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Sample records for bold signal responses

  1. Nonlinear coupling between evoked rCBF and BOLD signals: a simulation study of hemodynamic responses.

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    Mechelli, A; Price, C J; Friston, K J

    2001-10-01

    The aim of this work was to investigate the dependence of BOLD responses on different patterns of stimulus input/neuronal changes. In an earlier report, we described an input-state-output model that combined (i) the Balloon/Windkessel model of nonlinear coupling between rCBF and BOLD signals, and (ii) a linear model of how regional flow changes with synaptic activity. In the present investigation, the input-state-output model was used to explore the dependence of simulated PET (rCBF) and fMRI (BOLD) signals on various parameters pertaining to experimental design. Biophysical simulations were used to estimate rCBF and BOLD responses as functions of (a) a prior stimulus, (b) epoch length (for a fixed SOA), (c) SOA (for a fixed number of events), and (d) stimulus amplitude. We also addressed the notion that a single neuronal response may differ, in terms of the relative contributions of early and late neural components, and investigated the effect of (e) the relative size of the late or "endogenous" neural component. We were interested in the estimated average rCBF and BOLD responses per stimulus or event, not in the statistical efficiency with which these responses are detected. The BOLD response was underestimated relative to rCBF with a preceding stimulus, increasing epoch length, and increasing SOA. Furthermore, the BOLD response showed some highly nonlinear behaviour when varying stimulus amplitude, suggesting some form of hemodynamic "rectification." Finally, the BOLD response was underestimated in the context of large late neuronal components. The difference between rCBF and BOLD is attributed to the nonlinear transduction of rCBF to BOLD signal. Our simulations support the idea that varying parameters that specify the experimental design may have differential effects in PET and fMRI. Moreover, they show that fMRI can be asymmetric in its ability to detect deactivations relative to activations when an absolute baseline is stipulated. Finally, our simulations

  2. One pair of hands is not like another: caudate BOLD response in dogs depends on signal source and canine temperament.

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    Cook, Peter F; Spivak, Mark; Berns, Gregory S

    2014-01-01

    Having previously used functional MRI to map the response to a reward signal in the ventral caudate in awake unrestrained dogs, here we examined the importance of signal source to canine caudate activation. Hand signals representing either incipient reward or no reward were presented by a familiar human (each dog's respective handler), an unfamiliar human, and via illustrated images of hands on a computer screen to 13 dogs undergoing voluntary fMRI. All dogs had received extensive training with the reward and no-reward signals from their handlers and with the computer images and had minimal exposure to the signals from strangers. All dogs showed differentially higher BOLD response in the ventral caudate to the reward versus no reward signals, and there was a robust effect at the group level. Further, differential response to the signal source had a highly significant interaction with a dog's general aggressivity as measured by the C-BARQ canine personality assessment. Dogs with greater aggressivity showed a higher differential response to the reward signal versus no-reward signal presented by the unfamiliar human and computer, while dogs with lower aggressivity showed a higher differential response to the reward signal versus no-reward signal from their handler. This suggests that specific facets of canine temperament bear more strongly on the perceived reward value of relevant communication signals than does reinforcement history, as each of the dogs were reinforced similarly for each signal, regardless of the source (familiar human, unfamiliar human, or computer). A group-level psychophysiological interaction (PPI) connectivity analysis showed increased functional coupling between the caudate and a region of cortex associated with visual discrimination and learning on reward versus no-reward trials. Our findings emphasize the sensitivity of the domestic dog to human social interaction, and may have other implications and applications pertinent to the training and

  3. One pair of hands is not like another: caudate BOLD response in dogs depends on signal source and canine temperament

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    Peter F. Cook

    2014-09-01

    Full Text Available Having previously used functional MRI to map the response to a reward signal in the ventral caudate in awake unrestrained dogs, here we examined the importance of signal source to canine caudate activation. Hand signals representing either incipient reward or no reward were presented by a familiar human (each dog’s respective handler, an unfamiliar human, and via illustrated images of hands on a computer screen to 13 dogs undergoing voluntary fMRI. All dogs had received extensive training with the reward and no-reward signals from their handlers and with the computer images and had minimal exposure to the signals from strangers. All dogs showed differentially higher BOLD response in the ventral caudate to the reward versus no reward signals, and there was a robust effect at the group level. Further, differential response to the signal source had a highly significant interaction with a dog’s general aggressivity as measured by the C-BARQ canine personality assessment. Dogs with greater aggressivity showed a higher differential response to the reward signal versus no-reward signal presented by the unfamiliar human and computer, while dogs with lower aggressivity showed a higher differential response to the reward signal versus no-reward signal from their handler. This suggests that specific facets of canine temperament bear more strongly on the perceived reward value of relevant communication signals than does reinforcement history, as each of the dogs were reinforced similarly for each signal, regardless of the source (familiar human, unfamiliar human, or computer. A group-level psychophysiological interaction (PPI connectivity analysis showed increased functional coupling between the caudate and a region of cortex associated with visual discrimination and learning on reward versus no-reward trials. Our findings emphasize the sensitivity of the domestic dog to human social interaction, and may have other implications and applications

  4. Dorsal root ganglion stimulation attenuates the BOLD signal response to noxious sensory input in specific brain regions: Insights into a possible mechanism for analgesia.

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    Pawela, Christopher P; Kramer, Jeffery M; Hogan, Quinn H

    2017-02-15

    Targeted dorsal root ganglion (DRG) electrical stimulation (i.e. ganglionic field stimulation - GFS) is an emerging therapeutic approach to alleviate chronic pain. Here we describe blood oxygen-level dependent (BOLD) functional magnetic resonance imaging (fMRI) responses to noxious hind-limb stimulation in a rat model that replicates clinical GFS using an electrode implanted adjacent to the DRG. Acute noxious sensory stimulation in the absence of GFS caused robust BOLD fMRI response in brain regions previously associated with sensory and pain-related response, such as primary/secondary somatosensory cortex, retrosplenial granular cortex, thalamus, caudate putamen, nucleus accumbens, globus pallidus, and amygdala. These regions differentially demonstrated either positive or negative correlation to the acute noxious stimulation paradigm, in agreement with previous rat fMRI studies. Therapeutic-level GFS significantly attenuated the global BOLD response to noxious stimulation in these regions. This BOLD signal attenuation persisted for 20minutes after the GFS was discontinued. Control experiments in sham-operated animals showed that the attenuation was not due to the effect of repetitive noxious stimulation. Additional control experiments also revealed minimal BOLD fMRI response to GFS at therapeutic intensity when presented in a standard block-design paradigm. High intensity GFS produced a BOLD signal map similar to acute noxious stimulation when presented in a block-design. These findings are the first to identify the specific brain region responses to neuromodulation at the DRG level and suggest possible mechanisms for GFS-induced treatment of chronic pain. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Larger Neural Responses Produce BOLD Signals That Begin Earlier in Time

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    Serena eThompson

    2014-06-01

    Full Text Available Functional MRI analyses commonly rely on the assumption that the temporal dynamics of hemodynamic response functions (HRFs are independent of the amplitude of the neural signals that give rise to them. The validity of this assumption is particularly important for techniques that use fMRI to resolve sub-second timing distinctions between responses, in order to make inferences about the ordering of neural processes. Whether or not the detailed shape of the HRF is independent of neural response amplitude remains an open question, however. We performed experiments in which we measured responses in primary visual cortex (V1 to large, contrast-reversing checkerboards at a range of contrast levels, which should produce varying amounts of neural activity. Ten subjects (ages 22-52 were studied in each of two experiments using 3 Tesla scanners. We used rapid, 250 msec, temporal sampling (repetition time, or TR and both short and long inter-stimulus interval (ISI stimulus presentations. We tested for a systematic relationship between the onset of the HRF and its amplitude across conditions, and found a strong negative correlation between the two measures when stimuli were separated in time (long- and medium-ISI experiments, but not the short-ISI experiment. Thus, stimuli that produce larger neural responses, as indexed by HRF amplitude, also produced HRFs with shorter onsets. The relationship between amplitude and latency was strongest in voxels with lowest mean-normalized variance (i.e., parenchymal voxels. The onset differences observed in the longer-ISI experiments are likely attributable to mechanisms of neurovascular coupling, since they are substantially larger than reported differences in the onset of action potentials in V1 as a function of response amplitude.

  6. Reproducibility of BOLD signal change induced by breath holding.

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    Magon, Stefano; Basso, Gianpaolo; Farace, Paolo; Ricciardi, Giuseppe Kenneth; Beltramello, Alberto; Sbarbati, Andrea

    2009-04-15

    Blood oxygen level dependent (BOLD) contrast is influenced by some physiological factors such as blood flow and blood volume that can be a source of variability in fMRI analysis. Previous studies proposed to use the cerebrovascular response data to normalize or calibrate BOLD maps in order to reduce variability of fMRI data both among brain areas in single subject analysis and across subjects. Breath holding is one of the most widely used methods to investigate the vascular reactivity. However, little is known about the robustness and reproducibility of this procedure. In this study we investigated three different breath holding periods. Subjects were asked to hold their breath for 9, 15 or 21 s in three separate runs and the fMRI protocol was repeated after 15 to 20 days. Our data show that the BOLD response to breath holding after inspiration results in a complex shape due to physiological factors that influence the signal variation with a timing that is highly reproducible. Nevertheless, the reproducibility of the magnitude of the cerebrovascular response to CO(2), expressed as amplitude of BOLD signal and number of responding voxels, strongly depends on duration of breath holding periods. Breath holding period of 9 s results in high variability of the magnitude of the response while longer breath holding durations produce more robust and reproducible BOLD responses.

  7. Pattern of BOLD signal in auditory cortex relates acoustic response to perceptual streaming

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    Yadav Deepak

    2011-08-01

    Full Text Available Abstract Background Segregating auditory scenes into distinct objects or streams is one of our brain's greatest perceptual challenges. Streaming has classically been studied with bistable sound stimuli, perceived alternately as a single group or two separate groups. Throughout the last decade different methodologies have yielded inconsistent evidence about the role of auditory cortex in the maintenance of streams. In particular, studies using functional magnetic resonance imaging (fMRI have been unable to show persistent activity within auditory cortex (AC that distinguishes between perceptual states. Results We use bistable stimuli, an explicit perceptual categorization task, and a focused region of interest (ROI analysis to demonstrate an effect of perceptual state within AC. We find that AC has more activity when listeners perceive the split percept rather than the grouped percept. In addition, within this ROI the pattern of acoustic response across voxels is significantly correlated with the pattern of perceptual modulation. In a whole-brain exploratory test, we corroborate previous work showing an effect of perceptual state in the intraparietal sulcus. Conclusions Our results show that the maintenance of auditory streams is reflected in AC activity, directly relating sound responses to perception, and that perceptual state is further represented in multiple, higher level cortical regions.

  8. Cortical layers, rhythms and BOLD signals.

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    Scheeringa, René; Fries, Pascal

    2017-11-03

    This review investigates how laminar fMRI can complement insights into brain function derived from the study of rhythmic neuronal synchronization. Neuronal synchronization in various frequency bands plays an important role in neuronal communication between brain areas, and it does so on the backbone of layer-specific interareal anatomical projections. Feedforward projections originate predominantly in supragranular cortical layers and terminate in layer 4, and this pattern is reflected in inter-laminar and interareal directed gamma-band influences. Thus, gamma-band synchronization likely subserves feedforward signaling. By contrast, anatomical feedback projections originate predominantly in infragranular layers and terminate outside layer 4, and this pattern is reflected in inter-laminar and interareal directed alpha- and/or beta-band influences. Thus, alpha-beta band synchronization likely subserves feedback signaling. Furthermore, these rhythms explain part of the BOLD signal, with independent contributions of alpha-beta and gamma. These findings suggest that laminar fMRI can provide us with a potentially useful method to test some of the predictions derived from the study of neuronal synchronization. We review central findings regarding the role of layer-specific neuronal synchronization for brain function, and regarding the link between neuronal synchronization and the BOLD signal. We discuss the role that laminar fMRI could play by comparing it to invasive and non-invasive electrophysiological recordings. Compared to direct electrophysiological recordings, this method provides a metric of neuronal activity that is slow and indirect, but that is uniquely non-invasive and layer-specific with potentially whole brain coverage. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  9. Controlled inspiration depth reduces variance in breath-holding induced BOLD signal

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    Thomason, Moriah E.; Glover, Gary H.

    2007-01-01

    Recent studies have shown that Blood Oxygen Level Dependent (BOLD) response amplitude during short periods of breath holding (BH) measured by functional Magnetic Resonance Imaging (fMRI) can be an effective metric for intersubject calibration procedures. However, inconsistency in the depth of inspiration during the BH scan may account for a portion of BOLD variation observed in such scans, and it is likely to reduce the effectiveness of the calibration measurement. While modulation of BOLD signal has been correlated with end-tidal CO2 and other measures of breathing, fluctuations in performance of BH have not been studied in the context of their impact on BOLD signal. Here, we studied the degree to which inspiration depth corresponds to BOLD signal change, and tested the effectiveness of a method designed to control inspiration level through visual cues during the BH task paradigm. We observed reliable differences in BOLD signal amplitude corresponding to the depth of inspiration. It was determined that variance in BOLD signal response to BH could be significantly reduced when subjects were given visual feedback during task inspiration periods. The implications of these findings for routine BH studies of BOLD-derived neurovascular response are discussed. PMID:17905599

  10. Controlled inspiration depth reduces variance in breath-holding-induced BOLD signal.

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    Thomason, Moriah E; Glover, Gary H

    2008-01-01

    Recent studies have shown that blood oxygen level dependent (BOLD) response amplitude during short periods of breath holding (BH) measured by functional magnetic resonance imaging (fMRI) can be an effective metric for intersubject calibration procedures. However, inconsistency in the depth of inspiration during the BH scan may account for a portion of BOLD variation observed in such scans, and it is likely to reduce the effectiveness of the calibration measurement. While modulation of BOLD signal has been correlated with end-tidal CO2 and other measures of breathing, fluctuations in performance of BH have not been studied in the context of their impact on BOLD signal. Here, we studied the degree to which inspiration depth corresponds to BOLD signal change and tested the effectiveness of a method designed to control inspiration level through visual cues during the BH task paradigm. We observed reliable differences in BOLD signal amplitude corresponding to the depth of inspiration. It was determined that variance in BOLD signal response to BH could be significantly reduced when subjects were given visual feedback during task inspiration periods. The implications of these findings for routine BH studies of BOLD-derived neurovascular response are discussed.

  11. Metabolic Changes Underlying Bold Signal Variations after Administration of Zolpidem

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    Rodriguez-Rojas, Rafael; Machado, Calixto; Alvarez, Lazaro; Carballo, Maylen; Perez-Nellar, Jesus; Estevez, Mario; Pavon, Nancy; Chinchilla, Mauricio

    2010-12-01

    Zolpidem is a non-benzodiazepine drug belonging to the imidazopiridine class, which has selectivity for stimulating the effect of gamma aminobutyric acid [GABA] and is used for the therapy of insomnia. Nonetheless, several reports have been published over recent years about a paradoxical arousing effect of Zolpidem in patients with severe brain damage. We studied a PVS case using 1 H-MRS and BOLD signal, before and after Zolpidem administration. Significantly increased BOLD signal was localized in left frontal superior cortex, bilateral cingulated areas, left thalamus and right head of the caudate nucleus. A transient activation was observed in frontal cortex, comprising portions of anterior cingulate, medial, and orbito-frontal cortices. Additionally, significant pharmacological activation in sensory-motor cortex is observed 1 hour after Zolpidem intake. Significant linear correlations of BOLD signal changes were found with primary concentrations of NAA, Glx and Lac in the right frontal cortex. We discussed that when Zolpidem attaches to the modified GABA receptors of the neurodormant cells, dormancy is switched off, inducing brain activation. This might explain the significant correlations of BOLD signal changes and 1 H-MRS metabolites in our patient. We concluded that 1 H-MRS and BOLD signal assessment might contribute to study neurovascular coupling in PVS cases after Zolpidem administration. Although this is a report of a single case, considering our results we recommend to apply this methodology in series of PVS and MCS patients. (author)

  12. Analysis of time and space invariance of BOLD responses in the rat visual system

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    Bailey, Christopher; Sanganahalli, Basavaraju G; Herman, Peter

    2013-01-01

    superior colliculus (SC) and primary visual cortex (V1) in rat brain--regions with different basal blood flow and energy demand. Our goal was to assess neurovascular coupling in V1 and SC as reflected by temporal/spatial variances of impulse response functions (IRFs) and assess, if any, implications......Neuroimaging studies of functional magnetic resonance imaging (fMRI) and electrophysiology provide the linkage between neural activity and the blood oxygenation level-dependent (BOLD) response. Here, BOLD responses to light flashes were imaged at 11.7T and compared with neural recordings from...... for general linear modeling (GLM) of BOLD responses. Light flashes induced high magnitude neural/BOLD responses reproducibly from both regions. However, neural/BOLD responses from SC and V1 were markedly different. SC signals followed the boxcar shape of the stimulation paradigm at all flash rates, whereas V1...

  13. Generate the scale-free brain music from BOLD signals.

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    Lu, Jing; Guo, Sijia; Chen, Mingming; Wang, Weixia; Yang, Hua; Guo, Daqing; Yao, Dezhong

    2018-01-01

    Many methods have been developed to translate a human electroencephalogram (EEG) into music. In addition to EEG, functional magnetic resonance imaging (fMRI) is another method used to study the brain and can reflect physiological processes. In 2012, we established a method to use simultaneously recorded fMRI and EEG signals to produce EEG-fMRI music, which represents a step toward scale-free brain music. In this study, we used a neural mass model, the Jansen-Rit model, to simulate activity in several cortical brain regions. The interactions between different brain regions were represented by the average normalized diffusion tensor imaging (DTI) structural connectivity with a coupling coefficient that modulated the coupling strength. Seventy-eight brain regions were adopted from the Automated Anatomical Labeling (AAL) template. Furthermore, we used the Balloon-Windkessel hemodynamic model to transform neural activity into a blood-oxygen-level dependent (BOLD) signal. Because the fMRI BOLD signal changes slowly, we used a sampling rate of 250 Hz to produce the temporal series for music generation. Then, the BOLD music was generated for each region using these simulated BOLD signals. Because the BOLD signal is scale free, these music pieces were also scale free, which is similar to classic music. Here, to simulate the case of an epileptic patient, we changed the parameter that determined the amplitude of the excitatory postsynaptic potential (EPSP) in the neural mass model. Finally, we obtained BOLD music for healthy and epileptic patients. The differences in levels of arousal between the 2 pieces of music may provide a potential tool for discriminating the different populations if the differences can be confirmed by more real data. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

  14. Time courses of MRI BOLD signals in prolonged visual stimulation. Comparison between colors and orders

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    Kashikura, Kenichi; Fujita, Hideaki; Kershaw, J.B.; Matsuura, Tetsuya; Seki, Chie; Kashikura, Akemi; Ardekani, B.A.; Kanno, Iwao

    1998-01-01

    We investigated: the BOLD signal response during 270 second photic stimulation using an EPI pulse sequence; the BOLD signal response for two different color checkerboards; and the BOLD signal response during six consecutive stimulation series. Ten healthy human subjects (age 25±5.5 years) were studied with a 1.5 T MRI system (Siemens Vision, Erlangen, Germany). Black and white (BW) and red and white (RW) checkerboards alternating at 8 Hz were applied in turns for a total series of six. Stimulation timing was: 30 sec. off, 15 sec. on, 15 sec. off, 270 sec. on, 15 sec. off, 15 sec. on, 15 sec. off. Acquired data were analyzed according to color and/or order: color (without considering the order); color and order (1st BW vs. 1st RW, 2nd BW vs. 2nd RW, 3rd BW vs. 3rd RW); and order (without considering the color). A t-test (p<0.001) was used for obtaining the activated areas, and simple regression and two-way repeated-measures ANOVA were used for testing the statistical significance of the BOLD response. Results were: the BOLD signal responses during sustained photic stimulation maintained a constant level for the full duration and all series, suggesting stable levels of oxygen extraction and metabolism during cortical activation; the BOLD signal responses in two colors showed no significant difference in time response, suggesting that the neuronal populations perceiving black and red give a similar time response; and the effect of habituation or fatigue as observed by a signal decrease was not obtained, although the S.D. for each subject greatly increased with time and might be an indicator for evaluation fatigue or attention. (author)

  15. Using pulse oximetry to account for high and low frequency physiological artifacts in the BOLD signal.

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    Verstynen, Timothy D; Deshpande, Vibhas

    2011-04-15

    The BOLD signal not only reflects changes in local neural activity, but also exhibits variability from physiological processes like cardiac rhythms and breathing. We investigated how both of these physiological sources are reflected in the pulse oximetry (PO) signal, a direct measure of blood oxygenation, and how this information can be used to account for different types of noise in the BOLD response. Measures of heart rate, respiration and PO were simultaneously recorded while neurologically healthy participants performed an eye-movement task in a 3T MRI. PO exhibited power in frequencies that matched those found in the independently recorded cardiac and respiration signals. Using the phasic and aphasic properties of these signals as nuisance regressors, we found that the different frequency components of the PO signal could be used to identify different types of physiological artifacts in the BOLD response. A comparison of different physiological noise models found that a simple, down-sampled version of the PO signal improves the estimation of task-relevant statistics nearly as well as more established noise models that may run the risk of over-parameterization. These findings suggest that the PO signal captures multiple sources of physiological noise in the BOLD response and provides a simple and efficient way of modeling these noise sources in subsequent analysis. Copyright © 2011 Elsevier Inc. All rights reserved.

  16. Differentiating BOLD and non-BOLD signals in fMRI time series using multi-echo EPI.

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    Kundu, Prantik; Inati, Souheil J; Evans, Jennifer W; Luh, Wen-Ming; Bandettini, Peter A

    2012-04-15

    A central challenge in the fMRI based study of functional connectivity is distinguishing neuronally related signal fluctuations from the effects of motion, physiology, and other nuisance sources. Conventional techniques for removing nuisance effects include modeling of noise time courses based on external measurements followed by temporal filtering. These techniques have limited effectiveness. Previous studies have shown using multi-echo fMRI that neuronally related fluctuations are Blood Oxygen Level Dependent (BOLD) signals that can be characterized in terms of changes in R(2)* and initial signal intensity (S(0)) based on the analysis of echo-time (TE) dependence. We hypothesized that if TE-dependence could be used to differentiate BOLD and non-BOLD signals, non-BOLD signal could be removed to denoise data without conventional noise modeling. To test this hypothesis, whole brain multi-echo data were acquired at 3 TEs and decomposed with Independent Components Analysis (ICA) after spatially concatenating data across space and TE. Components were analyzed for the degree to which their signal changes fit models for R(2)* and S(0) change, and summary scores were developed to characterize each component as BOLD-like or not BOLD-like. These scores clearly differentiated BOLD-like "functional network" components from non BOLD-like components related to motion, pulsatility, and other nuisance effects. Using non BOLD-like component time courses as noise regressors dramatically improved seed-based correlation mapping by reducing the effects of high and low frequency non-BOLD fluctuations. A comparison with seed-based correlation mapping using conventional noise regressors demonstrated the superiority of the proposed technique for both individual and group level seed-based connectivity analysis, especially in mapping subcortical-cortical connectivity. The differentiation of BOLD and non-BOLD components based on TE-dependence was highly robust, which allowed for the

  17. The BOLD cerebrovascular reactivity response to progressive hypercapnia in young and elderly.

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    Bhogal, Alex A; De Vis, Jill B; Siero, Jeroen C W; Petersen, Esben T; Luijten, Peter R; Hendrikse, Jeroen; Philippens, Marielle E P; Hoogduin, Hans

    2016-10-01

    Blood Oxygenation Level Dependent (BOLD) imaging in combination with vasoactive stimuli can be used to probe cerebrovascular reactivity (CVR). Characterizing the healthy, age-related changes in the BOLD-CVR response can provide a reference point from which to distinguish abnormal CVR from the otherwise normal effects of ageing. Using a computer controlled gas delivery system, we examine differences in BOLD-CVR response to progressive hypercapnia between 16 young (28±3years, 9 female) and 30 elderly subjects (66±4years, 13 female). Furthermore, we incorporate baseline T 2 * information to broaden our interpretation of the BOLD-CVR response. Significant age-related differences were observed. Grey matter CVR at 7mmHg above resting PetCO 2 was lower amongst elderly (0.19±0.06%ΔBOLD/mmHg) as compared to young subjects (0.26±0.07%ΔBOLD/mmHg). White matter CVR at 7mmHg above baseline PetCO 2 showed no significant difference between young (0.04±0.02%ΔBOLD/mmHg) and elderly subjects (0.05±0.03%ΔBOLD/mmHg). We saw no significant differences in the BOLD signal response to progressive hypercapnia between male and female subjects in either grey or white matter. The observed differences in the healthy BOLD-CVR response could be explained by age-related changes in vascular mechanical properties. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Developmental changes of BOLD signal correlations with global human EEG power and synchronization during working memory.

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    Lars Michels

    Full Text Available In humans, theta band (5-7 Hz power typically increases when performing cognitively demanding working memory (WM tasks, and simultaneous EEG-fMRI recordings have revealed an inverse relationship between theta power and the BOLD (blood oxygen level dependent signal in the default mode network during WM. However, synchronization also plays a fundamental role in cognitive processing, and the level of theta and higher frequency band synchronization is modulated during WM. Yet, little is known about the link between BOLD, EEG power, and EEG synchronization during WM, and how these measures develop with human brain maturation or relate to behavioral changes. We examined EEG-BOLD signal correlations from 18 young adults and 15 school-aged children for age-dependent effects during a load-modulated Sternberg WM task. Frontal load (in-dependent EEG theta power was significantly enhanced in children compared to adults, while adults showed stronger fMRI load effects. Children demonstrated a stronger negative correlation between global theta power and the BOLD signal in the default mode network relative to adults. Therefore, we conclude that theta power mediates the suppression of a task-irrelevant network. We further conclude that children suppress this network even more than adults, probably from an increased level of task-preparedness to compensate for not fully mature cognitive functions, reflected in lower response accuracy and increased reaction time. In contrast to power, correlations between instantaneous theta global field synchronization and the BOLD signal were exclusively positive in both age groups but only significant in adults in the frontal-parietal and posterior cingulate cortices. Furthermore, theta synchronization was weaker in children and was--in contrast to EEG power--positively correlated with response accuracy in both age groups. In summary we conclude that theta EEG-BOLD signal correlations differ between spectral power and

  19. Re-examine tumor-induced alterations in hemodynamic responses of BOLD fMRI. Implications in presurgical brain mapping

    International Nuclear Information System (INIS)

    Wang, Liya; Ali, Shazia; Fa, Tianning; Mao, Hui; Dandan, Chen; Olson, Jeffrey

    2012-01-01

    Background: Blood oxygenation level dependent (BOLD) fMRI is used for presurgical functional mapping of brain tumor patients. Abnormal tumor blood supply may affect hemodynamic responses and BOLD fMRI signals. Purpose: To perform a multivariate and quantitative investigation of the effect of brain tumors on the hemodynamic responses and its impact on BOLD MRI signal time course, data analysis in order to better understand tumor-induced alterations in hemodynamic responses, and accurately mapping cortical regions in brain tumor patients. Material and Methods: BOLD fMRI data from 42 glioma patients who underwent presurgical mapping of the primary motor cortex (PMC) with a block designed finger tapping paradigm were analyzed, retrospectively. Cases were divided into high grade (n = 24) and low grade (n = 18) groups based on pathology. The tumor volume and distance to the activated PMCs were measured. BOLD signal time courses from selected regions of interest (ROIs) in the PMCs of tumor affected and contralateral unaffected hemispheres were obtained from each patient. Tumor-induced changes of BOLD signal intensity and time to peak (TTP) of BOLD signal time courses were analyzed statistically. Results: The BOLD signal intensity and TTP in the tumor-affected PMCs are altered when compared to that of the unaffected hemisphere. The average BOLD signal level is statistically significant lower in the affected PMCs. The average TTP in the affected PMCs is shorter in the high grade group, but longer in the low grade tumor group compared to the contralateral unaffected hemisphere. Degrees of alterations in BOLD signal time courses are related to both the distance to activated foci and tumor volume with the stronger effect in tumor distance to activated PMC. Conclusion: Alterations in BOLD signal time courses are strongly related to the tumor grade, the tumor volume, and the distance to the activated foci. Such alterations may impair accurate mapping of tumor-affected functional

  20. The BOLD cerebrovascular reactivity response to progressive hypercapnia in young and elderly

    DEFF Research Database (Denmark)

    Bhogal, Alex A.; De Vis, Jill B.; Siero, Jeroen C.W.

    2016-01-01

    the otherwise normal effects of ageing. Using a computer controlled gas delivery system, we examine differences in BOLD-CVR response to progressive hypercapnia between 16 young (28 ± 3 years, 9 female) and 30 elderly subjects (66 ± 4 years, 13 female). Furthermore, we incorporate baseline T2* information...... to broaden our interpretation of the BOLD-CVR response. Significant age-related differences were observed. Grey matter CVR at 7 mm Hg above resting PetCO2 was lower amongst elderly (0.19 ± 0.06%ΔBOLD/mm Hg) as compared to young subjects (0.26 ± 0.07%ΔBOLD/mm Hg). White matter CVR at 7 mm Hg above baseline...... PetCO2 showed no significant difference between young (0.04 ± 0.02%ΔBOLD/mm Hg) and elderly subjects (0.05 ± 0.03%ΔBOLD/mm Hg). We saw no significant differences in the BOLD signal response to progressive hypercapnia between male and female subjects in either grey or white matter. The observed...

  1. Effects of age on negative BOLD signal changes in the primary somatosensory cortex.

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    Gröschel, Sonja; Sohns, Jan Martin; Schmidt-Samoa, Carsten; Baudewig, Jürgen; Becker, Lars; Dechent, Peter; Kastrup, Andreas

    2013-05-01

    In addition to a contralateral activation of the primary and secondary somatosensory cortices, peripheral sensory stimulation has been shown to elicit responses in the ipsilateral primary somatosensory cortex (SI). In particular, evidence is accumulating that processes of interhemispheric inhibition as depicted by negative blood oxygenation level dependent (BOLD) signal changes are part of somatosensory processes. The aim of the study was to analyze age-related differences in patterns of cerebral activation in the somatosensory system in general and processes of interhemispheric inhibition in particular. For this, a functional magnetic resonance imaging (fMRI) study was performed including 14 younger (mean age 23.3±0.9years) and 13 healthy older participants (mean age 73.2±8.3years). All subjects were scanned during peripheral electrical median nerve stimulation (40Hz) to obtain BOLD responses in the somatosensory system. Moreover, the individual current perception threshold (CPT) as a quantitative measure of sensory function was determined in a separate psychophysical testing. Significant increases in BOLD signal across the entire group could be measured within the contralateral SI, in the bilateral secondary somatosensory cortex (SII), the contralateral supplementary motor area and the insula. Negative BOLD signal changes were delineated in ipsilateral SI/MI as well as in the ipsilateral thalamus and basal ganglia. After comparing the two groups, only the cortical deactivation in ipsilateral SI in the early stimulation phase as well as the activation in contralateral SI and SII in the late stimulation block remained as statistically significant differences between the two groups. The psychophysical experiments yielded a significant age-dependent effect of CPT change with less difference in the older group which is in line with the significantly smaller alterations in maximal BOLD signal change in the contra- and ipsilateral SI found between the two groups

  2. A neuronal MCT2 knockdown in the rat somatosensory cortex reduces both the NMR lactate signal and the BOLD response during whisker stimulation.

    Science.gov (United States)

    Mazuel, Leslie; Blanc, Jordy; Repond, Cendrine; Bouchaud, Véronique; Raffard, Gérard; Déglon, Nicole; Bonvento, Gilles; Pellerin, Luc; Bouzier-Sore, Anne-Karine

    2017-01-01

    Although several in vitro and ex vivo evidence support the existence of lactate exchange between astrocytes and neurons, a direct demonstration in vivo is still lacking. In the present study, a lentiviral vector carrying a short hairpin RNA (shRNA) was used to downregulate the expression of the monocarboxylate transporter type 2 (MCT2) in neurons of the rat somatosensory cortex (called S1BF) by ~ 25%. After one hour of whisker stimulation, HRMAS 1H-NMR spectroscopy analysis of S1BF perchloric acid extracts showed that while an increase in lactate content is observed in both uninjected and shRNA-control injected extracts, such an effect was abrogated in shMCT2 injected rats. A 13C-incorporation analysis following [1-13C]glucose infusion during the stimulation confirmed that the elevated lactate observed during activation originates from newly synthesized [3-13C]lactate, with blood-derived [1-13C]glucose being the precursor. Moreover, the analysis of the 13C-labeling of glutamate in position C3 and C4 indicates that upon activation, there is an increase in TCA cycle velocity for control rats while a decrease is observed for MCT2 knockdown animals. Using in vivo localized 1H-NMR spectroscopy, an increase in lactate levels is observed in the S1BF area upon whisker stimulation for shRNA-control injected rats but not for MCT2 knockdown animals. Finally, while a robust BOLD fMRI response was evidenced in control rats, it was absent in MCT2 knockdown rats. These data not only demonstrate that glucose-derived lactate is locally produced following neuronal activation but also suggest that its use by neurons via MCT2 is probably essential to maintain synaptic activity within the barrel cortex.

