pandas. Our findings provide new insight into the molecular basis of mammalian sensory evolution and the process of adaptation to new ecological niches. © 2017 The Authors. Integrative Zoology published by International Society of Zoological Sciences, Institute of Zoology/Chinese Academy of Sciences and John Wiley & Sons Australia, Ltd.

  7. Customizing Countermeasure Prescriptions using Predictive Measures of Sensorimotor Adaptability

    NASA Technical Reports Server (NTRS)

    Bloomberg, J. J.; Peters, B. T.; Mulavara, A. P.; Miller, C. A.; Batson, C. D.; Wood, S. J.; Guined, J. R.; Cohen, H. S.; Buccello-Stout, R.; DeDios, Y. E.; hide

    2014-01-01

    Astronauts experience sensorimotor disturbances during the initial exposure to microgravity and during the readapation phase following a return to a gravitational environment. These alterations may lead to disruption in the ability to perform mission critical functional tasks during and after these gravitational transitions. Astronauts show significant inter-subject variation in adaptive capability following gravitational transitions. The ability to predict the manner and degree to which each individual astronaut will be affected would improve the effectiveness of a countermeasure comprised of a training program designed to enhance sensorimotor adaptability. Due to this inherent individual variability we need to develop predictive measures of sensorimotor adaptability that will allow us to predict, before actual space flight, which crewmember will experience challenges in adaptive capacity. Thus, obtaining this information will allow us to design and implement better sensorimotor adaptability training countermeasures that will be customized for each crewmember's unique adaptive capabilities. Therefore the goals of this project are to: 1) develop a set of predictive measures capable of identifying individual differences in sensorimotor adaptability, and 2) use this information to design sensorimotor adaptability training countermeasures that are customized for each crewmember's individual sensorimotor adaptive characteristics. To achieve these goals we are currently pursuing the following specific aims: Aim 1: Determine whether behavioral metrics of individual sensory bias predict sensorimotor adaptability. For this aim, subjects perform tests that delineate individual sensory biases in tests of visual, vestibular, and proprioceptive function. Aim 2: Determine if individual capability for strategic and plastic-adaptive responses predicts sensorimotor adaptability. For this aim, each subject's strategic and plastic-adaptive motor learning abilities are assessed using a test of locomotor function designed specifically to delineate both mechanisms. Aim 3: Develop predictors of sensorimotor adaptability using brain structural and functional metrics. We will measure individual differences in regional brain volumes (structural MRI), white matter integrity (diffusion tensor imaging, or DTI), functional network integrity (resting state functional connectivity MRI), and sensorimotor adaptation task-related functional brain activation (functional MRI). We decided to complete the data collection for Specific Aims 1, 2 and 3 simultaneously on the same subjects to increase data capture. By having the same subjects perform all three specific aims we can enhance our ability to detect how a wider range of factors can predict adaptability in a specific individual. This provides a much richer database and potentially a better understanding of the predictive power of the selected factors. In this presentation I will discuss preliminary data obtained to date.

  8. In-Vitro Induced Immunosuppression in a Rotary Cell Culture System

    NASA Technical Reports Server (NTRS)

    Grimm, Elizabeth A.

    1998-01-01

    The function of the innate immune system is to provide a first-line of defense against infectious organisms, via control of bacterial and viral growth using antigen nonspecific means. These nonspecific immune effectors include macrophages and Natural Killing (NK) cells, and certain cytokines elicited in response to "super antigens" on the infectious agents. This innate system usually keeps most infectious agents from rapidly growing while the adaptive immune system is generating a specific response complete with immunologic memory. Compelling evidence suggests that space flight results in various immunosuppressive effects, including reduced innate and adaptive immune responses. We were particularly concerned with reduced NK activity at landing, and have asked whether the microgravity component of space flight could be responsible for the previously observed NK defect. We have conclusively demonstrated that simulated microgravity as provided by the Synthecon bioreactors does not inhibit the NK function nor the IL-2 activation of lymphokine-activated killing (LAK). Interleukin-2 is the key cytokine responsible for activation of NK cells to express LAK, as well as to support differentiation of lymphocytes during adaptive immune responses. Therefore, we have disproved our original hypothesis based on poor NK in many of the astronauts upon landing.

  9. Induction, adaptation and recovery of biological responses: implications for environmental monitoring.

    PubMed

    Wu, Rudolf S S; Siu, William H L; Shin, Paul K S

    2005-01-01

    A wide range of biological responses have been used to identify exposure to contaminants, monitor spatial and temporal changes in contamination levels, provide early warning of environmental deterioration and indicate occurrences of adverse ecological consequences. To be useful in environmental monitoring, a biological response must reflect the environmental stress over time in a quantitative way. We here argue that the time required for initial induction, maximum induction, adaptation and recovery of these stress responses must first be fully understood and considered before they can be used in environmental monitoring, or else erroneous conclusions (both false-negative and false-positive) may be drawn when interpreting results. In this study, data on initial induction, maximum induction, adaptation and recovery of stress responses at various biological hierarchies (i.e., molecular, biochemical, physiological, behavioral, cytological, population and community responses) upon exposure to environmentally relevant levels of contaminants (i.e., metals, oil, polycyclic aromatic hydrocarbons (PAHs), organochlorines, organophosphates, endocrine disruptors) were extracted from 922 papers in the biomarker literature and analyzed. Statistical analyses showed that: (a) many stress responses may decline with time after induction (i.e., adaptation), even if the level of stress remains constant; (b) times for maximum induction and recovery of biochemical responses are positively related; (c) there is no evidence to support the general belief that time for induction of responses at a lower biological hierarchy (i.e., molecular responses and biochemical responses) is shorter than that at higher hierarchy (i.e., physiological, cytological and behavioral responses), although longer recovery time is found for population and community responses; (d) there are significant differences in times required for induction and adaptation of biological responses caused by different types of contaminants; (e) times required for initial and maximum induction of physiological responses in fish are significantly longer than those in crustaceans; and (f) there is a paucity of data on adaptation and recovery of responses, especially those at population and community levels. The above analyses highlight: (1) the limitations and possible erroneous conclusions in the present use of biomarkers in biomonitoring programs, (2) the importance of understanding the details of temporal changes of biological responses before employing them in environmental management, and (3) the suitability of using specific animal groups as bioindicator species.

  10. Theta dynamics reveal domain-specific control over stimulus and response conflict.

    PubMed

    Nigbur, Roland; Cohen, Michael X; Ridderinkhof, K Richard; Stürmer, Birgit

    2012-05-01

    Cognitive control allows us to adjust to environmental changes. The medial frontal cortex (MFC) is thought to detect conflicts and recruit additional resources from other brain areas including the lateral prefrontal cortices. Here we investigated how the MFC acts in concert with visual, motor, and lateral prefrontal cortices to support adaptations of goal-directed behavior. Physiologically, these interactions may occur through local and long-range synchronized oscillation dynamics, particularly in the theta range (4-8 Hz). A speeded flanker task allowed us to investigate conflict-type-specific control networks for perceptual and response conflicts. Theta power over MFC was sensitive to both perceptual and response conflict. Interareal theta phase synchrony, however, indicated a selective enhancement specific for response conflicts between MFC and left frontal cortex as well as between MFC and the presumed motor cortex contralateral to the response hand. These findings suggest that MFC theta-band activity is both generally involved in conflict processing and specifically involved in linking a neural network controlling response conflict.

  11. Does greater specific leaf area plasticity help plants to maintain a high performance when shaded?

    PubMed

    Liu, Yanjie; Dawson, Wayne; Prati, Daniel; Haeuser, Emily; Feng, Yanhao; van Kleunen, Mark

    2016-12-01

    It is frequently assumed that phenotypic plasticity can be very advantageous for plants, because it may increase environmental tolerance (fitness homeostasis). This should, however, only hold for plastic responses that are adaptive, i.e. increase fitness. Numerous studies have shown shade-induced increases in specific leaf area (SLA), and there is wide consensus that this plastic response optimizes light capture and thus has to be adaptive. However, it has rarely been tested whether this is really the case. In order to identify whether SLA plasticity does contribute to the maintenance of high biomass of plant species under shaded conditions, a meta-analytical approach was employed. The data set included 280 species and 467 individual studies from 32 publications and two unpublished experiments. Plants increased their SLA by 55·4 % on average when shaded, while they decreased their biomass by 59·9 %. Species with a high SLA under high-light control conditions showed a significantly greater ability to maintain biomass production under shade overall. However, in contrast to the expectation of a positive relationship between SLA plasticity and maintenance of plant biomass, the results indicated that species with greater SLA plasticity were less able to maintain biomass under shade. Although a high SLA per se contributes to biomass homeostasis, there was no evidence that plasticity in SLA contributes to this. Therefore, it is argued that some of the plastic changes that are frequently thought to be adaptive might simply reflect passive responses to the environment, or result as by-products of adaptive plastic responses in other traits. © The Author 2016. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  12. Auditory-visual integration modulates location-specific repetition suppression of auditory responses.

    PubMed

    Shrem, Talia; Murray, Micah M; Deouell, Leon Y

    2017-11-01

    Space is a dimension shared by different modalities, but at what stage spatial encoding is affected by multisensory processes is unclear. Early studies observed attenuation of N1/P2 auditory evoked responses following repetition of sounds from the same location. Here, we asked whether this effect is modulated by audiovisual interactions. In two experiments, using a repetition-suppression paradigm, we presented pairs of tones in free field, where the test stimulus was a tone presented at a fixed lateral location. Experiment 1 established a neural index of auditory spatial sensitivity, by comparing the degree of attenuation of the response to test stimuli when they were preceded by an adapter sound at the same location versus 30° or 60° away. We found that the degree of attenuation at the P2 latency was inversely related to the spatial distance between the test stimulus and the adapter stimulus. In Experiment 2, the adapter stimulus was a tone presented from the same location or a more medial location than the test stimulus. The adapter stimulus was accompanied by a simultaneous flash displayed orthogonally from one of the two locations. Sound-flash incongruence reduced accuracy in a same-different location discrimination task (i.e., the ventriloquism effect) and reduced the location-specific repetition-suppression at the P2 latency. Importantly, this multisensory effect included topographic modulations, indicative of changes in the relative contribution of underlying sources across conditions. Our findings suggest that the auditory response at the P2 latency is affected by spatially selective brain activity, which is affected crossmodally by visual information. © 2017 Society for Psychophysiological Research.

  13. Gender-specific responses to climate variability in a semi-arid ecosystem in northern Benin.

    PubMed

    Dah-Gbeto, Afiavi P; Villamor, Grace B

    2016-12-01

    Highly erratic rainfall patterns in northern Benin complicate the ability of rural farmers to engage in subsistence agriculture. This research explores gender-specific responses to climate variability in the context of agrarian Benin through a household survey (n = 260) and an experimental gaming exercise among a subset of the survey respondents. Although men and women from the sample population are equally aware of climate variability and share similar coping strategies, their specific land-use strategies, preferences, and motivations are distinct. Over the long term, these differences would likely lead to dissimilar coping strategies and vulnerability to the effects of climate change. Examination of gender-specific land-use responses to climate change and anticipatory learning can enhance efforts to improve adaptability and resilience among rural subsistence farmers.

  14. Choice and Design of Adjuvants for Parenteral and Mucosal Vaccines

    PubMed Central

    Savelkoul, Huub F. J.; Ferro, Valerie A.; Strioga, Marius M.; Schijns, Virgil E. J. C.

    2015-01-01

    The existence of pathogens that escape recognition by specific vaccines, the need to improve existing vaccines and the increased availability of therapeutic (non-infectious disease) vaccines necessitate the rational development of novel vaccine concepts based on the induction of protective cell-mediated immune responses. For naive T-cell activation, several signals resulting from innate and adaptive interactions need to be integrated, and adjuvants may interfere with some or all of these signals. Adjuvants, for example, are used to promote the immunogenicity of antigens in vaccines, by inducing a pro-inflammatory environment that enables the recruitment and promotion of the infiltration of phagocytic cells, particularly antigen-presenting cells (APC), to the injection site. Adjuvants can enhance antigen presentation, induce cytokine expression, activate APC and modulate more downstream adaptive immune reactions (vaccine delivery systems, facilitating immune Signal 1). In addition, adjuvants can act as immunopotentiators (facilitating Signals 2 and 3) exhibiting immune stimulatory effects during antigen presentation by inducing the expression of co-stimulatory molecules on APC. Together, these signals determine the strength of activation of specific T-cells, thereby also influencing the quality of the downstream T helper cytokine profiles and the differentiation of antigen-specific T helper populations (Signal 3). New adjuvants should also target specific (innate) immune cells in order to facilitate proper activation of downstream adaptive immune responses and homing (Signal 4). It is desirable that these adjuvants should be able to exert such responses in the context of mucosal administered vaccines. This review focuses on the understanding of the potential working mechanisms of the most well-known classes of adjuvants to be used effectively in vaccines. PMID:26344951

  15. Patterns of ecological specialization among microbial populations in the Red Sea and diverse oligotrophic marine environments

    PubMed Central

    Thompson, Luke R; Field, Chris; Romanuk, Tamara; Ngugi, David; Siam, Rania; El Dorry, Hamza; Stingl, Ulrich

    2013-01-01

    Large swaths of the nutrient-poor surface ocean are dominated numerically by cyanobacteria (Prochlorococcus), cyanobacterial viruses (cyanophage), and alphaproteobacteria (SAR11). How these groups thrive in the diverse physicochemical environments of different oceanic regions remains poorly understood. Comparative metagenomics can reveal adaptive responses linked to ecosystem-specific selective pressures. The Red Sea is well-suited for studying adaptation of pelagic-microbes, with salinities, temperatures, and light levels at the extreme end for the surface ocean, and low nutrient concentrations, yet no metagenomic studies have been done there. The Red Sea (high salinity, high light, low N and P) compares favorably with the Mediterranean Sea (high salinity, low P), Sargasso Sea (low P), and North Pacific Subtropical Gyre (high light, low N). We quantified the relative abundance of genetic functions among Prochlorococcus, cyanophage, and SAR11 from these four regions. Gene frequencies indicate selection for phosphorus acquisition (Mediterranean/Sargasso), DNA repair and high-light responses (Red Sea/Pacific Prochlorococcus), and osmolyte C1 oxidation (Red Sea/Mediterranean SAR11). The unexpected connection between salinity-dependent osmolyte production and SAR11 C1 metabolism represents a potentially major coevolutionary adaptation and biogeochemical flux. Among Prochlorococcus and cyanophage, genes enriched in specific environments had ecotype distributions similar to nonenriched genes, suggesting that inter-ecotype gene transfer is not a major source of environment-specific adaptation. Clustering of metagenomes using gene frequencies shows similarities in populations (Red Sea with Pacific, Mediterranean with Sargasso) that belie their geographic distances. Taken together, the genetic functions enriched in specific environments indicate competitive strategies for maintaining carrying capacity in the face of physical stressors and low nutrient availability. PMID:23789085

  16. Patterns of ecological specialization among microbial populations in the Red Sea and diverse oligotrophic marine environments.

    PubMed

    Thompson, Luke R; Field, Chris; Romanuk, Tamara; Ngugi, David; Siam, Rania; El Dorry, Hamza; Stingl, Ulrich

    2013-06-01

    Large swaths of the nutrient-poor surface ocean are dominated numerically by cyanobacteria (Prochlorococcus), cyanobacterial viruses (cyanophage), and alphaproteobacteria (SAR11). How these groups thrive in the diverse physicochemical environments of different oceanic regions remains poorly understood. Comparative metagenomics can reveal adaptive responses linked to ecosystem-specific selective pressures. The Red Sea is well-suited for studying adaptation of pelagic-microbes, with salinities, temperatures, and light levels at the extreme end for the surface ocean, and low nutrient concentrations, yet no metagenomic studies have been done there. The Red Sea (high salinity, high light, low N and P) compares favorably with the Mediterranean Sea (high salinity, low P), Sargasso Sea (low P), and North Pacific Subtropical Gyre (high light, low N). We quantified the relative abundance of genetic functions among Prochlorococcus, cyanophage, and SAR11 from these four regions. Gene frequencies indicate selection for phosphorus acquisition (Mediterranean/Sargasso), DNA repair and high-light responses (Red Sea/Pacific Prochlorococcus), and osmolyte C1 oxidation (Red Sea/Mediterranean SAR11). The unexpected connection between salinity-dependent osmolyte production and SAR11 C1 metabolism represents a potentially major coevolutionary adaptation and biogeochemical flux. Among Prochlorococcus and cyanophage, genes enriched in specific environments had ecotype distributions similar to nonenriched genes, suggesting that inter-ecotype gene transfer is not a major source of environment-specific adaptation. Clustering of metagenomes using gene frequencies shows similarities in populations (Red Sea with Pacific, Mediterranean with Sargasso) that belie their geographic distances. Taken together, the genetic functions enriched in specific environments indicate competitive strategies for maintaining carrying capacity in the face of physical stressors and low nutrient availability.

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

    PubMed

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

    2015-09-01

    Oysters are representative bivalve molluscs that are widely distributed in world oceans. As successful colonizers of estuaries and intertidal zones, oysters are remarkably resilient against harsh environmental conditions including wide fluctuations in temperature and salinity as well as prolonged air exposure. Oysters have no adaptive immunity but can thrive in microbe-rich estuaries as filter-feeders. These unique adaptations make oysters interesting models to study the evolution of host-defense systems. Recent advances in genomic studies including sequencing of the oyster genome have provided insights into oyster's immune and stress responses underlying their amazing resilience. Studies show that the oyster genomes are highly polymorphic and complex, which may be key to their resilience. The oyster genome has a large gene repertoire that is enriched for immune and stress response genes. Thousands of genes are involved in oyster's immune and stress responses, through complex interactions, with many gene families expanded showing high sequence, structural and functional diversity. The high diversity of immune receptors and effectors may provide oysters with enhanced specificity in immune recognition and response to cope with diverse pathogens in the absence of adaptive immunity. Some members of expanded immune gene families have diverged to function at different temperatures and salinities or assumed new roles in abiotic stress response. Most canonical innate immunity pathways are conserved in oysters and supported by a large number of diverse and often novel genes. The great diversity in immune and stress response genes exhibited by expanded gene families as well as high sequence and structural polymorphisms may be central to oyster's adaptation to highly stressful and widely changing environments. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Intraspecific variation of a dominant grass and local adaptation in reciprocal garden communities along a US Great Plains’ precipitation gradient: implications for grassland restoration with climate change

    PubMed Central

    Johnson, Loretta C; Olsen, Jacob T; Tetreault, Hannah; DeLaCruz, Angel; Bryant, Johnny; Morgan, Theodore J; Knapp, Mary; Bello, Nora M; Baer, Sara G; Maricle, Brian R

    2015-01-01

    Identifying suitable genetic stock for restoration often employs a ‘best guess’ approach. Without adaptive variation studies, restoration may be misguided. We test the extent to which climate in central US grasslands exerts selection pressure on a foundation grass big bluestem (Andropogon gerardii), widely used in restorations, and resulting in local adaptation. We seeded three regional ecotypes of A. gerardii in reciprocal transplant garden communities across 1150 km precipitation gradient. We measured ecological responses over several timescales (instantaneous gas exchange, medium-term chlorophyll absorbance, and long-term responses of establishment and cover) in response to climate and biotic factors and tested if ecotypes could expand range. The ecotype from the driest region exhibited greatest cover under low rainfall, suggesting local adaptation under abiotic stress. Unexpectedly, no evidence for cover differences between ecotypes exists at mesic sites where establishment and cover of all ecotypes were low, perhaps due to strong biotic pressures. Expression of adaptive differences is strongly environment specific. Given observed adaptive variation, the most conservative restoration strategy would be to plant the local ecotype, especially in drier locations. With superior performance of the most xeric ecotype under dry conditions and predicted drought, this ecotype may migrate eastward, naturally or with assistance in restorations. PMID:26240607

  19. Intraspecific variation of a dominant grass and local adaptation in reciprocal garden communities along a US Great Plains' precipitation gradient: implications for grassland restoration with climate change.

    PubMed

    Johnson, Loretta C; Olsen, Jacob T; Tetreault, Hannah; DeLaCruz, Angel; Bryant, Johnny; Morgan, Theodore J; Knapp, Mary; Bello, Nora M; Baer, Sara G; Maricle, Brian R

    2015-08-01

    Identifying suitable genetic stock for restoration often employs a 'best guess' approach. Without adaptive variation studies, restoration may be misguided. We test the extent to which climate in central US grasslands exerts selection pressure on a foundation grass big bluestem (Andropogon gerardii), widely used in restorations, and resulting in local adaptation. We seeded three regional ecotypes of A. gerardii in reciprocal transplant garden communities across 1150 km precipitation gradient. We measured ecological responses over several timescales (instantaneous gas exchange, medium-term chlorophyll absorbance, and long-term responses of establishment and cover) in response to climate and biotic factors and tested if ecotypes could expand range. The ecotype from the driest region exhibited greatest cover under low rainfall, suggesting local adaptation under abiotic stress. Unexpectedly, no evidence for cover differences between ecotypes exists at mesic sites where establishment and cover of all ecotypes were low, perhaps due to strong biotic pressures. Expression of adaptive differences is strongly environment specific. Given observed adaptive variation, the most conservative restoration strategy would be to plant the local ecotype, especially in drier locations. With superior performance of the most xeric ecotype under dry conditions and predicted drought, this ecotype may migrate eastward, naturally or with assistance in restorations.

  20. Mitochondria-specific antioxidant supplementation does not influence endurance exercise training-induced adaptations in circulating angiogenic cells, skeletal muscle oxidative capacity or maximal oxygen uptake.

    PubMed

    Shill, Daniel D; Southern, W Michael; Willingham, T Bradley; Lansford, Kasey A; McCully, Kevin K; Jenkins, Nathan T

    2016-12-01

    Reducing excessive oxidative stress, through chronic exercise or antioxidants, can decrease the negative effects induced by excessive amounts of oxidative stress. Transient increases in oxidative stress produced during acute exercise facilitate beneficial vascular training adaptations, but the effects of non-specific antioxidants on exercise training-induced vascular adaptations remain elusive. Circulating angiogenic cells (CACs) are an exercise-inducible subset of white blood cells that maintain vascular integrity. We investigated whether mitochondria-specific antioxidant (MitoQ) supplementation would affect the response to 3 weeks of endurance exercise training in CACs, muscle mitochondrial capacity and maximal oxygen uptake in young healthy men. We show that endurance exercise training increases multiple CAC types, an adaptation that is not altered by MitoQ supplementation. Additionally, MitoQ does not affect skeletal muscle or whole-body aerobic adaptations to exercise training. These results indicate that MitoQ supplementation neither enhances nor attenuates endurance training adaptations in young healthy men. Antioxidants have been shown to improve endothelial function and cardiovascular outcomes. However, the effects of antioxidants on exercise training-induced vascular adaptations remain elusive. General acting antioxidants combined with exercise have not impacted circulating angiogenic cells (CACs). We investigated whether mitochondria-specific antioxidant (MitoQ) supplementation would affect the response to 3 weeks of endurance exercise training on CD3 + , CD3 + /CD31 + , CD14 + /CD31 + , CD31 + , CD34 + /VEGFR2 + and CD62E + peripheral blood mononuclear cells (PBMCs), muscle mitochondrial capacity, and maximal oxygen uptake (VO2 max ) in healthy men aged 22.1 ± 0.7 years, with a body mass index of 26.9 ± 0.9 kg m -2 , and 24.8 ± 1.3% body fat. Analysis of main effects revealed that training induced 33, 105 and 285% increases in CD14 + /CD31 + , CD62E + and CD34 + /VEGFR2 + CACs, respectively, and reduced CD3 + /CD31 - PBMCs by 14%. There was no effect of MitoQ on CAC levels. Also independent of MitoQ supplementation, exercise training significantly increased quadriceps muscle mitochondrial capacity by 24% and VO2 max by roughly 7%. In conclusion, endurance exercise training induced increases in multiple CAC types, and this adaptation is not modified by MitoQ supplementation. Furthermore, we demonstrate that a mitochondrial-targeted antioxidant does not influence skeletal muscle or whole-body aerobic adaptations to exercise training. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

  1. Mitochondria‐specific antioxidant supplementation does not influence endurance exercise training‐induced adaptations in circulating angiogenic cells, skeletal muscle oxidative capacity or maximal oxygen uptake

    PubMed Central

    Shill, Daniel D.; Southern, W. Michael; Willingham, T. Bradley; Lansford, Kasey A.; McCully, Kevin K.

    2016-01-01

    Key points Reducing excessive oxidative stress, through chronic exercise or antioxidants, can decrease the negative effects induced by excessive amounts of oxidative stress. Transient increases in oxidative stress produced during acute exercise facilitate beneficial vascular training adaptations, but the effects of non‐specific antioxidants on exercise training‐induced vascular adaptations remain elusive.Circulating angiogenic cells (CACs) are an exercise‐inducible subset of white blood cells that maintain vascular integrity.We investigated whether mitochondria‐specific antioxidant (MitoQ) supplementation would affect the response to 3 weeks of endurance exercise training in CACs, muscle mitochondrial capacity and maximal oxygen uptake in young healthy men.We show that endurance exercise training increases multiple CAC types, an adaptation that is not altered by MitoQ supplementation. Additionally, MitoQ does not affect skeletal muscle or whole‐body aerobic adaptations to exercise training.These results indicate that MitoQ supplementation neither enhances nor attenuates endurance training adaptations in young healthy men. Abstract Antioxidants have been shown to improve endothelial function and cardiovascular outcomes. However, the effects of antioxidants on exercise training‐induced vascular adaptations remain elusive. General acting antioxidants combined with exercise have not impacted circulating angiogenic cells (CACs). We investigated whether mitochondria‐specific antioxidant (MitoQ) supplementation would affect the response to 3 weeks of endurance exercise training on CD3+, CD3+/CD31+, CD14+/CD31+, CD31+, CD34+/VEGFR2+ and CD62E+ peripheral blood mononuclear cells (PBMCs), muscle mitochondrial capacity, and maximal oxygen uptake (VO2 max ) in healthy men aged 22.1 ± 0.7 years, with a body mass index of 26.9 ± 0.9 kg m–2, and 24.8 ± 1.3% body fat. Analysis of main effects revealed that training induced 33, 105 and 285% increases in CD14+/CD31+, CD62E+ and CD34+/VEGFR2+ CACs, respectively, and reduced CD3+/CD31− PBMCs by 14%. There was no effect of MitoQ on CAC levels. Also independent of MitoQ supplementation, exercise training significantly increased quadriceps muscle mitochondrial capacity by 24% and VO2 max by roughly 7%. In conclusion, endurance exercise training induced increases in multiple CAC types, and this adaptation is not modified by MitoQ supplementation. Furthermore, we demonstrate that a mitochondrial‐targeted antioxidant does not influence skeletal muscle or whole‐body aerobic adaptations to exercise training. PMID:27501153

  2. Dual function of CD70 in viral infection: modulator of early cytokine responses and activator of adaptive responses1

    PubMed Central

    Allam, Atef; Swiecki, Melissa; Vermi, William; Ashwell, Jonathan D.; Colonna, Marco

    2014-01-01

    The role of the tumor necrosis factor family member CD70 in adaptive T cell responses has been intensively studied but its function in innate responses is still under investigation. Here we show that CD70 inhibits the early innate response to murine cytomegalovirus (MCMV) but is essential for the optimal generation of virus-specific CD8 T cells. CD70-/- mice reacted to MCMV infection with a robust type I interferon and proinflammatory cytokine response. This response was sufficient for initial control of MCMV, although at later time points, CD70-/- mice became more susceptible to MCMV infection. The heightened cytokine response during the early phase of MCMV infection in CD70-/- mice was paralleled by a reduction in regulatory T cells (Treg). Treg from naïve CD70-/- mice were not as efficient at suppressing T cell proliferation compared to Treg from naïve WT mice and depletion of Treg during MCMV infection in Foxp3-DTR mice or in WT mice recapitulated the phenotype observed in CD70-/- mice. Our study demonstrates that while CD70 is required for the activation of the antiviral adaptive response, it has a regulatory role in early cytokine responses to viruses such as MCMV, possibly through maintenance of Treg survival and function. PMID:24913981

  3. Thermal adaptation in North American cicadas (Hemiptera: Cicadidae).

    PubMed

    Sanborn, Allen F; Heath, James E; Heath, Maxine S; Phillips, Polly K

    2017-10-01

    We determine and summarize the thermal responses for 118 species and subspecies of North American cicadas representing more than 50 years of fieldwork and experimentation. We investigate the role that habitat and behavior have on the thermal adaptation of the North American cicadas. There are general patterns of increasing thermal responses in warmer floristic provinces and increasing maximum potential temperature within a habitat. Altitude shows an inverse relationship with thermal responses. Comparison of thermal responses of species emerging early or late in the season within the same habitat show increases in the thermal responses along with the increasing environmental temperatures late in the summer. However, behavior, specifically the use of endothermy as a thermoregulatory strategy, can influence the values determined in a particular habitat. Subspecies generally do not differ in their thermal tolerances and thermal tolerances are consistent within a species over distances of more than 7600km. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Neuromuscular adaptations predict functional disability independently of clinical pain and psychological factors in patients with chronic non-specific low back pain.

    PubMed

    Dubois, Jean-Daniel; Abboud, Jacques; St-Pierre, Charles; Piché, Mathieu; Descarreaux, Martin

    2014-08-01

    Patients with chronic low back pain exhibit characteristics such as clinical pain, psychological symptoms and neuromuscular adaptations. The purpose of this study was to determine the independent contribution of clinical pain, psychological factors and neuromuscular adaptations to disability in patients with chronic low back pain. Clinical pain intensity, pain catastrophizing, fear-avoidance beliefs, anxiety, neuromuscular adaptations to chronic pain and neuromuscular responses to experimental pain were assessed in 52 patients with chronic low back pain. Lumbar muscle electromyographic activity was assessed during a flexion-extension task (flexion relaxation phenomenon) to assess both chronic neuromuscular adaptations and neuromuscular responses to experimental pain during the task. Multiple regressions showed that independent predictors of disability included neuromuscular adaptations to chronic pain (β=0.25, p=0.006, sr(2)=0.06), neuromuscular responses to experimental pain (β=-0.24, p=0.011, sr(2)=0.05), clinical pain intensity (β=0.28, p=0.002, sr(2)=0.08) and psychological factors (β=0.58, p<0.001, sr(2)=0.32). Together, these predictors accounted for 65% of variance in disability (R(2)=0.65 p<0.001). The current investigation revealed that neuromuscular adaptations are independent from clinical pain intensity and psychological factors, and contribute to inter-individual differences in patients' disability. This suggests that disability, in chronic low back pain patients, is determined by a combination of factors, including clinical pain, psychological factors and neuromuscular adaptations. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. Genome Resequencing Identifies Unique Adaptations of Tibetan Chickens to Hypoxia and High-Dose Ultraviolet Radiation in High-Altitude Environments.

    PubMed

    Zhang, Qian; Gou, Wenyu; Wang, Xiaotong; Zhang, Yawen; Ma, Jun; Zhang, Hongliang; Zhang, Ying; Zhang, Hao

    2016-02-23

    Tibetan chicken, unlike their lowland counterparts, exhibit specific adaptations to high-altitude conditions. The genetic mechanisms of such adaptations in highland chickens were determined by resequencing the genomes of four highland (Tibetan and Lhasa White) and four lowland (White Leghorn, Lindian, and Chahua) chicken populations. Our results showed an evident genetic admixture in Tibetan chickens, suggesting a history of introgression from lowland gene pools. Genes showing positive selection in highland populations were related to cardiovascular and respiratory system development, DNA repair, response to radiation, inflammation, and immune responses, indicating a strong adaptation to oxygen scarcity and high-intensity solar radiation. The distribution of allele frequencies of nonsynonymous single nucleotide polymorphisms between highland and lowland populations was analyzed using chi-square test, which showed that several differentially distributed genes with missense mutations were enriched in several functional categories, especially in blood vessel development and adaptations to hypoxia and intense radiation. RNA sequencing revealed that several differentially expressed genes were enriched in gene ontology terms related to blood vessel and respiratory system development. Several candidate genes involved in the development of cardiorespiratory system (FGFR1, CTGF, ADAM9, JPH2, SATB1, BMP4, LOX, LPR, ANGPTL4, and HYAL1), inflammation and immune responses (AIRE, MYO1F, ZAP70, DDX60, CCL19, CD47, JSC, and FAS), DNA repair, and responses to radiation (VCP, ASH2L, and FANCG) were identified to play key roles in the adaptation to high-altitude conditions. Our data provide new insights into the unique adaptations of highland animals to extreme environments. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  6. Amplifying IFN-γ Signaling in Dendritic Cells by CD11c-Specific Loss of SOCS1 Increases Innate Immunity to Infection while Decreasing Adaptive Immunity.

    PubMed

    Alice, Alejandro F; Kramer, Gwen; Bambina, Shelly; Baird, Jason R; Bahjat, Keith S; Gough, Michael J; Crittenden, Marka R

    2018-01-01

    Although prophylactic vaccines provide protective humoral immunity against infectious agents, vaccines that elicit potent CD8 T cell responses are valuable tools to shape and drive cellular immunity against cancer and intracellular infection. In particular, IFN-γ-polarized cytotoxic CD8 T cell immunity is considered optimal for protective immunity against intracellular Ags. Suppressor of cytokine signaling (SOCS)1 is a cross-functional negative regulator of TLR and cytokine receptor signaling via degradation of the receptor-signaling complex. We hypothesized that loss of SOCS1 in dendritic cells (DCs) would improve T cell responses by accentuating IFN-γ-directed immune responses. We tested this hypothesis using a recombinant Listeria monocytogenes vaccine platform that targets CD11c + DCs in mice in which SOCS1 is selectively deleted in all CD11c + cells. Unexpectedly, in mice lacking SOCS1 expression in CD11c + cells, we observed a decrease in CD8 + T cell response to the L. monocytogenes vaccine. NK cell responses were also decreased in mice lacking SOCS1 expression in CD11c + cells but did not explain the defect in CD8 + T cell immunity. We found that DCs lacking SOCS1 expression were functional in driving Ag-specific CD8 + T cell expansion in vitro but that this process was defective following infection in vivo. Instead, monocyte-derived innate TNF-α and inducible NO synthase-producing DCs dominated the antibacterial response. Thus, loss of SOCS1 in CD11c + cells skewed the balance of immune response to infection by increasing innate responses while decreasing Ag-specific adaptive responses to infectious Ags. Copyright © 2017 by The American Association of Immunologists, Inc.

  7. Surveillance and response for high-risk populations: what can malaria elimination programmes learn from the experience of HIV?

    PubMed

    Jacobson, Jerry O; Cueto, Carmen; Smith, Jennifer L; Hwang, Jimee; Gosling, Roly; Bennett, Adam

    2017-01-18

    To eliminate malaria, malaria programmes need to develop new strategies for surveillance and response appropriate for the changing epidemiology that accompanies transmission decline, in which transmission is increasingly driven by population subgroups whose behaviours place them at increased exposure. Conventional tools of malaria surveillance and response are likely not sufficient in many elimination settings for accessing high-risk population subgroups, such as mobile and migrant populations (MMPs), given their greater likelihood of asymptomatic infections, illegal risk behaviours, limited access to public health facilities, and high mobility including extended periods travelling away from home. More adaptive, targeted strategies are needed to monitor transmission and intervention coverage effectively in these groups. Much can be learned from HIV programmes' experience with "second generation surveillance", including how to rapidly adapt surveillance and response strategies to changing transmission patterns, biological and behavioural surveys that utilize targeted sampling methods for specific behavioural subgroups, and methods for population size estimation. This paper reviews the strategies employed effectively for HIV programmes and offers considerations and recommendations for adapting them to the malaria elimination context.

  8. Cognition and balance control: does processing of explicit contextual cues of impending perturbations modulate automatic postural responses?

    PubMed

    Coelho, Daniel Boari; Teixeira, Luis Augusto

    2017-08-01

    Processing of predictive contextual cues of an impending perturbation is thought to induce adaptive postural responses. Cueing in previous research has been provided through repeated perturbations with a constant foreperiod. This experimental strategy confounds explicit predictive cueing with adaptation and non-specific properties of temporal cueing. Two experiments were performed to assess those factors separately. To perturb upright balance, the base of support was suddenly displaced backwards in three amplitudes: 5, 10 and 15 cm. In Experiment 1, we tested the effect of cueing the amplitude of the impending postural perturbation by means of visual signals, and the effect of adaptation to repeated exposures by comparing block versus random sequences of perturbation. In Experiment 2, we evaluated separately the effects of cueing the characteristics of an impending balance perturbation and cueing the timing of perturbation onset. Results from Experiment 1 showed that the block sequence of perturbations led to increased stability of automatic postural responses, and modulation of magnitude and onset latency of muscular responses. Results from Experiment 2 showed that only the condition cueing timing of platform translation onset led to increased balance stability and modulation of onset latency of muscular responses. Conversely, cueing platform displacement amplitude failed to induce any effects on automatic postural responses in both experiments. Our findings support the interpretation of improved postural responses via optimized sensorimotor processes, at the same time that cast doubt on the notion that cognitive processing of explicit contextual cues advancing the magnitude of an impending perturbation can preset adaptive postural responses.

  9. Microbially induced separation of quartz from hematite using sulfate reducing bacteria.

    PubMed

    Prakasan, M R Sabari; Natarajan, K A

    2010-07-01

    Cells and metabolic products of Desulfovibrio desulfuricans were successfully used to separate quartz from hematite through environmentally benign microbially induced flotation. Bacterial metabolic products such as extracellular proteins and polysaccharides were isolated from both unadapted and mineral-adapted bacterial metabolite and their basic characteristics were studied in order to get insight into the changes brought about on bioreagents during adaptation. Interaction between bacterial cells and metabolites with minerals like hematite and quartz brought about significant surface-chemical changes on both the minerals. Quartz was rendered more hydrophobic, while hematite became more hydrophilic after biotreatment. The predominance of bacterial polysaccharides on interacted hematite and of proteins on quartz was responsible for the above surface-chemical changes, as attested through adsorption studies. Surface-chemical changes were also observed on bacterial cells after adaptation to the above minerals. Selective separation of quartz from hematite was achieved through interaction with quartz-adapted bacterial cells and metabolite. Mineral-specific proteins secreted by quartz-adapted cells were responsible for conferment of hydrophobicity on quartz resulting in enhanced separation from hematite through flotation. 2010 Elsevier B.V. All rights reserved.

  10. Transcriptome analysis in tardigrade species reveals specific molecular pathways for stress adaptations.

    PubMed

    Förster, Frank; Beisser, Daniela; Grohme, Markus A; Liang, Chunguang; Mali, Brahim; Siegl, Alexander Matthias; Engelmann, Julia C; Shkumatov, Alexander V; Schokraie, Elham; Müller, Tobias; Schnölzer, Martina; Schill, Ralph O; Frohme, Marcus; Dandekar, Thomas

    2012-01-01

    Tardigrades have unique stress-adaptations that allow them to survive extremes of cold, heat, radiation and vacuum. To study this, encoded protein clusters and pathways from an ongoing transcriptome study on the tardigrade Milnesium tardigradum were analyzed using bioinformatics tools and compared to expressed sequence tags (ESTs) from Hypsibius dujardini, revealing major pathways involved in resistance against extreme environmental conditions. ESTs are available on the Tardigrade Workbench along with software and databank updates. Our analysis reveals that RNA stability motifs for M. tardigradum are different from typical motifs known from higher animals. M. tardigradum and H. dujardini protein clusters and conserved domains imply metabolic storage pathways for glycogen, glycolipids and specific secondary metabolism as well as stress response pathways (including heat shock proteins, bmh2, and specific repair pathways). Redox-, DNA-, stress- and protein protection pathways complement specific repair capabilities to achieve the strong robustness of M. tardigradum. These pathways are partly conserved in other animals and their manipulation could boost stress adaptation even in human cells. However, the unique combination of resistance and repair pathways make tardigrades and M. tardigradum in particular so highly stress resistant.

  11. Characterization of host immune responses in Ebola virus infections.

    PubMed

    Wong, Gary; Kobinger, Gary P; Qiu, Xiangguo

    2014-06-01

    Ebola causes highly lethal hemorrhagic fever in humans with no licensed countermeasures. Its virulence can be attributed to several immunoevasion mechanisms: an early inhibition of innate immunity started by the downregulation of type I interferon, epitope masking and subversion of the adaptive humoural immunity by secreting a truncated form of the viral glycoprotein. Deficiencies in specific and non-specific antiviral responses result in unrestricted viral replication and dissemination in the host, causing death typically within 10 days after the appearance of symptoms. This review summarizes the host immune response to Ebola infection, and highlights the short- and long-term immune responses crucial for protection, which holds implications for the design of future vaccines and therapeutics.

  12. Adapted shared reading at school for minimally verbal students with autism.

    PubMed

    Mucchetti, Charlotte A

    2013-05-01

    Almost nothing is known about the capacity of minimally verbal students with autism to develop literacy skills. Shared reading is a regular practice in early education settings and is widely thought to encourage language and literacy development. There is some evidence that children with severe disabilities can be engaged in adapted shared reading activities. The current study examines the impact of teacher-led adapted shared reading activities on engagement and story comprehension in minimally verbal 5-6-year-old children with autism using a multiple baseline/alternating treatment design. Four students and three teachers participated. Teachers conducted adapted shared reading activities with modified books (visual supports, three-dimensional objects, simplified text) and used specific strategies for increasing student engagement. Student performance during adapted activities was compared to performance during standard shared reading sessions. All four students showed increased story comprehension and engagement during adapted shared reading. Average percentage of session engaged was 87%-100% during adapted sessions, compared with 41%-52% during baseline. Average number of correct responses to story comprehension questions was 4.2-4.8 out of 6 during adapted sessions compared with 1.2-2 during baseline. Visual supports, tactile objects, and specific teaching strategies offer ways for minimally verbal students to meaningfully participate in literacy activities. Future research should investigate adapted shared reading activities implemented classroom-wide as well as joint engagement, language, and literacy outcomes after using such activities over time.

  13. Modulation of the specific glutathionylation of mitochondrial proteins in the yeast Saccharomyces cerevisiae under basal and stress conditions.

    PubMed

    Gergondey, Rachel; Garcia, Camille; Marchand, Christophe H; Lemaire, Stephane D; Camadro, Jean-Michel; Auchère, Françoise

    2017-03-15

    The potential biological consequences of oxidative stress and changes in glutathione levels include the oxidation of susceptible protein thiols and reversible covalent binding of glutathione to the -SH groups of proteins by S-glutathionylation. Mitochondria are central to the response to oxidative stress and redox signaling. It is therefore crucial to explore the adaptive response to changes in thiol-dependent redox status in these organelles. We optimized the purification protocol of glutathionylated proteins in the yeast Saccharomyces cerevisiae and present a detailed proteomic analysis of the targets of protein glutathionylation in cells undergoing constitutive metabolism and after exposure to various stress conditions. This work establishes the physiological importance of the glutathionylation process in S. cerevisiae under basal conditions and provides evidence for an atypical and unexpected cellular distribution of the process between the cytosol and mitochondria. In addition, our data indicate that each oxidative condition (diamide, GSSG, H 2 O 2 , or the presence of iron) elicits an adaptive metabolic response affecting specific mitochondrial metabolic pathways, mainly involved in the energetic maintenance of the cells. The correlation of protein modifications with intracellular glutathione levels suggests that protein deglutathionylation may play a role in protecting mitochondria from oxidative stress. This work provides further insights into the diversity of proteins undergoing glutathionylation and the role of this post-translational modification as a regulatory process in the adaptive response of the cell. © 2017 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

  14. Visual adaptation provides objective electrophysiological evidence of facial identity discrimination.

    PubMed

    Retter, Talia L; Rossion, Bruno

    2016-07-01

    Discrimination of facial identities is a fundamental function of the human brain that is challenging to examine with macroscopic measurements of neural activity, such as those obtained with functional magnetic resonance imaging (fMRI) and electroencephalography (EEG). Although visual adaptation or repetition suppression (RS) stimulation paradigms have been successfully implemented to this end with such recording techniques, objective evidence of an identity-specific discrimination response due to adaptation at the level of the visual representation is lacking. Here, we addressed this issue with fast periodic visual stimulation (FPVS) and EEG recording combined with a symmetry/asymmetry adaptation paradigm. Adaptation to one facial identity is induced through repeated presentation of that identity at a rate of 6 images per second (6 Hz) over 10 sec. Subsequently, this identity is presented in alternation with another facial identity (i.e., its anti-face, both faces being equidistant from an average face), producing an identity repetition rate of 3 Hz over a 20 sec testing sequence. A clear EEG response at 3 Hz is observed over the right occipito-temporal (ROT) cortex, indexing discrimination between the two facial identities in the absence of an explicit behavioral discrimination measure. This face identity discrimination occurs immediately after adaptation and disappears rapidly within 20 sec. Importantly, this 3 Hz response is not observed in a control condition without the single-identity 10 sec adaptation period. These results indicate that visual adaptation to a given facial identity produces an objective (i.e., at a pre-defined stimulation frequency) electrophysiological index of visual discrimination between that identity and another, and provides a unique behavior-free quantification of the effect of visual adaptation. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. A qualitative examination of the health workforce needs during climate change disaster response in Pacific Island Countries

    PubMed Central

    2014-01-01

    Background There is a growing body of evidence that the impacts of climate change are affecting population health negatively. The Pacific region is particularly vulnerable to climate change; a strong health-care system is required to respond during times of disaster. This paper examines the capacity of the health sector in Pacific Island Countries to adapt to changing disaster response needs, in terms of: (i) health workforce governance, management, policy and involvement; (ii) health-care capacity and skills; and (iii) human resources for health training and workforce development. Methods Key stakeholder interviews informed the assessment of the capacity of the health sector and disaster response organizations in Pacific Island Countries to adapt to disaster response needs under a changing climate. The research specifically drew upon and examined the adaptive capacity of individual organizations and the broader system of disaster response in four case study countries (Fiji, Cook Islands, Vanuatu and Samoa). Results ‘Capacity’ including health-care capacity was one of the objective determinants identified as most significant in influencing the adaptive capacity of disaster response systems in the Pacific. The research identified several elements that could support the adaptive capacity of the health sector such as: inclusive involvement in disaster coordination; policies in place for health workforce coordination; belief in their abilities; and strong donor support. Factors constraining adaptive capacity included: weak coordination of international health personnel; lack of policies to address health worker welfare; limited human resources and material resources; shortages of personnel to deal with psychosocial needs; inadequate skills in field triage and counselling; and limited capacity for training. Conclusion Findings from this study can be used to inform the development of human resources for health policies and strategic plans, and to support the development of a coordinated and collaborative approach to disaster response training across the Pacific and other developing contexts. This study also provides an overview of health-care capacity and some of the challenges and strengths that can inform future development work by humanitarian organizations, regional and international donors involved in climate change adaptation, and disaster risk reduction in the Pacific region. PMID:24521057

  16. Protein kinase CK2 enables regulatory T cells to suppress excessive TH2 responses in vivo.

    PubMed

    Ulges, Alexander; Klein, Matthias; Reuter, Sebastian; Gerlitzki, Bastian; Hoffmann, Markus; Grebe, Nadine; Staudt, Valérie; Stergiou, Natascha; Bohn, Toszka; Brühl, Till-Julius; Muth, Sabine; Yurugi, Hajime; Rajalingam, Krishnaraj; Bellinghausen, Iris; Tuettenberg, Andrea; Hahn, Susanne; Reißig, Sonja; Haben, Irma; Zipp, Frauke; Waisman, Ari; Probst, Hans-Christian; Beilhack, Andreas; Buchou, Thierry; Filhol-Cochet, Odile; Boldyreff, Brigitte; Breloer, Minka; Jonuleit, Helmut; Schild, Hansjörg; Schmitt, Edgar; Bopp, Tobias

    2015-03-01

    The quality of the adaptive immune response depends on the differentiation of distinct CD4(+) helper T cell subsets, and the magnitude of an immune response is controlled by CD4(+)Foxp3(+) regulatory T cells (Treg cells). However, how a tissue- and cell type-specific suppressor program of Treg cells is mechanistically orchestrated has remained largely unexplored. Through the use of Treg cell-specific gene targeting, we found that the suppression of allergic immune responses in the lungs mediated by T helper type 2 (TH2) cells was dependent on the activity of the protein kinase CK2. Genetic ablation of the β-subunit of CK2 specifically in Treg cells resulted in the proliferation of a hitherto-unexplored ILT3(+) Treg cell subpopulation that was unable to control the maturation of IRF4(+)PD-L2(+) dendritic cells required for the development of TH2 responses in vivo.

  17. The Heat Shock Response and Acute Lung Injury

    PubMed Central

    Wheeler, Derek S.; Wong, Hector R.

    2006-01-01

    All cells respond to stress through the activation of primitive, evolutionarily conserved genetic programs that maintain homeostasis and assure cell survival. Stress adaptation, which is known in the literature by a myriad of terms, including tolerance, desensitization, conditioning, and reprogramming, is a common paradigm found throughout nature, in which a primary exposure of a cell or organism to a stressful stimulus (e.g., heat) results in an adaptive response by which a second exposure to the same stimulus produces a minimal response. More interesting is the phenomenon of cross-tolerance, by which a primary exposure to a stressful stimulus results in an adaptive response whereby the cell or organism is resistant to a subsequent stress that is different from the initial stress (i.e. exposure to heat stress leading to resistance to oxidant stress). The heat shock response is one of the more commonly described examples of stress adaptation and is characterized by the rapid expression of a unique group of proteins collectively known as heat shock proteins (also commonly referred to as stress proteins). The expression of heat shock proteins is well described in both whole lungs and in specific lung cells from a variety of species and in response to a variety of stressors. More importantly, in vitro data, as well as data from various animal models of acute lung injury, demonstrate that heat shock proteins, especially Hsp27, Hsp32, Hsp60, and Hsp70 have an important cytoprotective role during lung inflammation and injury. PMID:17157189

  18. Cities and Sea Level Rise: A Roadmap for Flood Hazard Adaptation

    NASA Astrophysics Data System (ADS)

    Horn, D. P.; Cousins, A.

    2015-12-01

    Coastal cities will face a range of increasingly severe challenges as sea level rises, and adaptation to future flood risk will require more than structural defences. Many cities will not be able to rely solely on engineering structures for protection and will need to develop a suite of policy responses to increase their resilience to impacts of rising sea level. Local governments generally maintain day-to-day responsibility and control over the use of the vast majority of property at risk of flooding, and the tools to promote flood risk adaptation are already within the capacity of most cities. Policy tools available to address other land-use problems can be refashioned and used to adapt to sea level rise. This study reviews approaches for urban adaptation through case studies of cities which have developed flood adaptation strategies that combine structural defences with innovative approaches to living with flood risk. The aim of the overall project is to produce a 'roadmap' to guide practitioners through the process of analysing coastal flood risk in urban areas. Technical knowledge of flood risk reduction measures is complemented with a consideration of the essential impact that local policy has on the treatment of coastal flooding and the constraints and opportunities that result from the specific country or locality characteristics in relation to economic, political, social and environmental priorities, which are likely to dictate the approach to coastal flooding and the actions proposed. Detailed analyses of the adaptation strategies used by Rotterdam (Netherlands), Bristol (UK), and Norfolk (Virginia) are used to draw out a range of good practice elements that promote effective adaptation to sea level rise. These can be grouped into risk reduction, governance issues, and insurance, and can be used to provide examples of how other cities could adopt and implement flood adaptation strategies from a relatively limited starting position. Most cities will neither be able to defend all areas nor retreat entirely and will need to make a decision to retreat from certain locations or to relocate particular assets in areas at lower risk. We identify a series of specific questions which should be answered by city managers when selecting the most appropriate response for a particular location.

  19. Human adaptive immune system Rag2-/-gamma(c)-/- mice.

    PubMed

    Chicha, Laurie; Tussiwand, Roxane; Traggiai, Elisabetta; Mazzucchelli, Luca; Bronz, Lucio; Piffaretti, Jean-Claude; Lanzavecchia, Antonio; Manz, Markus G

    2005-06-01

    Although many biologic principles are conserved in mice and humans, species-specific differences exist, for example, in susceptibility and response to pathogens, that often do not allow direct implementation of findings in experimental mice to humans. Research in humans, however, for ethical and practical reasons, is largely restricted to in vitro assays that lack components and the complexity of a living organism. To nevertheless study the human hematopoietic and immune system in vivo, xenotransplantation assays have been developed that substitute human components to small animals. Here, we summarize our recent findings that transplantation of human cord blood CD34(+) cells to newborn Rag2(-/-)gamma(c)(-/-) mice leads to de novo development of major functional components of the human adaptive immune system. These human adaptive immune system Rag2(-/-)gamma(c)(-/-) (huAIS-RG) mice can now be used as a technically straightforward preclinical model to evaluate in vivo human adaptive immune system development as well as immune responses, for example, to vaccines or live infectious pathogens.