  3. Acute Nicotine Administration Increases BOLD fMRI Signal in Brain Regions Involved in Reward Signaling and Compulsive Drug Intake in Rats

    Science.gov (United States)

    Alexander, Jon C.; Perez, Pablo D.; Bauzo-Rodriguez, Rayna; Hall, Gabrielle; Klausner, Rachel; Guerra, Valerie; Zeng, Huadong; Igari, Moe; Febo, Marcelo

    2015-01-01

    Background: Acute nicotine administration potentiates brain reward function and enhances motor and cognitive function. These studies investigated which brain areas are being activated by a wide range of doses of nicotine, and if this is diminished by pretreatment with the nonselective nicotinic receptor antagonist mecamylamine. Methods: Drug-induced changes in brain activity were assessed by measuring changes in the blood oxygen level dependent (BOLD) signal using an 11.1-Tesla magnetic resonance scanner. In the first experiment, nicotine naïve rats were mildly anesthetized and the effect of nicotine (0.03–0.6mg/kg) on the BOLD signal was investigated for 10min. In the second experiment, the effect of mecamylamine on nicotine-induced brain activity was investigated. Results: A high dose of nicotine increased the BOLD signal in brain areas implicated in reward signaling, such as the nucleus accumbens shell and the prelimbic area. Nicotine also induced a dose-dependent increase in the BOLD signal in the striato-thalamo-orbitofrontal circuit, which plays a role in compulsive drug intake, and in the insular cortex, which contributes to nicotine craving and relapse. In addition, nicotine induced a large increase in the BOLD signal in motor and somatosensory cortices. Mecamylamine alone did not affect the BOLD signal in most brain areas, but induced a negative BOLD response in cortical areas, including insular, motor, and somatosensory cortices. Pretreatment with mecamylamine completely blocked the nicotine-induced increase in the BOLD signal. Conclusions: These studies demonstrate that acute nicotine administration activates brain areas that play a role in reward signaling, compulsive behavior, and motor and cognitive function. PMID:25552431

  4. BOLD signal and functional connectivity associated with loving kindness meditation.

    Science.gov (United States)

    Garrison, Kathleen A; Scheinost, Dustin; Constable, R Todd; Brewer, Judson A

    2014-05-01

    Loving kindness is a form of meditation involving directed well-wishing, typically supported by the silent repetition of phrases such as "may all beings be happy," to foster a feeling of selfless love. Here we used functional magnetic resonance imaging to assess the neural substrate of loving kindness meditation in experienced meditators and novices. We first assessed group differences in blood oxygen level-dependent (BOLD) signal during loving kindness meditation. We next used a relatively novel approach, the intrinsic connectivity distribution of functional connectivity, to identify regions that differ in intrinsic connectivity between groups, and then used a data-driven approach to seed-based connectivity analysis to identify which connections differ between groups. Our findings suggest group differences in brain regions involved in self-related processing and mind wandering, emotional processing, inner speech, and memory. Meditators showed overall reduced BOLD signal and intrinsic connectivity during loving kindness as compared to novices, more specifically in the posterior cingulate cortex/precuneus (PCC/PCu), a finding that is consistent with our prior work and other recent neuroimaging studies of meditation. Furthermore, meditators showed greater functional connectivity during loving kindness between the PCC/PCu and the left inferior frontal gyrus, whereas novices showed greater functional connectivity during loving kindness between the PCC/PCu and other cortical midline regions of the default mode network, the bilateral posterior insula lobe, and the bilateral parahippocampus/hippocampus. These novel findings suggest that loving kindness meditation involves a present-centered, selfless focus for meditators as compared to novices.

  5. Decoding neural events from fMRI BOLD signal: a comparison of existing approaches and development of a new algorithm.

    Science.gov (United States)

    Bush, Keith; Cisler, Josh

    2013-07-01

    Neuroimaging methodology predominantly relies on the blood oxygenation level dependent (BOLD) signal. While the BOLD signal is a valid measure of neuronal activity, variances in fluctuations of the BOLD signal are not only due to fluctuations in neural activity. Thus, a remaining problem in neuroimaging analyses is developing methods that ensure specific inferences about neural activity that are not confounded by unrelated sources of noise in the BOLD signal. Here, we develop and test a new algorithm for performing semiblind (i.e., no knowledge of stimulus timings) deconvolution of the BOLD signal that treats the neural event as an observable, but intermediate, probabilistic representation of the system's state. We test and compare this new algorithm against three other recent deconvolution algorithms under varied levels of autocorrelated and Gaussian noise, hemodynamic response function (HRF) misspecification and observation sampling rate. Further, we compare the algorithms' performance using two models to simulate BOLD data: a convolution of neural events with a known (or misspecified) HRF versus a biophysically accurate balloon model of hemodynamics. We also examine the algorithms' performance on real task data. The results demonstrated good performance of all algorithms, though the new algorithm generally outperformed the others (3.0% improvement) under simulated resting-state experimental conditions exhibiting multiple, realistic confounding factors (as well as 10.3% improvement on a real Stroop task). The simulations also demonstrate that the greatest negative influence on deconvolution accuracy is observation sampling rate. Practical and theoretical implications of these results for improving inferences about neural activity from fMRI BOLD signal are discussed. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. Comparison of fMRI analysis methods for heterogeneous BOLD responses in block design studies.

    Science.gov (United States)

    Liu, Jia; Duffy, Ben A; Bernal-Casas, David; Fang, Zhongnan; Lee, Jin Hyung

    2017-02-15

    A large number of fMRI studies have shown that the temporal dynamics of evoked BOLD responses can be highly heterogeneous. Failing to model heterogeneous responses in statistical analysis can lead to significant errors in signal detection and characterization and alter the neurobiological interpretation. However, to date it is not clear that, out of a large number of options, which methods are robust against variability in the temporal dynamics of BOLD responses in block-design studies. Here, we used rodent optogenetic fMRI data with heterogeneous BOLD responses and simulations guided by experimental data as a means to investigate different analysis methods' performance against heterogeneous BOLD responses. Evaluations are carried out within the general linear model (GLM) framework and consist of standard basis sets as well as independent component analysis (ICA). Analyses show that, in the presence of heterogeneous BOLD responses, conventionally used GLM with a canonical basis set leads to considerable errors in the detection and characterization of BOLD responses. Our results suggest that the 3rd and 4th order gamma basis sets, the 7th to 9th order finite impulse response (FIR) basis sets, the 5th to 9th order B-spline basis sets, and the 2nd to 5th order Fourier basis sets are optimal for good balance between detection and characterization, while the 1st order Fourier basis set (coherence analysis) used in our earlier studies show good detection capability. ICA has mostly good detection and characterization capabilities, but detects a large volume of spurious activation with the control fMRI data. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Increased BOLD Signals Elicited by High Gamma Auditory Stimulation of the Left Auditory Cortex in Acute State Schizophrenia

    Directory of Open Access Journals (Sweden)

    Hironori Kuga, M.D.

    2016-10-01

    We acquired BOLD responses elicited by click trains of 20, 30, 40 and 80-Hz frequencies from 15 patients with acute episode schizophrenia (AESZ, 14 symptom-severity-matched patients with non-acute episode schizophrenia (NASZ, and 24 healthy controls (HC, assessed via a standard general linear-model-based analysis. The AESZ group showed significantly increased ASSR-BOLD signals to 80-Hz stimuli in the left auditory cortex compared with the HC and NASZ groups. In addition, enhanced 80-Hz ASSR-BOLD signals were associated with more severe auditory hallucination experiences in AESZ participants. The present results indicate that neural over activation occurs during 80-Hz auditory stimulation of the left auditory cortex in individuals with acute state schizophrenia. Given the possible association between abnormal gamma activity and increased glutamate levels, our data may reflect glutamate toxicity in the auditory cortex in the acute state of schizophrenia, which might lead to progressive changes in the left transverse temporal gyrus.

  8. Neurochemical and BOLD responses during neuronal activation measured in the human visual cortex at 7 Tesla.

    Science.gov (United States)

    Bednařík, Petr; Tkáč, Ivan; Giove, Federico; DiNuzzo, Mauro; Deelchand, Dinesh K; Emir, Uzay E; Eberly, Lynn E; Mangia, Silvia

    2015-03-31

    Several laboratories have consistently reported small concentration changes in lactate, glutamate, aspartate, and glucose in the human cortex during prolonged stimuli. However, whether such changes correlate with blood oxygenation level-dependent functional magnetic resonance imaging (BOLD-fMRI) signals have not been determined. The present study aimed at characterizing the relationship between metabolite concentrations and BOLD-fMRI signals during a block-designed paradigm of visual stimulation. Functional magnetic resonance spectroscopy (fMRS) and fMRI data were acquired from 12 volunteers. A short echo-time semi-LASER localization sequence optimized for 7 Tesla was used to achieve full signal-intensity MRS data. The group analysis confirmed that during stimulation lactate and glutamate increased by 0.26 ± 0.06 μmol/g (~30%) and 0.28 ± 0.03 μmol/g (~3%), respectively, while aspartate and glucose decreased by 0.20 ± 0.04 μmol/g (~5%) and 0.19 ± 0.03 μmol/g (~16%), respectively. The single-subject analysis revealed that BOLD-fMRI signals were positively correlated with glutamate and lactate concentration changes. The results show a linear relationship between metabolic and BOLD responses in the presence of strong excitatory sensory inputs, and support the notion that increased functional energy demands are sustained by oxidative metabolism. In addition, BOLD signals were inversely correlated with baseline γ-aminobutyric acid concentration. Finally, we discussed the critical importance of taking into account linewidth effects on metabolite quantification in fMRS paradigms.

  9. Comparison of diffusion-weighted fMRI and BOLD fMRI responses in a verbal working memory task

    International Nuclear Information System (INIS)

    Aso, Toshihiko; Urayama, Shin-ichi; Fukuyama, Hidenao; Le Bihan, Denis

    2013-01-01

    Diffusion-weighted functional MRI (DfMRI) has been reported to have a different response pattern in the visual cortex than that of BOLD-fMRI. Especially, the DfMRI signal shows a constantly faster response at both onset and offset of the stimulus, suggesting that the DfMRI signal might be more directly linked to neuronal events than the hemodynamic response. However, because the DfMRI response also contains a residual sensitivity to BOLD this hypothesis has been challenged. Using a verbal working memory task we show that the DfMRI time-course features are preserved outside visual cortices, but also less liable to between-subject/between-regional variation than the BOLD response. The overall findings not only support the feasibility of DfMRI as an approach for functional brain imaging, but also strengthen the uniqueness of the DfMRI signal origin. (authors)

  10. Examining the regional and cerebral depth-dependent BOLD cerebrovascular reactivity response at 7T.

    Science.gov (United States)

    Bhogal, Alex A; Philippens, Marielle E P; Siero, Jeroen C W; Fisher, Joseph A; Petersen, Esben Thade; Luijten, Peter R; Hoogduin, Hans

    2015-07-01

    Changes in cerebral blood flow (CBF) in response to hypercapnia induced changes in vascular tone, known as cerebrovascular reactivity (CVR), can be measured using the Blood Oxygenation Level Dependent (BOLD) MR contrast. We examine regional differences in the BOLD-CVR response to a progressively increasing hypercapnic stimulus as well as regional BOLD characteristics for the return to baseline normocapnia. CVR across 9 subjects was highest in the cerebral lobes and deep gray matter. Peak CVR in these regions was measured at 3.6±1.6mmHg above baseline end-tidal CO2. White matter CVR was generally reduced compared to that of the gray matter (peak white matter CVR was ~48% lower). A positive relationship between the end-tidal CO2 value at which peak CVR was measured and white matter depth is observed. Furthermore, the time required for the BOLD signal to return to baseline after cessation of the hypercapnic stimulus, was also related to white matter depth; the return, expressed as a time constant, was ~25% longer in white matter. To explain the observed differences in regional CVR response, a model is proposed that takes into account the local architecture of the cerebrovascular, which can result in changes in regional blood flow distribution as a function of end-tidal CO2. Copyright © 2015. Published by Elsevier Inc.

  11. Luminance contrast of a visual stimulus modulates the BOLD response more than the cerebral blood flow response in the human brain.

    Science.gov (United States)

    Liang, Christine L; Ances, Beau M; Perthen, Joanna E; Moradi, Farshad; Liau, Joy; Buracas, Giedrius T; Hopkins, Susan R; Buxton, Richard B

    2013-01-01

    The blood oxygenation level dependent (BOLD) response measured with functional magnetic resonance imaging (fMRI) depends on the evoked changes in cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO(2)) in response to changes in neural activity. This response is strongly modulated by the CBF/CMRO(2) coupling relationship with activation, defined as n, the ratio of the fractional changes. The reliability of the BOLD signal as a quantitative reflection of underlying physiological changes depends on the stability of n in response to different stimuli. The effect of visual stimulus contrast on this coupling ratio was tested in 9 healthy human subjects, measuring CBF and BOLD responses to a flickering checkerboard at four visual contrast levels. The theory of the BOLD effect makes a robust prediction-independent of details of the model-that if the CBF/CMRO(2) coupling ratio n remains constant, then the response ratio between the lowest and highest contrast levels should be higher for the BOLD response than the CBF response because of the ceiling effect on the BOLD response. Instead, this response ratio was significantly lower for the BOLD response (BOLD response: 0.23 ± 0.13, mean ± SD; CBF response: 0.42 ± 0.18; p=0.0054). This data is consistent with a reduced dynamic range (strongest/weakest response ratio) of the CMRO(2) response (~1.7-fold) compared to that of the CBF response (~2.4-fold) as luminance contrast increases, corresponding to an increase of n from 1.7 at the lowest contrast level to 2.3 at the highest contrast level. The implication of these results for fMRI studies is that the magnitude of the BOLD response does not accurately reflect the magnitude of underlying physiological processes. Copyright © 2012 Elsevier Inc. All rights reserved.

  12. Luminance contrast of a visual stimulus modulates the BOLD response more than the cerebral blood flow response in the human brain

    OpenAIRE

    Liang, Christine L.; Ances, Beau M.; Perthen, Joanna E.; Moradi, Farshad; Liau, Joy; Buracas, Giedrius T.; Hopkins, Susan R.; Buxton, Richard B.

    2012-01-01

    The blood oxygenation level dependent (BOLD) response measured with functional magnetic resonance imaging (fMRI) depends on the evoked changes in cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) in response to changes in neural activity. This response is strongly modulated by the CBF/CMRO2 coupling relationship with activation, defined as n, the ratio of the fractional changes. The reliability of the BOLD signal as a quantitative reflection of underlying physiological c...

  13. Latencies in BOLD response during visual attention processes.

    Science.gov (United States)

    Kellermann, Thilo; Reske, Martina; Jansen, Andreas; Satrapi, Peyman; Shah, N Jon; Schneider, Frank; Habel, Ute

    2011-04-22

    One well-investigated division of attentional processes focuses on alerting, orienting and executive control, which can be assessed applying the attentional network test (ANT). The goal of the present study was to add further knowledge about the temporal dynamics of relevant neural correlates. As a right hemispheric dominance for alerting and orienting has previously been reported for intrinsic but not for phasic alertness, we additionally addressed a potential impact of this lateralization of attention by employing a lateralized version of the ANT, capturing phasic alertness processes. Sixteen healthy subjects underwent event-related functional magnetic resonance imaging (fMRI) while performing the ANT. Analyses of BOLD magnitude replicated the engagement of a fronto-parietal network in the attentional subsystems. The amplitudes of the attentional contrasts interacted with visual field presentation in the sense that the thalamus revealed a greater involvement for spatially cued items presented in the left visual field. Comparisons of BOLD latencies in visual cortices, first, verified faster BOLD responses following contra-lateral stimulus presentation. Second and more importantly, we identified attention-modulated activation in secondary visual and anterior cingulate cortices. Results are discussed in terms of bottom-up and lateralization processes. Although intrinsic and phasic alertness are distinct cognitive processes, we propose that neural substrates of intrinsic alertness may be accessed by phasic alertness provided that the attention-dominant (i.e., the right) hemisphere is activated directly by a warning stimulus. Copyright © 2011 Elsevier B.V. All rights reserved.

  14. Positive Allosteric Modulator of GABA Lowers BOLD Responses in the Cingulate Cortex.

    Directory of Open Access Journals (Sweden)

    Susanna A Walter

    Full Text Available Knowledge about the neural underpinnings of the negative blood oxygen level dependent (BOLD responses in functional magnetic resonance imaging (fMRI is still limited. We hypothesized that pharmacological GABAergic modulation attenuates BOLD responses, and that blood concentrations of a positive allosteric modulator of GABA correlate inversely with BOLD responses in the cingulate cortex. We investigated whether or not pure task-related negative BOLD responses were co-localized with pharmacologically modulated BOLD responses. Twenty healthy adults received either 5 mg diazepam or placebo in a double blind, randomized design. During fMRI the subjects performed a working memory task. Results showed that BOLD responses in the cingulate cortex were inversely correlated with diazepam blood concentrations; that is, the higher the blood diazepam concentration, the lower the BOLD response. This inverse correlation was most pronounced in the pregenual anterior cingulate cortex and the anterior mid-cingulate cortex. For subjects with diazepam plasma concentration > 0.1 mg/L we observed negative BOLD responses with respect to fixation baseline. There was minor overlap between cingulate regions with task-related negative BOLD responses and regions where the BOLD responses were inversely correlated with diazepam concentration. We interpret that the inverse correlation between the BOLD response and diazepam was caused by GABA-related neural inhibition. Thus, this study supports the hypothesis that GABA attenuates BOLD responses in fMRI. The minimal overlap between task-related negative BOLD responses and responses attenuated by diazepam suggests that these responses might be caused by different mechanisms.

  15. Effect of hypoxia on BOLD fMRI response and total cerebral blood flow in migraine with aura patients

    DEFF Research Database (Denmark)

    Arngrim, Nanna; Hougaard, Anders; Schytz, Henrik W

    2018-01-01

    was measured in the visual cortex ROIs V1-V5. Total cerebral blood flow (CBF) was calculated by measuring the blood velocity in the internal carotid arteries and the basilar artery using phase-contrast mapping (PCM) MRI. Hypoxia induced a greater decrease in BOLD response to visual stimulation in V1-V4 in MA......Experimentally induced hypoxia triggers migraine and aura attacks in patients suffering from migraine with aura (MA). We investigated the blood oxygenation level-dependent (BOLD) signal response to visual stimulation during hypoxia in MA patients and healthy volunteers. In a randomized double......-blind crossover study design, 15 MA patients were allocated to 180 min of normobaric poikilocapnic hypoxia (capillary oxygen saturation 70-75%) or sham (normoxia) on two separate days and 14 healthy volunteers were exposed to hypoxia. The BOLD functional MRI (fMRI) signal response to visual stimulation...

  16. Multimodal investigation of fMRI and fNIRS derived breath hold BOLD signals with an expanded balloon model

    International Nuclear Information System (INIS)

    Emir, U E; Ozturk, C; Akin, A

    2008-01-01

    Multimodal investigation of blood oxygenation level-dependent (BOLD) signals, using both functional near-infrared spectroscopy (fNIRS) and functional magnetic resonance imaging (fMRI), may give further insight to the underlying physiological principles and the detailed transient dynamics of the vascular response. Utilizing a breath hold task (BHT), we measured deoxy-hemoglobin (HbR) and oxy-hemoglobin (HbO) changes via fNIRS and blood oxygen level dependent (BOLD) changes by fMRI. Measurements were taken in four volunteers asynchronously and carefully aligned for comparative analysis. In order to describe the main stimulus in BHT, partial pressure of carbon dioxide (PaCO 2 ) parameter was integrated into the balloon model as the driving function of cerebral blood flow (CBF) which led to the development of an expanded balloon model (EBM). During BHT, the increase in HbR was observed later than the BOLD peak and coincided temporally with its post-stimulus undershoot. Further investigation of these transients with a PaCO 2 integrated balloon model suggests that post-stimulus undershoot measured by fMRI is dominated by slow return of cerebral blood volume (CBV). This was confirmed by fNIRS measurements. In addition, the BOLD signal decreased with the increase of the initial level of PaCO 2 derived from EBM, indicating an effect of basal CBF level on the BOLD signal. In conclusion, a multimodal approach with an appropriate biophysical model gave a comprehensive description of the hemodynamic response during BHT

  17. Ghrelin modulates the fMRI BOLD response of homeostatic and hedonic brain centers regulating energy balance in the rat.

    Directory of Open Access Journals (Sweden)

    Miklós Sárvári

    Full Text Available The orexigenic gut-brain peptide, ghrelin and its G-protein coupled receptor, the growth hormone secretagogue receptor 1a (GHS-R1A are pivotal regulators of hypothalamic feeding centers and reward processing neuronal circuits of the brain. These systems operate in a cooperative manner and receive a wide array of neuronal hormone/transmitter messages and metabolic signals. Functional magnetic resonance imaging was employed in the current study to map BOLD responses to ghrelin in different brain regions with special reference on homeostatic and hedonic regulatory centers of energy balance. Experimental groups involved male, ovariectomized female and ovariectomized estradiol-replaced rats. Putative modulation of ghrelin signaling by endocannabinoids was also studied. Ghrelin-evoked effects were calculated as mean of the BOLD responses 30 minutes after administration. In the male rat, ghrelin evoked a slowly decreasing BOLD response in all studied regions of interest (ROI within the limbic system. This effect was antagonized by pretreatment with GHS-R1A antagonist JMV2959. The comparison of ghrelin effects in the presence or absence of JMV2959 in individual ROIs revealed significant changes in the prefrontal cortex, nucleus accumbens of the telencephalon, and also within hypothalamic centers like the lateral hypothalamus, ventromedial nucleus, paraventricular nucleus and suprachiasmatic nucleus. In the female rat, the ghrelin effects were almost identical to those observed in males. Ovariectomy and chronic estradiol replacement had no effect on the BOLD response. Inhibition of the endocannabinoid signaling by rimonabant significantly attenuated the response of the nucleus accumbens and septum. In summary, ghrelin can modulate hypothalamic and mesolimbic structures controlling energy balance in both sexes. The endocannabinoid signaling system contributes to the manifestation of ghrelin's BOLD effect in a region specific manner. In females, the

  18. Effects of glyceryl trinitrate and calcitonin-gene-related peptide on BOLD signal and arterial diameter –methodological studies by fMRI and MRA

    DEFF Research Database (Denmark)

    Asghar, Mohammed Sohail; Ashina, Messoud

    2013-01-01

    of measuring task-related hemodynamic changes. Pharmacological substances that induce hemodynamic changes can therefore potentially alter the BOLD-signal that in turn falsely can be interpreted as changes in neuronal activity. It is therefore important to characterize possible effects of a pharmacological...... substance on the BOLD-response per see before that substance can be used in an fMRI experiment. Furthermore MR-angiography is useful in determining the vascular site-of-action of vasoactive substances....

  19. Significant feed-forward connectivity revealed by high frequency components of BOLD fMRI signals.

    Science.gov (United States)

    Lin, Fa-Hsuan; Chu, Ying-Hua; Hsu, Yi-Cheng; Lin, Jo-Fu Lotus; Tsai, Kevin W-K; Tsai, Shang-Yueh; Kuo, Wen-Jui

    2015-11-01

    Granger causality analysis has been suggested as a method of estimating causal modulation without specifying the direction of information flow a priori. Using BOLD-contrast functional MRI (fMRI) data, such analysis has been typically implemented in the time domain. In this study, we used magnetic resonance inverse imaging, a method of fast fMRI enabled by massively parallel detection allowing up to 10 Hz sampling rate, to investigate the causal modulation at different frequencies up to 5 Hz. Using a visuomotor two-choice reaction-time task, both the spectral decomposition of Granger causality and isolated effective coherence revealed that the BOLD signal at frequency up to 3 Hz can still be used to estimate significant dominant directions of information flow consistent with results from the time-domain Granger causality analysis. We showed the specificity of estimated dominant directions of information flow at high frequencies by contrasting causality estimates using data collected during the visuomotor task and resting state. Our data suggest that hemodynamic responses carry physiological information related to inter-regional modulation at frequency higher than what has been commonly considered. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Spatial attention related SEP amplitude modulations covary with BOLD signal in S1--a simultaneous EEG--fMRI study.

    Science.gov (United States)

    Schubert, Ruth; Ritter, Petra; Wüstenberg, Torsten; Preuschhof, Claudia; Curio, Gabriel; Sommer, Werner; Villringer, Arno

    2008-11-01

    Recent studies investigating the influence of spatial-selective attention on primary somatosensory processing have produced inconsistent results. The aim of this study was to explore the influence of tactile spatial-selective attention on spatiotemporal aspects of evoked neuronal activity in the primary somatosensory cortex (S1). We employed simultaneous electroencephalography (EEG)-functional magnetic resonance imaging (fMRI) in 14 right-handed subjects during bilateral index finger Braille stimulation to investigate the relationship between attentional effects on somatosensory evoked potential (SEP) components and the blood oxygenation level-dependent (BOLD) signal. The 1st reliable EEG response following left tactile stimulation (P50) was significantly enhanced by spatial-selective attention, which has not been reported before. FMRI analysis revealed increased activity in contralateral S1. Remarkably, the effect of attention on the P50 component as well as long-latency SEP components starting at 190 ms for left stimuli correlated with attentional effects on the BOLD signal in contralateral S1. The implications are 2-fold: First, the correlation between early and long-latency SEP components and the BOLD effect suggest that spatial-selective attention enhances processing in S1 at 2 time points: During an early passage of the signal and during a later passage, probably via re-entrant feedback from higher cortical areas. Second, attentional modulations of the fast electrophysiological signals and the slow hemodynamic response are linearly related in S1.

  1. Negative BOLD response and serotonin concentration within rostral subgenual portion of the anterior cingulate cortex for long-allele carriers during perceptual processing of emotional tasks

    Science.gov (United States)

    Hadi, Shamil M.; Siadat, Mohamad R.; Babajani-Feremi, Abbas

    2012-03-01

    We investigated the effect of synaptic serotonin concentration on hemodynamic responses. The stimuli paradigm involved the presentation of fearful and threatening facial expressions to a set of 24 subjects who were either5HTTLPR long- or short-allele carriers (12 of each type in each group). The BOLD signals of the rACC from subjects of each group were averaged to increase the signal-to-noise ratio. We used a Bayesian approach to estimate the parameters of the underlying hemodynamic model. Our results, during this perceptual processing of emotional task, showed a negative BOLD signal in the rACC in the subjects with long-alleles. In contrast, the subjects with short-alleles showed positive BOLD signals in the rACC. These results suggest that high synaptic serotonin concentration in the rACC inhibits neuronal activity in a fashion similar to GABA, and a consequent negative BOLD signal ensues.

  2. Quantification of fMRI BOLD signal and volume applied to the somatosensory cortex

    Energy Technology Data Exchange (ETDEWEB)

    Luedemann, L.; Wust, P. [Universitaetsklinikum Charite, CVK, Berlin (Germany). Klinik fuer Radiologie, Nuklearmedizin und Strahlenheilkunde; Foerschler, A.; Zimmer, C. [Universitaetsklinikum Leipzig (Germany). Abt. fuer Neuroradiologie

    2007-07-01

    Functional magnetic resonance imaging based on blood-oxygenation-level-dependent (BOLD) signal variations is clinically used to investigate the impact of neurological disorders on brain function. Such disorders effect not only the localization but also the amplitude and extent of the BOLD signal. Statistical methods are useful to localize the BOLD signal but fail to quantify functional activity because they rely on arbitrary thresholds. This article presents a method that uses a priori defined VOI (volume of interest) and independently quantifies the mean BOLD signal and extent of the activated volume. The technique is based on the separation of the VOI signal difference distribution into a noise and an activation contribution. The technique does not require any threshold and is nearly independent of the preselected VOI size. The technique was verified in a test group of 17 subjects performing bilateral finger tapping. The results were compared with those of conventional analysis based on statistical tools. A standard imaging technique using FID-EPI (free induction decay echo-planar imaging, TR = 4000 ms, TE = 66 ms, 60 images activation, 60 images rest) was employed. The activated volume, V, and signal difference, {delta}S, of the motor cortex were determined with an accuracy of {sigma}(V)=17.1% and {sigma}({delta}S)=3.6%, respectively. The activated volume of the left hemispheric motor area was significantly greater (P=0.025) then in the right hemispheric, V{sub L} = 7.35 {+-} 2.29 cm{sup 3} versus V{sub L} = 6.39 {+-} 2.34 cm{sup 3}. The result is consistent with the findings obtained by other techniques. On the other hand, the statistical methods did not yield any significant difference in activation between both hemispheres. The VOI-based method presented here is an additional tool to study the extent and amplitude of the BOLD signal. (orig.)

  3. Interictal functional connectivity of human epileptic networks assessed by intracerebral EEG and BOLD signal fluctuations.

    Directory of Open Access Journals (Sweden)

    Gaelle Bettus

    Full Text Available In this study, we aimed to demonstrate whether spontaneous fluctuations in the blood oxygen level dependent (BOLD signal derived from resting state functional magnetic resonance imaging (fMRI reflect spontaneous neuronal activity in pathological brain regions as well as in regions spared by epileptiform discharges. This is a crucial issue as coherent fluctuations of fMRI signals between remote brain areas are now widely used to define functional connectivity in physiology and in pathophysiology. We quantified functional connectivity using non-linear measures of cross-correlation between signals obtained from intracerebral EEG (iEEG and resting-state functional MRI (fMRI in 5 patients suffering from intractable temporal lobe epilepsy (TLE. Functional connectivity was quantified with both modalities in areas exhibiting different electrophysiological states (epileptic and non affected regions during the interictal period. Functional connectivity as measured from the iEEG signal was higher in regions affected by electrical epileptiform abnormalities relative to non-affected areas, whereas an opposite pattern was found for functional connectivity measured from the BOLD signal. Significant negative correlations were found between the functional connectivities of iEEG and BOLD signal when considering all pairs of signals (theta, alpha, beta and broadband and when considering pairs of signals in regions spared by epileptiform discharges (in broadband signal. This suggests differential effects of epileptic phenomena on electrophysiological and hemodynamic signals and/or an alteration of the neurovascular coupling secondary to pathological plasticity in TLE even in regions spared by epileptiform discharges. In addition, indices of directionality calculated from both modalities were consistent showing that the epileptogenic regions exert a significant influence onto the non epileptic areas during the interictal period. This study shows that functional

  4. Mapping transient hyperventilation induced alterations with estimates of the multi-scale dynamics of BOLD signal.

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    Vesa J Kiviniemi

    2009-07-01

    Full Text Available Temporal blood oxygen level dependent (BOLD contrast signals in functional MRI during rest may be characterized by power spectral distribution (PSD trends of the form 1/f α. Trends with 1/f characteristics comprise fractal properties with repeating oscillation patterns in multiple time scales. Estimates of the fractal properties enable the quantification of phenomena that may otherwise be difficult to measure, such as transient, non-linear changes. In this study it was hypothesized that the fractal metrics of 1/f BOLD signal trends can map changes related to dynamic, multi-scale alterations in cerebral blood flow (CBF after a transient hyperventilation challenge. Twenty-three normal adults were imaged in a resting-state before and after hyperventilation. Different variables (1/f trend constant α, fractal dimension Df, and, Hurst exponent H characterizing the trends were measured from BOLD signals. The results show that fractal metrics of the BOLD signal follow the fractional Gaussian noise model, even during the dynamic CBF change that follows hyperventilation. The most dominant effect on the fractal metrics was detected in grey matter, in line with previous hyperventilation vaso-reactivity studies. The α was able to differentiate also blood vessels from grey matter changes. Df was most sensitive to grey matter. H correlated with default mode network areas before hyperventilation but this pattern vanished after hyperventilation due to a global increase in H. In the future, resting-state fMRI combined with fractal metrics of the BOLD signal may be used for analyzing multi-scale alterations of cerebral blood flow.

  5. Fractal analysis of spontaneous fluctuations of the BOLD signal in the human brain networks.

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    Li, Yi-Chia; Huang, Yun-An

    2014-05-01

    To investigate what extent brain regions are continuously interacting during resting-state, independent component analyses (ICA) was applied to analyze resting-state functional MRI (RS-fMRI) data. According to the analyzed results, it was surprisingly found that low frequency fluctuations (LFFs), which belong to the 1/f signal (a signal with power spectrum whose power spectral density is inversely proportional to the frequency), have been classified into groups using ICA; furthermore, the spatial distributions of these groups within the brain were found to resemble the spatial distributions of different networks, which manifests that the signal characteristics of RS LFFs are distinct across networks. In our work, we applied the 1/f model in the fractal analyses to further investigate this distinction. Twenty healthy participants got involved in this study. They were scanned to acquire the RS-fMRI data. The acquired data were first processed with ICA to obtain the networks of the resting brain. Afterward, the blood-oxygenation level dependent (BOLD) signals of these networks were processed with the fractal analyses for obtaining the fractal parameter α. α was found to significantly vary across networks, which reveals that the fractal characteristic of LFFs differs across networks. According to prior literatures, this difference could be brought by the discrepancy of hemodynamic response amplitude (HRA) between networks. Hence, in our work, we also performed the computational simulation to discover the relationship between α and HRA. Based on the simulation results, HRA is highly linear-correlated with the fractal characteristics of LFFs which is revealed by α. Our results support that the origin of RS-fMRI signals contains arterial fluctuations. Hence, in addition to the commonly used method such as synchrony analysis and power spectral analysis, another approach, the fractal analysis, is suggested for acquiring the information of hemodynamic responses by means

  6. Investigating the non-linearity of the BOLD cerebrovascular reactivity response to targeted hypo/hypercapnia at 7T.

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    Bhogal, Alex A; Siero, Jeroen C W; Fisher, Joseph A; Froeling, Martijn; Luijten, Peter; Philippens, Marielle; Hoogduin, Hans

    2014-09-01

    Cerebrovascular reactivity (CVR) is a mechanism responsible for maintaining stable perfusion pressure within the brain via smooth muscle mediated modulations of vascular tone. The amplitude of cerebral blood flow (CBF) change in response to a stimulus has been evaluated using Blood Oxygen Level Dependent (BOLD) MRI, however the relationship between the stimulus and the measured signal remains unclear. CVR measured invasively in animal models and using blood-velocity based measurements in humans has demonstrated a sigmoidal relationship between cerebral blood flow and CO2 partial pressure. Using an ultra-high magnetic field strength (7T) MRI scanner and a computer controlled gas delivery system, we examined the regional and voxel-wise CVR response in relation to a targeted progressively increasing hypo- to hypercapnic stimulus. The aim of this study was to assess the non-linearity/sigmoidal behavior of the CVR response at varying arterial CO2 (PaCO2) levels. We find that a sigmoidal model provides a better description of the BOLD signal response to increasing PaCO2 than a linear model. A distinct whole-brain and gray matter BOLD-CVR signal plateau was observed in both voxel-wise and regional analysis. Furthermore, we demonstrate that a progressively increasing stimulus in combination with a sigmoidal response model can be used to obtain CVR values and provides additional physiologically relevant information (such as linear and non-linear response domains, and maximum response amplitudes) that may be more difficult to obtain from blocked CVR experiments. Considering these results, we propose an alternative way in which to define CVR based on the derivative of the BOLD-CVR response curve, which can potentially be used to differentiate between healthy and diseased vascular states. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Gestational Valproate Alters BOLD Activation in Response to Complex Social and Primary Sensory Stimuli

    Science.gov (United States)

    Felix-Ortiz, Ada C.; Febo, Marcelo

    2012-01-01

    Valproic acid (VPA) has been used clinically as an anticonvulsant medication during pregnancy; however, it poses a neurodevelopmental risk due to its high teratogenicity. We hypothesized that midgestational (GD) exposure to VPA will lead to lasting deficits in social behavior and the processing of social stimuli. To test this, animals were given a single IP injection of 600 mg/kg of VPA on GD 12.5. Starting on postnatal day 2 (PND2), animals were examined for physical and behavior abnormalities. Functional MRI studies were carried out after PND60. VPA and control animals were given vehicle or a central infusion of a V1a antagonist 90 minutes before imaging. During imaging sessions, rats were presented with a juvenile test male followed by a primary visual stimulus (2 Hz pulsed light) to examine the effects of prenatal VPA on neural processing. VPA rats showed greater increases in BOLD signal response to the social stimulus compared to controls in the temporal cortex, thalamus, midbrain and the hypothalamus. Blocking the V1a receptor reduced the BOLD response in VPA animals only. Neural responses to the visual stimulus, however, were lower in VPA animals. Blockade with the V1a antagonist did not revert this latter effect. Our data suggest that prenatal VPA affects the processing of social stimuli and perhaps social memory, partly through a mechanism that may involve vasopressin V1a neurotransmission. PMID:22615973

  8. Gestational valproate alters BOLD activation in response to complex social and primary sensory stimuli.

    Directory of Open Access Journals (Sweden)

    Ada C Felix-Ortiz

    Full Text Available Valproic acid (VPA has been used clinically as an anticonvulsant medication during pregnancy; however, it poses a neurodevelopmental risk due to its high teratogenicity. We hypothesized that midgestational (GD exposure to VPA will lead to lasting deficits in social behavior and the processing of social stimuli. To test this, animals were given a single IP injection of 600 mg/kg of VPA on GD 12.5. Starting on postnatal day 2 (PND2, animals were examined for physical and behavior abnormalities. Functional MRI studies were carried out after PND60. VPA and control animals were given vehicle or a central infusion of a V(1a antagonist 90 minutes before imaging. During imaging sessions, rats were presented with a juvenile test male followed by a primary visual stimulus (2 Hz pulsed light to examine the effects of prenatal VPA on neural processing. VPA rats showed greater increases in BOLD signal response to the social stimulus compared to controls in the temporal cortex, thalamus, midbrain and the hypothalamus. Blocking the V(1a receptor reduced the BOLD response in VPA animals only. Neural responses to the visual stimulus, however, were lower in VPA animals. Blockade with the V(1a antagonist did not revert this latter effect. Our data suggest that prenatal VPA affects the processing of social stimuli and perhaps social memory, partly through a mechanism that may involve vasopressin V(1a neurotransmission.

  9. Olfactory responses to natal stream water in sockeye salmon by BOLD fMRI.

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    Hiroshi Bandoh

    Full Text Available Many studies have shown that juvenile salmon imprint olfactory memory of natal stream odors during downstream migration, and adults recall this stream-specific odor information to discriminate their natal stream during upstream migration for spawning. The odor information processing of the natal stream in the salmon brain, however, has not been clarified. We applied blood oxygenation level-dependent (BOLD functional magnetic resonance imaging to investigate the odor information processing of the natal stream in the olfactory bulb and telencephalon of lacustrine sockeye salmon (Oncorhynchus nerka. The strong responses to the natal stream water were mainly observed in the lateral area of dorsal telencephalon (Dl, which are homologous to the medial pallium (hippocampus in terrestrial vertebrates. Although the concentration of L-serine (1 mM in the control water was 20,000-times higher than that of total amino acid in the natal stream water (47.5 nM, the BOLD signals resulting from the natal stream water were stronger than those by L-serine in the Dl. We concluded that sockeye salmon could process the odor information of the natal stream by integrating information in the Dl area of the telencephalon.

  10. Visual BOLD Response in Late Blind Subjects with Argus II Retinal Prosthesis.

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    E Castaldi

    2016-10-01

    Full Text Available Retinal prosthesis technologies require that the visual system downstream of the retinal circuitry be capable of transmitting and elaborating visual signals. We studied the capability of plastic remodeling in late blind subjects implanted with the Argus II Retinal Prosthesis with psychophysics and functional MRI (fMRI. After surgery, six out of seven retinitis pigmentosa (RP blind subjects were able to detect high-contrast stimuli using the prosthetic implant. However, direction discrimination to contrast modulated stimuli remained at chance level in all of them. No subject showed any improvement of contrast sensitivity in either eye when not using the Argus II. Before the implant, the Blood Oxygenation Level Dependent (BOLD activity in V1 and the lateral geniculate nucleus (LGN was very weak or absent. Surprisingly, after prolonged use of Argus II, BOLD responses to visual input were enhanced. This is, to our knowledge, the first study tracking the neural changes of visual areas in patients after retinal implant, revealing a capacity to respond to restored visual input even after years of deprivation.

  11. Accounting for the role of hematocrit in between-subject variations of MRI-derived baseline cerebral hemodynamic parameters and functional BOLD responses.

    Science.gov (United States)

    Xu, Feng; Li, Wenbo; Liu, Peiying; Hua, Jun; Strouse, John J; Pekar, James J; Lu, Hanzhang; van Zijl, Peter C M; Qin, Qin

    2018-01-01

    Baseline hematocrit fraction (Hct) is a determinant for baseline cerebral blood flow (CBF) and between-subject variation of Hct thus causes variation in task-based BOLD fMRI signal changes. We first verified in healthy volunteers (n = 12) that Hct values can be derived reliably from venous blood T 1 values by comparison with the conventional lab test. Together with CBF measured using phase-contrast MRI, this noninvasive estimation of Hct, instead of using a population-averaged Hct value, enabled more individual determination of oxygen delivery (DO 2 ), oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen (CMRO 2 ). The inverse correlation of CBF and Hct explained about 80% of between-subject variation of CBF in this relatively uniform cohort of subjects, as expected based on the regulation of DO 2 to maintain constant CMRO 2 . Furthermore, we compared the relationships of visual task-evoked BOLD response with Hct and CBF. We showed that Hct and CBF contributed 22%-33% of variance in BOLD signal and removing the positive correlation with Hct and negative correlation with CBF allowed normalization of BOLD signal with 16%-22% lower variability. The results of this study suggest that adjustment for Hct effects is useful for studies of MRI perfusion and BOLD fMRI. Hum Brain Mapp 39:344-353, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  12. Distributed BOLD-response in association cortex vector state space predicts reaction time during selective attention.

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    Musso, Francesco; Konrad, Andreas; Vucurevic, Goran; Schäffner, Cornelius; Friedrich, Britta; Frech, Peter; Stoeter, Peter; Winterer, Georg

    2006-02-15

    Human cortical information processing is thought to be dominated by distributed activity in vector state space (Churchland, P.S., Sejnowski, T.J., 1992. The Computational Brain. MIT Press, Cambridge.). In principle, it should be possible to quantify distributed brain activation with independent component analysis (ICA) through vector-based decomposition, i.e., through a separation of a mixture of sources. Using event-related functional magnetic resonance imaging (fMRI) during a selective attention-requiring task (visual oddball), we explored how the number of independent components within activated cortical areas is related to reaction time. Prior to ICA, the activated cortical areas were determined on the basis of a General linear model (GLM) voxel-by-voxel analysis of the target stimuli (checkerboard reversal). Two activated cortical areas (temporoparietal cortex, medial prefrontal cortex) were further investigated as these cortical regions are known to be the sites of simultaneously active electromagnetic generators which give rise to the compound event-related potential P300 during oddball task conditions. We found that the number of independent components more strongly predicted reaction time than the overall level of "activation" (GLM BOLD-response) in the left temporoparietal area whereas in the medial prefrontal cortex both ICA and GLM predicted reaction time equally well. Comparable correlations were not seen when principle components were used instead of independent components. These results indicate that the number of independently activated components, i.e., a high level of cortical activation complexity in cortical vector state space, may index particularly efficient information processing during selective attention-requiring tasks. To our best knowledge, this is the first report describing a potential relationship between neuronal generators of cognitive processes, the associated electrophysiological evidence for the existence of distributed networks

  13. Effects of intranasal insulin application on the hypothalamic BOLD response to glucose ingestion

    DEFF Research Database (Denmark)

    van Opstal, Anna M.; Akintola, Abimbola A.; Elst, Marjan van der

    2017-01-01

    The hypothalamus is a crucial structure in the brain that responds to metabolic cues and regulates energy homeostasis. Patients with type 2 diabetes demonstrate a lack of hypothalamic neuronal response after glucose ingestion, which is suggested to be an underlying cause of the disease. In this s......The hypothalamus is a crucial structure in the brain that responds to metabolic cues and regulates energy homeostasis. Patients with type 2 diabetes demonstrate a lack of hypothalamic neuronal response after glucose ingestion, which is suggested to be an underlying cause of the disease....... In this study, we assessed whether intranasal insulin can be used to enhance neuronal hypothalamic responses to glucose ingestion. In a randomized, double-blinded, placebo-controlled 4-double cross-over experiment, hypothalamic activation was measured in young non- diabetic subjects by determining blood......-oxygen-level dependent MRI signals over 30 minutes before and after ingestion of 75 g glucose dissolved in 300 ml water, under intranasal insulin or placebo condition. Glucose ingestion under placebo condition lead to an average 1.4% hypothalamic BOLD decrease, under insulin condition the average response to glucose...

  14. MEG and fMRI fusion for nonlinear estimation of neural and BOLD signal changes

    Directory of Open Access Journals (Sweden)

    Sergey M Plis

    2010-11-01

    Full Text Available The combined analysis of MEG/EEG and functional MRI measurements can lead to improvement in the description of the dynamical and spatial properties of brain activity. In this paper we empirically demonstrate this improvement using simulated and recorded task related MEG and fMRI activity. Neural activity estimates were derived using a dynamic Bayesian network with continuous real valued parameters by means of a sequential Monte Carlo technique. In synthetic data, we show that MEG and fMRI fusion improves estimation of the indirectly observed neural activity and smooths tracking of the BOLD response. In recordings of task related neural activity the combination of MEG and fMRI produces a result with greater SNR, that confirms the expectation arising from the nature of the experiment. The highly nonlinear model of the BOLD response poses a difficult inference problem for neural activity estimation; computational requirements are also high due to the time and space complexity. We show that joint analysis of the data improves the system's behavior by stabilizing the differential equations system and by requiring fewer computational resources.

  15. BOLD fMRI of C-Fiber Mediated Nociceptive Processing in Mouse Brain in Response to Thermal Stimulation of the Forepaws.

    Directory of Open Access Journals (Sweden)

    Simone C Bosshard

    Full Text Available Functional magnetic resonance imaging (fMRI in rodents enables non-invasive studies of brain function in response to peripheral input or at rest. In this study we describe a thermal stimulation paradigm using infrared laser diodes to apply noxious heat to the forepaw of mice in order to study nociceptive processing. Stimulation at 45 and 46°C led to robust BOLD signal changes in various brain structures including the somatosensory cortices and the thalamus. The BOLD signal amplitude scaled with the temperature applied but not with the area irradiated by the laser beam. To demonstrate the specificity of the paradigm for assessing nociceptive signaling we administered the quaternary lidocaine derivative QX-314 to the forepaws, which due to its positive charge cannot readily cross biological membranes. However, upon activation of TRPV1 channels following the administration of capsaicin the BOLD signal was largely abolished, indicative of a selective block of the C-fiber nociceptors due to QX-314 having entered the cells via the now open TRPV1 channels. This demonstrates that the cerebral BOLD response to thermal noxious paw stimulation is specifically mediated by C-fibers.

  16. Comparison between subjects with long- and short-allele carriers in the BOLD signal within amygdala during emotional tasks

    Science.gov (United States)

    Hadi, Shamil; Siadat, Mohamad R.; Babajani-Feremi, Abbas

    2012-03-01

    Emotional tasks may result in a strong blood oxygen level-dependent (BOLD) signal in the amygdala in 5- HTTLRP short-allele. Reduced anterior cingulate cortex (ACC)-amygdala connectivity in short-allele provides a potential mechanistic account for the observed increase in amygdala activity. In our study, fearful and threatening facial expressions were presented to two groups of 12 subjects with long- and short-allele carriers. The BOLD signals of the left amygdala of each group were averaged to increase the signal-to-noise ratio. A Bayesian approach was used to estimate the model parameters to elucidate the underlying hemodynamic mechanism. Our results showed a positive BOLD signal in the left amygdala for short-allele individuals, and a negative BOLD signal in the same region for long-allele individuals. This is due to the fact that short-allele is associated with lower availability of serotonin transporter (5-HTT) and this leads to an increase of serotonin (5-HT) concentration in the cACC-amygdala synapse.

  17. Negative BOLD signal changes in ipsilateral primary somatosensory cortex are associated with perfusion decreases and behavioral evidence for functional inhibition

    DEFF Research Database (Denmark)

    Schäfer, Katharina; Blankenburg, Felix; Kupers, Ron

    2012-01-01

    We used functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) to study the negative blood oxygenation level dependent (BOLD) signal and its underlying blood flow changes in healthy human subjects. This was combined with psychophysiological measurements to test that t...

  18. Temporal fractal analysis of the rs-BOLD signal identifies brain abnormalities in autism spectrum disorder.

    Science.gov (United States)

    Dona, Olga; Hall, Geoffrey B; Noseworthy, Michael D

    2017-01-01

    Brain connectivity in autism spectrum disorders (ASD) has proven difficult to characterize due to the heterogeneous nature of the spectrum. Connectivity in the brain occurs in a complex, multilevel and multi-temporal manner, driving the fluctuations observed in local oxygen demand. These fluctuations can be characterized as fractals, as they auto-correlate at different time scales. In this study, we propose a model-free complexity analysis based on the fractal dimension of the rs-BOLD signal, acquired with magnetic resonance imaging. The fractal dimension can be interpreted as measure of signal complexity and connectivity. Previous studies have suggested that reduction in signal complexity can be associated with disease. Therefore, we hypothesized that a detectable difference in rs-BOLD signal complexity could be observed between ASD patients and Controls. Anatomical and functional data from fifty-five subjects with ASD (12.7 ± 2.4 y/o) and 55 age-matched (14.1 ± 3.1 y/o) healthy controls were accessed through the NITRC database and the ABIDE project. Subjects were scanned using a 3T GE Signa MRI and a 32-channel RF-coil. Axial FSPGR-3D images were used to prescribe rs-BOLD (TE/TR = 30/2000ms) where 300 time points were acquired. Motion correction was performed on the functional data and anatomical and functional images were aligned and spatially warped to the N27 standard brain atlas. Fractal analysis, performed on a grey matter mask, was done by estimating the Hurst exponent in the frequency domain using a power spectral density approach and refining the estimation in the time domain with de-trended fluctuation analysis and signal summation conversion methods. Voxel-wise fractal dimension (FD) was calculated for every subject in the control group and in the ASD group to create ROI-based Z-scores for the ASD patients. Voxel-wise validation of FD normality across controls was confirmed, and non-Gaussian voxels were eliminated from subsequent analysis. To maintain

  19. Apnea-induced cortical BOLD-fMRI and peripheral sympathoneural firing response patterns of awake healthy humans.

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    Derek S Kimmerly

    Full Text Available End-expiratory breath-holds (BH and Mueller manoeuvres (MM elicit large increases in muscle sympathetic nerve activity (MSNA. In 16 healthy humans (9♀, 35 ± 4 years we used functional magnetic resonance imaging with blood oxygen level-dependent (BOLD contrast to determine the cortical network associated with such sympathoexcitation. We hypothesized that increases in MSNA evoked by these simulated apneas are accompanied by BOLD contrast changes in the insular cortex, thalamus and limbic cortex. A series of 150 whole-brain images were collected during 3 randomly performed 16-second end-expiratory BHs and MMs (-30 mmHg. The identical protocol was repeated separately with MSNA recorded from the fibular nerve. The time course of the sympathoexcitatory response to both breathing tasks were correlated with whole-brain BOLD signal changes. Brain sites demonstrating both positive (activation and negative (deactivation correlations with the MSNA time course were identified. Sympathetic burst incidence increased (p<0.001 from 29 ± 6 (rest to 49 ± 6 (BH and 47 ± 6 bursts/100 heartbeats (MM. Increased neural activity (Z-scores was identified in the right posterior and anterior insular cortices (3.74, 3.64, dorsal anterior cingulate (3.42, fastigial and dentate cerebellar nuclei (3.02, 3.34. Signal intensity decreased in the left posterior insula (3.28 and ventral anterior cingulate (3.01. Apnea both activates and inhibits elements of a cortical network involved in the generation of sympathetic outflow. These findings identify a neuroanatomical substrate to guide future investigations into central mechanisms contributing to disorders characterized by elevated basal MSNA and exaggerated sympathetic responses to simulated apneas such as sleep apnea and heart failure.

  20. Exploiting magnetic resonance angiography imaging improves model estimation of BOLD signal.

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    Zhenghui Hu

    Full Text Available The change of BOLD signal relies heavily upon the resting blood volume fraction ([Formula: see text] associated with regional vasculature. However, existing hemodynamic data assimilation studies pretermit such concern. They simply assign the value in a physiologically plausible range to get over ill-conditioning of the assimilation problem and fail to explore actual [Formula: see text]. Such performance might lead to unreliable model estimation. In this work, we present the first exploration of the influence of [Formula: see text] on fMRI data assimilation, where actual [Formula: see text] within a given cortical area was calibrated by an MR angiography experiment and then was augmented into the assimilation scheme. We have investigated the impact of [Formula: see text] on single-region data assimilation and multi-region data assimilation (dynamic cause modeling, DCM in a classical flashing checkerboard experiment. Results show that the employment of an assumed [Formula: see text] in fMRI data assimilation is only suitable for fMRI signal reconstruction and activation detection grounded on this signal, and not suitable for estimation of unobserved states and effective connectivity study. We thereby argue that introducing physically realistic [Formula: see text] in the assimilation process may provide more reliable estimation of physiological information, which contributes to a better understanding of the underlying hemodynamic processes. Such an effort is valuable and should be well appreciated.

  1. The fMRI BOLD response to unisensory and multisensory smoking cues in nicotine-dependent adults.

    Science.gov (United States)

    Cortese, Bernadette M; Uhde, Thomas W; Brady, Kathleen T; McClernon, F Joseph; Yang, Qing X; Collins, Heather R; LeMatty, Todd; Hartwell, Karen J

    2015-12-30

    Given that the vast majority of functional magnetic resonance imaging (fMRI) studies of drug cue reactivity use unisensory visual cues, but that multisensory cues may elicit greater craving-related brain responses, the current study sought to compare the fMRI BOLD response to unisensory visual and multisensory, visual plus odor, smoking cues in 17 nicotine-dependent adult cigarette smokers. Brain activation to smoking-related, compared to neutral, pictures was assessed under cigarette smoke and odorless odor conditions. While smoking pictures elicited a pattern of activation consistent with the addiction literature, the multisensory (odor+picture) smoking cues elicited significantly greater and more widespread activation in mainly frontal and temporal regions. BOLD signal elicited by the multisensory, but not unisensory cues, was significantly related to participants' level of control over craving as well. Results demonstrated that the co-presentation of cigarette smoke odor with smoking-related visual cues, compared to the visual cues alone, elicited greater levels of craving-related brain activation in key regions implicated in reward. These preliminary findings support future research aimed at a better understanding of multisensory integration of drug cues and craving. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  2. Correlations of noninvasive BOLD and TOLD MRI with pO2 and relevance to tumor radiation response.

    Science.gov (United States)

    Hallac, Rami R; Zhou, Heling; Pidikiti, Rajesh; Song, Kwang; Stojadinovic, Strahinja; Zhao, Dawen; Solberg, Timothy; Peschke, Peter; Mason, Ralph P

    2014-05-01

    To examine the potential use of blood oxygenation level dependent (BOLD) and tissue oxygenation level dependent (TOLD) contrast MRI to assess tumor oxygenation and predict radiation response. BOLD and TOLD MRI were performed on Dunning R3327-AT1 rat prostate tumors during hyperoxic gas breathing challenge at 4.7 T. Animals were divided into two groups. In Group 1 (n = 9), subsequent (19) F MRI based on spin lattice relaxation of hexafluorobenzene reporter molecule provided quantitative oximetry for comparison. For Group 2 rats (n = 13) growth delay following a single dose of 30 Gy was compared with preirradiation BOLD and TOLD assessments. Oxygen (100%O2 ) and carbogen (95%O2 /5%CO2 ) challenge elicited similar BOLD, TOLD and pO2 responses. Strong correlations were observed between BOLD or R2* response and quantitative (19) F pO2 measurements. TOLD response showed a general trend with weaker correlation. Irradiation caused a significant tumor growth delay and tumors with larger changes in TOLD and R1 values upon oxygen breathing exhibited significantly increased tumor growth delay. These results provide further insight into the relationships between oxygen sensitive (BOLD/TOLD) MRI and tumor pO2 . Moreover, a larger increase in R1 response to hyperoxic gas challenge coincided with greater tumor growth delay following irradiation. Copyright © 2013 Wiley Periodicals, Inc.

  3. In contrast to BOLD: signal enhancement by extravascular water protons as an alternative mechanism of endogenous fMRI signal change.

    Science.gov (United States)

    Figley, Chase R; Leitch, Jordan K; Stroman, Patrick W

    2010-10-01

    Despite the popularity and widespread application of functional magnetic resonance imaging (fMRI) in recent years, the physiological bases of signal change are not yet fully understood. Blood oxygen level-dependant (BOLD) contrast - attributed to local changes in blood flow and oxygenation, and therefore magnetic susceptibility - has become the most prevalent means of functional neuroimaging. However, at short echo times, spin-echo sequences show considerable deviations from the BOLD model, implying a second, non-BOLD component of signal change. This has been dubbed "signal enhancement by extravascular water protons" (SEEP) and is proposed to result from proton-density changes associated with cellular swelling. Given that such changes are independent of magnetic susceptibility, SEEP may offer new and improved opportunities for carrying out fMRI in regions with close proximity to air-tissue and/or bone-tissue interfaces (e.g., the prefrontal cortex and spinal cord), as well as regions close to large blood vessels, which may not be ideally suited for BOLD imaging. However, because of the interdisciplinary nature of the literature, there has yet to be a thorough synthesis, tying together the various and sometimes disparate aspects of SEEP theory. As such, we aim to provide a concise yet comprehensive overview of SEEP, including recent and compelling evidence for its validity, its current applications and its future relevance to the rapidly expanding field of functional neuroimaging. Before presenting the evidence for a non-BOLD component of endogenous functional contrast, and to enable a more critical review for the nonexpert reader, we begin by reviewing the fundamental principles underlying BOLD theory. Copyright © 2010 Elsevier Inc. All rights reserved.

  4. Consecutive TMS-fMRI reveals an inverse relationship in BOLD signal between object and scene processing.

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    Mullin, Caitlin R; Steeves, Jennifer K E

    2013-12-04

    The human visual system is capable of recognizing an infinite number of scenes containing an abundance of rich visual information. There are several cortical regions associated with the representation of a scene, including those specialized for object processing (the lateral occipital area [LO]) and for the spatial layout of scenes (the parahippocampal place area). Although behavioral studies have demonstrated that these image categories (scenes and objects) exert an influence on each other such that scene context can facilitate object identification or that scene categorization can be impaired by the presence of a salient object, little is known about the apparent cortical interactions involved in building the conscious representation of a complete scene. It has been shown that transcranial magnetic stimulation (TMS) to the left LO disrupts object categorization but facilitates scene categorization. Here, we show that this effect is also reflected by changes in the BOLD signal such that TMS to the left LO decreases BOLD signal at the stimulation site (LO) while viewing objects and increases BOLD signal in the left PPA when viewing scenes. This suggests that these regions, although likely not on a strict hierarchy of bottom-up coding, share functional communication likely in the form of inhibitory connections.

  5. Measurement of oxygen extraction fraction (OEF): An optimized BOLD signal model for use with hypercapnic and hyperoxic calibration.

    Science.gov (United States)

    Merola, Alberto; Murphy, Kevin; Stone, Alan J; Germuska, Michael A; Griffeth, Valerie E M; Blockley, Nicholas P; Buxton, Richard B; Wise, Richard G

    2016-04-01

    Several techniques have been proposed to estimate relative changes in cerebral metabolic rate of oxygen consumption (CMRO2) by exploiting combined BOLD fMRI and cerebral blood flow data in conjunction with hypercapnic or hyperoxic respiratory challenges. More recently, methods based on respiratory challenges that include both hypercapnia and hyperoxia have been developed to assess absolute CMRO2, an important parameter for understanding brain energetics. In this paper, we empirically optimize a previously presented "original calibration model" relating BOLD and blood flow signals specifically for the estimation of oxygen extraction fraction (OEF) and absolute CMRO2. To do so, we have created a set of synthetic BOLD signals using a detailed BOLD signal model to reproduce experiments incorporating hypercapnic and hyperoxic respiratory challenges at 3T. A wide range of physiological conditions was simulated by varying input parameter values (baseline cerebral blood volume (CBV0), baseline cerebral blood flow (CBF0), baseline oxygen extraction fraction (OEF0) and hematocrit (Hct)). From the optimization of the calibration model for estimation of OEF and practical considerations of hypercapnic and hyperoxic respiratory challenges, a new "simplified calibration model" is established which reduces the complexity of the original calibration model by substituting the standard parameters α and β with a single parameter θ. The optimal value of θ is determined (θ=0.06) across a range of experimental respiratory challenges. The simplified calibration model gives estimates of OEF0 and absolute CMRO2 closer to the true values used to simulate the experimental data compared to those estimated using the original model incorporating literature values of α and β. Finally, an error propagation analysis demonstrates the susceptibility of the original and simplified calibration models to measurement errors and potential violations in the underlying assumptions of isometabolism

  6. Neural Correlates of Facial Mimicry: Simultaneous Measurements of EMG and BOLD Responses during Perception of Dynamic Compared to Static Facial Expressions

    Science.gov (United States)

    Rymarczyk, Krystyna; Żurawski, Łukasz; Jankowiak-Siuda, Kamila; Szatkowska, Iwona

    2018-01-01

    Facial mimicry (FM) is an automatic response to imitate the facial expressions of others. However, neural correlates of the phenomenon are as yet not well established. We investigated this issue using simultaneously recorded EMG and BOLD signals during perception of dynamic and static emotional facial expressions of happiness and anger. During display presentations, BOLD signals and zygomaticus major (ZM), corrugator supercilii (CS) and orbicularis oculi (OO) EMG responses were recorded simultaneously from 46 healthy individuals. Subjects reacted spontaneously to happy facial expressions with increased EMG activity in ZM and OO muscles and decreased CS activity, which was interpreted as FM. Facial muscle responses correlated with BOLD activity in regions associated with motor simulation of facial expressions [i.e., inferior frontal gyrus, a classical Mirror Neuron System (MNS)]. Further, we also found correlations for regions associated with emotional processing (i.e., insula, part of the extended MNS). It is concluded that FM involves both motor and emotional brain structures, especially during perception of natural emotional expressions. PMID:29467691

  7. Multiband multi-echo simultaneous ASL/BOLD for task-induced functional MRI.

    Directory of Open Access Journals (Sweden)

    Alexander D Cohen

    Full Text Available Typical simultaneous blood oxygenation-level dependent (BOLD and arterial spin labeling (ASL sequences acquire two echoes, one perfusion-sensitive and one BOLD-sensitive. However, for ASL, spatial resolution and brain coverage are limited due to the T1 decay of the labeled blood. This study applies a sequence combining a multiband acquisition with four echoes for simultaneous BOLD and pseudo-continuous ASL (pCASL echo planar imaging (MBME ASL/BOLD for block-design task-fMRI. A multiband acceleration of four was employed to increase brain coverage and reduce slice-timing effects on the ASL signal. Multi-echo independent component analysis (MEICA was implemented to automatically denoise the BOLD signal by regressing non-BOLD components. This technique led to increased temporal signal-to-noise ratio (tSNR and BOLD sensitivity. The MEICA technique was also modified to denoise the ASL signal by regressing artifact and BOLD signals from the first echo time-series. The MBME ASL/BOLD sequence was applied to a finger-tapping task functional MRI (fMRI experiment. Signal characteristics and activation were evaluated using single echo BOLD, combined ME BOLD, combined ME BOLD after MEICA denoising, perfusion-weighted (PW, and perfusion-weighted after MEICA denoising time-series. The PW data was extracted using both surround subtraction and high-pass filtering followed by demodulation. In addition, the CBF/BOLD response ratio and CBF/BOLD coupling were analyzed. Results showed that the MEICA denoising procedure significantly improved the BOLD signal, leading to increased BOLD sensitivity, tSNR, and activation statistics compared to conventional single echo BOLD data. At the same time, the denoised PW data showed increased tSNR and activation statistics compared to the non-denoised PW data. CBF/BOLD coupling was also increased using the denoised ASL and BOLD data. Our preliminary data suggest that the MBME ASL/BOLD sequence can be employed to collect whole

  8. A two-stage cascade model of BOLD responses in human visual cortex.

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    Kendrick N Kay

    Full Text Available Visual neuroscientists have discovered fundamental properties of neural representation through careful analysis of responses to controlled stimuli. Typically, different properties are studied and modeled separately. To integrate our knowledge, it is necessary to build general models that begin with an input image and predict responses to a wide range of stimuli. In this study, we develop a model that accepts an arbitrary band-pass grayscale image as input and predicts blood oxygenation level dependent (BOLD responses in early visual cortex as output. The model has a cascade architecture, consisting of two stages of linear and nonlinear operations. The first stage involves well-established computations-local oriented filters and divisive normalization-whereas the second stage involves novel computations-compressive spatial summation (a form of normalization and a variance-like nonlinearity that generates selectivity for second-order contrast. The parameters of the model, which are estimated from BOLD data, vary systematically across visual field maps: compared to primary visual cortex, extrastriate maps generally have larger receptive field size, stronger levels of normalization, and increased selectivity for second-order contrast. Our results provide insight into how stimuli are encoded and transformed in successive stages of visual processing.

  9. Mapping of the brain hemodynamic responses to sensorimotor stimulation in a rodent model: A BOLD fMRI study.

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    Salem Boussida

    Full Text Available Blood Oxygenation Level Dependent functional MRI (BOLD fMRI during electrical paw stimulation has been widely used in studies aimed at the understanding of the somatosensory network in rats. However, despite the well-established anatomical connections between cortical and subcortical structures of the sensorimotor system, most of these functional studies have been concentrated on the cortical effects of sensory electrical stimulation. BOLD fMRI study of the integration of a sensorimotor input across the sensorimotor network requires an appropriate methodology to elicit functional activation in cortical and subcortical areas owing to the regional differences in both neuronal and vascular architectures between these brain regions. Here, using a combination of low level anesthesia, long pulse duration of the electrical stimulation along with improved spatial and temporal signal to noise ratios, we provide a functional description of the main cortical and subcortical structures of the sensorimotor rat brain. With this calibrated fMRI protocol, unilateral non-noxious sensorimotor electrical hindpaw stimulation resulted in robust positive activations in the contralateral sensorimotor cortex and bilaterally in the sensorimotor thalamus nuclei, whereas negative activations were observed bilaterally in the dorsolateral caudate-putamen. These results demonstrate that, once the experimental setup allowing necessary spatial and temporal signal to noise ratios is reached, hemodynamic changes related to neuronal activity, as preserved by the combination of a soft anesthesia with a soft muscle relaxation, can be measured within the sensorimotor network. Moreover, the observed responses suggest that increasing pulse duration of the electrical stimulus adds a proprioceptive component to the sensory input that activates sensorimotor network in the brain, and that these activation patterns are similar to those induced by digits paw's movements. These findings may

  10. A Resilient, Non-neuronal Source of the Spatiotemporal Lag Structure Detected by BOLD Signal-Based Blood Flow Tracking

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    Toshihiko Aso

    2017-05-01

    Full Text Available Recent evidence has suggested that blood oxygenation level-dependent (BOLD signals convey information about brain circulation via low frequency oscillation of systemic origin (sLFO that travels through the vascular structure (“lag mapping”. Prompted by its promising application in both physiology and pathology, we examined this signal component using multiple approaches. A total of 30 healthy volunteers were recruited to perform two reproducibility experiments at 3 Tesla using multiband echo planar imaging. The first experiment investigated the effect of denoising and the second was designed to study the effect of subject behavior on lag mapping. The lag map's intersession test-retest reproducibility and image contrast were both diminished by removal of either the neuronal or the non-neuronal (e.g., cardiac, respiratory components by independent component analysis-based denoising, suggesting that the neurovascular coupling also comprises a part of the BOLD lag structure. The lag maps were, at the same time, robust against local perfusion increases due to visuomotor task and global changes in perfusion induced by breath-holding at the same level as the intrasession reliability. The lag structure was preserved after time-locked averaging to the visuomotor task and breath-holding events, while any preceding signal changes were canceled out for the visuomotor task, consistent with the passive effect of neurovascular coupling in the venous side of the vasculature. These findings support the current assumption that lag mapping primarily reflects vascular structure despite the presence of sLFO perturbation of neuronal or non-neuronal origin and, thus, emphasize the vascular origin of the lag map, encouraging application of BOLD-based blood flow tracking.

  11. Shy and bold great tits (Parus major): body temperature and breath rate in response to handling stress

    NARCIS (Netherlands)

    Carere, C.; Van Oers, K.