  20. Genes of the major histocompatibility complex highlight interactions of the innate and adaptive immune system

    PubMed Central

    Lukasch, Barbara; Westerdahl, Helena; Strandh, Maria; Winkler, Hans; Moodley, Yoshan; Knauer, Felix

    2017-01-01

    Background A well-functioning immune defence is crucial for fitness, but our knowledge about the immune system and its complex interactions is still limited. Major histocompatibility complex (MHC) molecules are involved in T-cell mediated adaptive immune responses, but MHC is also highly upregulated during the initial innate immune response. The aim of our study was therefore to determine to what extent the highly polymorphic MHC is involved in interactions of the innate and adaptive immune defence and if specific functional MHC alleles (FA) or heterozygosity at the MHC are more important. Methods To do this we used captive house sparrows (Passer domesticus) to survey MHC diversity and immune function controlling for several environmental factors. MHC class I alleles were identified using parallel amplicon sequencing and to mirror immune function, several immunological tests that correspond to the innate and adaptive immunity were conducted. Results Our results reveal that MHC was linked to all immune tests, highlighting its importance for the immune defence. While all innate responses were associated with one single FA, adaptive responses (cell-mediated and humoral) were associated with several different alleles. Discussion We found that repeated injections of an antibody in nestlings and adults were linked to different FA and hence might affect different areas of the immune system. Also, individuals with a higher number of different FA produced a smaller secondary response, indicating a disadvantage of having numerous MHC alleles. These results demonstrate the complexity of the immune system in relation to the MHC and lay the foundation for other studies to further investigate this topic. PMID:28875066

  1. Genes of the major histocompatibility complex highlight interactions of the innate and adaptive immune system.

    PubMed

    Lukasch, Barbara; Westerdahl, Helena; Strandh, Maria; Winkler, Hans; Moodley, Yoshan; Knauer, Felix; Hoi, Herbert

    2017-01-01

    A well-functioning immune defence is crucial for fitness, but our knowledge about the immune system and its complex interactions is still limited. Major histocompatibility complex (MHC) molecules are involved in T-cell mediated adaptive immune responses, but MHC is also highly upregulated during the initial innate immune response. The aim of our study was therefore to determine to what extent the highly polymorphic MHC is involved in interactions of the innate and adaptive immune defence and if specific functional MHC alleles (FA) or heterozygosity at the MHC are more important. To do this we used captive house sparrows ( Passer domesticus ) to survey MHC diversity and immune function controlling for several environmental factors. MHC class I alleles were identified using parallel amplicon sequencing and to mirror immune function, several immunological tests that correspond to the innate and adaptive immunity were conducted. Our results reveal that MHC was linked to all immune tests, highlighting its importance for the immune defence. While all innate responses were associated with one single FA, adaptive responses (cell-mediated and humoral) were associated with several different alleles. We found that repeated injections of an antibody in nestlings and adults were linked to different FA and hence might affect different areas of the immune system. Also, individuals with a higher number of different FA produced a smaller secondary response, indicating a disadvantage of having numerous MHC alleles. These results demonstrate the complexity of the immune system in relation to the MHC and lay the foundation for other studies to further investigate this topic.

  2. Innate and adaptive immune correlates of vaccine and adjuvant-induced control of mucosal transmission of SIV in macaques.

    PubMed

    Sui, Yongjun; Zhu, Qing; Gagnon, Susan; Dzutsev, Amiran; Terabe, Masaki; Vaccari, Monica; Venzon, David; Klinman, Dennis; Strober, Warren; Kelsall, Brian; Franchini, Genoveffa; Belyakov, Igor M; Berzofsky, Jay A

    2010-05-25

    Adjuvant effects on innate as well as adaptive immunity may be critical for inducing protection against mucosal HIV and simian immunodeficiency virus (SIV) exposure. We therefore studied effects of Toll-like receptor agonists and IL-15 as mucosal adjuvants on both innate and adaptive immunity in a peptide/poxvirus HIV/SIV mucosal vaccine in macaques, and made three critical observations regarding both innate and adaptive correlates of protection: (i) adjuvant-alone without vaccine antigen impacted the intrarectal SIVmac251 challenge outcome, correlating with surprisingly long-lived APOBEC3G (A3G)-mediated innate immunity; in addition, even among animals receiving vaccine with adjuvants, viral load correlated inversely with A3G levels; (ii) a surprising threshold-like effect existed for vaccine-induced adaptive immunity control of viral load, and only antigen-specific polyfunctional CD8(+) T cells correlated with protection, not tetramer(+) T cells, demonstrating the importance of T-cell quality; (iii) synergy was observed between Toll-like receptor agonists and IL-15 for driving adaptive responses through the up-regulation of IL-15Ralpha, which can present IL-15 in trans, as well as for driving the innate A3G response. Thus, strategic use of molecular adjuvants can provide better mucosal protection through induction of both innate and adaptive immunity.

  3. Toward a method of collaborative, evidence-based response to desertification

    USDA-ARS?s Scientific Manuscript database

    Overgeneralized narratives about how desertified ecosystems will respond to restoration actions may result in wasted resources, missed opportunities, or accelerated degradation. Evidence-based collaborative adaptive management (CAM) could solve this problem by providing site-specific information tha...

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

    PubMed

    Hawley, John A

    2013-01-01

    In recent years, advances in molecular biology have allowed scientists to elucidate how endurance exercise training stimulates skeletal muscle remodeling (i.e. promotes mitochondrial biogenesis). A growing field of interest directly arising from our understanding of the molecular bases of training adaptation is how nutrient availability can alter the regulation of many contraction-induced events in muscle in response to endurance exercise. Acutely manipulating substrate availability can exert profound effects on muscle energy stores and patterns of fuel metabolism during exercise, as well as many processes activating gene expression and cell signaling. Accordingly, such interventions when repeated over weeks and months have the potential to modulate numerous adaptive processes in skeletal muscle that ultimately drive the phenotype-specific characteristics observed in highly trained athletes. In this review, the molecular and cellular events that occur in skeletal muscle during and after endurance exercise are discussed and evidence provided to demonstrate that nutrient availability plays an important role in modulating many of the adaptive responses to training. Emphasis is on human studies that have determined the regulatory role of muscle glycogen availability on cell metabolism, endurance training capacity and performance. Copyright © 2013 Nestec Ltd., Vevey/S. Karger AG, Basel.

  5. Alkanols and chlorophenols cause different physiological adaptive responses on the level of cell surface properties and membrane vesicle formation in Pseudomonas putida DOT-T1E.

    PubMed

    Baumgarten, Thomas; Vazquez, José; Bastisch, Christian; Veron, Wilfried; Feuilloley, Marc G J; Nietzsche, Sandor; Wick, Lukas Y; Heipieper, Hermann J

    2012-01-01

    In order to cope with the toxicity imposed by the exposure to environmental hydrocarbons, many bacteria have developed specific adaptive responses such as modifications in the cell envelope. Here we compared the influence of n-alkanols and chlorophenols on the surface properties of the solvent-tolerant bacterium Pseudomonas putida DOT-T1E. In the presence of toxic concentrations of n-alkanols, this strain significantly increased its cell surface charge and hydrophobicity with changes depending on the chain length of the added n-alkanols. The adaptive response occurred within 10 min after the addition of the solvent and was demonstrated to be of physiological nature. Contrary to that, chlorophenols of similar hydrophobicity and potential toxicity as the corresponding alkanols caused only minor effects in the surface properties. To our knowledge, this is the first observation of differences in the cellular adaptive response of bacteria to compound classes of quasi equal hydrophobicity and toxicity. The observed adaptation of the physico-chemical surface properties of strain DOT-T1E to the presence of alkanols was reversible and correlated with changes in the composition of the lipopolysaccharide content of the cells. The reaction is explained by previously described reactions allowing the release of membrane vesicles that was demonstrated for cells affected by 1-octanol and heat shock, whereas no membrane vesicles were released after the addition of chlorophenols.

  6. The evolution of the major hepatitis C genotypes correlates with clinical response to interferon therapy.

    PubMed

    Pang, Phillip S; Planet, Paul J; Glenn, Jeffrey S

    2009-08-11

    Patients chronically infected with hepatitis C virus (HCV) require significantly different durations of therapy and achieve substantially different sustained virologic response rates to interferon-based therapies, depending on the HCV genotype with which they are infected. There currently exists no systematic framework that explains these genotype-specific response rates. Since humans are the only known natural hosts for HCV-a virus that is at least hundreds of years old-one possibility is that over the time frame of this relationship, HCV accumulated adaptive mutations that confer increasing resistance to the human immune system. Given that interferon therapy functions by triggering an immune response, we hypothesized that clinical response rates are a reflection of viral evolutionary adaptations to the immune system. We have performed the first phylogenetic analysis to include all available full-length HCV genomic sequences (n = 345). This resulted in a new cladogram of HCV. This tree establishes for the first time the relative evolutionary ages of the major HCV genotypes. The outcome data from prospective clinical trials that studied interferon and ribavirin therapy was then mapped onto this new tree. This mapping revealed a correlation between genotype-specific responses to therapy and respective genotype age. This correlation allows us to predict that genotypes 5 and 6, for which there currently are no published prospective trials, will likely have intermediate response rates, similar to genotype 3. Ancestral protein sequence reconstruction was also performed, which identified the HCV proteins E2 and NS5A as potential determinants of genotype-specific clinical outcome. Biochemical studies have independently identified these same two proteins as having genotype-specific abilities to inhibit the innate immune factor double-stranded RNA-dependent protein kinase (PKR). An evolutionary analysis of all available HCV genomes supports the hypothesis that immune selection was a significant driving force in the divergence of the major HCV genotypes and that viral factors that acquired the ability to inhibit the immune response may play a role in determining genotype-specific response rates to interferon therapy.

  7. Evolutionarily conserved coding properties of auditory neurons across grasshopper species

    PubMed Central

    Neuhofer, Daniela; Wohlgemuth, Sandra; Stumpner, Andreas; Ronacher, Bernhard

    2008-01-01

    We investigated encoding properties of identified auditory interneurons in two not closely related grasshopper species (Acrididae). The neurons can be homologized on the basis of their similar morphologies and physiologies. As test stimuli, we used the species-specific stridulation signals of Chorthippus biguttulus, which evidently are not relevant for the other species, Locusta migratoria. We recorded spike trains produced in response to these signals from several neuron types at the first levels of the auditory pathway in both species. Using a spike train metric to quantify differences between neuronal responses, we found a high similarity in the responses of homologous neurons: interspecific differences between the responses of homologous neurons in the two species were not significantly larger than intraspecific differences (between several specimens of a neuron in one species). These results suggest that the elements of the thoracic auditory pathway have been strongly conserved during the evolutionary divergence of these species. According to the ‘efficient coding’ hypothesis, an adaptation of the thoracic auditory pathway to the specific needs of acoustic communication could be expected. We conclude that there must have been stabilizing selective forces at work that conserved coding characteristics and prevented such an adaptation. PMID:18505715

  8. A map of local adaptation in Arabidopsis thaliana.

    PubMed

    Fournier-Level, A; Korte, A; Cooper, M D; Nordborg, M; Schmitt, J; Wilczek, A M

    2011-10-07

    Local adaptation is critical for species persistence in the face of rapid environmental change, but its genetic basis is not well understood. Growing the model plant Arabidopsis thaliana in field experiments in four sites across the species' native range, we identified candidate loci for local adaptation from a genome-wide association study of lifetime fitness in geographically diverse accessions. Fitness-associated loci exhibited both geographic and climatic signatures of local adaptation. Relative to genomic controls, high-fitness alleles were generally distributed closer to the site where they increased fitness, occupying specific and distinct climate spaces. Independent loci with different molecular functions contributed most strongly to fitness variation in each site. Independent local adaptation by distinct genetic mechanisms may facilitate a flexible evolutionary response to changing environment across a species range.

  9. Identification of variant-specific surface proteins in Giardia muris trophozoites.

    PubMed

    Ropolo, Andrea S; Saura, Alicia; Carranza, Pedro G; Lujan, Hugo D

    2005-08-01

    Giardia lamblia undergoes antigenic variation, a process that might allow the parasite to evade the host's immune response and adapt to different environments. Here we show that Giardia muris, a related species that naturally infects rodents, possesses multiple variant-specific surface proteins (VSPs) and expresses VSPs on its surface, suggesting that it undergoes antigenic variation similar to that of G. lamblia.

  10. Evidence for sex differences in cardiovascular aging and adaptive responses to physical activity.

    PubMed

    Parker, Beth A; Kalasky, Martha J; Proctor, David N

    2010-09-01

    There are considerable data addressing sex-related differences in cardiovascular system aging and disease risk/progression. Sex differences in cardiovascular aging are evident during resting conditions, exercise, and other acute physiological challenges (e.g., orthostasis). In conjunction with these sex-related differences-or perhaps even as an underlying cause-the impact of cardiorespiratory fitness and/or physical activity on the aging cardiovascular system also appears to be sex-specific. Potential mechanisms contributing to sex-related differences in cardiovascular aging and adaptability include changes in sex hormones with age as well as sex differences in baseline fitness and the dose of activity needed to elicit cardiovascular adaptations. The purpose of the present paper is thus to review the primary research regarding sex-specific plasticity of the cardiovascular system to fitness and physical activity in older adults. Specifically, the paper will (1) briefly review known sex differences in cardiovascular aging, (2) detail emerging evidence regarding observed cardiovascular outcomes in investigations of exercise and physical activity in older men versus women, (3) explore mechanisms underlying the differing adaptations to exercise and habitual activity in men versus women, and (4) discuss implications of these findings with respect to chronic disease risk and exercise prescription.

  11. Evidence for sex differences in cardiovascular aging and adaptive responses to physical activity

    PubMed Central

    Parker, Beth A.; Kalasky, Martha J.; Proctor, David N.

    2010-01-01

    There are considerable data addressing sex-related differences in cardiovascular system aging and disease risk/progression. Sex differences in cardiovascular aging are evident during resting conditions, exercise, and other acute physiological challenges (e.g., orthostasis). In conjunction with these sex-related differences—or perhaps even as an underlying cause—the impact of cardiorespiratory fitness and/or physical activity on the aging cardiovascular system also appears to be sex-specific. Potential mechanisms contributing to sex-related differences in cardiovascular aging and adaptability include changes in sex hormones with age as well as sex differences in baseline fitness and the dose of activity needed to elicit cardiovascular adaptations. The purpose of the present paper is thus to review the primary research regarding sex-specific plasticity of the cardiovascular system to fitness and physical activity in older adults. Specifically, the paper will (1) briefly review known sex differences in cardiovascular aging, (2) detail emerging evidence regarding observed cardiovascular outcomes in investigations of exercise and physical activity in older men versus women, (3) explore mechanisms underlying the differing adaptations to exercise and habitual activity in men versus women, and (4) discuss implications of these findings with respect to chronic disease risk and exercise prescription. PMID:20480371

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

    PubMed Central

    Avloniti, Alexandra; Chatzinikolaou, Athanasios; Deli, Chariklia K.; Vlachopoulos, Dimitris; Gracia-Marco, Luis; Leontsini, Diamanda; Draganidis, Dimitrios; Jamurtas, Athanasios Z.; Mastorakos, George; Fatouros, Ioannis G.

    2017-01-01

    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. PMID:28106721

  13. Female cats, but not males, adjust responsiveness to arousal in the voice of kittens.

    PubMed

    Konerding, Wiebke S; Zimmermann, Elke; Bleich, Eva; Hedrich, Hans-Jürgen; Scheumann, Marina

    2016-08-12

    The infant cry is the most important communicative tool to elicit adaptive parental behaviour. Sex-specific adaptation, linked to parental investment, may have evolutionary shaped the responsiveness to changes in the voice of the infant cries. The emotional content of infant cries may trigger distinctive responsiveness either based on their general arousing properties, being part of a general affect encoding rule, or based on affective perception, linked to parental investment, differing between species. To address this question, we performed playback experiments using infant isolation calls in a species without paternal care, the domestic cat. We used kitten calls recorded in isolation contexts inducing either Low arousal (i.e., isolation only) or High arousal (i.e., additional handling), leading to respective differences in escape response of the kittens. We predicted that only females respond differently to playbacks of Low versus High arousal kitten isolation calls, based on sex-differences in parental investment. Findings showed sex-specific responsiveness of adult cats listening to kitten isolation calls of different arousal conditions, with only females responding faster towards calls of the High versus the Low arousal condition. Breeding experience of females did not affect the result. Furthermore, female responsiveness correlated with acoustic parameters related to spectral characteristics of the fundamental frequency (F0): Females responded faster to kitten calls with lower F0 at call onset, lower minimum F0 and a steeper slope of the F0. Our study revealed sex-specific differences in the responsiveness to kitten isolation calls of different arousal conditions independent of female breeding experience. The findings indicated that features of F0 are important to convey the arousal state of an infant. Taken together, the results suggest that differences in parental investment evolutionary shaped responsiveness (auditory sensitivity/ motivation) to infant calls in a sex-specific manner in the domestic cat.

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

    PubMed Central

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

    2013-01-01

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

  15. De novo assembly and characterization of tissue specific transcriptomes in the emerald notothen, Trematomus bernacchii.

    PubMed

    Huth, Troy J; Place, Sean P

    2013-11-20

    The notothenioids comprise a diverse group of fishes that rapidly radiated after isolation by the Antarctic Circumpolar Current approximately 14-25 million years ago. Given that evolutionary adaptation has led to finely tuned traits with narrow physiological limits in these organisms, this system provides a unique opportunity to examine physiological trade-offs and limits of adaptive responses to environmental perturbation. As such, notothenioids have a rich history with respect to studies attempting to understand the vulnerability of polar ecosystems to the negative impacts associated with global climate change. Unfortunately, despite being a model system for understanding physiological adaptations to extreme environments, we still lack fundamental molecular tools for much of the Nototheniidae family. Specimens of the emerald notothen, Trematomus bernacchii, were acclimated for 28 days in flow-through seawater tanks maintained near ambient seawater temperatures (-1.5°C) or at +4°C. Following acclimation, tissue specific cDNA libraries for liver, gill and brain were created by pooling RNA from n = 5 individuals per temperature treatment. The tissue specific libraries were bar-coded and used for 454 pyrosequencing, which yielded over 700 thousand sequencing reads. A de novo assembly and annotation of these reads produced a functional transcriptome library of T. bernacchii containing 30,107 unigenes, 13,003 of which possessed significant homology to a known protein product. Digital gene expression analysis of these extremely cold adapted fish reinforced the loss of an inducible heat shock response and allowed the preliminary exploration into other elements of the cellular stress response. Preliminary exploration of the transcriptome of T. bernacchii under elevated temperatures enabled a semi-quantitative comparison to prior studies aimed at characterizing the thermal response of this endemic fish whose size, abundance and distribution has established it as a pivotal species in polar research spanning several decades. The comparison of these findings to previous studies demonstrates the efficacy of transcriptomics and digital gene expression analysis as tools in future studies of polar organisms and has greatly increased the available genomic resources for the suborder Notothenioidei, particularly in the Trematominae subfamily.

  16. De novo assembly and characterization of tissue specific transcriptomes in the emerald notothen, Trematomus bernacchii

    PubMed Central

    2013-01-01

    Background The notothenioids comprise a diverse group of fishes that rapidly radiated after isolation by the Antarctic Circumpolar Current approximately 14–25 million years ago. Given that evolutionary adaptation has led to finely tuned traits with narrow physiological limits in these organisms, this system provides a unique opportunity to examine physiological trade-offs and limits of adaptive responses to environmental perturbation. As such, notothenioids have a rich history with respect to studies attempting to understand the vulnerability of polar ecosystems to the negative impacts associated with global climate change. Unfortunately, despite being a model system for understanding physiological adaptations to extreme environments, we still lack fundamental molecular tools for much of the Nototheniidae family. Results Specimens of the emerald notothen, Trematomus bernacchii, were acclimated for 28 days in flow-through seawater tanks maintained near ambient seawater temperatures (−1.5°C) or at +4°C. Following acclimation, tissue specific cDNA libraries for liver, gill and brain were created by pooling RNA from n = 5 individuals per temperature treatment. The tissue specific libraries were bar-coded and used for 454 pyrosequencing, which yielded over 700 thousand sequencing reads. A de novo assembly and annotation of these reads produced a functional transcriptome library of T. bernacchii containing 30,107 unigenes, 13,003 of which possessed significant homology to a known protein product. Digital gene expression analysis of these extremely cold adapted fish reinforced the loss of an inducible heat shock response and allowed the preliminary exploration into other elements of the cellular stress response. Conclusions Preliminary exploration of the transcriptome of T. bernacchii under elevated temperatures enabled a semi-quantitative comparison to prior studies aimed at characterizing the thermal response of this endemic fish whose size, abundance and distribution has established it as a pivotal species in polar research spanning several decades. The comparison of these findings to previous studies demonstrates the efficacy of transcriptomics and digital gene expression analysis as tools in future studies of polar organisms and has greatly increased the available genomic resources for the suborder Notothenioidei, particularly in the Trematominae subfamily. PMID:24252228

  17. Innate immunity against HIV-1 infection.

    PubMed

    Altfeld, Marcus; Gale, Michael

    2015-06-01

    During acute HIV-1 infection, viral pathogen-associated molecular patterns are recognized by pathogen-recognition receptors (PRRs) of infected cells, which triggers a signaling cascade that initiates innate intracellular antiviral defenses aimed at restricting the replication and spread of the virus. This cell-intrinsic response propagates outward via the action of secreted factors such as cytokines and chemokines that activate innate immune cells and attract them to the site of infection and to local lymphatic tissue. Antiviral innate effector cells can subsequently contribute to the control of viremia and modulate the quality of the adaptive immune response to HIV-1. The concerted actions of PRR signaling, specific viral-restriction factors, innate immune cells, innate-adaptive immune crosstalk and viral evasion strategies determine the outcome of HIV-1 infection and immune responses.

  18. Evidence of Molecular Adaptation to Extreme Environments and Applicability to Space Environments

    NASA Astrophysics Data System (ADS)

    Filipovic, M. D.; Ognjanovic, S.; Ognjanovic, M.

    2008-06-01

    This is initial investigation of gene signatures responsible for adapting microscopic life to the extreme Earth environments. We present preliminary results on identification of the clusters of orthologous groups (COGs) common to several hyperthermophiles and exclusion of those common to a mesophile (non-hyperthermophile): Escherichia coli (E. coli K12), will yield a group of proteins possibly involved in adaptation to life under extreme temperatures. Comparative genome analyses represent a powerful tool in discovery of novel genes responsible for adaptation to specific extreme environments. Methanogens stand out as the only group of organisms that have species capable of growth at 0° C (Metarhizium frigidum (M.~frigidum) and Methanococcoides burtonii (M.~burtonii)) and 110° C (Methanopyrus kandleri (M.~kandleri)). Although not all the components of heat adaptation can be attributed to novel genes, the chaperones known as heat shock proteins stabilize the enzymes under elevated temperature. However, highly conserved chaperons found in bacteria and eukaryots are not present in hyperthermophilic Archea, rather, they have a unique chaperone TF55. Our aim was to use software which we specifically developed for extremophile genome comparative analyses in order to search for additional novel genes involved in hyperthermophile adaptation. The following hyperthermophile genomes incorporated in this software were used for these studies: Methanocaldococcus jannaschii (M.~jannaschii), M.~kandleri, Archaeoglobus fulgidus (A.~fulgidus) and three species of Pyrococcus. Common genes were annotated and grouped according to their roles in cellular processes where such information was available and proteins not previously implicated in the heat-adaptation of hyperthermophiles were identified. Additional experimental data are needed in order to learn more about these proteins. To address non-gene based components of thermal adaptation, all sequenced extremophiles were analysed for their GC contents and aminoacid hydrophobicity. Finally, we develop a prediction model for optimal growth temperature.

  19. In vitro leukocyte response of three-spined sticklebacks (Gasterosteus aculeatus) to helminth parasite antigens.

    PubMed

    Franke, Frederik; Rahn, Anna K; Dittmar, Janine; Erin, Noémie; Rieger, Jennifer K; Haase, David; Samonte-Padilla, Irene E; Lange, Joseph; Jakobsen, Per J; Hermida, Miguel; Fernández, Carlos; Kurtz, Joachim; Bakker, Theo C M; Reusch, Thorsten B H; Kalbe, Martin; Scharsack, Jörn P

    2014-01-01

    Helminth parasites of teleost fish have evolved strategies to evade and manipulate the immune responses of their hosts. Responsiveness of fish host immunity to helminth antigens may therefore vary depending on the degree of host-parasite counter-adaptation. Generalist parasites, infective for a number of host species, might be unable to adapt optimally to the immune system of a certain host species, while specialist parasites might display high levels of adaptation to a particular host species. The degree of adaptations may further differ between sympatric and allopatric host-parasite combinations. Here, we test these hypotheses by in vitro exposure of head kidney leukocytes from three-spined sticklebacks (Gasterosteus aculeatus) to antigens from parasites with a broad fish host range (Diplostomum pseudospathaceum, Triaenophorus nodulosus), a specific fish parasite of cyprinids (Ligula intestinalis) and parasites highly specific only to a single fish species as second intermediate host (Schistocephalus pungitii, which does not infect G. aculeatus, and Schistocephalus solidus, infecting G. aculeatus). In vitro responses of stickleback leukocytes to S. solidus antigens from six European populations, with S. solidus prevalence from <1% to 66% were tested in a fully crossed experimental design. Leukocyte cultures were analysed by means of flow cytometry and a chemiluminescence assay to quantify respiratory burst activity. We detected decreasing magnitudes of in vitro responses to antigens from generalist to specialist parasites and among specialists, from parasites that do not infect G. aculeatus to a G. aculeatus-infecting species. Generalist parasites seem to maintain their ability to infect different host species at the costs of relatively higher immunogenicity compared to specialist parasites. In a comparison of sympatric and allopatric combinations of stickleback leukocytes and antigens from S. solidus, magnitudes of in vitro responses were dependent on the prevalence of the parasite in the population of origin, rather than on sympatry. Antigens from Norwegian (prevalence 30-50%) and Spanish (40-66%) S. solidus induced generally higher in vitro responses compared to S. solidus from two German (<1%) populations. Likewise, leukocytes from stickleback populations with a high S. solidus prevalence showed higher in vitro responses to S. solidus antigens compared to populations with low S. solidus prevalence. This suggests a rather low degree of local adaptation in S. solidus populations, which might be due to high gene flow among populations because of their extremely mobile final hosts, fish-eating birds. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. Quantitative proteomics and terminomics to elucidate the role of ubiquitination and proteolysis in adaptive immunity.

    PubMed

    Klein, Theo; Viner, Rosa I; Overall, Christopher M

    2016-10-28

    Adaptive immunity is the specialized defence mechanism in vertebrates that evolved to eliminate pathogens. Specialized lymphocytes recognize specific protein epitopes through antigen receptors to mount potent immune responses, many of which are initiated by nuclear factor-kappa B activation and gene transcription. Most, if not all, pathways in adaptive immunity are further regulated by post-translational modification (PTM) of signalling proteins, e.g. phosphorylation, citrullination, ubiquitination and proteolytic processing. The importance of PTMs is reflected by genetic or acquired defects in these pathways that lead to a dysfunctional immune response. Here we discuss the state of the art in targeted proteomics and systems biology approaches to dissect the PTM landscape specifically regarding ubiquitination and proteolysis in B- and T-cell activation. Recent advances have occurred in methods for specific enrichment and targeted quantitation. Together with improved instrument sensitivity, these advances enable the accurate analysis of often rare PTM events that are opaque to conventional proteomics approaches, now rendering in-depth analysis and pathway dissection possible. We discuss published approaches, including as a case study the profiling of the N-terminome of lymphocytes of a rare patient with a genetic defect in the paracaspase protease MALT1, a key regulator protease in antigen-driven signalling, which was manifested by elevated linear ubiquitination.This article is part of the themed issue 'Quantitative mass spectrometry'. © 2016 The Authors.

  1. Shyness and boldness in pumpkinseed sunfish: individual differences are context-specific.

    PubMed

    Coleman; Wilson

    1998-10-01

    Natural selection often promotes a mix of behavioural phenotypes in a population. Adaptive variation in the propensity to take risks might explain individual differences in shyness and boldness in humans and other species. It is often implicitly assumed that shyness and boldness are general personality traits expressed across many situations. From the evolutionary standpoint, however, individual differences that are adaptive in one context (e.g. predator defence) may not be adaptive in other contexts (e.g. exploration of the physical environment or intraspecific social interactions). We measured the context specificity of shyness and boldness in a natural population of juvenile pumpkinseed sunfish, Lepomis gibbosus, by exposing the fish to a potentially threatening stimulus (a red-tipped metrestick extended towards the individual) and a nonthreatening stimulus (a novel food source). We also related these measures of shyness and boldness to behaviours observed during focal observations, both before and after the introduction of a predator (largemouth bass, Micropterus salmoides). Consistent individual differences were found within both contexts, but individual differences did not correlate across contexts. Furthermore, fish that were scored as intermediate in their response to the metrestick behaved most boldly as foragers and in response to the bass predators. These results suggest that shyness and boldness are context-specific and may not exist as a one-dimensional behavioural continuum even within a single context. Copyright 1998 The Association for the Study of Animal Behaviour.

  2. γδ T cells recognize a microbial encoded B cell antigen to initiate a rapid antigen specific Interleukin 17 response

    PubMed Central

    Zeng, Xun; Wei, Yu-ling; Huang, Jun; Newell, Evan W.; Yu, Hongxiang; Kidd, Brian A.; Kuhns, Michael S.; Waters, Ray W.; Davis, Mark M.; Weaver, Casey T.; Chien, Yueh-hsiu

    2012-01-01

    Summary γδ T cells contribute uniquely to host immune defense. However, how they function remains an enigma. Although it is unclear what most γδ T cells recognize, common dogma asserts that they recognize self-antigens. While they are the major initial Interleukin-17 (IL-17) producers in infections, it is unclear what is required to trigger these cells to act. Here, we report that a noted B cell antigen, the algae protein-phycoerythrin (PE) is an antigen for murine and human γδ T cells. PE also stained specific bovine γδ T cells. Employing this specificity, we demonstrated that antigen recognition, but not extensive clonal expansion, was required to activate naïve γδ T cells to make IL-17. In this activated state, γδ T cells gained the ability to respond to cytokine signals that perpetuated the IL-17 production. These results underscore the adaptability of lymphocyte antigen receptors and suggest a previously unrecognized antigen-driven rapid response in protective immunity prior to the maturation of classical adaptive immunity. PMID:22960222

  3. From vision to action: roadmapping as a strategic method and tool to implement climate change adaptation - the example of the roadmap 'water sensitive urban design 2020'.

    PubMed

    Hasse, J U; Weingaertner, D E

    2016-01-01

    As the central product of the BMBF-KLIMZUG-funded Joint Network and Research Project (JNRP) 'dynaklim - Dynamic adaptation of regional planning and development processes to the effects of climate change in the Emscher-Lippe region (North Rhine Westphalia, Germany)', the Roadmap 2020 'Regional Climate Adaptation' has been developed by the various regional stakeholders and institutions containing specific regional scenarios, strategies and adaptation measures applicable throughout the region. This paper presents the method, elements and main results of this regional roadmap process by using the example of the thematic sub-roadmap 'Water Sensitive Urban Design 2020'. With a focus on the process support tool 'KlimaFLEX', one of the main adaptation measures of the WSUD 2020 roadmap, typical challenges for integrated climate change adaptation like scattered knowledge, knowledge gaps and divided responsibilities but also potential solutions and promising chances for urban development and urban water management are discussed. With the roadmap and the related tool, the relevant stakeholders of the Emscher-Lippe region have jointly developed important prerequisites to integrate their knowledge, to clarify vulnerabilities, adaptation goals, responsibilities and interests, and to foresightedly coordinate measures, resources, priorities and schedules for an efficient joint urban planning, well-grounded decision-making in times of continued uncertainties and step-by-step implementation of adaptation measures from now on.

  4. Natural selection in avian protein-coding genes expressed in brain.

    PubMed

    Axelsson, Erik; Hultin-Rosenberg, Lina; Brandström, Mikael; Zwahlén, Martin; Clayton, David F; Ellegren, Hans

    2008-06-01

    The evolution of birds from theropod dinosaurs took place approximately 150 million years ago, and was associated with a number of specific adaptations that are still evident among extant birds, including feathers, song and extravagant secondary sexual characteristics. Knowledge about the molecular evolutionary background to such adaptations is lacking. Here, we analyse the evolution of > 5000 protein-coding gene sequences expressed in zebra finch brain by comparison to orthologous sequences in chicken. Mean d(N)/d(S) is 0.085 and genes with their maximal expression in the eye and central nervous system have the lowest mean d(N)/d(S) value, while those expressed in digestive and reproductive tissues exhibit the highest. We find that fast-evolving genes (those which have higher than expected rate of nonsynonymous substitution, indicative of adaptive evolution) are enriched for biological functions such as fertilization, muscle contraction, defence response, response to stress, wounding and endogenous stimulus, and cell death. After alignment to mammalian orthologues, we identify a catalogue of 228 genes that show a significantly higher rate of protein evolution in the two bird lineages than in mammals. These accelerated bird genes, representing candidates for avian-specific adaptations, include genes implicated in vocal learning and other cognitive processes. Moreover, colouration genes evolve faster in birds than in mammals, which may have been driven by sexual selection for extravagant plumage characteristics.

  5. Maternal programming of sex-specific responses to predator odor stress in adult rats.

    PubMed

    St-Cyr, Sophie; Abuaish, Sameera; Sivanathan, Shathveekan; McGowan, Patrick O

    2017-08-01

    Prenatal stress mediated through the mother can lead to long-term adaptations in stress-related phenotypes in offspring. This study tested the long-lasting effect of prenatal exposure to predator odor, an ethologically relevant and psychogenic stressor, in the second half of pregnancy. As adults, the offspring of predator odor-exposed mothers showed increased anxiety-like behaviors in commonly used laboratory tasks assessing novelty-induced anxiety, increased defensive behavior in males and increased ACTH stress reactivity in females in response to predator odor. Female offspring from predator odor-exposed dams showed increased transcript abundance of glucocorticoid receptor (NR3C1) on the day of birth and FK506 binding protein 5 (FKBP5) in adulthood in the amygdala. The increase in FKBP5 expression was associated with decreased DNA methylation in Fkbp5 intron V. These results indicate a sex-specific response to maternal programming by prenatal predator odor exposure and a potential epigenetic mechanism linking these responses with modifications of the stress axis in females. These results are in accordance with the mismatch hypothesis stating that an animal's response to cues within its life history reflects environmental conditions anticipated during important developmental periods and should be adaptive when these conditions are concurring. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Auditory Responses and Stimulus-Specific Adaptation in Rat Auditory Cortex are Preserved Across NREM and REM Sleep

    PubMed Central

    Nir, Yuval; Vyazovskiy, Vladyslav V.; Cirelli, Chiara; Banks, Matthew I.; Tononi, Giulio

    2015-01-01

    Sleep entails a disconnection from the external environment. By and large, sensory stimuli do not trigger behavioral responses and are not consciously perceived as they usually are in wakefulness. Traditionally, sleep disconnection was ascribed to a thalamic “gate,” which would prevent signal propagation along ascending sensory pathways to primary cortical areas. Here, we compared single-unit and LFP responses in core auditory cortex as freely moving rats spontaneously switched between wakefulness and sleep states. Despite robust differences in baseline neuronal activity, both the selectivity and the magnitude of auditory-evoked responses were comparable across wakefulness, Nonrapid eye movement (NREM) and rapid eye movement (REM) sleep (pairwise differences <8% between states). The processing of deviant tones was also compared in sleep and wakefulness using an oddball paradigm. Robust stimulus-specific adaptation (SSA) was observed following the onset of repetitive tones, and the strength of SSA effects (13–20%) was comparable across vigilance states. Thus, responses in core auditory cortex are preserved across sleep states, suggesting that evoked activity in primary sensory cortices is driven by external physical stimuli with little modulation by vigilance state. We suggest that sensory disconnection during sleep occurs at a stage later than primary sensory areas. PMID:24323498

  7. Antigen-Specific CD8+ T Cells Fail To Respond to Shigella flexneri ▿

    PubMed Central

    Jehl, Stephanie P.; Doling, Amy M.; Giddings, Kara S.; Phalipon, Armelle; Sansonetti, Philippe J.; Goldberg, Marcia B.; Starnbach, Michael N.

    2011-01-01

    CD8+ T lymphocytes often play a primary role in adaptive immunity to cytosolic microbial pathogens. Surprisingly, CD8+ T cells are not required for protective immunity to the enteric pathogen Shigella flexneri, despite the ability of Shigella to actively secrete proteins into the host cytoplasm, a location from which antigenic peptides are processed for presentation to CD8+ T cells. To determine why CD8+ T cells fail to play a role in adaptive immunity to S. flexneri, we investigated whether antigen-specific CD8+ T cells are primed during infection but are unable to confer protection or, alternatively, whether T cells fail to be primed. To test whether Shigella is capable of stimulating an antigen-specific CD8+ T-cell response, we created an S. flexneri strain that constitutively secretes a viral CD8+ T-cell epitope via the Shigella type III secretion system and characterized the CD8+ T-cell response to this strain both in mice and in cultured cells. Surprisingly, no T cells specific for the viral epitope were stimulated in mice infected with this strain, and cells infected with the recombinant strain were not targeted by epitope-specific T cells. Additionally, we found that the usually robust T-cell response to antigens artificially introduced into the cytoplasm of cultured cells was significantly reduced when the antigen-presenting cell was infected with Shigella. Collectively, these results suggest that antigen-specific CD8+ T cells are not primed during S. flexneri infection and, as a result, afford little protection to the host during primary or subsequent infection. PMID:21357720

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

    PubMed

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

    2002-10-01

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

  9. fMRI-adaptation studies of viewpoint tuning in the extrastriate and fusiform body areas.

    PubMed

    Taylor, John C; Wiggett, Alison J; Downing, Paul E

    2010-03-01

    People are easily able to perceive the human body across different viewpoints, but the neural mechanisms underpinning this ability are currently unclear. In three experiments, we used functional MRI (fMRI) adaptation to study the view-invariance of representations in two cortical regions that have previously been shown to be sensitive to visual depictions of the human body--the extrastriate and fusiform body areas (EBA and FBA). The BOLD response to sequentially presented pairs of bodies was treated as an index of view invariance. Specifically, we compared trials in which the bodies in each image held identical poses (seen from different views) to trials containing different poses. EBA and FBA adapted to identical views of the same pose, and both showed a progressive rebound from adaptation as a function of the angular difference between views, up to approximately 30 degrees. However, these adaptation effects were eliminated when the body stimuli were followed by a pattern mask. Delaying the mask onset increased the response (but not the adaptation effect) in EBA, leaving FBA unaffected. We interpret these masking effects as evidence that view-dependent fMRI adaptation is driven by later waves of neuronal responses in the regions of interest. Finally, in a whole brain analysis, we identified an anterior region of the left inferior temporal sulcus (l-aITS) that responded linearly to stimulus rotation, but showed no selectivity for bodies. Our results show that body-selective cortical areas exhibit a similar degree of view-invariance as other object selective areas--such as the lateral occipitotemporal area (LO) and posterior fusiform gyrus (pFs).

  10. Climate change/variability science and adaptive strategies for state and regional transportation decision making.

    DOT National Transportation Integrated Search

    2010-04-01

    The objective of this study was to generate a baseline understanding of current policy responses to climate : change/variability at the state and regional transportation-planning and -decision levels. Specifically, : researchers were interested in th...

  11. The role of stimulus-specific adaptation in songbird syntax generation

    NASA Astrophysics Data System (ADS)

    Wittenbach, Jason D.

    Sequential behaviors are an important part of the behavioral repertoire of many animals and understanding how neural circuits encode and generate such sequences is a long-standing question in neuroscience. The Bengalese finch is a useful model system for studying variable action sequences. The songs of these birds consist of well-defined vocal elements (syllables) that are strung together to form sequences. The ordering of the syllables within the sequence is variable but not random - it shows complex statistical patterns (syntax). While often thought to be first-order, the syntax of the Bengalese finch song shows a distinct form of history dependence where the probability of repeating a syllable decreases as a function of the number of repetitions that have already occurred. Current models of the Bengalese finch song control circuitry offer no explanation for this repetition adaptation. The Bengalese finch also uses real-time auditory feedback to control the song syntax. Considering these facts, we hypothesize that repetition adaptation in the Bengalese finch syntax may be caused by stimulus-specific adaptation - a wide-spread phenomenon where neural responses to a specific stimulus become weaker with repeated presentations of the same stimulus. We begin by proposing a computational model for the song-control circuit where an auditory feedback signal that undergoes stimulus-specific adaptation helps drive repeated syllables. We show that this model does indeed capture the repetition adaptation observed in Bengalese finch syntax; along the way, we derive a new probabilistic model for repetition adaptation. Key predictions of our model are analyzed in light of experiments performed by collaborators. Next we extend the model in order to predict how the syntax will change as a function of brain temperature. These predictions are compared to experimental results from collaborators where portions of the Bengalese finch song circuit are cooled in awake and behaving birds. Finally we show that repetition adaptation persists even in a simplified dynamical system model when a parameter controlling the repeat probability changes slowly over repetitions.

  12. Effects of Acute Stress on Thrombosis.

    PubMed

    Bentur, Ohad S; Sarig, Galit; Brenner, Benjamin; Jacob, Giris

    2018-06-18

    Stress, the nonspecific response to any demand for change, is an adaptive response of the human body to various stimulants. As such, stress-induced hypercoagulation may represent an adaptive response to bleeding. Numerous epidemiological studies have revealed that a correlation exists between stress and thrombotic risk and biochemically, links of the relationship between psychological stress and coagulation pathways have been made. The stress reaction is coupled with neurohormonal changes mediated mainly by the sympathetic neural system and the hypothalamic-pituitary-adrenal axis. Singling out the specific pathways affecting coagulation in this complex response is hampered by many confounders. The mediators of the stress reaction (neurotransmitters and hormones) can directly affect platelets and the coagulation cascade and indirectly affect hemostasis via changes in hemodynamics. In this review, the authors will delineate the distinct neurobiological mechanisms that govern the effects of stress on coagulation, and report their recent findings. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  13. Endocrine correlates of susceptibility to motion sickness

    NASA Technical Reports Server (NTRS)

    Kohl, R. L.

    1985-01-01

    Motion sickness releases ACTH, epinerphrine, and norepinephrine. The endocrine responses to motion sickness, adaptive responses leading to the resolution of the syndrome, and the way in which antimotion-sickness drugs influence the endocrine responses were studied. Susceptible or insusceptible subjects were administered antimotion-sickness drugs prior to stressful stimulation. Insusceptible subjects displayed more pronounced elevations of ACTH, epinephrine, and norepinephrine after stressful motion. Predrug levels of ACTH were higher in insusceptible subjects (p less than 0.01). Acute blockade of hormone responses to stressful motion or alteration of levels of ACTH by drugs were not correlated with individual susceptibility. No correlation was apparent between epinephrine and ACTH release. These endocrine differences may represent neurochemical markers for susceptibility to motion, stress, or general adaptability, and it may be that the chronic modulation of their levels might be more effective in preventing motion sickness than the acute blockage or stimulation of specific receptors.

  14. TLR10 is a B-cell Intrinsic Suppressor of Adaptive Immune Responses

    PubMed Central

    Hess, Nicholas J.; Jiang, Song; Li, Xinyan; Guan, Yue; Tapping, Richard I.

    2016-01-01

    Toll-like receptors (TLRs) play a central role in the initiation of adaptive immune responses with several TLR agonists acting as known B-cell mitogens. Despite thousands of publications on TLRs, the function of TLR10 remains unknown. We have found that antibody mediated engagement of TLR10 on primary human B-cells suppresses B-cell proliferation, cytokine production and signal transduction. When challenged with either a T-independent or T-dependent antigen, TLR10 transgenic mice exhibit diminished antibody responses. Adoptive transfer of splenic B-cells into B-cell deficient mice revealed that the suppressive effects on antigen-specific humoral immune responses are entirely B-cell intrinsic. Our results demonstrate that TLR10 has a functional role within the B-cell lineage that is distinct from that of other TLR family members and may provide a potential therapeutic target for diseases characterized by dysregulated B-cell activity. PMID:27956526

  15. More pain, more gain: Blocking the opioid system boosts adaptive cognitive control.

    PubMed

    van Steenbergen, Henk; Weissman, Daniel H; Stein, Dan J; Malcolm-Smith, Susan; van Honk, Jack

    2017-06-01

    The ability to adaptively increase cognitive control in response to cognitive challenges is crucial for goal-directed behavior. Recent findings suggest that aversive arousal triggers adaptive increases of control, but the neurochemical mechanisms underlying these effects remain unclear. Given the known contributions of the opioid system to hedonic states, we investigated whether blocking this system increases adaptive control modulations. To do so, we conducted a double-blind, placebo-controlled psychopharmacological study (n=52 females) involving a Stroop-like task. Specifically, we assessed the effect of naltrexone, an opioid blocker most selective to the mu-opioid system, on two measures of adaptive control that are thought to depend differentially on aversive arousal: post-error slowing and conflict adaptation. Consistent with our hypothesis, relative to placebo, naltrexone increased post-error slowing without influencing conflict adaptation. This finding not only supports the view that aversive arousal triggers adaptive control but also reveals a novel role for the opioid system in modulating such effects. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. How can crop intra-specific biodiversity mitigate the vulnerability of agricultural systems to climate change? A case study on durum wheat in Southern Italy

    NASA Astrophysics Data System (ADS)

    Monaco, Eugenia; Alfieri, Silvia Maria; Basile, Angelo; Menenti, Massimo; Bonfante, Antonello; De Lorenzi, Fracesca

    2014-05-01

    Climate evolution may lead to changes in the amount and distribution of precipitations and to reduced water availability, with constraints on the cultivation of some crops. Recently, foreseen crop responses to climate change raise a crucial question for the agricultural stakeholders: are the current production systems resilient to this change? An active debate is in progress about the definition of adaptation of agricultural systems, particularly about the integrated assessment of climate stressors, vulnerability and resilece towards the evaluation of climate impact on agricultural systems. Climate change represents a risk for rain-fed agricultural systems, where irrigations cannot compensate reductions in precipitations. The intra-specific biodiversity of crops can be a resource towards adaptation. The knowledge of the responses to environmental conditions (temperature and water availability) of different cultivars can allow to identify options for adaptation to future climate. Simulation models of water flow in the soil-plant-atmosphere system, driven by different climate scenarios, can describe present and foreseen soil water regime. The present work deals with a case-study on the adaptive capacity of durum wheat to climate change. The selected study area is a hilly region in Southern Italy (Fortore Beneventano, Campania Region). Two climate cases were studied: "reference" (1961-1990) and "future" (2021-2050). A mechanistic model of water flow in the soil-plant-atmosphere system (SWAP) was run to determine the water regime in some soil units, representative of the soil variability in the study area. From model output, the Relative Evapotranspiration Deficit (RETD) was determined as an indicator of hydrological conditions during the crop growing period for each year and climate case; and periods with higher frequencies of soil water deficits were identified. The timing of main crop development stages was calculated. The occurrence of water deficit at different development stages was thus assessed. Moreover, the yield response functions to water availability of several durum wheat cultivars were determined; cultivars' hydrologic requirements were thus defined and compared with the simulated values of RETD. The latter was evaluated against requirements for each soil unit, cultivar and year in both climate cases to assess adaptability. In the future climate scenario a significant reduction (about 80 mm) of rainfall is foreseen. The analyses of inter- and intra-annual courses of the indicator (RETD) showed higher RETD in one soil unit, which resulted less suitable for durum wheat cultivation. According to the soils' water regime and to the cultivar-specific yield responses, the adaptability of durum wheat cultivars was assessed. The difference between the two climate cases was significant; the adaptability of the cultivars was strongly influenced by the different rainfall regime and by the soil physical properties, which strongly affected the soil water balance. The case study showed how in the future climate case, for rainfed durum wheat, the intra-specific variability will allow to maintain the current crop production system. The work was carried out within the Italian national project AGROSCENARI funded by the Ministry for Agricultural, Food and Forest Policies (MIPAAF, D.M. 8608/7303/2008)

  17. The neural response properties and cortical organization of a rapidly adapting muscle sensory group response that overlaps with the frequencies that elicit the kinesthetic illusion.

    PubMed

    Marasco, Paul D; Bourbeau, Dennis J; Shell, Courtney E; Granja-Vazquez, Rafael; Ina, Jason G

    2017-01-01

    Kinesthesia is the sense of limb movement. It is fundamental to efficient motor control, yet its neurophysiological components remain poorly understood. The contributions of primary muscle spindles and cutaneous afferents to the kinesthetic sense have been well studied; however, potential contributions from muscle sensory group responses that are different than the muscle spindles have not been ruled out. Electrophysiological recordings in peripheral nerves and brains of male Sprague Dawley rats with a degloved forelimb preparation provide evidence of a rapidly adapting muscle sensory group response that overlaps with vibratory inputs known to generate illusionary perceptions of limb movement in humans (kinesthetic illusion). This group was characteristically distinct from type Ia muscle spindle fibers, the receptor historically attributed to limb movement sensation, suggesting that type Ia muscle spindle fibers may not be the sole carrier of kinesthetic information. The sensory-neural structure of muscles is complex and there are a number of possible sources for this response group; with Golgi tendon organs being the most likely candidate. The rapidly adapting muscle sensory group response projected to proprioceptive brain regions, the rodent homolog of cortical area 3a and the second somatosensory area (S2), with similar adaption and frequency response profiles between the brain and peripheral nerves. Their representational organization was muscle-specific (myocentric) and magnified for proximal and multi-articulate limb joints. Projection to proprioceptive brain areas, myocentric representational magnification of muscles prone to movement error, overlap with illusionary vibrational input, and resonant frequencies of volitional motor unit contraction suggest that this group response may be involved with limb movement processing.

  18. The neural response properties and cortical organization of a rapidly adapting muscle sensory group response that overlaps with the frequencies that elicit the kinesthetic illusion

    PubMed Central

    Marasco, Paul D.; Bourbeau, Dennis J.; Shell, Courtney E.; Granja-Vazquez, Rafael; Ina, Jason G.

    2017-01-01

    Kinesthesia is the sense of limb movement. It is fundamental to efficient motor control, yet its neurophysiological components remain poorly understood. The contributions of primary muscle spindles and cutaneous afferents to the kinesthetic sense have been well studied; however, potential contributions from muscle sensory group responses that are different than the muscle spindles have not been ruled out. Electrophysiological recordings in peripheral nerves and brains of male Sprague Dawley rats with a degloved forelimb preparation provide evidence of a rapidly adapting muscle sensory group response that overlaps with vibratory inputs known to generate illusionary perceptions of limb movement in humans (kinesthetic illusion). This group was characteristically distinct from type Ia muscle spindle fibers, the receptor historically attributed to limb movement sensation, suggesting that type Ia muscle spindle fibers may not be the sole carrier of kinesthetic information. The sensory-neural structure of muscles is complex and there are a number of possible sources for this response group; with Golgi tendon organs being the most likely candidate. The rapidly adapting muscle sensory group response projected to proprioceptive brain regions, the rodent homolog of cortical area 3a and the second somatosensory area (S2), with similar adaption and frequency response profiles between the brain and peripheral nerves. Their representational organization was muscle-specific (myocentric) and magnified for proximal and multi-articulate limb joints. Projection to proprioceptive brain areas, myocentric representational magnification of muscles prone to movement error, overlap with illusionary vibrational input, and resonant frequencies of volitional motor unit contraction suggest that this group response may be involved with limb movement processing. PMID:29182648

  19. Pancreatic Islet Responses to Metabolic Trauma

    PubMed Central

    Burke, Susan J.; Karlstad, Michael D.; Collier, J. Jason

    2016-01-01

    Carbohydrate, lipid, and protein metabolism are largely controlled by the interplay of various hormones, which includes those secreted by the pancreatic islets of Langerhans. While typically representing only 1–2% of the total pancreatic mass, the islets have a remarkable ability to adapt to disparate situations demanding a change in hormone release, such as peripheral insulin resistance. There are many different routes to the onset of insulin resistance, including obesity, lipodystrophy, glucocorticoid excess, and the chronic usage of atypical anti-psychotic drugs. All of these situations are coupled to an increase in pancreatic islet size, often with a corresponding increase in insulin production. These adaptive responses within the islets are ultimately intended to maintain glycemic control and to promote macronutrient homeostasis during times of stress. Herein, we review the consequences of specific metabolic trauma that lead to insulin resistance and the corresponding adaptive alterations within the pancreatic islets. PMID:26974425

  20. Dynamic hyper-editing underlies temperature adaptation in Drosophila

    PubMed Central

    Ashwal-Fluss, Reut; Pandey, Varun; Levanon, Erez Y.; Kadener, Sebastian

    2017-01-01

    In Drosophila, A-to-I editing is prevalent in the brain, and mutations in the editing enzyme ADAR correlate with specific behavioral defects. Here we demonstrate a role for ADAR in behavioral temperature adaptation in Drosophila. Although there is a higher level of editing at lower temperatures, at 29°C more sites are edited. These sites are less evolutionarily conserved, more disperse, less likely to be involved in secondary structures, and more likely to be located in exons. Interestingly, hypomorph mutants for ADAR display a weaker transcriptional response to temperature changes than wild-type flies and a highly abnormal behavioral response upon temperature increase. In sum, our data shows that ADAR is essential for proper temperature adaptation, a key behavior trait that is essential for survival of flies in the wild. Moreover, our results suggest a more general role of ADAR in regulating RNA secondary structures in vivo. PMID:28746393

  1. Afterimage induced neural activity during emotional face perception.

    PubMed

    Cheal, Jenna L; Heisz, Jennifer J; Walsh, Jennifer A; Shedden, Judith M; Rutherford, M D

    2014-02-26

    The N170 response differs when positive versus negative facial expressions are viewed. This neural response could be associated with the perception of emotions, or some feature of the stimulus. We used an aftereffect paradigm to clarify. Consistent with previous reports of emotional aftereffects, a neutral face was more likely to be described as happy following a sad face adaptation, and more likely to be described as sad following a happy face adaptation. In addition, similar to previous observations with actual emotional faces, we found differences in the latency of the N170 elicited by the neutral face following sad versus happy face adaptation, demonstrating that the emotion-specific effect on the N170 emerges even when emotion expressions are perceptually different but physically identical. The re-entry of emotional information from other brain regions may be driving the emotional aftereffects and the N170 latency differences. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Encoding of Discriminative Fear Memory by Input-Specific LTP in the Amygdala.