    2004-01-01

    A standard handling protocol was used to test the hypothesis that boldness predicts stress responsiveness in body temperature and breath rate. Great tit (Parus major) nestlings were taken from the field, hand reared until independence, and their response to a novel object was assessed. At the age of

  12. Opposing BOLD responses to reciprocated and unreciprocated altruism in putative reward pathways.

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    Rilling, James K; Sanfey, Alan G; Aronson, Jessica A; Nystrom, Leigh E; Cohen, Jonathan D

    2004-11-15

    Mesencephalic dopamine neurons are believed to facilitate reward-dependent learning by computing errors in reward predictions. We used fMRI to test whether this system was activated as expected in response to errors in predictions about whether a social partner would reciprocate an act of altruism. Nineteen subjects received fMRI scans as they played a series of single-shot Prisoner's Dilemma games with partners who were outside the scanner. In both ventromedial prefrontal cortex and ventral striatum, reciprocated and unreciprocated cooperation were associated with positive and negative BOLD responses, respectively. Our results are consistent with the hypothesis that mesencephalic dopamine projection sites carry information about errors in reward prediction that allow us to learn who can and cannot be trusted to reciprocate favors.

  13. The 'where' and the 'when' of the BOLD response to pain in the insular cortex. Discussion on amplitudes and latencies.

    Science.gov (United States)

    Pomares, Florence B; Faillenot, Isabelle; Barral, Fabrice Guy; Peyron, Roland

    2013-01-01

    The operculo-insular cortex has been recently pointed out to be the main area of the pain matrix to be involved in the integration of pain intensity. This fMRI study specified the pattern of response to laser stimuli by focusing on this cortical area, by optimizing the temporal sampling and by investigating pain-related differences in the amplitudes and latencies of the BOLD responses. Canonical and temporal derivative hemodynamic response function (HRF) and finite impulse response (FIR) modeling provided consistent results. Amplitude of BOLD response discriminated painful from non-painful conditions in posterior and mid-insular cortices, bilaterally. Pain conditions were characterized by a shortened latency (as compared to non-painful conditions) in the anterior insula. In the functional organization of the insula, these results suggest a double dissociation that can be summarized as the 'where' and the 'when' of the BOLD response to pain. These results suggest that differences in the amplitude of the BOLD activity in the posterior and in the mid-insular cortices as well as shortened latency of the response in the anterior insula deal with discriminative processes related to painful conditions. Copyright © 2012 Elsevier Inc. All rights reserved.

  14. Evolution of boldness and life-history in response to selective harvesting

    DEFF Research Database (Denmark)

    Andersen, Ken Haste; Marty, Lise; Arlinghaus, Robert

    2018-01-01

    Whether intensive harvesting alters the behavioral repertoire of exploited fishes is currently unknown, but plausible. We extend a fish life-history model to account for boldness as a personality trait that affects foraging intensity, which affects energy intake and risk from predation and fishing...... gear. We systematically investigate life-history and behavioral trait evolution along the boldness–timidity axis in response to the full range of common selectivity and exploitation patterns in fisheries. In agreement with previous studies, we find that any type of harvesting selects for fast life...... individuals common to passive gears, whether in combination with selection on size or not. Altered behavior caused by intensive harvesting should be commonplace in nature, which can have far-reaching ecological, evolutionary, and managerial impacts. Evolution of timidity is expected to strongly erode...

  15. Cerebral Asymmetry of fMRI-BOLD Responses to Visual Stimulation

    DEFF Research Database (Denmark)

    Hougaard, Anders; Jensen, Bettina Hagström; Amin, Faisal Mohammad

    2015-01-01

    was correlated with subject age, suggesting a shift towards the left hemisphere with increasing age. Our findings suggest a right-hemispheric dominance of these areas, which could lend support to the generally observed leftward visual attentional bias and to the left hemifield advantage for some visual......Hemispheric asymmetry of a wide range of functions is a hallmark of the human brain. The visual system has traditionally been thought of as symmetrically distributed in the brain, but a growing body of evidence has challenged this view. Some highly specific visual tasks have been shown to depend...... on hemispheric specialization. However, the possible lateralization of cerebral responses to a simple checkerboard visual stimulation has not been a focus of previous studies. To investigate this, we performed two sessions of blood-oxygenation level dependent (BOLD) functional magnetic resonance imaging (f...

  16. BOLD-fMRI response vs. transcranial magnetic stimulation (TMS) pulse-train length: testing for linearity.

    Science.gov (United States)

    Bohning, Daryl E; Shastri, Ananda; Lomarev, Mikhail P; Lorberbaum, Jeffrey P; Nahas, Ziad; George, Mark S

    2003-03-01

    To measure motor and auditory cortex blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) response to impulse-like transcranial magnetic stimulation (TMS) pulses as a function of train length. Interleaved with fMRI at 1.5 T, TMS pulses 0.3-msec long were applied at 1 Hz to the motor cortex area for thumb. Six subjects were studied in a TR = 1 second session administering trains of 1, 2, 4, 8, and 16 pulses, and a TR = 3 seconds session administering trains of 1, 2, 4, 8, 16, and 24 pulses. A simple hemodynamic model with finite recovery and saturation was used to quantitatively characterize the BOLD-fMRI response as a function of train length. In both the activations directly induced in motor cortex by TMS and the indirect activations in auditory cortex caused by the sound of the TMS coil firing, the BOLD-fMRI responses to multiple pulses were well described by a summation of single-pulse impulse functions. Up to 24 discrete pulses, BOLD-fMRI response to 1 Hz TMS in both motor cortex and auditory cortex were consistent with a linear increase in amplitude and length with train length, possibly suggesting that stimuli of 1 to 2 seconds may be too long to represent impulses. Copyright 2003 Wiley-Liss, Inc.

  17. Mapping and characterization of positive and negative BOLD responses to visual stimulation in multiple brain regions at 7T

    NARCIS (Netherlands)

    Jorge, João; Figueiredo, Patrícia; Gruetter, Rolf; Van der Zwaag, W.

    External stimuli and tasks often elicit negative BOLD responses in various brain regions, and growing experimental evidence supports that these phenomena are functionally meaningful. In this work, the high sensitivity available at 7T was explored to map and characterize both positive (PBRs) and

  18. Altered auditory BOLD response to conspecific birdsong in zebra finches with stuttered syllables.

    Directory of Open Access Journals (Sweden)

    Henning U Voss

    2010-12-01

    Full Text Available How well a songbird learns a song appears to depend on the formation of a robust auditory template of its tutor's song. Using functional magnetic resonance neuroimaging we examine auditory responses in two groups of zebra finches that differ in the type of song they sing after being tutored by birds producing stuttering-like syllable repetitions in their songs. We find that birds that learn to produce the stuttered syntax show attenuated blood oxygenation level-dependent (BOLD responses to tutor's song, and more pronounced responses to conspecific song primarily in the auditory area field L of the avian forebrain, when compared to birds that produce normal song. These findings are consistent with the presence of a sensory song template critical for song learning in auditory areas of the zebra finch forebrain. In addition, they suggest a relationship between an altered response related to familiarity and/or saliency of song stimuli and the production of variant songs with stuttered syllables.

  19. Linear Discriminant Analysis Achieves High Classification Accuracy for the BOLD fMRI Response to Naturalistic Movie Stimuli.

    Science.gov (United States)

    Mandelkow, Hendrik; de Zwart, Jacco A; Duyn, Jeff H

    2016-01-01

    Naturalistic stimuli like movies evoke complex perceptual processes, which are of great interest in the study of human cognition by functional MRI (fMRI). However, conventional fMRI analysis based on statistical parametric mapping (SPM) and the general linear model (GLM) is hampered by a lack of accurate parametric models of the BOLD response to complex stimuli. In this situation, statistical machine-learning methods, a.k.a. multivariate pattern analysis (MVPA), have received growing attention for their ability to generate stimulus response models in a data-driven fashion. However, machine-learning methods typically require large amounts of training data as well as computational resources. In the past, this has largely limited their application to fMRI experiments involving small sets of stimulus categories and small regions of interest in the brain. By contrast, the present study compares several classification algorithms known as Nearest Neighbor (NN), Gaussian Naïve Bayes (GNB), and (regularized) Linear Discriminant Analysis (LDA) in terms of their classification accuracy in discriminating the global fMRI response patterns evoked by a large number of naturalistic visual stimuli presented as a movie. Results show that LDA regularized by principal component analysis (PCA) achieved high classification accuracies, above 90% on average for single fMRI volumes acquired 2 s apart during a 300 s movie (chance level 0.7% = 2 s/300 s). The largest source of classification errors were autocorrelations in the BOLD signal compounded by the similarity of consecutive stimuli. All classifiers performed best when given input features from a large region of interest comprising around 25% of the voxels that responded significantly to the visual stimulus. Consistent with this, the most informative principal components represented widespread distributions of co-activated brain regions that were similar between subjects and may represent functional networks. In light of these

  20. Acute Alcohol Effects on Contextual Memory BOLD Response: Differences Based on Fragmentary Blackout History

    Science.gov (United States)

    Wetherill, Reagan R.; Schnyer, David M.; Fromme, Kim

    2011-01-01

    Background Contextual memory, or memory for source details, is an important aspect of episodic memory and has been implicated in alcohol-induced fragmentary blackouts (FB). Little is known, however, about how neural functioning during contextual memory processes may differ between individuals with and without a history of fragmentary blackouts. This study examined whether neural activation during a contextual memory task differed by history of fragmentary blackout and acute alcohol consumption. Methods Twenty-four matched individuals with (FB+; n = 12) and without (FB−; n = 12) a history of FBs were recruited from a longitudinal study of alcohol use and behavioral risks and completed a laboratory beverage challenge followed by two functional magnetic resonance imaging (fMRI) sessions under no alcohol and alcohol [breath alcohol concentration (BrAC) = 0.08%] conditions. Task performance and brain hemodynamic activity during a block design contextual memory task were examined across 48 fMRI sessions. Results Groups demonstrated no differences in performance on the contextual memory task, yet exhibited different brain response patterns after alcohol intoxication. A significant FB group by beverage interaction emerged in bilateral dorsolateral prefrontal cortex and posterior parietal cortex with FB− individuals showing greater BOLD response after alcohol exposure (p blackouts. PMID:22420742

  1. Effect of CGRP and sumatriptan on the BOLD response in visual cortex

    DEFF Research Database (Denmark)

    Asghar, Mohammed Sohail; Hansen, Adam E; Larsson, Henrik B W

    2012-01-01

    To test the hypothesis that calcitonin gene-related peptide (CGRP) modulates brain activity, we investigated the effect of intravenous CGRP on brain activity in response to a visual stimulus. In addition, we examined if possible alteration in brain activity was reversed by the anti-migraine drug...... sumatriptan. Eighteen healthy volunteers were randomly allocated to receive CGRP infusion (1.5 µg/min for 20 min) or placebo. In vivo activity in the visual cortex was recorded before, during and after infusion and after 6 mg subcutaneous sumatriptan by functional magnetic resonance imaging (3 T). 77......% of the participants reported headache after CGRP. We found no changes in brain activity after CGRP (P = 0.12) or after placebo (P = 0.41). Sumatriptan did not affect brain activity after CGRP (P = 0.71) or after placebo (P = 0.98). Systemic CGRP or sumatriptan has no direct effects on the BOLD activity in visual...

  2. Patterns of cortical oscillations organize neural activity into whole-brain functional networks evident in the fMRI BOLD signal

    Directory of Open Access Journals (Sweden)

    Jennifer C Whitman

    2013-03-01

    Full Text Available Recent findings from electrophysiology and multimodal neuroimaging have elucidated the relationship between patterns of cortical oscillations evident in EEG / MEG and the functional brain networks evident in the BOLD signal. Much of the existing literature emphasized how high-frequency cortical oscillations are thought to coordinate neural activity locally, while low-frequency oscillations play a role in coordinating activity between more distant brain regions. However, the assignment of different frequencies to different spatial scales is an oversimplification. A more informative approach is to explore the arrangements by which these low- and high-frequency oscillations work in concert, coordinating neural activity into whole-brain functional networks. When relating such networks to the BOLD signal, we must consider how the patterns of cortical oscillations change at the same speed as cognitive states, which often last less than a second. Consequently, the slower BOLD signal may often reflect the summed neural activity of several transient network configurations. This temporal mismatch can be circumvented if we use spatial maps to assess correspondence between oscillatory networks and BOLD networks.

  3. The impact of temporal regularization on estimates of the BOLD hemodynamic response function: a comparative analysis.

    Science.gov (United States)

    Casanova, Ramon; Ryali, Srikanth; Serences, John; Yang, Lucie; Kraft, Robert; Laurienti, Paul J; Maldjian, Joseph A

    2008-05-01

    In fMRI data analysis it has been shown that for a wide range of situations the hemodynamic response function (HRF) can be reasonably characterized as the impulse response function of a linear and time invariant system. An accurate and robust extraction of the HRF is essential to infer quantitative information about the relative timing of the neuronal events in different brain regions. When no assumptions are made about the HRF shape, it is most commonly estimated using time windowed averaging or a least squares estimated general linear model based on either Fourier or delta basis functions. Recently, regularization methods have been employed to increase the estimation efficiency of the HRF; typically these methods produce more accurate HRF estimates than the least squares approach [Goutte, C., Nielsen, F.A., Hansen, L.K., 2000. Modeling the Haemodynamic Response in fMRI Using Smooth FIR Filters. IEEE Trans. Med. Imag. 19(12), 1188-1201.]. Here, we use simulations to clarify the relative merit of temporal regularization based methods compared to the least squares methods with respect to the accuracy of estimating certain characteristics of the HRF such as time to peak (TTP), height (HR) and width (W) of the response. We implemented a Bayesian approach proposed by Marrelec et al. [Marrelec, G., Benali, H., Ciuciu, P., Pelegrini-Issac, M., Poline, J.-B., 2003. Robust Estimation of the Hemodynamic Response Function in Event-Related BOLD fMRI Using Basic Physiological Information. Hum. Brain Mapp. 19, 1-17., Marrelec, G., Benali, H., Ciuciu, P., Poline, J.B. Bayesian estimation of the hemodynamic of the hemodynamic response function in functional MRI. In: R. F, editor; 2001; Melville. p 229-247.] and its deterministic counterpart based on a combination of Tikhonov regularization [Tikhonov, A.N., Arsenin, V.Y., 1977. Solution of ill-posed problems. Washington DC: W.H. Winston.] and generalized cross-validation (GCV) [Wahba, G., 1990. Spline Models for Observational Data

  4. Co-localization between the BOLD response and epileptiform discharges recorded by simultaneous intracranial EEG-fMRI at 3 T

    Directory of Open Access Journals (Sweden)

    Yahya Aghakhani

    2015-01-01

    Conclusions: iEEG-fMRI is a feasible and low-risk method for assessment of hemodynamic changes of very focal IEDs that may not be recorded by scalp EEG. A high concordance rate between the location of the BOLD response and IEDs was seen for mesial temporal (6/7 IEDs. Significant BOLD activation was also seen in areas distant from the active electrode and these sites exhibited maximal BOLD activation in the majority of cases. This implies that iEEG-fMRI may further describe the areas involved in the generation of IEDs beyond the vicinity of the electrode(s.

  5. Mapping and characterization of positive and negative BOLD responses to visual stimulation in multiple brain regions at 7T.

    Science.gov (United States)

    Jorge, João; Figueiredo, Patrícia; Gruetter, Rolf; van der Zwaag, Wietske

    2018-02-20

    External stimuli and tasks often elicit negative BOLD responses in various brain regions, and growing experimental evidence supports that these phenomena are functionally meaningful. In this work, the high sensitivity available at 7T was explored to map and characterize both positive (PBRs) and negative BOLD responses (NBRs) to visual checkerboard stimulation, occurring in various brain regions within and beyond the visual cortex. Recently-proposed accelerated fMRI techniques were employed for data acquisition, and procedures for exclusion of large draining vein contributions, together with ICA-assisted denoising, were included in the analysis to improve response estimation. Besides the visual cortex, significant PBRs were found in the lateral geniculate nucleus and superior colliculus, as well as the pre-central sulcus; in these regions, response durations increased monotonically with stimulus duration, in tight covariation with the visual PBR duration. Significant NBRs were found in the visual cortex, auditory cortex, default-mode network (DMN) and superior parietal lobule; NBR durations also tended to increase with stimulus duration, but were significantly less sustained than the visual PBR, especially for the DMN and superior parietal lobule. Responses in visual and auditory cortex were further studied for checkerboard contrast dependence, and their amplitudes were found to increase monotonically with contrast, linearly correlated with the visual PBR amplitude. Overall, these findings suggest the presence of dynamic neuronal interactions across multiple brain regions, sensitive to stimulus intensity and duration, and demonstrate the richness of information obtainable when jointly mapping positive and negative BOLD responses at a whole-brain scale, with ultra-high field fMRI. © 2018 Wiley Periodicals, Inc.

  6. Anatomical and functional assemblies of brain BOLD oscillations

    Science.gov (United States)

    Baria, Alexis T.; Baliki, Marwan N.; Parrish, Todd; Apkarian, A. Vania

    2011-01-01

    Brain oscillatory activity has long been thought to have spatial properties, the details of which are unresolved. Here we examine spatial organizational rules for the human brain oscillatory activity as measured by blood oxygen level-dependent (BOLD). Resting state BOLD signal was transformed into frequency space (Welch’s method), averaged across subjects, and its spatial distribution studied as a function of four frequency bands, spanning the full bandwidth of BOLD. The brain showed anatomically constrained distribution of power for each frequency band. This result was replicated on a repository dataset of 195 subjects. Next, we examined larger-scale organization by parceling the neocortex into regions approximating Brodmann Areas (BAs). This indicated that BAs of simple function/connectivity (unimodal), vs. complex properties (transmodal), are dominated by low frequency BOLD oscillations, and within the visual ventral stream we observe a graded shift of power to higher frequency bands for BAs further removed from the primary visual cortex (increased complexity), linking frequency properties of BOLD to hodology. Additionally, BOLD oscillation properties for the default mode network demonstrated that it is composed of distinct frequency dependent regions. When the same analysis was performed on a visual-motor task, frequency-dependent global and voxel-wise shifts in BOLD oscillations could be detected at brain sites mostly outside those identified with general linear modeling. Thus, analysis of BOLD oscillations in full bandwidth uncovers novel brain organizational rules, linking anatomical structures and functional networks to characteristic BOLD oscillations. The approach also identifies changes in brain intrinsic properties in relation to responses to external inputs. PMID:21613505

  7. Structural connectome topology relates to regional BOLD signal dynamics in the mouse brain

    Science.gov (United States)

    Sethi, Sarab S.; Zerbi, Valerio; Wenderoth, Nicole; Fornito, Alex; Fulcher, Ben D.

    2017-04-01

    Brain dynamics are thought to unfold on a network determined by the pattern of axonal connections linking pairs of neuronal elements; the so-called connectome. Prior work has indicated that structural brain connectivity constrains pairwise correlations of brain dynamics ("functional connectivity"), but it is not known whether inter-regional axonal connectivity is related to the intrinsic dynamics of individual brain areas. Here we investigate this relationship using a weighted, directed mesoscale mouse connectome from the Allen Mouse Brain Connectivity Atlas and resting state functional MRI (rs-fMRI) time-series data measured in 184 brain regions in eighteen anesthetized mice. For each brain region, we measured degree, betweenness, and clustering coefficient from weighted and unweighted, and directed and undirected versions of the connectome. We then characterized the univariate rs-fMRI dynamics in each brain region by computing 6930 time-series properties using the time-series analysis toolbox, hctsa. After correcting for regional volume variations, strong and robust correlations between structural connectivity properties and rs-fMRI dynamics were found only when edge weights were accounted for, and were associated with variations in the autocorrelation properties of the rs-fMRI signal. The strongest relationships were found for weighted in-degree, which was positively correlated to the autocorrelation of fMRI time series at time lag τ = 34 s (partial Spearman correlation ρ = 0.58 ), as well as a range of related measures such as relative high frequency power (f > 0.4 Hz: ρ = - 0.43 ). Our results indicate that the topology of inter-regional axonal connections of the mouse brain is closely related to intrinsic, spontaneous dynamics such that regions with a greater aggregate strength of incoming projections display longer timescales of activity fluctuations.

  8. Brain functional BOLD perturbation modelling for forward fMRI and inverse mapping

    Science.gov (United States)

    Robinson, Jennifer; Calhoun, Vince

    2018-01-01

    Purpose To computationally separate dynamic brain functional BOLD responses from static background in a brain functional activity for forward fMRI signal analysis and inverse mapping. Methods A brain functional activity is represented in terms of magnetic source by a perturbation model: χ = χ0 +δχ, with δχ for BOLD magnetic perturbations and χ0 for background. A brain fMRI experiment produces a timeseries of complex-valued images (T2* images), whereby we extract the BOLD phase signals (denoted by δP) by a complex division. By solving an inverse problem, we reconstruct the BOLD δχ dataset from the δP dataset, and the brain χ distribution from a (unwrapped) T2* phase image. Given a 4D dataset of task BOLD fMRI, we implement brain functional mapping by temporal correlation analysis. Results Through a high-field (7T) and high-resolution (0.5mm in plane) task fMRI experiment, we demonstrated in detail the BOLD perturbation model for fMRI phase signal separation (P + δP) and reconstructing intrinsic brain magnetic source (χ and δχ). We also provided to a low-field (3T) and low-resolution (2mm) task fMRI experiment in support of single-subject fMRI study. Our experiments show that the δχ-depicted functional map reveals bidirectional BOLD χ perturbations during the task performance. Conclusions The BOLD perturbation model allows us to separate fMRI phase signal (by complex division) and to perform inverse mapping for pure BOLD δχ reconstruction for intrinsic functional χ mapping. The full brain χ reconstruction (from unwrapped fMRI phase) provides a new brain tissue image that allows to scrutinize the brain tissue idiosyncrasy for the pure BOLD δχ response through an automatic function/structure co-localization. PMID:29351339

  9. Brain functional BOLD perturbation modelling for forward fMRI and inverse mapping.

    Science.gov (United States)

    Chen, Zikuan; Robinson, Jennifer; Calhoun, Vince

    2018-01-01

    To computationally separate dynamic brain functional BOLD responses from static background in a brain functional activity for forward fMRI signal analysis and inverse mapping. A brain functional activity is represented in terms of magnetic source by a perturbation model: χ = χ0 +δχ, with δχ for BOLD magnetic perturbations and χ0 for background. A brain fMRI experiment produces a timeseries of complex-valued images (T2* images), whereby we extract the BOLD phase signals (denoted by δP) by a complex division. By solving an inverse problem, we reconstruct the BOLD δχ dataset from the δP dataset, and the brain χ distribution from a (unwrapped) T2* phase image. Given a 4D dataset of task BOLD fMRI, we implement brain functional mapping by temporal correlation analysis. Through a high-field (7T) and high-resolution (0.5mm in plane) task fMRI experiment, we demonstrated in detail the BOLD perturbation model for fMRI phase signal separation (P + δP) and reconstructing intrinsic brain magnetic source (χ and δχ). We also provided to a low-field (3T) and low-resolution (2mm) task fMRI experiment in support of single-subject fMRI study. Our experiments show that the δχ-depicted functional map reveals bidirectional BOLD χ perturbations during the task performance. The BOLD perturbation model allows us to separate fMRI phase signal (by complex division) and to perform inverse mapping for pure BOLD δχ reconstruction for intrinsic functional χ mapping. The full brain χ reconstruction (from unwrapped fMRI phase) provides a new brain tissue image that allows to scrutinize the brain tissue idiosyncrasy for the pure BOLD δχ response through an automatic function/structure co-localization.

  10. Complex motor task associated with non-linear BOLD responses in cerebro-cortical areas and cerebellum.

    Science.gov (United States)

    Alahmadi, Adnan A S; Samson, Rebecca S; Gasston, David; Pardini, Matteo; Friston, Karl J; D'Angelo, Egidio; Toosy, Ahmed T; Wheeler-Kingshott, Claudia A M

    2016-06-01

    Previous studies have used fMRI to address the relationship between grip force (GF) applied to an object and BOLD response. However, whilst the majority of these studies showed a linear relationship between GF and neural activity in the contralateral M1 and ipsilateral cerebellum, animal studies have suggested the presence of non-linear components in the GF-neural activity relationship. Here, we present a methodology for assessing non-linearities in the BOLD response to different GF levels, within primary motor as well as sensory and cognitive areas and the cerebellum. To be sensitive to complex forms, we designed a feasible grip task with five GF targets using an event-related visually guided paradigm and studied a cohort of 13 healthy volunteers. Polynomial functions of increasing order were fitted to the data. (1) activated motor areas irrespective of GF; (2) positive higher-order responses in and outside M1, involving premotor, sensory and visual areas and cerebellum; (3) negative correlations with GF, predominantly involving the visual domain. Overall, our results suggest that there are physiologically consistent behaviour patterns in cerebral and cerebellar cortices; for example, we observed the presence of a second-order effect in sensorimotor areas, consistent with an optimum metabolic response at intermediate GF levels, while higher-order behaviour was found in associative and cognitive areas. At higher GF levels, sensory-related cortical areas showed reduced activation, interpretable as a redistribution of the neural activity for more demanding tasks. These results have the potential of opening new avenues for investigating pathological mechanisms of neurological diseases.

  11. Differential Localization of Pain-Related and Pain-Unrelated Neural Responses for Acupuncture at BL60 Using BOLD fMRI

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    Na-Hee Kim

    2013-01-01

    Full Text Available The objective of this study was to differentiate between pain-related and pain-unrelated neural responses of acupuncture at BL60 to investigate the specific effects of acupuncture. A total of 19 healthy volunteers were evaluated. fMRI was performed with sham or verum acupuncture stimulation at the left BL60 before and after local anesthesia. To investigate the relative BOLD signal effect for each session, a one-sample t-test was performed for individual contrast maps, and a paired t-test to investigate the differences between the pre- and post-anesthetic signal effects. Regarding verum acupuncture, areas that were more activated before local anesthesia included the superior, middle, and medial frontal gyri, inferior parietal lobule, superior temporal gyrus, thalamus, middle temporal gyrus, cingulate gyrus, culmen, and cerebellar tonsil. The postcentral gyrus was more deactivated before local anesthesia. After local anesthesia, the middle occipital gyrus, inferior temporal gyrus, postcentral gyrus, precuneus, superior parietal lobule, and declive were deactivated. Pre-anesthetic verum acupuncture at BL60 activated areas of vision and pain transmission. Post-anesthetic verum acupuncture deactivated brain areas of visual function, which is considered to be a pain-unrelated acupuncture response. It indicates that specific effects of acupoint BL60 are to control vision sense as used in the clinical setting.

  12. Analysis of Neural-BOLD Coupling through Four Models of the Neural Metabolic Demand

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    Christopher W Tyler

    2015-12-01

    Full Text Available The coupling of the neuronal energetics to the blood-oxygen-level-dependent (BOLD response is still incompletely understood. To address this issue, we compared the fits of four plausible models of neurometabolic coupling dynamics to available data for simultaneous recordings of the local field potential (LFP and the local BOLD response recorded from monkey primary visual cortex over a wide range of stimulus durations. The four models of the metabolic demand driving the BOLD response were: direct coupling with the overall LFP; rectified coupling to the LFP; coupling with a slow adaptive component of the implied neural population response; and coupling with the non-adaptive intracellular input signal defined by the stimulus time course. Taking all stimulus durations into account, the results imply that the BOLD response is most closely coupled with metabolic demand derived from the intracellular input waveform, without significant influence from the adaptive transients and nonlinearities exhibited by the LFP waveform.

  13. Distinct BOLD fMRI Responses of Capsaicin-Induced Thermal Sensation Reveal Pain-Related Brain Activation in Nonhuman Primates.

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    Abu Bakar Ali Asad

    Full Text Available Approximately 20% of the adult population suffer from chronic pain that is not adequately treated by current therapies, highlighting a great need for improved treatment options. To develop effective analgesics, experimental human and animal models of pain are critical. Topically/intra-dermally applied capsaicin induces hyperalgesia and allodynia to thermal and tactile stimuli that mimics chronic pain and is a useful translation from preclinical research to clinical investigation. Many behavioral and self-report studies of pain have exploited the use of the capsaicin pain model, but objective biomarker correlates of the capsaicin augmented nociceptive response in nonhuman primates remains to be explored.Here we establish an aversive capsaicin-induced fMRI model using non-noxious heat stimuli in Cynomolgus monkeys (n = 8. BOLD fMRI data were collected during thermal challenge (ON:20 s/42°C; OFF:40 s/35°C, 4-cycle at baseline and 30 min post-capsaicin (0.1 mg, topical, forearm application. Tail withdrawal behavioral studies were also conducted in the same animals using 42°C or 48°C water bath pre- and post- capsaicin application (0.1 mg, subcutaneous, tail.Group comparisons between pre- and post-capsaicin application revealed significant BOLD signal increases in brain regions associated with the 'pain matrix', including somatosensory, frontal, and cingulate cortices, as well as the cerebellum (paired t-test, p<0.02, n = 8, while no significant change was found after the vehicle application. The tail withdrawal behavioral study demonstrated a significant main effect of temperature and a trend towards capsaicin induced reduction of latency at both temperatures.These findings provide insights into the specific brain regions involved with aversive, 'pain-like', responses in a nonhuman primate model. Future studies may employ both behavioral and fMRI measures as translational biomarkers to gain deeper understanding of pain processing and evaluate

  14. Detection and Characterization of Single-Trial fMRI BOLD Responses : Paradigm Free Mapping

    NARCIS (Netherlands)

    Gaudes, Cesar Caballero; Petridou, Natalia; Dryden, Ian L.; Bai, Li; Francis, Susan T.; Gowland, Penny A.

    This work presents a novel method of mapping the brain's response to single stimuli in space and time without prior knowledge of the paradigm timing: paradigm free mapping (PFM). This method is based on deconvolution of the hemodynamic response from the voxel time series assuming a linear response

  15. Transverse patterning dissociates human EEG theta power and hippocampal BOLD activation.

    Science.gov (United States)

    Meltzer, Jed A; Fonzo, Greg A; Constable, R Todd

    2009-01-01

    Theta oscillations (4-8 Hz) are often modulated in human electroencephalogram (EEG) studies of memory, whereas overlapping frequencies dominate rodent hippocampal EEG. An emerging parallelism between theta reactivity and hippocampal functional magnetic resonance imaging activation has suggested a homology between theta activity in humans and rodents, representing a process of cortico-hippocampal interaction involved in memory. In the present study, we investigated EEG reactivity during performance of a relational memory task that induces a negative hippocampal blood oxygenation level dependent (BOLD) signal change, compared to a nonrelational control condition. Relational trials induced theta increases and alpha decreases. Low Resolution Electromagnetic Brain Tomography estimates localized theta and alpha modulation to frontal midline and parietal midline cortices, respectively, both of which exhibit negative BOLD responses in this task. Thus, theta and alpha dynamics are dissociable from positive BOLD activation, and may, in fact, colocalize with negative BOLD responses.

  16. Music reduces pain and increases resting state fMRI BOLD signal amplitude in the left angular gyrus in fibromyalgia patients

    DEFF Research Database (Denmark)

    Garza-Villarreal, Eduardo A; Jiang, Zhiguo; Vuust, Peter

    2015-01-01

    Music reduces pain in fibromyalgia (FM), a chronic pain disease, but the functional neural correlates of music-induced analgesia (MIA) are still largely unknown. We recruited FM patients (n = 22) who listened to their preferred relaxing music and an auditory control (pink noise) for 5 min without...... external noise from fMRI image acquisition. Resting state fMRI was then acquired before and after the music and control conditions. A significant increase in the amplitude of low frequency fluctuations of the BOLD signal was evident in the left angular gyrus (lAnG) after listening to music, which in turn......, correlated to the analgesia reports. The post-hoc seed-based functional connectivity analysis of the lAnG showed found higher connectivity after listening to music with right dorsolateral prefrontal cortex (rdlPFC), the left caudate (lCau), and decreased connectivity with right anterior cingulate cortex (r...

  17. Left fusiform BOLD responses are inversely related to word-likeness in a one-back task.

    Science.gov (United States)

    Wang, Xiaojuan; Yang, Jianfeng; Shu, Hua; Zevin, Jason D

    2011-04-01

    Although its precise functional contribution to reading remains unclear, there is broad consensus that an activity in the left mid-fusiform gyrus is highly sensitive to written words and word-like stimuli. In the current study, we take advantage of a particularity of the Chinese writing system in order to manipulate word-likeness parametrically, from real characters, to pseudo-characters that vary in whether they contain phonological and semantic cues, to artificial stimuli with varying surface similarity to real characters. In a one-back task, BOLD activity in the left mid-fusiform was inversely related to word-likeness, such that the least activity was observed in response to real characters, and the greatest to artificial stimuli that violate the orthotactic constraints of the writing system. One possible explanation for this surprising result is that the short-term memory demands of the one-back task put more pressure on the visual system when other sources of information cannot be used to aid in detecting repeated stimuli. For real characters and, to a lesser extent for pseudo-characters, information about meaning and pronunciation can contribute to performance, whereas artificial stimuli are entirely dependent on visual information. Consistent with this view, functional connectivity analyses revealed a strong positive relationship between left mid-fusiform and other visual areas, whereas areas typically involved in phonological and semantic processing for text were negatively correlated with this region. Copyright © 2011 Elsevier Inc. All rights reserved.

  18. Comparison of fMRI BOLD Response Patterns by Electrical Stimulation of the Ventroposterior Complex and Medial Thalamus of the Rat

    Science.gov (United States)

    Yang, Pai-Feng; Chen, You-Yin; Chen, Der-Yow; Hu, James W.; Chen, Jyh-Horng; Yen, Chen-Tung

    2013-01-01

    The objective of this study was to compare the functional connectivity of the lateral and medial thalamocortical pain pathways by investigating the blood oxygen level-dependent (BOLD) activation patterns in the forebrain elicited by direct electrical stimulation of the ventroposterior (VP) and medial (MT) thalamus. An MRI-compatible stimulation electrode was implanted in the VP or MT of α-chloralose-anesthetized rats. Electrical stimulation was applied to the VP or MT at various intensities (50 µA to 300 µA) and frequencies (1 Hz to 12 Hz). BOLD responses were analyzed in the ipsilateral forelimb region of the primary somatosensory cortex (iS1FL) after VP stimulation and in the ipsilateral cingulate cortex (iCC) after MT stimulation. When stimulating the VP, the strongest activation occurred at 3 Hz. The stimulation intensity threshold was 50 µA and the response rapidly peaked at 100 µA. When stimulating the MT, The optimal frequency for stimulation was 9 Hz or 12 Hz, the stimulation intensity threshold was 100 µA and we observed a graded increase in the BOLD response following the application of higher intensity stimuli. We also evaluated c-Fos expression following the application of a 200-µA stimulus. Ventroposterior thalamic stimulation elicited c-Fos-positivity in few cells in the iS1FL and caudate putamen (iCPu). Medial thalamic stimulation, however, produced numerous c-Fos-positive cells in the iCC and iCPu. The differential BOLD responses and c-Fos expressions elicited by VP and MT stimulation indicate differences in stimulus-response properties of the medial and lateral thalamic pain pathways. PMID:23826146

  19. Comparison of fMRI BOLD response patterns by electrical stimulation of the ventroposterior complex and medial thalamus of the rat.

    Directory of Open Access Journals (Sweden)

    Pai-Feng Yang

    Full Text Available The objective of this study was to compare the functional connectivity of the lateral and medial thalamocortical pain pathways by investigating the blood oxygen level-dependent (BOLD activation patterns in the forebrain elicited by direct electrical stimulation of the ventroposterior (VP and medial (MT thalamus. An MRI-compatible stimulation electrode was implanted in the VP or MT of α-chloralose-anesthetized rats. Electrical stimulation was applied to the VP or MT at various intensities (50 µA to 300 µA and frequencies (1 Hz to 12 Hz. BOLD responses were analyzed in the ipsilateral forelimb region of the primary somatosensory cortex (iS1FL after VP stimulation and in the ipsilateral cingulate cortex (iCC after MT stimulation. When stimulating the VP, the strongest activation occurred at 3 Hz. The stimulation intensity threshold was 50 µA and the response rapidly peaked at 100 µA. When stimulating the MT, The optimal frequency for stimulation was 9 Hz or 12 Hz, the stimulation intensity threshold was 100 µA and we observed a graded increase in the BOLD response following the application of higher intensity stimuli. We also evaluated c-Fos expression following the application of a 200-µA stimulus. Ventroposterior thalamic stimulation elicited c-Fos-positivity in few cells in the iS1FL and caudate putamen (iCPu. Medial thalamic stimulation, however, produced numerous c-Fos-positive cells in the iCC and iCPu. The differential BOLD responses and c-Fos expressions elicited by VP and MT stimulation indicate differences in stimulus-response properties of the medial and lateral thalamic pain pathways.

  20. Fourier power, subjective distance, and object categories all provide plausible models of BOLD responses in scene-selective visual areas

    Science.gov (United States)

    Lescroart, Mark D.; Stansbury, Dustin E.; Gallant, Jack L.

    2015-01-01

    Perception of natural visual scenes activates several functional areas in the human brain, including the Parahippocampal Place Area (PPA), Retrosplenial Complex (RSC), and the Occipital Place Area (OPA). It is currently unclear what specific scene-related features are represented in these areas. Previous studies have suggested that PPA, RSC, and/or OPA might represent at least three qualitatively different classes of features: (1) 2D features related to Fourier power; (2) 3D spatial features such as the distance to objects in a scene; or (3) abstract features such as the categories of objects in a scene. To determine which of these hypotheses best describes the visual representation in scene-selective areas, we applied voxel-wise modeling (VM) to BOLD fMRI responses elicited by a set of 1386 images of natural scenes. VM provides an efficient method for testing competing hypotheses by comparing predictions of brain activity based on encoding models that instantiate each hypothesis. Here we evaluated three different encoding models that instantiate each of the three hypotheses listed above. We used linear regression to fit each encoding model to the fMRI data recorded from each voxel, and we evaluated each fit model by estimating the amount of variance it predicted in a withheld portion of the data set. We found that voxel-wise models based on Fourier power or the subjective distance to objects in each scene predicted much of the variance predicted by a model based on object categories. Furthermore, the response variance explained by these three models is largely shared, and the individual models explain little unique variance in responses. Based on an evaluation of previous studies and the data we present here, we conclude that there is currently no good basis to favor any one of the three alternative hypotheses about visual representation in scene-selective areas. We offer suggestions for further studies that may help resolve this issue. PMID:26594164

  1. Fourier power, subjective distance and object categories all provide plausible models of BOLD responses in scene-selective visual areas

    Directory of Open Access Journals (Sweden)

    Mark Daniel Lescroart

    2015-11-01

    Full Text Available Perception of natural visual scenes activates several functional areas in the human brain, including the Parahippocampal Place Area (PPA, Retrosplenial Complex (RSC, and the Occipital Place Area (OPA. It is currently unclear what specific scene-related features are represented in these areas. Previous studies have suggested that PPA, RSC, and/or OPA might represent at least three qualitatively different classes of features: (1 2D features related to Fourier power; (2 3D spatial features such as the distance to objects in a scene; or (3 abstract features such as the categories of objects in a scene. To determine which of these hypotheses best describes the visual representation in scene-selective areas, we applied voxel-wise modeling (VM to BOLD fMRI responses elicited by a set of 1,386 images of natural scenes. VM provides an efficient method for testing competing hypotheses by comparing predictions of brain activity based on encoding models that instantiate each hypothesis. Here we evaluated three different encoding models that instantiate each of the three hypotheses listed above. We used linear regression to fit each encoding model to the fMRI data recorded from each voxel, and we evaluated each fit model by estimating the amount of variance it predicted in a withheld portion of the data set. We found that voxel-wise models based on Fourier power or the subjective distance to objects in each scene predicted much of the variance predicted by a model based on object categories. Furthermore, the response variance explained by these three models is largely shared, and the individual models explain little unique variance in responses. Based on an evaluation of previous studies and the data we present here, we conclude that there is currently no good basis to favor any one of the three alternative hypotheses about visual representation in scene-selective areas. We offer suggestions for further studies that may help resolve this issue.

  2. The 5-HT2Creceptor agonist meta-chlorophenylpiperazine (mCPP) reduces palatable food consumption and BOLD fMRI responses to food images in healthy female volunteers.

    Science.gov (United States)

    Thomas, Jason M; Dourish, Colin T; Tomlinson, Jeremy; Hassan-Smith, Zaki; Hansen, Peter C; Higgs, Suzanne

    2018-01-01

    Brain 5-HT 2C receptors form part of a neural network that controls eating behaviour. 5-HT 2C receptor agonists decrease food intake by activating proopiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus, but recent research in rodents has suggested that 5-HT 2C receptor agonists may also act via dopaminergic circuitry to reduce the rewarding value of food and other reinforcers. No mechanistic studies on the effects of 5-HT 2C agonists on food intake in humans have been conducted to date. The present study examined the effects of the 5-HT 2C receptor agonist meta-chlorophenylpiperazine (mCPP) on food consumption, eating microstructure and blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) responses to food pictures in healthy female volunteers. In a double-blind, placebo-controlled, crossover design, participants were randomized immediately after screening to receive oral mCPP (30mg) in a single morning dose, or placebo, in a counterbalanced order. Test foods were served from a Universal Eating Monitor (UEM) that measured eating rate and fMRI BOLD signals to the sight of food and non-food images were recorded. mCPP decreased rated appetite and intake of a palatable snack eaten in the absence of hunger but had no significant effect on the consumption of a pasta lunch (although pasta eating rate was reduced). mCPP also decreased BOLD fMRI responses to the sight of food pictures in areas of reward-associated circuitry. A post hoc analysis identified individual variability in the response to mCPP (exploratory responder-non-responder analysis). Some participants did not reduce their cookie intake after treatment with mCPP and this lack of response was associated with enhanced ratings of cookie pleasantness and enhanced baseline BOLD responses to food images in key reward and appetite circuitry. These results suggest that 5-HT 2C receptor activation in humans inhibits food reward-related responding and that further

  3. Striatal BOLD Response Reflects the Impact of Herd Information on Financial Decisions.

    Science.gov (United States)

    Burke, Christopher J; Tobler, Philippe N; Schultz, Wolfram; Baddeley, Michelle

    2010-01-01

    Like other species, humans are sensitive to the decisions and actions of conspecifics, which can lead to herd behavior and undesirable outcomes such as stock market bubbles and bank runs. However, how the brain processes this socially derived influence is only poorly understood. Using functional magnetic resonance imaging (fMRI), we scanned participants as they made decisions on whether to buy stocks after observing others' buying decisions. We demonstrate that activity in the ventral striatum, an area heavily implicated in reward processing, tracked the degree of influence on participants' decisions arising from the observation of other peoples' decisions. The signal did not track non-human, non-social control decisions. These findings lend weight to the notion that the ventral striatum is involved in the processing of complex social aspects of decision making and identify a possible neural basis for herd behavior.

  4. Striatal BOLD response reflects the impact of herd information on financial decisions

    Directory of Open Access Journals (Sweden)

    Christopher J Burke

    2010-06-01

    Full Text Available Like other species, humans are sensitive to the decisions and actions of conspecifics, which can lead to herd behavior and undesirable outcomes such as stock market bubbles and bank runs. However, how the brain processes this socially derived influence is only poorly understood. Using functional magnetic resonance imaging (fMRI, we scanned participants as they made decisions on whether to buy stocks after observing others’ buying decisions. We demonstrate that activity in the ventral striatum, an area heavily implicated in reward processing, tracked the degree of influence on participants’ decisions arising from the observation of other peoples’ decisions. The signal did not track non-human, non-social control decisions. These findings lend weight to the notion that the ventral striatum is involved in the processing of complex social aspects of decision-making and identify a possible neural basis for herd behavior.

  5. Altered BOLD response during inhibitory and error processing in adolescents with anorexia nervosa.

    Directory of Open Access Journals (Sweden)

    Christina Wierenga

    Full Text Available BACKGROUND: Individuals with anorexia nervosa (AN are often cognitively rigid and behaviorally over-controlled. We previously showed that adult females recovered from AN relative to healthy comparison females had less prefrontal activation during an inhibition task, which suggested a functional brain correlate of altered inhibitory processing in individuals recovered from AN. However, the degree to which these functional brain alterations are related to disease state and whether error processing is altered in AN individuals is unknown. METHODOLOGY/PRINCIPAL FINDINGS: In the current study, ill adolescent AN females (n = 11 and matched healthy comparison adolescents (CA with no history of an eating disorder (n = 12 performed a validated stop signal task (SST during functional magnetic resonance imaging (fMRI to explore differences in error and inhibitory processing. The groups did not differ on sociodemographic variables or on SST performance. During inhibitory processing, a significant group x difficulty (hard, easy interaction was detected in the right dorsal anterior cingulate cortex (ACC, right middle frontal gyrus (MFG, and left posterior cingulate cortex (PCC, which was characterized by less activation in AN compared to CA participants during hard trials. During error processing, a significant group x accuracy (successful inhibit, failed inhibit interaction in bilateral MFG and right PCC was observed, which was characterized by less activation in AN compared to CA participants during error (i.e., failed inhibit trials. CONCLUSION/SIGNIFICANCE: Consistent with our prior findings in recovered AN, ill AN adolescents, relative to CA, showed less inhibition-related activation within the dorsal ACC, MFG and PCC as inhibitory demand increased. In addition, ill AN adolescents, relative to CA, also showed reduced activation to errors in the bilateral MFG and left PCC. These findings suggest that altered prefrontal and cingulate activation during

  6. Photosynthesis and growth responses of mustard (Brassica juncea L. cv Pusa Bold) plants to free air carbon dioxide enrichment (FACE).

    Science.gov (United States)

    Ruhil, Kamal; Sheeba; Ahmad, Altaf; Iqbal, Muhammad; Tripathy, Baishnab C

    2015-07-01

    Increased atmospheric [CO2] is likely to affect photosynthesis, plant growth, and yield potential of plants. Mustard (Brassica juncea L.) is an important oil seed crop that is widely grown in India. Therefore, the impact of elevated [CO2] (585 μmol mol(-1)) on pigment and protein content, chlorophyll a fluorescence, photosynthetic electron transport reactions, CO2 assimilation, biomass production, and seed yield potential was measured in B. juncea cv Pusa Bold, grown inside free air carbon dioxide enrichment (FACE) rings installed on the campus of Jawaharlal Nehru University, New Delhi, India. Plants were grown for three consecutive winter seasons (2010-2013), in ambient (385 μmol mol(-1)) or elevated [CO2], in field conditions. Elevated [CO2] had no significant effect on the minimal chlorophyll fluorescence (F 0), while the quantum efficiency of Photosystem II, measured as variable fluorescence (F v = F m-F 0) to maximum fluoresence (F m), increased by 3 %. Electron transport rate, photosystem I, photosystem II, and whole chain electron transport rates increased by 8 % in elevated [CO2]. However, the net photosynthesis rate increased by ≈50 % in three growing seasons under elevated [CO2] condition. The stomatal conductance and transpiration rate decreased resulting in higher photosynthetic water use efficiency. The photosynthesizing surface, i.e., leaf area index substantially increased leading to higher biomass and seed yield under elevated [CO2] condition. Acclimatory downregulation of photosynthesis and plant productivity was not observed in three consecutive growing years suggesting that in the absence of nutrient limitation, B. juncea is highly responsive to elevated CO2 whose yield potential shall increase in changing climatic conditions.

  7. Limits of 2D-TCA in detecting BOLD responses to epileptic activity.

    Science.gov (United States)

    Khatamian, Yasha Borna; Fahoum, Firas; Gotman, Jean

    2011-05-01

    Two-dimensional temporal clustering analysis (2D-TCA) is a relatively new functional MRI (fMRI) based technique that breaks blood oxygen level dependent activity into separate components based on timing and has shown potential for localizing epileptic activity independently of electroencephalography (EEG). 2D-TCA has only been applied to detect epileptic activity in a few studies and its limits in detecting activity of various forms (i.e. activation size, amplitude, and frequency) have not been investigated. This study evaluated 2D-TCA's ability to detect various forms of both simulated epileptic activity and EEG-fMRI activity detected in patients. When applied to simulated data, 2D-TCA consistently detected activity in 6min runs containing 5 spikes/run, 10 spikes/run, and one 5s long event with hemodynamic response function amplitudes of at least 1.5%, 1.25%, and 1% above baseline respectively. When applied to patient data, while detection of interictal spikes was inconsistent, 2D-TCA consistently produced results similar to those obtained by EEG-fMRI when at least 2 prolonged interictal events (a few seconds each) occurred during the run. However, even for such cases it was determined that 2D-TCA can only be used to validate localization by other means or to create hypotheses as to where activity may occur, as it also detects changes not caused by epileptic activity. Copyright © 2011 Elsevier B.V. All rights reserved.

  8. Explicit authenticity and stimulus features interact to modulate BOLD response induced by emotional speech.

    Science.gov (United States)

    Drolet, Matthis; Schubotz, Ricarda I; Fischer, Julia

    2013-06-01

    Context has been found to have a profound effect on the recognition of social stimuli and correlated brain activation. The present study was designed to determine whether knowledge about emotional authenticity influences emotion recognition expressed through speech intonation. Participants classified emotionally expressive speech in an fMRI experimental design as sad, happy, angry, or fearful. For some trials, stimuli were cued as either authentic or play-acted in order to manipulate participant top-down belief about authenticity, and these labels were presented both congruently and incongruently to the emotional authenticity of the stimulus. Contrasting authentic versus play-acted stimuli during uncued trials indicated that play-acted stimuli spontaneously up-regulate activity in the auditory cortex and regions associated with emotional speech processing. In addition, a clear interaction effect of cue and stimulus authenticity showed up-regulation in the posterior superior temporal sulcus and the anterior cingulate cortex, indicating that cueing had an impact on the perception of authenticity. In particular, when a cue indicating an authentic stimulus was followed by a play-acted stimulus, additional activation occurred in the temporoparietal junction, probably pointing to increased load on perspective taking in such trials. While actual authenticity has a significant impact on brain activation, individual belief about stimulus authenticity can additionally modulate the brain response to differences in emotionally expressive speech.

  9. Music reduces pain and increases resting state fMRI BOLD signal amplitude in the left angular gyrus in fibromyalgia patients.

    Science.gov (United States)

    Garza-Villarreal, Eduardo A; Jiang, Zhiguo; Vuust, Peter; Alcauter, Sarael; Vase, Lene; Pasaye, Erick H; Cavazos-Rodriguez, Roberto; Brattico, Elvira; Jensen, Troels S; Barrios, Fernando A

    2015-01-01

    Music reduces pain in fibromyalgia (FM), a chronic pain disease, but the functional neural correlates of music-induced analgesia (MIA) are still largely unknown. We recruited FM patients (n = 22) who listened to their preferred relaxing music and an auditory control (pink noise) for 5 min without external noise from fMRI image acquisition. Resting state fMRI was then acquired before and after the music and control conditions. A significant increase in the amplitude of low frequency fluctuations of the BOLD signal was evident in the left angular gyrus (lAnG) after listening to music, which in turn, correlated to the analgesia reports. The post-hoc seed-based functional connectivity analysis of the lAnG showed found higher connectivity after listening to music with right dorsolateral prefrontal cortex (rdlPFC), the left caudate (lCau), and decreased connectivity with right anterior cingulate cortex (rACC), right supplementary motor area (rSMA), precuneus and right precentral gyrus (rPreG). Pain intensity (PI) analgesia was correlated (r = 0.61) to the connectivity of the lAnG with the rPreG. Our results show that MIA in FM is related to top-down regulation of the pain modulatory network by the default mode network (DMN).

  10. Music reduces pain and increases resting state fMRI BOLD signal amplitude in the left angular gyrus in fibromyalgia patients

    Directory of Open Access Journals (Sweden)

    Eduardo A. Garza-Villarreal

    2015-07-01

    Full Text Available Music reduces pain in fibromyalgia (FM, a chronic pain disease, but the functional neural correlates of music-induced analgesia are still largely unknown. We recruited FM patients (n = 22 who listened to their preferred relaxing music and an auditory control (pink noise for 5 minutes without external noise from fMRI image acquisition. Resting state fMRI was then acquired before and after the music and control conditions. A significant increase in the amplitude of low frequency fluctuations of the BOLD signal was evident in the left angular gyrus after listening to music, which in turn, correlated to the analgesia reports. The post-hoc seed-based functional connectivity analysis of the left angular gyrus showed found higher connectivity after listening to music with right dorsolateral prefrontal cortex, the left caudate, and decreased connectivity with right anterior cingulate cortex, right supplementary motor area, precuneus and right precentral gyrus. Pain intensity analgesia was correlated (r = .61 to the connectivity of the left angular gyrus with the right precentral gyrus. Our results show that music-induced analgesia in FM is related to top-down regulation of the pain modulatory network by the default-mode network.

  11. Regional differences in the CBF and BOLD responses to hypercapnia: a combined PET and fMRI study

    DEFF Research Database (Denmark)

    Rostrup, Egill; Law, I; Blinkenberg, M

    2000-01-01

    Previous fMRI studies of the cerebrovascular response to hypercapnia have shown signal change in cerebral gray matter, but not in white matter. Therefore, the objective of the present study was to compare (15)O PET and T *(2)-weighted MRI during a hypercapnic challenge. The measurements were perf...

  12. Hypercapnic normalization of BOLD fMRI: comparison across field strengths and pulse sequences

    DEFF Research Database (Denmark)

    Cohen, Eric R.; Rostrup, Egill; Sidaros, Karam

    2004-01-01

    The blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) signal response to neural stimulation is influenced by many factors that are unrelated to the stimulus. These factors are physiological, such as the resting venous cerebral blood volume (CBV(v)) and vessel s...

  13. Role of 3T multiparametric-MRI with BOLD hypoxia imaging for diagnosis and post therapy response evaluation of postoperative recurrent cervical cancers

    International Nuclear Information System (INIS)

    Mahajan, Abhishek; Engineer, Reena; Chopra, Supriya; Mahanshetty, Umesh; Juvekar, S.L.; Shrivastava, S.K.; Desekar, Naresh; Thakur, M.H.

    2015-01-01

    vaginal vault/local recurrence following primary surgery for cervical cancer. With institutional review board approval and written informed consent 30 women (median age: 45 years) from October 2009 to March 2010 with previous operated carcinoma cervix and suspected clinical vaginal vault/local recurrence were examined with 3.0T-MRI. MRI imaging included conventional and MPMRI sequences [dynamic contrast enhanced (DCE), diffusion weighted (DW), 1H-MR spectroscopy (1HMRS), blood oxygen level dependent hypoxia imaging (BOLD)]. Two radiologists, blinded to pathologic findings, independently assessed the pretherapy MRI findings and then correlated it with histopathology findings. Sensitivity, specificity, positive predictive value, negative predictive value and their confidence intervals were calculated. The pre and post therapy conventional and MPMRI parameters were analyzed and correlated with response to therapy. Of the 30 patients, there were 24 recurrent tumors and 6 benign lesions. The accuracy of diagnosing recurrent vault lesions was highest at combined MPMRI and conventional MRI (100%) than at conventional-MRI (70%) or MPMRI (96.7%) alone. Significant correlation was seen between percentage tumor regression and pre-treatment parameters such as negative enhancement integral (NEI) (p = 0.02), the maximum slope (p = 0.04), mADC value (p = 0.001) and amount of hypoxic fraction on the pretherapy MRI (p = 0.01). Conventional-MR with MPMRI significantly increases the diagnostic accuracy for suspected vaginal vault/local recurrence. Post therapy serial MPMRI with hypoxia imaging follow-up objectively documents the response. MPMRI and BOLD hypoxia imaging provide information regarding tumor biology at the molecular, subcellular, cellular and tissue levels and this information may be used as an appropriate and reliable biologic target for radiation dose painting to optimize therapy in future

  14. Interpreting BOLD: towards a dialogue between cognitive and cellular neuroscience.

    Science.gov (United States)

    Hall, Catherine N; Howarth, Clare; Kurth-Nelson, Zebulun; Mishra, Anusha

    2016-10-05

    Cognitive neuroscience depends on the use of blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) to probe brain function. Although commonly used as a surrogate measure of neuronal activity, BOLD signals actually reflect changes in brain blood oxygenation. Understanding the mechanisms linking neuronal activity to vascular perfusion is, therefore, critical in interpreting BOLD. Advances in cellular neuroscience demonstrating differences in this neurovascular relationship in different brain regions, conditions or pathologies are often not accounted for when interpreting BOLD. Meanwhile, within cognitive neuroscience, the increasing use of high magnetic field strengths and the development of model-based tasks and analyses have broadened the capability of BOLD signals to inform us about the underlying neuronal activity, but these methods are less well understood by cellular neuroscientists. In 2016, a Royal Society Theo Murphy Meeting brought scientists from the two communities together to discuss these issues. Here, we consolidate the main conclusions arising from that meeting. We discuss areas of consensus about what BOLD fMRI can tell us about underlying neuronal activity, and how advanced modelling techniques have improved our ability to use and interpret BOLD. We also highlight areas of controversy in understanding BOLD and suggest research directions required to resolve these issues.This article is part of the themed issue 'Interpreting BOLD: a dialogue between cognitive and cellular neuroscience'. © 2016 The Author(s).

  15. Variable reflectivity signal mirrors and signal response measurements

    International Nuclear Information System (INIS)

    Vine, Glenn de; Shaddock, Daniel A; McClelland, David E

    2002-01-01

    Future gravitational wave detectors will include some form of signal mirror in order to alter the signal response of the device. We introduce interferometer configurations which utilize a variable reflectivity signal mirror allowing a tunable peak frequency and variable signal bandwidth. A detector configured with a Fabry-Perot cavity as the signal mirror is compared theoretically with one using a Michelson interferometer for a signal mirror. A system for the measurement of the interferometer signal responses is introduced. This technique is applied to a power-recycled Michelson interferometer with resonant sideband extraction. We present broadband measurements of the benchtop prototype's signal response for a range of signal cavity detunings. This technique is also applicable to most other gravitational wave detector configurations

  16. Variable reflectivity signal mirrors and signal response measurements

    CERN Document Server

    Vine, G D; McClelland, D E

    2002-01-01

    Future gravitational wave detectors will include some form of signal mirror in order to alter the signal response of the device. We introduce interferometer configurations which utilize a variable reflectivity signal mirror allowing a tunable peak frequency and variable signal bandwidth. A detector configured with a Fabry-Perot cavity as the signal mirror is compared theoretically with one using a Michelson interferometer for a signal mirror. A system for the measurement of the interferometer signal responses is introduced. This technique is applied to a power-recycled Michelson interferometer with resonant sideband extraction. We present broadband measurements of the benchtop prototype's signal response for a range of signal cavity detunings. This technique is also applicable to most other gravitational wave detector configurations.

  17. Systematic protocol for assessment of the validity of BOLD MRI in a rabbit model of inflammatory arthritis at 1.5 tesla

    Energy Technology Data Exchange (ETDEWEB)

    Chan, Michael W.; Nathanael, George; Kis, Antonella; Amirabadi, Afsaneh; Zhong, Anguo; Rayner, Tammy; Weiss, Ruth; Detzler, Garry; Gahunia, Harpal [The Hospital for Sick Children, Department of Diagnostic Imaging, Toronto (Canada); Jong, Roland [Mount Sinai Hospital, Department of Pathology and Laboratory Medicine, Toronto (Canada); Moineddin, Rahim [Family and Community Medicine, Department of Public Health, Toronto (Canada); Crawley, Adrian [University of Toronto, Department of Medical Imaging, Toronto (Canada); Toronto Western Hospital, Department of Medical Imaging, Toronto (Canada); Doria, Andrea S. [The Hospital for Sick Children, Department of Diagnostic Imaging, Toronto (Canada); University of Toronto, Department of Medical Imaging, Toronto (Canada)

    2014-05-15

    Blood-oxygen-level-dependent (BOLD) MRI has the potential to identify regions of early hypoxic and vascular joint changes in inflammatory arthritis. There is no standard protocol for analysis of BOLD MRI measurements in musculoskeletal disorders. To optimize the following BOLD MRI reading parameters: (1) statistical threshold values (low, r > 0.01 versus high, r > 0.2); (2) summary measures of BOLD contrast (percentage of activated voxels [PT%] versus percentage signal difference between on-and-off signal intensities [diff{sub o}n{sub o}ff]); and (3) direction of BOLD response (positive, negative and positive + negative). Using BOLD MRI protocols at 1.5 T, arthritic (n = 21) and contralateral (n = 21) knees of 21 juvenile rabbits were imaged at baseline and on days 1, 14 and 28 after a unilateral intra-articular injection of carrageenan. Nine non-injected rabbits served as external control knees (n = 18). By comparing arthritic to contralateral knees, receiver operating characteristic curves were used to determine diagnostic accuracy. Using diff{sub o}n{sub o}ff and positive + negative responses, a threshold of r > 0.01 was more accurate than r > 0.2 (P = 0.03 at day 28). Comparison of summary measures yielded no statistically significant difference (P > 0.05). Although positive + negative (AUC = 0.86 at day 28) and negative responses (AUC = 0.90 at day 28) for PT% were the most diagnostically accurate, positive + negative responses for diff{sub o}n{sub o}ff (AUC = 0.78 at day 28) also had acceptable accuracy. The most clinically relevant reading parameters included a lower threshold of r > 0.01 and a positive + negative BOLD response. We propose that diff{sub o}n{sub o}ff is a more clinically relevant summary measure of BOLD MRI, while PT% can be used as an ancillary measure. (orig.)

  18. Effect of luminance contrast on BOLD-fMRI response in deaf and normal occipital visual cortex

    International Nuclear Information System (INIS)

    Xue Yanping; Zhai Renyou; Jiang Tao; Cui Yong; Zhou Tiangang; Rao Hengyi; Zhuo Yan

    2002-01-01

    Objective: To examine the effect of luminance contrast stimulus by using blood oxygenation level dependent functional magnetic resonance imaging (BOLD-fMRI) within deaf occipital visual cortex, and to compare the distribution, extent, and intensity of activated areas between deaf subjects and normal hearing subjects. Methods: Twelve deaf subjects (average age 16.5) and 15 normal hearing subjects (average age 23.7) were stimulated by 4 kinds of luminance contrast (0.7, 2.2, 50.0, 180.0 lm). The fMRI data were collected on GE 1.5 T Signa Horizon LX MRI system and analyzed by AFNI to generate the activation map. Results: Responding to all 4 kinds of stimulus luminance contrast, all deaf and normal subjects showed significant activations in occipital visual cortex. For both deaf and normal subjects, the number of activated pixels increased significantly with increasing luminance contrast (F normal = 4.27, P deaf = 6.41, P 0.05). The local mean activation level for all activated pixels remained constant with increasing luminance contrast. However, there was an increase in the mean activation level for those activated pixels common to all trials as the stimulus luminance contrast was increased, but no significant difference was found within them (F normal = 0.79, P > 0.05; F deaf = 1.6, P > 0.05). Conclusion: The effect of luminance contrast on occipital visual cortex of deaf is similar to but somewhat higher than that of normal hearing subjects. In addition, it also proved that fMRI is a feasible method in the study of the deaf visual cortex

  19. Efecto del tamaño kernel en el suavizado de señal BOLD en paradigmas funcionales (RMf (Effect of kernel size for BOLD signal smoothing in functional paradigms (fMRI

    Directory of Open Access Journals (Sweden)

    Laia Farràs-Permanyer

    2015-04-01

    Full Text Available Smoothing is a filtering technique that is essential for brain signal analysis and consists in calculating and comparing the average activation of a voxel to that of its neighbours. Several authors have proposed alternatives or modifications to this process; nonetheless, articles that compare the effect of different sizes of smoothing remain scarce. Thus, the aim of this study was to investigate the effect of applying different smoothing sizes and to highlight the importance of choosing the correct smoothing size. Five smoothing criteria were applied to brain images obtained during an easy motor task performed by five adult participants. Significant differences were found between different smoothing sizes, mainly between the non-smoothing application and the smallest smoothing size versus the two largest smoothing sizes. The signals from the most activated brain areas did not disappear with increased smoothing, whereas signals from less active or smaller areas disappeared. Despite the study sample size, the results suggest that smoothing is relevant in functional magnetic resonance image processing and that the optimum smoothing size is 2.5 and 3.

  20. Evaluating the impact of spatio-temporal smoothness constraints on the BOLD hemodynamic response function estimation: an analysis based on Tikhonov regularization

    International Nuclear Information System (INIS)

    Casanova, R; Yang, L; Hairston, W D; Laurienti, P J; Maldjian, J A

    2009-01-01

    Recently we have proposed the use of Tikhonov regularization with temporal smoothness constraints to estimate the BOLD fMRI hemodynamic response function (HRF). The temporal smoothness constraint was imposed on the estimates by using second derivative information while the regularization parameter was selected based on the generalized cross-validation function (GCV). Using one-dimensional simulations, we previously found this method to produce reliable estimates of the HRF time course, especially its time to peak (TTP), being at the same time fast and robust to over-sampling in the HRF estimation. Here, we extend the method to include simultaneous temporal and spatial smoothness constraints. This method does not need Gaussian smoothing as a pre-processing step as usually done in fMRI data analysis. We carried out two-dimensional simulations to compare the two methods: Tikhonov regularization with temporal (Tik-GCV-T) and spatio-temporal (Tik-GCV-ST) smoothness constraints on the estimated HRF. We focus our attention on quantifying the influence of the Gaussian data smoothing and the presence of edges on the performance of these techniques. Our results suggest that the spatial smoothing introduced by regularization is less severe than that produced by Gaussian smoothing. This allows more accurate estimates of the response amplitudes while producing similar estimates of the TTP. We illustrate these ideas using real data. (note)

  1. Searching for Conservation Laws in Brain Dynamics—BOLD Flux and Source Imaging

    Directory of Open Access Journals (Sweden)

    Henning U. Voss

    2014-07-01

    Full Text Available Blood-oxygen-level-dependent (BOLD imaging is the most important noninvasive tool to map human brain function. It relies on local blood-flow changes controlled by neurovascular coupling effects, usually in response to some cognitive or perceptual task. In this contribution we ask if the spatiotemporal dynamics of the BOLD signal can be modeled by a conservation law. In analogy to the description of physical laws, which often can be derived from some underlying conservation law, identification of conservation laws in the brain could lead to new models for the functional organization of the brain. Our model is independent of the nature of the conservation law, but we discuss possible hints and motivations for conservation laws. For example, globally limited blood supply and local competition between brain regions for blood might restrict the large scale BOLD signal in certain ways that could be observable. One proposed selective pressure for the evolution of such conservation laws is the closed volume of the skull limiting the expansion of brain tissue by increases in blood volume. These ideas are demonstrated on a mental motor imagery fMRI experiment, in which functional brain activation was mapped in a group of volunteers imagining themselves swimming. In order to search for local conservation laws during this complex cognitive process, we derived maps of quantities resulting from spatial interaction of the BOLD amplitudes. Specifically, we mapped fluxes and sources of the BOLD signal, terms that would appear in a description by a continuity equation. Whereas we cannot present final answers with the particular analysis of this particular experiment, some results seem to be non-trivial. For example, we found that during task the group BOLD flux covered more widespread regions than identified by conventional BOLD mapping and was always increasing during task. It is our hope that these results motivate more work towards the search for conservation

  2. Subcortical BOLD responses during visual sexual stimulation vary as a function of implicit porn associations in women.

    Science.gov (United States)

    Borg, Charmaine; de Jong, Peter J; Georgiadis, Janniko R

    2014-02-01

    Lifetime experiences shape people's attitudes toward sexual stimuli. Visual sexual stimulation (VSS), for instance, may be perceived as pleasurable by some, but as disgusting or ambiguous by others. VSS depicting explicit penile-vaginal penetration (PEN) is relevant in this respect, because the act of penetration is a core sexual activity. In this study, 20 women without sexual complaints participated. We used functional magnetic resonance imaging and a single-target implicit association task to investigate how brain responses to PEN were modulated by the initial associations in memory (PEN-'hot' vs PEN-disgust) with such hardcore pornographic stimuli. Many brain areas responded to PEN in the same way they responded to disgust stimuli, and PEN-induced brain activity was prone to modulation by subjective disgust ratings toward PEN stimuli. The relative implicit PEN-disgust (relative to PEN-'hot') associations exclusively modulated PEN-induced brain responses: comparatively negative (PEN-disgust) implicit associations with pornography predicted the strongest PEN-related responses in the basal forebrain (including nucleus accumbens and bed nucleus of stria terminalis), midbrain and amygdala. Since these areas are often implicated in visual sexual processing, the present findings should be taken as a warning: apparently their involvement may also indicate a negative or ambivalent attitude toward sexual stimuli.