    PubMed

    Kim, Woong Bin; Cho, Jun-Hyeong

    2017-08-30

    In auditory fear conditioning, experimental subjects learn to associate an auditory conditioned stimulus (CS) with an aversive unconditioned stimulus. With sufficient training, animals fear conditioned to an auditory CS show fear response to the CS, but not to irrelevant auditory stimuli. Although long-term potentiation (LTP) in the lateral amygdala (LA) plays an essential role in auditory fear conditioning, it is unknown whether LTP is induced selectively in the neural pathways conveying specific CS information to the LA in discriminative fear learning. Here, we show that postsynaptically expressed LTP is induced selectively in the CS-specific auditory pathways to the LA in a mouse model of auditory discriminative fear conditioning. Moreover, optogenetically induced depotentiation of the CS-specific auditory pathways to the LA suppressed conditioned fear responses to the CS. Our results suggest that input-specific LTP in the LA contributes to fear memory specificity, enabling adaptive fear responses only to the relevant sensory cue. VIDEO ABSTRACT. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Host Sexual Dimorphism and Parasite Adaptation

    PubMed Central

    Duneau, David; Ebert, Dieter

    2012-01-01

    In species with separate sexes, parasite prevalence and disease expression is often different between males and females. This effect has mainly been attributed to sex differences in host traits, such as immune response. Here, we make the case for how properties of the parasites themselves can also matter. Specifically, we suggest that differences between host sexes in many different traits, such as morphology and hormone levels, can impose selection on parasites. This selection can eventually lead to parasite adaptations specific to the host sex more commonly encountered, or to differential expression of parasite traits depending on which host sex they find themselves in. Parasites adapted to the sex of the host in this way can contribute to differences between males and females in disease prevalence and expression. Considering those possibilities can help shed light on host–parasite interactions, and impact epidemiological and medical science. PMID:22389630

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

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Steel, Christina D.; Hahto, Suzanne M.; Ciavarra, Richard P., E-mail: ciavarrp@evms.ed

    2009-04-25

    Intranasal application of vesicular stomatitis virus (VSV) causes acute infection of the central nervous system (CNS). However, VSV encephalitis is not invariably fatal, suggesting that the CNS may contain a professional antigen-presenting cell (APC) capable of inducing or propagating a protective antiviral immune response. To examine this possibility, we first characterized the cellular elements that infiltrate the brain as well as the activation status of resident microglia in the brains of normal and transgenic mice acutely ablated of peripheral dendritic cells (DCs) in vivo. VSV encephalitis was characterized by a pronounced infiltrate of myeloid cells (CD45{sup high}CD11b{sup +}) and CD8{supmore » +} T cells containing a subset that was specific for the immunodominant VSV nuclear protein epitope. This T cell response correlated temporally with a rapid and sustained upregulation of MHC class I expression on microglia, whereas class II expression was markedly delayed. Ablation of peripheral DCs profoundly inhibited the inflammatory response as well as infiltration of virus-specific CD8{sup +} T cells. Unexpectedly, the VSV-induced interferon-gamma (IFN-gamma) response in the CNS remained intact in DC-deficient mice. Thus, both the inflammatory and certain components of the adaptive primary antiviral immune response in the CNS are dependent on peripheral DCs in vivo.« less

  5. Adaptive evolution and functional constraint at TLR4 during the secondary aquatic adaptation and diversification of cetaceans.

    PubMed

    Shen, Tong; Xu, Shixia; Wang, Xiaohong; Yu, Wenhua; Zhou, Kaiya; Yang, Guang

    2012-03-24

    Cetaceans (whales, dolphins and porpoises) are a group of adapted marine mammals with an enigmatic history of transition from terrestrial to full aquatic habitat and rapid radiation in waters around the world. Throughout this evolution, the pathogen stress-response proteins must have faced challenges from the dramatic change of environmental pathogens in the completely different ecological niches cetaceans occupied. For this reason, cetaceans could be one of the most ideal candidate taxa for studying evolutionary process and associated driving mechanism of vertebrate innate immune systems such as Toll-like receptors (TLRs), which are located at the direct interface between the host and the microbial environment, act at the first line in recognizing specific conserved components of microorganisms, and translate them rapidly into a defense reaction. We used TLR4 as an example to test whether this traditionally regarded pattern recognition receptor molecule was driven by positive selection across cetacean evolutionary history. Overall, the lineage-specific selection test showed that the dN/dS (ω) values along most (30 out of 33) examined cetartiodactylan lineages were less than 1, suggesting a common effect of functional constraint. However, some specific codons made radical changes, fell adjacent to the residues interacting with lipopolysaccharides (LPS), and showed parallel evolution between independent lineages, suggesting that TLR4 was under positive selection. Especially, strong signatures of adaptive evolution on TLR4 were identified in two periods, one corresponding to the early evolutionary transition of the terrestrial ancestors of cetaceans from land to semi-aquatic (represented by the branch leading to whale + hippo) and from semi-aquatic to full aquatic (represented by the ancestral branch leading to cetaceans) habitat, and the other to the rapid diversification and radiation of oceanic dolphins. This is the first study thus far to characterize the TLR gene in cetaceans. Our data present evidences that cetacean TLR4 has undergone adaptive evolution against the background of purifying selection in response to the secondary aquatic adaptation and rapid diversification in the sea. It is suggested that microbial pathogens in different environments are important factors that promote adaptive changes at cetacean TLR4 and new functions of some amino acid sites specialized for recognizing pathogens in dramatically contrasted environments to enhance the fitness for the adaptation and survival of cetaceans.

  6. Adaptive evolution and functional constraint at TLR4 during the secondary aquatic adaptation and diversification of cetaceans

    PubMed Central

    2012-01-01

    Background Cetaceans (whales, dolphins and porpoises) are a group of adapted marine mammals with an enigmatic history of transition from terrestrial to full aquatic habitat and rapid radiation in waters around the world. Throughout this evolution, the pathogen stress-response proteins must have faced challenges from the dramatic change of environmental pathogens in the completely different ecological niches cetaceans occupied. For this reason, cetaceans could be one of the most ideal candidate taxa for studying evolutionary process and associated driving mechanism of vertebrate innate immune systems such as Toll-like receptors (TLRs), which are located at the direct interface between the host and the microbial environment, act at the first line in recognizing specific conserved components of microorganisms, and translate them rapidly into a defense reaction. Results We used TLR4 as an example to test whether this traditionally regarded pattern recognition receptor molecule was driven by positive selection across cetacean evolutionary history. Overall, the lineage-specific selection test showed that the dN/dS (ω) values along most (30 out of 33) examined cetartiodactylan lineages were less than 1, suggesting a common effect of functional constraint. However, some specific codons made radical changes, fell adjacent to the residues interacting with lipopolysaccharides (LPS), and showed parallel evolution between independent lineages, suggesting that TLR4 was under positive selection. Especially, strong signatures of adaptive evolution on TLR4 were identified in two periods, one corresponding to the early evolutionary transition of the terrestrial ancestors of cetaceans from land to semi-aquatic (represented by the branch leading to whale + hippo) and from semi-aquatic to full aquatic (represented by the ancestral branch leading to cetaceans) habitat, and the other to the rapid diversification and radiation of oceanic dolphins. Conclusions This is the first study thus far to characterize the TLR gene in cetaceans. Our data present evidences that cetacean TLR4 has undergone adaptive evolution against the background of purifying selection in response to the secondary aquatic adaptation and rapid diversification in the sea. It is suggested that microbial pathogens in different environments are important factors that promote adaptive changes at cetacean TLR4 and new functions of some amino acid sites specialized for recognizing pathogens in dramatically contrasted environments to enhance the fitness for the adaptation and survival of cetaceans. PMID:22443485

  7. Enhanced Muscle Afferent Signals during Motor Learning in Humans.

    PubMed

    Dimitriou, Michael

    2016-04-25

    Much has been revealed concerning human motor learning at the behavioral level [1, 2], but less is known about changes in the involved neural circuits and signals. By examining muscle spindle responses during a classic visuomotor adaptation task [3-6] performed by fully alert humans, I found substantial modulation of sensory afferent signals as a function of adaptation state. Specifically, spindle control was independent of concurrent muscle activity but was specific to movement direction (representing muscle lengthening versus shortening) and to different stages of learning. Increased spindle afferent responses to muscle stretch occurring early during learning reflected individual error size and were negatively related to subsequent antagonist activity (i.e., 60-80 ms thereafter). Relative increases in tonic afferent output early during learning were predictive of the subjects' adaptation rate. I also found that independent spindle control during sensory realignment (the "washout" stage) induced afferent signal "linearization" with respect to muscle length (i.e., signals were more tuned to hand position). The results demonstrate for the first time that motor learning also involves independent and state-related modulation of sensory mechanoreceptor signals. The current findings suggest that adaptive motor performance also relies on the independent control of sensors, not just of muscles. I propose that the "γ" motor system innervating spindles acts to facilitate the acquisition and extraction of task-relevant information at the early stages of sensorimotor adaptation. This designates a more active and targeted role for the human proprioceptive system during motor learning. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Evolutionary adaptations for the temporal processing of natural sounds by the anuran peripheral auditory system

    PubMed Central

    Schrode, Katrina M.; Bee, Mark A.

    2015-01-01

    ABSTRACT Sensory systems function most efficiently when processing natural stimuli, such as vocalizations, and it is thought that this reflects evolutionary adaptation. Among the best-described examples of evolutionary adaptation in the auditory system are the frequent matches between spectral tuning in both the peripheral and central auditory systems of anurans (frogs and toads) and the frequency spectra of conspecific calls. Tuning to the temporal properties of conspecific calls is less well established, and in anurans has so far been documented only in the central auditory system. Using auditory-evoked potentials, we asked whether there are species-specific or sex-specific adaptations of the auditory systems of gray treefrogs (Hyla chrysoscelis) and green treefrogs (H. cinerea) to the temporal modulations present in conspecific calls. Modulation rate transfer functions (MRTFs) constructed from auditory steady-state responses revealed that each species was more sensitive than the other to the modulation rates typical of conspecific advertisement calls. In addition, auditory brainstem responses (ABRs) to paired clicks indicated relatively better temporal resolution in green treefrogs, which could represent an adaptation to the faster modulation rates present in the calls of this species. MRTFs and recovery of ABRs to paired clicks were generally similar between the sexes, and we found no evidence that males were more sensitive than females to the temporal modulation patterns characteristic of the aggressive calls used in male–male competition. Together, our results suggest that efficient processing of the temporal properties of behaviorally relevant sounds begins at potentially very early stages of the anuran auditory system that include the periphery. PMID:25617467

  9. Cetuximab-activated natural killer (NK) and dendritic cells (DC) collaborate to trigger tumor antigen-specific T cell immunity in head and neck cancer patients

    PubMed Central

    Srivastava, Raghvendra M.; Lee, Steve C.; Filho, Pedro A. Andrade; Lord, Christopher A.; Jie, Hyun-bae; Davidson, H. Carter; López-Albaitero, Andrés; Gibson, Sandra P.; Gooding, William E.; Ferrone, Soldano; Ferris, Robert L.

    2013-01-01

    Purpose Tumor antigen (TA)-specific monoclonal antibodies (mAb) block oncogenic signaling and induce Fcγ receptor (FcγR)-mediated cytotoxicity. However, the role of CD8+ cytotoxic T lymphocyte (CTL) and FcγR in initiating innate and adaptive immune responses in mAb-treated human cancer patients is still emerging. Experimental Design FcγRIIIa codon 158 polymorphism was correlated with survival in 107 cetuximab-treated head and neck cancer (HNC) patients. Flow cytometry was performed to quantify EGFR-specific T cells in cetuximab-treated HNC patients. The effect of cetuximab on NK cell, dendritic cell (DC), and T cell activation was measured using IFN-γ release assays and flow cytometry. Results FcγR IIIa polymorphism did not predict clinical outcome in cetuximab-treated HNC patients, however elevated circulating EGFR -specific CD8+ 853-861 T cells were found in cetuximab-treated HNC patients (p<0.005). Cetuximab promoted EGFR-specific cellular immunity through the interaction of EGFR+ tumor cells and FcγRIIIa on NK cells, but not on the polymorphism per se. Cetuximab-activated NK cells induced IFN-γ dependent expression of DC maturation markers, antigen presentation machinery (APM) components such as TAP-1/2, and Th1 chemokines through NKG2D/MICA binding. Cetuximab initiated adaptive immune responses via NK-cell induced DC maturation, which enhanced cross-presentation to CTL specific for EGFR as well as another TA, MAGE-3. Conclusion Cetuximab-activated NK cells promote DC maturation and CD8+ T cell priming, leading to TA spreading and Th1 cytokine release through ‘NK-DC cross-talk.’ FcγRIIIa polymorphism did not predict clinical response to cetuximab, but was necessary for NK-DC interaction and mAb induced cross-presentation. EGFR-specific T cells in cetuximab treated HNC patients may contribute to clinical response. PMID:23444227

  10. Identification of Variant-Specific Surface Proteins in Giardia muris Trophozoites

    PubMed Central

    Ropolo, Andrea S.; Saura, Alicia; Carranza, Pedro G.; Lujan, Hugo D.

    2005-01-01

    Giardia lamblia undergoes antigenic variation, a process that might allow the parasite to evade the host's immune response and adapt to different environments. Here we show that Giardia muris, a related species that naturally infects rodents, possesses multiple variant-specific surface proteins (VSPs) and expresses VSPs on its surface, suggesting that it undergoes antigenic variation similar to that of G. lamblia. PMID:16041041

  11. The Phosphorylation State of the Drosophila TRP Channel Modulates the Frequency Response to Oscillating Light In Vivo

    PubMed Central

    Rhodes-Mordov, Elisheva; Katz, Ben; Oberegelsbacher, Claudia; Yasin, Bushra; Tzadok, Hanan; Huber, Armin

    2017-01-01

    Drosophila photoreceptors respond to oscillating light of high frequency (∼100 Hz), while the detected maximal frequency is modulated by the light rearing conditions, thus enabling high sensitivity to light and high temporal resolution. However, the molecular basis for this adaptive process is unclear. Here, we report that dephosphorylation of the light-activated transient receptor potential (TRP) ion channel at S936 is a fast, graded, light-dependent, and Ca2+-dependent process that is partially modulated by the rhodopsin phosphatase retinal degeneration C (RDGC). Electroretinogram measurements of the frequency response to oscillating lights in vivo revealed that dark-reared flies expressing wild-type TRP exhibited a detection limit of oscillating light at relatively low frequencies, which was shifted to higher frequencies upon light adaptation. Strikingly, preventing phosphorylation of the S936-TRP site by alanine substitution in transgenic Drosophila (trpS936A) abolished the difference in frequency response between dark-adapted and light-adapted flies, resulting in high-frequency response also in dark-adapted flies. In contrast, inserting a phosphomimetic mutation by substituting the S936-TRP site to aspartic acid (trpS936D) set the frequency response of light-adapted flies to low frequencies typical of dark-adapted flies. Light-adapted rdgC mutant flies showed relatively high S936-TRP phosphorylation levels and light–dark phosphorylation dynamics. These findings suggest that RDGC is one but not the only phosphatase involved in pS936-TRP dephosphorylation. Together, this study indicates that TRP channel dephosphorylation is a regulatory process that affects the detection limit of oscillating light according to the light rearing condition, thus adjusting dynamic processing of visual information under varying light conditions. SIGNIFICANCE STATEMENT Drosophila photoreceptors exhibit high temporal resolution as manifested in frequency response to oscillating light of high frequency (≤∼100 Hz). Light rearing conditions modulate the maximal frequency detected by photoreceptors, thus enabling them to maintain high sensitivity to light and high temporal resolution. However, the precise mechanisms for this process are not fully understood. Here, we show by combination of biochemistry and in vivo electrophysiology that transient receptor potential (TRP) channel dephosphorylation at a specific site is a fast, light-activated and Ca2+-dependent regulatory process. TRP dephosphorylation affects the detection limit of oscillating light according to the adaptation state of the photoreceptor cells by shifting the detection limit to higher frequencies upon light adaptation. This novel mechanism thus adjusts dynamic processing of visual information under varying light conditions. PMID:28314815

  12. Adaptive Response Criteria in Road Hazard Detection Among Older Drivers

    PubMed Central

    Feng, Jing; Choi, HeeSun; Craik, Fergus I. M.; Levine, Brian; Moreno, Sylvain; Naglie, Gary; Zhu, Motao

    2018-01-01

    OBJECTIVES The majority of existing investigations on attention, aging, and driving have focused on the negative impacts of age-related declines in attention on hazard detection and driver performance. However, driving skills and behavioral compensation may accommodate the negative effects that age-related attentional decline places on driving performance. In this study, we examined an important question that had been largely neglected in the literature linking attention, aging, and driving: can top-down factors such as behavioral compensation, specifically adaptive response criteria, accommodate the negative impacts from age-related attention declines on hazard detection during driving? METHODS In the experiment, we used the Drive Aware Task, a task combining the driving context with well-controlled laboratory procedures measuring attention. We compared younger (n = 16, age 21 – 30) and older drivers (n = 21, age 65 – 79) on their attentional processing of hazards in driving scenes, indexed by percentage of correct and reaction time of hazard detection, as well as sensitivity and response criterion using the signal detection analysis. RESULTS Older drivers, in general, were less accurate and slower on the task than younger drivers. However, results from this experiment also revealed that older, but not younger, drivers adapted their response criteria when the traffic condition changed in the driving scenes. When there was more traffic in the driving scene, older drivers became more liberal in their responses, meaning that they were more likely to report that a driving hazard was detected. CONCLUSIONS Older drivers adopt compensatory strategies on hazard detection during driving . Our findings showed that, in the driving context, even at an old age our attentional functions are still adaptive according to environmental conditions. This leads to considerations on potential training methods to promote adaptive strategies which may help older drivers maintaining performance in road hazard detection. PMID:28898116

  13. Drought responsive gene expression regulatory divergence between upland and lowland ecotypes of a perennial C4 grass.

    PubMed

    Lovell, John T; Schwartz, Scott; Lowry, David B; Shakirov, Eugene V; Bonnette, Jason E; Weng, Xiaoyu; Wang, Mei; Johnson, Jenifer; Sreedasyam, Avinash; Plott, Christopher; Jenkins, Jerry; Schmutz, Jeremy; Juenger, Thomas E

    2016-04-01

    Climatic adaptation is an example of a genotype-by-environment interaction (G×E) of fitness. Selection upon gene expression regulatory variation can contribute to adaptive phenotypic diversity; however, surprisingly few studies have examined how genome-wide patterns of gene expression G×E are manifested in response to environmental stress and other selective agents that cause climatic adaptation. Here, we characterize drought-responsive expression divergence between upland (drought-adapted) and lowland (mesic) ecotypes of the perennial C4 grass,Panicum hallii, in natural field conditions. Overall, we find that cis-regulatory elements contributed to gene expression divergence across 47% of genes, 7.2% of which exhibit drought-responsive G×E. While less well-represented, we observe 1294 genes (7.8%) with transeffects.Trans-by-environment interactions are weaker and much less common than cis G×E, occurring in only 0.7% oft rans-regulated genes. Finally, gene expression heterosis is highly enriched in expression phenotypes with significant G×E. As such, modes of inheritance that drive heterosis, such as dominance or overdominance, may be common among G×E genes. Interestingly, motifs specific to drought-responsive transcription factors are highly enriched in the promoters of genes exhibiting G×E and transregulation, indicating that expression G×E and heterosis may result from the evolution of transcription factors or their binding sites.P. hallii serves as the genomic model for its close relative and emerging biofuel crop, switchgrass (Panicum virgatum). Accordingly, the results here not only aid in the discovery of the genetic mechanisms that underlie local adaptation but also provide a foundation to improve switchgrass yield under water-limited conditions. © 2016 Lovell et al.; Published by Cold Spring Harbor Laboratory Press.

  14. Drought responsive gene expression regulatory divergence between upland and lowland ecotypes of a perennial C4 grass

    PubMed Central

    Lovell, John T.; Schwartz, Scott; Lowry, David B.; Shakirov, Eugene V.; Bonnette, Jason E.; Weng, Xiaoyu; Wang, Mei; Johnson, Jenifer; Sreedasyam, Avinash; Plott, Christopher; Jenkins, Jerry; Schmutz, Jeremy; Juenger, Thomas E.

    2016-01-01

    Climatic adaptation is an example of a genotype-by-environment interaction (G×E) of fitness. Selection upon gene expression regulatory variation can contribute to adaptive phenotypic diversity; however, surprisingly few studies have examined how genome-wide patterns of gene expression G×E are manifested in response to environmental stress and other selective agents that cause climatic adaptation. Here, we characterize drought-responsive expression divergence between upland (drought-adapted) and lowland (mesic) ecotypes of the perennial C4 grass, Panicum hallii, in natural field conditions. Overall, we find that cis-regulatory elements contributed to gene expression divergence across 47% of genes, 7.2% of which exhibit drought-responsive G×E. While less well-represented, we observe 1294 genes (7.8%) with trans effects. Trans-by-environment interactions are weaker and much less common than cis G×E, occurring in only 0.7% of trans-regulated genes. Finally, gene expression heterosis is highly enriched in expression phenotypes with significant G×E. As such, modes of inheritance that drive heterosis, such as dominance or overdominance, may be common among G×E genes. Interestingly, motifs specific to drought-responsive transcription factors are highly enriched in the promoters of genes exhibiting G×E and trans regulation, indicating that expression G×E and heterosis may result from the evolution of transcription factors or their binding sites. P. hallii serves as the genomic model for its close relative and emerging biofuel crop, switchgrass (Panicum virgatum). Accordingly, the results here not only aid in the discovery of the genetic mechanisms that underlie local adaptation but also provide a foundation to improve switchgrass yield under water-limited conditions. PMID:26953271

  15. Plasma Cytokine Levels During Long-Duration Spaceflight

    NASA Technical Reports Server (NTRS)

    Crucian, Brian E.; Zwart, Sara R.; Quiriarte, Heather A.; Smith, Scott M.; Sams, Clarence F.

    2011-01-01

    Reduced T cell, granulocyte, NK and monocyte function have all been reported following both long and short duration spaceflight, however these data indicate crews are generally not experiencing inflammatory or adaptive immune activation during spaceflight. There appear to be varied individual crew responses, and specific relationships between cytokines and markers of iron status and muscle turnover that warrant further evaluation. Increases in growth factors and chemokines may indicate other types of adaptation occurring during spaceflight, such as attempts to overcome diminished immunocyte function.

  16. Adaptation of primate vestibuloocular reflex to altered peripheral vestibular inputs. I. Frequency-specific recovery of horizontal VOR after inactivation of the lateral semicircular canals

    NASA Technical Reports Server (NTRS)

    Angelaki, D. E.; Hess, B. J.; Arai, Y.; Suzuki, J.

    1996-01-01

    1. The adaptive plasticity of the vestibuloocular reflex (VOR) following a selective lesion of the peripheral vestibular organs was investigated in rhesus monkeys whose lateral semicircular canals were inactivated by plugging of the canal lumen in both ears. Gain and phase of horizontal, vertical, and torsional slow-phase eye velocity were determined from three-dimensional eye movement recordings obtained acutely after the plugging operation, as well as in regular intervals up to 10 mo later. 2. Acutely after plugging, horizontal VOR was minimal during yaw rotation with gains of < 0.1 at all frequencies. Horizontal VOR gain gradually increased over time, reaching gains of 0.4-0.5 for yaw oscillations at 1.1 Hz approximately 5 mo after lateral canal inactivation. This response recovery was strongly frequency dependent: horizontal VOR gains were largest at the highest frequency tested and progressively decreased for lower frequencies. Below approximately 0.1 Hz, no consistent horizontal VOR could be elicited even 10 mo after plugging. 3. The frequency-dependent changes in gain paralleled changes in horizontal VOR phase. Below approximately 0.1-0.05 Hz large phase leads were present, similarly as in semicircular canal primary afferents. Smaller phase leads were also present at higher frequencies, particularly at 1.1 Hz (the highest frequency tested). 4. Consistent with the afferent-like dynamics of the adapted horizontal VOR, per- and postrotatory horizontal responses to constant-velocity yaw rotations were short lasting. Time constants of the slow-phase eye velocity envelope of the horizontal postrotatory nystagmus were approximately 2 s. Nonetheless, a consistent horizontal optokinetic afternystagmus was evoked in plugged animals. 5. A torsional component that was absent in intact animals was consistently present during yaw rotation acutely after lateral canal inactivation and remained approximately constant thereafter. The frequency response characteristics of this torsional component resembled those of the adapted horizontal slow-phase responses: gain decreased and large phase leads were introduced at frequencies below approximately 0.05-0.1 Hz. Torsional responses elicited by roll oscillations in supine position, on the other hand, were indistinguishable in their dynamics from intact animals. No consistent vertical nystagmus was elicited during yaw rotation. 6. Our results show that there is a slow, frequency-specific recovery of horizontal VOR after selective inactivation of the lateral semicircular canals. Both the spatial organization and the dynamic properties of the adapted VOR responses are distinctly different from responses in intact animals, suggesting complex changes in the underlying vestibuloocular circuitry.

  17. Antibiotic Stimulation of a Bacillus subtilis Migratory Response

    PubMed Central

    Liu, Yongjin; Kyle, Steven

    2018-01-01

    ABSTRACT Competitive interactions between bacteria reveal physiological adaptations that benefit fitness. Bacillus subtilis is a Gram-positive species with several adaptive mechanisms for competition and environmental stress. Biofilm formation, sporulation, and motility are the outcomes of widespread changes in a population of B. subtilis. These changes emerge from complex, regulated pathways for adapting to external stresses, including competition from other species. To identify competition-specific functions, we cultured B. subtilis with multiple species of Streptomyces and observed altered patterns of growth for each organism. In particular, when plated on agar medium near Streptomyces venezuelae, B. subtilis initiates a robust and reproducible mobile response. To investigate the mechanistic basis for the interaction, we determined the type of motility used by B. subtilis and isolated inducing metabolites produced by S. venezuelae. Bacillus subtilis has three defined forms of motility: swimming, swarming, and sliding. Streptomyces venezuelae induced sliding motility specifically in our experiments. The inducing agents produced by S. venezuelae were identified as chloramphenicol and a brominated derivative at subinhibitory concentrations. Upon further characterization of the mobile response, our results demonstrated that subinhibitory concentrations of chloramphenicol, erythromycin, tetracycline, and spectinomycin all activate a sliding motility response by B. subtilis. Our data are consistent with sliding motility initiating under conditions of protein translation stress. This report underscores the importance of hormesis as an early warning system for potential bacterial competitors and antibiotic exposure. IMPORTANCE Antibiotic resistance is a major challenge for the effective treatment of infectious diseases. Identifying adaptive mechanisms that bacteria use to survive low levels of antibiotic stress is important for understanding pathways to antibiotic resistance. Furthermore, little is known about the effects of individual bacterial interactions on multispecies communities. This work demonstrates that subinhibitory amounts of some antibiotics produced by streptomycetes induce active motility in B. subtilis, which may alter species interaction dynamics among species-diverse bacterial communities in natural environments. The use of antibiotics at subinhibitory concentrations results in many changes in bacteria, including changes in biofilm formation, small-colony variants, formation of persisters, and motility. Identifying the mechanistic bases of these adaptations is crucial for understanding how bacterial communities are impacted by antibiotics. PMID:29507890

  18. Spontaneous mutations in CYC8 and MIG1 suppress the short chronological lifespan of budding yeast lacking SNF1/AMPK

    PubMed Central

    Maqani, Nazif; Fine, Ryan D.; Shahid, Mehreen; Li, Mingguang; Enriquez-Hesles, Elisa; Smith, Jeffrey S.

    2018-01-01

    Chronologically aging yeast cells are prone to adaptive regrowth, whereby mutants with a survival advantage spontaneously appear and re-enter the cell cycle in stationary phase cultures. Adaptive regrowth is especially noticeable with short-lived strains, including those defective for SNF1, the homolog of mammalian AMP-activated protein kinase (AMPK). SNF1 becomes active in response to multiple environmental stresses that occur in chronologically aging cells, including glucose depletion and oxidative stress. SNF1 is also required for the extension of chronological lifespan (CLS) by caloric restriction (CR) as defined as limiting glucose at the time of culture inoculation. To identify specific downstream SNF1 targets responsible for CLS extension during CR, we screened for adaptive regrowth mutants that restore chronological longevity to a short-lived snf1∆ parental strain. Whole genome sequencing of the adapted mutants revealed missense mutations in TPR motifs 9 and 10 of the transcriptional co-repressor Cyc8 that specifically mediate repression through the transcriptional repressor Mig1. Another mutation occurred in MIG1 itself, thus implicating the activation of Mig1-repressed genes as a key function of SNF1 in maintaining CLS. Consistent with this conclusion, the cyc8 TPR mutations partially restored growth on alternative carbon sources and significantly extended CLS compared to the snf1∆ parent. Furthermore, cyc8 TPR mutations reactivated multiple Mig1-repressed genes, including the transcription factor gene CAT8, which is responsible for activating genes of the glyoxylate and gluconeogenesis pathways. Deleting CAT8 completely blocked CLS extension by the cyc8 TPR mutations on CLS, identifying these pathways as key Snf1-regulated CLS determinants.

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

    PubMed

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

    2015-12-01

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

  20. Adaptive evolution of Mediterranean pines.

    PubMed

    Grivet, Delphine; Climent, José; Zabal-Aguirre, Mario; Neale, David B; Vendramin, Giovanni G; González-Martínez, Santiago C

    2013-09-01

    Mediterranean pines represent an extremely heterogeneous assembly. Although they have evolved under similar environmental conditions, they diversified long ago, ca. 10 Mya, and present distinct biogeographic and demographic histories. Therefore, it is of special interest to understand whether and to what extent they have developed specific strategies of adaptive evolution through time and space. To explore evolutionary patterns, the Mediterranean pines' phylogeny was first reconstructed analyzing a new set of 21 low-copy nuclear genes with multilocus Bayesian tree reconstruction methods. Secondly, a phylogenetic approach was used to search for footprints of natural selection and to examine the evolution of multiple phenotypic traits. We identified two genes (involved in pines' defense and stress responses) that have likely played a role in the adaptation of Mediterranean pines to their environment. Moreover, few life-history traits showed historical or evolutionary adaptive convergence in Mediterranean lineages, while patterns of character evolution revealed various evolutionary trade-offs linking growth-development, reproduction and fire-related traits. Assessing the evolutionary path of important life-history traits, as well as the genomic basis of adaptive variation is central to understanding the past evolutionary success of Mediterranean pines and their future response to environmental changes. Copyright © 2013 Elsevier Inc. All rights reserved.

  1. Effect of prism adaptation on left dichotic listening deficit in neglect patients: glasses to hear better?

    PubMed

    Jacquin-Courtois, S; Rode, G; Pavani, F; O'Shea, J; Giard, M H; Boisson, D; Rossetti, Y

    2010-03-01

    Unilateral neglect is a disabling syndrome frequently observed following right hemisphere brain damage. Symptoms range from visuo-motor impairments through to deficient visuo-spatial imagery, but impairment can also affect the auditory modality. A short period of adaptation to a rightward prismatic shift of the visual field is known to improve a wide range of hemispatial neglect symptoms, including visuo-manual tasks, mental imagery, postural imbalance, visuo-verbal measures and number bisection. The aim of the present study was to assess whether the beneficial effects of prism adaptation may generalize to auditory manifestations of neglect. Auditory extinction, whose clinical manifestations are independent of the sensory modalities engaged in visuo-manual adaptation, was examined in neglect patients before and after prism adaptation. Two separate groups of neglect patients (all of whom exhibited left auditory extinction) underwent prism adaptation: one group (n = 6) received a classical prism treatment ('Prism' group), the other group (n = 6) was submitted to the same procedure, but wore neutral glasses creating no optical shift (placebo 'Control' group). Auditory extinction was assessed by means of a dichotic listening task performed three times: prior to prism exposure (pre-test), upon prism removal (0 h post-test) and 2 h later (2 h post-test). The total number of correct responses, the lateralization index (detection asymmetry between the two ears) and the number of left-right fusion errors were analysed. Our results demonstrate that prism adaptation can improve left auditory extinction, thus revealing transfer of benefit to a sensory modality that is orthogonal to the visual, proprioceptive and motor modalities directly implicated in the visuo-motor adaptive process. The observed benefit was specific to the detection asymmetry between the two ears and did not affect the total number of responses. This indicates a specific effect of prism adaptation on lateralized processes rather than on general arousal. Our results suggest that the effects of prism adaptation can extend to unexposed sensory systems. The bottom-up approach of visuo-motor adaptation appears to interact with higher order brain functions related to multisensory integration and can have beneficial effects on sensory processing in different modalities. These findings should stimulate the development of therapeutic approaches aimed at bypassing the affected sensory processing modality by adapting other sensory modalities.

  2. CD98 at the crossroads of adaptive immunity and cancer

    PubMed Central

    Cantor, Joseph M.; Ginsberg, Mark H.

    2012-01-01

    Adaptive immunity, a vertebrate specialization, adds memory and exquisite specificity to the basic innate immune responses present in invertebrates while conserving metabolic resources. In adaptive immunity, antigenic challenge requires extremely rapid proliferation of rare antigen-specific lymphocytes to produce large, clonally expanded effector populations that neutralize pathogens. Rapid proliferation and resulting clonal expansion are dependent on CD98, a protein whose well-conserved orthologs appear restricted to vertebrates. Thus, CD98 supports lymphocyte clonal expansion to enable protective adaptive immunity, an advantage that could account for the presence of CD98 in vertebrates. CD98 supports lymphocyte clonal expansion by amplifying integrin signals that enable proliferation and prevent apoptosis. These integrin-dependent signals can also provoke cancer development and invasion, anchorage-independence and the rapid proliferation of tumor cells. CD98 is highly expressed in many cancers and contributes to formation of tumors in experimental models. Strikingly, vertebrates, which possess highly conserved CD98 proteins, CD98-binding integrins and adaptive immunity, also display propensity towards invasive and metastatic tumors. In this Commentary, we review the roles of CD98 in lymphocyte biology and cancer. We suggest that the CD98 amplification of integrin signaling in adaptive immunity provides survival benefits to vertebrates, which, in turn, bear the price of increased susceptibility to cancer. PMID:22499670

  3. Adaptation of global land use and management intensity to changes in climate and atmospheric carbon dioxide.

    PubMed

    Alexander, Peter; Rabin, Sam; Anthoni, Peter; Henry, Roslyn; Pugh, Thomas A M; Rounsevell, Mark D A; Arneth, Almut

    2018-02-27

    Land use contributes to environmental change, but is also influenced by such changes. Climate and atmospheric carbon dioxide (CO 2 ) levels' changes alter agricultural crop productivity, plant water requirements and irrigation water availability. The global food system needs to respond and adapt to these changes, for example, by altering agricultural practices, including the crop types or intensity of management, or shifting cultivated areas within and between countries. As impacts and associated adaptation responses are spatially specific, understanding the land use adaptation to environmental changes requires crop productivity representations that capture spatial variations. The impact of variation in management practices, including fertiliser and irrigation rates, also needs to be considered. To date, models of global land use have selected agricultural expansion or intensification levels using relatively aggregate spatial representations, typically at a regional level, that are not able to characterise the details of these spatially differentiated responses. Here, we show results from a novel global modelling approach using more detailed biophysically derived yield responses to inputs with greater spatial specificity than previously possible. The approach couples a dynamic global vegetative model (LPJ-GUESS) with a new land use and food system model (PLUMv2), with results benchmarked against historical land use change from 1970. Land use outcomes to 2100 were explored, suggesting that increased intensity of climate forcing reduces the inputs required for food production, due to the fertilisation and enhanced water use efficiency effects of elevated atmospheric CO 2 concentrations, but requiring substantial shifts in the global and local patterns of production. The results suggest that adaptation in the global agriculture and food system has substantial capacity to diminish the negative impacts and gain greater benefits from positive outcomes of climate change. Consequently, agricultural expansion and intensification may be lower than found in previous studies where spatial details and processes consideration were more constrained. © 2018 The Authors. Global Change Biology Published by John Wiley & Sons Ltd.

  4. Adaptor Identity Modulates Adaptation Effects in Familiar Face Identification and Their Neural Correlates

    PubMed Central

    Walther, Christian; Schweinberger, Stefan R.; Kovács, Gyula

    2013-01-01

    Adaptation-related aftereffects (AEs) show how face perception can be altered by recent perceptual experiences. Along with contrastive behavioural biases, modulations of the early event-related potentials (ERPs) were typically reported on categorical levels. Nevertheless, the role of the adaptor stimulus per se for face identity-specific AEs is not completely understood and was therefore investigated in the present study. Participants were adapted to faces (S1s) varying systematically on a morphing continuum between pairs of famous identities (identities A and B), or to Fourier phase-randomized faces, and had to match the subsequently presented ambiguous faces (S2s; 50/50% identity A/B) to one of the respective original faces. We found that S1s identical with or near to the original identities led to strong contrastive biases with more identity B responses following A adaptation and vice versa. In addition, the closer S1s were to the 50/50% S2 on the morphing continuum, the smaller the magnitude of the AE was. The relation between S1s and AE was, however, not linear. Additionally, stronger AEs were accompanied by faster reaction times. Analyses of the simultaneously recorded ERPs revealed categorical adaptation effects starting at 100 ms post-stimulus onset, that were most pronounced at around 125–240 ms for occipito-temporal sites over both hemispheres. S1-specific amplitude modulations were found at around 300–400 ms. Response-specific analyses of ERPs showed reduced voltages starting at around 125 ms when the S1 biased perception in a contrastive way as compared to when it did not. Our results suggest that face identity AEs do not only depend on physical differences between S1 and S2, but also on perceptual factors, such as the ambiguity of S1. Furthermore, short-term plasticity of face identity processing might work in parallel to object-category processing, and is reflected in the first 400 ms of the ERP. PMID:23990908

  5. The genomic landscape of rapid repeated evolutionary ...

    EPA Pesticide Factsheets

    Atlantic killifish populations have rapidly adapted to normally lethal levels of pollution in four urban estuaries. Through analysis of 384 whole killifish genome sequences and comparative transcriptomics in four pairs of sensitive and tolerant populations, we identify the aryl hydrocarbon receptor–based signaling pathway as a shared target of selection. This suggests evolutionary constraint on adaptive solutions to complex toxicant mixtures at each site. However, distinct molecular variants apparently contribute to adaptive pathway modification among tolerant populations. Selection also targets other toxicity-mediatinggenes and genes of connected signaling pathways; this indicates complex tolerance phenotypes and potentially compensatory adaptations. Molecular changes are consistent with selection on standing genetic variation. In killifish, high nucleotide diversityhas likely been a crucial substrate for selective sweeps to propel rapid adaptation. This manuscript describes genomic evaluations that contribute to our understanding of the ecological and evolutionary risks associated with chronic contaminant exposures to wildlife populations. Here, we assessed genetic patterns associated with long-term response to an important class of highly toxic environmental pollutants. Specifically, chemical-specific tolerance has rapidly and repeatedly evolved in an estuarine fish species resident to estuaries of the Atlantic U.S. coast. We used laboratory studies to ch

  6. Recent Developments in Copper and Zinc Homeostasis in Bacterial Pathogens

    PubMed Central

    Braymer, Joseph J.; Giedroc, David P.

    2014-01-01

    Copper and zinc homeostasis systems in pathogenic bacteria are required to resist host efforts to manipulate the availability and toxicity of these metal ions. Central to this microbial adaptive response is the involvement of metal-trafficking and -sensing proteins that ultimately exercise control of metal speciation in the cell. Cu- and Zn-specific metalloregulatory proteins regulate the transcription of metal-responsive genes while metallochaperones and related proteins ensure that these metals are appropriately buffered by the intracellular milieu and delivered to correct intracellular targets. In this review, we summarize recent findings on how bacterial pathogens mount a metal-specific response to derail host efforts to win the “fight over metals.” PMID:24463765

  7. Transcriptome Analysis in Tardigrade Species Reveals Specific Molecular Pathways for Stress Adaptations

    PubMed Central

    Förster, Frank; Beisser, Daniela; Grohme, Markus A.; Liang, Chunguang; Mali, Brahim; Siegl, Alexander Matthias; Engelmann, Julia C.; Shkumatov, Alexander V.; Schokraie, Elham; Müller, Tobias; Schnölzer, Martina; Schill, Ralph O.; Frohme, Marcus; Dandekar, Thomas

    2012-01-01

    Tardigrades have unique stress-adaptations that allow them to survive extremes of cold, heat, radiation and vacuum. To study this, encoded protein clusters and pathways from an ongoing transcriptome study on the tardigrade Milnesium tardigradum were analyzed using bioinformatics tools and compared to expressed sequence tags (ESTs) from Hypsibius dujardini, revealing major pathways involved in resistance against extreme environmental conditions. ESTs are available on the Tardigrade Workbench along with software and databank updates. Our analysis reveals that RNA stability motifs for M. tardigradum are different from typical motifs known from higher animals. M. tardigradum and H. dujardini protein clusters and conserved domains imply metabolic storage pathways for glycogen, glycolipids and specific secondary metabolism as well as stress response pathways (including heat shock proteins, bmh2, and specific repair pathways). Redox-, DNA-, stress- and protein protection pathways complement specific repair capabilities to achieve the strong robustness of M. tardigradum. These pathways are partly conserved in other animals and their manipulation could boost stress adaptation even in human cells. However, the unique combination of resistance and repair pathways make tardigrades and M. tardigradum in particular so highly stress resistant. PMID:22563243

  8. Theory, methods and tools for determining environmental flows for riparian vegetation: Riparian vegetation-flow response guilds

    USGS Publications Warehouse

    Merritt, D.M.; Scott, M.L.; Leroy, Poff N.; Auble, G.T.; Lytle, D.A.

    2010-01-01

    Riparian vegetation composition, structure and abundance are governed to a large degree by river flow regime and flow-mediated fluvial processes. Streamflow regime exerts selective pressures on riparian vegetation, resulting in adaptations (trait syndromes) to specific flow attributes. Widespread modification of flow regimes by humans has resulted in extensive alteration of riparian vegetation communities. Some of the negative effects of altered flow regimes on vegetation may be reversed by restoring components of the natural flow regime. 2. Models have been developed that quantitatively relate components of the flow regime to attributes of riparian vegetation at the individual, population and community levels. Predictive models range from simple statistical relationships, to more complex stochastic matrix population models and dynamic simulation models. Of the dozens of predictive models reviewed here, most treat one or a few species, have many simplifying assumptions such as stable channel form, and do not specify the time-scale of response. In many cases, these models are very effective in developing alternative streamflow management plans for specific river reaches or segments but are not directly transferable to other rivers or other regions. 3. A primary goal in riparian ecology is to develop general frameworks for prediction of vegetation response to changing environmental conditions. The development of riparian vegetation-flow response guilds offers a framework for transferring information from rivers where flow standards have been developed to maintain desirable vegetation attributes, to rivers with little or no existing information. 4. We propose to organise riparian plants into non-phylogenetic groupings of species with shared traits that are related to components of hydrologic regime: life history, reproductive strategy, morphology, adaptations to fluvial disturbance and adaptations to water availability. Plants from any river or region may be grouped into these guilds and related to hydrologic attributes of a specific class of river using probabilistic response curves. 5. Probabilistic models based on riparian response guilds enable prediction of the likelihood of change in each of the response guilds given projected changes in flow, and facilitate examination of trade-offs and risks associated with various flow management strategies. Riparian response guilds can be decomposed to the species level for individual projects or used to develop flow management guidelines for regional water management plans. ?? 2009 Published.

  9. Distinct Effects of Monophosphoryl Lipid A, Oligodeoxynucleotide CpG, and Combination Adjuvants on Modulating Innate and Adaptive Immune Responses to Influenza Vaccination.

    PubMed

    Ko, Eun-Ju; Lee, Young-Tae; Lee, Youri; Kim, Ki-Hye; Kang, Sang-Moo

    2017-10-01

    Monophosphoryl lipid A (MPL) and oligodeoxynucleotide CpG are toll-like receptor (TLR) 4 and 9 agonist, respectively. Here, we investigated the effects of MPL, CpG, and combination adjuvants on stimulating in vitro dendritic cells (DCs), in vivo innate and adaptive immune responses, and protective efficacy of influenza vaccination. Combination of MPL and CpG was found to exhibit distinct effects on stimulating DCs in vitro to secrete IL-12p70 and tumor necrosis factor (TNF)-α and proliferate allogeneic CD8 T cells. Prime immunization of mice with inactivated split influenza vaccine in the presence of low dose MPL+CpG adjuvants increased the induction of virus-specific IgG and IgG2a isotype antibodies. MPL and CpG adjuvants contribute to improving the efficacy of prime influenza vaccination against lethal influenza challenge as determined by body weight monitoring, lung function, viral titers, and histology. A combination of MPL and CpG adjuvants was effective in improving vaccine efficacy as well as in reducing inflammatory immune responses locally and in inducing cellular immune responses upon lethal influenza virus challenge. This study demonstrates unique adjuvant effects of MPL, CpG, and combination adjuvants on modulating innate and adaptive immune responses to influenza prime vaccination.

  10. Perceptual Bias and Loudness Change: An Investigation of Memory, Masking, and Psychophysiology

    NASA Astrophysics Data System (ADS)

    Olsen, Kirk N.

    Loudness is a fundamental aspect of human auditory perception that is closely associated with a sound's physical acoustic intensity. The dynamic quality of intensity change is an inherent acoustic feature in real-world listening domains such as speech and music. However, perception of loudness change in response to continuous intensity increases (up-ramps) and decreases (down-ramps) has received relatively little empirical investigation. Overestimation of loudness change in response to up-ramps is said to be linked to an adaptive survival response associated with looming (or approaching) motion in the environment. The hypothesised 'perceptual bias' to looming auditory motion suggests why perceptual overestimation of up-ramps may occur; however it does not offer a causal explanation. It is concluded that post-stimulus judgements of perceived loudness change are significantly affected by a cognitive recency response bias that, until now, has been an artefact of experimental procedure. Perceptual end-level differences caused by duration specific sensory adaptation at peripheral and/or central stages of auditory processing may explain differences in post-stimulus judgements of loudness change. Experiments that investigate human responses to acoustic intensity dynamics, encompassing topics from basic auditory psychophysics (e.g., sensory adaptation) to cognitive-emotional appraisal of increasingly complex stimulus events such as music and auditory warnings, are proposed for future research.

  11. Variation in short-term and long-term responses of photosynthesis and isoprenoid-mediated photoprotection to soil water availability in four Douglas-fir provenances

    PubMed Central

    Junker, Laura Verena; Kleiber, Anita; Jansen, Kirstin; Wildhagen, Henning; Hess, Moritz; Kayler, Zachary; Kammerer, Bernd; Schnitzler, Jörg-Peter; Kreuzwieser, Jürgen; Gessler, Arthur; Ensminger, Ingo

    2017-01-01

    For long-lived forest tree species, the understanding of intraspecific variation among populations and their response to water availability can reveal their ability to cope with and adapt to climate change. Dissipation of excess excitation energy, mediated by photoprotective isoprenoids, is an important defense mechanism against drought and high light when photosynthesis is hampered. We used 50-year-old Douglas-fir trees of four provenances at two common garden experiments to characterize provenance-specific variation in photosynthesis and photoprotective mechanisms mediated by essential and non-essential isoprenoids in response to soil water availability and solar radiation. All provenances revealed uniform photoprotective responses to high solar radiation, including increased de-epoxidation of photoprotective xanthophyll cycle pigments and enhanced emission of volatile monoterpenes. In contrast, we observed differences between provenances in response to drought, where provenances sustaining higher CO2 assimilation rates also revealed increased water-use efficiency, carotenoid-chlorophyll ratios, pools of xanthophyll cycle pigments, β-carotene and stored monoterpenes. Our results demonstrate that local adaptation to contrasting habitats affected chlorophyll-carotenoid ratios, pool sizes of photoprotective xanthophylls, β-carotene, and stored volatile isoprenoids. We conclude that intraspecific variation in isoprenoid-mediated photoprotective mechanisms contributes to the adaptive potential of Douglas-fir provenances to climate change. PMID:28071755

  12. Close Encounters of Lymphoid Cells and Bacteria

    PubMed Central

    Cruz-Adalia, Aranzazu; Veiga, Esteban

    2016-01-01

    During infections, the first reaction of the host against microbial pathogens is carried out by innate immune cells, which recognize conserved structures on pathogens, called pathogen-associated molecular patterns. Afterward, some of these innate cells can phagocytose and destroy the pathogens, secreting cytokines that would modulate the immune response to the challenge. This rapid response is normally followed by the adaptive immunity, more specific and essential for a complete pathogen clearance in many cases. Some innate immune cells, usually named antigen-presenting cells, such as macrophages or dendritic cells, are able to process internalized invaders and present their antigens to lymphocytes, triggering the adaptive immune response. Nevertheless, the traditional boundary of separated roles between innate and adaptive immunity has been blurred by several studies, showing that very specialized populations of lymphocytes (cells of the adaptive immunity) behave similarly to cells of the innate immunity. These “innate-like” lymphocytes include γδ T cells, invariant NKT cells, B-1 cells, mucosal-associated invariant T cells, marginal zone B cells, and innate response activator cells, and together with the newly described innate lymphoid cells are able to rapidly respond to bacterial infections. Strikingly, our recent data suggest that conventional CD4+ T cells, the paradigm of cells of the adaptive immunity, also present innate-like behavior, capturing bacteria in a process called transinfection. Transinfected CD4+ T cells digest internalized bacteria like professional phagocytes and secrete large amounts of proinflammatory cytokines, protecting for further bacterial challenges. In the present review, we will focus on the data showing such innate-like behavior of lymphocytes following bacteria encounter. PMID:27774092

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

    PubMed

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

    2013-10-01

    Pathogenic New World hantaviruses cause severe disease in humans characterized by a vascular leak syndrome, leading to pulmonary oedema and respiratory distress with case fatality rates approaching 40%. Hantaviruses infect microvascular endothelial cells without conspicuous cytopathic effects, indicating that destruction of the endothelium is not a mechanism of disease. In humans, high levels of inflammatory cytokines are present in the lungs of patients that succumb to infection. This, along with other observations, suggests that disease has an immunopathogenic component. Currently the only animal model available to study hantavirus disease is the Syrian hamster, where infection with Andes virus (ANDV), the primary agent of disease in South America, results in disease that closely mimics that seen in humans. Conversely, inoculation of hamsters with a passaged Sin Nombre virus (SNV), the virus responsible for most cases of disease in North America, results in persistent infection with high levels of viral replication. We found that ANDV elicited a stronger innate immune response, whereas SNV elicited a more robust adaptive response in the lung. Additionally, ANDV infection resulted in significant changes in the blood lymphocyte populations. To determine whether the adaptive immune response influences infection outcome, we depleted hamsters of CD4(+) and CD8(+) T cells before infection with hantaviruses. Depletion resulted in inhibition of virus-specific antibody responses, although the pathogenesis and replication of these viruses were unaltered. These data show that neither hantavirus replication, nor pathogenesis caused by these viruses, is influenced by the adaptive immune response in the Syrian hamster. Published 2013. This article is a U.S. Government work and is in the public domain in the USA.

  14. Adaptive and Innate Immune Responsiveness to Borrelia burgdorferi sensu lato in Exposed Asymptomatic Children and Children with Previous Clinical Lyme Borreliosis

    PubMed Central

    Skogman, Barbro H.; Hellberg, Sandra; Ekerfelt, Christina; Jenmalm, Maria C.; Forsberg, Pia; Ludvigsson, Johnny; Bergström, Sven; Ernerudh, Jan

    2012-01-01

    Why some individuals develop clinical manifestations in Lyme borreliosis (LB) while others remain asymptomatic is largely unknown. Therefore, we wanted to investigate adaptive and innate immune responsiveness to Borrelia burgdorferi sensu lato in exposed Borrelia-antibody-positive asymptomatic children (n = 20), children with previous clinical LB (n = 24), and controls (n = 20). Blood samples were analyzed for Borrelia-specific interferon (IFN)-γ, interleukin (IL)-4, and IL-17 secretion by ELISPOT and Borrelia-induced IL-1β, IL-6, IL-10, IL-12(p70), and tumor necrosis factor (TNF) secretion by Luminex. We found no significant differences in cytokine secretion between groups, but a tendency towards an increased spontaneous secretion of IL-6 was found among children with previous clinical LB. In conclusion, the adaptive or innate immune responsiveness to Borrelia burgdorferi sensu lato was similar in Borrelia-exposed asymptomatic children and children with previous clinical LB. Thus, the immunological mechanisms of importance for eradicating the spirochete effectively without developing clinical manifestations of LB remain unknown. PMID:22190976

  15. Immunology.

    PubMed

    Toskala, Elina

    2014-09-01

    Knowledge of our immune system functions is critical for understanding allergic airway disease development as well as for selection of appropriate diagnostic and therapeutic options for patients with respiratory allergies. This review explains the current understanding of the basic immunology of the upper airways and the pathophysiology of allergic responses, including the mechanisms behind allergic rhinitis. The immune system can be divided to 2 main defense systems that function differently-innate immunity and adaptive immunity. Innate immunity includes several defensive mechanisms such as anatomic or physical barriers, physiological barriers, phagocytosis, and inflammation. The adaptive immune response is activated in an antigen-specific way to provide for the elimination of antigen and induce lasting protection. Hypersensitivity reactions occur when an exaggerated adaptive immune response is activated. Allergic rhinitis is an example of a type I, immunoglobulin E, mediated hypersensitivity reaction. Today we have several immunomodulatory treatment options for patients with allergic airway diseases, such as subcutaneous and sublingual immunotherapy. An understanding of the basics of our immune system and its method of functions is key for using these therapies appropriately. © 2014 ARS-AAOA, LLC.