  3. Echo-time and field strength dependence of BOLD reactivity in veins and parenchyma using flow-normalized hypercapnic manipulation.

    Directory of Open Access Journals (Sweden)

    Christina Triantafyllou

    Full Text Available While the BOLD (Blood Oxygenation Level Dependent contrast mechanism has demonstrated excellent sensitivity to neuronal activation, its specificity with regards to differentiating vascular and parenchymal responses has been an area of ongoing concern. By inducing a global increase in Cerebral Blood Flow (CBF, we examined the effect of magnetic field strength and echo-time (TE on the gradient-echo BOLD response in areas of cortical gray matter and in resolvable veins. In order to define a quantitative index of BOLD reactivity, we measured the percent BOLD response per unit fractional change in global gray matter CBF induced by inhaling carbon dioxide (CO(2. By normalizing the BOLD response to the underlying CBF change and determining the BOLD response as a function of TE, we calculated the change in R(2(* (ΔR(2(* per unit fractional flow change; the Flow Relaxation Coefficient, (FRC for 3T and 1.5T in parenchymal and large vein compartments. The FRC in parenchymal voxels was 1.76±0.54 fold higher at 3T than at 1.5T and was 2.96±0.66 and 3.12±0.76 fold higher for veins than parenchyma at 1.5T and 3T respectively, showing a quantitative measure of the increase in specificity to parenchymal sources at 3T compared to 1.5T. Additionally, the results allow optimization of the TE to prioritize either maximum parenchymal BOLD response or maximum parenchymal specificity. Parenchymal signals peaked at TE values of 62.0±11.5 ms and 41.5±7.5 ms for 1.5T and 3T, respectively, while the response in the major veins peaked at shorter TE values; 41.0±6.9 ms and 21.5±1.0 ms for 1.5T and 3T. These experiments showed that at 3T, the BOLD CNR in parenchymal voxels exceeded that of 1.5T by a factor of 1.9±0.4 at the optimal TE for each field.

  4. Quantitative aspects of brain perfusion dynamic induced by BOLD fMRI Aspectos quantitativos da dinâmica perfusional do cérebro induzida pelo BOLD fMRI

    Directory of Open Access Journals (Sweden)

    Katia C. Andrade

    2006-12-01

    Full Text Available The increase of relative cerebral blood flow (rCBF may contribute for a change in blood oxygenation level dependent signal (BOLD. The main purpose of this study is to investigate some aspects of perfusional alterations in the human brain in response to a uniform stimulation: hypercapnia induced by breath holding. It was observed that the BOLD signal increased globally during hypercapnia and that it is correlated with the time of breath holding. This signal increase shows a clear distinction between gray and white matter, being greater in the grey matter.O aumento relativo do fluxo cerebral sangüíneo (relative Cerebral Blood Flow - rCBF pode contribuir para uma mudança no sinal dependente da oxigenação do sangue (Blood Oxygenation Level Dependent - BOLD. O objetivo principal deste trabalho foi estudar alguns aspectos da alteração perfusional no cérebro humano em resposta a um estímulo uniforme: hipercapnia, causada por um estado de apnéia induzida. Foi observado um aumento global no sinal BOLD durante a hipercapnia. Este aumento é correlacionado com a duração da apnéia e mostra uma clara distinção entre a substância branca e cinzenta, sendo maior na substância cinzenta.

  5. Simultaneous estimation of population receptive field and hemodynamic parameters from single point BOLD responses using Metropolis-Hastings sampling.

    Science.gov (United States)

    Adaszewski, Stanisław; Slater, David; Melie-Garcia, Lester; Draganski, Bogdan; Bogorodzki, Piotr

    2018-01-30

    We introduce a new approach to Bayesian pRF model estimation using Markov Chain Monte Carlo (MCMC) sampling for simultaneous estimation of pRF and hemodynamic parameters. To obtain high performance on commonly accessible hardware we present a novel heuristic consisting of interpolation between precomputed responses for predetermined stimuli and a large cross-section of receptive field parameters. We investigate the validity of the proposed approach with respect to MCMC convergence, tuning and biases. We compare different combinations of pRF - Compressive Spatial Summation (CSS), Dumoulin-Wandell (DW) and hemodynamic (5-parameter and 3-parameter Balloon-Windkessel) models within our framework with and without the usage of the new heuristic. We evaluate estimation consistency and log probability across models. We perform as well a comparison of one model with and without lookup table within the RStan framework using its No-U-Turn Sampler. We present accelerated computation of whole-ROI parameters for one subject. Finally, we discuss risks and limitations associated with the usage of the new heuristic as well as the means of resolving them. We found that the new algorithm is a valid sampling approach to joint pRF/hemodynamic parameter estimation and that it exhibits very high performance. Copyright © 2018. Published by Elsevier Inc.

  6. Serotonin 2A Receptor Signaling Underlies LSD-induced Alteration of the Neural Response to Dynamic Changes in Music.

    Science.gov (United States)

    Barrett, Frederick S; Preller, Katrin H; Herdener, Marcus; Janata, Petr; Vollenweider, Franz X

    2017-09-28

    Classic psychedelic drugs (serotonin 2A, or 5HT2A, receptor agonists) have notable effects on music listening. In the current report, blood oxygen level-dependent (BOLD) signal was collected during music listening in 25 healthy adults after administration of placebo, lysergic acid diethylamide (LSD), and LSD pretreated with the 5HT2A antagonist ketanserin, to investigate the role of 5HT2A receptor signaling in the neural response to the time-varying tonal structure of music. Tonality-tracking analysis of BOLD data revealed that 5HT2A receptor signaling alters the neural response to music in brain regions supporting basic and higher-level musical and auditory processing, and areas involved in memory, emotion, and self-referential processing. This suggests a critical role of 5HT2A receptor signaling in supporting the neural tracking of dynamic tonal structure in music, as well as in supporting the associated increases in emotionality, connectedness, and meaningfulness in response to music that are commonly observed after the administration of LSD and other psychedelics. Together, these findings inform the neuropsychopharmacology of music perception and cognition, meaningful music listening experiences, and altered perception of music during psychedelic experiences. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  7. Distinct BOLD activation profiles following central and peripheral oxytocin administration in awake rats

    Directory of Open Access Journals (Sweden)

    Craig F Ferris

    2015-09-01

    Full Text Available A growing body of literature has suggested that intranasal oxytocin (OT or other systemic routes of administration can alter prosocial behavior, presumably by directly activating OT sensitive neural circuits in the brain. Yet there is no clear evidence that OT given peripherally can cross the blood-brain-barrier at levels sufficient to engage the OT receptor. To address this issue we examined changes in blood oxygen level dependent (BOLD signal intensity in response to peripheral OT injections (0.1, 0.5 or 2.5 mg/kg during functional magnetic resonance (fMRI in awake rats imaged at 7.0 tesla. These data were compared to OT (1ug/5 µl given directly to the brain via the lateral cerebroventricle. Using a 3D annotated MRI atlas of the rat brain segmented into 171 brain areas and computational analysis we reconstructed the distributed integrated neural circuits identified with BOLD fMRI following central and peripheral OT. Both routes of administration caused significant changes in BOLD signal within the first 10 min of administration. As expected, central OT activated a majority of brain areas known to express a high density of OT receptors e.g., lateral septum, subiculum, shell of the accumbens, bed nucleus of the stria terminalis. This profile of activation was not matched by peripheral OT. The change in BOLD signal to peripheral OT did not show any discernible dose-response. Interestingly, peripheral OT affected all subdivisions of the olfactory bulb, in addition to the cerebellum and several brainstem areas relevant to the autonomic nervous system, including the solitary tract nucleus. The results from this imaging study do not support a direct central action of peripheral OT on the brain. Instead, the patterns of brain activity suggest that peripheral OT may interact at the level of the olfactory bulb and through sensory afferents from the autonomic nervous system to influence brain activity.

  8. Abiotic stress signaling and responses in plants

    Science.gov (United States)

    Zhu, Jian-Kang

    2016-01-01

    Summary As sessile organisms, plants must cope with abiotic stress such as soil salinity, drought, and extreme temperatures. Core stress signaling pathways involve protein kinases related to the yeast SNF1 and mammalian AMPK, suggesting that stress signaling in plants evolved from energy sensing. Stress signaling regulates proteins critical for ion and water transport and for metabolic and gene-expression reprogramming to bring about ionic and water homeostasis and cellular stability under stress conditions. Understanding stress signaling and responses will increase our ability to improve stress resistance in crops to achieve agricultural sustainability and food security for a growing world population. PMID:27716505

  9. Identifying and characterizing systematic temporally-lagged BOLD artifacts.

    Science.gov (United States)

    Byrge, Lisa; Kennedy, Daniel P

    2018-05-01

    Residual noise in the BOLD signal remains problematic for fMRI - particularly for techniques such as functional connectivity, where findings can be spuriously influenced by noise sources that can covary with individual differences. Many such potential noise sources - for instance, motion and respiration - can have a temporally lagged effect on the BOLD signal. Thus, here we present a tool for assessing residual lagged structure in the BOLD signal that is associated with nuisance signals, using a construction similar to a peri-event time histogram. Using this method, we find that framewise displacements - both large and very small - were followed by structured, prolonged, and global changes in the BOLD signal that depend on the magnitude of the preceding displacement and extend for tens of seconds. This residual lagged BOLD structure was consistent across datasets, and independently predicted considerable variance in the global cortical signal (as much as 30-40% in some subjects). Mean functional connectivity estimates varied similarly as a function of displacements occurring many seconds in the past, even after strict censoring. Similar patterns of residual lagged BOLD structure were apparent following respiratory fluctuations (which covaried with framewise displacements), implicating respiration as one likely mechanism underlying the displacement-linked structure observed. Global signal regression largely attenuates this artifactual structure. These findings suggest the need for caution in interpreting results of individual difference studies where noise sources might covary with the individual differences of interest, and highlight the need for further development of preprocessing techniques for mitigating such structure in a more nuanced and targeted manner. Copyright © 2018 Elsevier Inc. All rights reserved.

  10. A NO way to BOLD?

    DEFF Research Database (Denmark)

    Aamand, Rasmus; Dalsgaard, Thomas; Ho, Yi-Ching Lynn

    2013-01-01

    Neurovascular coupling links neuronal activity to vasodilation. Nitric oxide (NO) is a potent vasodilator, and in neurovascular coupling NO production from NO synthases plays an important role. However, another pathway for NO production also exists, namely the nitrate-nitrite-NO pathway. On this ......Neurovascular coupling links neuronal activity to vasodilation. Nitric oxide (NO) is a potent vasodilator, and in neurovascular coupling NO production from NO synthases plays an important role. However, another pathway for NO production also exists, namely the nitrate-nitrite-NO pathway...... to stimuli. A faster and smaller BOLD response, with less variation across local cortex, is consistent with an enhanced hemodynamic coupling during elevated nitrate intake. These findings suggest that dietary patterns, via the nitrate-nitrite-NO pathway, may be a potential way to affect key properties....... On this basis, we hypothesized that dietary nitrate (NO3-) could influence the brain's hemodynamic response to neuronal stimulation. In the present study, 20 healthy male participants were given either sodium nitrate (NaNO3) or sodium chloride (NaCl) (saline placebo) in a crossover study and were shown visual...

  11. Approaches to brain stress testing: BOLD magnetic resonance imaging with computer-controlled delivery of carbon dioxide.

    Directory of Open Access Journals (Sweden)

    W Alan C Mutch

    Full Text Available BACKGROUND: An impaired vascular response in the brain regionally may indicate reduced vascular reserve and vulnerability to ischemic injury. Changing the carbon dioxide (CO(2 tension in arterial blood is commonly used as a cerebral vasoactive stimulus to assess the cerebral vascular response, changing cerebral blood flow (CBF by up to 5-11 percent/mmHg in normal adults. Here we describe two approaches to generating the CO(2 challenge using a computer-controlled gas blender to administer: i a square wave change in CO(2 and, ii a ramp stimulus, consisting of a continuously graded change in CO(2 over a range. Responses were assessed regionally by blood oxygen level dependent (BOLD magnetic resonance imaging (MRI. METHODOLOGY/PRINCIPAL FINDINGS: We studied 8 patients with known cerebrovascular disease (carotid stenosis or occlusion and 2 healthy subjects. The square wave stimulus was used to study the dynamics of the vascular response, while the ramp stimulus assessed the steady-state response to CO(2. Cerebrovascular reactivity (CVR maps were registered by color coding and overlaid on the anatomical scans generated with 3 Tesla MRI to assess the corresponding BOLD signal change/mmHg change in CO(2, voxel-by-voxel. Using a fractal temporal approach, detrended fluctuation analysis (DFA maps of the processed raw BOLD signal per voxel over the same CO(2 range were generated. Regions of BOLD signal decrease with increased CO(2 (coded blue were seen in all of these high-risk patients, indicating regions of impaired CVR. All patients also demonstrated regions of altered signal structure on DFA maps (Hurst exponents less than 0.5; coded blue indicative of anti-persistent noise. While 'blue' CVR maps remained essentially stable over the time of analysis, 'blue' DFA maps improved. CONCLUSIONS/SIGNIFICANCE: This combined dual stimulus and dual analysis approach may be complementary in identifying vulnerable brain regions and thus constitute a regional as

  12. CNS BOLD fMRI effects of sham-controlled transcutaneous electrical nerve stimulation in the left outer auditory canal - a pilot study.

    Science.gov (United States)

    Kraus, Thomas; Kiess, Olga; Hösl, Katharina; Terekhin, Pavel; Kornhuber, Johannes; Forster, Clemens

    2013-09-01

    It has recently been shown that electrical stimulation of sensory afferents within the outer auditory canal may facilitate a transcutaneous form of central nervous system stimulation. Functional magnetic resonance imaging (fMRI) blood oxygenation level dependent (BOLD) effects in limbic and temporal structures have been detected in two independent studies. In the present study, we investigated BOLD fMRI effects in response to transcutaneous electrical stimulation of two different zones in the left outer auditory canal. It is hypothesized that different central nervous system (CNS) activation patterns might help to localize and specifically stimulate auricular cutaneous vagal afferents. 16 healthy subjects aged between 20 and 37 years were divided into two groups. 8 subjects were stimulated in the anterior wall, the other 8 persons received transcutaneous vagus nervous stimulation (tVNS) at the posterior side of their left outer auditory canal. For sham control, both groups were also stimulated in an alternating manner on their corresponding ear lobe, which is generally known to be free of cutaneous vagal innervation. Functional MR data from the cortex and brain stem level were collected and a group analysis was performed. In most cortical areas, BOLD changes were in the opposite direction when comparing anterior vs. posterior stimulation of the left auditory canal. The only exception was in the insular cortex, where both stimulation types evoked positive BOLD changes. Prominent decreases of the BOLD signals were detected in the parahippocampal gyrus, posterior cingulate cortex and right thalamus (pulvinar) following anterior stimulation. In subcortical areas at brain stem level, a stronger BOLD decrease as compared with sham stimulation was found in the locus coeruleus and the solitary tract only during stimulation of the anterior part of the auditory canal. The results of the study are in line with previous fMRI studies showing robust BOLD signal decreases in

  13. Measuring vascular reactivity with resting-state blood oxygenation level-dependent (BOLD) signal fluctuations: A potential alternative to the breath-holding challenge?

    Science.gov (United States)

    Jahanian, Hesamoddin; Christen, Thomas; Moseley, Michael E; Pajewski, Nicholas M; Wright, Clinton B; Tamura, Manjula K; Zaharchuk, Greg

    2017-07-01

    Measurement of the ability of blood vessels to dilate and constrict, known as vascular reactivity, is often performed with breath-holding tasks that transiently raise arterial blood carbon dioxide (P a CO 2 ) levels. However, following the proper commands for a breath-holding experiment may be difficult or impossible for many patients. In this study, we evaluated two approaches for obtaining vascular reactivity information using blood oxygenation level-dependent signal fluctuations obtained from resting-state functional magnetic resonance imaging data: physiological fluctuation regression and coefficient of variation of the resting-state functional magnetic resonance imaging signal. We studied a cohort of 28 older adults (69 ± 7 years) and found that six of them (21%) could not perform the breath-holding protocol, based on an objective comparison with an idealized respiratory waveform. In the subjects that could comply, we found a strong linear correlation between data extracted from spontaneous resting-state functional magnetic resonance imaging signal fluctuations and the blood oxygenation level-dependent percentage signal change during breath-holding challenge ( R 2  = 0.57 and 0.61 for resting-state physiological fluctuation regression and resting-state coefficient of variation methods, respectively). This technique may eliminate the need for subject cooperation, thus allowing the evaluation of vascular reactivity in a wider range of clinical and research conditions in which it may otherwise be impractical.

  14. BOLD temporal dynamics of rat superior colliculus and lateral geniculate nucleus following short duration visual stimulation.

    Directory of Open Access Journals (Sweden)

    Condon Lau

    Full Text Available BACKGROUND: The superior colliculus (SC and lateral geniculate nucleus (LGN are important subcortical structures for vision. Much of our understanding of vision was obtained using invasive and small field of view (FOV techniques. In this study, we use non-invasive, large FOV blood oxygenation level-dependent (BOLD fMRI to measure the SC and LGN's response temporal dynamics following short duration (1 s visual stimulation. METHODOLOGY/PRINCIPAL FINDINGS: Experiments are performed at 7 tesla on Sprague Dawley rats stimulated in one eye with flashing light. Gradient-echo and spin-echo sequences are used to provide complementary information. An anatomical image is acquired from one rat after injection of monocrystalline iron oxide nanoparticles (MION, a blood vessel contrast agent. BOLD responses are concentrated in the contralateral SC and LGN. The SC BOLD signal measured with gradient-echo rises to 50% of maximum amplitude (PEAK 0.2±0.2 s before the LGN signal (p<0.05. The LGN signal returns to 50% of PEAK 1.4±1.2 s before the SC signal (p<0.05. These results indicate the SC signal rises faster than the LGN signal but settles slower. Spin-echo results support these findings. The post-MION image shows the SC and LGN lie beneath large blood vessels. This subcortical vasculature is similar to that in the cortex, which also lies beneath large vessels. The LGN lies closer to the large vessels than much of the SC. CONCLUSIONS/SIGNIFICANCE: The differences in response timing between SC and LGN are very similar to those between deep and shallow cortical layers following electrical stimulation, which are related to depth-dependent blood vessel dilation rates. This combined with the similarities in vasculature between subcortex and cortex suggest the SC and LGN timing differences are also related to depth-dependent dilation rates. This study shows for the first time that BOLD responses in the rat SC and LGN following short duration visual stimulation are

  15. BOLD MRI in sheep fetuses: a non-invasive method for measuring changes in tissue oxygenation.

    Science.gov (United States)

    Sørensen, A; Pedersen, M; Tietze, A; Ottosen, L; Duus, L; Uldbjerg, N

    2009-12-01

    The purpose of this descriptive study was to correlate changes in the blood oxygen level-dependent (BOLD) magnetic resonance imaging (MRI) signal with direct measurements of fetal tissue oxygenation. Seven anesthetized ewes carrying singleton fetuses at 125 days' gestation (term 145 days) underwent BOLD MRI, covering the entire fetus in a multislice approach. The fetuses were subjected to normoxic, hypoxic and hyperoxic conditions by changing the O(2)/N(2)O ratio in the maternal ventilated gas supply. The partial pressure of oxygen (pO2) in the fetal liver was measured using an oxygen-sensitive optode. Maternal arterial blood samples were simultaneously withdrawn for blood gas analysis. These measurements were compared with BOLD MRI signals in the fetal liver, kidney, spleen and brain. We demonstrated a consistent increase in the BOLD MRI signal with increasing tissue pO(2). For the fetal liver, spleen and kidney we observed a clear association between changes in maternal arterial blood pO2 and changes in BOLD MRI signal. Interestingly, we found that the BOLD signal of the fetal brain remained unchanged during hypoxic, normoxic and hyperoxic conditions. This experimental study demonstrated that BOLD MRI is a reliable non-invasive method for measuring changes in tissue oxygenation in fetal sheep. The unchanged signal in the fetal brain during altered maternal oxygen conditions is probably explained by the brain-sparing mechanism. Copyright 2009 ISUOG. Published by John Wiley & Sons, Ltd.

  16. An efficient multi-stage algorithm for full calibration of the hemodynamic model from BOLD signal responses

    KAUST Repository

    Zambri, Brian

    2017-02-22

    We propose a computational strategy that falls into the category of prediction/correction iterative-type approaches, for calibrating the hemodynamic model introduced by Friston et al. (2000). The proposed method is employed to estimate consecutively the values of the biophysiological system parameters and the external stimulus characteristics of the model. Numerical results corresponding to both synthetic and real functional Magnetic Resonance Imaging (fMRI) measurements for a single stimulus as well as for multiple stimuli are reported to highlight the capability of this computational methodology to fully calibrate the considered hemodynamic model. This article is protected by copyright. All rights reserved.

  17. Dataset for: An efficient multi-stage algorithm for full calibration of the hemodynamic model from BOLD signal responses

    KAUST Repository

    Djellouli, Rabia

    2017-01-01

    We propose a computational strategy that falls into the category of prediction/correction iterative-type approaches, for calibrating the hemodynamic model introduced by Friston et al. (2000). The proposed method is employed to estimate consecutively the values of the biophysiological system parameters and the external stimulus characteristics of the model. Numerical results corresponding to both synthetic and real functional Magnetic Resonance Imaging (fMRI) measurements for a single stimulus as well as for multiple stimuli are reported to highlight the capability of this computational methodology to fully calibrate the considered hemodynamic model.

  18. Linear ubiquitination signals in adaptive immune responses.

    Science.gov (United States)

    Ikeda, Fumiyo

    2015-07-01

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

  19. Arm-in-Arm Response Regulator Dimers Promote Intermolecular Signal Transduction

    Energy Technology Data Exchange (ETDEWEB)

    Baker, Anna W.; Satyshur, Kenneth A.; Morales, Neydis Moreno; Forest, Katrina T. (UW)

    2016-02-01

    ABSTRACT

    Bacteriophytochrome photoreceptors (BphPs) and their cognate response regulators make up two-component signal transduction systems which direct bacteria to mount phenotypic responses to changes in environmental light quality. Most of these systems utilize single-domain response regulators to transduce signals through unknown pathways and mechanisms. Here we describe the photocycle and autophosphorylation kinetics of RtBphP1, a red light-regulated histidine kinase from the desert bacteriumRamlibacter tataouinensis. RtBphP1 undergoes red to far-red photoconversion with rapid thermal reversion to the dark state. RtBphP1 is autophosphorylated in the dark; this activity is inhibited under red light. The RtBphP1 cognate response regulator, theR. tataouinensisbacteriophytochrome response regulator (RtBRR), and a homolog, AtBRR fromAgrobacterium tumefaciens, crystallize unexpectedly as arm-in-arm dimers, reliant on a conserved hydrophobic motif, hFWAhL (where h is a hydrophobic M, V, L, or I residue). RtBRR and AtBRR dimerize distinctly from four structurally characterized phytochrome response regulators found in photosynthetic organisms and from all other receiver domain homodimers in the Protein Data Bank. A unique cacodylate-zinc-histidine tag metal organic framework yielded single-wavelength anomalous diffraction phases and may be of general interest. Examination of the effect of the BRR stoichiometry on signal transduction showed that phosphorylated RtBRR is accumulated more efficiently than the engineered monomeric RtBRR (RtBRRmon) in phosphotransfer reactions. Thus, we conclude that arm-in-arm dimers are a relevant signaling intermediate in this class of two-component regulatory systems.

    <bold>IMPORTANCE

  20. Hemodynamic modelling of BOLD fMRI - A machine learning approach

    DEFF Research Database (Denmark)

    Jacobsen, Danjal Jakup

    2007-01-01

    This Ph.D. thesis concerns the application of machine learning methods to hemodynamic models for BOLD fMRI data. Several such models have been proposed by different researchers, and they have in common a basis in physiological knowledge of the hemodynamic processes involved in the generation...... of the BOLD signal. The BOLD signal is modelled as a non-linear function of underlying, hidden (non-measurable) hemodynamic state variables. The focus of this thesis work has been to develop methods for learning the parameters of such models, both in their traditional formulation, and in a state space...... formulation. In the latter, noise enters at the level of the hidden states, as well as in the BOLD measurements themselves. A framework has been developed to allow approximate posterior distributions of model parameters to be learned from real fMRI data. This is accomplished with Markov chain Monte Carlo...

  1. Comparison of regional skeletal muscle tissue oxygenation in college athletes and sedentary control subjects using quantitative BOLD MR imaging.

    Science.gov (United States)

    Stacy, Mitchel R; Caracciolo, Christopher M; Qiu, Maolin; Pal, Prasanta; Varga, Tyler; Constable, Robert Todd; Sinusas, Albert J

    2016-08-01

    Blood oxygen level-dependent (BOLD) magnetic resonance (MR) imaging permits noninvasive assessment of tissue oxygenation. We hypothesized that BOLD imaging would allow for regional evaluation of differences in skeletal muscle oxygenation between athletes and sedentary control subjects, and dynamic BOLD responses to ischemia (i.e., proximal cuff occlusion) and reactive hyperemia (i.e., rapid cuff deflation) would relate to lower extremity function, as assessed by jumping ability. College football athletes (linemen, defensive backs/wide receivers) were compared to sedentary healthy controls. BOLD signal of the gastrocnemius, soleus, anterior tibialis, and peroneus longus was assessed for peak hyperemic value (PHV), time to peak (TTP), minimum ischemic value (MIV), and time to recovery (TTR). Significantly higher PHVs were identified in athletes versus controls for the gastrocnemius (linemen, 15.8 ± 9.1%; defensive backs/wide receivers, 17.9 ± 5.1%; controls, 7.4 ± 3.5%), soleus (linemen, 25.9 ± 11.5%; backs/receivers, 22.0 ± 9.4%; controls, 12.9 ± 5.8%), and anterior tibialis (linemen, 12.8 ± 5.3%; backs/receivers, 12.6 ± 3.9%; controls, 7.7 ± 4.0%), whereas no differences in PHV were found for the peroneus longus (linemen, 14.1 ± 6.9%; backs/receivers, 11.7 ± 4.6%; controls, 9.0 ± 4.9%). In all subject groups, the gastrocnemius and soleus muscles exhibited the lowest MIVs during cuff occlusion. No differences in TTR were found between muscles for any subject group. PHV of the gastrocnemius muscle was significantly and positively related to maximal vertical (r = 0.56, P = 0.002) and broad jump (r = 0.47, P = 0.01). These results suggest that BOLD MR imaging is a useful noninvasive tool for evaluating differences in tissue oxygenation of specific muscles between active and sedentary individuals, and peak BOLD responses may relate to functional capacity. © 2016 The Authors. Physiological Reports published by Wiley

  2. BOLD delay times using group delay in sickle cell disease

    Science.gov (United States)

    Coloigner, Julie; Vu, Chau; Bush, Adam; Borzage, Matt; Rajagopalan, Vidya; Lepore, Natasha; Wood, John

    2016-03-01

    Sickle cell disease (SCD) is an inherited blood disorder that effects red blood cells, which can lead to vasoocclusion, ischemia and infarct. This disease often results in neurological damage and strokes, leading to morbidity and mortality. Functional Magnetic Resonance Imaging (fMRI) is a non-invasive technique for measuring and mapping the brain activity. Blood Oxygenation Level-Dependent (BOLD) signals contain also information about the neurovascular coupling, vascular reactivity, oxygenation and blood propagation. Temporal relationship between BOLD fluctuations in different parts of the brain provides also a mean to investigate the blood delay information. We used the induced desaturation as a label to profile transit times through different brain areas, reflecting oxygen utilization of tissue. In this study, we aimed to compare blood flow propagation delay times between these patients and healthy subjects in areas vascularized by anterior, middle and posterior cerebral arteries. In a group comparison analysis with control subjects, BOLD changes in these areas were found to be almost simultaneous and shorter in the SCD patients, because of their increased brain blood flow. Secondly, the analysis of a patient with a stenosis on the anterior cerebral artery indicated that signal of the area vascularized by this artery lagged the MCA signal. These findings suggest that sickle cell disease causes blood propagation modifications, and that these changes could be used as a biomarker of vascular damage.

  3. "Extreme Bold" in the Faculty Ranks

    Science.gov (United States)

    Kuusisto, Stephen

    2013-01-01

    Boldness, defense, and the necessity of talking back remain as central to life with disability in one's time as in Francis Bacon's age. "Therefore all deformed persons are extreme bold," Bacon wrote, "first, as in their own defence, as being exposed to scorn, but in process of time, by a general habit." Perhaps no word carries…

  4. Background MR gradient noise and non-auditory BOLD activations: a data-driven perspective.

    Science.gov (United States)

    Haller, Sven; Homola, György A; Scheffler, Klaus; Beckmann, Christian F; Bartsch, Andreas J

    2009-07-28

    The effect of echoplanar imaging (EPI) acoustic background noise on blood oxygenation level dependent (BOLD) activations was investigated. Two EPI pulse sequences were compared: (i) conventional EPI with a pulsating sound component of typically 8-10 Hz, which is a potent physiological stimulus, and (ii) the more recently developed continuous-sound EPI, which is perceived as less distractive despite equivalent peak sound pressure levels. Sixteen healthy subjects performed an established demanding visual n-back working memory task. Using an exploratory data analysis technique (tensorial probabilistic independent component analysis; tensor-PICA), we studied the inter-session/within-subject response variability introduced by continuous-sound versus conventional EPI acoustic background noise in addition to temporal and spatial signal characteristics. The analysis revealed a task-related component associated with the established higher-level working memory and motor feedback response network, which exhibited a significant 19% increase in its average effect size for the continuous-sound as opposed to conventional EPI. Stimulus-related lower-level activations, such as primary visual areas, were not modified. EPI acoustic background noise influences much more than the auditory system per se. This analysis provides additional evidence for an enhancement of task-related, extra-auditory BOLD activations by continuous-sound EPI due to less distractive acoustic background gradient noise.

  5. Evidence that neurovascular coupling underlying the BOLD effect increases with age during childhood.

    Science.gov (United States)

    Schmithorst, Vincent J; Vannest, Jennifer; Lee, Gregory; Hernandez-Garcia, Luis; Plante, Elena; Rajagopal, Akila; Holland, Scott K

    2015-01-01

    Functional MRI using blood-oxygen-level-dependent (BOLD) imaging has provided unprecedented insights into the maturation of the human brain. Task-based fMRI studies have shown BOLD signal increases with age during development (ages 5-18) for many cognitive domains such as language and executive function, while functional connectivity (resting-state) fMRI studies investigating regionally synchronous BOLD fluctuations have revealed a developing functional organization of the brain from a local into a more distributed architecture. However, interpretation of these results is confounded by the fact that the BOLD signal is directly related to blood oxygenation driven by changes in blood flow and only indirectly related to neuronal activity, and may thus be affected by changing neuronal-vascular coupling. BOLD signal and cerebral blood flow (CBF) were measured simultaneously in a cohort of 113 typically developing awake participants ages 3-18 performing a narrative comprehension task. Using a novel voxelwise wild bootstrap analysis technique, an increased ratio of BOLD signal to relative CBF signal change with age (indicative of increased neuronal-vascular coupling) was seen in the middle temporal gyri and the left inferior frontal gyrus. Additionally, evidence of decreased relative oxygen metabolism (indicative of decreased neuronal activity) with age was found in the same regions. These findings raise concern that results of developmental BOLD studies cannot be unambiguously attributed to neuronal activity. Astrocytes and astrocytic processes may significantly affect the maturing functional architecture of the brain, consistent with recent research demonstrating a key role for astrocytes in mediating increased CBF following neuronal activity and for astrocyte processes in modulating synaptic connectivity. © 2014 Wiley Periodicals, Inc.

  6. Modeling the BOLD correlates of competitive neural dynamics.

    Science.gov (United States)

    Bonaiuto, James; Arbib, Michael A

    2014-01-01

    Winner-take-all models are commonly used to model decision-making tasks where one outcome must be selected from several competing options. Related random walk and diffusion models have been used to explain such processes and apply them to psychometric and neurophysiological data. Recent model-based fMRI studies have sought to find the neural correlates of decision-making processes. However, due to the fact that hemodynamic responses likely reflect synaptic rather than spiking activity, the expected BOLD signature of winner-take-all circuits is not clear. A powerful way to integrate data from neurophysiology and brain imaging is by developing biologically plausible neural network models constrained and testable by neural and behavioral data, and then using Synthetic Brain Imaging - transforming the output of simulations with the model to make predictions testable against neuroimaging data. We developed a biologically realistic spiking winner-take-all model comprised of coupled excitatory and inhibitory neural populations. We varied the difficulty of a decision-making task by adjusting the contrast, or relative strength of inputs representing two response options. Synthetic brain imaging was used to estimate the BOLD response of the model and analyze its peak as a function of input contrast. We performed a parameter space analysis to determine values for which the model performs the task accurately, and given accurate performance, the distribution of the input contrast-BOLD response relationship. This underscores the need for models grounded in neurophysiological data for brain imaging analyses which attempt to localize the neural correlates of cognitive processes based on predicted BOLD responses. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. Task-Related Modulations of BOLD Low-Frequency Fluctuations within the Default Mode Network

    Directory of Open Access Journals (Sweden)

    Silvia Tommasin

    2017-07-01

    Full Text Available Spontaneous low-frequency Blood-Oxygenation Level-Dependent (BOLD signals acquired during resting state are characterized by spatial patterns of synchronous fluctuations, ultimately leading to the identification of robust brain networks. The resting-state brain networks, including the Default Mode Network (DMN, are demonstrated to persist during sustained task execution, but the exact features of task-related changes of network properties are still not well characterized. In this work we sought to examine in a group of 20 healthy volunteers (age 33 ± 6 years, 8 F/12 M the relationship between changes of spectral and spatiotemporal features of one prominent resting-state network, namely the DMN, during the continuous execution of a working memory n-back task. We found that task execution impacted on both functional connectivity and amplitude of BOLD fluctuations within large parts of the DMN, but these changes correlated between each other only in a small area of the posterior cingulate. We conclude that combined analysis of multiple parameters related to connectivity, and their changes during the transition from resting state to continuous task execution, can contribute to a better understanding of how brain networks rearrange themselves in response to a task.