  16. Modulation of Dendritic Cell Innate and Adaptive Immune Functions by Oral and Sublingual Immunotherapy

    PubMed Central

    Frischmeyer-Guerrerio, Pamela A.; Keet, Corinne A.; Guerrerio, Anthony L.; Chichester, Kristin L.; Bieneman, Anja P.; Hamilton, Robert G.; Wood, Robert A.; Schroeder, John T.

    2014-01-01

    Sublingual (SLIT) and oral immunotherapy (OIT) are promising treatments for food allergy, but underlying mechanisms are poorly understood. Dendritic cells (DC) induce and maintain Th2-type allergen-specific T cells, and also regulate innate immunity through their expression of Toll-like receptors (TLRs). We examined how SLIT and OIT influenced DC innate and adaptive immune responses in children with IgE-mediated cow's milk (CM) allergy. SLIT, but not OIT, decreased TLR-induced IL-6 secretion by myeloid DCs (mDCs). SLIT and OIT altered mDC IL-10 secretion, a potent inhibitor of FcεRI-dependent pro-inflammatory responses. OIT uniquely augmented IFN-α and decreased IL-6 secretion by plasmacytoid DCs (pDCs), which was associated with reduced TLR-induced IL-13 release in pDC-T cell co-cultures. Both SLIT and OIT decreased Th2 cytokine secretion to CM in pDC-T, but not mDC-T, co-cultures. Therefore, SLIT and OIT exert unique effects on DC-driven innate and adaptive immune responses, which may inhibit allergic inflammation and promote tolerance. PMID:25173802

  17. Evaluating Cognitive Action Control Using Eye-Movement Analysis: An Oculomotor Adaptation of the Simon Task.

    PubMed

    Duprez, Joan; Houvenaghel, Jean-François; Naudet, Florian; Dondaine, Thibaut; Auffret, Manon; Robert, Gabriel; Drapier, Dominique; Argaud, Soizic; Vérin, Marc; Sauleau, Paul

    2016-01-01

    Cognitive action control has been extensively studied using conflict tasks such as the Simon task. In most recent studies, this process has been investigated in the light of the dual route hypothesis and more specifically of the activation-suppression model using distributional analyses. Some authors have suggested that cognitive action control assessment is not specific to response modes. In this study we adapted the Simon task, using oculomotor responses instead of manual responses, in order to evaluate whether the resolution of conflict induced by a two-dimensional stimulus yielded similar results to what is usually reported in tasks with manual responses. Results obtained from 43 young healthy participants revealed the typical congruence effect, with longer reaction times (RT) and lesser accuracy in the incongruent condition. Conditional accuracy functions (CAF) also revealed a higher proportion of fast errors in the incongruent condition and delta plots confirmed that conflict resolution was easier, as the time taken to respond increased. These results are very similar to what has been reported in the literature. Furthermore, our observations are in line with the assumptions of the activation-suppression model, in which automatic activation in conflict situations is captured in the fastest responses and selective inhibition of cognitive action control needs time to build up. Altogether, our results suggest that conflict resolution has core mechanisms whatever the response mode, manual or oculomotor. Using oculomotor responses in such tasks could be of interest when investigating cognitive action control in patients with severe motor disorders.

  18. Gene regulation network behind drought escape, avoidance and tolerance strategies in black poplar (Populus nigra L.).

    PubMed

    Yıldırım, Kubilay; Kaya, Zeki

    2017-06-01

    Drought is the major environmental problem limiting the productivity and survival of plant species. Here, previously identified three black poplar genotypes having contrasting response to drought were subjected to gradual soil water depletion in a pot trial to identify their physiological, morphological and antioxidation related adaptations. We also performed a microarray based transcriptome analyses on the leaves of genotypes by using Affymetrix poplar Genome Array containing 56,000 transcripts. Phenotypic analyses of each genotype confirmed their differential adaptations to drought that could be classified as drought escape, avoidance and tolerance. Comparative transcriptomic analysis indicated highly divergent gene expression patterns among the genotypes in response to drought and post drought re-watering (PDR). We identified 10641, 3824 and 9411 transcripts exclusively regulated in drought escape, avoidance and tolerant genotypes, respectively. The key genes involved in metabolic pathways, such as carbohydrate metabolism, photosynthesis, lipid metabolism, generation of precursor metabolites/energy, protein folding, redox homeostasis, secondary metabolic process and cell wall component biogenesis, were affected by drought stresses in the leaves of these genotypes. Transcript isoforms showed increased expression specificity in the genes coding for bark storage proteins and small heat shock proteins in drought tolerant genotype. On the other hand, drought-avoiding genotype specifically induced the transcripts annotated to the genes functional in secondary metabolite production that linked to enhanced leaf water content and growth performance under drought stress. Transcriptome profiling of drought escape genotype indicated specific regulation of the genes functional in programmed cell death and leaf senescence. Specific upregulation of GTP cyclohydrolase II and transcription factors (WRKY and ERFs) in only this genotype were associated to ROS dependent signalling pathways and gene regulation network responsible in induction of many degrading enzymes acting on cell wall carbohydrates, fatty acids and proteins under drought stress. Our findings provide new insights into the transcriptome dynamics and components of regulatory network associated with drought adaptation strategies. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  19. Overcoming scepticism: Interacting influences of geographical location on perceived climate change adaptation measures to water resources in Spain

    NASA Astrophysics Data System (ADS)

    Iglesias, Ana; Garrote, Luis; Bardaji, Isabel; Iglesias, Pedro; Granados, Alfredo

    2016-04-01

    Though many climate adaptation efforts attempt to be defined with the participation of local communities, these strategies may be ineffective because among citizens affected equally, a local risk perception rather than scientific understanding largely drives adaptation choices. Further, the geographical location may polarize climate risk perceptions, making some adaptation efforts ineffective among sceptics. This study examines how the local degradation of the environment and water resources relates to adaption choices and in turn, climate change risk perception among a range of citizens in the Tagus basin, Spain (n = 300). We find respondents of less degraded areas have individualistic responses, and are significantly less likely to accept adaptation strategies than respondents in water stressed communities. The interaction between climate knowledge and adaptation choices is positively related to acceptance of adaptation choices in both groups, and had a stronger positive relationship among individualists. There is no statistical difference in acceptance of adaptation between individualists and communitarians at high levels of knowledge (top decile). Thus, education efforts specific to climate change may counteract divisions based geographical location and environmental stress.

  20. Mechanisms of Antibiotic Resistance

    PubMed Central

    Munita, Jose M.; Arias, Cesar A.

    2015-01-01

    Emergence of resistance among the most important bacterial pathogens is recognized as a major public health threat affecting humans worldwide. Multidrug-resistant organisms have emerged not only in the hospital environment but are now often identified in community settings, suggesting that reservoirs of antibiotic-resistant bacteria are present outside the hospital. The bacterial response to the antibiotic “attack” is the prime example of bacterial adaptation and the pinnacle of evolution. “Survival of the fittest” is a consequence of an immense genetic plasticity of bacterial pathogens that trigger specific responses that result in mutational adaptations, acquisition of genetic material or alteration of gene expression producing resistance to virtually all antibiotics currently available in clinical practice. Therefore, understanding the biochemical and genetic basis of resistance is of paramount importance to design strategies to curtail the emergence and spread of resistance and devise innovative therapeutic approaches against multidrug-resistant organisms. In this chapter, we will describe in detail the major mechanisms of antibiotic resistance encountered in clinical practice providing specific examples in relevant bacterial pathogens. PMID:27227291

  1. Operant Conditioning of Primate Prefrontal Neurons

    PubMed Central

    Schultz, Wolfram; Sakagami, Masamichi

    2010-01-01

    An operant is a behavioral act that has an impact on the environment to produce an outcome, constituting an important component of voluntary behavior. Because the environment can be volatile, the same action may cause different consequences. Thus to obtain an optimal outcome, it is crucial to detect action–outcome relationships and adapt the behavior accordingly. Although prefrontal neurons are known to change activity depending on expected reward, it remains unknown whether prefrontal activity contributes to obtaining reward. We investigated this issue by setting variable relationships between levels of single-neuron activity and rewarding outcomes. Lateral prefrontal neurons changed their spiking activity according to the specific requirements for gaining reward, without the animals making a motor response. Thus spiking activity constituted an operant response. Data from a control task suggested that these changes were unlikely to reflect simple reward predictions. These data demonstrate a remarkable capacity of prefrontal neurons to adapt to specific operant requirements at the single-neuron level. PMID:20107129

  2. Time-Varying, Multi-Scale Adaptive System Reliability Analysis of Lifeline Infrastructure Networks

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Gearhart, Jared Lee; Kurtz, Nolan Scot

    2014-09-01

    The majority of current societal and economic needs world-wide are met by the existing networked, civil infrastructure. Because the cost of managing such infrastructure is high and increases with time, risk-informed decision making is essential for those with management responsibilities for these systems. To address such concerns, a methodology that accounts for new information, deterioration, component models, component importance, group importance, network reliability, hierarchical structure organization, and efficiency concerns has been developed. This methodology analyzes the use of new information through the lens of adaptive Importance Sampling for structural reliability problems. Deterioration, multi-scale bridge models, and time-variant component importance aremore » investigated for a specific network. Furthermore, both bridge and pipeline networks are studied for group and component importance, as well as for hierarchical structures in the context of specific networks. Efficiency is the primary driver throughout this study. With this risk-informed approach, those responsible for management can address deteriorating infrastructure networks in an organized manner.« less

  3. Grizzly bears exhibit augmented insulin sensitivity while obese prior to a reversible insulin resistance during hibernation.

    PubMed

    Nelson, O Lynne; Jansen, Heiko T; Galbreath, Elizabeth; Morgenstern, Kurt; Gehring, Jamie Lauren; Rigano, Kimberly Scott; Lee, Jae; Gong, Jianhua; Shaywitz, Adam J; Vella, Chantal A; Robbins, Charles T; Corbit, Kevin C

    2014-08-05

    The confluence of obesity and diabetes as a worldwide epidemic necessitates the discovery of new therapies. Success in this endeavor requires translatable preclinical studies, which traditionally employ rodent models. As an alternative approach, we explored hibernation where obesity is a natural adaptation to survive months of fasting. Here we report that grizzly bears exhibit seasonal tripartite insulin responsiveness such that obese animals augment insulin sensitivity but only weeks later enter hibernation-specific insulin resistance (IR) and subsequently reinitiate responsiveness upon awakening. Preparation for hibernation is characterized by adiposity coupled to increased insulin sensitivity via modified PTEN/AKT signaling specifically in adipose tissue, suggesting a state of "healthy" obesity analogous to humans with PTEN haploinsufficiency. Collectively, we show that bears reversibly cope with homeostatic perturbations considered detrimental to humans and describe a mechanism whereby IR functions not as a late-stage metabolic adaptation to obesity, but rather a gatekeeper of the fed-fasting transition. Copyright © 2014 Elsevier Inc. All rights reserved.

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

    PubMed Central

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

    2017-01-01

    Objective To identify a causal mechanism responsible for the enhancement of insulin resistance and hyperglycaemia following periodontitis in mice fed a fat-enriched diet. Design We set-up a unique animal model of periodontitis in C57Bl/6 female mice by infecting the periodontal tissue with specific and alive pathogens like Porphyromonas gingivalis (Pg), Fusobacterium nucleatum and Prevotella intermedia. The mice were then fed with a diabetogenic/non-obesogenic fat-enriched diet for up to 3 months. Alveolar bone loss, periodontal microbiota dysbiosis and features of glucose metabolism were quantified. Eventually, adoptive transfer of cervical (regional) and systemic immune cells was performed to demonstrate the causal role of the cervical immune system. Results Periodontitis induced a periodontal microbiota dysbiosis without mainly affecting gut microbiota. The disease concomitantly impacted on the regional and systemic immune response impairing glucose metabolism. The transfer of cervical lymph-node cells from infected mice to naive recipients guarded against periodontitis-aggravated metabolic disease. A treatment with inactivated Pg prior to the periodontal infection induced specific antibodies against Pg and protected the mouse from periodontitis-induced dysmetabolism. Finally, a 1-month subcutaneous chronic infusion of low rates of lipopolysaccharides from Pg mimicked the impact of periodontitis on immune and metabolic parameters. Conclusions We identified that insulin resistance in the high-fat fed mouse is enhanced by pathogen-induced periodontitis. This is caused by an adaptive immune response specifically directed against pathogens and associated with a periodontal dysbiosis. PMID:26838600

  5. Genomic and Transcriptomic Analysis of Growth-Supporting Dehalogenation of Chlorinated Methanes in Methylobacterium

    PubMed Central

    Chaignaud, Pauline; Maucourt, Bruno; Weiman, Marion; Alberti, Adriana; Kolb, Steffen; Cruveiller, Stéphane; Vuilleumier, Stéphane; Bringel, Françoise

    2017-01-01

    Bacterial adaptation to growth with toxic halogenated chemicals was explored in the context of methylotrophic metabolism of Methylobacterium extorquens, by comparing strains CM4 and DM4, which show robust growth with chloromethane and dichloromethane, respectively. Dehalogenation of chlorinated methanes initiates growth-supporting degradation, with intracellular release of protons and chloride ions in both cases. The core, variable and strain-specific genomes of strains CM4 and DM4 were defined by comparison with genomes of non-dechlorinating strains. In terms of gene content, adaptation toward dehalogenation appears limited, strains CM4 and DM4 sharing between 75 and 85% of their genome with other strains of M. extorquens. Transcript abundance in cultures of strain CM4 grown with chloromethane and of strain DM4 grown with dichloromethane was compared to growth with methanol as a reference C1 growth substrate. Previously identified strain-specific dehalogenase-encoding genes were the most transcribed with chlorinated methanes, alongside other genes encoded by genomic islands (GEIs) and plasmids involved in growth with chlorinated compounds as carbon and energy source. None of the 163 genes shared by strains CM4 and DM4 but not by other strains of M. extorquens showed higher transcript abundance in cells grown with chlorinated methanes. Among the several thousand genes of the M. extorquens core genome, 12 genes were only differentially abundant in either strain CM4 or strain DM4. Of these, 2 genes of known function were detected, for the membrane-bound proton translocating pyrophosphatase HppA and the housekeeping molecular chaperone protein DegP. This indicates that the adaptive response common to chloromethane and dichloromethane is limited at the transcriptional level, and involves aspects of the general stress response as well as of a dehalogenation-specific response to intracellular hydrochloric acid production. Core genes only differentially abundant in either strain CM4 or strain DM4 total 13 and 58 CDS, respectively. Taken together, the obtained results suggest different transcriptional responses of chloromethane- and dichloromethane-degrading M. extorquens strains to dehalogenative metabolism, and substrate- and pathway-specific modes of growth optimization with chlorinated methanes. PMID:28919881

  6. Genomic and Transcriptomic Analysis of Growth-Supporting Dehalogenation of Chlorinated Methanes in Methylobacterium.

    PubMed

    Chaignaud, Pauline; Maucourt, Bruno; Weiman, Marion; Alberti, Adriana; Kolb, Steffen; Cruveiller, Stéphane; Vuilleumier, Stéphane; Bringel, Françoise

    2017-01-01

    Bacterial adaptation to growth with toxic halogenated chemicals was explored in the context of methylotrophic metabolism of Methylobacterium extorquens , by comparing strains CM4 and DM4, which show robust growth with chloromethane and dichloromethane, respectively. Dehalogenation of chlorinated methanes initiates growth-supporting degradation, with intracellular release of protons and chloride ions in both cases. The core, variable and strain-specific genomes of strains CM4 and DM4 were defined by comparison with genomes of non-dechlorinating strains. In terms of gene content, adaptation toward dehalogenation appears limited, strains CM4 and DM4 sharing between 75 and 85% of their genome with other strains of M. extorquens . Transcript abundance in cultures of strain CM4 grown with chloromethane and of strain DM4 grown with dichloromethane was compared to growth with methanol as a reference C 1 growth substrate. Previously identified strain-specific dehalogenase-encoding genes were the most transcribed with chlorinated methanes, alongside other genes encoded by genomic islands (GEIs) and plasmids involved in growth with chlorinated compounds as carbon and energy source. None of the 163 genes shared by strains CM4 and DM4 but not by other strains of M. extorquens showed higher transcript abundance in cells grown with chlorinated methanes. Among the several thousand genes of the M. extorquens core genome, 12 genes were only differentially abundant in either strain CM4 or strain DM4. Of these, 2 genes of known function were detected, for the membrane-bound proton translocating pyrophosphatase HppA and the housekeeping molecular chaperone protein DegP. This indicates that the adaptive response common to chloromethane and dichloromethane is limited at the transcriptional level, and involves aspects of the general stress response as well as of a dehalogenation-specific response to intracellular hydrochloric acid production. Core genes only differentially abundant in either strain CM4 or strain DM4 total 13 and 58 CDS, respectively. Taken together, the obtained results suggest different transcriptional responses of chloromethane- and dichloromethane-degrading M. extorquens strains to dehalogenative metabolism, and substrate- and pathway-specific modes of growth optimization with chlorinated methanes.

  7. Innate Immune Cytokines, Fibroblast Phenotypes, and Regulation of Extracellular Matrix in Lung.

    PubMed

    Richards, Carl D

    2017-02-01

    Chronic inflammation can be caused by adaptive immune responses in autoimmune and allergic conditions, driven by a T lymphocyte subset balance (TH1, TH2, Th17, Th22, and/or Treg) and skewed cellular profiles in an antigen-specific manner. However, several chronic inflammatory diseases have no clearly defined adaptive immune mechanisms that drive chronicity. These conditions include those that affect the lung such as nonatopic asthma or idiopathic pulmonary fibrosis comprising significant health problems. The remodeling of extracellular matrix (ECM) causes organ dysfunction, and it is largely generated by fibroblasts as the major cell controlling net ECM. As such, these are potential targets of treatment approaches in the context of ECM pathology. Fibroblast phenotypes contribute to ECM and inflammatory cell accumulation, and they are integrated into chronic disease mechanisms including cancer. Evidence suggests that innate cytokine responses may be critical in nonallergic/nonautoimmune disease, and they enable environmental agent exposure mechanisms that are independent of adaptive immunity. Innate immune cytokines derived from macrophage subsets (M1/M2) and innate lymphoid cell (ILC) subsets can directly regulate fibroblast function. We also suggest that STAT3-activating gp130 cytokines can sensitize fibroblasts to the innate cytokine milieu to drive phenotypes and exacerbate existing adaptive responses. Here, we review evidence exploring innate cytokine regulation of fibroblast behavior.

  8. Antioxidant systems in supporting environmental and programmed adaptations to low temperatures.

    PubMed

    Blagojević, Dusko P

    2007-01-01

    Hetero and endothermic adaptive responses arising as a result of natural responses to environmental cues include antioxidant systems that support adaptations to environmental low temperatures in the broadest sense. These temperatures induce phase changes in energy production and consequently changes in the concentration of reactive oxygen species (ROS). The latter may lead to oxidative stress and the impairment of cellular homeostasis and antioxidant defence systems (ADS) scavenge the ROS so generated. In endotherms the ADS responds to oxidative pressure during acute cold stress conditions, this response is tissue specific and does not extend to prevent other oxidative damage. The early acute phase of cold exposure is accompanied by a significant depletion in redox equivalents. Under such conditions it is questionable if ADS has the capacity to neutralize elevated levels of ROS since there is also an increased energy demand and enhanced ATP consumption. Prolonged exposure to cold leads to ADS adaptation. Hibernators and freeze-tolerant species elevate their ADS before hibernation or freezing in order to prepare for and cope with re-awakening. The involvement of ROS and the role of the ADS in organisms subjected to low temperatures are features intercalated into physiological mechanisms of homestasis. The exact mechanisms for ADS regulation have not been fully defined and are the subject of many ongoing intriguing scientific investigations.

  9. GABAB receptor-mediated, layer-specific synaptic plasticity reorganizes gamma-frequency neocortical response to stimulation

    PubMed Central

    Ainsworth, Matthew; Lee, Shane; Kaiser, Marcus; Simonotto, Jennifer; Kopell, Nancy J.

    2016-01-01

    Repeated presentations of sensory stimuli generate transient gamma-frequency (30–80 Hz) responses in neocortex that show plasticity in a task-dependent manner. Complex relationships between individual neuronal outputs and the mean, local field potential (population activity) accompany these changes, but little is known about the underlying mechanisms responsible. Here we show that transient stimulation of input layer 4 sufficient to generate gamma oscillations induced two different, lamina-specific plastic processes that correlated with lamina-specific changes in responses to further, repeated stimulation: Unit rates and recruitment showed overall enhancement in supragranular layers and suppression in infragranular layers associated with excitatory or inhibitory synaptic potentiation onto principal cells, respectively. Both synaptic processes were critically dependent on activation of GABAB receptors and, together, appeared to temporally segregate the cortical representation. These data suggest that adaptation to repetitive sensory input dramatically alters the spatiotemporal properties of the neocortical response in a manner that may both refine and minimize cortical output simultaneously. PMID:27118845

  10. Functional analysis of HPV-like particle-activated Langerhans cells in vitro.

    PubMed

    Yan, Lisa; Woodham, Andrew W; Da Silva, Diane M; Kast, W Martin

    2015-01-01

    Langerhans cells (LCs) are antigen-presenting cells responsible for initiating an immune response against human papillomaviruses (HPVs) entering the epithelial layer in vivo as they are the first immune cell that HPV comes into contact with. LCs become activated in response to foreign antigens, which causes internal signaling resulting in the increased expression of co-stimulatory molecules and the secretion of inflammatory cytokines. Functionally activated LCs are then capable of migrating to the lymph nodes where they interact with antigen-specific T cells and initiate an adaptive T-cell response in vivo. However, HPV has evolved in a manner that suppresses LC function, and thus the induction of antigen-specific T cells is hindered. While many methods exist to monitor the activity of LCs in vitro, the migration and induction of cytotoxic T cells is ultimately indicative of a functional immune response. Here, methods in analyzing functional migration and induction of antigen-specific T cells after stimulation of LCs with HPV virus-like particles in vitro are described.

  11. GABAB receptor-mediated, layer-specific synaptic plasticity reorganizes gamma-frequency neocortical response to stimulation.

    PubMed

    Ainsworth, Matthew; Lee, Shane; Kaiser, Marcus; Simonotto, Jennifer; Kopell, Nancy J; Whittington, Miles A

    2016-05-10

    Repeated presentations of sensory stimuli generate transient gamma-frequency (30-80 Hz) responses in neocortex that show plasticity in a task-dependent manner. Complex relationships between individual neuronal outputs and the mean, local field potential (population activity) accompany these changes, but little is known about the underlying mechanisms responsible. Here we show that transient stimulation of input layer 4 sufficient to generate gamma oscillations induced two different, lamina-specific plastic processes that correlated with lamina-specific changes in responses to further, repeated stimulation: Unit rates and recruitment showed overall enhancement in supragranular layers and suppression in infragranular layers associated with excitatory or inhibitory synaptic potentiation onto principal cells, respectively. Both synaptic processes were critically dependent on activation of GABAB receptors and, together, appeared to temporally segregate the cortical representation. These data suggest that adaptation to repetitive sensory input dramatically alters the spatiotemporal properties of the neocortical response in a manner that may both refine and minimize cortical output simultaneously.

  12. Control of cognition and adaptive behavior by the GLP/G9a epigenetic suppressor complex

    PubMed Central

    Schaefer, Anne; Sampath, Srihari C.; Intrator, Adam; Min, Alice; Gertler, Tracy S.; Surmeier, D. James; Tarakhovsky, Alexander; Greengard, Paul

    2009-01-01

    SUMMARY The genetic basis of cognition and behavioral adaptation to the environment remains poorly understood. Here we demonstrate that the histone methyltransferase complex GLP/G9a controls cognition and adaptive responses in a region-specific fashion in the adult brain. Using conditional mutagenesis in mice, we show that postnatal, neuron-specific deficiency of GLP/G9a leads to de-repression of numerous non-neuronal and neuron progenitor genes in adult neurons. This transcriptional alteration is associated with complex behavioral abnormalities, including defects in learning, motivation and environmental adaptation. The behavioral changes triggered by GLP/G9a deficiency are similar to key symptoms of the human 9q34 mental retardation syndrome that is associated with structural alterations of the GLP gene. The likely causal role of GLP/G9a in mental retardation in mice and humans suggests a key role for the GLP/G9a controlled histone H3K9 di-methylation in regulation of brain function through maintenance of the transcriptional homeostasis in adult neurons. PMID:20005824

  13. Aneuploidy as a mechanism for stress-induced liver adaptation

    PubMed Central

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

    2012-01-01

    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. PMID:22863619

  14. Dendritic Cell Immune Responses in HIV-1 Controllers.

    PubMed

    Martin-Gayo, Enrique; Yu, Xu G

    2017-02-01

    Robust HIV-1-specific CD8 T cell responses are currently regarded as the main correlate of immune defense in rare individuals who achieve natural, drug-free control of HIV-1; however, the mechanisms that support evolution of such powerful immune responses are not well understood. Dendritic cells (DCs) are specialized innate immune cells critical for immune recognition, immune regulation, and immune induction, but their possible contribution to HIV-1 immune defense in controllers remains ill-defined. Recent studies suggest that myeloid DCs from controllers have improved abilities to recognize HIV-1 through cytoplasmic immune sensors, resulting in more potent, cell-intrinsic type I interferon secretion in response to viral infection. This innate immune response may facilitate DC-mediated induction of highly potent antiviral HIV-1-specific T cells. Moreover, protective HLA class I isotypes restricting HIV-1-specific CD8 T cells may influence DC function through specific interactions with innate myelomonocytic MHC class I receptors from the leukocyte immunoglobulin-like receptor family. Bi-directional interactions between dendritic cells and HIV-1-specific T cells may contribute to natural HIV-1 immune control, highlighting the importance of a fine-tuned interplay between innate and adaptive immune activities for effective antiviral immune defense.

  15. Validation of the Mandarin Chinese version of the Leicester Cough Questionnaire in bronchiectasis.

    PubMed

    Gao, Y-H; Guan, W-J; Xu, G; Gao, Y; Lin, Z-Y; Tang, Y; Lin, Z-M; Li, H-M; Luo, Q; Zhong, N-S; Birring, S S; Chen, R-C

    2014-12-01

    The Leicester Cough Questionnaire (LCQ) has been validated for assessing cough-specific health status in bronchiectasis. We translated the LCQ into Mandarin Chinese and investigated its validity, reliability and responsiveness. The LCQ was translated into Mandarin Chinese using the forward-backward translation procedure. A total of 144 out-patients completed the Mandarin Chinese version of the LCQ (LCQ-MC), the Hospital Anxiety and Depression Scale (HADS) and the St George's Respiratory Questionnaire. Reassessments were performed during exacerbations and at 6 months. Concurrent validation, internal consistency, repeatability and responsiveness were determined. Minor cultural adaptations were made to the wording of LCQ-MC. No other difficulties were found during the translation process, with all items easily adapted to acceptable Mandarin Chinese. The questionnaire was not changed in terms of content layout and the order of the questions. In cognitive debriefing interviews, participants reported that the questionnaire was acceptable, relevant, comprehensive and easy to complete. The LCQ-MC showed good concurrent validity, internal consistency and test-retest reliability. Responsiveness was shown by significant changes in LCQ-MC scores between steady state, the first exacerbation and following 2-week antibiotic treatment (both interval changes, P < 0.01) CONCLUSION: The LCQ-MC is a valid, reliable and responsive instrument for determining cough-specific health status in Chinese bronchiectasis patients.

  16. Large-Scale Phenomics Identifies Primary and Fine-Tuning Roles for CRKs in Responses Related to Oxidative Stress

    PubMed Central

    Rayapuram, Channabasavangowda; Idänheimo, Niina; Hunter, Kerri; Kimura, Sachie; Merilo, Ebe; Vaattovaara, Aleksia; Oracz, Krystyna; Kaufholdt, David; Pallon, Andres; Anggoro, Damar Tri; Glów, Dawid; Lowe, Jennifer; Zhou, Ji; Mohammadi, Omid; Puukko, Tuomas; Albert, Andreas; Lang, Hans; Ernst, Dieter; Kollist, Hannes; Brosché, Mikael; Durner, Jörg; Borst, Jan Willem; Collinge, David B.; Karpiński, Stanisław; Lyngkjær, Michael F.; Robatzek, Silke; Wrzaczek, Michael; Kangasjärvi, Jaakko

    2015-01-01

    Cysteine-rich receptor-like kinases (CRKs) are transmembrane proteins characterized by the presence of two domains of unknown function 26 (DUF26) in their ectodomain. The CRKs form one of the largest groups of receptor-like protein kinases in plants, but their biological functions have so far remained largely uncharacterized. We conducted a large-scale phenotyping approach of a nearly complete crk T-DNA insertion line collection showing that CRKs control important aspects of plant development and stress adaptation in response to biotic and abiotic stimuli in a non-redundant fashion. In particular, the analysis of reactive oxygen species (ROS)-related stress responses, such as regulation of the stomatal aperture, suggests that CRKs participate in ROS/redox signalling and sensing. CRKs play general and fine-tuning roles in the regulation of stomatal closure induced by microbial and abiotic cues. Despite their great number and high similarity, large-scale phenotyping identified specific functions in diverse processes for many CRKs and indicated that CRK2 and CRK5 play predominant roles in growth regulation and stress adaptation, respectively. As a whole, the CRKs contribute to specificity in ROS signalling. Individual CRKs control distinct responses in an antagonistic fashion suggesting future potential for using CRKs in genetic approaches to improve plant performance and stress tolerance. PMID:26197346

  17. Sultr4;1 mutant seeds of Arabidopsis have an enhanced sulphate content and modified proteome suggesting metabolic adaptations to altered sulphate compartmentalization

    PubMed Central

    2010-01-01

    Background Sulphur is an essential macronutrient needed for the synthesis of many cellular components. Sulphur containing amino acids and stress response-related compounds, such as glutathione, are derived from reduction of root-absorbed sulphate. Sulphate distribution in cell compartments necessitates specific transport systems. The low-affinity sulphate transporters SULTR4;1 and SULTR4;2 have been localized to the vacuolar membrane, where they may facilitate sulphate efflux from the vacuole. Results In the present study, we demonstrated that the Sultr4;1 gene is expressed in developing Arabidopsis seeds to a level over 10-fold higher than the Sultr4;2 gene. A characterization of dry mature seeds from a Sultr4;1 T-DNA mutant revealed a higher sulphate content, implying a function for this transporter in developing seeds. A fine dissection of the Sultr4;1 seed proteome identified 29 spots whose abundance varied compared to wild-type. Specific metabolic features characteristic of an adaptive response were revealed, such as an up-accumulation of various proteins involved in sugar metabolism and in detoxification processes. Conclusions This study revealed a role for SULTR4;1 in determining sulphate content of mature Arabidopsis seeds. Moreover, the adaptive response of sultr4;1 mutant seeds as revealed by proteomics suggests a function of SULTR4;1 in redox homeostasis, a mechanism that has to be tightly controlled during development of orthodox seeds. PMID:20426829

  18. Review of Adaptive Programmable Materials and Their Bioapplications.

    PubMed

    Fan, Xiaoshan; Chung, Jing Yang; Lim, Yong Xiang; Li, Zibiao; Loh, Xian Jun

    2016-12-14

    Adaptive programmable materials have attracted increasing attention due to their high functionality, autonomous behavior, encapsulation, and site-specific confinement capabilities in various applications. Compared to conventional materials, adaptive programmable materials possess unique single-material architecture that can maintain, respond, and change their shapes and dimensions when they are subjected to surrounding environment changes, such as alternation in temperature, pH, and ionic strength. In this review, the most-recent advances in the design strategies of adaptive programmable materials are presented with respect to different types of architectural polymers, including stimuli-responsive polymers and shape-memory polymers. The diverse functions of these sophisticated materials and their significance in therapeutic agent delivery systems are also summarized in this review. Finally, the challenges for facile fabrication of these materials and future prospective are also discussed.

  19. Frequency-specific attentional modulation in human primary auditory cortex and midbrain.

    PubMed

    Riecke, Lars; Peters, Judith C; Valente, Giancarlo; Poser, Benedikt A; Kemper, Valentin G; Formisano, Elia; Sorger, Bettina

    2018-07-01

    Paying selective attention to an audio frequency selectively enhances activity within primary auditory cortex (PAC) at the tonotopic site (frequency channel) representing that frequency. Animal PAC neurons achieve this 'frequency-specific attentional spotlight' by adapting their frequency tuning, yet comparable evidence in humans is scarce. Moreover, whether the spotlight operates in human midbrain is unknown. To address these issues, we studied the spectral tuning of frequency channels in human PAC and inferior colliculus (IC), using 7-T functional magnetic resonance imaging (FMRI) and frequency mapping, while participants focused on different frequency-specific sounds. We found that shifts in frequency-specific attention alter the response gain, but not tuning profile, of PAC frequency channels. The gain modulation was strongest in low-frequency channels and varied near-monotonically across the tonotopic axis, giving rise to the attentional spotlight. We observed less prominent, non-tonotopic spatial patterns of attentional modulation in IC. These results indicate that the frequency-specific attentional spotlight in human PAC as measured with FMRI arises primarily from tonotopic gain modulation, rather than adapted frequency tuning. Moreover, frequency-specific attentional modulation of afferent sound processing in human IC seems to be considerably weaker, suggesting that the spotlight diminishes toward this lower-order processing stage. Our study sheds light on how the human auditory pathway adapts to the different demands of selective hearing. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  20. Evaluation of cross-cultural adaptation and measurement properties of breast cancer-specific quality-of-life questionnaires: a systematic review.

    PubMed

    Oliveira, Indiara Soares; da Cunha Menezes Costa, Lucíola; Fagundes, Felipe Ribeiro Cabral; Cabral, Cristina Maria Nunes

    2015-05-01

    To assess the procedures of translation, cross-cultural adaptation, and measurement properties of breast cancer-specific quality-of-life questionnaires. Searches were conducted in the databases MEDLINE, EMBASE, CINAHL, and SciELO using the keywords: "Questionnaires," "Quality of life," and "Breast cancer." The studies were analyzed in terms of methodological quality according to the guidelines for the procedure of cross-cultural adaptation and the quality criteria for measurement properties of questionnaires. We found 24 eligible studies. Most of the articles assessed the translation and measurement properties of the instrument EORTC QLQ-BR23. Description about translation and cross-cultural adaptation was incomplete in 11 studies. Translation and back translation were the most tested phases, and synthesis of the translation was the most omitted phase in the articles. Information on assessing measurement properties was provided incompletely in 23 articles. Internal consistency was the most tested property in all of the eligible articles, but none of them provided information on agreement. Construct validity was adequately tested in only three studies that used the FACT-B and QLQ-BR23. Eight articles provided information on reliability; however, only four found positive classification. Responsiveness was tested in four articles, and ceiling and floor effects were tested in only three articles. None of the instruments showed fully adequate quality. There is limited evidence on cross-cultural adaptations and measurement properties; therefore, it is recommended that caution be exercised when using breast cancer-specific quality-of-life questionnaires that have been translated, adapted, and tested.

  1. Active and passive immunization for cancer.

    PubMed

    Baxter, David

    2014-01-01

    Vaccination started around the 10th century AD as a means of preventing smallpox. By the end of the 19th century such therapeutic vaccines were well established with both active and passive preparations being used in clinical practice. Active immunization involved administering an immunogen that might be live/ attenuated, killed/ inactivated, toxoid or subunit in origin. Passive immunization involved giving pre-formed antibodies, usually to very recently exposed individuals. At about the same time such approaches were also tried to treat a variety of cancers - proof of principle for the protective role of the immune response against malignancy was established by the observation that tumors transplanted into syngeneic hosts were rejected by the host innate and adaptive responses. The impact of these therapeutic vaccination has taken a considerable time to become established - in part because target antigens against which an adaptive response can be directed do not appear to be uniquely expressed on malignant transformed cells; and also because tumor cells are able to manipulate their environment to downregulate the host immune response. Therapeutic cancer vaccines are also divided into active and passive types - the latter being subdivided into specific and non-specific vaccines. Active immunization utilizes an immunogen to generate a host response designed to eliminate the malignant cells, whereas in passive immunization preformed antibodies or cells are administered to directly eliminate the transformed cells - examples of each are considered in this review.

  2. Gene expression profiling of dendritic cells by microarray.

    PubMed

    Foti, Maria; Ricciardi-Castagnoli, Paola; Granucci, Francesca

    2007-01-01

    The immune system of vertebrate animals has evolved to respond to different types of perturbations (invading pathogens, stress signals), limiting self-tissue damage. The decision to activate an immune response is made by antigen-presenting cells (APCs) that are quiescent until they encounter a foreign microorganism or inflammatory stimuli. Early activated APCs trigger innate immune responses that represent the first line of reaction against invading pathogens to limit the infections. At later times, activated APCs acquire the ability to prime antigen-specific immune responses that clear the infections and give rise to memory. During the immune response self-tissue damage is limited and tolerance to self is maintained through life. Among the cells that constitute the immune system, dendritic cells (DC) play a central role. They are extremely versatile APCs involved in the initiation of both innate and adaptive immunity and also in the differentiation of regulatory T cells required for the maintenance of self-tolerance. How DC can mediate these diverse and almost contradictory functions has recently been investigated. The plasticity of these cells allows them to undergo a complete genetic reprogramming in response to external microbial stimuli with the sequential acquisition of different regulatory functions in innate and adaptive immunity. The specific genetic reprogramming DC undergo upon activation can be easily investigated by using microarrays to perform global gene expression analysis in different conditions.

  3. Active and passive immunization for cancer

    PubMed Central

    Baxter, David

    2014-01-01

    Vaccination started around the 10th century AD as a means of preventing smallpox. By the end of the 19th century such therapeutic vaccines were well established with both active and passive preparations being used in clinical practice. Active immunization involved administering an immunogen that might be live/ attenuated, killed/ inactivated, toxoid or subunit in origin. Passive immunization involved giving pre-formed antibodies, usually to very recently exposed individuals. At about the same time such approaches were also tried to treat a variety of cancers – proof of principle for the protective role of the immune response against malignancy was established by the observation that tumors transplanted into syngeneic hosts were rejected by the host innate and adaptive responses. The impact of these therapeutic vaccination has taken a considerable time to become established - in part because target antigens against which an adaptive response can be directed do not appear to be uniquely expressed on malignant transformed cells; and also because tumor cells are able to manipulate their environment to downregulate the host immune response. Therapeutic cancer vaccines are also divided into active and passive types – the latter being subdivided into specific and non-specific vaccines. Active immunization utilizes an immunogen to generate a host response designed to eliminate the malignant cells, whereas in passive immunization preformed antibodies or cells are administered to directly eliminate the transformed cells - examples of each are considered in this review. PMID:25424829

  4. Innate immunity and effector and regulatory mechanisms involved in allergic contact dermatitis.

    PubMed

    Silvestre, Marilene Chaves; Sato, Maria Notomi; Reis, Vitor Manoel Silva Dos

    2018-03-01

    Skin's innate immunity is the initial activator of immune response mechanisms, influencing the development of adaptive immunity. Some contact allergens are detected by Toll-like receptors (TLRs) and inflammasome NLR3. Keratinocytes participate in innate immunity and, in addition to functioning as an anatomical barrier, secrete cytokines, such as TNF, IL-1β, and IL-18, contributing to the development of Allergic Contact Dermatitis. Dendritic cells recognize and process antigenic peptides into T cells. Neutrophils cause pro-inflammatory reactions, mast cells induce migration/maturation of skin DCs, the natural killer cells have natural cytotoxic capacity, the γδ T cells favor contact with hapten during the sensitization phase, and the innate lymphoid cells act in the early stages by secreting cytokines, as well as act in inflammation and tissue homeostasis. The antigen-specific inflammation is mediated by T cells, and each subtype of T cells (Th1/Tc1, Th2/Tc2, and Th17/Tc17) activates resident skin cells, thus contributing to inflammation. Skin's regulatory T cells have a strong ability to inhibit the proliferation of hapten-specific T cells, acting at the end of the Allergic Contact Dermatitis response and in the control of systemic immune responses. In this review, we report how cutaneous innate immunity is the first line of defense and focus its role in the activation of the adaptive immune response, with effector response induction and its regulation.

  5. Growing pains and pleasures: how emotional learning guides development.

    PubMed

    Nelson, Eric E; Lau, Jennifer Y F; Jarcho, Johanna M

    2014-02-01

    The nervous system promotes adaptive responding to myriad environmental stimuli by ascribing emotion to specific stimulus domains. This affects the salience of different stimuli, facilitates learning, and likely involves the amygdala. Recent studies suggest a strong homology between adaptive responses that result from learning and those that emerge during development. As in motivated learning, developmental studies have found the salience of different classes of stimulus (e.g., peers) undergoes marked fluctuation across maturation and may involve differential amygdala engagement. In this review, by highlighting the importance of particular stimulus categories during sensitive periods of development, we suggest that variability in amygdala response to different stimulus domains has an active and functional role in shaping emerging cortical circuits across development. Published by Elsevier Ltd.

  6. Growing Pains and Pleasures: How Emotional Learning Guides Development

    PubMed Central

    Nelson, Eric E.; Lau, Jennifer Y.F.; Jarcho, Johanna M.

    2014-01-01

    SUMMARY The nervous system promotes adaptive responding to myriad environmental stimuli by ascribing emotion to specific stimulus domains. This affects the salience of different stimuli, facilitates learning, and likely involves the amygdala. Recent studies suggest a strong homology between adaptive responses that result from learning and those that emerge during development. As in motivated learning, developmental studies have found the salience of different classes of stimuli (eg peers) undergoes marked fluctuation across maturation and may involve differential amygdala engagement. We suggest that variability in amygdala response to different stimulus domains may play an active and functional role in shaping emerging cortical circuits across development by highlighting the importance of particular stimulus categories during sensitive periods of development. PMID:24405846

  7. Coregulation of host-adapted metabolism and virulence by pathogenic yersiniae

    PubMed Central

    Heroven, Ann Kathrin; Dersch, Petra

    2014-01-01

    Deciphering the principles how pathogenic bacteria adapt their metabolism to a specific host microenvironment is critical for understanding bacterial pathogenesis. The enteric pathogenic Yersinia species Yersinia pseudotuberculosis and Yersinia enterocolitica and the causative agent of plague, Yersinia pestis, are able to survive in a large variety of environmental reservoirs (e.g., soil, plants, insects) as well as warm-blooded animals (e.g., rodents, pigs, humans) with a particular preference for lymphatic tissues. In order to manage rapidly changing environmental conditions and interbacterial competition, Yersinia senses the nutritional composition during the course of an infection by special molecular devices, integrates this information and adapts its metabolism accordingly. In addition, nutrient availability has an impact on expression of virulence genes in response to C-sources, demonstrating a tight link between the pathogenicity of yersiniae and utilization of nutrients. Recent studies revealed that global regulatory factors such as the cAMP receptor protein (Crp) and the carbon storage regulator (Csr) system are part of a large network of transcriptional and posttranscriptional control strategies adjusting metabolic changes and virulence in response to temperature, ion and nutrient availability. Gained knowledge about the specific metabolic requirements and the correlation between metabolic and virulence gene expression that enable efficient host colonization led to the identification of new potential antimicrobial targets. PMID:25368845

  8. Adaptation of the Estuarine Fish, Fundulus heterclitus (Atlantic Killifish) to Polychlorinated Biphenyls (PCBs)

    EPA Science Inventory

    To characterize intra-specific variation in sensitivity to highly toxic pollutants in the non-migratory estuarine Atlantic killifish (Fundulus heteroclitus), we compared early life stage responses to the prototypical dioxin-like compound, 3,3’4,4’,5 hexachlorobiphenyl (PCB126). ...

  9. Future directions in bladder cancer immunotherapy: towards adaptive immunity

    PubMed Central

    Smith, Sean G; Zaharoff, David A

    2016-01-01

    The clinical management of bladder cancer has not changed significantly in several decades. In particular, intravesical bacillus Calmette–Guérin (BCG) immunotherapy has been a mainstay for high-risk nonmuscle invasive bladder cancer since the late 1970s/early 1980s. This is despite the fact that bladder cancer has the highest recurrence rates of any cancer and BCG immunotherapy has not been shown to induce a tumor-specific immune response. We and others have hypothesized that immunotherapies capable of inducing tumor-specific adaptive immunity are needed to impact bladder cancer morbidity and mortality. This article summarizes the preclinical and clinical development of bladder cancer immunotherapies with an emphasis on the last 5 years. Expected progress in the near future is also discussed. PMID:26860539

  10. Future directions in bladder cancer immunotherapy: towards adaptive immunity.

    PubMed

    Smith, Sean G; Zaharoff, David A

    2016-01-01

    The clinical management of bladder cancer has not changed significantly in several decades. In particular, intravesical bacillus Calmette-Guérin (BCG) immunotherapy has been a mainstay for high-risk nonmuscle invasive bladder cancer since the late 1970s/early 1980s. This is despite the fact that bladder cancer has the highest recurrence rates of any cancer and BCG immunotherapy has not been shown to induce a tumor-specific immune response. We and others have hypothesized that immunotherapies capable of inducing tumor-specific adaptive immunity are needed to impact bladder cancer morbidity and mortality. This article summarizes the preclinical and clinical development of bladder cancer immunotherapies with an emphasis on the last 5 years. Expected progress in the near future is also discussed.

  11. Changing appetites: The adaptive advantages of fuel choice

    PubMed Central

    Stanley, Illana A.; Ribeiro, Sofia M.; Giménez-Cassina, Alfredo; Norberg, Erik; Danial, Nika N.

    2013-01-01

    Cells are capable of metabolizing a variety of carbon substrates, including glucose, fatty acids, ketone bodies, and amino acids. Cellular fuel choice not only fulfills specific biosynthetic needs, but also enables programmatic adaptations to stress conditions beyond compensating for changes in nutrient availability. Emerging evidence indicates that specific switches from utilization of one substrate to another can have protective or permissive roles in disease pathogenesis. Understanding the molecular determinants of cellular fuel preference may provide insights into the homeostatic control of stress responses, and unveil therapeutic targets. Here, we highlight overarching themes encompassing cellular fuel choice, its link to cell fate and function, its advantages in stress protection, and its contribution to metabolic dependencies and maladaptations in pathologic conditions. PMID:24018218

  12. CARs in Chronic Lymphocytic Leukemia – Ready to Drive

    PubMed Central

    Wierda, William; Jena, Bipulendu; Cooper, Laurence J. N.; Shpall, Elizabeth

    2013-01-01

    Adoptive transfer of antigen-specific T cells has been adapted by investigators for treatment of chronic lymphocytic leukemia (CLL). To overcome issues of immune tolerance which limits the endogenous adaptive immune response to tumor-associated antigens (TAAs), robust systems for the genetic modification and characterization of T cells expressing chimeric antigen receptors (CARs) to redirect specificity have been produced. Refinements with regards to persistence and trafficking of the genetically modified T cells are underway to help improve potency. Clinical trials utilizing this technology demonstrate feasibility, and increasingly, these early-phase trials are demonstrating impressive anti-tumor effects, particularly for CLL patients, paving the way for multi-center trials to establish the efficacy of CAR+ T cell therapy. PMID:23225251

  13. Brain-wide neuronal dynamics during motor adaptation in zebrafish.

    PubMed

    Ahrens, Misha B; Li, Jennifer M; Orger, Michael B; Robson, Drew N; Schier, Alexander F; Engert, Florian; Portugues, Ruben

    2012-05-09

    A fundamental question in neuroscience is how entire neural circuits generate behaviour and adapt it to changes in sensory feedback. Here we use two-photon calcium imaging to record the activity of large populations of neurons at the cellular level, throughout the brain of larval zebrafish expressing a genetically encoded calcium sensor, while the paralysed animals interact fictively with a virtual environment and rapidly adapt their motor output to changes in visual feedback. We decompose the network dynamics involved in adaptive locomotion into four types of neuronal response properties, and provide anatomical maps of the corresponding sites. A subset of these signals occurred during behavioural adjustments and are candidates for the functional elements that drive motor learning. Lesions to the inferior olive indicate a specific functional role for olivocerebellar circuitry in adaptive locomotion. This study enables the analysis of brain-wide dynamics at single-cell resolution during behaviour.

  14. Brain-wide neuronal dynamics during motor adaptation in zebrafish

    PubMed Central

    Ahrens, Misha B; Li, Jennifer M; Orger, Michael B; Robson, Drew N; Schier, Alexander F; Engert, Florian; Portugues, Ruben

    2013-01-01

    A fundamental question in neuroscience is how entire neural circuits generate behavior and adapt it to changes in sensory feedback. Here we use two-photon calcium imaging to record activity of large populations of neurons at the cellular level throughout the brain of larval zebrafish expressing a genetically-encoded calcium sensor, while the paralyzed animals interact fictively with a virtual environment and rapidly adapt their motor output to changes in visual feedback. We decompose the network dynamics involved in adaptive locomotion into four types of neural response properties, and provide anatomical maps of the corresponding sites. A subset of these signals occurred during behavioral adjustments and are candidates for the functional elements that drive motor learning. Lesions to the inferior olive indicate a specific functional role for olivocerebellar circuitry in adaptive locomotion. This study enables the analysis of brain-wide dynamics at single-cell resolution during behavior. PMID:22622571

  15. Contributions of feature shapes and surface cues to the recognition and neural representation of facial identity.

    PubMed

    Andrews, Timothy J; Baseler, Heidi; Jenkins, Rob; Burton, A Mike; Young, Andrew W

    2016-10-01

    A full understanding of face recognition will involve identifying the visual information that is used to discriminate different identities and how this is represented in the brain. The aim of this study was to explore the importance of shape and surface properties in the recognition and neural representation of familiar faces. We used image morphing techniques to generate hybrid faces that mixed shape properties (more specifically, second order spatial configural information as defined by feature positions in the 2D-image) from one identity and surface properties from a different identity. Behavioural responses showed that recognition and matching of these hybrid faces was primarily based on their surface properties. These behavioural findings contrasted with neural responses recorded using a block design fMRI adaptation paradigm to test the sensitivity of Haxby et al.'s (2000) core face-selective regions in the human brain to the shape or surface properties of the face. The fusiform face area (FFA) and occipital face area (OFA) showed a lower response (adaptation) to repeated images of the same face (same shape, same surface) compared to different faces (different shapes, different surfaces). From the behavioural data indicating the critical contribution of surface properties to the recognition of identity, we predicted that brain regions responsible for familiar face recognition should continue to adapt to faces that vary in shape but not surface properties, but show a release from adaptation to faces that vary in surface properties but not shape. However, we found that the FFA and OFA showed an equivalent release from adaptation to changes in both shape and surface properties. The dissociation between the neural and perceptual responses suggests that, although they may play a role in the process, these core face regions are not solely responsible for the recognition of facial identity. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

    NASA Astrophysics Data System (ADS)

    Sun, Jun; Deem, Michael

    2006-03-01

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

  17. Multiple cone pathways are involved in photic regulation of retinal dopamine.

    PubMed

    Qiao, Sheng-Nan; Zhang, Zhijing; Ribelayga, Christophe P; Zhong, Yong-Mei; Zhang, Dao-Qi

    2016-06-30

    Dopamine is a key neurotransmitter in the retina and plays a central role in the light adaptive processes of the visual system. The sole source of retinal dopamine is dopaminergic amacrine cells (DACs). We and others have previously demonstrated that DACs are activated by rods, cones, and intrinsically photosensitive retinal ganglion cells (ipRGCs) upon illumination. However, it is still not clear how each class of photosensitive cells generates light responses in DACs. We genetically isolated cone function in mice to specifically examine the cone-mediated responses of DACs and their neural pathways. In addition to the reported excitatory input to DACs from light-increment (ON) bipolar cells, we found that cones alternatively signal to DACs via a retrograde signalling pathway from ipRGCs. Cones also produce ON and light-decrement (OFF) inhibitory responses in DACs, which are mediated by other amacrine cells, likely driven by type 1 and type 2/3a OFF bipolar cells, respectively. Dye injections indicated that DACs had similar morphological profiles with or without ON/OFF inhibition. Our data demonstrate that cones utilize specific parallel excitatory and inhibitory circuits to modulate DAC activity and efficiently regulate dopamine release and the light-adaptive state of the retina.

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

    PubMed

    Rentzeperis, Ilias; Nikolaev, Andrey R; Kiper, Daniel C; van Leeuwen, Cees

    2012-01-01

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

  19. Active hexose correlated compound enhances tumor surveillance through regulating both innate and adaptive immune responses.

    PubMed

    Gao, Yunfei; Zhang, Dongqing; Sun, Buxiang; Fujii, Hajime; Kosuna, Ken-Ichi; Yin, Zhinan

    2006-10-01

    Active hexose correlated compound (AHCC) is a mixture of polysaccharides, amino acids, lipids and minerals derived from cocultured mycelia of several species of Basidiomycete mushrooms. AHCC has been implicated to modulate immune functions and plays a protective role against infection. However, the potential role of AHCC in tumor immune surveillance is unknown. In this study, C57BL/6 mice were orally administered AHCC or water, followed by tumor cell inoculation. We showed that compared to pure water-treated mice, AHCC treatment significantly delayed tumor development after inoculation of either melanoma cell line B16F0 or lymphoma cell line EL4. Treatment with AHCC enhanced both Ag-specific activation and proliferation of CD4(+) and CD8(+) T cells, increased the number of tumor Ag-specific CD8(+) T cells, and more importantly, increased the frequency of tumor Ag-specific IFN-gamma producing CD8(+) T cells. Interestingly, AHCC treatment also showed increased cell number of NK and gammadelta T cells, indicating the role of AHCC in activating these innate-like lymphocytes. In summary, our results demonstrate that AHCC can enhance tumor immune surveillance through regulating both innate and adaptive immune responses.