  8. Task-Related Modulations of BOLD Low-Frequency Fluctuations within the Default Mode Network

    Science.gov (United States)

    Tommasin, Silvia; Mascali, Daniele; Gili, Tommaso; Assan, Ibrahim Eid; Moraschi, Marta; Fratini, Michela; Wise, Richard G.; Macaluso, Emiliano; Mangia, Silvia; Giove, Federico

    2017-01-01

    Spontaneous low-frequency Blood-Oxygenation Level-Dependent (BOLD) signals acquired during resting state are characterized by spatial patterns of synchronous fluctuations, ultimately leading to the identification of robust brain networks. The resting-state brain networks, including the Default Mode Network (DMN), are demonstrated to persist during sustained task execution, but the exact features of task-related changes of network properties are still not well characterized. In this work we sought to examine in a group of 20 healthy volunteers (age 33 ± 6 years, 8 F/12 M) the relationship between changes of spectral and spatiotemporal features of one prominent resting-state network, namely the DMN, during the continuous execution of a working memory n-back task. We found that task execution impacted on both functional connectivity and amplitude of BOLD fluctuations within large parts of the DMN, but these changes correlated between each other only in a small area of the posterior cingulate. We conclude that combined analysis of multiple parameters related to connectivity, and their changes during the transition from resting state to continuous task execution, can contribute to a better understanding of how brain networks rearrange themselves in response to a task. PMID:28845420

  9. Exploring BOLD changes during spatial attention in non-stimulated visual cortex.

    Directory of Open Access Journals (Sweden)

    Linda Heinemann

    Full Text Available Blood oxygen level-dependent (BOLD responses were measured in parts of primary visual cortex that represented unstimulated visual field regions at different distances from a stimulated central target location. The composition of the visual scene varied by the presence or absence of additional peripheral distracter stimuli. Bottom-up effects were assessed by comparing peripheral activity during central stimulation vs. no stimulation. Top-down effects were assessed by comparing active vs. passive conditions. In passive conditions subjects simply watched the central letter stimuli and in active conditions they had to report occurrence of pre-defined targets in a rapid serial letter stream. Onset of the central letter stream enhanced activity in V1 representations of the stimulated region. Within representations of the periphery activation decreased and finally turned into deactivation with increasing distance from the stimulated location. This pattern was most pronounced in the active conditions and during the presence of peripheral stimuli. Active search for a target did not lead to additional enhancement at areas representing the attentional focus but to a stronger deactivation in the vicinity. Suppressed neuronal activity was also found in the non distracter condition suggesting a top-down attention driven effect. Our observations suggest that BOLD signal decreases in primary visual cortex are modulated by bottom-up sensory-driven factors such as the presence of distracters in the visual field as well as by top-down attentional processes.

  10. Task-related modulations of BOLD low-frequency fluctuations within the default mode network

    Science.gov (United States)

    Tommasin, Silvia; Mascali, Daniele; Gili, Tommaso; Eid Assan, Ibrahim; Moraschi, Marta; Fratini, Michela; Wise, Richard G.; Macaluso, Emiliano; Mangia, Silvia; Giove, Federico

    2017-07-01

    Spontaneous low-frequency Blood-Oxygenation Level-Dependent (BOLD) signals acquired during resting state are characterized by spatial patterns of synchronous fluctuations, ultimately leading to the identification of robust brain networks. The resting-state brain networks, including the Default Mode Network (DMN), are demonstrated to persist during sustained task execution, but the exact features of task-related changes of network properties are still not well characterized. In this work we sought to examine in a group of 20 healthy volunteers (age 33±6 years, 8F/12M) the relationship between changes of spectral and spatiotemporal features of one prominent resting-state network, namely the DMN, during the steady-state execution of a sustained working memory n-back task. We found that the steady state execution of such a task impacted on both functional connectivity and amplitude of BOLD fluctuations within large parts of the DMN, but these changes correlated between each other only in a small area of the posterior cingulate. We conclude that combined analysis of multiple parameters related to connectivity, and their changes during the transition from resting state to steady-state task execution, can contribute to a better understanding of how brain networks rearrange themselves in response of a task.

  11. Acetazolamide-augmented dynamic BOLD (aczBOLD imaging for assessing cerebrovascular reactivity in chronic steno-occlusive disease of the anterior circulation: An initial experience

    Directory of Open Access Journals (Sweden)

    Junjie Wu

    2017-01-01

    Full Text Available The purpose of this study was to measure cerebrovascular reactivity (CVR in chronic steno-occlusive disease using a novel approach that couples BOLD imaging with acetazolamide (ACZ vasoreactivity (aczBOLD, to evaluate dynamic effects of ACZ on BOLD and to establish the relationship between aczBOLD and dynamic susceptibility contrast (DSC perfusion MRI. Eighteen patients with unilateral chronic steno-occlusive disease of the anterior circulation underwent a 20-min aczBOLD imaging protocol, with ACZ infusion starting at 5 min of scan initiation. AczBOLD reactivity was calculated on a voxel-by-voxel basis to generate CVR maps for subsequent quantitative analyses. Reduced CVR was observed in the diseased vs. the normal hemisphere both by qualitative and quantitative assessment (gray matter (GM: 4.13% ± 1.16% vs. 4.90% ± 0.98%, P = 0.002; white matter (WM: 2.83% ± 1.23% vs. 3.50% ± 0.94%, P = 0.005. In all cases BOLD signal began increasing immediately following ACZ infusion, approaching a plateau at ~8.5 min after infusion, with the tissue volume of reduced augmentation increasing progressively with time, peaking at 2.60 min (time range above 95% of the maximum value: 0–4.43 min for the GM and 1.80 min (time range above 95% of the maximum value: 1.40–3.53 min for the WM. In the diseased hemisphere, aczBOLD CVR significantly correlated with baseline DSC time-to-maximum of the residue function (Tmax (P = 0.008 for the WM and normalized cerebral blood flow (P = 0.003 for the GM, and P = 0.001 for the WM. AczBOLD provides a novel, safe, easily implementable approach to CVR measurement in the routine clinical environments. Further studies can establish quantitative thresholds from aczBOLD towards identification of patients at heightened risk of recurrent ischemia and cognitive decline.

  12. Acetazolamide-augmented dynamic BOLD (aczBOLD) imaging for assessing cerebrovascular reactivity in chronic steno-occlusive disease of the anterior circulation: An initial experience.

    Science.gov (United States)

    Wu, Junjie; Dehkharghani, Seena; Nahab, Fadi; Qiu, Deqiang

    2017-01-01

    The purpose of this study was to measure cerebrovascular reactivity (CVR) in chronic steno-occlusive disease using a novel approach that couples BOLD imaging with acetazolamide (ACZ) vasoreactivity (aczBOLD), to evaluate dynamic effects of ACZ on BOLD and to establish the relationship between aczBOLD and dynamic susceptibility contrast (DSC) perfusion MRI. Eighteen patients with unilateral chronic steno-occlusive disease of the anterior circulation underwent a 20-min aczBOLD imaging protocol, with ACZ infusion starting at 5 min of scan initiation. AczBOLD reactivity was calculated on a voxel-by-voxel basis to generate CVR maps for subsequent quantitative analyses. Reduced CVR was observed in the diseased vs. the normal hemisphere both by qualitative and quantitative assessment (gray matter (GM): 4.13% ± 1.16% vs. 4.90% ± 0.98%, P  = 0.002; white matter (WM): 2.83% ± 1.23% vs. 3.50% ± 0.94%, P  = 0.005). In all cases BOLD signal began increasing immediately following ACZ infusion, approaching a plateau at ~ 8.5 min after infusion, with the tissue volume of reduced augmentation increasing progressively with time, peaking at 2.60 min (time range above 95% of the maximum value: 0-4.43 min) for the GM and 1.80 min (time range above 95% of the maximum value: 1.40-3.53 min) for the WM. In the diseased hemisphere, aczBOLD CVR significantly correlated with baseline DSC time-to-maximum of the residue function (T max ) ( P  = 0.008 for the WM) and normalized cerebral blood flow ( P  = 0.003 for the GM, and P  = 0.001 for the WM). AczBOLD provides a novel, safe, easily implementable approach to CVR measurement in the routine clinical environments. Further studies can establish quantitative thresholds from aczBOLD towards identification of patients at heightened risk of recurrent ischemia and cognitive decline.

  13. Representations of Invariant Musical Categories Are Decodable by Pattern Analysis of Locally Distributed BOLD Responses in Superior Temporal and Intraparietal Sulci.

    Science.gov (United States)

    Klein, Mike E; Zatorre, Robert J

    2015-07-01

    In categorical perception (CP), continuous physical signals are mapped to discrete perceptual bins: mental categories not found in the physical world. CP has been demonstrated across multiple sensory modalities and, in audition, for certain over-learned speech and musical sounds. The neural basis of auditory CP, however, remains ambiguous, including its robustness in nonspeech processes and the relative roles of left/right hemispheres; primary/nonprimary cortices; and ventral/dorsal perceptual processing streams. Here, highly trained musicians listened to 2-tone musical intervals, which they perceive categorically while undergoing functional magnetic resonance imaging. Multivariate pattern analyses were performed after grouping sounds by interval quality (determined by frequency ratio between tones) or pitch height (perceived noncategorically, frequency ratios remain constant). Distributed activity patterns in spheres of voxels were used to determine sound sample identities. For intervals, significant decoding accuracy was observed in the right superior temporal and left intraparietal sulci, with smaller peaks observed homologously in contralateral hemispheres. For pitch height, no significant decoding accuracy was observed, consistent with the non-CP of this dimension. These results suggest that similar mechanisms are operative for nonspeech categories as for speech; espouse roles for 2 segregated processing streams; and support hierarchical processing models for CP. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  14. Unsupervised Myocardial Segmentation for Cardiac BOLD.

    Science.gov (United States)

    Oksuz, Ilkay; Mukhopadhyay, Anirban; Dharmakumar, Rohan; Tsaftaris, Sotirios A

    2017-11-01

    A fully automated 2-D+time myocardial segmentation framework is proposed for cardiac magnetic resonance (CMR) blood-oxygen-level-dependent (BOLD) data sets. Ischemia detection with CINE BOLD CMR relies on spatio-temporal patterns in myocardial intensity, but these patterns also trouble supervised segmentation methods, the de facto standard for myocardial segmentation in cine MRI. Segmentation errors severely undermine the accurate extraction of these patterns. In this paper, we build a joint motion and appearance method that relies on dictionary learning to find a suitable subspace. Our method is based on variational pre-processing and spatial regularization using Markov random fields, to further improve performance. The superiority of the proposed segmentation technique is demonstrated on a data set containing cardiac phase-resolved BOLD MR and standard CINE MR image sequences acquired in baseline and ischemic condition across ten canine subjects. Our unsupervised approach outperforms even supervised state-of-the-art segmentation techniques by at least 10% when using Dice to measure accuracy on BOLD data and performs at par for standard CINE MR. Furthermore, a novel segmental analysis method attuned for BOLD time series is utilized to demonstrate the effectiveness of the proposed method in preserving key BOLD patterns.

  15. Abnormal response to photic stimulation in juvenile myoclonic epilepsy: an EEG-fMRI study.

    Science.gov (United States)

    Bartolini, Emanuele; Pesaresi, Ilaria; Fabbri, Serena; Cecchi, Paolo; Giorgi, Filippo Sean; Sartucci, Ferdinando; Bonuccelli, Ubaldo; Cosottini, Mirco

    2014-07-01

    Juvenile myoclonic epilepsy (JME) is a young-onset electroclinical syndrome, characterized by myoclonic, generalized tonic-clonic, and possibly typical absence seizures. Interictal electroencephalography (EEG) displays 3-6 Hz spike/polyspike and wave pattern. Photosensitivity is common. Our aim was to explore the blood oxygen level-dependent (BOLD) response evoked by a highly provocative photic stimulus in a cohort of people with JME compared to a group of nonphotosensitive healthy controls, and to investigate the hemodynamic phenomena seen in patients with photosensitive JME. We studied 13 JME patients and 18 healthy controls using EEG-functional magnetic resonance imaging (fMRI) performed during low luminance intermittent photic stimulation (IPS). The BOLD response to IPS was investigated both in JME and control groups. In photosensitive JME subjects, we also performed a dynamic evaluation of BOLD signal changes evoked by the photoparoxysmal response (PPR) in a time frame ranging from 10 s before the onset of the EEG paroxysm up until 10 s afterward. The IPS evoked a positive BOLD response in striate and extrastriate visual areas, which was less in JME patients than in controls. Moreover, people with JME had a reduced positive BOLD response in the frontoparietal areas and putamen but a stronger negative BOLD response in the primary sensorimotor cortex (SM1) and in cortical regions belonging to the default mode network (DMN). In JME, the dynamic evaluation of BOLD signal changes related to PPR revealed an early positive response in the putamen and SM1, followed by BOLD signal decrements in the putamen, caudate nuclei, thalami, and SM1. Our results confirm the hypothesis that people with JME might have an altered interaction between the motor circuit and other neuronal networks, with prominent involvement of basal ganglia circuitry. The PPR could be a final expression of pathogenic phenomena occurring in the striato-thalamocortical system, possibly a core feature

  16. fMRI BOLD response of high-risk college students (Part 2): during memory priming of alcohol, marijuana and polydrug picture cues.

    Science.gov (United States)

    Ray, Suchismita; Hanson, Catherine; Hanson, Stephen J; Rahman, Rifaquat M; Bates, Marsha E

    2010-01-01

    This study examined brain activity using functional magnetic resonance imaging (fMRI) and reaction time (RT) during an implicit repetition priming memory task involving alcohol, polydrug, marijuana and emotional picture cues. Participants were 5 male and 5 female high-risk college students who had just participated in a cue exposure study (Ray et al., this issue). fMRI and RT data were collected while participants made decisions about previously seen and new picture cues. Both behavioral RT and brain imaging data revealed strong memory priming for drug and alcohol cues. Neurologically, a repetition priming effect (suppression in neural activity for repeated cues) was observed in response to alcohol cues in the left prefrontal, bilateral occipital, and bilateral occipitotemporal regions, as well as right insula and right precuneus (Z ranged from 3.03 to 3.31 P marijuana cues in the occipital area. Prefrontal and insular cortex involvement both in reactivity to alcohol cues (Ray et al., this issue) and subsequent implicit memory processing of these cues, as found in this study, suggests their potential role in the maintenance of high-risk alcohol use behaviors.

  17. fMRI BOLD Response of High-risk College Students (Part 2): During Memory Priming of Alcohol, Marijuana and Polydrug Picture Cues

    Science.gov (United States)

    Ray, Suchismita; Hanson, Catherine; Hanson, Stephen J.; Rahman, Rifaquat M.; Bates, Marsha E.

    2010-01-01

    Aims: This study examined brain activity using functional magnetic resonance imaging (fMRI) and reaction time (RT) during an implicit repetition priming memory task involving alcohol, polydrug, marijuana and emotional picture cues. Methods: Participants were 5 male and 5 female high-risk college students who had just participated in a cue exposure study (Ray et al., this issue). fMRI and RT data were collected while participants made decisions about previously seen and new picture cues. Results: Both behavioral RT and brain imaging data revealed strong memory priming for drug and alcohol cues. Neurologically, a repetition priming effect (suppression in neural activity for repeated cues) was observed in response to alcohol cues in the left prefrontal, bilateral occipital, and bilateral occipitotemporal regions, as well as right insula and right precuneus (Z ranged from 3.03 to 3.31 P < 0.05). Polydrug cues elicited priming in the occipital and temporal areas, and marijuana cues in the occipital area. Conclusions: Prefrontal and insular cortex involvement both in reactivity to alcohol cues (Ray et al., this issue) and subsequent implicit memory processing of these cues, as found in this study, suggests their potential role in the maintenance of high-risk alcohol use behaviors. PMID:20729527

  18. Agrobacterium tumefaciens responses to plant-derived signaling molecules

    Directory of Open Access Journals (Sweden)

    Sujatha eSubramoni

    2014-07-01

    Full Text Available As a special phytopathogen, Agrobacterium tumefaciens infects a wide range of plant hosts and causes plant tumors also known as crown galls. The complexity of Agrobacterium-plant interaction has been studied for several decades. Agrobacterium pathogenicity is largely attributed to its evolved capabilities of precise recognition and response to plant-derived chemical signals. Agrobacterium perceives plant-derived signals to activate its virulence genes, which are responsible for transferring and integrating its T-DNA (Transferred DNA from its Tumour-inducing (Ti plasmid into the plant nucleus. The expression of T-DNA in plant hosts leads to the production of a large amount of indole-3-acetic acid (IAA, cytokinin (CK and opines. IAA and CK stimulate plant growth, resulting in tumor formation. Agrobacterium utilizes opines as nutrient sources as well as signals in order to activate its quorum sensing (QS to further promote virulence and opine metabolism. Intriguingly, Agrobacterium also recognizes plant-derived signals including -amino butyric acid (GABA and salicylic acid (SA to activate quorum quenching that reduces the level of QS signals, thereby avoiding the elicitation of plant defense and preserving energy. In addition, Agrobacterium hijacks plant-derived signals including SA, IAA, and ethylene (ET to down-regulate its virulence genes located on the Ti plasmid. Moreover, certain metabolites from corn (Zea mays also inhibit the expression of Agrobacterium virulence genes. Here we outline the responses of Agrobacterium to major plant-derived signals that impact Agrobacterium-plant interactions.

  19. Agrobacterium tumefaciens responses to plant-derived signaling molecules

    Science.gov (United States)

    Subramoni, Sujatha; Nathoo, Naeem; Klimov, Eugene; Yuan, Ze-Chun

    2014-01-01

    As a special phytopathogen, Agrobacterium tumefaciens infects a wide range of plant hosts and causes plant tumors also known as crown galls. The complexity of Agrobacterium–plant interaction has been studied for several decades. Agrobacterium pathogenicity is largely attributed to its evolved capabilities of precise recognition and response to plant-derived chemical signals. Agrobacterium perceives plant-derived signals to activate its virulence genes, which are responsible for transferring and integrating its Transferred DNA (T-DNA) from its Tumor-inducing (Ti) plasmid into the plant nucleus. The expression of T-DNA in plant hosts leads to the production of a large amount of indole-3-acetic acid (IAA), cytokinin (CK), and opines. IAA and CK stimulate plant growth, resulting in tumor formation. Agrobacterium utilizes opines as nutrient sources as well as signals in order to activate its quorum sensing (QS) to further promote virulence and opine metabolism. Intriguingly, Agrobacterium also recognizes plant-derived signals including γ-amino butyric acid and salicylic acid (SA) to activate quorum quenching that reduces the level of QS signals, thereby avoiding the elicitation of plant defense and preserving energy. In addition, Agrobacterium hijacks plant-derived signals including SA, IAA, and ethylene to down-regulate its virulence genes located on the Ti plasmid. Moreover, certain metabolites from corn (Zea mays) also inhibit the expression of Agrobacterium virulence genes. Here we outline the responses of Agrobacterium to major plant-derived signals that impact Agrobacterium–plant interactions. PMID:25071805

  20. Left-right difference in fetal liver oxygenation during hypoxia estimated by BOLD MRI in a fetal sheep model.

    Science.gov (United States)

    Sørensen, A; Holm, D; Pedersen, M; Tietze, A; Stausbøl-Grøn, B; Duus, L; Uldbjerg, N

    2011-12-01

    The purpose of this study was to measure differences in oxygenation between the left and right sides of the fetal liver during varying oxygenation levels. Eight ewes carrying singleton fetuses at gestational age 125 days (term, 145 days) were included in the study. Under anesthesia the ewes were ventilated with gas containing different levels of oxygen, thereby subjecting the fetuses to hyperoxia (mean ± SD maternal arterial partial pressure of oxygen (pO2), 23.2 ± 8.2 kPa) and hypoxia (mean maternal arterial pO2, 7.1 ± 0.5 kPa). Changes in oxygenation within the fetal liver were assessed by blood oxygen level-dependent (BOLD) magnetic resonance imaging (MRI). During hyperoxia there was no difference between the BOLD signal in the left and right sides of the fetal liver; mean change in BOLDBOLD)(hyperox), -0.9 ± 3.7%. During hypoxia, however, the decrease in the BOLD signal was more pronounced in the right side as compared with the left side, thereby creating a significant increase in the left-right difference in the BOLD signal; mean ΔBOLD(hypox), 5.2 ± 2.2% (P = 0.002, paired t-test). The left-right difference was directly proportional to the degree of hypoxia (R2 = 0.86, P = 0.007). To our knowledge, this is the first study demonstrating differences in oxygenation between the left and right sides of the fetal liver during hypoxia, a difference that can be explained by increased ductus venosus shunting. Thus, the BOLD MRI technique is a promising non-invasive tool that might be useful for the future monitoring of the human fetus. Copyright © 2011 ISUOG. Published by John Wiley & Sons, Ltd.

  1. Chance-constrained optimization of demand response to price signals

    DEFF Research Database (Denmark)

    Dorini, Gianluca Fabio; Pinson, Pierre; Madsen, Henrik

    2013-01-01

    Household-based demand response is expected to play an increasing role in supporting the large scale integration of renewable energy generation in existing power systems and electricity markets. While the direct control of the consumption level of households is envisaged as a possibility......, a credible alternative is that of indirect control based on price signals to be sent to these end-consumers. A methodology is described here allowing to estimate in advance the potential response of flexible end-consumers to price variations, subsequently embedded in an optimal price-signal generator...

  2. Danger Signals Activating the Immune Response after Trauma

    Directory of Open Access Journals (Sweden)

    Stefanie Hirsiger

    2012-01-01

    Full Text Available Sterile injury can cause a systemic inflammatory response syndrome (SIRS that resembles the host response during sepsis. The inflammatory response following trauma comprises various systems of the human body which are cross-linked with each other within a highly complex network of inflammation. Endogenous danger signals (danger-associated molecular patterns; DAMPs; alarmins as well as exogenous pathogen-associated molecular patterns (PAMPs play a crucial role in the initiation of the immune response. With popularization of the “danger theory,” numerous DAMPs and PAMPs and their corresponding pathogen-recognition receptors have been identified. In this paper, we highlight the role of the DAMPs high-mobility group box protein 1 (HMGB1, interleukin-1α (IL-1α, and interleukin-33 (IL-33 as unique dual-function mediators as well as mitochondrial danger signals released upon cellular trauma and necrosis.

  3. Signalling through C-type lectin receptors: shaping immune responses

    NARCIS (Netherlands)

    Geijtenbeek, Teunis B. H.; Gringhuis, Sonja I.

    2009-01-01

    C-type lectin receptors (CLRs) expressed by dendritic cells are crucial for tailoring immune responses to pathogens. Following pathogen binding, CLRs trigger distinct signalling pathways that induce the expression of specific cytokines which determine T cell polarization fates. Some CLRs can induce

  4. New Modeling Approaches to Investigate Cell Signaling in Radiation Response

    Science.gov (United States)

    Plante, Ianik; Cucinotta, Francis A.; Ponomarev, Artem L.

    2011-01-01

    Ionizing radiation damages individual cells and tissues leading to harmful biological effects. Among many radiation-induced lesions, DNA double-strand breaks (DSB) are considered the key precursors of most early and late effects [1] leading to direct mutation or aberrant signal transduction processes. In response to damage, a flow of information is communicated to cells not directly hit by the radiation through signal transduction pathways [2]. Non-targeted effects (NTE), which includes bystander effects and genomic instability in the progeny of irradiated cells and tissues, may be particularly important for space radiation risk assessment [1], because astronauts are exposed to a low fluence of heavy ions and only a small fraction of cells are traversed by an ion. NTE may also have important consequences clinical radiotherapy [3]. In the recent years, new simulation tools and modeling approaches have become available to study the tissue response to radiation. The simulation of signal transduction pathways require many elements such as detailed track structure calculations, a tissue or cell culture model, knowledge of biochemical pathways and Brownian Dynamics (BD) propagators of the signaling molecules in their micro-environment. Recently, the Monte-Carlo simulation code of radiation track structure RITRACKS was used for micro and nano-dosimetry calculations [4]. RITRACKS will be used to calculate the fraction of cells traversed by an ion and delta-rays and the energy deposited in cells in a tissue model. RITRACKS also simulates the formation of chemical species by the radiolysis of water [5], notably the .OH radical. This molecule is implicated in DNA damage and in the activation of the transforming growth factor beta (TGF), a signaling molecule involved in NTE. BD algorithms for a particle near a membrane comprising receptors were also developed and will be used to simulate trajectories of signaling molecules in the micro-environment and characterize autocrine

  5. Signalling network construction for modelling plant defence response.

    Directory of Open Access Journals (Sweden)

    Dragana Miljkovic

    Full Text Available Plant defence signalling response against various pathogens, including viruses, is a complex phenomenon. In resistant interaction a plant cell perceives the pathogen signal, transduces it within the cell and performs a reprogramming of the cell metabolism leading to the pathogen replication arrest. This work focuses on signalling pathways crucial for the plant defence response, i.e., the salicylic acid, jasmonic acid and ethylene signal transduction pathways, in the Arabidopsis thaliana model plant. The initial signalling network topology was constructed manually by defining the representation formalism, encoding the information from public databases and literature, and composing a pathway diagram. The manually constructed network structure consists of 175 components and 387 reactions. In order to complement the network topology with possibly missing relations, a new approach to automated information extraction from biological literature was developed. This approach, named Bio3graph, allows for automated extraction of biological relations from the literature, resulting in a set of (component1, reaction, component2 triplets and composing a graph structure which can be visualised, compared to the manually constructed topology and examined by the experts. Using a plant defence response vocabulary of components and reaction types, Bio3graph was applied to a set of 9,586 relevant full text articles, resulting in 137 newly detected reactions between the components. Finally, the manually constructed topology and the new reactions were merged to form a network structure consisting of 175 components and 524 reactions. The resulting pathway diagram of plant defence signalling represents a valuable source for further computational modelling and interpretation of omics data. The developed Bio3graph approach, implemented as an executable language processing and graph visualisation workflow, is publically available at http://ropot.ijs.si/bio3graph/and can be

  6. BOLD effect on calf muscle groups in elderly females with different bone mineral density.

    Science.gov (United States)

    Ma, Heather T; Griffith, James F; Ye, Chenfei; Yeung, David K; Xing, Xu; Leung, Ping-Chung; Yuan, Jing

    2014-01-01

    This study examined the BOLD effect on calf muscles in elderly subjects with different bone mineral density. The purpose was to investigate the oxygenation characteristics in different calf muscle groups for the elderly females and compare the muscle oxygenation among groups with different bone mineral density. Temporary vascular occlusion was induced with air-cuff compression of the thigh and BOLD-MRI data curve was fitted to derive quantitative parameters. Three muscle groups, gastrocnemius muscle (lateral head), soleus muscle, and tibialis anterior muscle, were investigated individually. Quantitative CT measurement was conducted on each subject, based on which subjects were classified into normal, osteopenia, and osteoporosis groups. The BOLD signal in soleus muscle showed the lowest minimum ischemic value during ischemia and the steepest slope during hyperemia. As soleus muscle is mainly composed by slow-twitch oxidative muscle fibers, current results may be due to a higher vascular bed density and better endothelial function in such muscle. By t-test, the half-life of the BOLD signal decay during ischemia in both gastrocnemius and soleus muscles was significantly prolonged in osteoporosis group, indicating a degenerated muscular oxygen metabolic capacity in osteoporotic patients.

  7. The response to inositol: regulation of glycerolipid metabolism and stress response signaling in yeast

    Science.gov (United States)

    Henry, Susan A.; Gaspar, Maria L.; Jesch, Stephen A.

    2014-01-01

    This article focuses on discoveries of the mechanisms governing the regulation of glycerolipid metabolism and stress response signaling in response to the phospholipid precursor, inositol. The regulation of glycerolipid lipid metabolism in yeast in response to inositol is highly complex, but increasingly well understood, and the roles of individual lipids in stress response are also increasingly well characterized. Discoveries that have emerged over several decades of genetic, molecular and biochemical analyses of metabolic, regulatory and signaling responses of yeast cells, both mutant and wild type, to the availability of the phospholipid precursor, inositol are discussed. PMID:24418527

  8. Stress response signaling and virulence: insights from entomopathogenic fungi.

    Science.gov (United States)

    Ortiz-Urquiza, Almudena; Keyhani, Nemat O

    2015-08-01

    The Ascomycete fungal insect pathogens, Beauveria and Metarhizium spp. have emerged as model systems with which to probe diverse aspects of fungal growth, stress response, and pathogenesis. Due to the availability of genomic resources and the development of robust methods for genetic manipulation, the last 5 years have witnessed a rapid increase in the molecular characterization of genes and their pathways involved in stress response and signal transduction in these fungi. These studies have been performed mainly via characterization of gene deletion/knockout mutants and have included the targeting of general proteins involved in stress response and/or virulence, e.g. catalases, superoxide dismutases, and osmolyte balance maintenance enzymes, membrane proteins and signaling pathways including GPI anchored proteins and G-protein coupled membrane receptors, MAPK pathways, e.g. (i) the pheromone/nutrient sensing, Fus3/Kss1, (ii) the cell wall integrity, Mpk1, and (iii) the high osmolarity, Hog1, the PKA/adenyl cyclase pathway, and various downstream transcription factors, e.g. Msn2, CreA and Pac1. Here, we will discuss current research that strongly suggests extensive underlying contributions of these biochemical and signaling pathways to both abiotic stress response and virulence.

  9. Enhancement of Temporal Resolution and BOLD Sensitivity in Real-Time fMRI using Multi-Slab Echo-Volumar Imaging

    Science.gov (United States)

    Posse, Stefan; Ackley, Elena; Mutihac, Radu; Rick, Jochen; Shane, Matthew; Murray-Krezan, Cristina; Zaitsev, Maxim; Speck, Oliver

    2012-01-01

    In this study, a new approach to high-speed fMRI using multi-slab echo-volumar imaging (EVI) is developed that minimizes geometrical image distortion and spatial blurring, and enables nonaliased sampling of physiological signal fluctuation to increase BOLD sensitivity compared to conventional echo-planar imaging (EPI). Real-time fMRI using whole brain 4-slab EVI with 286 ms temporal resolution (4 mm isotropic voxel size) and partial brain 2-slab EVI with 136 ms temporal resolution (4×4×6 mm3 voxel size) was performed on a clinical 3 Tesla MRI scanner equipped with 12-channel head coil. Four-slab EVI of visual and motor tasks significantly increased mean (visual: 96%, motor: 66%) and maximum t-score (visual: 263%, motor: 124%) and mean (visual: 59%, motor: 131%) and maximum (visual: 29%, motor: 67%) BOLD signal amplitude compared with EPI. Time domain moving average filtering (2 s width) to suppress physiological noise from cardiac and respiratory fluctuations further improved mean (visual: 196%, motor: 140%) and maximum (visual: 384%, motor: 200%) t-scores and increased extents of activation (visual: 73%, motor: 70%) compared to EPI. Similar sensitivity enhancement, which is attributed to high sampling rate at only moderately reduced temporal signal-to-noise ratio (mean: − 52%) and longer sampling of the BOLD effect in the echo-time domain compared to EPI, was measured in auditory cortex. Two-slab EVI further improved temporal resolution for measuring task-related activation and enabled mapping of five major resting state networks (RSNs) in individual subjects in 5 min scans. The bilateral sensorimotor, the default mode and the occipital RSNs were detectable in time frames as short as 75 s. In conclusion, the high sampling rate of real-time multi-slab EVI significantly improves sensitivity for studying the temporal dynamics of hemodynamic responses and for characterizing functional networks at high field strength in short measurement times. PMID:22398395

  10. Entry Mistakes, Entrepreneurial Boldness and Optimism

    OpenAIRE

    Brocas, Isabelle; Carrillo, Juan D

    1999-01-01

    We analyze the investment decision of a population of time inconsistent entrepreneurs who overweight current payoffs relative to future returns. We show that, in order to avoid inefficient procrastination, agents may find it optimal to keep optimistic priors about their chances of success and 'blindly invest'. This explains entrepreneurial boldness and entry mistakes (or an excessive level of investment in the economy) without assuming the existence of boundedly rational, 'intrinsically optim...

  11. Response inhibition signals and miscoding of direction in dorsomedial striatum

    Directory of Open Access Journals (Sweden)

    Daniel W Bryden

    2012-09-01

    Full Text Available The ability to inhibit action is critical for everyday behavior and is affected by a variety of disorders. Behavioral control and response inhibition is thought to depend on a neural circuit that includes the dorsal striatum, yet the neural signals that lead to response inhibition and its failure are unclear. To address this issue, we recorded from neurons in rat dorsomedial striatum (mDS in a novel task in which rats responded to a spatial cue that signaled that reward would be delivered either to the left or to the right. On 80% of trials rats were instructed to respond in the direction cued by the light (GO. On 20% of trials a second light illuminated instructing the rat to refrain from making the cued movement and move in the opposite direction (STOP. Many neurons in mDS encoded direction, firing more or less strongly for GO movements made ipsilateral or contralateral to the recording electrode. Neurons that fired more strongly for contralateral GO responses were more active when rats were faster, showed reduced activity on STOP trials, and miscoded direction on errors, suggesting that when these neurons were overly active, response inhibition failed. Neurons that decreased firing for contralateral movement were excited during trials in which the rat was required to stop the ipsilateral movement. For these neurons activity was reduced when errors were made and was negatively correlated with movement time suggesting that when these neurons were less active on STOP trials, response inhibition failed. Finally, the activity of a significant number of neurons represented a global inhibitory signal, firing more strongly during response inhibition regardless of response direction. Breakdown by cell type suggests that putative medium spiny neurons tended to fire more strongly under STOP trials, whereas putative interneurons exhibited both activity patterns. 

  12. Blood oxygenation level dependent signal and neuronal adaptation to optogenetic and sensory stimulation in somatosensory cortex in awake animals.