  20. The influence of environmental factors on heart rate chronostructure depending on the individual characteristics of autonomic regulation. Results of long-term medical-ecological studies.

    NASA Astrophysics Data System (ADS)

    Isaeva, Olga; Zenchenko, Tatiana; Breus, Tamara; Chernikova, Anna; Baevsky, Roman

    It was previously shown [Baevsky, Petrov, 1998] that during space flight under influence of geomagnetic disturbances there are both specific response of the autonomic regulation system in the form of vasomotor cardiovascular center activation (LF spectral components) and non-specific stress response, which depends on the actual autonomic balance [Breus, Baevsky, 2002]. Within the project "Mars-500" the parallel medical-ecological studies were conducted in 10 groups (10-16 people), that lived in different regions of the world under the influence of various environmental factors - climatic, geographic, industrial, social and other. It allowed us to obtain a sufficiently large number of variants of adaptive reactions caused by differences in external impacts. The main research method was the heart rate variability (HRV) analysis in short ECG samples (5 minutes) for assessing heart rate chronostructure and functional status of autonomic regulation. Results of studies have demonstrated that environmental loads on the regulatory mechanisms is higher in the northern and north-eastern regions of Russia - Magadan and Syktyvkar. Stress-index of regulatory systems and adaptive risk indicator is significantly higher in these groups [Baevsky, Berseneva, 2013]. The preliminary search of weather factors (atmospheric pressure, air temperature, humidity and magnetic index Kp) influence on the autonomic regulation of heart rate showed that there are no any significant changes and relationships in the entire group of participants. We have assumed that the character of adaptive responses, including responses to changing weather and geomagnetic conditions, is associated with the individual characteristics and the initial functional state of autonomic regulation. To test this hypothesis, we have identified two groups of subjects with different autonomic balance. The first group included individuals with a pronounced predominance of sympathetic regulation (n = 127), the second - with a strong predominance of parasympathetic activity (n = 64). The analysis of correlations between weather and heart rate chronostructure and functional condition of autonomic regulation revealed that attitude of low frequency (LF) and high frequency (HF) of heart rhythm spectrum higher in both groups at declining geomagnetic activity and lower at its growth. The comparison of other HRV indicators at decreasing and increasing geomagnetic activity displayed the opposite trends in these groups. Stress-index of regulatory systems (SI), which reflects the sympathetic activity, rises in group with sympathetic dominance at reducing geomagnetic activity, and at its growth - in group with parasympathetic dominance. So, we can see that specific adaptive reaction as response to changing geomagnetic situation, which manifested in activation of vasomotor cardiovascular center, is the similar in subjects with different autonomic balance. Non-specific component depends on initial dominance of one or another regulatory mechanism.

  1. Correlates of Vaccine-Induced Protection against Mycobacterium tuberculosis Revealed in Comparative Analyses of Lymphocyte Populations

    PubMed Central

    Kurtz, Sherry L.

    2015-01-01

    A critical hindrance to the development of a novel vaccine against Mycobacterium tuberculosis is a lack of understanding of protective correlates of immunity and of host factors involved in a successful adaptive immune response. Studies from our group and others have used a mouse-based in vitro model system to assess correlates of protection. Here, using this coculture system and a panel of whole-cell vaccines with varied efficacy, we developed a comprehensive approach to understand correlates of protection. We compared the gene and protein expression profiles of vaccine-generated immune peripheral blood lymphocytes (PBLs) to the profiles found in immune splenocytes. PBLs not only represent a clinically relevant cell population, but comparing the expression in these populations gave insight into compartmentally specific mechanisms of protection. Additionally, we performed a direct comparison of host responses induced when immune cells were cocultured with either the vaccine strain Mycobacterium bovis BCG or virulent M. tuberculosis. These comparisons revealed host-specific and bacterium-specific factors involved in protection against virulent M. tuberculosis. Most significantly, we identified a set of 13 core molecules induced in the most protective vaccines under all of the conditions tested. Further validation of this panel of mediators as a predictor of vaccine efficacy will facilitate vaccine development, and determining how each promotes adaptive immunity will advance our understanding of antimycobacterial immune responses. PMID:26269537

  2. Dominant-negative TLR5 polymorphism reduces adaptive immune response to flagellin and negatively associates with Crohn's disease.

    PubMed

    Gewirtz, Andrew T; Vijay-Kumar, Matam; Brant, Steven R; Duerr, Richard H; Nicolae, Dan L; Cho, Judy H

    2006-06-01

    Crohn's disease (CD) is associated with elevated adaptive immunity to commensal microbes, with flagellin being a dominant antigen. In light of heightened awareness of the importance of innate immunity in regulating adaptive immunity and ambiguity as to the role of CD-associated immune responses in CD pathophysiology, we sought to determine whether natural acquisition of immune responses to flagellin were regulated by the innate immune flagellin receptor toll-like receptor 5 (TLR5) and determine whether persons carrying a recently defined common dominant-negative TLR5 polymorphism (TLR5-stop) might be protected from developing CD. Carriage rates of a recently defined dominant-negative TLR5 polymorphism (TLR5-stop) and levels of serum immunoreactivity to bacterial products were measured in inflammatory bowel disease patients, first-degree relatives, and unrelated controls. We observed that, in healthy subjects, persons carrying TLR5-stop had significantly lower levels of flagellin-specific IgG and IgA but had similar levels of total and LPS-specific Ig. Moreover, we observed that, among Jewish subjects, the carriage rate of TLR5-stop (in heterozygous state) was significantly less in CD patients, but not ulcerative colitis (UC) patients, compared with unaffected relatives and unrelated controls (5.4, 0.9, 6.0, and 6.5% for unaffected relatives, CD, UC, and unrelated Jewish controls, respectively, n = 296, 215, 185, and 416, respectively; P = 0.037 by likelihood calculation for CD vs. controls), indicating that TLR5-stop can protect persons of Jewish ethnicity against CD. We did not observe a significant association of TLR5-stop with CD in a non-Jewish cohort (11.1, 10.4, and 11.7% for unaffected relatives, CD, and UC, respectively; n = 841, 543, and 300 for unaffected relatives, respectively). These results demonstrate that natural acquisition of immune responses to flagellin are regulated by TLR5 and suggest that immune responses to flagellin are not merely associated with CD but rather promote the pathogenic response.

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

    PubMed Central

    Ibraheem, Omodele; Ndimba, Bongani K.

    2013-01-01

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

  4. Evolutionary adaptations for the temporal processing of natural sounds by the anuran peripheral auditory system.

    PubMed

    Schrode, Katrina M; Bee, Mark A

    2015-03-01

    Sensory systems function most efficiently when processing natural stimuli, such as vocalizations, and it is thought that this reflects evolutionary adaptation. Among the best-described examples of evolutionary adaptation in the auditory system are the frequent matches between spectral tuning in both the peripheral and central auditory systems of anurans (frogs and toads) and the frequency spectra of conspecific calls. Tuning to the temporal properties of conspecific calls is less well established, and in anurans has so far been documented only in the central auditory system. Using auditory-evoked potentials, we asked whether there are species-specific or sex-specific adaptations of the auditory systems of gray treefrogs (Hyla chrysoscelis) and green treefrogs (H. cinerea) to the temporal modulations present in conspecific calls. Modulation rate transfer functions (MRTFs) constructed from auditory steady-state responses revealed that each species was more sensitive than the other to the modulation rates typical of conspecific advertisement calls. In addition, auditory brainstem responses (ABRs) to paired clicks indicated relatively better temporal resolution in green treefrogs, which could represent an adaptation to the faster modulation rates present in the calls of this species. MRTFs and recovery of ABRs to paired clicks were generally similar between the sexes, and we found no evidence that males were more sensitive than females to the temporal modulation patterns characteristic of the aggressive calls used in male-male competition. Together, our results suggest that efficient processing of the temporal properties of behaviorally relevant sounds begins at potentially very early stages of the anuran auditory system that include the periphery. © 2015. Published by The Company of Biologists Ltd.

  5. Stimulation of Dorsolateral Prefrontal Cortex Enhances Adaptive Cognitive Control: A High-Definition Transcranial Direct Current Stimulation Study.

    PubMed

    Gbadeyan, Oyetunde; McMahon, Katie; Steinhauser, Marco; Meinzer, Marcus

    2016-12-14

    Conflict adaptation is a hallmark effect of adaptive cognitive control and refers to the adjustment of control to the level of previously experienced conflict. Conflict monitoring theory assumes that the dorsolateral prefrontal cortex (DLPFC) is causally involved in this adjustment. However, to date, evidence in humans is predominantly correlational, and heterogeneous with respect to the lateralization of control in the DLPFC. We used high-definition transcranial direct current stimulation (HD-tDCS), which allows for more focal current delivery than conventional tDCS, to clarify the causal involvement of the DLPFC in conflict adaptation. Specifically, we investigated the regional specificity and lateralization of potential beneficial stimulation effects on conflict adaptation during a visual flanker task. One hundred twenty healthy participants were assigned to four HD-tDCS conditions: left or right DLPFC or left or right primary motor cortex (M1). Each group underwent both active and sham HD-tDCS in crossover, double-blind designs. We obtained a sizeable conflict adaptation effect (measured as the modulation of the flanker effect as a function of previous response conflict) in all groups and conditions. However, this effect was larger under active HD-tDCS than under sham stimulation in both DLPFC groups. In contrast, active stimulation had no effect on conflict adaptation in the M1 groups. In sum, the present results indicate that the DLPFC plays a causal role in adaptive cognitive control, but that the involvement of DLPFC in control is not restricted to the left or right hemisphere. Moreover, our study confirms the potential of HD-tDCS to modulate cognition in a regionally specific manner. Conflict adaptation is a hallmark effect of adaptive cognitive control. While animal studies have suggested causal involvement of the DLPFC in this phenomenon, such evidence is currently lacking in humans. The present study used high-definition transcranial direct current stimulation (HD-tDCS) to demonstrate that the DLPFC is causally involved in conflict adaptation in humans. Our study confirms a central claim of conflict monitoring theory, which up to now has predominantly relied on correlational studies. Our results further indicate an equal involvement of the left and right DLPFC in adaptive control, whereas stimulation of a control region-the primary motor cortex-had no effect on adaptive control. The study thus confirms the potential of HD-tDCS to modulate cognition in a regionally specific manner. Copyright © 2016 the authors 0270-6474/16/3612530-07$15.00/0.

  6. Responses of alloplasmic (cytoplasm=Triticum timopheevii) and euplasmic wheats (Triticum aestivum) to photoperiod and vernalization.

    PubMed

    Ward, R W; Heyne, E G; Paulsen, G M

    1983-07-01

    Studies were conducted to determine the influence of the male sterility-inducing cytoplasm of Triticum timopheevii (Zhuk.) Zhuk. on response of several common winter wheat (T. aestivum L.) nuclear genotypes to photoperiod and vernalization. Comparative studies of cytoplasmic substitution lines provide information on the role of the cytoplasmic genetic mechanism in growth and development. In the case of cytoplasmic male sterility-based hybrid production systems, ubiquity of sterility-inducing cytoplasm in derived hybrids warrants thorough characterization of its influence on plant phenotype. Factorial combinations of cytoplasm (T. timopheevii and T. aestivum), nuclear genotype, and photoperiod or vernalization treatments were evaluated under hydroponic conditions in controlled environment chambers. Interaction of cytoplasm, photoperiod, and nuclear genotype was significant in one or more experiments for days to anthesis and potential spikelet number, and interaction of cytoplasm, vernalization, and nuclear genotype was significant for days to spike emergence. Long day length was associated with increased percentage seed set in one study, but interactions of photoperiod and cytoplasm were not detected for percentage seed set. Interactions involving cytoplasm and photoperiod or vernalization were interpreted as evidence of the existence of genetic factors in cytoplsam of T. timopheevii which alter photoperiod or vernalization responses of alloplasmic plants relative to responses exhibited by euplasmic plants. Since photoperiod and vernalization responses are critical to adaptation, T. timopheevii cytoplasm can alter adaptability of T. aestivum. The specific effect would be nuclear genotype dependent, and does not appear to be of a magnitude greater than that induced by nuclear genetic variability at loci conditioning photoperiod or vernalization responses or other adaptation-determining characteristics. Normal multilocation/year testing of alloplasmic hybrids should therefore adequately identify zones of adaptation.

  7. A correlation of measles specific antibodies and the number of plasmacytoid dendritic cells is observed after measles vaccination in 9 month old infants

    PubMed Central

    García-León, Miguel L; Bonifaz, Laura C; Espinosa-Torres, Bogart; Hernández-Pérez, Brenda; Cardiel-Marmolejo, Lino; Santos-Preciado, José I; Wong-Chew, Rosa M

    2015-01-01

    Measles virus (MeV) represents one of the main causes of death among young children, particularly in developing countries. Upon infection, MeV controls both interferon induction (IFN) and the interferon signaling pathway which results in a severe host immunosuppression that can persists for up to 6 mo after infection. Despite the global biology of MeV infection is well studied, the role of the plasmacytoid dendritic cells (pDCs) during the host innate immune response after measles vaccination remains largely uncharacterized. Here we investigated the role of pDCs, the major producers of interferon in response to viral infections, in the development of adaptive immune response against MeV vaccine. We report that there is a strong correlation between pDCs population and the humoral immune response to Edmonston Zagreb (EZ) measles vaccination in 9-month-old mexican infants. Five infants were further evaluated after vaccination, showing a clear increase in pDCs at baseline, one week and 3 months after immunization. Three months postvaccination they showed increase in memory T-cells and pDCs populations, high induction of adaptive immunity and also observed a correlation between pDCs number and the humoral immune response. These findings suggest that the development and magnitude of the adaptive immune response following measles immunization is directly dependent on the number of pDCs of the innate immune response. PMID:26075901

  8. Using Instructive Feedback to Increase Response Variability During Intraverbal Training for Children with Autism Spectrum Disorder.

    PubMed

    Carroll, Regina A; Kodak, Tiffany

    2015-10-01

    We evaluated the effects of instructive feedback on the variability of intraverbal responses for two children with autism spectrum disorder. Specifically, we used an adapted alternating treatments design to compare participants' novel responses and response combinations during an intraverbal category program across conditions with and without instructive feedback. During instructive feedback, secondary targets were presented during the consequence event of the learning trial and consisted of a therapist's model of response variability. The results showed that participants engaged in more novel response combinations during instructive feedback conditions. We discussed the clinical implications of these results as well as areas for future research.

  9. Patient-based radiographic exposure factor selection: a systematic review

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ching, William; Robinson, John; McEntee, Mark, E-mail: mark.mcentee@sydney.edu.au

    Digital technology has wider exposure latitude and post-processing algorithms which can mask the evidence of underexposure and overexposure. Underexposure produces noisy, grainy images which can impede diagnosis and overexposure results in a greater radiation dose to the patient. These exposure errors can result from inaccurate adjustment of exposure factors in response to changes in patient thickness. This study aims to identify all published radiographic exposure adaptation systems which have been, or are being, used in general radiography and discuss their applicability to digital systems. Studies in EMBASE, MEDLINE, CINAHL and SCOPUS were systematically reviewed. Some of the search terms usedmore » were exposure adaptation, exposure selection, exposure technique, 25% rule, 15% rule, DuPont™ Bit System and radiography. A manual journal-specific search was also conducted in The Radiographer and Radiologic Technology. Studies were included if they demonstrated a system of altering exposure factors to compensate for variations in patients for general radiography. Studies were excluded if they focused on finding optimal exposures for an ‘average’ patient or focused on the relationship between exposure factors and dose. The database search uncovered 11 articles and the journal-specific search uncovered 13 articles discussing systems of exposure adaptation. They can be categorised as simple one-step guidelines, comprehensive charts and computer programs. Only two papers assessed the efficacy of exposure adjustment systems. No literature compares the efficacy of exposure adaptations system for film/screen radiography with digital radiography technology nor is there literature on a digital specific exposure adaptation system.« less

  10. Response of Korean pine’s functional traits to geography and climate

    PubMed Central

    Dong, Yichen

    2017-01-01

    This study analyzed the characteristics of Korean pine (Pinus koraiensis) functional trait responses to geographic and climatic factors in the eastern region of Northeast China (41°–48°N) and the linear relationships among Korean pine functional traits, to explore this species’ adaptability and ecological regulation strategies under different environmental conditions. Korean pine samples were collected from eight sites located at different latitudes, and the following factors were determined for each site: geographic factors—latitude, longitude, and altitude; temperature factors—mean annual temperature (MAT), growth season mean temperature (GST), and mean temperature of the coldest month (MTCM); and moisture factors—annual precipitation (AP), growth season precipitation (GSP), and potential evapotranspiration (PET). The Korean pine functional traits examined were specific leaf area (SLA), leaf thickness (LT), leaf dry matter content (LDMC), specific root length (SRL), leaf nitrogen content (LNC), leaf phosphorus content (LPC), root nitrogen content (RNC), and root phosphorus content (RPC). The results showed that Korean pine functional traits were significantly correlated to latitude, altitude, GST, MTCM, AP, GSP, and PET. Among the Korean pine functional traits, SLA showed significant linear relationships with LT, LDMC, LNC, LPC, and RPC, and LT showed significant linear relationships with LDMC, SRL, LNC, LPC, RNC, and RPC; the linear relationships between LNC, LPC, RNC, and RPC were also significant. In conclusion, Korean pine functional trait responses to latitude resulted in its adaptation to geographic and climatic factors. The main limiting factors were precipitation and evapotranspiration, followed by altitude, latitude, GST, and MTCM. The impacts of longitude and MAT were not obvious. Changes in precipitation and temperature were most responsible for the close correlation among Korean pine functional traits, reflecting its adaption to habitat variation. PMID:28886053

  11. Rapid transcriptional acclimation following transgenerational exposure of oysters to ocean acidification.

    PubMed

    Goncalves, Priscila; Anderson, Kelli; Thompson, Emma L; Melwani, Aroon; Parker, Laura M; Ross, Pauline M; Raftos, David A

    2016-10-01

    Marine organisms need to adapt in order to cope with the adverse effects of ocean acidification and warming. Transgenerational exposure to CO2 stress has been shown to enhance resilience to ocean acidification in offspring from a number of species. However, the molecular basis underlying such adaptive responses is currently unknown. Here, we compared the transcriptional profiles of two genetically distinct oyster breeding lines following transgenerational exposure to elevated CO2 in order to explore the molecular basis of acclimation or adaptation to ocean acidification in these organisms. The expression of key target genes associated with antioxidant defence, metabolism and the cytoskeleton was assessed in oysters exposed to elevated CO2 over three consecutive generations. This set of target genes was chosen specifically to test whether altered responsiveness of intracellular stress mechanisms contributes to the differential acclimation of oyster populations to climate stressors. Transgenerational exposure to elevated CO2 resulted in changes to both basal and inducible expression of those key target genes (e.g. ecSOD, catalase and peroxiredoxin 6), particularly in oysters derived from the disease-resistant, fast-growing B2 line. Exposure to CO2 stress over consecutive generations produced opposite and less evident effects on transcription in a second population that was derived from wild-type (nonselected) oysters. The analysis of key target genes revealed that the acute responses of oysters to CO2 stress appear to be affected by population-specific genetic and/or phenotypic traits and by the CO2 conditions to which their parents had been exposed. This supports the contention that the capacity for heritable change in response to ocean acidification varies between oyster breeding lines and is mediated by parental conditioning. © 2016 John Wiley & Sons Ltd.

  12. Mutagenic frequencies of site-specifically located O6-methylguanine in wild-type Escherichia coli and in a strain deficient in ada-methyltransferase.

    PubMed

    Rossi, S C; Topal, M D

    1991-02-01

    The adaptive response of Escherichia coli involves protection of the cells against the toxic and mutagenic consequences of exposure to high doses of a methylating agent by prior exposure to low doses of the agent. Ada protein, a major repair activity for O6-methylguanine, is activated to positively control the adaptive response; O6-methylguanine is one of the major mutagenic lesions produced by methylating agents. We investigated the mutation frequency of wild-type Escherichia coli and strains containing the ada-5 mutation in response to site-specifically synthesized O6-methylguanine under conditions in which the adaptive response was not induced. Site-directed mutagenesis and oligonucleotide self-selection techniques were used to isolate the progeny of M13mp18 DNAs constructed to contain O6-methylguanine at any of eight different positions. The progeny were isolated from E. coli strains isogeneic except for deficiency in Ada-methyltransferase repair, UvrABC excision repair, or both. The resulting O6-methylguanine mutation levels at each position were determined by using differential oligonucleotide hybridization. We found that the wild type had up to a 2.6-fold higher mutation frequency than ada-5 mutants. In addition, the mutation frequency varied with the position of the O6-methylguanine in the DNA in the wild type but not in ada-5 mutants; O6-methylguanine lesions at the 5' ends of runs of consecutive guanines gave the highest mutation frequencies. Determination of the mutation frequency of O6-methylguanine in wild-type and mutS cells showed that mismatch repair can affect O6-methylguanine mutation levels.

  13. Response of Korean pine's functional traits to geography and climate.

    PubMed

    Dong, Yichen; Liu, Yanhong

    2017-01-01

    This study analyzed the characteristics of Korean pine (Pinus koraiensis) functional trait responses to geographic and climatic factors in the eastern region of Northeast China (41°-48°N) and the linear relationships among Korean pine functional traits, to explore this species' adaptability and ecological regulation strategies under different environmental conditions. Korean pine samples were collected from eight sites located at different latitudes, and the following factors were determined for each site: geographic factors-latitude, longitude, and altitude; temperature factors-mean annual temperature (MAT), growth season mean temperature (GST), and mean temperature of the coldest month (MTCM); and moisture factors-annual precipitation (AP), growth season precipitation (GSP), and potential evapotranspiration (PET). The Korean pine functional traits examined were specific leaf area (SLA), leaf thickness (LT), leaf dry matter content (LDMC), specific root length (SRL), leaf nitrogen content (LNC), leaf phosphorus content (LPC), root nitrogen content (RNC), and root phosphorus content (RPC). The results showed that Korean pine functional traits were significantly correlated to latitude, altitude, GST, MTCM, AP, GSP, and PET. Among the Korean pine functional traits, SLA showed significant linear relationships with LT, LDMC, LNC, LPC, and RPC, and LT showed significant linear relationships with LDMC, SRL, LNC, LPC, RNC, and RPC; the linear relationships between LNC, LPC, RNC, and RPC were also significant. In conclusion, Korean pine functional trait responses to latitude resulted in its adaptation to geographic and climatic factors. The main limiting factors were precipitation and evapotranspiration, followed by altitude, latitude, GST, and MTCM. The impacts of longitude and MAT were not obvious. Changes in precipitation and temperature were most responsible for the close correlation among Korean pine functional traits, reflecting its adaption to habitat variation.

  14. [Specific features of blood cell composition and structure in fishes from the pelagial and coastal zones of Lake Baikal].

    PubMed

    Iakhnenko, V M; Klimenkov, I V

    2009-01-01

    Differences in the proportions and ultrastructure of peripheral blood cells between the Baikal cisco and roach have been revealed. Both species contain all main cell types involved in the immune response in higher vertebrates. However, cells mediating the innate immune response are represented in the Baikal cisco only by monocytes and pseudogranulocytes, whereas the blood of roach additionally contains true granulocytes. Significantly greater numbers of leukocytes and thrombocytes per unit volume in the roach are evidence for mobilization of the immune system in this species. The peripheral blood of both species contains lymphocytes, which are responsible for adaptive immunity. The content of hemoglobin in erythrocytes is lower in the roach than in the Baikal cisco. The state of blood in the two species may be considered adapted to typical conditions in their habitats.

  15. Yersinia pestis and Yersinia pseudotuberculosis infection: a regulatory RNA perspective

    PubMed Central

    Martínez-Chavarría, Luary C.; Vadyvaloo, Viveka

    2015-01-01

    Yersinia pestis, responsible for causing fulminant plague, has evolved clonally from the enteric pathogen, Y. pseudotuberculosis, which in contrast, causes a relatively benign enteric illness. An ~97% nucleotide identity over 75% of their shared protein coding genes is maintained between these two pathogens, leaving much conjecture regarding the molecular determinants responsible for producing these vastly different disease etiologies, host preferences and transmission routes. One idea is that coordinated production of distinct factors required for host adaptation and virulence in response to specific environmental cues could contribute to the distinct pathogenicity distinguishing these two species. Small non-coding RNAs that direct posttranscriptional regulation have recently been identified as key molecules that may provide such timeous expression of appropriate disease enabling factors. Here the burgeoning field of small non-coding regulatory RNAs in Yersinia pathogenesis is reviewed from the viewpoint of adaptive colonization, virulence and divergent evolution of these pathogens. PMID:26441890

  16. The T Cell Response to Staphylococcus aureus

    PubMed Central

    Bröker, Barbara M.; Mrochen, Daniel; Péton, Vincent

    2016-01-01

    Staphylococcus aureus (S. aureus) is a dangerous pathogen and a leading cause of both nosocomial and community acquired bacterial infection worldwide. However, on the other hand, we are all exposed to this bacterium, often within the first hours of life, and usually manage to establish equilibrium and coexist with it. What does the adaptive immune system contribute toward lifelong control of S. aureus? Will it become possible to raise or enhance protective immune memory by vaccination? While in the past the S. aureus-specific antibody response has dominated this discussion, the research community is now coming to appreciate the role that the cellular arm of adaptive immunity, the T cells, plays. There are numerous T cell subsets, each with differing functions, which together have the ability to orchestrate the immune response to S. aureus and hence to tip the balance between protection and pathology. This review summarizes the state of the art in this dynamic field of research. PMID:26999219

  17. Transcriptomic Analyses Elucidate Adaptive Differences of Closely Related Strains of Pseudomonas aeruginosa in Fuel

    PubMed Central

    Gunasekera, Thusitha S.; Bowen, Loryn L.; Zhou, Carol E.; Howard-Byerly, Susan C.; Foley, William S.; Striebich, Richard C.; Dugan, Larry C.

    2017-01-01

    ABSTRACT Pseudomonas aeruginosa can utilize hydrocarbons, but different strains have various degrees of adaptation despite their highly conserved genome. P. aeruginosa ATCC 33988 is highly adapted to hydrocarbons, while P. aeruginosa strain PAO1, a human pathogen, is less adapted and degrades jet fuel at a lower rate than does ATCC 33988. We investigated fuel-specific transcriptomic differences between these strains in order to ascertain the underlying mechanisms utilized by the adapted strain to proliferate in fuel. During growth in fuel, the genes related to alkane degradation, heat shock response, membrane proteins, efflux pumps, and several novel genes were upregulated in ATCC 33988. Overexpression of alk genes in PAO1 provided some improvement in growth, but it was not as robust as that of ATCC 33988, suggesting the role of other genes in adaptation. Expression of the function unknown gene PA5359 from ATCC 33988 in PAO1 increased the growth in fuel. Bioinformatic analysis revealed that PA5359 is a predicted lipoprotein with a conserved Yx(FWY)xxD motif, which is shared among bacterial adhesins. Overexpression of the putative resistance-nodulation-division (RND) efflux pump PA3521 to PA3523 increased the growth of the ATCC 33988 strain, suggesting a possible role in fuel tolerance. Interestingly, the PAO1 strain cannot utilize n-C8 and n-C10. The expression of green fluorescent protein (GFP) under the control of alkB promoters confirmed that alk gene promoter polymorphism affects the expression of alk genes. Promoter fusion assays further confirmed that the regulation of alk genes was different in the two strains. Protein sequence analysis showed low amino acid differences for many of the upregulated genes, further supporting transcriptional control as the main mechanism for enhanced adaptation. IMPORTANCE These results support that specific signal transduction, gene regulation, and coordination of multiple biological responses are required to improve the survival, growth, and metabolism of fuel in adapted strains. This study provides new insight into the mechanistic differences between strains and helpful information that may be applied in the improvement of bacterial strains for resistance to biotic and abiotic factors encountered during bioremediation and industrial biotechnological processes. PMID:28314727

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

    PubMed

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

    2016-09-01

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

  19. High-Throughput Assay Optimization and Statistical Interpolation of Rubella-Specific Neutralizing Antibody Titers

    PubMed Central

    Lambert, Nathaniel D.; Pankratz, V. Shane; Larrabee, Beth R.; Ogee-Nwankwo, Adaeze; Chen, Min-hsin; Icenogle, Joseph P.

    2014-01-01

    Rubella remains a social and economic burden due to the high incidence of congenital rubella syndrome (CRS) in some countries. For this reason, an accurate and efficient high-throughput measure of antibody response to vaccination is an important tool. In order to measure rubella-specific neutralizing antibodies in a large cohort of vaccinated individuals, a high-throughput immunocolorimetric system was developed. Statistical interpolation models were applied to the resulting titers to refine quantitative estimates of neutralizing antibody titers relative to the assayed neutralizing antibody dilutions. This assay, including the statistical methods developed, can be used to assess the neutralizing humoral immune response to rubella virus and may be adaptable for assessing the response to other viral vaccines and infectious agents. PMID:24391140

  20. Specificity, cross-talk and adaptation in Interferon signaling

    NASA Astrophysics Data System (ADS)

    Zilman, Anton

    Innate immune system is the first line of defense of higher organisms against pathogens. It coordinates the behavior of millions of cells of multiple types, achieved through numerous signaling molecules. This talk focuses on the signaling specificity of a major class of signaling molecules - Type I Interferons - which are also used therapeutically in the treatment of a number of diseases, such as Hepatitis C, multiple sclerosis and some cancers. Puzzlingly, different Interferons act through the same cell surface receptor but have different effects on the target cells. They also exhibit a strange pattern of temporal cross-talk resulting in a serious clinical problem - loss of response to Interferon therapy. We combined mathematical modeling with quantitative experiments to develop a quantitative model of specificity and adaptation in the Interferon signaling pathway. The model resolves several outstanding experimental puzzles and directly affects the clinical use of Type I Interferons in treatment of viral hepatitis and other diseases.

  1. Has Sarcocystis neurona Dubey et al., 1991 (Sporozoa: Apicomplexa: Sarcocystidae) cospeciated with its intermediate hosts?

    PubMed

    Elsheikha, Hany M

    2009-08-26

    The question of how Sarcocystis neurona is able to overcome species barrier and adapt to new hosts is central to the understanding of both the evolutionary origin of S. neurona and the prediction of its field host range. Therefore, it is worth reviewing current knowledge on S. neurona host specificity. The available host range data for S. neurona are discussed in relation to a subject of evolutionary importance-specialist or generalist and its implications to understand the strategies of host adaptation. Current evidences demonstrate that a wide range of hosts exists for S. neurona. This parasite tends to be highly specific for its definitive host but much less so for its intermediate host (I.H.). The unique specificity of S. neurona for its definitive host may be mediated by a probable long coevolutionary relationship of the parasite and carnivores in a restricted ecological niche 'New World'. This might be taken as evidence that carnivores are the 'original' host group for S. neurona. Rather, the capacity of S. neurona to exploit an unusually large number of I.H. species probably indicates that S. neurona maintains non-specificity to its I.H. as an adaptive response to insure the survival of the parasite in areas in which the 'preferred' host is not available. This review concludes with the view that adaptation of S. neurona to a new host is a complex interplay that involves a large number of determinants.

  2. Systems biology of immunity to MF59-adjuvanted versus nonadjuvanted trivalent seasonal influenza vaccines in early childhood

    PubMed Central

    Nakaya, Helder I.; Clutterbuck, Elizabeth; Kazmin, Dmitri; Wang, Lili; Cortese, Mario; Bosinger, Steven E.; Patel, Nirav B.; Zak, Daniel E.; Aderem, Alan; Dong, Tao; Del Giudice, Giuseppe; Rappuoli, Rino; Cerundolo, Vincenzo; Pollard, Andrew J.; Pulendran, Bali; Siegrist, Claire-Anne

    2016-01-01

    The dynamics and molecular mechanisms underlying vaccine immunity in early childhood remain poorly understood. Here we applied systems approaches to investigate the innate and adaptive responses to trivalent inactivated influenza vaccine (TIV) and MF59-adjuvanted TIV (ATIV) in 90 14- to 24-mo-old healthy children. MF59 enhanced the magnitude and kinetics of serum antibody titers following vaccination, and induced a greater frequency of vaccine specific, multicytokine-producing CD4+ T cells. Compared with transcriptional responses to TIV vaccination previously reported in adults, responses to TIV in infants were markedly attenuated, limited to genes regulating antiviral and antigen presentation pathways, and observed only in a subset of vaccinees. In contrast, transcriptional responses to ATIV boost were more homogenous and robust. Interestingly, a day 1 gene signature characteristic of the innate response (antiviral IFN genes, dendritic cell, and monocyte responses) correlated with hemagglutination at day 28. These findings demonstrate that MF59 enhances the magnitude, kinetics, and consistency of the innate and adaptive response to vaccination with the seasonal influenza vaccine during early childhood, and identify potential molecular correlates of antibody responses. PMID:26755593

  3. Systems analysis of transcriptome data provides new hypotheses about Arabidopsis root response to nitrate treatments

    PubMed Central

    Canales, Javier; Moyano, Tomás C.; Villarroel, Eva; Gutiérrez, Rodrigo A.

    2014-01-01

    Nitrogen (N) is an essential macronutrient for plant growth and development. Plants adapt to changes in N availability partly by changes in global gene expression. We integrated publicly available root microarray data under contrasting nitrate conditions to identify new genes and functions important for adaptive nitrate responses in Arabidopsis thaliana roots. Overall, more than 2000 genes exhibited changes in expression in response to nitrate treatments in Arabidopsis thaliana root organs. Global regulation of gene expression by nitrate depends largely on the experimental context. However, despite significant differences from experiment to experiment in the identity of regulated genes, there is a robust nitrate response of specific biological functions. Integrative gene network analysis uncovered relationships between nitrate-responsive genes and 11 highly co-expressed gene clusters (modules). Four of these gene network modules have robust nitrate responsive functions such as transport, signaling, and metabolism. Network analysis hypothesized G2-like transcription factors are key regulatory factors controlling transport and signaling functions. Our meta-analysis highlights the role of biological processes not studied before in the context of the nitrate response such as root hair development and provides testable hypothesis to advance our understanding of nitrate responses in plants. PMID:24570678

  4. Whose Recovery, of What? Relationships and Environments Promoting Grief and Growth

    ERIC Educational Resources Information Center

    Shapiro, Ester R.

    2008-01-01

    This article explores the concept of recovery in the wake of a loved one's death, using a cultural and developmental systems approach to understanding child, adult, and family bereavement outcomes as evolving, interdependent adaptive responses to changed circumstances of development within highly specific contexts in intergenerational time and…

  5. The Nature and Treatment of Speech Fright.

    ERIC Educational Resources Information Center

    Cronin, Michael

    This paper reviews the literature on speech fright in the workplace and examines its symptoms, effects, and causes. The paper also identifies various methods of treatment that have proven effective when adapted to individual and situational factors responsible for anxiety. The paper lists seven specific treatments directed toward improving public…

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

    PubMed

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

    2017-09-07

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

  7. Effects of sex and gender on adaptations to space: reproductive health.

    PubMed

    Ronca, April E; Baker, Ellen S; Bavendam, Tamara G; Beck, Kevin D; Miller, Virginia M; Tash, Joseph S; Jenkins, Marjorie

    2014-11-01

    In this report, sex/gender research relevant to reproduction on Earth, in conjunction with the extant human and animal observations in space, was used to identify knowledge gaps and prioritize recommendations for future sex- and gender-specific surveillance and monitoring of male and female astronauts. With overall increased durations of contemporary space missions, a deeper understanding of sex/gender effects on reproduction-related responses and adaptations to the space environment is warranted to minimize risks and insure healthy aging of the men and women who travel into space.

  8. Effects of Sex and Gender on Adaptations to Space: Reproductive Health

    PubMed Central

    Baker, Ellen S.; Bavendam, Tamara G.; Beck, Kevin D.; Miller, Virginia M.; Tash, Joseph S.; Jenkins, Marjorie

    2014-01-01

    Abstract In this report, sex/gender research relevant to reproduction on Earth, in conjunction with the extant human and animal observations in space, was used to identify knowledge gaps and prioritize recommendations for future sex- and gender-specific surveillance and monitoring of male and female astronauts. With overall increased durations of contemporary space missions, a deeper understanding of sex/gender effects on reproduction-related responses and adaptations to the space environment is warranted to minimize risks and insure healthy aging of the men and women who travel into space. PMID:25401943

  9. Responses to Microbial Challenges by SLAMF Receptors

    PubMed Central

    van Driel, Boaz Job; Liao, Gongxian; Engel, Pablo; Terhorst, Cox

    2016-01-01

    The SLAMF family (SLAMF) of cell surface glycoproteins is comprised of nine glycoproteins and while SLAMF1, 3, 5, 6, 7, 8, and 9 are self-ligand receptors, SLAMF2 and SLAMF4 interact with each other. Their interactions induce signal transduction networks in trans, thereby shaping immune cell–cell communications. Collectively, these receptors modulate a wide range of functions, such as myeloid cell and lymphocyte development, and T and B cell responses to microbes and parasites. In addition, several SLAMF receptors serve as microbial sensors, which either positively or negatively modulate the function of macrophages, dendritic cells, neutrophils, and NK cells in response to microbial challenges. The SLAMF receptor–microbe interactions contribute both to intracellular microbicidal activity as well as to migration of phagocytes to the site of inflammation. In this review, we describe the current knowledge on how the SLAMF receptors and their specific adapters SLAM-associated protein and EAT-2 regulate innate and adaptive immune responses to microbes. PMID:26834746

  10. Immunity to intestinal pathogens: lessons learned from Salmonella

    PubMed Central

    McSorley, Stephen J.

    2014-01-01

    Summary Salmonella are a common source of food or water-borne infection and cause a wide range of clinical disease in human and animal hosts. Salmonella are relatively easy to culture and manipulate in a laboratory setting, and the infection of laboratory animals induces robust innate and adaptive immune responses. Thus, immunologists have frequently turned to Salmonella infection models to expand understanding of immunity to intestinal pathogens. In this review, I summarize current knowledge of innate and adaptive immunity to Salmonella and highlight features of this response that have emerged from recent studies. These include the heterogeneity of the antigen-specific T-cell response to intestinal infection, the prominence of microbial mechanisms to impede T and B-cell responses, and the contribution of non-cognate pathways for elicitation of T-cell effector functions. Together, these different issues challenge an overly simplistic view of host-pathogen interaction during mucosal infection but also allow deeper insight into the real-world dynamic of protective immunity to intestinal pathogens. PMID:24942689

  11. Effects of Exercise Training and Social Environment on Stress Resilience in Male and Female Long-Evans Rats

    DTIC Science & Technology

    2010-03-15

    1976) described the stress response as a process, named the general adaptation syndrome (GAS). The GAS is a non-specific stress response that...individual attempts to return to normal functioning. The exhaustion phase is also known as burnout , and occurs when the individual no longer has...including cardiovascular disease, obesity, diabetes, and metabolic syndrome . Physical activity is defined as any bodily movement produced by skeletal

  12. Stretch-activated ion channel blockade attenuates adaptations to eccentric exercise.

    PubMed

    Butterfield, Timothy A; Best, Thomas M

    2009-02-01

    The purpose of this study was to test the hypothesis that stretch-activated ion channel (SAC) function is essential for the repeated bout effect (RBE) in skeletal muscle. Specifically, we investigated if daily injections of streptomycin (a known SAC blocker) would abrogate the muscle's adaptive resistance to the damaging effects of eccentric exercise over a 4-wk period. Furthermore, we hypothesized that the lack of an RBE would be due to the lack of functional adaptations that typically result from repeated bouts of eccentric exercise, including increased peak isometric torque, muscle hypertrophy, and rightward shift of the torque-angle relationship. Twelve New Zealand white rabbits were each subjected to 12 bouts of eccentric exercise over a 4-wk period while receiving either daily injections of streptomycin or sham injections. Although blocking the SAC function completely eliminated the expected adaptive response in biomechanical parameters during the exercise regimen, there remained evidence of an acquired RBE, albeit with an attenuated response when compared with the muscles with intact SAC function. Blocking sarcolemmal SAC eliminates functional adaptations of muscle after eccentric exercise. In the absence of SAC function, muscles subjected to chronic eccentric exercise still exhibit some degree of the RBE. As such, it appears that the signaling cascade that results in functional, biomechanical adaptations associated with the RBE during eccentric exercise is dependent upon intact SAC function.

  13. How the Dynamics of a Supramolecular Polymer Determines Its Dynamic Adaptivity and Stimuli-Responsiveness: Structure-Dynamics-Property Relationships From Coarse-Grained Simulations.

    PubMed

    Torchi, Andrea; Bochicchio, Davide; Pavan, Giovanni M

    2018-04-12

    The rational design of supramolecular polymers that can adapt or respond in time to specific stimuli in a controlled way is interesting for many applications, but this requires understanding the molecular factors that make the material faster or slower in responding to the stimulus. To this end, it is necessary to study the dynamic adaptive properties at submolecular resolution, which is difficult at an experimental level. Here we show coarse-grained molecular dynamics simulations (<5 Å resolution) demonstrating how the dynamic adaptivity and stimuli responsiveness of a supramolecular polymer is controlled by the intrinsic dynamics of the assembly, which is in turn determined by the structure of the monomers. As a representative case, we focus on a water-soluble 1,3,5-benzenetricarboxamide (BTA) supramolecular polymer incorporating (charged) receptor monomers, experimentally seen to undergo dynamic clustering following the superselective binding to a multivalent recruiter. Our simulations show that the dynamic reorganization of the supramolecular structure proceeds via monomer diffusion on the dynamic fiber surface (exchange within the fiber). Rationally changing the structure of the monomers to make the fiber surface more or less dynamic allows tuning the rate of response to the stimulus and of supramolecular reconfiguration. Simple in silico experiments draw a structure-dynamics-property relationship revealing the key factors underpinning the dynamic adaptivity and stimuli-responsiveness of these supramolecular polymers. We come out with clear evidence that to master the bioinspired properties of these fibers, it is necessary to control their intrinsic dynamics, while the high-resolution of our molecular models permits us to show how.

  14. Sulfate production depicts fed-state adaptation to protein restriction in humans.

    PubMed

    Hamadeh, M J; Schiffrin, A; Hoffer, L J

    2001-08-01

    One feature of the adaptation to dietary protein restriction is reduced urea production over the hours after consumption of a test meal of fixed composition. This adaptation is impaired in conventionally treated insulin-dependent diabetes mellitus (Hoffer LJ, Taveroff A, and Schiffrin A. Am J Physiol Endocrinol Metab 272: E59--E67, 1997). We have now tested the response to a test meal containing less protein and included as a main outcome variable the production of sulfate, a specific indicator of sulfur amino acid catabolism. Six normal men consumed a mixed test meal containing 0.25 g protein/kg and 10 kcal/kg while adapted to high (1.5 g x kg(-1) x day(-1)) and low (0.3 g. kg(-1) x day(-1)) protein intakes. They followed the identical protocol twice. Six subjects with insulin-dependent diabetes consumed the test meal while adapted to their customary high-protein diet. Adaptation to protein restriction reproducibly reduced 9-h cumulative postmeal urea N and S production by 22--29% and 49--52%, respectively (both P < 0.05). Similar results were obtained for a postmeal collection period of 6 h. The response of the diabetic subjects was normal. We conclude that reductions in postmeal urea and sulfate production after protein restriction are reproducible and are evident using a postmeal collection period as short as 6 h. Sulfate production effectively depicts fed-state adaptation to protein restriction.

  15. Stomatal density and metabolic determinants mediate salt stress adaptation and water use efficiency in basil (Ocimum basilicum L.).

    PubMed

    Barbieri, Giancarlo; Vallone, Simona; Orsini, Francesco; Paradiso, Roberta; De Pascale, Stefania; Negre-Zakharov, Florence; Maggio, Albino

    2012-11-15

    Increasing salinity tolerance and water-use efficiency in crop plants are two major challenges that agriculture must face in the next decades. Many physiological mechanisms and molecular components mediating crop response to environmental stresses have been identified. However, the functional inter-links between stress adaptation responses have not been completely understood. Using two basil cultivars (Napoletano and Genovese) with contrasting ability to respond to salt stress, here we demonstrate that reduced stomatal density, high ascorbate level and polyphenol oxidase (PPO) activity coordinately contribute to improve basil adaptation and water use efficiency (WUE) in saline environment. The constitutively reduced stomatal density was associated with a "delayed" accumulation of stress molecules (and growth inhibiting signals) such as abscisic acid (ABA) and proline, in the more tolerant Genovese. Leaf volatile profiling also revealed cultivar-specific patterns, which may suggest a role for the volatile phenylpropanoid eugenol and monoterpenes in conferring stress tolerance via antioxidant and signalling functions. Copyright © 2012 Elsevier GmbH. All rights reserved.

  16. Root adaptations to soils with low fertility and aluminium toxicity

    PubMed Central

    Rao, Idupulapati M.; Miles, John W.; Beebe, Stephen E.; Horst, Walter J.

    2016-01-01

    Background Plants depend on their root systems to acquire the water and nutrients necessary for their survival in nature, and for their yield and nutritional quality in agriculture. Root systems are complex and a variety of root phenes have been identified as contributors to adaptation to soils with low fertility and aluminium (Al) toxicity. Phenotypic characterization of root adaptations to infertile soils is enabling plant breeders to develop improved cultivars that not only yield more, but also contribute to yield stability and nutritional security in the face of climate variability. Scope In this review the adaptive responses of root systems to soils with low fertility and Al toxicity are described. After a brief introduction, the purpose and focus of the review are outlined. This is followed by a description of the adaptive responses of roots to low supply of mineral nutrients [with an emphasis on low availability of nitrogen (N) and phosphorus (P) and on toxic levels of Al]. We describe progress in developing germplasm adapted to soils with low fertility or Al toxicity using selected examples from ongoing breeding programmes on food (maize, common bean) and forage/feed (Brachiaria spp.) crops. A number of root architectural, morphological, anatomical and metabolic phenes contribute to the superior performance and yield on soils with low fertility and Al toxicity. Major advances have been made in identifying root phenes in improving adaptation to low N (maize), low P (common bean) or high Al [maize, common bean, species and hybrids of brachiariagrass, bulbous canarygrass (Phalaris aquatica) and lucerne (Medicago sativa)]. Conclusions Advanced root phenotyping tools will allow dissection of root responses into specific root phenes that will aid both conventional and molecular breeders to develop superior cultivars. These new cultivars will play a key role in sustainable intensification of crop–livestock systems, particularly in smallholder systems of the tropics. Development of these new cultivars adapted to soils with low fertility and Al toxicity is needed to improve global food and nutritional security and environmental sustainability. PMID:27255099

  17. Learning to Link Visual Contours

    PubMed Central

    Li, Wu; Piëch, Valentin; Gilbert, Charles D.

    2008-01-01

    SUMMARY In complex visual scenes, linking related contour elements is important for object recognition. This process, thought to be stimulus driven and hard wired, has substrates in primary visual cortex (V1). Here, however, we find contour integration in V1 to depend strongly on perceptual learning and top-down influences that are specific to contour detection. In naive monkeys the information about contours embedded in complex backgrounds is absent in V1 neuronal responses, and is independent of the locus of spatial attention. Training animals to find embedded contours induces strong contour-related responses specific to the trained retinotopic region. These responses are most robust when animals perform the contour detection task, but disappear under anesthesia. Our findings suggest that top-down influences dynamically adapt neural circuits according to specific perceptual tasks. This may serve as a general neuronal mechanism of perceptual learning, and reflect top-down mediated changes in cortical states. PMID:18255036

  18. Specific inflammatory response of Anemonia sulcata (Cnidaria) after bacterial injection causes tissue reaction and enzymatic activity alteration.

    PubMed

    Trapani, M R; Parisi, M G; Parrinello, D; Sanfratello, M A; Benenati, G; Palla, F; Cammarata, M

    2016-03-01

    The evolution of multicellular organisms was marked by adaptations to protect against pathogens. The mechanisms for discriminating the ''self'' from ''non-self" have evolved into a long history of cellular and molecular strategies, from damage repair to the co-evolution of host-pathogen interactions. We investigated the inflammatory response in Anemonia sulcata (Cnidaria: Anthozoa) following injection of substances that varied in type and dimension, and observed clear, strong and specific reactions, especially after injection of Escherichia coli and Vibrio alginolyticus. Moreover, we analyzed enzymatic activity of protease, phosphatase and esterase, showing how the injection of different bacterial strains alters the expression of these enzymes and suggesting a correlation between the appearance of the inflammatory reaction and the modification of enzymatic activities. Our study shows for the first time, a specific reaction and enzymatic responses following injection of bacteria in a cnidarian. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. The benefits of a camp designed for children with epilepsy: evaluating adaptive behaviors over 3 years.

    PubMed

    Cushner-Weinstein, Sandra; Berl, Madison; Salpekar, Jay A; Johnson, Jami L; Pearl, Phillip L; Conry, Joan A; Kolodgie, Marian; Scully, Audrey; Gaillard, William D; Weinstein, Steven L

    2007-02-01

    Children with epilepsy attending a condition-specific overnight camp were evaluated for behavioral changes over 3 consecutive years, using a modification of the Vineland Adaptive Behavioral Scale. Trained counselors completed pre- and postcamp assessments for each camper. Repeated-measures MANOVA was used to analyze effects of the camp experience for each year, with respect to gender and age. Repeated-measures ANOVA was conducted to evaluate long-term effects from year-to-year comparisons for return campers, following three successive camp experiences. A significant change in social interaction was observed over 3 years. Despite some decline at the start of camp in consecutive years, the overall trend for return campers suggests a positive cumulative impact of continued camp participation, with improvements in the domains of social interaction, responsibility, and communication. A condition-specific camp designed for children with epilepsy can improve adaptive behaviors and social interactions. Overall net gains appear to increase over time, suggesting additional benefits for return campers.

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

    PubMed

    Dauvrin, Marie; Lorant, Vincent

    2014-07-08

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

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

    PubMed Central

    2014-01-01

    Background In a context of increasing ethnic diversity, culturally competent strategies have been recommended to improve care quality and access to health care for ethnic minorities and migrants; their implementation by health professionals, however, has remained patchy. Most programs of cultural competence assume that health professionals accept that they have a responsibility to adapt to migrants, but this assumption has often remained at the level of theory. In this paper, we surveyed health professionals’ views on their responsibility to adapt. Methods Five hundred-and-sixty-nine health professionals from twenty-four inpatient and outpatient health services were selected according to their geographic location. All health care professionals were requested to complete a questionnaire about who should adapt to ethnic diversity: health professionals or patients. After a factorial analysis to identify the underlying responsibility dimensions, we performed a multilevel regression model in order to investigate individual and service covariates of responsibility attribution. Results Three dimensions emerged from the factor analysis: responsibility for the adaptation of communication, responsibility for the adaptation to the negotiation of values, and responsibility for the adaptation to health beliefs. Our results showed that the sense of responsibility for the adaptation of health care depended on the nature of the adaptation required: when the adaptation directly concerned communication with the patient, health professionals declared that they should be the ones to adapt; in relation to cultural preferences, however, the responsibility felt on the patient’s shoulders. Most respondents were unclear in relation to adaptation to health beliefs. Regression indicated that being Belgian, not being a physician, and working in a primary-care service were associated with placing the burden of responsibility on the patient. Conclusions Health care professionals do not consider it to be their responsibility to adapt to ethnic diversity. If health professionals do not feel a responsibility to adapt, they are less likely to be involved in culturally competent health care. PMID:25005021

  2. Variation in short-term and long-term responses of photosynthesis and isoprenoid-mediated photoprotection to soil water availability in four Douglas-fir provenances

    DOE PAGES

    Junker, Laura Verena; Kleiber, Anita; Jansen, Kirstin; ...

    2017-01-10

    For long-lived forest tree species, the understanding of intraspecific variation among populations and their response to water availability can reveal their ability to cope with and adapt to climate change. Dissipation of excess excitation energy, mediated by photoprotective isoprenoids, is an important defense mechanism against drought and high light when photosynthesis is hampered. We used 50-year-old Douglas-fir trees of four provenances at two common garden experiments to characterize provenance-specific variation in photosynthesis and photoprotective mechanisms mediated by essential and non-essential isoprenoids in response to soil water availability and solar radiation. All provenances revealed uniform photoprotective responses to high solar radiation,more » including increased de-epoxidation of photoprotective xanthophyll cycle pigments and enhanced emission of volatile monoterpenes. In contrast, we observed differences between provenances in response to drought, where provenances sustaining higher CO2 assimilation rates also revealed increased water-use efficiency, carotenoid-chlorophyll ratios, pools of xanthophyll cycle pigments, β-carotene and stored monoterpenes. Our results demonstrate that local adaptation to contrasting habitats affected chlorophyll-carotenoid ratios, pool sizes of photoprotective xanthophylls, β-carotene, and stored volatile isoprenoids. We conclude that intraspecific variation in isoprenoid-mediated photoprotective mechanisms contributes to the adaptive potential of Douglas-fir provenances to climate change.« less

  3. Variation in short-term and long-term responses of photosynthesis and isoprenoid-mediated photoprotection to soil water availability in four Douglas-fir provenances

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Junker, Laura Verena; Kleiber, Anita; Jansen, Kirstin

    For long-lived forest tree species, the understanding of intraspecific variation among populations and their response to water availability can reveal their ability to cope with and adapt to climate change. Dissipation of excess excitation energy, mediated by photoprotective isoprenoids, is an important defense mechanism against drought and high light when photosynthesis is hampered. We used 50-year-old Douglas-fir trees of four provenances at two common garden experiments to characterize provenance-specific variation in photosynthesis and photoprotective mechanisms mediated by essential and non-essential isoprenoids in response to soil water availability and solar radiation. All provenances revealed uniform photoprotective responses to high solar radiation,more » including increased de-epoxidation of photoprotective xanthophyll cycle pigments and enhanced emission of volatile monoterpenes. In contrast, we observed differences between provenances in response to drought, where provenances sustaining higher CO2 assimilation rates also revealed increased water-use efficiency, carotenoid-chlorophyll ratios, pools of xanthophyll cycle pigments, β-carotene and stored monoterpenes. Our results demonstrate that local adaptation to contrasting habitats affected chlorophyll-carotenoid ratios, pool sizes of photoprotective xanthophylls, β-carotene, and stored volatile isoprenoids. We conclude that intraspecific variation in isoprenoid-mediated photoprotective mechanisms contributes to the adaptive potential of Douglas-fir provenances to climate change.« less

  4. Distinct Effects of Monophosphoryl Lipid A, Oligodeoxynucleotide CpG, and Combination Adjuvants on Modulating Innate and Adaptive Immune Responses to Influenza Vaccination

    PubMed Central

    Ko, Eun-Ju; Lee, Young-Tae; Lee, Youri; Kim, Ki-Hye

    2017-01-01

    Monophosphoryl lipid A (MPL) and oligodeoxynucleotide CpG are toll-like receptor (TLR) 4 and 9 agonist, respectively. Here, we investigated the effects of MPL, CpG, and combination adjuvants on stimulating in vitro dendritic cells (DCs), in vivo innate and adaptive immune responses, and protective efficacy of influenza vaccination. Combination of MPL and CpG was found to exhibit distinct effects on stimulating DCs in vitro to secrete IL-12p70 and tumor necrosis factor (TNF)-α and proliferate allogeneic CD8 T cells. Prime immunization of mice with inactivated split influenza vaccine in the presence of low dose MPL+CpG adjuvants increased the induction of virus-specific IgG and IgG2a isotype antibodies. MPL and CpG adjuvants contribute to improving the efficacy of prime influenza vaccination against lethal influenza challenge as determined by body weight monitoring, lung function, viral titers, and histology. A combination of MPL and CpG adjuvants was effective in improving vaccine efficacy as well as in reducing inflammatory immune responses locally and in inducing cellular immune responses upon lethal influenza virus challenge. This study demonstrates unique adjuvant effects of MPL, CpG, and combination adjuvants on modulating innate and adaptive immune responses to influenza prime vaccination. PMID:29093654

  5. Functional requirements driving the gene duplication in 12 Drosophila species.

    PubMed

    Zhong, Yan; Jia, Yanxiao; Gao, Yang; Tian, Dacheng; Yang, Sihai; Zhang, Xiaohui

    2013-08-15

    Gene duplication supplies the raw materials for novel gene functions and many gene families arisen from duplication experience adaptive evolution. Most studies of young duplicates have focused on mammals, especially humans, whereas reports describing their genome-wide evolutionary patterns across the closely related Drosophila species are rare. The sequenced 12 Drosophila genomes provide the opportunity to address this issue. In our study, 3,647 young duplicate gene families were identified across the 12 Drosophila species and three types of expansions, species-specific, lineage-specific and complex expansions, were detected in these gene families. Our data showed that the species-specific young duplicate genes predominated (86.6%) over the other two types. Interestingly, many independent species-specific expansions in the same gene family have been observed in many species, even including 11 or 12 Drosophila species. Our data also showed that the functional bias observed in these young duplicate genes was mainly related to responses to environmental stimuli and biotic stresses. This study reveals the evolutionary patterns of young duplicates across 12 Drosophila species on a genomic scale. Our results suggest that convergent evolution acts on young duplicate genes after the species differentiation and adaptive evolution may play an important role in duplicate genes for adaption to ecological factors and environmental changes in Drosophila.

  6. Evidence for Adaptation to the Tibetan Plateau Inferred from Tibetan Loach Transcriptomes

    PubMed Central

    Wang, Ying; Yang, Liandong; Zhou, Kun; Zhang, Yanping; Song, Zhaobin; He, Shunping

    2015-01-01

    Abstract Triplophysa fishes are the primary component of the fish fauna on the Tibetan Plateau and are well adapted to the high-altitude environment. Despite the importance of Triplophysa fishes on the plateau, the genetic mechanisms of the adaptations of these fishes to this high-altitude environment remain poorly understood. In this study, we generated the transcriptome sequences for three Triplophysa fishes, that is, Triplophysa siluroides, Triplophysa scleroptera, and Triplophysa dalaica, and used these and the previously available transcriptome and genome sequences from fishes living at low altitudes to identify potential genetic mechanisms for the high-altitude adaptations in Triplophysa fishes. An analysis of 2,269 orthologous genes among cave fish (Astyanax mexicanus), zebrafish (Danio rerio), large-scale loach (Paramisgurnus dabryanus), and Triplophysa fishes revealed that each of the terminal branches of the Triplophysa fishes had a significantly higher ratio of nonsynonymous to synonymous substitutions than that of the branches of the fishes from low altitudes, which provided consistent evidence for genome-wide rapid evolution in the Triplophysa genus. Many of the GO (Gene Ontology) categories associated with energy metabolism and hypoxia response exhibited accelerated evolution in the Triplophysa fishes compared with the large-scale loach. The genes that exhibited signs of positive selection and rapid evolution in the Triplophysa fishes were also significantly enriched in energy metabolism and hypoxia response categories. Our analysis identified widespread Triplophysa-specific nonsynonymous mutations in the fast evolving genes and positively selected genes. Moreover, we detected significant evidence of positive selection in the HIF (hypoxia-inducible factor)-1A and HIF-2B genes in Triplophysa fishes and found that the Triplophysa-specific nonsynonymous mutations in the HIF-1A and HIF-2B genes were associated with functional changes. Overall, our study provides new insights into the adaptations and evolution of fishes in the high-altitude environment of the Tibetan Plateau and complements previous findings on the adaptations of mammals and birds to high altitudes. PMID:26454018

  7. Evolution of Caenorhabditis elegans host defense under selection by the bacterial parasite Serratia marcescens.

    PubMed

    Penley, McKenna J; Ha, Giang T; Morran, Levi T

    2017-01-01

    Parasites can impose strong selection on hosts. In response, some host populations have adapted via the evolution of defenses that prevent or impede infection by parasites. However, host populations have also evolved life history shifts that maximize host fitness despite infection. Outcrossing and self-fertilization can have contrasting effects on evolutionary trajectories of host populations. While selfing and outcrossing are known to affect the rate at which host populations adapt in response to parasites, these mating systems may also influence the specific traits that underlie adaptation to parasites. Here, we determined the role of evolved host defense versus altered life history,in mixed mating (selfing and outcrossing) and obligately outcrossing C. elegans host populations after experimental evolution with the bacterial parasite, S. marcescens. Similar to previous studies, we found that both mixed mating and obligately outcrossing host populations adapted to S. marcescens exposure, and that the obligately outcrossing populations exhibited the greatest rates of adaptation. Regardless of the host population mating system, exposure to parasites did not significantly alter reproductive timing or total fecundity over the course of experimental evolution. However, both mixed mating and obligately outcrossing host populations exhibited significantly reduced mortality rates in the presence of the parasite after experimental evolution. Therefore, adaptation in both the mixed mating and obligately outcrossing populations was driven, at least in part, by the evolution of increased host defense and not changes in host life history. Thus, the host mating system altered the rate of adaptation, but not the nature of adaptive change in the host populations.

  8. Evolution of Caenorhabditis elegans host defense under selection by the bacterial parasite Serratia marcescens

    PubMed Central

    Penley, McKenna J.; Ha, Giang T.; Morran, Levi T.

    2017-01-01

    Parasites can impose strong selection on hosts. In response, some host populations have adapted via the evolution of defenses that prevent or impede infection by parasites. However, host populations have also evolved life history shifts that maximize host fitness despite infection. Outcrossing and self-fertilization can have contrasting effects on evolutionary trajectories of host populations. While selfing and outcrossing are known to affect the rate at which host populations adapt in response to parasites, these mating systems may also influence the specific traits that underlie adaptation to parasites. Here, we determined the role of evolved host defense versus altered life history,in mixed mating (selfing and outcrossing) and obligately outcrossing C. elegans host populations after experimental evolution with the bacterial parasite, S. marcescens. Similar to previous studies, we found that both mixed mating and obligately outcrossing host populations adapted to S. marcescens exposure, and that the obligately outcrossing populations exhibited the greatest rates of adaptation. Regardless of the host population mating system, exposure to parasites did not significantly alter reproductive timing or total fecundity over the course of experimental evolution. However, both mixed mating and obligately outcrossing host populations exhibited significantly reduced mortality rates in the presence of the parasite after experimental evolution. Therefore, adaptation in both the mixed mating and obligately outcrossing populations was driven, at least in part, by the evolution of increased host defense and not changes in host life history. Thus, the host mating system altered the rate of adaptation, but not the nature of adaptive change in the host populations. PMID:28792961

  9. Adaptation of Arabidopsis to nitrogen limitation involves induction of anthocyanin synthesis which is controlled by the NLA gene

    PubMed Central

    Peng, Mingsheng; Hudson, Darryl; Schofield, Andrew; Tsao, Rong; Yang, Raymond; Gu, Honglan; Bi, Yong-Mei; Rothstein, Steven. J.

    2008-01-01

    Plants can survive a limiting nitrogen (N) supply by developing a set of N limitation adaptive responses. However, the Arabidopsis nla (nitrogen limitation adaptation) mutant fails to produce such responses, and cannot adapt to N limitation. In this study, the nla mutant was utilized to understand further the effect of NLA on Arabidopsis adaptation to N limitation. Grown with limiting N, the nla mutant could not accumulate anthocyanins and instead produced an N limitation-induced early senescence phenotype. In contrast, when supplied with limiting N and limiting phosphorus (Pi), the nla mutants accumulated abundant anthocyanins and did not show the N limitation-induced early senescence phenotype. These results support the hypothesis that Arabidopsis has a specific pathway to control N limitation-induced anthocyanin synthesis, and the nla mutation disrupts this pathway. However, the nla mutation does not affect the Pi limitation-induced anthocyanin synthesis pathway. Therefore, Pi limitation induced the nla mutant to accumulate anthocyanins under N limitation and allowed this mutant to adapt to N limitation. Under N limitation, the nla mutant had a significantly down-regulated expression of many genes functioning in anthocyanin synthesis, and an enhanced expression of genes involved in lignin production. Correspondingly, the nla mutant grown with limiting N showed a significantly lower production of anthocyanins (particularly cyanidins) and an increase in lignin contents compared with wild-type plants. These data suggest that NLA controls Arabidopsis adaptability to N limitation by channelling the phenylpropanoid metabolic flux to the induced anthocyanin synthesis, which is important for Arabidopsis to adapt to N limitation. PMID:18552353

  10. A multi-layered governance framework for incorporating social science insights into adapting to the health impacts of climate change.

    PubMed

    Bowen, Kathryn J; Ebi, Kristie; Friel, Sharon; McMichael, Anthony J

    2013-09-10

    Addressing climate change and its associated effects is a multi-dimensional and ongoing challenge. This includes recognizing that climate change will affect the health and wellbeing of all populations over short and longer terms, albeit in varied ways and intensities. That recognition has drawn attention to the need to take adaptive actions to lessen adverse impacts over the next few decades from unavoidable climate change, particularly in developing country settings. A range of sectors is responsible for appropriate adaptive policies and measures to address the health risks of climate change, including health services, water and sanitation, trade, agriculture, disaster management, and development. To broaden the framing of governance and decision-making processes by using innovative methods and assessments to illustrate the multi-sectoral nature of health-related adaptation to climate change. This is a shift from sector-specific to multi-level systems encompassing sectors and actors, across temporal and spatial scales. A review and synthesis of the current knowledge in the areas of health and climate change adaptation governance and decision-making processes. A novel framework is presented that incorporates social science insights into the formulation and implementation of adaptation activities and policies to lessen the health risks posed by climate change. Clarification of the roles that different sectors, organizations, and individuals occupy in relation to the development of health-related adaptation strategies will facilitate the inclusion of health and wellbeing within multi-sector adaptation policies, thereby strengthening the overall set of responses to minimize the adverse health effects of climate change.

  11. A multi-layered governance framework for incorporating social science insights into adapting to the health impacts of climate change

    PubMed Central

    Bowen, Kathryn J.; Ebi, Kristie; Friel, Sharon; McMichael, Anthony J.

    2013-01-01

    Background Addressing climate change and its associated effects is a multi-dimensional and ongoing challenge. This includes recognizing that climate change will affect the health and wellbeing of all populations over short and longer terms, albeit in varied ways and intensities. That recognition has drawn attention to the need to take adaptive actions to lessen adverse impacts over the next few decades from unavoidable climate change, particularly in developing country settings. A range of sectors is responsible for appropriate adaptive policies and measures to address the health risks of climate change, including health services, water and sanitation, trade, agriculture, disaster management, and development. Objectives To broaden the framing of governance and decision-making processes by using innovative methods and assessments to illustrate the multi-sectoral nature of health-related adaptation to climate change. This is a shift from sector-specific to multi-level systems encompassing sectors and actors, across temporal and spatial scales. Design A review and synthesis of the current knowledge in the areas of health and climate change adaptation governance and decision-making processes. Results A novel framework is presented that incorporates social science insights into the formulation and implementation of adaptation activities and policies to lessen the health risks posed by climate change. Conclusion Clarification of the roles that different sectors, organizations, and individuals occupy in relation to the development of health-related adaptation strategies will facilitate the inclusion of health and wellbeing within multi-sector adaptation policies, thereby strengthening the overall set of responses to minimize the adverse health effects of climate change. PMID:24028938

  12. EEG frequency tagging using ultra-slow periodic heat stimulation of the skin reveals cortical activity specifically related to C fiber thermonociceptors

    PubMed Central

    Colon, Elisabeth; Liberati, Giulia; Mouraux, André

    2017-01-01

    The recording of event-related brain potentials triggered by a transient heat stimulus is used extensively to study nociception and diagnose lesions or dysfunctions of the nociceptive system in humans. However, these responses are related exclusively to the activation of a specific subclass of nociceptive afferents: quickly-adapting thermonociceptors. In fact, except if the activation of Aδ fibers is avoided or if A fibers are blocked, these responses specifically reflect activity triggered by the activation of Type 2 quickly-adapting A fiber mechano-heat nociceptors (AMH-2). Here, we propose a novel method to isolate, in the human electroencephalogram (EEG), cortical activity related to the sustained periodic activation of heat-sensitive thermonociceptors, using very slow (0.2 Hz) and long-lasting (75 s) sinusoidal heat stimulation of the skin between baseline and 50°C. In a first experiment, we show that when such long-lasting thermal stimuli are applied to the hand dorsum of healthy volunteers, the slow rises and decreases of skin temperature elicit a consistent periodic EEG response at 0.2 Hz and its harmonics, as well as a periodic modulation of the magnitude of theta, alpha and beta band EEG oscillations. In a second experiment, we demonstrate using an A fiber block that these EEG responses are predominantly conveyed by unmyelinated C fiber nociceptors. The proposed approach constitutes a novel mean to study C fiber function in humans, and to explore the cortical processing of tonic heat pain in physiological and pathological conditions. PMID:27871921

  13. Pegylated Interferon α-2a Triggers NK-Cell Functionality and Specific T-Cell Responses in Patients with Chronic HBV Infection without HBsAg Seroconversion

    PubMed Central

    Bruder Costa, Juliana; Dufeu-Duchesne, Tania; Leroy, Vincent; Bertucci, Inga; Bouvier-Alias, Magali; Pouget, Noelle; Brevot-Lutton, Ophelie; Bourliere, Marc; Zoulim, Fabien

    2016-01-01

    Pegylated interferon α-2a (Peg-IFN-α) represents a therapeutic alternative to the prolonged use of nucleos(t)ide analog (NA) in chronic hepatitis B (CHB) infection. The mechanisms leading to a positive clinical outcome remain unclear. As immune responses are critical for virus control, we investigated the effects of Peg-IFN-α on both innate and adaptive immunity, and related it to the clinical evolution. The phenotypic and functional features of the dendritic cells (DCs), natural killer (NK) cells and HBV-specific CD4/CD8 T cells were analyzed in HBeAg-negative CHB patients treated for 48-weeks with NA alone or together with Peg-IFN-α, before, during and up to 2-years after therapy. Peg-IFN-α induced an early activation of DCs, a potent expansion of the CD56bright NK subset, and enhanced the activation and functionality of the CD56dim NK subset. Peg-IFN-α triggered an increase in the frequencies of Th1- and Th17-oriented HBV-specific CD4/CD8 T cells. Peg-IFN-α reversed the unresponsiveness of patients to a specific stimulation. Most of the parameters returned to baseline after the stop of Peg-IFN-α therapy. Peg-IFN-α impacts both innate and adaptive immunity, overcoming dysfunctional immune responses in CHB patients. These modulations were not associated with seroconversion, which questioned the benefit of the add-on Peg-IFN-α treatment. PMID:27348813

  14. Immunomodulating activity of Pidotimod in children with Down syndrome.

    PubMed

    Zuccotti, G V; Mameli, C; Trabattoni, D; Beretta, S; Biasin, M; Guazzarotti, L; Clerici, M

    2013-01-01

    Acute respiratory tract infections (ARTIs) are the most frequent illnesses in pediatric age, frequently experienced in children with Down Syndrome (DS) due to the associated immune defects of both specific and non-specific immunity. Pidotimod, a synthetic immunostimulant, was shown to reduce the rates of ARTIs in children with DS, however the mechanisms associated with this effect is currently unknown. We analyzed immune parameters in DS children who received the seasonal 2011–2012 virosomal-adjuvanted influenza vaccine. Eighteen children aged 3-10 years (mean age 7.1+/-2.6 years) were randomly assigned (1:1 ratio) to receive Pidotimod 400 mg, administered orally once a day for 90 days or placebo. At the recruitment (T0) all children received a single dose of virosomal-adjuvanted influenza vaccine (Flu). Blood samples were collected at T0 and 3 months after the recruitment (T3) in order to evaluate innate and adaptative immune responses pathway. Flu-specific IgG1 and IgG3 levels in plasma samples were determined at pre-vaccination (T0), and 1 (T1) and 3 months (T3) post-vaccination. The use of Pidotimod was associated with the upregulation of a number of genes involved in the activation of innate immune responses and in antimicrobial activity. Interestingly the ratio of Flu-specific IgG1/IgG3 was skewed in pidotimod-treated individuals, suggesting a preferential activation of complement-dependent effector mechanisms. Although preliminary these data suggest that Pidotimod can potentiate the beneficial effect of immunization, possibly resulting in a stronger activity of both innate and adaptive immune responses.

  15. Application of Protein Microarrays for Multiplexed Detection of Antibodies to Tumor Antigens in Breast Cancer

    PubMed Central

    Anderson, Karen S.; Ramachandran, Niroshan; Wong, Jessica; Raphael, Jacob V.; Hainsworth, Eugenie; Demirkan, Gokhan; Cramer, Daniel; Aronzon, Diana; Hodi, F. Stephen; Harris, Lyndsay; Logvinenko, Tanya; LaBaer, Joshua

    2012-01-01

    There is strong preclinical evidence that cancer, including breast cancer, undergoes immune surveillance. This continual monitoring, by both the innate and the adaptive immune systems, recognizes changes in protein expression, mutation, folding, glycosylation, and degradation. Local immune responses to tumor antigens are amplified in draining lymph nodes, and then enter the systemic circulation. The antibody response to tumor antigens, such as p53 protein, are robust, stable, and easily detected in serum, may exist in greater concentrations than their cognate antigens, and are potential highly specific biomarkers for cancer. However, antibodies have limited sensitivities as single analytes, and differences in protein purification and assay characteristics have limited their clinical application. For example, p53 autoantibodies in the sera are highly specific for cancer patients, but are only detected in the sera of 10-20% of patients with breast cancer. Detection of p53 autoantibodies is dependent on tumor burden, p53 mutation, rapidly decreases with effective therapy, but is relatively independent of breast cancer subtype. Although antibodies to hundreds of other tumor antigens have been identified in the sera of breast cancer patients, very little is known about the specificity and clinical impact of the antibody immune repertoire to breast cancer. Recent advances in proteomic technologies have the potential for rapid identification of immune response signatures for breast cancer diagnosis and monitoring. We have adapted programmable protein microarrays for the specific detection of autoantibodies in breast cancer. Here, we present the first demonstration of the application of programmable protein microarray ELISAs for the rapid identification of breast cancer autoantibodies. PMID:18311903

  16. The diversity of gendered adaptation strategies to climate change of Indian farmers: A feminist intersectional approach.

    PubMed

    Ravera, Federica; Martín-López, Berta; Pascual, Unai; Drucker, Adam

    2016-12-01

    This paper examines climate change adaptation and gender issues through an application of a feminist intersectional approach. This approach permits the identification of diverse adaptation responses arising from the existence of multiple and fragmented dimensions of identity (including gender) that intersect with power relations to shape situation-specific interactions between farmers and ecosystems. Based on results from contrasting research cases in Bihar and Uttarakhand, India, this paper demonstrates, inter alia, that there are geographically determined gendered preferences and adoption strategies regarding adaptation options and that these are influenced by the socio-ecological context and institutional dynamics. Intersecting identities, such as caste, wealth, age and gender, influence decisions and reveal power dynamics and negotiation within the household and the community, as well as barriers to adaptation among groups. Overall, the findings suggest that a feminist intersectional approach does appear to be useful and worth further exploration in the context of climate change adaptation. In particular, future research could benefit from more emphasis on a nuanced analysis of the intra-gender differences that shape adaptive capacity to climate change.

  17. Conflict adaptation in patients diagnosed with schizophrenia.

    PubMed

    Abrahamse, Elger; Ruitenberg, Marit; Boddewyn, Sarah; Oreel, Edith; de Schryver, Maarten; Morrens, Manuel; van Dijck, Jean-Philippe

    2017-11-01

    Cognitive control impairments may contribute strongly to the overall cognitive deficits observed in patients diagnosed with schizophrenia. In the current study we explore a specific cognitive control function referred to as conflict adaptation. Previous studies on conflict adaptation in schizophrenia showed equivocal results, and, moreover, were plagued by confounded research designs. Here we assessed for the first time conflict adaptation in schizophrenia with a design that avoided the major confounds of feature integration and stimulus-response contingency learning. Sixteen patients diagnosed with schizophrenia and sixteen healthy, matched controls performed a vocal Stroop task to determine the congruency sequence effect - a marker of conflict adaptation. A reliable congruency sequence effect was observed for both healthy controls and patients diagnosed with schizophrenia. These findings indicate that schizophrenia is not necessarily accompanied by impaired conflict adaptation. As schizophrenia has been related to abnormal functioning in core conflict adaptation areas such as anterior cingulate and dorsolateral prefrontal cortex, further research is required to better understand the precise impact of such abnormal brain functioning at the behavioral level. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Nociceptin/Orphanin FQ Suppresses Adaptive Immune Responses in Vivo and at Picomolar Levels in Vitro

    PubMed Central

    Anton, Benito; Calva, Juan C.; Acevedo, Rodolfo; Salazar, Alberto; Matus, Maura; Flores, Anabel; Martinez, Martin; Adler, Martin W.; Gaughan, John P.; Eisenstein, Toby K.

    2014-01-01

    Nociceptin/orphanin FQ (N/OFQ), added in vitro to murine spleen cells in the picomolar range, suppressed antibody formation to sheep red blood cells in a primary and a secondary plaque-forming cell (PFC) assay. The activity of the peptide was maximal at 10−12 M, with an asymmetric U-shaped dose response curve that extended activity to 10−14 M. Suppression was not blocked by pretreatment with naloxone. Specificity of the suppressive response was shown using affinity purified rabbit antibodies against two N/OFQ peptides, and with a pharmacological antagonist. Antisera against both peptides were active, in a dose related manner, in neutralizing N/OFQ -mediated immunosuppression, when the peptide was used at concentrations from 10−12.3 to 10−11.6 M. In addition, nociceptin given in vivo by osmotic pump for 48 hr suppressed the capacity of spleen cells placed ex vivo to make an anti-sheep red blood cell response. These studies show that nociceptin directly inhibits an adaptive immune response, i.e. antibody formation, both in vitro and in vivo. PMID:20119853

  19. NK cells influence both innate and adaptive immune responses after mucosal immunisation with antigen and mucosal adjuvant*

    PubMed Central

    Hall, Lindsay J; Clare, Simon; Dougan, Gordon

    2012-01-01

    NK cells were found to be recruited in a temporally controlled manner to the nasal-associated lymphoid tissue and the cervical lymph nodes of mice following intranasal immunisation with Ag85B-ESAT6 antigen from Mycobacterium tuberculosis mixed with Escherichia coli heat-labile toxin as adjuvant. These NK cells were activated and they secreted a diverse range of cytokines and other immunmodulators. Using antibody depletion targeting anti-asialo GM1, we found evidence for altered trafficking, impaired activation and cytokine secretion of dendritic cells, macrophages and neutrophils in immunised NK cell depleted mice compared to control animals. Analysis of antigen-specific immune responses revealed an attenuated antibody and cytokine response in immunised NK cell depleted animals. Systemic administration of rIL-6 but not rIFN-γ significantly restored immune responses in mice depleted of NK cells. In conclusion, cytokine production, particularly IL-6, via NK cells and NK cell activated immune populations, plays an important role in the establishment of local innate immune responses and the consequent development of adaptive immunity after mucosal immunisation. PMID:20220095

  20. A trait-based framework for predicting when and where microbial adaptation to climate change will affect ecosystem functioning

    USGS Publications Warehouse

    Wallenstein, Matthew D.; Hall, Edward K.

    2012-01-01

    As the earth system changes in response to human activities, a critical objective is to predict how biogeochemical process rates (e.g. nitrification, decomposition) and ecosystem function (e.g. net ecosystem productivity) will change under future conditions. A particular challenge is that the microbial communities that drive many of these processes are capable of adapting to environmental change in ways that alter ecosystem functioning. Despite evidence that microbes can adapt to temperature, precipitation regimes, and redox fluctuations, microbial communities are typically not optimally adapted to their local environment. For example, temperature optima for growth and enzyme activity are often greater than in situ temperatures in their environment. Here we discuss fundamental constraints on microbial adaptation and suggest specific environments where microbial adaptation to climate change (or lack thereof) is most likely to alter ecosystem functioning. Our framework is based on two principal assumptions. First, there are fundamental ecological trade-offs in microbial community traits that occur across environmental gradients (in time and space). These trade-offs result in shifting of microbial function (e.g. ability to take up resources at low temperature) in response to adaptation of another trait (e.g. limiting maintenance respiration at high temperature). Second, the mechanism and level of microbial community adaptation to changing environmental parameters is a function of the potential rate of change in community composition relative to the rate of environmental change. Together, this framework provides a basis for developing testable predictions about how the rate and degree of microbial adaptation to climate change will alter biogeochemical processes in aquatic and terrestrial ecosystems across the planet.

  1. Epigenomic Adaptation to Low Dose Radiation

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Gould, Michael N.

    2015-06-30

    The overall hypothesis of this grant application is that the adaptive responses elicited by low dose ionizing radiation (LDIR) result in part from heritable DNA methylation changes in the epigenome. In the final budget period at the University of Wisconsin-Madison, we will specifically address this hypothesis by determining if the epigenetically labile, differentially methylated regions (DMRs) that regulate parental-specific expression of imprinted genes are deregulated in agouti mice by low dose radiation exposure during gestation. This information is particularly important to ascertain given the 1) increased human exposure to medical sources of radiation; 2) increased number of people predicted tomore » live and work in space; and 3) enhanced citizen concern about radiation exposure from nuclear power plant accidents and terrorist ‘dirty bombs.’« less

  2. Developmental exposure to bisphenol A modulates innate but not adaptive immune responses to influenza A virus infection.

    PubMed

    Roy, Anirban; Bauer, Stephen M; Lawrence, B Paige

    2012-01-01

    Bisphenol A (BPA) is used in numerous products, such as plastic bottles and food containers, from which it frequently leaches out and is consumed by humans. There is a growing public concern that BPA exposure may pose a significant threat to human health. Moreover, due to the widespread and constant nature of BPA exposure, not only adults but fetuses and neonates are also exposed to BPA. There is mounting evidence that developmental exposures to chemicals from our environment, including BPA, contribute to diseases late in life; yet, studies of how early life exposures specifically alter the immune system are limited. Herein we report an examination of how maternal exposure to a low, environmentally relevant dose of BPA affects the immune response to infection with influenza A virus. We exposed female mice during pregnancy and through lactation to the oral reference dose for BPA listed by the US Environmental Protection Agency, and comprehensively examined immune parameters directly linked to disease outcomes in adult offspring following infection with influenza A virus. We found that developmental exposure to BPA did not compromise disease-specific adaptive immunity against virus infection, or reduce the host's ability to clear the virus from the infected lung. However, maternal exposure to BPA transiently reduced the extent of infection-associated pulmonary inflammation and anti-viral gene expression in lung tissue. From these observations, we conclude that maternal exposure to BPA slightly modulates innate immunity in adult offspring, but does not impair the anti-viral adaptive immune response, which is critical for virus clearance and survival following influenza virus infection.

  3. Two-component signal transduction in Corynebacterium glutamicum and other corynebacteria: on the way towards stimuli and targets.

    PubMed

    Bott, Michael; Brocker, Melanie

    2012-06-01

    In bacteria, adaptation to changing environmental conditions is often mediated by two-component signal transduction systems. In the prototypical case, a specific stimulus is sensed by a membrane-bound histidine kinase and triggers autophosphorylation of a histidine residue. Subsequently, the phosphoryl group is transferred to an aspartate residue of the cognate response regulator, which then becomes active and mediates a specific response, usually by activating and/or repressing a set of target genes. In this review, we summarize the current knowledge on two-component signal transduction in Corynebacterium glutamicum. This Gram-positive soil bacterium is used for the large-scale biotechnological production of amino acids and can also be applied for the synthesis of a wide variety of other products, such as organic acids, biofuels, or proteins. Therefore, C. glutamicum has become an important model organism in industrial biotechnology and in systems biology. The type strain ATCC 13032 possesses 13 two-component systems and the role of five has been elucidated in recent years. They are involved in citrate utilization (CitAB), osmoregulation and cell wall homeostasis (MtrAB), adaptation to phosphate starvation (PhoSR), adaptation to copper stress (CopSR), and heme homeostasis (HrrSA). As C. glutamicum does not only face changing conditions in its natural environment, but also during cultivation in industrial bioreactors of up to 500 m(3) volume, adaptability can also be crucial for good performance in biotechnological production processes. Detailed knowledge on two-component signal transduction and regulatory networks therefore will contribute to both the application and the systemic understanding of C. glutamicum and related species.

  4. Adaptive evolution of Escherichia coli to Ciprofloxacin in controlled stress environments: emergence of tolerance in spatial and temporal gradients

    NASA Astrophysics Data System (ADS)

    Deng, J.; Sanford, R. A.; Dong, Y.; Shechtman, L. A.; Zhou, L.; Alcalde, R.; Werth, C. J.; Fouke, B. W.

    2016-12-01

    Microorganisms in nature have evolved in response to a variety of environmental stresses, including gradients of temperature, pH, substrate availability and aqueous chemistry. While environmental stresses are considered to be the driving forces of adaptive evolution, the impact and extent of any specific stress needed to drive such changes has not been well characterized. In this study, the antibiotic Ciprofloxacin was used as a stressor and systematically applied to E. coli st. 307 cells via a spatial gradient in a microfluidic pore network and a temporal gradient in batch cultures. The microfluidic device facilitated in vitro real-time tracking of bacterial abundances and dynamic spatial distributions in response to the gradients of both the antibiotic and nutrients. Cells collected from the microfluidic device showed growth on plates containing up to 10-times the original minimum inhibition concentration (MIC). In batch systems, Ciprofloxacin was used to evaluate adaptive responses via temporal gradients, in which the stressor concentration was incrementally increased over time with each transfer of the culture after 24 hours of growth. Responses of E. coli 307 to these stress patterns were measured by quantifying changes in the MIC for Ciprofloxacin. Over a period of 18 days of step-wise concentration increments, bacterial cells were observed to acquire tolerance gradually and eventually adapt to a 28-fold increase in the original MIC. Samples at different stages within the temporal Ciprofloxacin gradient treatment show different extents of resistance. All samples exhibited resistance exceeding the highest exposure stress concentration. In combination with the spatial and temporal gradient systems, this work provides the first comprehensive measure of the dynamic resistance of E. coli in response to Ciprofloxacin concentration gradients. These will provide invaluable insights to understand the effects of antibiotic stresses on bacterial adaptive evolution in medical settings and shed light on understanding the mechanics of microbial evolution.

  5. Pressure Induced Changes in Adaptive Immune Function in Belugas (Delphinapterus leucas); Implications for Dive Physiology and Health

    PubMed Central

    Thompson, Laura A.; Romano, Tracy A.

    2016-01-01

    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 Bristol Bay 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 Bristol Bay 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 to fight infection or avoid dive related pathologies. PMID:27746745

  6. Pressure Induced Changes in Adaptive Immune Function in Belugas (Delphinapterus leucas); Implications for Dive Physiology and Health.

    PubMed

    Thompson, Laura A; Romano, Tracy A

    2016-01-01

    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 Bristol Bay 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 Bristol Bay 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 to fight infection or avoid dive related pathologies.

  7. Statistical Model of Dynamic Markers of the Alzheimer's Pathological Cascade.

    PubMed

    Balsis, Steve; Geraci, Lisa; Benge, Jared; Lowe, Deborah A; Choudhury, Tabina K; Tirso, Robert; Doody, Rachelle S

    2018-05-05

    Alzheimer's disease (AD) is a progressive disease reflected in markers across assessment modalities, including neuroimaging, cognitive testing, and evaluation of adaptive function. Identifying a single continuum of decline across assessment modalities in a single sample is statistically challenging because of the multivariate nature of the data. To address this challenge, we implemented advanced statistical analyses designed specifically to model complex data across a single continuum. We analyzed data from the Alzheimer's Disease Neuroimaging Initiative (ADNI; N = 1,056), focusing on indicators from the assessments of magnetic resonance imaging (MRI) volume, fluorodeoxyglucose positron emission tomography (FDG-PET) metabolic activity, cognitive performance, and adaptive function. Item response theory was used to identify the continuum of decline. Then, through a process of statistical scaling, indicators across all modalities were linked to that continuum and analyzed. Findings revealed that measures of MRI volume, FDG-PET metabolic activity, and adaptive function added measurement precision beyond that provided by cognitive measures, particularly in the relatively mild range of disease severity. More specifically, MRI volume, and FDG-PET metabolic activity become compromised in the very mild range of severity, followed by cognitive performance and finally adaptive function. Our statistically derived models of the AD pathological cascade are consistent with existing theoretical models.

  8. Plasmids foster diversification and adaptation of bacterial populations in soil.

    PubMed

    Heuer, Holger; Smalla, Kornelia

    2012-11-01

    It is increasingly being recognized that the transfer of conjugative plasmids across species boundaries plays a vital role in the adaptability of bacterial populations in soil. There are specific driving forces and constraints of plasmid transfer within bacterial communities in soils. Plasmid-mediated genetic variation allows bacteria to respond rapidly with adaptive responses to challenges such as irregular antibiotic or metal concentrations, or opportunities such as the utilization of xenobiotic compounds. Cultivation-independent detection and capture of plasmids from soil bacteria, and complete sequencing have provided new insights into the role and ecology of plasmids. Broad host range plasmids such as those belonging to IncP-1 transfer a wealth of accessory functions which are carried by similar plasmid backbones. Plasmids with a narrower host range can be more specifically adapted to particular species and often transfer genes which complement chromosomally encoded functions. Plasmids seem to be an ancient and successful strategy to ensure survival of a soil population in spatial and temporal heterogeneous conditions with various environmental stresses or opportunities that occur irregularly or as a novel challenge in soil. © 2012 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

  9. Immune-Related Functions of the Hivep Gene Family in East African Cichlid Fishes

    PubMed Central

    Diepeveen, Eveline T.; Roth, Olivia; Salzburger, Walter

    2013-01-01

    Immune-related genes are often characterized by adaptive protein evolution. Selection on immune genes can be particularly strong when hosts encounter novel parasites, for instance, after the colonization of a new habitat or upon the exploitation of vacant ecological niches in an adaptive radiation. We examined a set of new candidate immune genes in East African cichlid fishes. More specifically, we studied the signatures of selection in five paralogs of the human immunodeficiency virus type I enhancer-binding protein (Hivep) gene family, tested their involvement in the immune defense, and related our results to explosive speciation and adaptive radiation events in cichlids. We found signatures of long-term positive selection in four Hivep paralogs and lineage-specific positive selection in Hivep3b in two radiating cichlid lineages. Exposure of the cichlid Astatotilapia burtoni to a vaccination with Vibrio anguillarum bacteria resulted in a positive correlation between immune response parameters and expression levels of three Hivep loci. This work provides the first evidence for a role of Hivep paralogs in teleost immune defense and links the signatures of positive selection to host–pathogen interactions within an adaptive radiation. PMID:24142922

  10. Yellow fever vaccine YF-17D activates multiple dendritic cell subsets via TLR2, 7, 8, and 9 to stimulate polyvalent immunity.

    PubMed

    Querec, Troy; Bennouna, Soumaya; Alkan, Sefik; Laouar, Yasmina; Gorden, Keith; Flavell, Richard; Akira, Shizuo; Ahmed, Rafi; Pulendran, Bali

    2006-02-20

    The live attenuated yellow fever vaccine 17D (YF-17D) is one of the most effective vaccines available, with a 65-yr history of use in >400 million people globally. Despite this efficacy, there is presently no information about the immunological mechanisms by which YF-17D acts. Here, we present data that suggest that YF-17D activates multiple Toll-like receptors (TLRs) on dendritic cells (DCs) to elicit a broad spectrum of innate and adaptive immune responses. Specifically, YF-17D activates multiple DC subsets via TLRs 2, 7, 8, and 9 to elicit the proinflammatory cytokines interleukin (IL)-12p40, IL-6, and interferon-alpha. Interestingly, the resulting adaptive immune responses are characterized by a mixed T helper cell (Th)1/Th2 cytokine profile and antigen-specific CD8+ T cells. Furthermore, distinct TLRs appear to differentially control the Th1/Th2 balance; thus, whilst MyD88-deficient mice show a profound impairment of Th1 cytokines, TLR2-deficient mice show greatly enhanced Th1 and Tc1 responses to YF-17D. Together, these data enhance our understanding of the molecular mechanism of action of YF-17D, and highlight the potential of vaccination strategies that use combinations of different TLR ligands to stimulate polyvalent immune responses.

  11. A Systematic Review of Cross-cultural Adaptation of the Oswestry Disability Index.

    PubMed

    Yao, Min; Wang, Qiong; Li, Zun; Yang, Long; Huang, Pin-Xian; Sun, Yue-Li; Wang, Jing; Wang, Yong-Jun; Cui, Xue-Jun

    2016-12-15

    Systematic review of cross-cultural adaptation of the Oswestry Disability Index (ODI). The aim of this study was to evaluate the translation procedures for and measurement properties of cross-cultural adaptations of the ODI. The ODI is the most commonly used questionnaire to determine the outcome of low back pain, and has been translated into many other languages, such as Danish, Greek, and Korean, and adapted for use in different countries. PubMed, the Cochrane Library, Medline, and EMBASE were searched from the time they were established to January 2015. Studies related to cross-cultural adaptation of the ODI in a specific language/culture were included. Guidelines for the Process of Cross-Cultural Adaptation of Self-Report Measures and Quality Criteria for Psychometric Properties of Health Status Questionnaire were used for assessment. This study included 27 versions of ODI adaptations in 24 different languages/cultures. Only the Danish-Danish adaptation employed all six of the cross-cultural adaptation processes. Expert committee review (three of 27), back translation (eight of 27), and pretesting (nine of 27) were conducted in very few studies. The Polish-Polish (two) adaptation reported all (nine of nine) the measurement properties, whereas the Traditional Chinese-Taiwan and Hungarian-Hungarian adaptations reported six of them. Content validity (16/27), construct validity (17/27), and reliability (22/27) were determined in a relatively high number of studies, whereas agreement (three of 27), responsiveness (12/27), floor and ceiling effects (six of 27), and interpretability (one of 27) were only determined in some studies. We recommend the Traditional Chinese-Taiwan, Simplified Chinese-Mandarin Chinese, Danish-Danish, German-Swiss, Hungarian-Hungarian, Italian-Italian, and Polish-Polish (two) versions for application, but Traditional Chinese-Hong Kong, French-Swiss, Japanese-Japanese (two), Polish-Polish (two), Tamil-Indian, and Thai-Thai versions may need more research. Furthermore, supplementary tests for the adaptations are necessary, especially for assessing agreement, responsiveness, and interpretability. 1.

  12. Innate immunity and effector and regulatory mechanisms involved in allergic contact dermatitis*

    PubMed Central

    Silvestre, Marilene Chaves; Sato, Maria Notomi; dos Reis, Vitor Manoel Silva

    2018-01-01

    Skin's innate immunity is the initial activator of immune response mechanisms, influencing the development of adaptive immunity. Some contact allergens are detected by Toll-like receptors (TLRs) and inflammasome NLR3. Keratinocytes participate in innate immunity and, in addition to functioning as an anatomical barrier, secrete cytokines, such as TNF, IL-1β, and IL-18, contributing to the development of Allergic Contact Dermatitis. Dendritic cells recognize and process antigenic peptides into T cells. Neutrophils cause pro-inflammatory reactions, mast cells induce migration/maturation of skin DCs, the natural killer cells have natural cytotoxic capacity, the γδ T cells favor contact with hapten during the sensitization phase, and the innate lymphoid cells act in the early stages by secreting cytokines, as well as act in inflammation and tissue homeostasis. The antigen-specific inflammation is mediated by T cells, and each subtype of T cells (Th1/Tc1, Th2/Tc2, and Th17/Tc17) activates resident skin cells, thus contributing to inflammation. Skin's regulatory T cells have a strong ability to inhibit the proliferation of hapten-specific T cells, acting at the end of the Allergic Contact Dermatitis response and in the control of systemic immune responses. In this review, we report how cutaneous innate immunity is the first line of defense and focus its role in the activation of the adaptive immune response, with effector response induction and its regulation. PMID:29723367

  13. Cathepsin-mediated Necrosis Controls the Adaptive Immune Response by Th2 (T helper type 2)-associated Adjuvants*

    PubMed Central

    Jacobson, Lee S.; Lima, Heriberto; Goldberg, Michael F.; Gocheva, Vasilena; Tsiperson, Vladislav; Sutterwala, Fayyaz S.; Joyce, Johanna A.; Gapp, Bianca V.; Blomen, Vincent A.; Chandran, Kartik; Brummelkamp, Thijn R.; Diaz-Griffero, Felipe; Brojatsch, Jürgen

    2013-01-01

    Immunologic adjuvants are critical components of vaccines, but it remains unclear how prototypical adjuvants enhance the adaptive immune response. Recent studies have shown that necrotic cells could trigger an immune response. Although most adjuvants have been shown to be cytotoxic, this activity has traditionally been considered a side effect. We set out to test the role of adjuvant-mediated cell death in immunity and found that alum, the most commonly used adjuvant worldwide, triggers a novel form of cell death in myeloid leukocytes characterized by cathepsin-dependent lysosome-disruption. We demonstrated that direct lysosome-permeabilization with a soluble peptide, Leu-Leu-OMe, mimics the alum-like form of necrotic cell death in terms of cathepsin dependence and cell-type specificity. Using a combination of a haploid genetic screen and cathepsin-deficient cells, we identified specific cathepsins that control lysosome-mediated necrosis. We identified cathepsin C as critical for Leu-Leu-OMe-induced cell death, whereas cathepsins B and S were required for alum-mediated necrosis. Consistent with a role of necrotic cell death in adjuvant effects, Leu-Leu-OMe replicated an alum-like immune response in vivo, characterized by dendritic cell activation, granulocyte recruitment, and production of Th2-associated antibodies. Strikingly, cathepsin C deficiency not only blocked Leu-Leu-OMe-mediated necrosis but also impaired Leu-Leu-OMe-enhanced immunity. Together our findings suggest that necrotic cell death is a powerful mediator of a Th2-associated immune response. PMID:23297415

  14. A predictive computational model of the kinetic mechanism of stimulus-induced transducer methylation and feedback regulation through CheY in archaeal phototaxis and chemotaxis.

    PubMed

    Streif, Stefan; Oesterhelt, Dieter; Marwan, Wolfgang

    2010-03-18

    Photo- and chemotaxis of the archaeon Halobacterium salinarum is based on the control of flagellar motor switching through stimulus-specific methyl-accepting transducer proteins that relay the sensory input signal to a two-component system. Certain members of the transducer family function as receptor proteins by directly sensing specific chemical or physical stimuli. Others interact with specific receptor proteins like the phototaxis photoreceptors sensory rhodopsin I and II, or require specific binding proteins as for example some chemotaxis transducers. Receptor activation by light or a change in receptor occupancy by chemical stimuli results in reversible methylation of glutamate residues of the transducer proteins. Both, methylation and demethylation reactions are involved in sensory adaptation and are modulated by the response regulator CheY. By mathematical modeling we infer the kinetic mechanisms of stimulus-induced transducer methylation and adaptation. The model (deterministic and in the form of ordinary differential equations) correctly predicts experimentally observed transducer demethylation (as detected by released methanol) in response to attractant and repellent stimuli of wildtype cells, a cheY deletion mutant, and a mutant in which the stimulated transducer species is methylation-deficient. We provide a kinetic model for signal processing in photo- and chemotaxis in the archaeon H. salinarum suggesting an essential role of receptor cooperativity, antagonistic reversible methylation, and a CheY-dependent feedback on transducer demethylation.

  15. Cal-Adapt: California's Climate Data Resource and Interactive Toolkit

    NASA Astrophysics Data System (ADS)

    Thomas, N.; Mukhtyar, S.; Wilhelm, S.; Galey, B.; Lehmer, E.

    2016-12-01

    Cal-Adapt is a web-based application that provides an interactive toolkit and information clearinghouse to help agencies, communities, local planners, resource managers, and the public understand climate change risks and impacts at the local level. The website offers interactive, visually compelling, and useful data visualization tools that show how climate change might affect California using downscaled continental climate data. Cal-Adapt is supporting California's Fourth Climate Change Assessment through providing access to the wealth of modeled and observed data and adaption-related information produced by California's scientific community. The site has been developed by UC Berkeley's Geospatial Innovation Facility (GIF) in collaboration with the California Energy Commission's (CEC) Research Program. The Cal-Adapt website allows decision makers, scientists and residents of California to turn research results and climate projections into effective adaptation decisions and policies. Since its release to the public in June 2011, Cal-Adapt has been visited by more than 94,000 unique visitors from over 180 countries, all 50 U.S. states, and 689 California localities. We will present several key visualizations that have been employed by Cal-Adapt's users to support their efforts to understand local impacts of climate change, indicate the breadth of data available, and delineate specific use cases. Recently, CEC and GIF have been developing and releasing Cal-Adapt 2.0, which includes updates and enhancements that are increasing its ease of use, information value, visualization tools, and data accessibility. We showcase how Cal-Adapt is evolving in response to feedback from a variety of sources to present finer-resolution downscaled data, and offer an open API that allows other organization to access Cal-Adapt climate data and build domain specific visualization and planning tools. Through a combination of locally relevant information, visualization tools, and access to primary data, Cal-Adapt allows users to investigate how the climate is projected to change in their areas of interest.

  16. Reciprocal Interactions of the Intestinal Microbiota and Immune System

    PubMed Central

    Maynard, Craig L.; Elson, Charles O.; Hatton, Robin D.; Weaver, Casey T.

    2013-01-01

    Preface Emergence of the adaptive immune system in vertebrates set the stage for evolution of an advanced symbiotic relationship with the intestinal microbiota. The defining features of specificity and memory that characterize adaptive immunity have afforded vertebrates mechanisms for efficiently tailoring immune responses to diverse types of microbes, whether to promote mutualism or host defense. These same attributes carry risk for immune-mediated diseases that are increasingly linked to the intestinal microbiota. Understanding how the adaptive immune system copes with the remarkable number and diversity of microbes that colonize the digestive tract, and how it integrates with more primitive innate immune mechanisms to maintain immune homeostasis, holds considerable promise for new approaches to modulate immune networks in order to treat and prevent disease. PMID:22972296

  17. Repeated Exposure of Epithelial Cells to Apoptotic Cells Induces the Specific Selection of an Adaptive Phenotype: Implications for Tumorigenesis.

    PubMed

    Feng, Lanfei; Vujicic, Snezana; Dietrich, Michael E; Litbarg, Natalia; Setty, Suman; Antoni, Angelika; Rauch, Joyce; Levine, Jerrold S

    2018-05-16

    The consequences of apoptosis extend beyond mere death of the cell. We have shown that receptor-mediated recognition of apoptotic target cells by viable kidney proximal tubular epithelial cells (PTECs) inhibits PTEC proliferation, growth, and survival. Here we tested the hypothesis that continual exposure to apoptotic targets can induce a phenotypic change in responding PTECs, as in other instances of natural selection. In particular, we demonstrate that repeated exposure to apoptotic targets leads to emergence of a PTEC line (denoted BU.MPT SEL ) resistant to apoptotic target-induced death. Resistance is exquisitely specific. Not only are BU.MPT SEL responders fully resistant to apoptotic target-induced death (~85% survival versus <10% survival of non-selected cells), but do so while retaining sensitivity to all other target-induced responses, including inhibition of proliferation and growth. Moreover, the resistance of BU.MPT SEL responders is specific to target-induced apoptosis, as apoptosis in response to other suicidal stimuli occurs normally. Comparison of the signaling events induced by apoptotic target exposure in selected versus non-selected responders indicated that the acquired resistance of BU.MPT SEL cells lies in a regulatory step affecting the generation of the pro-apoptotic protein, truncated BH3 interacting-domain death agonist (tBID), most likely at the level of BID cleavage by caspase-8. This specific adaptation has especial relevance for cancer, in which the prominence and persistence of cell death entail magnification of the post-mortem effects of apoptotic cells. Just as cancer cells acquire specific resistance to chemotherapeutic agents, we propose that cancer cells may also adapt to their ongoing exposure to apoptotic targets. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

  18. Complementing DIGE proteomics and DNA subarray analyses to shed light on Oenococcus oeni adaptation to ethanol in wine-simulated conditions.

    PubMed

    Costantini, Antonella; Rantsiou, Kalliopi; Majumder, Avishek; Jacobsen, Susanne; Pessione, Enrica; Svensson, Birte; Garcia-Moruno, Emilia; Cocolin, Luca

    2015-06-18

    Direct addition of Oenococcus oeni starters into wine can cause viability problems. In the present study, the influence of ethanol in wine-simulated conditions on O. oeni has been evaluated by complementing microarray techniques and DIGE proteomics. Two different ethanol concentrations were studied. In 12% ethanol, pyrimidine anabolism was stimulated, but in 8% ethanol some energy-consuming biosynthetic pathways were limited. The most significant result was the stress response induced by alcohol that concerned both the cell-envelope and specific stress proteins. Interestingly, 8% and 12% ethanol triggered different stress responses: in mild ethanol stress (8%), chaperones with prevalent refolding activity (like HSP20) were over-expressed, whereas at higher alcohol concentration (12%), together with HSP20 and the refolding DNAJ/K, also chaperones having proteolytic activity (like ClpP) were induced. Furthermore the stress response repressor HrcA was downregulated only at 12% ethanol, suggesting that it controls stress pathways, which are different from those active at 8% alcohol. This result confirms that the HrcA system is operative in O. oeni where the CtrS system is prevalent. The use of malolactic starter cultures has become widespread to control the MLF process and to prevent off-flavors. There is significant interest in understanding the molecular mechanisms that O. oeni uses to adapt to harsh wine conditions. The overall results highlight that the alcohol-induced stress response involves not only biosynthesis of stress proteins but also envelope-linked mechanisms. From a practical point of view this research underlines the importance of starters acclimation to induce responses that would allow better adaptation to the wine. As a consequence, a well adapted starter can complete malolactic fermentation and improve the final wine quality. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. All "Trashed" Out: An Activity Guide to Solid Waste Management for Grades K-6.

    ERIC Educational Resources Information Center

    Illinois Univ., Springfield. Center for Solid Waste Management and Research, Springfield.

    This activity guide, specifically designed for Illinois classrooms but adaptable for other states, seeks to encourage primary students to make their own personal statement and responses to the environment through increased awareness of reducing, reusing, recycling, and composting of solid waste materials. The activities incorporate environmental…

  20. NT-PGC-1α protein is sufficient to link β3-adrenergic receptor activation to transcriptional and physiological components of adaptive thermogenesis.

    PubMed

    Chang, Ji Suk; Fernand, Vivian; Zhang, Yubin; Shin, Jeho; Jun, Hee-Jin; Joshi, Yagini; Gettys, Thomas W

    2012-03-16

    PGC-1α is an inducible transcriptional coactivator that regulates cellular energy metabolism and adaptation to environmental and nutritional stimuli. In tissues expressing PGC-1α, alternative splicing produces a truncated protein (NT-PGC-1α) corresponding to the first 267 amino acids of PGC-1α. Brown adipose tissue also expresses two novel exon 1b-derived isoforms of PGC-1α and NT-PGC-1α, which are 4 and 13 amino acids shorter in the N termini than canonical PGC-1α and NT-PGC-1α, respectively. To evaluate the ability of NT-PGC-1α to substitute for PGC-1α and assess the isoform-specific role of NT-PGC-1α, adaptive thermogenic responses of adipose tissue were evaluated in mice lacking full-length PGC-1α (FL-PGC-1(-/-)) but expressing slightly shorter but functionally equivalent forms of NT-PGC-1α (NT-PGC-1α(254)). At room temperature, NT-PGC-1α and NT-PGC-1α(254) were produced from conventional exon 1a-derived transcripts in brown adipose tissue of wild type and FL-PGC-1α(-/-) mice, respectively. However, cold exposure shifted transcription to exon 1b, increasing exon 1b-derived mRNA levels. The resulting transcriptional responses produced comparable increases in energy expenditure and maintenance of core body temperature in WT and FL-PGC-1α(-/-) mice. Moreover, treatment of the two genotypes with a selective β(3)-adrenergic receptor agonist produced similar increases in energy expenditure, mitochondrial DNA, and reductions in adiposity. Collectively, these findings illustrate that the transcriptional and physiological responses to sympathetic input are unabridged in FL-PGC-1α(-/-) mice, and that NT-PGC-1α is sufficient to link β(3)-androgenic receptor activation to adaptive thermogenesis in adipose tissue. Furthermore, the transcriptional shift from exon 1a to 1b supports isoform-specific roles for NT-PGC-1α in basal and adaptive thermogenesis.

  1. Phenotypic changes contributing to Enterobacter gergoviae biocide resistance.

    PubMed

    Périamé, M; Philippe, N; Condell, O; Fanning, S; Pagès, J-M; Davin-Regli, A

    2015-08-01

    Enterobacter gergoviae is a recurrent contaminant of cosmetic and hygiene products. To understand how this bacterium adapts to biocides, we studied Ent. gergoviae CIP 76.01 and its triclosan and Methylisothiazolinone-chloromethylisothiazolinone (MIT-CMIT) tolerant isogenic mutants. They were compared with others also isolated from contaminated cosmetics. Phenotypic differences were noted and these included changes in the bacterial envelope and flagella along with differences in motility, and biofilm growth rates. Triclosan and MIT-CMIT derivatives expressed flagella and other MIT-CMIT derivatives exhibited some external appendages. Those bacteria expressing a high-level minimal inhibitory concentration to MIT-CMIT, expressed a strong biofilm formation. No differential phenotypes were noted for carbon source utilisation. Enterobacter gergoviae demonstrated a diverse response to both of these preservatives contained in cosmetic preparations, depending on their concentrations. Interestingly, this adaptive response is associated with modifications of filament structure-related proteins contributing to increase the organism motility and the production of biofilm. Recurrent contaminations of cosmetics products by Ent. gergoviae, needed a better understanding concerning the bacterial adaptation to preservative agents, with particular concern to triclosan and MIT-CMIT. We demonstrated that bacteria response is associated to various mechanisms represented by expression of external appendages (pili or fimbriae) that control cell motility and biofilm formation and evolving as the concentration of biocides adaptation increased. Such mechanisms which are not chemical specific can also promote a cross-resistance to other biocidal agents. The characterization of Ent. gergoviae adaptability to biocides allows industry to adjust the ranges of concentrations and composition of preservatives in formula. © 2015 The Society for Applied Microbiology.

  2. Streptococci Engage TLR13 on Myeloid Cells in a Site-Specific Fashion.

    PubMed

    Kolter, Julia; Feuerstein, Reinhild; Spoeri, Evelyne; Gharun, Kourosh; Elling, Roland; Trieu-Cuot, Patrick; Goldmann, Tobias; Waskow, Claudia; Chen, Zhijian J; Kirschning, Carsten J; Deshmukh, Sachin D; Henneke, Philipp

    2016-03-15

    Streptococci are common human colonizers with a species-specific mucocutaneous distribution. At the same time, they are among the most important and most virulent invasive bacterial pathogens. Thus, site-specific cellular innate immunity, which is predominantly executed by resident and invading myeloid cells, has to be adapted with respect to streptococcal sensing, handling, and response. In this article, we show that TLR13 is the critical mouse macrophage (MΦ) receptor in the response to group B Streptococcus, both in bone marrow-derived MΦs and in mature tissue MΦs, such as those residing in the lamina propria of the colon and the dermis, as well as in microglia. In contrast, TLR13 and its chaperone UNC-93B are dispensable for a potent cytokine response of blood monocytes to group B Streptococcus, although monocytes serve as the key progenitors of intestinal and dermal MΦs. Furthermore, a specific role for TLR13 with respect to MΦ function is supported by the response to staphylococci, where TLR13 and UNC-93B limit the cytokine response in bone marrow-derived MΦs and microglia, but not in dermal MΦs. In summary, TLR13 is a critical and site-specific receptor in the single MΦ response to β-hemolytic streptococci. Copyright © 2016 by The American Association of Immunologists, Inc.

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

    ERIC Educational Resources Information Center

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

    2011-01-01

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

  4. Migration and Tissue Tropism of Innate Lymphoid Cells

    PubMed Central

    Kim, Chang H.; Hashimoto-Hill, Seika; Kim, Myunghoo

    2016-01-01

    Innate lymphoid cell (ILCs) subsets differentially populate various barrier and non-barrier tissues, where they play important roles in tissue homeostasis and tissue-specific responses to pathogen attack. Recent findings have provided insight into the molecular mechanisms that guide ILC migration into peripheral tissues, revealing common features among different ILC subsets as well as important distinctions. Recent studies have also highlighted the impact of tissue-specific cues on ILC migration, and the importance of the local immunological milieu. We review these findings here and discuss how the migratory patterns and tissue tropism of different ILC subsets relate to the development and differentiation of these cells, and to ILC-mediated tissue-specific regulation of innate and adaptive immune responses. In this context we outline open questions and important areas of future research. PMID:26708278

  5. Moving through the Stressed Genome: Emerging Regulatory Roles for Transposons in Plant Stress Response.

    PubMed

    Negi, Pooja; Rai, Archana N; Suprasanna, Penna

    2016-01-01

    The recognition of a positive correlation between organism genome size with its transposable element (TE) content, represents a key discovery of the field of genome biology. Considerable evidence accumulated since then suggests the involvement of TEs in genome structure, evolution and function. The global genome reorganization brought about by transposon activity might play an adaptive/regulatory role in the host response to environmental challenges, reminiscent of McClintock's original 'Controlling Element' hypothesis. This regulatory aspect of TEs is also garnering support in light of the recent evidences, which project TEs as "distributed genomic control modules." According to this view, TEs are capable of actively reprogramming host genes circuits and ultimately fine-tuning the host response to specific environmental stimuli. Moreover, the stress-induced changes in epigenetic status of TE activity may allow TEs to propagate their stress responsive elements to host genes; the resulting genome fluidity can permit phenotypic plasticity and adaptation to stress. Given their predominating presence in the plant genomes, nested organization in the genic regions and potential regulatory role in stress response, TEs hold unexplored potential for crop improvement programs. This review intends to present the current information about the roles played by TEs in plant genome organization, evolution, and function and highlight the regulatory mechanisms in plant stress responses. We will also briefly discuss the connection between TE activity, host epigenetic response and phenotypic plasticity as a critical link for traversing the translational bridge from a purely basic study of TEs, to the applied field of stress adaptation and crop improvement.

  6. Moving through the Stressed Genome: Emerging Regulatory Roles for Transposons in Plant Stress Response

    PubMed Central

    Negi, Pooja; Rai, Archana N.; Suprasanna, Penna

    2016-01-01

    The recognition of a positive correlation between organism genome size with its transposable element (TE) content, represents a key discovery of the field of genome biology. Considerable evidence accumulated since then suggests the involvement of TEs in genome structure, evolution and function. The global genome reorganization brought about by transposon activity might play an adaptive/regulatory role in the host response to environmental challenges, reminiscent of McClintock's original ‘Controlling Element’ hypothesis. This regulatory aspect of TEs is also garnering support in light of the recent evidences, which project TEs as “distributed genomic control modules.” According to this view, TEs are capable of actively reprogramming host genes circuits and ultimately fine-tuning the host response to specific environmental stimuli. Moreover, the stress-induced changes in epigenetic status of TE activity may allow TEs to propagate their stress responsive elements to host genes; the resulting genome fluidity can permit phenotypic plasticity and adaptation to stress. Given their predominating presence in the plant genomes, nested organization in the genic regions and potential regulatory role in stress response, TEs hold unexplored potential for crop improvement programs. This review intends to present the current information about the roles played by TEs in plant genome organization, evolution, and function and highlight the regulatory mechanisms in plant stress responses. We will also briefly discuss the connection between TE activity, host epigenetic response and phenotypic plasticity as a critical link for traversing the translational bridge from a purely basic study of TEs, to the applied field of stress adaptation and crop improvement. PMID:27777577

  7. Molecular biodiversity of mycotoxigenic fungi that threaten food safety.

    PubMed

    Moretti, A; Susca, A; Mulé, G; Logrieco, A F; Proctor, R H

    2013-10-01

    Fungal biodiversity is one of the most important contributors to the occurrence and severity of mycotoxin contamination of crop plants. Phenotypic and metabolic plasticity has enabled mycotoxigenic fungi to colonize a broad range of agriculturally important crops and to adapt to a range of environmental conditions. New mycotoxin-commodity combinations provide evidence for the ability of fungi to adapt to changing conditions and the emergence of genotypes that confer enhanced aggressiveness toward plants and/or altered mycotoxin production profiles. Perhaps the most important contributor to qualitative differences in mycotoxin production among fungi is variation in mycotoxin biosynthetic genes. Molecular genetic and biochemical analyses of toxigenic fungi have elucidated specific differences in biosynthetic genes that are responsible for intra- and inter-specific differences in mycotoxin production. For Aspergillus and Fusarium, the mycotoxigenic genera of greatest concern, variation in biosynthetic genes responsible for production of individual families of mycotoxins appears to be the result of evolutionary adaptation. Examples of such variation have been reported for: a) aflatoxin biosynthetic genes in Aspergillus flavus and Aspergillus parasiticus; b) trichothecene biosynthetic genes within and among Fusarium species; and c) fumonisin biosynthetic genes in Aspergillus and Fusarium species. Understanding the variation in these biosynthetic genes and the basis for variation in mycotoxin production is important for accurate assessment of the risks that fungi pose to food safety and for prevention of mycotoxin contamination of crops in the field and in storage. © 2013.

  8. Distinct effects of brief and prolonged adaptation on orientation tuning in primary visual cortex

    PubMed Central

    Patterson, Carlyn A.; Wissig, Stephanie C.; Kohn, Adam

    2013-01-01

    Recent stimulus history–adaptation–alters neuronal responses and perception. Previous electrophysiological and perceptual studies suggest that prolonged adaptation strengthens and makes more persistent the effects seen after briefer exposures. However, no systematic comparison has been made between the effects of adaptation lasting hundreds of milliseconds, which might arise during a single fixation, and the more prolonged adaptation typically used in imaging and perceptual studies. Here we determine how 0.4 s, 4 s, and 40 s of adaptation alters orientation tuning in primary visual cortex of anesthetized macaque monkeys, and how quickly responses recover after adapter offset. We measured responses to small (1.3 deg) and large (7.4 deg) gratings because previous work has shown that adaptation effects can depend on stimulus size. Adaptation with small gratings reduced responsivity and caused tuning to shift away from the adapter. These effects strengthened with more prolonged adaptation. For responses to large gratings, brief and prolonged adaptation produced indistinguishable effects on responsivity but caused opposite shifts in tuning preference. Recovery from adaptation was notably slower after prolonged adaptation, even when this did not induce stronger effects. We show that our results can be explained by an adaptation-induced weakening of surround suppression, the dynamics of this suppression, and differential effects of brief and prolonged adaptation across response epochs. Our findings show that effects do not simply scale with adaptation duration, and suggest that distinct strategies exist for adjusting to moment-to-moment fluctuations in input and to more persistent visual stimuli. PMID:23303933

  9. [Connective tissue and inflammation].

    PubMed

    Jakab, Lajos

    2014-03-23

    The author summarizes the structure of the connective tissues, the increasing motion of the constituents, which determine the role in establishing the structure and function of that. The structure and function of the connective tissue are related to each other in the resting as well as inflammatory states. It is emphasized that cellular events in the connective tissue are part of the defence of the organism, the localisation of the damage and, if possible, the maintenance of restitutio ad integrum. The organism responds to damage with inflammation, the non specific immune response, as well as specific, adaptive immunity. These processes are located in the connective tissue. Sterile and pathogenic inflammation are relatively similar processes, but inevitable differences are present, too. Sialic acids and glycoproteins containing sialic acids have important roles, and the role of Siglecs is also highlighted. Also, similarities and differences in damages caused by pathogens and sterile agents are briefly summarized. In addition, the roles of adhesion molecules linked to each other, and the whole event of inflammatory processes are presented. When considering practical consequences it is stressed that the structure (building up) of the organism and the defending function of inflammation both have fundamental importance. Inflammation has a crucial role in maintaining the integrity and the unimpaired somato-psychological state of the organism. Thus, inflammation serves as a tool of organism identical with the natural immune response, inseparably connected with the specific, adaptive immune response. The main events of the inflammatory processes take place in the connective tissue.

  10. Mechanisms for Rapid Adaptive Control of Motion Processing in Macaque Visual Cortex.

    PubMed

    McLelland, Douglas; Baker, Pamela M; Ahmed, Bashir; Kohn, Adam; Bair, Wyeth

    2015-07-15

    A key feature of neural networks is their ability to rapidly adjust their function, including signal gain and temporal dynamics, in response to changes in sensory inputs. These adjustments are thought to be important for optimizing the sensitivity of the system, yet their mechanisms remain poorly understood. We studied adaptive changes in temporal integration in direction-selective cells in macaque primary visual cortex, where specific hypotheses have been proposed to account for rapid adaptation. By independently stimulating direction-specific channels, we found that the control of temporal integration of motion at one direction was independent of motion signals driven at the orthogonal direction. We also found that individual neurons can simultaneously support two different profiles of temporal integration for motion in orthogonal directions. These findings rule out a broad range of adaptive mechanisms as being key to the control of temporal integration, including untuned normalization and nonlinearities of spike generation and somatic adaptation in the recorded direction-selective cells. Such mechanisms are too broadly tuned, or occur too far downstream, to explain the channel-specific and multiplexed temporal integration that we observe in single neurons. Instead, we are compelled to conclude that parallel processing pathways are involved, and we demonstrate one such circuit using a computer model. This solution allows processing in different direction/orientation channels to be separately optimized and is sensible given that, under typical motion conditions (e.g., translation or looming), speed on the retina is a function of the orientation of image components. Many neurons in visual cortex are understood in terms of their spatial and temporal receptive fields. It is now known that the spatiotemporal integration underlying visual responses is not fixed but depends on the visual input. For example, neurons that respond selectively to motion direction integrate signals over a shorter time window when visual motion is fast and a longer window when motion is slow. We investigated the mechanisms underlying this useful adaptation by recording from neurons as they responded to stimuli moving in two different directions at different speeds. Computer simulations of our results enabled us to rule out several candidate theories in favor of a model that integrates across multiple parallel channels that operate at different time scales. Copyright © 2015 the authors 0270-6474/15/3510268-13$15.00/0.

  11. CARMA3 Is Critical for the Initiation of Allergic Airway Inflammation

    PubMed Central

    Causton, Benjamin; Ramadas, Ravisankar A.; Cho, Josalyn L.; Jones, Khristianna; Pardo-Saganta, Ana; Rajagopal, Jayaraj; Xavier, Ramnik J.

    2015-01-01

    Innate immune responses to allergens by airway epithelial cells (AECs) help initiate and propagate the adaptive immune response associated with allergic airway inflammation in asthma. Activation of the transcription factor NF-κB in AECs by allergens or secondary mediators via G protein–coupled receptors (GPCRs) is an important component of this multifaceted inflammatory cascade. Members of the caspase recruitment domain family of proteins display tissue-specific expression and help mediate NF-κB activity in response to numerous stimuli. We have previously shown that caspase recruitment domain–containing membrane-associated guanylate kinase protein (CARMA)3 is specifically expressed in AECs and mediates NF-κB activation in these cells in response to stimulation with the GPCR agonist lysophosphatidic acid. In this study, we demonstrate that reduced levels of CARMA3 in normal human bronchial epithelial cells decreases the production of proasthmatic mediators in response to a panel of asthma-relevant GPCR ligands such as lysophosphatidic acid, adenosine triphosphate, and allergens that activate GPCRs such as Alternaria alternata and house dust mite. We then show that genetically modified mice with CARMA3-deficient AECs have reduced airway eosinophilia and proinflammatory cytokine production in a murine model of allergic airway inflammation. Additionally, we demonstrate that these mice have impaired dendritic cell maturation in the lung and that dendritic cells from mice with CARMA3-deficient AECs have impaired Ag processing. In conclusion, we show that AEC CARMA3 helps mediate allergic airway inflammation, and that CARMA3 is a critical signaling molecule bridging the innate and adaptive immune responses in the lung. PMID:26041536

  12. Development of a genotype-by-sequencing immunogenetic assay as exemplified by screening for variation in red fox with and without endemic rabies exposure.

    PubMed

    Donaldson, Michael E; Rico, Yessica; Hueffer, Karsten; Rando, Halie M; Kukekova, Anna V; Kyle, Christopher J

    2018-01-01

    Pathogens are recognized as major drivers of local adaptation in wildlife systems. By determining which gene variants are favored in local interactions among populations with and without disease, spatially explicit adaptive responses to pathogens can be elucidated. Much of our current understanding of host responses to disease comes from a small number of genes associated with an immune response. High-throughput sequencing (HTS) technologies, such as genotype-by-sequencing (GBS), facilitate expanded explorations of genomic variation among populations. Hybridization-based GBS techniques can be leveraged in systems not well characterized for specific variants associated with disease outcome to "capture" specific genes and regulatory regions known to influence expression and disease outcome. We developed a multiplexed, sequence capture assay for red foxes to simultaneously assess ~300-kbp of genomic sequence from 116 adaptive, intrinsic, and innate immunity genes of predicted adaptive significance and their putative upstream regulatory regions along with 23 neutral microsatellite regions to control for demographic effects. The assay was applied to 45 fox DNA samples from Alaska, where three arctic rabies strains are geographically restricted and endemic to coastal tundra regions, yet absent from the boreal interior. The assay provided 61.5% on-target enrichment with relatively even sequence coverage across all targeted loci and samples (mean = 50×), which allowed us to elucidate genetic variation across introns, exons, and potential regulatory regions (4,819 SNPs). Challenges remained in accurately describing microsatellite variation using this technique; however, longer-read HTS technologies should overcome these issues. We used these data to conduct preliminary analyses and detected genetic structure in a subset of red fox immune-related genes between regions with and without endemic arctic rabies. This assay provides a template to assess immunogenetic variation in wildlife disease systems.

  13. Systemic Cold Stress Adaptation of Chlamydomonas reinhardtii*

    PubMed Central

    Valledor, Luis; Furuhashi, Takeshi; Hanak, Anne-Mette; Weckwerth, Wolfram

    2013-01-01

    Chlamydomonas reinhardtii is one of the most important model organisms nowadays phylogenetically situated between higher plants and animals (Merchant et al. 2007). Stress adaptation of this unicellular model algae is in the focus because of its relevance to biomass and biofuel production. Here, we have studied cold stress adaptation of C. reinhardtii hitherto not described for this algae whereas intensively studied in higher plants. Toward this goal, high throughput mass spectrometry was employed to integrate proteome, metabolome, physiological and cell-morphological changes during a time-course from 0 to 120 h. These data were complemented with RT-qPCR for target genes involved in central metabolism, signaling, and lipid biosynthesis. Using this approach dynamics in central metabolism were linked to cold-stress dependent sugar and autophagy pathways as well as novel genes in C. reinhardtii such as CKIN1, CKIN2 and a hitherto functionally not annotated protein named CKIN3. Cold stress affected extensively the physiology and the organization of the cell. Gluconeogenesis and starch biosynthesis pathways are activated leading to a pronounced starch and sugar accumulation. Quantitative lipid profiles indicate a sharp decrease in the lipophilic fraction and an increase in polyunsaturated fatty acids suggesting this as a mechanism of maintaining membrane fluidity. The proteome is completely remodeled during cold stress: specific candidates of the ribosome and the spliceosome indicate altered biosynthesis and degradation of proteins important for adaptation to low temperatures. Specific proteasome degradation may be mediated by the observed cold-specific changes in the ubiquitinylation system. Sparse partial least squares regression analysis was applied for protein correlation network analysis using proteins as predictors and Fv/Fm, FW, total lipids, and starch as responses. We applied also Granger causality analysis and revealed correlations between proteins and metabolites otherwise not detectable. Twenty percent of the proteins responsive to cold are uncharacterized proteins. This presents a considerable resource for new discoveries in cold stress biology in alga and plants. PMID:23564937

  14. Adaptive mutation of Acetobacter pasteurianus SKU1108 enhances acetic acid fermentation ability at high temperature.

    PubMed

    Matsutani, Minenosuke; Nishikura, Mitsuteru; Saichana, Natsaran; Hatano, Tomoyuki; Masud-Tippayasak, Uraiwan; Theergool, Gunjana; Yakushi, Toshiharu; Matsushita, Kazunobu

    2013-05-20

    In vitro adaptation is one of the most challenging subjects in biology to understand adaptive evolution. Microbial adaptation to temperature is not only interesting in terms of understanding the adaptation mechanism, but also useful for industrial applications. In this study, we attempted the in vitro adaptation of Acetobacter pasteurianus SKU1108 by repeating its cultivation under high-temperature acetic acid fermentation conditions. As a result, thermo-adapted strains having the higher fermentation ability than the wild-type strain were obtained. Mutations and/or disruptions in several proteins of the adapted strains were detected with NGS sequencing technology. In particular, two different adapted strains had mutations or disruptions in three specific genes in common, suggesting that these genes are essential for thermotolerance or fermentation at higher temperature. In order to clarify their involvement in thermotolerance, two of the three genes were disrupted and their phenotype was examined. The results showed that mutations of the two proteins, MarR and an amino acid transporter, are partly responsible for higher fermentation ability and/or thermotolerance. Thus, it was suggested that these elevated abilities of the adapted strains are acquired by assembling several single gene mutations including the above two mutations. Copyright © 2013 Elsevier B.V. All rights reserved.

  15. Stimulus specificity and individual stereotypy of autonomic responses to motion stressors. M.S. Thesis

    NASA Technical Reports Server (NTRS)

    Morgan, M. G.

    1985-01-01

    Motion sickness research shows a lack of agreement regarding the contribution of the autonomic nervous system (ANS). The resolution of this question is exigent for Space Adaptation Syndrome, zero gravity sickness. A case is drawn for the necessity to apply a methodological approach that incorporates: (1) standardization of parameters in relation to the individual differences in variability and prestimulus levels; (2) a concern for patterning of responses; and (3) the physiological association with subjective reports. Vasomotor, heart rate, respiration rate, skin conductance and subjective reports of malaise were collected from 22 subjects while participating in three motion stressors; vertical acceleration, Coriolis stimulation, and combined optokinetic and Coriolis stimulation. The results demonstrate that ANS response patterns can be separated into three mutually exclusive components: (1) a generalized response to motion sickness; (2) a stimulus specific response to the type of stressor being presented; and (3) individualized stereotypical response patterns that are associated with subjective reports of malaise.

  16. Lineage-Specific Responses of Tooth Shape in Murine Rodents (Murinae, Rodentia) to Late Miocene Dietary Change in the Siwaliks of Pakistan

    PubMed Central

    Kimura, Yuri; Jacobs, Louis L.; Flynn, Lawrence J.

    2013-01-01

    Past ecological responses of mammals to climate change are recognized in the fossil record by adaptive significance of morphological variations. To understand the role of dietary behavior on functional adaptations of dental morphology in rodent evolution, we examine evolutionary change of tooth shape in late Miocene Siwalik murine rodents, which experienced a dietary shift toward C4 diets during late Miocene ecological change indicated by carbon isotopic evidence. Geometric morphometric analysis in the outline of upper first molars captures dichotomous lineages of Siwalik murines, in agreement with phylogenetic hypotheses of previous studies (two distinct clades: the Karnimata and Progonomys clades), and indicates lineage-specific functional responses to mechanical properties of their diets. Tooth shapes of the two clades are similar at their sympatric origin but deviate from each other with decreasing overlap through time. Shape change in the Karnimata clade is associated with greater efficiency of propalinal chewing for tough diets than in the Progonomys clade. Larger body mass in Karnimata may be related to exploitation of lower-quality food items, such as grasses, than in smaller-bodied Progonomys. The functional and ecophysiological aspects of Karnimata exploiting C4 grasses are concordant with their isotopic dietary preference relative to Progonomys. Lineage-specific selection was differentially greater in Karnimata, and a faster rate of shape change toward derived Karnimata facilitated inclusion of C4 grasses in the diet. Sympatric speciation in these clades is most plausibly explained by interspecific competition on resource utilization between the two, based on comparisons of our results with the carbon isotope data. Interspecific competition with Karnimata may have suppressed morphological innovation of the Progonomys clade. Pairwise analyses of morphological and carbon isotope data can uncover ecological causes of sympatric speciation and define functional adaptations of teeth to resources. PMID:24155885

  17. Lineage-specific responses of tooth shape in murine rodents (murinae, rodentia) to late Miocene dietary change in the Siwaliks of Pakistan.

    PubMed

    Kimura, Yuri; Jacobs, Louis L; Flynn, Lawrence J

    2013-01-01

    Past ecological responses of mammals to climate change are recognized in the fossil record by adaptive significance of morphological variations. To understand the role of dietary behavior on functional adaptations of dental morphology in rodent evolution, we examine evolutionary change of tooth shape in late Miocene Siwalik murine rodents, which experienced a dietary shift toward C4 diets during late Miocene ecological change indicated by carbon isotopic evidence. Geometric morphometric analysis in the outline of upper first molars captures dichotomous lineages of Siwalik murines, in agreement with phylogenetic hypotheses of previous studies (two distinct clades: the Karnimata and Progonomys clades), and indicates lineage-specific functional responses to mechanical properties of their diets. Tooth shapes of the two clades are similar at their sympatric origin but deviate from each other with decreasing overlap through time. Shape change in the Karnimata clade is associated with greater efficiency of propalinal chewing for tough diets than in the Progonomys clade. Larger body mass in Karnimata may be related to exploitation of lower-quality food items, such as grasses, than in smaller-bodied Progonomys. The functional and ecophysiological aspects of Karnimata exploiting C4 grasses are concordant with their isotopic dietary preference relative to Progonomys. Lineage-specific selection was differentially greater in Karnimata, and a faster rate of shape change toward derived Karnimata facilitated inclusion of C4 grasses in the diet. Sympatric speciation in these clades is most plausibly explained by interspecific competition on resource utilization between the two, based on comparisons of our results with the carbon isotope data. Interspecific competition with Karnimata may have suppressed morphological innovation of the Progonomys clade. Pairwise analyses of morphological and carbon isotope data can uncover ecological causes of sympatric speciation and define functional adaptations of teeth to resources.

  18. Pulmonary Regnase-1 orchestrates the interplay of epithelium and adaptive immune systems to protect against pneumonia.

    PubMed

    Nakatsuka, Yoshinari; Vandenbon, Alexis; Mino, Takashi; Yoshinaga, Masanori; Uehata, Takuya; Cui, Xiaotong; Sato, Ayuko; Tsujimura, Tohru; Suzuki, Yutaka; Sato, Atsuyasu; Handa, Tomohiro; Chin, Kazuo; Sawa, Teiji; Hirai, Toyohiro; Takeuchi, Osamu

    2018-04-25

    Inhaled pathogens including Pseudomonas aeruginosa initially encounter airway epithelial cells (AECs), which are poised to evoke cell-intrinsic innate defense, affecting second tier of hematopoietic cell-mediated immune reaction. However, it is largely unknown how pulmonary immune responses mediated by a variety of immune cells are coordinated. Here we show that Regnase-1, an endoribonuclease expressed in AECs and immune cells, plays an essential role in coordinating innate responses and adaptive immunity against P. aeruginosa infection. Intratracheal treatment of mice with heat-killed P. aeruginosa resulted in prolonged disappearance of Regnase-1 consistent with sustained expression of Regnase-1 target inflammatory genes, whereas the transcription factor NF-κB was only transiently activated. AEC-specific deletion of Regnase-1 not only augmented innate defenses against P. aeruginosa but also enhanced secretion of Pseudomonas-specific IgA and Th17 accumulation in the lung, culminating in conferring significant resistance against P. aeruginosa re-infection in vivo. Although Regnase-1 directly controls distinct sets of genes in each of AECs and T cells, degradation of Regnase-1 in both cell types is beneficial for maximizing acquired immune responses. Collectively, these results demonstrate that Regnase-1 orchestrates AEC-mediated and immune cell-mediated host defense against pulmonary bacterial infection.

  19. Neuromuscular adaptations associated with knee joint angle-specific force change.

    PubMed

    Noorkõiv, Marika; Nosaka, Kazunori; Blazevich, Anthony J

    2014-08-01

    Neuromuscular adaptations to joint angle-specific force increases after isometric training have not yet been fully elucidated. This study examined angle-specific neuromuscular adaptations in response to isometric knee extension training at short (SL, joint angle 38.1° ± 3.7°) versus long (LL, 87.5° ± 6.0°) muscle lengths. Sixteen men trained three times a week for 6 wk either at SL (n = 8) or LL (n = 8). Voluntary maximal isometric knee extensor (MVC) force, doublet twitch force, EMG amplitudes (EMG/Mmax), and voluntary activation during MVC force (VA%) were measured at eight knee joint angles (30°-100°) at weeks 0, 3, and 6. Muscle volume and cross-sectional area (CSA) were measured from magnetic resonance imaging scans, and fascicle length (Lf) was assessed using ultrasonography before and after training. Clear joint angle specificity of force increase was seen in SL but not in LL. The 13.4% ± 9.7% (P = 0.01) force increase around the training angle in SL was related to changes in vastus lateralis and vastus medialis EMG/Mmax around the training angle (r = 0.84-0.88, P < 0.05), without changes in the doublet twitch force-angle relation or muscle size. In LL, muscle volume and CSA increased and the changes in CSA at specific muscle regions were correlated with changes in MVC force. A 5.4% ± 4.9% (P = 0.001) increase in Lf found in both groups was not associated with angle-specific force changes. There were no angle-specific changes in VA%. The EMG/Mmax, although not VA%, results suggest that neural adaptations underpinned training-related changes at short quadriceps lengths, but hypertrophic changes predominated after training at long lengths. The findings of this study should contribute to the development of more effective and evidence-based rehabilitation and strength training protocols.

  20. A model for homeopathic remedy effects: low dose nanoparticles, allostatic cross-adaptation, and time-dependent sensitization in a complex adaptive system

    PubMed Central

    2012-01-01

    Background This paper proposes a novel model for homeopathic remedy action on living systems. Research indicates that homeopathic remedies (a) contain measurable source and silica nanoparticles heterogeneously dispersed in colloidal solution; (b) act by modulating biological function of the allostatic stress response network (c) evoke biphasic actions on living systems via organism-dependent adaptive and endogenously amplified effects; (d) improve systemic resilience. Discussion The proposed active components of homeopathic remedies are nanoparticles of source substance in water-based colloidal solution, not bulk-form drugs. Nanoparticles have unique biological and physico-chemical properties, including increased catalytic reactivity, protein and DNA adsorption, bioavailability, dose-sparing, electromagnetic, and quantum effects different from bulk-form materials. Trituration and/or liquid succussions during classical remedy preparation create “top-down” nanostructures. Plants can biosynthesize remedy-templated silica nanostructures. Nanoparticles stimulate hormesis, a beneficial low-dose adaptive response. Homeopathic remedies prescribed in low doses spaced intermittently over time act as biological signals that stimulate the organism’s allostatic biological stress response network, evoking nonlinear modulatory, self-organizing change. Potential mechanisms include time-dependent sensitization (TDS), a type of adaptive plasticity/metaplasticity involving progressive amplification of host responses, which reverse direction and oscillate at physiological limits. To mobilize hormesis and TDS, the remedy must be appraised as a salient, but low level, novel threat, stressor, or homeostatic disruption for the whole organism. Silica nanoparticles adsorb remedy source and amplify effects. Properly-timed remedy dosing elicits disease-primed compensatory reversal in direction of maladaptive dynamics of the allostatic network, thus promoting resilience and recovery from disease. Summary Homeopathic remedies are proposed as source nanoparticles that mobilize hormesis and time-dependent sensitization via non-pharmacological effects on specific biological adaptive and amplification mechanisms. The nanoparticle nature of remedies would distinguish them from conventional bulk drugs in structure, morphology, and functional properties. Outcomes would depend upon the ability of the organism to respond to the remedy as a novel stressor or heterotypic biological threat, initiating reversals of cumulative, cross-adapted biological maladaptations underlying disease in the allostatic stress response network. Systemic resilience would improve. This model provides a foundation for theory-driven research on the role of nanomaterials in living systems, mechanisms of homeopathic remedy actions and translational uses in nanomedicine. PMID:23088629

  1. A model for homeopathic remedy effects: low dose nanoparticles, allostatic cross-adaptation, and time-dependent sensitization in a complex adaptive system.

    PubMed

    Bell, Iris R; Koithan, Mary

    2012-10-22

    This paper proposes a novel model for homeopathic remedy action on living systems. Research indicates that homeopathic remedies (a) contain measurable source and silica nanoparticles heterogeneously dispersed in colloidal solution; (b) act by modulating biological function of the allostatic stress response network (c) evoke biphasic actions on living systems via organism-dependent adaptive and endogenously amplified effects; (d) improve systemic resilience. The proposed active components of homeopathic remedies are nanoparticles of source substance in water-based colloidal solution, not bulk-form drugs. Nanoparticles have unique biological and physico-chemical properties, including increased catalytic reactivity, protein and DNA adsorption, bioavailability, dose-sparing, electromagnetic, and quantum effects different from bulk-form materials. Trituration and/or liquid succussions during classical remedy preparation create "top-down" nanostructures. Plants can biosynthesize remedy-templated silica nanostructures. Nanoparticles stimulate hormesis, a beneficial low-dose adaptive response. Homeopathic remedies prescribed in low doses spaced intermittently over time act as biological signals that stimulate the organism's allostatic biological stress response network, evoking nonlinear modulatory, self-organizing change. Potential mechanisms include time-dependent sensitization (TDS), a type of adaptive plasticity/metaplasticity involving progressive amplification of host responses, which reverse direction and oscillate at physiological limits. To mobilize hormesis and TDS, the remedy must be appraised as a salient, but low level, novel threat, stressor, or homeostatic disruption for the whole organism. Silica nanoparticles adsorb remedy source and amplify effects. Properly-timed remedy dosing elicits disease-primed compensatory reversal in direction of maladaptive dynamics of the allostatic network, thus promoting resilience and recovery from disease. Homeopathic remedies are proposed as source nanoparticles that mobilize hormesis and time-dependent sensitization via non-pharmacological effects on specific biological adaptive and amplification mechanisms. The nanoparticle nature of remedies would distinguish them from conventional bulk drugs in structure, morphology, and functional properties. Outcomes would depend upon the ability of the organism to respond to the remedy as a novel stressor or heterotypic biological threat, initiating reversals of cumulative, cross-adapted biological maladaptations underlying disease in the allostatic stress response network. Systemic resilience would improve. This model provides a foundation for theory-driven research on the role of nanomaterials in living systems, mechanisms of homeopathic remedy actions and translational uses in nanomedicine.

  2. Chloride-associated adaptive response in aerobic methylotrophic dichloromethane-utilising bacteria.

    PubMed

    Torgonskaya, Maria L; Doronina, Nina V; Hourcade, Edith; Trotsenko, Yuri A; Vuilleumier, Stéphane

    2011-06-01

    Aerobic methylotrophic bacteria able to grow with dichloromethane (DCM) as the sole carbon and energy source possess a specific glutathione S-transferase, DCM dehalogenase, which transforms DCM to formaldehyde, used for biomass and energy production, and hydrochloric acid, which is excreted. Evidence is presented for chloride-specific responses for three DCM-degrading bacteria, Methylobacterium extorquens DM4, Methylopila helvetica DM6 and Albibacter methylovorans DM10. Chloride release into the medium was inhibited by sodium azide and m -chlorophenylhydrazone, suggesting an energy-dependent process. In contrast, only nigericin affected chloride excretion in Mb. extorquens DM4 and Mp. helvetica DM6, while valinomycin had the same effect in A. methylovorans DM10 only. Chloride ions stimulated DCM-dependent induction of DCM dehalogenase expression for Mp. helvetica DM6 and A. methylovorans DM10, and shortened the time for onset of chloride release into the medium. Striking chloride-containing structures were observed by electron microscopy and X-ray microanalysis on the cell surface of Mp. helvetica DM6 and A. methylovorans DM10 during growth with DCM, and with methanol in medium supplemented with sodium chloride. Taken together, these data suggest the existence of both general and specific chloride-associated adaptations in aerobic DCM-degrading bacteria. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Common and metal-specific proteomic responses to cadmium and zinc in the metal tolerant ericoid mycorrhizal fungus Oidiodendron maius Zn.

    PubMed

    Chiapello, M; Martino, E; Perotto, S

    2015-05-01

    Although adaptive metal tolerance may arise in fungal populations in polluted soils, the mechanisms underlying metal-specific tolerance are poorly understood. Comparative proteomics is a powerful tool to identify variation in protein profiles caused by changing environmental conditions, and was used to investigate protein accumulation in a metal tolerant isolate of the ericoid mycorrhizal fungus Oidiodendron maius exposed to zinc and cadmium. Two-dimensional gel electrophoresis and shotgun proteomics followed by mass spectrometry lead to the identification of common and metal-specific proteins and pathways. Proteins selectively induced by cadmium exposure were molecular chaperons of the Hsp90 family, cytoskeletal proteins and components of the translation machinery. Zinc significantly up-regulated metabolic pathways related to energy production and carbohydrates metabolism, likely mirroring zinc adaptation of this fungal isolate. Common proteins induced by the two metal ions were the antioxidant enzyme Cu/Zn superoxide dismutase and ubiquitin. In mycelia exposed to zinc and cadmium, both proteomic techniques also identified agmatinase, an enzyme involved in polyamine biosynthesis. This novel finding suggests that, like plants, polyamines may have important functions in response to abiotic environmental stress in fungi. Genetic evidence also suggests that the biosynthesis of polyamines via an alternative metabolic pathway may be widespread in fungi.

  4. Adaptation to conflict via context-driven anticipatory signals in the dorsomedial prefrontal cortex.

    PubMed

    Horga, Guillermo; Maia, Tiago V; Wang, Pengwei; Wang, Zhishun; Marsh, Rachel; Peterson, Bradley S

    2011-11-09

    Behavioral interference elicited by competing response tendencies adapts to contextual changes. Recent nonhuman primate research suggests a key mnemonic role of distinct prefrontal cells in supporting such context-driven behavioral adjustments by maintaining conflict information across trials, but corresponding prefrontal functions have yet to be probed in humans. Using event-related functional magnetic resonance imaging, we investigated the human neural substrates of contextual adaptations to conflict. We found that a neural system comprising the rostral dorsomedial prefrontal cortex and portions of the dorsolateral prefrontal cortex specifically encodes the history of previously experienced conflict and influences subsequent adaptation to conflict on a trial-by-trial basis. This neural system became active in anticipation of stimulus onsets during preparatory periods and interacted with a second neural system engaged during the processing of conflict. Our findings suggest that a dynamic interaction between a system that represents conflict history and a system that resolves conflict underlies the contextual adaptation to conflict.

  5. Adaptation to Conflict via Context-Driven Anticipatory Signals in the Dorsomedial Prefrontal Cortex

    PubMed Central

    Horga, Guillermo; Maia, Tiago V.; Wang, Pengwei; Wang, Zhishun; Marsh, Rachel; Peterson, Bradley S.

    2011-01-01

    Behavioral interference elicited by competing response tendencies adapts to contextual changes. Recent nonhuman primate research suggests a key mnemonic role of distinct prefrontal cells in supporting such context-driven behavioral adjustments by maintaining conflict information across trials, but corresponding prefrontal functions have yet to be probed in humans. Using event-related functional magnetic resonance imaging (fMRI), we investigated the human neural substrates of contextual adaptations to conflict. We found that a neural system comprising the rostral dorsomedial prefrontal cortex and portions of the dorsolateral prefrontal cortex specifically encodes the history of previously experienced conflict and influences subsequent adaptation to conflict on a trial-by-trial basis. This neural system became active in anticipation of stimulus onsets during preparatory periods and interacted with a second neural system engaged during the processing of conflict. Our findings suggest that a dynamic interaction between a system that represents conflict history and a system that resolves conflict underlies the contextual adaptation to conflict. PMID:22072672

  6. Technology-mediated therapy for chronic pain management: the challenges of adapting behavior change interventions for delivery with pervasive communication technology.

    PubMed

    Rosser, Benjamin A; McCullagh, Paul; Davies, Richard; Mountain, Gail A; McCracken, Lance; Eccleston, Christopher

    2011-04-01

    Adapting therapeutic practice from traditional face-to-face exchange to remote technology-based delivery presents challenges for the therapist, patient, and technical writer. This article documents the process of therapy adaptation and the resultant specification for the SMART2 project-a technology-based self-management system for assisting long-term health conditions, including chronic pain. Focus group discussions with healthcare professionals and patients were conducted to inform selection of therapeutic objectives and appropriate technology. Pertinent challenges are identified, relating to (1) reduction and definition of therapeutic objectives, and (2) how to approach adaptation of therapy to a form suited to technology delivery. The requirement of the system to provide dynamic and intelligent responses to patient experience and behavior is also emphasized. Solutions to these challenges are described in the context of the SMART2 technology-based intervention. More explicit discussion and documentation of therapy adaptation to technology-based delivery within the literature is encouraged.

  7. Developing Tests of Visual Dependency

    NASA Technical Reports Server (NTRS)

    Kindrat, Alexandra N.

    2011-01-01

    Astronauts develop neural adaptive responses to microgravity during space flight. Consequently these adaptive responses cause maladaptive disturbances in balance and gait function when astronauts return to Earth and are re-exposed to gravity. Current research in the Neuroscience Laboratories at NASA-JSC is focused on understanding how exposure to space flight produces post-flight disturbances in balance and gait control and developing training programs designed to facilitate the rapid recovery of functional mobility after space flight. In concert with these disturbances, astronauts also often report an increase in their visual dependency during space flight. To better understand this phenomenon, studies were conducted with specially designed training programs focusing on visual dependency with the aim to understand and enhance subjects ability to rapidly adapt to novel sensory situations. The Rod and Frame test (RFT) was used first to assess an individual s visual dependency, using a variety of testing techniques. Once assessed, subjects were asked to perform two novel tasks under transformation (both the Pegboard and Cube Construction tasks). Results indicate that head position cues and initial visual test conditions had no effect on an individual s visual dependency scores. Subjects were also able to adapt to the manual tasks after several trials. Individual visual dependency correlated with ability to adapt manual to a novel visual distortion only for the cube task. Subjects with higher visual dependency showed decreased ability to adapt to this task. Ultimately, it was revealed that the RFT may serve as an effective prediction tool to produce individualized adaptability training prescriptions that target the specific sensory profile of each crewmember.

  8. Phenotypically plastic neophobia: a response to variable predation risk.

    PubMed

    Brown, Grant E; Ferrari, Maud C O; Elvidge, Chris K; Ramnarine, Indar; Chivers, Douglas P

    2013-04-07

    Prey species possess a variety of morphological, life history and behavioural adaptations to evade predators. While specific evolutionary conditions have led to the expression of permanent, non-plastic anti-predator traits, the vast majority of prey species rely on experience to express adaptive anti-predator defences. While ecologists have identified highly sophisticated means through which naive prey can deal with predation threats, the potential for death upon the first encounter with a predator is still a remarkably important unresolved issue. Here, we used both laboratory and field studies to provide the first evidence for risk-induced neophobia in two taxa (fish and amphibians), and argue that phenotypically plastic neophobia acts as an adaptive anti-predator strategy for vulnerable prey dealing with spatial and temporal variation in predation risk. Our study also illustrates how risk-free maintenance conditions used in laboratory studies may blind researchers to adaptive anti-predator strategies that are only expressed in high-risk conditions.

  9. Genetic algorithms in adaptive fuzzy control

    NASA Technical Reports Server (NTRS)

    Karr, C. Lucas; Harper, Tony R.

    1992-01-01

    Researchers at the U.S. Bureau of Mines have developed adaptive process control systems in which genetic algorithms (GA's) are used to augment fuzzy logic controllers (FLC's). GA's are search algorithms that rapidly locate near-optimum solutions to a wide spectrum of problems by modeling the search procedures of natural genetics. FLC's are rule based systems that efficiently manipulate a problem environment by modeling the 'rule-of-thumb' strategy used in human decision making. Together, GA's and FLC's possess the capabilities necessary to produce powerful, efficient, and robust adaptive control systems. To perform efficiently, such control systems require a control element to manipulate the problem environment, an analysis element to recognize changes in the problem environment, and a learning element to adjust fuzzy membership functions in response to the changes in the problem environment. Details of an overall adaptive control system are discussed. A specific computer-simulated chemical system is used to demonstrate the ideas presented.

  10. Unfinished Business: Evolution of the MHC and the Adaptive Immune System of Jawed Vertebrates.

    PubMed

    Kaufman, Jim

    2018-04-26

    The major histocompatibility complex (MHC) is a large genetic region with many genes, including the highly polymorphic classical class I and II genes that play crucial roles in adaptive as well as innate immune responses. The organization of the MHC varies enormously among jawed vertebrates, but class I and II genes have not been found in other animals. How did the MHC arise, and are there underlying principles that can help us to understand the evolution of the MHC? This review considers what it means to be an MHC and the potential importance of genome-wide duplication, gene linkage, and gene coevolution for the emergence and evolution of an adaptive immune system. Then it considers what the original antigen-specific receptor and MHC molecule might have looked like, how peptide binding might have evolved, and finally the importance of adaptive immunity in general.

  11. Dynamic accommodation responses following adaptation to defocus.

    PubMed

    Cufflin, Matthew P; Mallen, Edward A H

    2008-10-01

    Adaptation to defocus is known to influence the subjective sensitivity to blur in both emmetropes and myopes. Blur is a major contributing factor in the closed-loop dynamic accommodation response. Previous investigations have examined the magnitude of the accommodation response following blur adaptation. We have investigated whether a period of blur adaptation influences the dynamic accommodation response to step and sinusoidal changes in target vergence. Eighteen subjects (six emmetropes, six early onset myopes, and six late onset myopes) underwent 30 min of adaptation to 0.00 D (control), +1.00 D or +3.00 D myopic defocus. Following this adaptation period, accommodation responses to a 2.00 D step change and 2.00 D sinusoidal change (0.2 Hz) in target vergence were recorded continuously using an autorefractor. Adaptation to defocus failed to influence accommodation latency times, but did influence response times to a step change in target vergence. Adaptation to both +1.00 and +3.00 D induced significant increases in response times (p = 0.002 and p = 0.012, respectively) and adaptation to +3.00 D increased the change in accommodation response magnitude (p = 0.014) for a 2.00 D step change in demand. Blur adaptation also significantly increased the peak-to-peak phase lag for accommodation responses to a sinusoidally oscillating target, although failed to influence the accommodation gain. These changes in accommodative response were equivalent across all refractive groups. Adaptation to a degraded stimulus causes an increased level of accommodation for dynamic targets moving towards an observer and increases response times and phase lags. It is suggested that the contrast constancy theory may explain these changes in dynamic behavior.

  12. Climate Adaptation is About More Than Climate: Value-Driven Science Delivery

    NASA Astrophysics Data System (ADS)

    Swanston, C.

    2015-12-01

    Efforts to deliver relevant scientific information and tools to diverse stakeholders have dramatically increased in recent years with the intention of promoting climate change adaptation. Much work has been done to understand the barriers to action, but these largely overlook the need to frame the discussion in terms of stakeholder values and co-create innovative solutions that meet their individual needs. A partnership-based effort in the upper Midwest and Northeast called the Climate Change Response Framework (CCRF; www.forestadaptation.org) ensures relevance, breadth, and credibility of its products through stakeholder inclusion at all levels. The fundamental role of the CCRF is to help people meet their land stewardship goals while minimizing climate risk. This represents a subtle but important shift in focus to people and their values, as opposed to climate change and its effects. The CCRF uses a climate planning tool, the Adaptation Workbook (www.adaptationworkbook.org), along with ecosystem vulnerability assessments and a diverse "menu" of adaptation approaches to generate site-specific adaptation actions that meet explicit conservation objectives. These tools are integrated into an Adaptation Planning and Practices workshop that leads organizations through this structured process of designing adaptation tactics for their projects and plans. All of these tools were developed with stakeholders, or in response to their direct and continuing feedback. The CCRF has involved thousands of people and over 100 organizations, published six ecoregional vulnerability assessments with more than 130 authors, and generated more than 125 intentional adaptation demonstrations in real-world land management projects on federal, state, tribal, county, conservancy, and private lands. The CCRF contributes strongly to the USDA Regional Climate Hubs, working on the applied end of the continuum of climate services occupied by providers such as the CSCs, LCCs, RISAs, and RCCs.

  13. Evaluation of the Physiological Challenges in Extreme Environments: Implications for Enhanced Training, Operational Performance and Sex-Specific Responses

    DTIC Science & Technology

    2017-10-01

    analyses for the first years project. 1. The University of Montana approved the IRB for study 2, “ Effects of Environmental Temperature on Exercise...surrounding phase 2 of the study series. Study 2: Effects of environmental temperature on exercise response and adaptation. We have previously...HH after exercise appears to have a greater effect on muscle oxygen transport (SpO2 and heart rate) than NH. Furthermore, MSTN tends to be further

  14. The Role of Mesenchymal Stem Cells in Promoting Ovarian Cancer Growth and Spread

    DTIC Science & Technology

    2014-12-01

    Immune Response Arm Cells MSC effects Innate Dendritic Cells (APC) Inhibition of maturation (CD80/86 expression) by STAT3 and IL10 (Beyth...are better understood. It is known that once MDSCs are 9 activated, they accumulate in lymphoid organs and tumors where they exert specific T cell 10...expressed on leukocyte 32 subsets and non-immune cells and may regulate important aspects of innate and adaptive 33 immune responses (Mempel, Voelcker et al

  15. Adapter molecule Grb2-associated binder 1 is specifically expressed in marginal zone B cells and negatively regulates thymus-independent antigen-2 responses.

    PubMed

    Itoh, Shousaku; Itoh, Motoyuki; Nishida, Keigo; Yamasaki, Satoru; Yoshida, Yuichi; Narimatsu, Masahiro; Park, Sung Joo; Hibi, Masahiko; Ishihara, Katsuhiko; Hirano, Toshio

    2002-05-15

    Grb2-associated binder 1 (Gab1) is a member of the Gab/daughter of sevenless family of adapter molecules involved in the signal transduction pathways of a variety of growth factors, cytokines, and Ag receptors. To know the role for Gab1 in hematopoiesis and immune responses in vivo, we analyzed radiation chimeras reconstituted with fetal liver (FL) cells of Gab1(-/-) mice, because Gab1(-/-) mice are lethal to embryos. Transfer of Gab1(-/-) FL cells of 14.5 days post-coitum rescued lethally irradiated mice, indicating that Gab1 is not essential for hematopoiesis. Although mature T and B cell subsets developed normally in the peripheral lymphoid organs, reduction of pre-B cells and increase of myeloid cells in the Gab1(-/-) FL chimeras suggested the regulatory roles for Gab1 in hematopoiesis. The chimera showed augmented IgM and IgG1 production to thymus-independent (TI)-2 Ag, although they showed normal responses for thymus-dependent and TI-1 Ags, indicating its negative role specific to TI-2 response. Gab1(-/-) splenic B cells stimulated with anti-delta-dextran plus IL-4 plus IL-5 showed augmented IgM and IgG1 production in vitro that was corrected by the retrovirus-mediated transfection of the wild-type Gab1 gene, clearly demonstrating the cell-autonomous, negative role of Gab1. Furthermore, we showed that the negative role of Gab1 required its Src homology 2-containing tyrosine phosphatase-2 binding sites. Cell fractionation analysis revealed that nonfollicular B cells were responsible for the augmented Ab production in vitro. Consistent with these results, the Gab1 gene was expressed in marginal zone B cells but not follicular B cells. These results indicated that Gab1 is a unique negative regulator specific for TI-2 responses.

  16. Component-specific modeling

    NASA Technical Reports Server (NTRS)

    Mcknight, R. L.

    1985-01-01

    Accomplishments are described for the second year effort of a 3-year program to develop methodology for component specific modeling of aircraft engine hot section components (turbine blades, turbine vanes, and burner liners). These accomplishments include: (1) engine thermodynamic and mission models; (2) geometry model generators; (3) remeshing; (4) specialty 3-D inelastic stuctural analysis; (5) computationally efficient solvers, (6) adaptive solution strategies; (7) engine performance parameters/component response variables decomposition and synthesis; (8) integrated software architecture and development, and (9) validation cases for software developed.

  17. Component-specific modeling. [jet engine hot section components

    NASA Technical Reports Server (NTRS)

    Mcknight, R. L.; Maffeo, R. J.; Tipton, M. T.; Weber, G.

    1992-01-01

    Accomplishments are described for a 3 year program to develop methodology for component-specific modeling of aircraft hot section components (turbine blades, turbine vanes, and burner liners). These accomplishments include: (1) engine thermodynamic and mission models, (2) geometry model generators, (3) remeshing, (4) specialty three-dimensional inelastic structural analysis, (5) computationally efficient solvers, (6) adaptive solution strategies, (7) engine performance parameters/component response variables decomposition and synthesis, (8) integrated software architecture and development, and (9) validation cases for software developed.

  18. Central gene expression changes associated with enhanced neuroendocrine and autonomic response habituation to repeated noise stress after voluntary wheel running in rats

    PubMed Central

    Sasse, Sarah K.; Nyhuis, Tara J.; Masini, Cher V.; Day, Heidi E. W.; Campeau, Serge

    2013-01-01

    Accumulating evidence indicates that regular physical exercise benefits health in part by counteracting some of the negative physiological impacts of stress. While some studies identified reductions in some measures of acute stress responses with prior exercise, limited data were available concerning effects on cardiovascular function, and reported effects on hypothalamic-pituitary-adrenocortical (HPA) axis responses were largely inconsistent. Given that exposure to repeated or prolonged stress is strongly implicated in the precipitation and exacerbation of illness, we proposed the novel hypothesis that physical exercise might facilitate adaptation to repeated stress, and subsequently demonstrated significant enhancement of both HPA axis (glucocorticoid) and cardiovascular (tachycardia) response habituation to repeated noise stress in rats with long-term access to running wheels compared to sedentary controls. Stress habituation has been attributed to modifications of brain circuits, but the specific sites of adaptation and the molecular changes driving its expression remain unclear. Here, in situ hybridization histochemistry was used to examine regulation of select stress-associated signaling systems in brain regions representing likely candidates to underlie exercise-enhanced stress habituation. Analyzed brains were collected from active (6 weeks of wheel running) and sedentary rats following control, acute, or repeated noise exposures that induced a significantly faster rate of glucocorticoid response habituation in active animals but preserved acute noise responsiveness. Nearly identical experimental manipulations also induce a faster rate of cardiovascular response habituation in exercised, repeatedly stressed rats. The observed regulation of the corticotropin-releasing factor and brain-derived neurotrophic factor systems across several brain regions suggests widespread effects of voluntary exercise on central functions and related adaptations to stress across multiple response modalities. PMID:24324441

  19. Visual adaptation and face perception

    PubMed Central

    Webster, Michael A.; MacLeod, Donald I. A.

    2011-01-01

    The appearance of faces can be strongly affected by the characteristics of faces viewed previously. These perceptual after-effects reflect processes of sensory adaptation that are found throughout the visual system, but which have been considered only relatively recently in the context of higher level perceptual judgements. In this review, we explore the consequences of adaptation for human face perception, and the implications of adaptation for understanding the neural-coding schemes underlying the visual representation of faces. The properties of face after-effects suggest that they, in part, reflect response changes at high and possibly face-specific levels of visual processing. Yet, the form of the after-effects and the norm-based codes that they point to show many parallels with the adaptations and functional organization that are thought to underlie the encoding of perceptual attributes like colour. The nature and basis for human colour vision have been studied extensively, and we draw on ideas and principles that have been developed to account for norms and normalization in colour vision to consider potential similarities and differences in the representation and adaptation of faces. PMID:21536555

  20. Cytological techniques to analyze meiosis in Arabidopsis arenosa for investigating adaptation to polyploidy.

    PubMed

    Higgins, James D; Wright, Kevin M; Bomblies, Kirsten; Franklin, F Chris H

    2014-01-01

    Arabidopsis arenosa is a close relative of the model plant A. thaliana, and exists in nature as stable diploid and autotetraploid populations. Natural tetraploids have adapted to whole genome duplication and do not commonly show meiotic errors such as multivalent and univalent formation, which can lead to chromosome non-disjunction and reduced fertility. A genome scan for genes strongly differentiated between diploid and autotetraploid A. arenosa identified a subset of meiotic genes that may be responsible for adaptation to polyploid meiosis. To investigate the mechanisms by which A. arenosa adapted to its polyploid state, and the functionality of the identified potentially adaptive polymorphisms, a thorough cytological analysis is required. Therefore, in this chapter we describe methods and techniques to analyze male meiosis in A. arenosa, including optimum plant growth conditions, and immunocytological and cytological approaches developed with the specific purpose of understanding meiotic adaptation in an autotetraploid. In addition we present a meiotic cytological atlas to be used as a reference for particular stages and discuss observations arising from a comparison of meiosis between diploid and autotetraploid A. arenosa.

  1. Visual adaptation and face perception.

    PubMed

    Webster, Michael A; MacLeod, Donald I A

    2011-06-12

    The appearance of faces can be strongly affected by the characteristics of faces viewed previously. These perceptual after-effects reflect processes of sensory adaptation that are found throughout the visual system, but which have been considered only relatively recently in the context of higher level perceptual judgements. In this review, we explore the consequences of adaptation for human face perception, and the implications of adaptation for understanding the neural-coding schemes underlying the visual representation of faces. The properties of face after-effects suggest that they, in part, reflect response changes at high and possibly face-specific levels of visual processing. Yet, the form of the after-effects and the norm-based codes that they point to show many parallels with the adaptations and functional organization that are thought to underlie the encoding of perceptual attributes like colour. The nature and basis for human colour vision have been studied extensively, and we draw on ideas and principles that have been developed to account for norms and normalization in colour vision to consider potential similarities and differences in the representation and adaptation of faces.

  2. Cognitive control adjustments in healthy older and younger adults: Conflict adaptation, the error-related negativity (ERN), and evidence of generalized decline with age.

    PubMed

    Larson, Michael J; Clayson, Peter E; Keith, Cierra M; Hunt, Isaac J; Hedges, Dawson W; Nielsen, Brent L; Call, Vaughn R A

    2016-03-01

    Older adults display alterations in neural reflections of conflict-related processing. We examined response times (RTs), error rates, and event-related potential (ERP; N2 and P3 components) indices of conflict adaptation (i.e., congruency sequence effects) a cognitive control process wherein previous-trial congruency influences current-trial performance, along with post-error slowing, correct-related negativity (CRN), error-related negativity (ERN) and error positivity (Pe) amplitudes in 65 healthy older adults and 94 healthy younger adults. Older adults showed generalized slowing, had decreased post-error slowing, and committed more errors than younger adults. Both older and younger adults showed conflict adaptation effects; magnitude of conflict adaptation did not differ by age. N2 amplitudes were similar between groups; younger, but not older, adults showed conflict adaptation effects for P3 component amplitudes. CRN and Pe, but not ERN, amplitudes differed between groups. Data support generalized declines in cognitive control processes in older adults without specific deficits in conflict adaptation. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Cytological techniques to analyze meiosis in Arabidopsis arenosa for investigating adaptation to polyploidy

    PubMed Central

    Higgins, James D.; Wright, Kevin M.; Bomblies, Kirsten; Franklin, F. Chris H.

    2014-01-01

    Arabidopsis arenosa is a close relative of the model plant A. thaliana, and exists in nature as stable diploid and autotetraploid populations. Natural tetraploids have adapted to whole genome duplication and do not commonly show meiotic errors such as multivalent and univalent formation, which can lead to chromosome non-disjunction and reduced fertility. A genome scan for genes strongly differentiated between diploid and autotetraploid A. arenosa identified a subset of meiotic genes that may be responsible for adaptation to polyploid meiosis. To investigate the mechanisms by which A. arenosa adapted to its polyploid state, and the functionality of the identified potentially adaptive polymorphisms, a thorough cytological analysis is required. Therefore, in this chapter we describe methods and techniques to analyze male meiosis in A. arenosa, including optimum plant growth conditions, and immunocytological and cytological approaches developed with the specific purpose of understanding meiotic adaptation in an autotetraploid. In addition we present a meiotic cytological atlas to be used as a reference for particular stages and discuss observations arising from a comparison of meiosis between diploid and autotetraploid A. arenosa. PMID:24427164

  4. Climate adaptation planning in practice: an evaluation of adaptation plans from three developed nations

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Preston, Benjamin L; Westaway, Richard M.; Yuen, Emma J.

    2011-04-01

    Formal planning for climate change adaptation is emerging rapidly at a range of geo-political scales. This first generation of adaptation plans provides useful information regarding how institutions are framing the issue of adaptation and the range of processes that are recognized as being part of an adaptation response. To better understand adaptation planning among developed nations, a set of 57 adaptation plans from Australia, the United Kingdom and the United States was evaluated against a suite of 19 planning processes identified from existing guidance instruments for adaptation planning. Total scores among evaluated plans ranged from 16% of the maximum possiblemore » score to 61%, with an average of 37%. These results suggest adaptation plans are largely under-developed. Critical weaknesses in adaptation planning are related to limited consideration for non-climatic factors as well as neglect for issues of adaptive capacity including entitlements to various forms of capital needed for effective adaptation. Such gaps in planning suggest there are opportunities for institutions to make better use of existing guidance for adaptation planning and the need to consider the broader governance context in which adaptation will occur. In addition, the adaptation options prescribed by adaptation plans reflect a preferential bias toward low-risk capacity-building (72% of identified options) over the delivery of specific actions to reduce vulnerability. To the extent these findings are representative of the state of developed nation adaptation planning, there appear to be significant deficiencies in climate change preparedness, even among those nations often assumed to have the greatest adaptive capacity.« less

  5. "What" precedes "which": developmental neural tuning in face- and place-related cortex.

    PubMed

    Scherf, K Suzanne; Luna, Beatriz; Avidan, Galia; Behrmann, Marlene

    2011-09-01

    Although category-specific activation for faces in the ventral visual pathway appears adult-like in adolescence, recognition abilities for individual faces are still immature. We investigated how the ability to represent "individual" faces and houses develops at the neural level. Category-selective regions of interest (ROIs) for faces in the fusiform gyrus (FG) and for places in the parahippocampal place area (PPA) were identified individually in children, adolescents, and adults. Then, using an functional magnetic resonance imaging adaptation paradigm, we measured category selectivity and individual-level adaptation for faces and houses in each ROI. Only adults exhibited both category selectivity and individual-level adaptation bilaterally for faces in the FG and for houses in the PPA. Adolescents showed category selectivity bilaterally for faces in the FG and houses in the PPA. Despite this profile of category selectivity, adolescents only exhibited individual-level adaptation for houses bilaterally in the PPA and for faces in the "left" FG. Children only showed category-selective responses for houses in the PPA, and they failed to exhibit category-selective responses for faces in the FG and individual-level adaptation effects anywhere in the brain. These results indicate that category-level neural tuning develops prior to individual-level neural tuning and that face-related cortex is disproportionately slower in this developmental transition than is place-related cortex.

  6. “What” Precedes “Which”: Developmental Neural Tuning in Face- and Place-Related Cortex

    PubMed Central

    Luna, Beatriz; Avidan, Galia; Behrmann, Marlene

    2011-01-01

    Although category-specific activation for faces in the ventral visual pathway appears adult-like in adolescence, recognition abilities for individual faces are still immature. We investigated how the ability to represent “individual” faces and houses develops at the neural level. Category-selective regions of interest (ROIs) for faces in the fusiform gyrus (FG) and for places in the parahippocampal place area (PPA) were identified individually in children, adolescents, and adults. Then, using an functional magnetic resonance imaging adaptation paradigm, we measured category selectivity and individual-level adaptation for faces and houses in each ROI. Only adults exhibited both category selectivity and individual-level adaptation bilaterally for faces in the FG and for houses in the PPA. Adolescents showed category selectivity bilaterally for faces in the FG and houses in the PPA. Despite this profile of category selectivity, adolescents only exhibited individual-level adaptation for houses bilaterally in the PPA and for faces in the “left” FG. Children only showed category-selective responses for houses in the PPA, and they failed to exhibit category-selective responses for faces in the FG and individual-level adaptation effects anywhere in the brain. These results indicate that category-level neural tuning develops prior to individual-level neural tuning and that face-related cortex is disproportionately slower in this developmental transition than is place-related cortex. PMID:21257673

  7. Shark immunity bites back: affinity maturation and memory response in the nurse shark, Ginglymostoma cirratum.

    PubMed

    Dooley, Helen; Flajnik, Martin F

    2005-03-01

    The cartilaginous fish are the oldest phylogenetic group in which all of the molecular components of the adaptive immune system have been found. Although early studies clearly showed that sharks could produce an IgM-based response following immunization, evidence for memory, affinity maturation and roles for the other isotypes (notably IgNAR) in this group remained inconclusive. The data presented here illustrate that the nurse shark (Ginglymostoma cirratum) is able to produce not only an IgM response, but we also show for the first time a highly antigen-specific IgNAR response. Additionally, under appropriate conditions, a memory response for both isotypes can be elicited. Analysis of the response shows differential expression of pentameric and monomeric IgM. Pentameric IgM provides the 'first line of defense' through high-avidity, low-affinity interaction with antigen. In contrast, monomeric IgM and IgNAR seem responsible for the specific, antigen-driven response. We propose the presence of distinct lineages of B cells in sharks. As there is no conventional isotype switching, each lineage seems pre-determined to express a single isotype (IgM versus IgNAR). However, our data suggest that there may also be specific lineages for the different forms (pentameric versus monomeric) of the IgM isotype.

  8. Constraint, natural selection, and the evolution of human body form

    PubMed Central

    Savell, Kristen R. R.; Auerbach, Benjamin M.; Roseman, Charles C.

    2016-01-01

    Variation in body form among human groups is structured by a blend of natural selection driven by local climatic conditions and random genetic drift. However, attempts to test ecogeographic hypotheses have not distinguished between adaptive traits (i.e., those that evolved as a result of selection) and those that evolved as a correlated response to selection on other traits (i.e., nonadaptive traits), complicating our understanding of the relationship between climate and morphological distinctions among populations. Here, we use evolutionary quantitative methods to test if traits previously identified as supporting ecogeographic hypotheses were actually adaptive by estimating the force of selection on individual traits needed to drive among-group differentiation. Our results show that not all associations between trait means and latitude were caused by selection acting directly on each individual trait. Although radial and tibial length and biiliac and femoral head breadth show signs of responses to directional selection matching ecogeographic hypotheses, the femur was subject to little or no directional selection despite having shorter values by latitude. Additionally, in contradiction to ecogeographic hypotheses, the humerus was under directional selection for longer values by latitude. Responses to directional selection in the tibia and radius induced a nonadaptive correlated response in the humerus that overwhelmed its own trait-specific response to selection. This result emphasizes that mean differences between groups are not good indicators of which traits are adaptations in the absence of information about covariation among characteristics. PMID:27482101

  9. Constraint, natural selection, and the evolution of human body form.

    PubMed

    Savell, Kristen R R; Auerbach, Benjamin M; Roseman, Charles C

    2016-08-23

    Variation in body form among human groups is structured by a blend of natural selection driven by local climatic conditions and random genetic drift. However, attempts to test ecogeographic hypotheses have not distinguished between adaptive traits (i.e., those that evolved as a result of selection) and those that evolved as a correlated response to selection on other traits (i.e., nonadaptive traits), complicating our understanding of the relationship between climate and morphological distinctions among populations. Here, we use evolutionary quantitative methods to test if traits previously identified as supporting ecogeographic hypotheses were actually adaptive by estimating the force of selection on individual traits needed to drive among-group differentiation. Our results show that not all associations between trait means and latitude were caused by selection acting directly on each individual trait. Although radial and tibial length and biiliac and femoral head breadth show signs of responses to directional selection matching ecogeographic hypotheses, the femur was subject to little or no directional selection despite having shorter values by latitude. Additionally, in contradiction to ecogeographic hypotheses, the humerus was under directional selection for longer values by latitude. Responses to directional selection in the tibia and radius induced a nonadaptive correlated response in the humerus that overwhelmed its own trait-specific response to selection. This result emphasizes that mean differences between groups are not good indicators of which traits are adaptations in the absence of information about covariation among characteristics.

  10. Adaptation of Candida albicans to Reactive Sulfur Species

    PubMed Central

    Chebaro, Yasmin; Lorenz, Michael; Fa, Alice; Zheng, Rui; Gustin, Michael

    2017-01-01

    Candida albicans is an opportunistic fungal pathogen that is highly resistant to different oxidative stresses. How reactive sulfur species (RSS) such as sulfite regulate gene expression and the role of the transcription factor Zcf2 and the sulfite exporter Ssu1 in such responses are not known. Here, we show that C. albicans specifically adapts to sulfite stress and that Zcf2 is required for that response as well as induction of genes predicted to remove sulfite from cells and to increase the intracellular amount of a subset of nitrogen metabolites. Analysis of mutants in the sulfate assimilation pathway show that sulfite conversion to sulfide accounts for part of sulfite toxicity and that Zcf2-dependent expression of the SSU1 sulfite exporter is induced by both sulfite and sulfide. Mutations in the SSU1 promoter that selectively inhibit induction by the reactive nitrogen species (RNS) nitrite, a previously reported activator of SSU1, support a model for C. albicans in which Cta4-dependent RNS induction and Zcf2-dependent RSS induction are mediated by parallel pathways, different from S. cerevisiae in which the transcription factor Fzf1 mediates responses to both RNS and RSS. Lastly, we found that endogenous sulfite production leads to an increase in resistance to exogenously added sulfite. These results demonstrate that C. albicans has a unique response to sulfite that differs from the general oxidative stress response, and that adaptation to internal and external sulfite is largely mediated by one transcription factor and one effector gene. PMID:28235888

  11. Improving the Response of Accelerometers for Automotive Applications by Using LMS Adaptive Filters

    PubMed Central

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

    2010-01-01

    In this paper, the least-mean-squares (LMS) algorithm was used to eliminate noise corrupting the important information coming from a piezoresisitive accelerometer for automotive applications. This kind of accelerometer is designed to be easily mounted in hard to reach places on vehicles under test, and they usually feature ranges from 50 to 2,000 g (where is the gravitational acceleration, 9.81 m/s2) and frequency responses to 3,000 Hz or higher, with DC response, durable cables, reliable performance and relatively low cost. However, here we show that the response of the sensor under test had a lot of noise and we carried out the signal processing stage by using both conventional and optimal adaptive filtering. Usually, designers have to build their specific analog and digital signal processing circuits, and this fact increases considerably the cost of the entire sensor system and the results are not always satisfactory, because the relevant signal is sometimes buried in a broad-band noise background where the unwanted information and the relevant signal sometimes share a very similar frequency band. Thus, in order to deal with this problem, here we used the LMS adaptive filtering algorithm and compare it with others based on the kind of filters that are typically used for automotive applications. The experimental results are satisfactory. PMID:22315542

  12. PD-L1 limits the mucosal CD8+ T cell response to Chlamydia trachomatis

    PubMed Central

    Fankhauser, Sarah C.; Starnbach, Michael N.

    2014-01-01

    Chlamydia trachomatis infection is the most common bacterial sexually transmitted disease in the United States. Repeated infections with C. trachomatis lead to serious sequelae such as infertility. It is unclear why the adaptive immune system, specifically the CD8+ T cell response, is unable to protect against subsequent C. trachomatis infections. In this article we characterize the mucosal CD8+ T cell response to C. trachomatis in the murine genital tract. We demonstrate that the immunoinhibitory ligand, PD-L1, contributes to the defective CD8+ T cell response. Deletion or inhibition of PD-L1 restores the CD8+ T cell response and enhances C. trachomatis clearance. PMID:24353266

  13. Specific Stimuli Induce Specific Adaptations: Sensorimotor Training vs. Reactive Balance Training

    PubMed Central

    Freyler, Kathrin; Krause, Anne; Gollhofer, Albert; Ritzmann, Ramona

    2016-01-01

    Typically, balance training has been used as an intervention paradigm either as static or as reactive balance training. Possible differences in functional outcomes between the two modalities have not been profoundly studied. The objective of the study was to investigate the specificity of neuromuscular adaptations in response to two balance intervention modalities within test and intervention paradigms containing characteristics of both profiles: classical sensorimotor training (SMT) referring to a static ledger pivoting around the ankle joint vs. reactive balance training (RBT) using externally applied perturbations to deteriorate body equilibrium. Thirty-eight subjects were assigned to either SMT or RBT. Before and after four weeks of intervention training, postural sway and electromyographic activities of shank and thigh muscles were recorded and co-contraction indices (CCI) were calculated. We argue that specificity of training interventions could be transferred into corresponding test settings containing properties of SMT and RBT, respectively. The results revealed that i) postural sway was reduced in both intervention groups in all test paradigms; magnitude of changes and effect sizes differed dependent on the paradigm: when training and paradigm coincided most, effects were augmented (P<0.05). ii) These specificities were accompanied by segmental modulations in the amount of CCI, with a greater reduction within the CCI of thigh muscles after RBT compared to the shank muscles after SMT (P<0.05). The results clearly indicate the relationship between test and intervention specificity in balance performance. Hence, specific training modalities of postural control cause multi-segmental and context-specific adaptations, depending upon the characteristics of the trained postural strategy. In relation to fall prevention, perturbation training could serve as an extension to SMT to include the proximal segment, and thus the control of structures near to the body’s centre of mass, into training. PMID:27911944

  14. Expression of collagen and related growth factors in rat tendon and skeletal muscle in response to specific contraction types

    PubMed Central

    Heinemeier, K M; Olesen, J L; Haddad, F; Langberg, H; Kjaer, M; Baldwin, K M; Schjerling, P

    2007-01-01

    Acute exercise induces collagen synthesis in both tendon and muscle, indicating an adaptive response in the connective tissue of the muscle–tendon unit. However, the mechanisms of this adaptation, potentially involving collagen-inducing growth factors (such as transforming growth factor-β-1 (TGF-β-1)), as well as enzymes related to collagen processing, are not clear. Furthermore, possible differential effects of specific contraction types on collagen regulation have not been investigated. Female Sprague–Dawley rats were subjected to 4 days of concentric, eccentric or isometric training (n = 7–9 per group) of the medial gastrocnemius, by stimulation of the sciatic nerve. RNA was extracted from medial gastrocnemius and Achilles tendon tissue 24 h after the last training bout, and mRNA levels for collagens I and III, TGF-β-1, connective tissue growth factor (CTGF), lysyl oxidase (LOX), metalloproteinases (MMP-2 and -9) and their inhibitors (TIMP-1 and 2) were measured by Northern blotting and/or real-time PCR. In tendon, expression of TGF-β-1 and collagens I and III (but not CTGF) increased in response to all types of training. Similarly, enzymes/factors involved in collagen processing were induced in tendon, especially LOX (up to 37-fold), which could indicate a loading-induced increase in cross-linking of tendon collagen. In skeletal muscle, a similar regulation of gene expression was observed, but in contrast to the tendon response, the effect of eccentric training was significantly greater than the effect of concentric training on the expression of several transcripts. In conclusion, the study supports an involvement of TGF-β-1 in loading-induced collagen synthesis in the muscle–tendon unit and importantly, it indicates that muscle tissue is more sensitive than tendon to the specific mechanical stimulus. PMID:17540706

  15. Expression of collagen and related growth factors in rat tendon and skeletal muscle in response to specific contraction types.

    PubMed

    Heinemeier, K M; Olesen, J L; Haddad, F; Langberg, H; Kjaer, M; Baldwin, K M; Schjerling, P

    2007-08-01

    Acute exercise induces collagen synthesis in both tendon and muscle, indicating an adaptive response in the connective tissue of the muscle-tendon unit. However, the mechanisms of this adaptation, potentially involving collagen-inducing growth factors (such as transforming growth factor-beta-1 (TGF-beta-1)), as well as enzymes related to collagen processing, are not clear. Furthermore, possible differential effects of specific contraction types on collagen regulation have not been investigated. Female Sprague-Dawley rats were subjected to 4 days of concentric, eccentric or isometric training (n = 7-9 per group) of the medial gastrocnemius, by stimulation of the sciatic nerve. RNA was extracted from medial gastrocnemius and Achilles tendon tissue 24 h after the last training bout, and mRNA levels for collagens I and III, TGF-beta-1, connective tissue growth factor (CTGF), lysyl oxidase (LOX), metalloproteinases (MMP-2 and -9) and their inhibitors (TIMP-1 and 2) were measured by Northern blotting and/or real-time PCR. In tendon, expression of TGF-beta-1 and collagens I and III (but not CTGF) increased in response to all types of training. Similarly, enzymes/factors involved in collagen processing were induced in tendon, especially LOX (up to 37-fold), which could indicate a loading-induced increase in cross-linking of tendon collagen. In skeletal muscle, a similar regulation of gene expression was observed, but in contrast to the tendon response, the effect of eccentric training was significantly greater than the effect of concentric training on the expression of several transcripts. In conclusion, the study supports an involvement of TGF-beta-1 in loading-induced collagen synthesis in the muscle-tendon unit and importantly, it indicates that muscle tissue is more sensitive than tendon to the specific mechanical stimulus.

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

    PubMed

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

    2017-05-01

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

  17. Integrated omics analyses of retrograde signaling mutant delineate interrelated stress-response strata.

    PubMed

    Bjornson, Marta; Balcke, Gerd Ulrich; Xiao, Yanmei; de Souza, Amancio; Wang, Jin-Zheng; Zhabinskaya, Dina; Tagkopoulos, Ilias; Tissier, Alain; Dehesh, Katayoon

    2017-07-01

    To maintain homeostasis in the face of intrinsic and extrinsic insults, cells have evolved elaborate quality control networks to resolve damage at multiple levels. Interorganellar communication is a key requirement for this maintenance, however the underlying mechanisms of this communication have remained an enigma. Here we integrate the outcome of transcriptomic, proteomic, and metabolomics analyses of genotypes including ceh1, a mutant with constitutively elevated levels of both the stress-specific plastidial retrograde signaling metabolite methyl-erythritol cyclodiphosphate (MEcPP) and the defense hormone salicylic acid (SA), as well as the high MEcPP but SA deficient genotype ceh1/eds16, along with corresponding controls. Integration of multi-omic analyses enabled us to delineate the function of MEcPP from SA, and expose the compartmentalized role of this retrograde signaling metabolite in induction of distinct but interdependent signaling cascades instrumental in adaptive responses. Specifically, here we identify strata of MEcPP-sensitive stress-response cascades, among which we focus on selected pathways including organelle-specific regulation of jasmonate biosynthesis; simultaneous induction of synthesis and breakdown of SA; and MEcPP-mediated alteration of cellular redox status in particular glutathione redox balance. Collectively, these integrated multi-omic analyses provided a vehicle to gain an in-depth knowledge of genome-metabolism interactions, and to further probe the extent of these interactions and delineate their functional contributions. Through this approach we were able to pinpoint stress-mediated transcriptional and metabolic signatures and identify the downstream processes modulated by the independent or overlapping functions of MEcPP and SA in adaptive responses. © 2017 The Authors The Plant Journal © 2017 John Wiley & Sons Ltd.

  18. Plant diversity does not buffer drought effects on early-stage litter mass loss rates and microbial properties.

    PubMed

    Vogel, Anja; Eisenhauer, Nico; Weigelt, Alexandra; Scherer-Lorenzen, Michael

    2013-09-01

    Human activities are decreasing biodiversity and changing the climate worldwide. Both global change drivers have been shown to affect ecosystem functioning, but they may also act in concert in a non-additive way. We studied early-stage litter mass loss rates and soil microbial properties (basal respiration and microbial biomass) during the summer season in response to plant species richness and summer drought in a large grassland biodiversity experiment, the Jena Experiment, Germany. In line with our expectations, decreasing plant diversity and summer drought decreased litter mass loss rates and soil microbial properties. In contrast to our hypotheses, however, this was only true for mass loss of standard litter (wheat straw) used in all plots, and not for plant community-specific litter mass loss. We found no interactive effects between global change drivers, that is, drought reduced litter mass loss rates and soil microbial properties irrespective of plant diversity. High mass loss rates of plant community-specific litter and low responsiveness to drought relative to the standard litter indicate that soil microbial communities were adapted to decomposing community-specific plant litter material including lower susceptibility to dry conditions during summer months. Moreover, higher microbial enzymatic diversity at high plant diversity may have caused elevated mass loss of standard litter. Our results indicate that plant diversity loss and summer drought independently impede soil processes. However, soil decomposer communities may be highly adapted to decomposing plant community-specific litter material, even in situations of environmental stress. Results of standard litter mass loss moreover suggest that decomposer communities under diverse plant communities are able to cope with a greater variety of plant inputs possibly making them less responsive to biotic changes. © 2013 John Wiley & Sons Ltd.

  19. NLRC5: a key regulator of MHC class I-dependent immune responses.

    PubMed

    Kobayashi, Koichi S; van den Elsen, Peter J

    2012-12-01

    The expression of MHC class I molecules is crucial for the initiation and regulation of adaptive immune responses against pathogens. NOD-, LRR- and CARD-containing 5 (NLRC5) was recently identified as a specific transactivator of MHC class I genes (CITA). NLRC5 and the master regulator for MHC class II genes, class II transactivator (CIITA), interact with similar MHC promoter-bound factors. Here, we provide a broad overview of the molecular mechanisms behind MHC class I transcription and the role of the class I transactivator NLRC5 in MHC class I-dependent immune responses.

  20. Bacterial Serine/Threonine Protein Kinases in Host-Pathogen Interactions*

    PubMed Central

    Canova, Marc J.; Molle, Virginie

    2014-01-01

    In bacterial pathogenesis, monitoring and adapting to the dynamically changing environment in the host and an ability to disrupt host immune responses are critical. The virulence determinants of pathogenic bacteria include the sensor/signaling proteins of the serine/threonine protein kinase (STPK) family that have a dual role of sensing the environment and subverting specific host defense processes. STPKs can sense a wide range of signals and coordinate multiple cellular processes to mount an appropriate response. Here, we review some of the well studied bacterial STPKs that are essential virulence factors and that modify global host responses during infection. PMID:24554701

  1. Bacterial serine/threonine protein kinases in host-pathogen interactions.

    PubMed

    Canova, Marc J; Molle, Virginie

    2014-04-04

    In bacterial pathogenesis, monitoring and adapting to the dynamically changing environment in the host and an ability to disrupt host immune responses are critical. The virulence determinants of pathogenic bacteria include the sensor/signaling proteins of the serine/threonine protein kinase (STPK) family that have a dual role of sensing the environment and subverting specific host defense processes. STPKs can sense a wide range of signals and coordinate multiple cellular processes to mount an appropriate response. Here, we review some of the well studied bacterial STPKs that are essential virulence factors and that modify global host responses during infection.

  2. Olive cultivars adaptability in Southern Italy in present and future climate

    NASA Astrophysics Data System (ADS)

    Riccardi, M.; Alfieri, S.; Bonfante, A.; Basile, A.; Di Tommasi, P.; Menenti, M.; De Lorenzi, F.

    2012-04-01

    The intra-specific biodiversity of agricultural crops is very significant and likely to provide the single major opportunity to cope with the effects of the changing climate on agricultural ecosystems. Assessment of adaptive capacity must rely on quantitative descriptions of plant responses to environmental factors (e.g. soil water availability, temperature). Moreover climate scenario needs to be downscaled to the spatial scale relevant to crop and farm management. Distributed models of crop response to environmental forcing might be used for this purpose, but severely constrained by the very scarce knowledge on variety-specific values of model parameters, thus limiting the potential exploitation of intra-specific biodiversity towards adaptation. We have developed an approach towards this objective that relies on two complementary elements: a)a distributed model of the soil plant atmosphere system to downscale climate scenarios to landscape units, where generic model parameters for each species are used; b)a data base on climatic requirements of as many varieties as feasible for each species relevant to the agricultural production system of a given region. By means of this approach, the adaptability of some olive cultivars was evaluated in a composite (hills and plains) area of Southern Italy (Valle Telesina, Campania Region, about 20.000 ha). The yearly average temperature is 22.5 °C and rainfall ranges between 600 and 900 mm. Two different climate scenarios were considered: current climate (1961-1990) and future climate (2021-2050). Future climate scenarios at low spatial resolution were generated with general circulation models (AOGCM) and down-scaled by means of a statistical model (Tomozeiu et al., 2007). The climate was represented by daily observations of minimum, maximum temperature and precipitation on a regular grid with a spatial resolution of 35 km; 50 realizations were used for future climate. The soil water regime of 45 soil units was described for the two climate scenarios by using an hydrological distributed model (SWAP). For 11 olive cultivars, the yield response function to soil water regime was determined through the re-analysis of experimental data (unpublished or derived from scientific literature). According to these responses, cultivar-specific threshold values of soil water (or evapotranspiration) deficit were defined. The soil water regime calculated by the distributed model was compared with the threshold values to identify cultivars compatible with present and expected climates. The operation is repeated for a set of realizations of each climate scenario. This analysis is performed in a distributed manner, i.e. using the time series for each model grid to assess possible variations in the extent and spatial distribution of cultivated area of olive cultivars. In the study area future climate scenarios predict an increase of monthly minimum and maximum air temperature of about 2°C during the summer (June, July and August) and a reduction of rainfall in autumn. Spatial pattern of cultivars distribution, according their threshold values and soil water regime, was determined in the present and future climate scenarios, thus assessing variations in cultivars adaptability to future climate with respect to the present. Key words: climate change, biodiversity, water availability, yield response. The work was carried out within the Italian national project AGROSCENARI funded by the Ministry for Agricultural, Food and Forest Policies (MIPAAF, D.M. 8608/7303/2008).

  3. Innate and Adaptive Immune Responses Both Contribute to Pathological CD4 T Cell Activation in HIV-1 Infected Ugandans

    DTIC Science & Technology

    2011-04-01

    vivo in macaques results in increased SIV-specific T cell function and longer survival of the animals [29,30]. In summary, uncontrolled activation...infected homosexual men: NIAID Multicenter AIDS cohort study. Clin Immunol Immunopathol 52: 10–18. 2. Hazenberg MD, Otto SA, van Benthem BH, Roos MT

  4. Evaluating the Mechanism of Oxalate Synthesis of Fibroporia Radiculosa Isolates Adapting to Copper-Tolerance

    Treesearch

    Katie Marie Jenkins

    2012-01-01

    Despite the drawbacks associated with tolerant organisms, copper is still used as the key component in current wood preservatives. Copper-tolerant fungi, like Fibroporia radiculosa, produce and accumulate high levels of oxalate in response to copper. The biosynthesis of oxalate has been connected to specific enzymes in the glyoxylate and...

  5. Cortical pyramidal cells as non-linear oscillators: experiment and spike-generation theory.

    PubMed

    Brumberg, Joshua C; Gutkin, Boris S

    2007-09-26

    Cortical neurons are capable of generating trains of action potentials in response to current injections. These discharges can take different forms, e.g., repetitive firing that adapts during the period of current injection or bursting behaviors. We have used a combined experimental and computational approach to characterize the dynamics leading to action potential responses in single neurons. Specifically we investigated the origin of complex firing patterns in response to sinusoidal current injections. Using a reduced model, the theta-neuron, alongside recordings from cortical pyramidal cells we show that both real and simulated neurons show phase-locking to sine wave stimuli up to a critical frequency, above which period skipping and 1-to-x phase-locking occurs. The locking behavior follows a complex "devil's staircase" phenomena, where locked modes are interleaved with irregular firing. We further show that the critical frequency depends on the time scale of spike generation and on the level of spike frequency adaptation. These results suggest that phase-locking of neuronal responses to complex input patterns can be explained by basic properties of the spike-generating machinery.

  6. LIGHT regulates inflamed draining lymph node hypertrophy

    PubMed Central

    Zhu, Mingzhao; Yang, Yajun; Wang, Yugang; Wang, Zhongnan; Fu, Yang-Xin

    2011-01-01

    Lymph node (LN) hypertrophy, the increased cellularity of LNs, is the major indication of the initiation and expansion of the immune response against infection, vaccination, cancer or autoimmunity. The mechanisms underlying LN hypertrophy remain poorly defined. Here, we demonstrate that LIGHT (TNFSF14) is a novel factor essential for LN hypertrophy after CFA immunization. Mechanistically, LIGHT is required for the influx of lymphocytes into but not egress out of LNs. In addition, LIGHT is required for DC migration from the skin to draining LNs. Compared with WT mice, LIGHT−/− mice express lower levels of chemokines in skin and addressins in LN vascular endothelial cells after CFA immunization. We unexpectedly observed that LIGHT from radioresistant rather than radiosensitive cells, likely Langerhans cells, is required for LN hypertrophy. Importantly, antigen-specific T cell responses were impaired in DLN of LIGHT−/− mice, suggesting the importance of LIGHT regulation of LN hypertrophy in the generation of an adaptive immune response. Collectively, our data reveal a novel cellular and molecular mechanism for the regulation of LN hypertrophy and its potential impact on the generation of an optimal adaptive immune response. PMID:21572030

  7. Neuronal adaptation, novelty detection and regularity encoding in audition

    PubMed Central

    Malmierca, Manuel S.; Sanchez-Vives, Maria V.; Escera, Carles; Bendixen, Alexandra

    2014-01-01

    The ability to detect unexpected stimuli in the acoustic environment and determine their behavioral relevance to plan an appropriate reaction is critical for survival. This perspective article brings together several viewpoints and discusses current advances in understanding the mechanisms the auditory system implements to extract relevant information from incoming inputs and to identify unexpected events. This extraordinary sensitivity relies on the capacity to codify acoustic regularities, and is based on encoding properties that are present as early as the auditory midbrain. We review state-of-the-art studies on the processing of stimulus changes using non-invasive methods to record the summed electrical potentials in humans, and those that examine single-neuron responses in animal models. Human data will be based on mismatch negativity (MMN) and enhanced middle latency responses (MLR). Animal data will be based on the activity of single neurons at the cortical and subcortical levels, relating selective responses to novel stimuli to the MMN and to stimulus-specific neural adaptation (SSA). Theoretical models of the neural mechanisms that could create SSA and novelty responses will also be discussed. PMID:25009474

  8. Modes of response to environmental change and the elusive empirical evidence for bet hedging

    PubMed Central

    Simons, Andrew M.

    2011-01-01

    Uncertainty is a problem not only in human decision-making, but is a prevalent quality of natural environments and thus requires evolutionary response. Unpredictable natural selection is expected to result in the evolution of bet-hedging strategies, which are adaptations to long-term fluctuating selection. Despite a recent surge of interest in bet hedging, its study remains mired in conceptual and practical difficulties, compounded by confusion over what constitutes evidence for its existence. Here, I attempt to resolve misunderstandings about bet hedging and its relationship with other modes of response to environmental change, identify the challenges inherent to its study and assess the state of existing empirical evidence. The variety and distribution of plausible bet-hedging traits found across 16 phyla in over 100 studies suggest their ubiquity. Thus, bet hedging should be considered a specific mode of response to environmental change. However, the distribution of bet-hedging studies across evidence categories—defined according to potential strength—is heavily skewed towards weaker categories, underscoring the need for direct appraisals of the adaptive significance of putative bet-hedging traits in nature. PMID:21411456

  9. Identification of pancreatic glycoprotein 2 as an endogenous immunomodulator of innate and adaptive immune responses.

    PubMed

    Werner, Lael; Paclik, Daniela; Fritz, Christina; Reinhold, Dirk; Roggenbuck, Dirk; Sturm, Andreas

    2012-09-15

    Pancreatic autoantibodies are Crohn disease-specific serologic markers. The function and immunological role of their recently identified autoantigen, glycoprotein 2 (GP2), are unknown. We therefore investigated the impact of GP2 on modulation of innate and adaptive immune responses to evaluate its potential therapeutic use in mucosal inflammation. Our data indicate a previously unknown function for GP2 as an immunomodulator. GP2 was ubiquitously expressed on cells vital to mucosal immune responses. The expression of GP2 was upregulated on activated human T cells, and it was further influenced by pharmaceutical TNF-α inhibitors. Recombinant GP2 significantly decreased human intestinal epithelial cells, mucosal and peripheral T cell proliferation, apoptosis, and activation, and it distinctly modulated cytokine secretion. Furthermore, intestinal epithelial cells stimulated with GP2 potently attracted T cells. In conclusion, we demonstrate a novel role for GP2 in immune regulation that could provide a platform for new therapeutic interventions in the treatment of Crohn disease.

  10. Anthocyanins of Coloured Wheat Genotypes in Specific Response to SalStress.

    PubMed

    Mbarki, Sonia; Sytar, Oksana; Zivcak, Marek; Abdelly, Chedly; Cerda, Artemio; Brestic, Marian

    2018-06-23

    The present study investigated the effect of salt stress on the development of adaptive responses and growth parameters of different coloured wheat genotypes. The different coloured wheat genotypes have revealed variation in the anthocyanin content, which may affect the development of adaptive responses under increasing salinity stress. In the early stage of treatment with salt at a lower NaCl concentration (100 mM), anthocyanins and proline accumulate, which shows rapid development of the stress reaction. A dose-dependent increase in flavonol content was observed for wheat genotypes with more intense purple-blue pigmentation after treatment with 150 mM and 200 mM NaCl. The content of Na⁺ and K⁺ obtained at different levels of salinity based on dry weight (DW) was more than 3 times greater than the control, with a significant increase of both ions under salt stress. Overall, our results demonstrated that coloured wheat genotypes with high anthocyanin content are able to maintain significantly higher dry matter production after salt stress treatment.

  11. Regulation of B1 cell migration by signals through Toll-like receptors

    PubMed Central

    Ha, Seon-ah; Tsuji, Masayuki; Suzuki, Keiichiro; Meek, Bob; Yasuda, Nobutaka; Kaisho, Tsuneyasu; Fagarasan, Sidonia

    2006-01-01

    Peritoneal B1 cells are known to generate large amounts of antibodies outside their residential site. These antibodies play an important role in the early defense against bacteria and viruses, before the establishment of adaptive immune responses. Although many stimuli, including antigen, lipopolysaccharide, or cytokines, have been shown to activate B1 cells and induce their differentiation into plasma cells, the molecular signals required for their egress from the peritoneal cavity are not understood. We demonstrate here that direct signals through Toll-like receptors (TLRs) induce specific, rapid, and transient down-regulation of integrins and CD9 on B1 cells, which is required for detachment from local matrix and a high velocity movement of cells in response to chemokines. Thus, we revealed an unexpected role for TLRs in governing the interplay between integrins, tetraspanins, and chemokine receptors required for B1 cell egress and, as such, in facilitating appropriate transition from innate to adaptive immune responses. PMID:17060475

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

    PubMed

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

    2015-09-01

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

  13. Initial Weight Loss Response as an Indicator for Providing Early Rescue Efforts to Improve Long-term Treatment Outcomes.

    PubMed

    Unick, Jessica L; Pellegrini, Christine A; Demos, Kathryn E; Dorfman, Leah

    2017-09-01

    There is a large variability in response to behavioral weight loss (WL) programs. Reducing rates of obesity and diabetes may require more individuals to achieve clinically significant WL post-treatment. Given that WL within the first 1-2 months of a WL program is associated with long-term WL, it may be possible to improve treatment outcomes by identifying and providing additional intervention to those with poor initial success (i.e., "early non-responders"). We review the current literature regarding early non-response to WL programs and discuss how adaptive interventions can be leveraged as a strategy to "rescue" early non-responders. Preliminary findings suggest that adaptive interventions, specifically stepped care approaches, offer promise for improving outcomes among early non-responders. Future studies need to determine the optimal time point and threshold for intervening and the type of early intervention to employ. Clinicians and researchers should consider the discussed factors when making treatment decisions.

  14. Dendritic cell targeted vaccines: Recent progresses and challenges

    PubMed Central

    Chen, Pengfei; Liu, Xinsheng; Sun, Yuefeng; Zhou, Peng; Wang, Yonglu; Zhang, Yongguang

    2016-01-01

    ABSTRACT Dendritic cells (DCs) are known to be a set of morphology, structure and function of heterogeneous professional antigen presenting cells (APCs), as well as the strongest functional antigen presenting cells, which can absorb, process and present antigens. As the key regulators of innate and adaptive immune responses, DCs are at the center of the immune system and capable of interacting with both B cells and T cells, thereby manipulating the humoral and cellular immune responses. DCs provide an essential link between the innate and adaptive immunity, and the strong immune activation function of DCs and their properties of natural adjuvants, make them a valuable target for antigen delivery. Targeting antigens to DC-specific endocytic receptors in combination with the relevant antibodies or ligands along with immunostimulatory adjuvants has been recently recognized as a promising strategy for designing an effective vaccine that elicits a strong and durable T cell response against intracellular pathogens and cancer. This opinion article provides a brief summary of the rationales, superiorities and challenges of existing DC-targeting approaches. PMID:26513200

  15. Transcriptomic Analyses Elucidate Adaptive Differences of Closely Related Strains of Pseudomonas aeruginosa in Fuel.

    PubMed

    Gunasekera, Thusitha S; Bowen, Loryn L; Zhou, Carol E; Howard-Byerly, Susan C; Foley, William S; Striebich, Richard C; Dugan, Larry C; Ruiz, Oscar N

    2017-05-15

    Pseudomonas aeruginosa can utilize hydrocarbons, but different strains have various degrees of adaptation despite their highly conserved genome. P. aeruginosa ATCC 33988 is highly adapted to hydrocarbons, while P. aeruginosa strain PAO1, a human pathogen, is less adapted and degrades jet fuel at a lower rate than does ATCC 33988. We investigated fuel-specific transcriptomic differences between these strains in order to ascertain the underlying mechanisms utilized by the adapted strain to proliferate in fuel. During growth in fuel, the genes related to alkane degradation, heat shock response, membrane proteins, efflux pumps, and several novel genes were upregulated in ATCC 33988. Overexpression of alk genes in PAO1 provided some improvement in growth, but it was not as robust as that of ATCC 33988, suggesting the role of other genes in adaptation. Expression of the function unknown gene PA5359 from ATCC 33988 in PAO1 increased the growth in fuel. Bioinformatic analysis revealed that PA5359 is a predicted lipoprotein with a conserved Yx(FWY)xxD motif, which is shared among bacterial adhesins. Overexpression of the putative resistance-nodulation-division (RND) efflux pump PA3521 to PA3523 increased the growth of the ATCC 33988 strain, suggesting a possible role in fuel tolerance. Interestingly, the PAO1 strain cannot utilize n -C 8 and n -C 10 The expression of green fluorescent protein (GFP) under the control of alkB promoters confirmed that alk gene promoter polymorphism affects the expression of alk genes. Promoter fusion assays further confirmed that the regulation of alk genes was different in the two strains. Protein sequence analysis showed low amino acid differences for many of the upregulated genes, further supporting transcriptional control as the main mechanism for enhanced adaptation. IMPORTANCE These results support that specific signal transduction, gene regulation, and coordination of multiple biological responses are required to improve the survival, growth, and metabolism of fuel in adapted strains. This study provides new insight into the mechanistic differences between strains and helpful information that may be applied in the improvement of bacterial strains for resistance to biotic and abiotic factors encountered during bioremediation and industrial biotechnological processes. Copyright © 2017 American Society for Microbiology.

  16. Objective assessment of chromatic and achromatic pattern adaptation reveals the temporal response properties of different visual pathways.

    PubMed

    Robson, Anthony G; Kulikowski, Janus J

    2012-11-01

    The aim was to investigate the temporal response properties of magnocellular, parvocellular, and koniocellular visual pathways using increment/decrement changes in contrast to elicit visual evoked potentials (VEPs). Static achromatic and isoluminant chromatic gratings were generated on a monitor. Chromatic gratings were modulated along red/green (R/G) or subject-specific tritanopic confusion axes, established using a minimum distinct border criterion. Isoluminance was determined using minimum flicker photometry. Achromatic and chromatic VEPs were recorded to contrast increments and decrements of 0.1 or 0.2 superimposed on the static gratings (masking contrast 0-0.6). Achromatic increment/decrement changes in contrast evoked a percept of apparent motion when the spatial frequency was low; VEPs to such stimuli were positive in polarity and largely unaffected by high levels of static contrast, consistent with transient response mechanisms. VEPs to finer achromatic gratings showed marked attenuation as static contrast was increased. Chromatic VEPs to R/G or tritan chromatic contrast increments were of negative polarity and showed progressive attenuation as static contrast was increased, in keeping with increasing desensitization of the sustained responses of the color-opponent visual pathways. Chromatic contrast decrement VEPs were of positive polarity and less sensitive to pattern adaptation. The relative contribution of sustained/transient mechanisms to achromatic processing is spatial frequency dependent. Chromatic contrast increment VEPs reflect the sustained temporal response properties of parvocellular and koniocellular pathways. Cortical VEPs can provide an objective measure of pattern adaptation and can be used to probe the temporal response characteristics of different visual pathways.

  17. Genome of Plant Maca (Lepidium meyenii) Illuminates Genomic Basis for High-Altitude Adaptation in the Central Andes.

    PubMed

    Zhang, Jing; Tian, Yang; Yan, Liang; Zhang, Guanghui; Wang, Xiao; Zeng, Yan; Zhang, Jiajin; Ma, Xiao; Tan, Yuntao; Long, Ni; Wang, Yangzi; Ma, Yujin; He, Yuqi; Xue, Yu; Hao, Shumei; Yang, Shengchao; Wang, Wen; Zhang, Liangsheng; Dong, Yang; Chen, Wei; Sheng, Jun

    2016-07-06

    Maca (Lepidium meyenii Walp, 2n = 8x = 64), belonging to the Brassicaceae family, is an economic plant cultivated in the central Andes sierra in Peru (4000-4500 m). Considering that the rapid uplift of the central Andes occurred 5-10 million years ago (Ma), an evolutionary question arises regarding how plants such as maca acquire high-altitude adaptation within a short geological period. Here, we report the high-quality genome assembly of maca, in which two closely spaced maca-specific whole-genome duplications (WGDs; ∼6.7 Ma) were identified. Comparative genomic analysis between maca and closely related Brassicaceae species revealed expansions of maca genes and gene families involved in abiotic stress response, hormone signaling pathway, and secondary metabolite biosynthesis via WGDs. The retention and subsequent functional divergence of many duplicated genes may account for the morphological and physiological changes (i.e., small leaf shape and self-fertility) in maca in a high-altitude environment. In addition, some duplicated maca genes were identified with functions in morphological adaptation (i.e., LEAF CURLING RESPONSIVENESS) and abiotic stress response (i.e., GLYCINE-RICH RNA-BINDING PROTEINS and DNA-DAMAGE-REPAIR/TOLERATION 2) under positive selection. Collectively, the maca genome provides useful information to understand the important roles of WGDs in the high-altitude adaptation of plants in the Andes. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

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

    PubMed

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

    2014-03-01

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

  19. The genomic response of the mouse kidney to low-phosphate diet is altered in X-linked hypophosphatemia.

    PubMed

    Meyer, Martha H; Dulde, Emily; Meyer, Ralph A

    2004-06-17

    The mechanism for the renal adaptation to low-phosphate diets is not well understood. Whether the Hyp mutation of the Phex gene blocks this adaptation is also not clear. To gain further insight into this, 5-wk-old normal and Hyp mice were fed a control (1.0% P) or low-phosphate diet (0.03% P) for 3-5 days. Renal RNA was hybridized to Affymetrix U74Av2 microarrays (5 arrays/group). Of the 5,719 detectable genes on each array, 290 responded significantly (P < 0.01) to low-phosphate diet in normal mice. This was reduced significantly (P < 0.001) to 7 in the Hyp mice. This suggested that the adaptations of the normal kidney to a low-phosphate environment were blocked by the Hyp mutation. The Npt2 phosphate transporter, vitamin D 1alpha- and 24-hydroxylases, and calbindins D9K and D28K responded in the expected fashion. Genes with significant (P < 0.05) diet-by-genotype interaction were analyzed by GenMAPP and MAPPFinder. This revealed a cluster of differentially expressed genes associated with microtubule-based processes. Most alpha- and beta-tubulins and most kinesins had responses to low-phosphate diet in normal mice which were abolished or reversed in Hyp mice. In summary, renal adaptation to low-phosphate diet involved changes in the mRNA expression of specific genes. Disruption of these responses in Hyp mice may contribute to their abnormal phosphate homeostasis.

  20. Adaptive Cellular Stress Pathways as Therapeutic Targets of Dietary Phytochemicals: Focus on the Nervous System

    PubMed Central

    Jo, Dong-Gyu; Park, Daeui; Chung, Hae Young

    2014-01-01

    During the past 5 decades, it has been widely promulgated that the chemicals in plants that are good for health act as direct scavengers of free radicals. Here we review evidence that favors a different hypothesis for the health benefits of plant consumption, namely, that some phytochemicals exert disease-preventive and therapeutic actions by engaging one or more adaptive cellular response pathways in cells. The evolutionary basis for the latter mechanism is grounded in the fact that plants produce natural antifeedant/noxious chemicals that discourage insects and other organisms from eating them. However, in the amounts typically consumed by humans, the phytochemicals activate one or more conserved adaptive cellular stress response pathways and thereby enhance the ability of cells to resist injury and disease. Examplesof such pathways include those involving the transcription factors nuclear factor erythroid 2-related factor 2, nuclear factor-κB, hypoxia-inducible factor 1α, peroxisome proliferator-activated receptor γ, and forkhead box subgroup O, as well as the production and action of trophic factors and hormones. Translational research to develop interventions that target these pathways may lead to new classes of therapeutic agents that act by stimulating adaptive stress response pathways to bolster endogenous defenses against tissue injury and disease. Because neurons are particularly sensitive to potentially noxious phytochemicals, we focus on the nervous system but also include findings from other cell types in which actions of phytochemicals on specific signal transduction pathways have been more thoroughly studied. PMID:24958636

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