    Science.gov (United States)

    Aksenov, Daniil P; Li, Limin; Miller, Michael J; Wyrwicz, Alice M

    2016-11-01

    The adaptation of neuronal responses to stimulation, in which a peak transient response is followed by a sustained plateau, has been well-studied. The blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) signal has also been shown to exhibit adaptation on a longer time scale. However, some regions such as the visual and auditory cortices exhibit significant BOLD adaptation, whereas other such as the whisker barrel cortex may not adapt. In the sensory cortex a combination of thalamic inputs and intracortical activity drives hemodynamic changes, although the relative contributions of these components are not entirely understood. The aim of this study is to assess the role of thalamic inputs vs. intracortical processing in shaping BOLD adaptation during stimulation in the somatosensory cortex. Using simultaneous fMRI and electrophysiology in awake rabbits, we measured BOLD, local field potentials (LFPs), single- and multi-unit activity in the cortex during whisker and optogenetic stimulation. This design allowed us to compare BOLD and haemodynamic responses during activation of the normal thalamocortical sensory pathway (i.e., both inputs and intracortical activity) vs. the direct optical activation of intracortical circuitry alone. Our findings show that whereas LFP and multi-unit (MUA) responses adapted, neither optogenetic nor sensory stimulation produced significant BOLD adaptation. We observed for both paradigms a variety of excitatory and inhibitory single unit responses. We conclude that sensory feed-forward thalamic inputs are not primarily responsible for shaping BOLD adaptation to stimuli; but the single-unit results point to a role in this behaviour for specific excitatory and inhibitory neuronal sub-populations, which may not correlate with aggregate neuronal activity. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  13. Reproducibility and signal response linearity of Alanine gel dosimeter

    International Nuclear Information System (INIS)

    Silva, Cleber Feijo Silva; Campos, Leticia Lucente

    2008-01-01

    Gel Dosimetry has been studied mainly for medical applications, because it presents signal response in the dose range used in radiotherapy treatments and it can be applied for three dimensional dosimetry. Alanine gel dosimeter is a new gel material developed at IPEN that presents significant improvement on previous alanine systems developed by Costa (1994). The DL-Alanine (C 3 H 7 NO 2 ) is an amino acid tissue equivalent that improves the production of ferric ions in the solution. These ferric ions concentration can be measured by spectrophotometry technique. This work aims to study the reproducibility of the alanine gel solutions and the signal response as a function of gamma radiation dose, considering that these two properties are very important for characterizing and standardizing any dosimeter. (author)

  14. Disentangling resting-state BOLD variability and PCC functional connectivity in 22q11.2 deletion syndrome.

    Science.gov (United States)

    Zöller, Daniela; Schaer, Marie; Scariati, Elisa; Padula, Maria Carmela; Eliez, Stephan; Van De Ville, Dimitri

    2017-04-01

    Although often ignored in fMRI studies, moment-to-moment variability of blood oxygenation level dependent (BOLD) signals reveals important information about brain function. Indeed, higher brain signal variability has been associated with better cognitive performance in young adults compared to children and elderly adults. Functional connectivity, a very common approach in resting-state fMRI analysis, is scaled for variance. Thus, alterations might be confounded or driven by BOLD signal variance alterations. Chromosome 22q11.2 deletion syndrome (22q11.2DS) is a neurodevelopmental disorder that is associated with a vast cognitive and clinical phenotype. To date, several resting-state fMRI studies reported altered functional connectivity in 22q11.2DS, however BOLD signal variance has not yet been analyzed. Here, we employed PLS correlation analysis to reveal multivariate patterns of diagnosis-related alterations and age-relationship throughout the cortex of 50 patients between 9 and 25 years old and 50 healthy controls in the same age range. To address how functional connectivity in the default mode network is influenced by BOLD signal fluctuations, we conducted the same analysis on seed-to-voxel connectivity of the posterior cingulate cortex (PCC) and compared resulting brain patterns. BOLD signal variance was lower mainly in regions of the default mode network and in the dorsolateral prefrontal cortex, but higher in large parts of the temporal lobes. In those regions, BOLD signal variance was correlated with age in healthy controls, but not in patients, suggesting deviant developmental trajectories from child- to adulthood. Positive connectivity of the PCC within the default mode network as well as negative connectivity towards the frontoparietal network were weaker in patients with 22q11.2DS. We furthermore showed that lower functional connectivity of the PCC was not driven by higher BOLD signal variability. Our results confirm the strong implication of BOLD

  15. Filter frequency response of time dependent signal using Laplace transform

    Energy Technology Data Exchange (ETDEWEB)

    Shestakov, Aleksei I. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2018-01-16

    We analyze the effect a filter has on a time dependent signal x(t). If X(s) is the Laplace transform of x and H (s) is the filter Transfer function, the response in frequency space is X (s) H (s). Consequently, in real space, the response is the convolution (x*h) (t), where hi is the Laplace inverse of H. Effects are analyzed and analytically for functions such as (t/tc)2 e-t/t$_c$, where tc = const. We consider lowpass, highpass and bandpass filters.

  16. BOLD-specific cerebral blood volume and blood flow changes during neuronal activation in humans.

    Science.gov (United States)

    Chen, J Jean; Pike, G Bruce

    2009-12-01

    To understand and predict the blood-oxygenation level-dependent (BOLD) fMRI signal, an accurate knowledge of the relationship between cerebral blood flow (DeltaCBF) and volume (DeltaCBV) changes is critical. Currently, this relationship is widely assumed to be characterized by Grubb's power-law, derived from primate data, where the power coefficient (alpha) was found to be 0.38. The validity of this general formulation has been examined previously, and an alpha of 0.38 has been frequently cited when calculating the cerebral oxygen metabolism change (DeltaCMRo(2)) using calibrated BOLD. However, the direct use of this relationship has been the subject of some debate, since it is well established that the BOLD signal is primarily modulated by changes in 'venous' CBV (DeltaCBV(v), comprising deoxygenated blood in the capillary, venular, and to a lesser extent, in the arteriolar compartments) instead of total CBV, and yet DeltaCBV(v) measurements in humans have been extremely scarce. In this work, we demonstrate reproducible DeltaCBV(v) measurements at 3 T using venous refocusing for the volume estimation (VERVE) technique, and report on steady-state DeltaCBV(v) and DeltaCBF measurements in human subjects undergoing graded visual and sensorimotor stimulation. We found that: (1) a BOLD-specific flow-volume power-law relationship is described by alpha = 0.23 +/- 0.05, significantly lower than Grubb's constant of 0.38 for total CBV; (2) this power-law constant was not found to vary significantly between the visual and sensorimotor areas; and (3) the use of Grubb's value of 0.38 in gradient-echo BOLD modeling results in an underestimation of DeltaCMRo(2).

  17. The circadian clock regulates auxin signaling and responses in Arabidopsis.

    Directory of Open Access Journals (Sweden)

    Michael F Covington

    2007-08-01

    Full Text Available The circadian clock plays a pervasive role in the temporal regulation of plant physiology, environmental responsiveness, and development. In contrast, the phytohormone auxin plays a similarly far-reaching role in the spatial regulation of plant growth and development. Went and Thimann noted 70 years ago that plant sensitivity to auxin varied according to the time of day, an observation that they could not explain. Here we present work that explains this puzzle, demonstrating that the circadian clock regulates auxin signal transduction. Using genome-wide transcriptional profiling, we found many auxin-induced genes are under clock regulation. We verified that endogenous auxin signaling is clock regulated with a luciferase-based assay. Exogenous auxin has only modest effects on the plant clock, but the clock controls plant sensitivity to applied auxin. Notably, we found both transcriptional and growth responses to exogenous auxin are gated by the clock. Thus the circadian clock regulates some, and perhaps all, auxin responses. Consequently, many aspects of plant physiology not previously thought to be under circadian control may show time-of-day-specific sensitivity, with likely important consequences for plant growth and environmental responses.

  18. Mechanisms and pharmacogenetic signals underlying thiazide diuretics blood pressure response.

    Science.gov (United States)

    Shahin, Mohamed H; Johnson, Julie A

    2016-04-01

    Thiazide (TZD) diuretics are among the most commonly prescribed antihypertensives globally; however their chronic blood pressure (BP) lowering mechanism remains unclear. Herein we discuss the current evidence regarding specific mechanisms regulating the antihypertensive effects of TZDs, suggesting that TZDs act via multiple complex and interacting mechanisms, including natriuresis with short term use and direct vasodilatory effects chronically. Additionally, we review pharmacogenomics signals that have been associated with TZDs BP-response in several cohorts (i.e. NEDD4L, PRKCA, EDNRA-GNAS, and YEATS4) and discuss how these genes might be related to TZD BP-response mechanism. Understanding the association between these genes and TZD BP mechanism might facilitate the development of new drugs and therapeutic approaches based on a deeper understanding of the determinants of BP-response. Copyright © 2016. Published by Elsevier Ltd.

  19. Vascular Steal Explains Early Paradoxical Blood Oxygen Level-Dependent Cerebrovascular Response in Brain Regions with Delayed Arterial Transit Times

    Directory of Open Access Journals (Sweden)

    Julien Poublanc

    2013-04-01

    Full Text Available Introduction: Blood oxygen level-dependent (BOLD magnetic resonance imaging (MRI during manipulation of inhaled carbon dioxide (CO2 can be used to measure cerebrovascular reactivity (CVR and map regions of exhausted cerebrovascular reserve. These regions exhibit a reduced or negative BOLD response to inhaled CO2. In this study, we sought to clarify the mechanism behind the negative BOLD response by investigating its time delay (TD. Dynamic susceptibility contrast (DSC MRI with the injection of a contrast agent was used as the gold standard in order to provide measurement of the blood arrival time to which CVR TD could be compared. We hypothesize that if negative BOLD responses are the result of a steal phenomenon, they should be synchronized with positive BOLD responses from healthy brain tissue, even though the blood arrival time would be delayed. Methods: On a 3-tesla MRI system, BOLD CVR and DSC images were collected in a group of 19 patients with steno-occlusive cerebrovascular disease. For each patient, we generated a CVR magnitude map by regressing the BOLD signal with the end-tidal partial pressure of CO2 (PETCO2, and a CVR TD map by extracting the time of maximum cross-correlation between the BOLD signal and PETCO2. In addition, a blood arrival time map was generated by fitting the DSC signal with a gamma variate function. ROI masks corresponding to varying degrees of reactivity were constructed. Within these masks, the mean CVR magnitude, CVR TD and DSC blood arrival time were extracted and averaged over the 19 patients. CVR magnitude and CVR TD were then plotted against DSC blood arrival time. Results: The results show that CVR magnitude is highly correlated to DSC blood arrival time. As expected, the most compromised tissues with the longest blood arrival time have the lowest (most negative CVR magnitude. However, CVR TD shows a noncontinuous relationship with DSC blood arrival time. CVR TD is well correlated to DSC blood arrival time

  20. Identification of non-linear models of neural activity in bold fmri

    DEFF Research Database (Denmark)

    Jacobsen, Daniel Jakup; Madsen, Kristoffer Hougaard; Hansen, Lars Kai

    2006-01-01

    Non-linear hemodynamic models express the BOLD signal as a nonlinear, parametric functional of the temporal sequence of local neural activity. Several models have been proposed for this neural activity. We identify one such parametric model by estimating the distribution of its parameters. These ....... These distributions are themselves stochastic, therefore we estimate their variance by epoch based leave-one-out cross validation, using a Metropolis-Hastings algorithm for sampling of the posterior parameter distribution....

  1. Pitfalls in fractal time series analysis: fMRI BOLD as an exemplary case

    Directory of Open Access Journals (Sweden)

    Andras eEke

    2012-11-01

    Full Text Available This article will be positioned on our previous work demonstrating the importance of adhering to a carefully selected set of criteria when choosing the suitable method from those available ensuring its adequate performance when applied to real temporal signals, such as fMRI BOLD, to evaluate one important facet of their behavior, fractality.Earlier, we have reviewed on a range of monofractal tools and evaluated their performance. Given the advance in the fractal field, in this article we will discuss the most widely used implementations of multifractal analyses, too.Our recommended flowchart for the fractal characterization of spontaneous, low frequency fluctuations in fMRI BOLD will be used as the framework for this article to make certain that it will provide a hands-on experience for the reader in handling the perplexed issues of fractal analysis. The reason why this particular signal modality and its fractal analysis has been chosen was due to its high impact on today's neuroscience given it had powerfully emerged as a new way of interpreting the complex functioning of the brain (see intrinsic activity.The reader will first be presented with the basic concepts of mono and multifractal time series analyses, followed by some of the most relevant implementations, characterization by numerical approaches. The notion of the dichotomy of fractional Gaussian noise (fGn and fractional Brownian motion (fBm signal classes and their impact on fractal time series analyses will be thoroughly discussed as the central theme of our application strategy. Sources of pitfalls and way how to avoid them will be identified followed by a demonstration on fractal studies of fMRI BOLD taken from the literature and that of our own in an attempt to consolidate the best practice in fractal analysis of empirical fMRI-BOLD signals mapped throughout the brain as an exemplary case of potentially wide interest.

  2. Pitfalls in Fractal Time Series Analysis: fMRI BOLD as an Exemplary Case

    Science.gov (United States)

    Eke, Andras; Herman, Peter; Sanganahalli, Basavaraju G.; Hyder, Fahmeed; Mukli, Peter; Nagy, Zoltan

    2012-01-01

    This article will be positioned on our previous work demonstrating the importance of adhering to a carefully selected set of criteria when choosing the suitable method from those available ensuring its adequate performance when applied to real temporal signals, such as fMRI BOLD, to evaluate one important facet of their behavior, fractality. Earlier, we have reviewed on a range of monofractal tools and evaluated their performance. Given the advance in the fractal field, in this article we will discuss the most widely used implementations of multifractal analyses, too. Our recommended flowchart for the fractal characterization of spontaneous, low frequency fluctuations in fMRI BOLD will be used as the framework for this article to make certain that it will provide a hands-on experience for the reader in handling the perplexed issues of fractal analysis. The reason why this particular signal modality and its fractal analysis has been chosen was due to its high impact on today’s neuroscience given it had powerfully emerged as a new way of interpreting the complex functioning of the brain (see “intrinsic activity”). The reader will first be presented with the basic concepts of mono and multifractal time series analyses, followed by some of the most relevant implementations, characterization by numerical approaches. The notion of the dichotomy of fractional Gaussian noise and fractional Brownian motion signal classes and their impact on fractal time series analyses will be thoroughly discussed as the central theme of our application strategy. Sources of pitfalls and way how to avoid them will be identified followed by a demonstration on fractal studies of fMRI BOLD taken from the literature and that of our own in an attempt to consolidate the best practice in fractal analysis of empirical fMRI BOLD signals mapped throughout the brain as an exemplary case of potentially wide interest. PMID:23227008

  3. Escape response of planktonic protists to fluid mechanical signals

    DEFF Research Database (Denmark)

    Jakobsen, Hans Henrik

    2001-01-01

    The escape response to fluid mechanical signals was examined in 6 protists, 4 ciliates and 2 dinoflagellates. When exposed to a siphon flow. 3 species of ciliates, Balanion comatum, Strobilidium sp., and Mesodinium pulex, responded with escape jumps. The threshold deformation rates required...... to elicit an escape ranged between 1.8 and 3 s(-1). Escape speeds varied between 100 to 150 body length s(-1). Jump directions were non- random in all jumping species and had a negative geotactic component. In a grazing experiment with copepods, the predation mortality of a jumping ciliate was about 15...

  4. BOLD fMRI in the white matter as a marker of aging and small vessel disease.

    Directory of Open Access Journals (Sweden)

    Ilia Makedonov

    Full Text Available Determine whether white matter signal fluctuation on T2* weighted BOLD contrast images are associated with aging and cerebral small vessel disease (SVD.Resting state BOLD data were collected with a 250 ms repetition time (TR to achieve unaliased, ungated cardiac sampled BOLD (cs-BOLD images on 11 young adult controls, 10 healthy older adult controls and 7 adults with extensive white matter hyperintensities (WMH from SVD. Tissue classes (WM and GM were segmented on T1 images. WMH were identified on FLAIR images in the SVD group. Raw physiological noise (σphysio and cardiac pulsatility (i.e. fluctuations at the cardiac frequency were calculated voxel wise and group differences were tested by ANOVA. It was also possible to calculate σphysio in 2s TR cardiac aliased whole-brain BOLD (wb-BOLD data (N = 84 obtained from the International Consortium for Brain Mapping.CS-BOLD metrics showed an aging and SVD effects (p<0.0005. Covariates such as thermal noise, WM volume and partial volume did not influence the significant aging effect seen on the cardiac pulsatility metric (p<0.017 but did influence the σphysio (p = 0.184. As a verification of the cs-BOLD findings, the wb-BOLD also showed a linear aging effect of σphysio in WM. In the SVD adults, cardiac pulsatility and σphysio were lower in WMH regions compared to normal appearing white matter (NAWM regions (p<0.0013 and p<0.002, respectively. Cardiac pulsatility was better able to distinguish WMH regions from NAWM than σphysio as measured by effect size (Cohen's d 2.2 and 0.88, respectively.NAWM was found to have graded increases in cardiac pulsations due to age and SVD, independently. Within SVD participants, WMH lesions had reduced physiological noise compared to NAWM. Cardiac pulsatility in resting BOLD data may provide a complementary dynamic measure of WM integrity to add to static FLAIR anatomical images.

  5. Development of visual cortical function in infant macaques: A BOLD fMRI study.

    Directory of Open Access Journals (Sweden)

    Tom J Van Grootel

    Full Text Available Functional brain development is not well understood. In the visual system, neurophysiological studies in nonhuman primates show quite mature neuronal properties near birth although visual function is itself quite immature and continues to develop over many months or years after birth. Our goal was to assess the relative development of two main visual processing streams, dorsal and ventral, using BOLD fMRI in an attempt to understand the global mechanisms that support the maturation of visual behavior. Seven infant macaque monkeys (Macaca mulatta were repeatedly scanned, while anesthetized, over an age range of 102 to 1431 days. Large rotating checkerboard stimuli induced BOLD activation in visual cortices at early ages. Additionally we used static and dynamic Glass pattern stimuli to probe BOLD responses in primary visual cortex and two extrastriate areas: V4 and MT-V5. The resulting activations were analyzed with standard GLM and multivoxel pattern analysis (MVPA approaches. We analyzed three contrasts: Glass pattern present/absent, static/dynamic Glass pattern presentation, and structured/random Glass pattern form. For both GLM and MVPA approaches, robust coherent BOLD activation appeared relatively late in comparison to the maturation of known neuronal properties and the development of behavioral sensitivity to Glass patterns. Robust differential activity to Glass pattern present/absent and dynamic/static stimulus presentation appeared first in V1, followed by V4 and MT-V5 at older ages; there was no reliable distinction between the two extrastriate areas. A similar pattern of results was obtained with the two analysis methods, although MVPA analysis showed reliable differential responses emerging at later ages than GLM. Although BOLD responses to large visual stimuli are detectable, our results with more refined stimuli indicate that global BOLD activity changes as behavioral performance matures. This reflects an hierarchical development of

  6. Purinergic signaling to terminate TLR responses in macrophages

    Directory of Open Access Journals (Sweden)

    Kajal eHamidzadeh

    2016-03-01

    Full Text Available Macrophages undergo profound physiological alterations when they encounter pathogen associated molecular patterns (PAMPs. These alterations can result in the elaboration of cytokines and mediators that promote immune responses and contribute to the clearance of pathogens. These innate immune responses by myeloid cells are transient. The termination of these secretory responses is not due to the dilution of stimuli, but rather to the active down-regulation of innate responses induced by the very PAMPs that initiated them. Here we describe a purinergic autoregulatory program whereby TLR-stimulated macrophages control their activation state. In this program, TLR stimulated macrophages undergo metabolic alterations that result in the production of ATP and its release through membrane pannexin channels. This purine nucleotide is rapidly hydrolyzed to adenosine by ectoenzymes on the macrophage surface, CD39 and CD73. Adenosine then signals through the P1 class of seven transmembrane receptors to induce a regulatory state that is characterized by the down-regulation of inflammatory cytokines and the production of anti-inflammatory cytokines and growth factors. This purinergic autoregulatory system mitigates the collateral damage that would be caused by the prolonged activation of macrophages, and rather allows the macrophage to maintain homeostasis. The transient activation of macrophages can be prolonged by treating macrophages with IFN-γ. IFN-γ treated macrophages become less sensitive to the regulatory effects of adenosine, allowing them to sustain macrophage activation for the duration of an adaptive immune response.

  7. Resting BOLD fluctuations in the primary somatosensory cortex correlate with tactile acuity.

    Science.gov (United States)

    Haag, Lauren M; Heba, Stefanie; Lenz, Melanie; Glaubitz, Benjamin; Höffken, Oliver; Kalisch, Tobias; Puts, Nicholaas A; Edden, Richard A E; Tegenthoff, Martin; Dinse, Hubert; Schmidt-Wilcke, Tobias

    2015-03-01

    Sensory perception, including 2-point discrimination (2 ptD), is tightly linked to cortical processing of tactile stimuli in primary somatosensory cortices. While the role of cortical activity in response to a tactile stimulus has been widely investigated, the role of baseline cortical activity is largely unknown. Using resting state fMRI we investigated the relationship between local BOLD fluctuations in the primary somatosensory cortex (the representational field of the hand) and 2 ptD of the corresponding index finger (right and left). Cortical activity was measured using fractional amplitudes of the low frequency BOLD fluctuations (fALFF) and synchronicity using regional homogeneity (ReHo) of the S1 hand region during rest. 2 ptD correlated with higher ReHo values in the representational areas of the contralateral S1 cortex (left hand: p = .028; right hand: p = .049). 2 ptD additionally correlated with higher fALFF in the representational area of the left hand (p = .007) and showed a trend for a significant correlation in the representational area of the right hand (p = .051). Thus, higher BOLD amplitudes and synchronicity at rest, as measures of cortical activity and synchronicity, respectively, are related to better tactile discrimination abilities of the contralateral hand. Our findings extend the relationship seen between spontaneous BOLD fluctuations and sensory perception. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Measuring Social Motivation Using Signal Detection and Reward Responsiveness.

    Science.gov (United States)

    Chevallier, Coralie; Tonge, Natasha; Safra, Lou; Kahn, David; Kohls, Gregor; Miller, Judith; Schultz, Robert T

    2016-01-01

    Recent trends in psychiatry have emphasized the need for a shift from categorical to dimensional approaches. Of critical importance to this transformation is the availability of tools to objectively quantify behaviors dimensionally. The present study focuses on social motivation, a dimension of behavior that is central to a range of psychiatric conditions but for which a particularly small number of assays currently exist. In Study 1 (N = 48), healthy adults completed a monetary reward task and a social reward task, followed by completion of the Chapman Physical and Social Anhedonia Scales. In Study 2 (N = 26), an independent sample was recruited to assess the robustness of Study 1's findings. The reward tasks were analyzed using signal detection theory to quantify how much reward cues bias participants' responses. In both Study 1 and Study 2, social anhedonia scores were negatively correlated with change in response bias in the social reward task but not in the monetary reward task. A median split on social anhedonia scores confirmed that participants with high social anhedonia showed less change in response bias in the social reward task compared to participants with low social anhedonia. This study confirms that social anhedonia selectively affects how much an individual changes their behavior based on the presence of socially rewarding cues and establishes a tool to quantify social reward responsiveness dimensionally.

  9. DMPD: Cytokine signaling modules in inflammatory responses. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 18400190 Cytokine signaling modules in inflammatory responses. O'Shea JJ, Murray PJ.... Immunity. 2008 Apr;28(4):477-87. (.png) (.svg) (.html) (.csml) Show Cytokine signaling modules in inflamma...tory responses. PubmedID 18400190 Title Cytokine signaling modules in inflammatory responses. Authors O'Shea

  10. DMPD: Innate immune responses: crosstalk of signaling and regulation of genetranscription. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 16753195 Innate immune responses: crosstalk of signaling and regulation of genetran...l) (.csml) Show Innate immune responses: crosstalk of signaling and regulation of genetranscription. PubmedI...D 16753195 Title Innate immune responses: crosstalk of signaling and regulation o

  11. Determination of relative CMRO2 from CBF and BOLD changes: significant increase of oxygen consumption rate during visual stimulation

    DEFF Research Database (Denmark)

    Kim, S.G.; Rostrup, Egill; Larsson, H.B.

    1999-01-01

    The blood oxygenation level-dependent (BOLD) effect in functional magnetic resonance imaging depends on at least partial uncoupling between cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) changes. By measuring CBF and BOLD simultaneously, the relative change in CMRO2 can...... be estimated during neural activity using a reference condition obtained with known CMRO2 change. In this work, nine subjects were studied at a magnetic field of 1.5 T; each subject underwent inhalation of a 5% carbon dioxide gas mixture as a reference and two visual stimulation studies. Relative CBF and BOLD...... signal changes were measured simultaneously using the flow-sensitive alternating inversion recovery (FAIR) technique. During hypercapnia established by an end-tidal CO2 increase of 1.46 kPa, CBF in the visual cortex increased by 47.3 +/- 17.3% (mean +/- SD; n = 9), and deltaR2* was -0.478 +/- 0.147 sec...

  12. Viral Infection: An Evolving Insight into the Signal Transduction Pathways Responsible for the Innate Immune Response

    Directory of Open Access Journals (Sweden)

    Girish J. Kotwal

    2012-01-01

    Full Text Available The innate immune response is initiated by the interaction of stereotypical pathogen components with genetically conserved receptors for extracytosolic pathogen-associated molecular patterns (PAMPs or intracytosolic nucleic acids. In multicellular organisms, this interaction typically clusters signal transduction molecules and leads to their activations, thereby initiating signals that activate innate immune effector mechanisms to protect the host. In some cases programmed cell death—a fundamental form of innate immunity—is initiated in response to genotoxic or biochemical stress that is associated with viral infection. In this paper we will summarize innate immune mechanisms that are relevant to viral pathogenesis and outline the continuing evolution of viral mechanisms that suppress the innate immunity in mammalian hosts. These mechanisms of viral innate immune evasion provide significant insight into the pathways of the antiviral innate immune response of many organisms. Examples of relevant mammalian innate immune defenses host defenses include signaling to interferon and cytokine response pathways as well as signaling to the inflammasome. Understanding which viral innate immune evasion mechanisms are linked to pathogenesis may translate into therapies and vaccines that are truly effective in eliminating the morbidity and mortality associated with viral infections in individuals.

  13. Viral Infection: An Evolving Insight into the Signal Transduction Pathways Responsible for the Innate Immune Response

    Science.gov (United States)

    Kotwal, Girish J.; Hatch, Steven; Marshall, William L.

    2012-01-01

    The innate immune response is initiated by the interaction of stereotypical pathogen components with genetically conserved receptors for extracytosolic pathogen-associated molecular patterns (PAMPs) or intracytosolic nucleic acids. In multicellular organisms, this interaction typically clusters signal transduction molecules and leads to their activations, thereby initiating signals that activate innate immune effector mechanisms to protect the host. In some cases programmed cell death—a fundamental form of innate immunity—is initiated in response to genotoxic or biochemical stress that is associated with viral infection. In this paper we will summarize innate immune mechanisms that are relevant to viral pathogenesis and outline the continuing evolution of viral mechanisms that suppress the innate immunity in mammalian hosts. These mechanisms of viral innate immune evasion provide significant insight into the pathways of the antiviral innate immune response of many organisms. Examples of relevant mammalian innate immune defenses host defenses include signaling to interferon and cytokine response pathways as well as signaling to the inflammasome. Understanding which viral innate immune evasion mechanisms are linked to pathogenesis may translate into therapies and vaccines that are truly effective in eliminating the morbidity and mortality associated with viral infections in individuals. PMID:22997518

  14. Customising the therapeutic response of signalling networks to promote antitumor responses by drug combinations

    Directory of Open Access Journals (Sweden)

    Alexey eGoltsov

    2014-02-01

    Full Text Available Drug resistance, de novo and acquired, pervades cellular signalling networks from one signalling motif to another as a result of cancer progression and/or drug intervention. This resistance is one of the key determinants of efficacy in targeted anticancer drug therapy. Although poorly understood, drug resistance is already being addressed in combination therapy by selecting drug targets where sensitivity increases due to combination components or as a result of de novo or acquired mutations. Additionally, successive drug combinations have shown low resistance potency. To promote a rational, systematic development of combination therapies, it is necessary to establish the underlying mechanisms that drive the advantages of drug combinations and design methods to determine advanced targets for drug combination therapy. Based on a joint systems analysis of cellular signalling network (SN response and its sensitivity to drug action and oncogenic mutations, we describe an in silico method to analyse the targets of drug combinations. The method explores mechanisms of sensitizing the SN through combination of two drugs targeting vertical signalling pathways. We propose a paradigm of SN response customization by one drug to both maximize the effect of another drug in combination and promote a robust therapeutic response against oncogenic mutations. The method was applied to the customization of the response of the ErbB/PI3K/PTEN/AKT pathway by combination of drugs targeting HER2 receptors and proteins in the downstream pathway. The results of a computational experiment showed that the modification of the SN response from hyperbolic to smooth sigmoid response by manipulation of two drugs in combination leads to greater robustness in therapeutic response against oncogenic mutations determining cancer heterogeneity. The application of this method in drug combination co-development suggests a combined evaluation of inhibition effects along with the

  15. Physiologic characterization of inflammatory arthritis in a rabbit model with BOLD and DCE MRI at 1.5 Tesla.

    Science.gov (United States)

    Nasui, Otilia C; Chan, Michael W; Nathanael, George; Crawley, Adrian; Miller, Elka; Belik, Jaques; Cheng, Hai-Ling; Kassner, Andrea; Rayner, Tammy; Weiss, Ruth; Detzler, Garry; Zhong, Anguo; Moineddin, Rahim; Jong, Roland; Rogers, Marianne; Doria, Andrea S

    2014-11-01

    Our aim was to test the feasibility of blood oxygen level dependent magnetic resonance imaging (BOLD MRI) and dynamic contrast-enhanced (DCE) MRI to monitor periarticular hypoxic/inflammatory changes over time in a juvenile rabbit model of arthritis. We examined arthritic and contralateral nonarthritic knees of 21 juvenile rabbits at baseline and days 1,14, and 28 after induction of arthritis by unilateral intra-articular injection of carrageenin with BOLD and DCE MRI at 1.5 Tesla (T). Nine noninjected rabbits served as controls. Associations between BOLD and DCE-MRI and corresponding intra-articular oxygen pressure (PO2) and blood flow [blood perfusion units (BPU)] (polarographic probes, reference standards) or clinical-histological data were measured by correlation coefficients. Percentage BOLD MRI change obtained in contralateral knees correlated moderately with BPU on day 0 (r = -0.51, p = 0.02) and excellently on day 28 (r = -0.84, p = 0.03). A moderate correlation was observed between peak enhancement DCE MRI (day 1) and BPU measurements in arthritic knees (r = 0.49, p = 0.04). In acute arthritis, BOLD and DCE MRI highly correlated (r = 0.89, p = 0.04; r = 1.0, p < 0.0001) with histological scores in arthritic knees. The proposed techniques are feasible to perform at 1.5 T, and they hold potential as surrogate measures to monitor hypoxic and inflammatory changes over time in arthritis at higher-strength MRI fields. • BOLD and DCE MRI detect interval perisynovial changes in a rabbit knee • BOLD and DCE MRI act as surrogate markers of physiologic changes in arthritis • BOLD MRI signal represents oxygen extraction compared with intra-articular PO 2 • DCE MRI measurements estimate physiologic periarticular vascular properties • In rabbit knees with acute arthritis, BOLD/DCE MRI highly correlated with histological scores.

  16. To boldly gulp: standard metabolic rate and boldness have context-dependent influences on risk-taking to breathe air in a catfish.

    Science.gov (United States)

    McKenzie, David J; Belão, Thiago C; Killen, Shaun S; Rantin, F Tadeu

    2015-12-01

    The African sharptooth catfish Clarias gariepinus has bimodal respiration, it has a suprabranchial air-breathing organ alongside substantial gills. We used automated bimodal respirometry to reveal that undisturbed juvenile catfish (N=29) breathed air continuously in normoxia, with a marked diurnal cycle. Air breathing and routine metabolic rate (RMR) increased in darkness when, in the wild, this nocturnal predator forages. Aquatic hypoxia (20% air saturation) greatly increased overall reliance on air breathing. We investigated whether two measures of risk taking to breathe air, namely absolute rates of aerial O2 uptake (ṀO2,air) and the percentage of RMR obtained from air (%ṀO2,air), were influenced by individual standard metabolic rate (SMR) and boldness. In particular, whether any influence varied with resource availability (normoxia versus hypoxia) or relative fear of predation (day versus night). Individual SMR, derived from respirometry, had an overall positive influence on ṀO2,air across all contexts but a positive influence on %ṀO2,air only in hypoxia. Thus, a pervasive effect of SMR on air breathing became most acute in hypoxia, when individuals with higher O2 demand took proportionally more risks. Boldness was estimated as time required to resume air breathing after a fearful stimulus in daylight normoxia (Tres). Although Tres had no overall influence on ṀO2,air or %ṀO2,air, there was a negative relationship between Tres and %ṀO2,air in daylight, in normoxia and hypoxia. There were two Tres response groups, 'bold' phenotypes with Tres below 75 min (N=13) which, in daylight, breathed proportionally more air than 'shy' phenotypes with Tres above 115 min (N=16). Therefore, individual boldness influenced air breathing when fear of predation was high. Thus, individual energy demand and personality did not have parallel influences on the emergent tendency to take risks to obtain a resource; their influences varied in strength with context. © 2015

  17. Precision analysis of the photomultiplier response to ultra low signals

    Science.gov (United States)

    Degtiarenko, Pavel

    2017-11-01

    A new computational model for the description of the photon detector response functions measured in conditions of low light is presented, together with examples of the observed photomultiplier signal amplitude distributions, successfully described using the parameterized model equation. In extension to the previously known approximations, the new model describes the underlying discrete statistical behavior of the photoelectron cascade multiplication processes in photon detectors with complex non-uniform gain structure of the first dynode. Important features of the model include the ability to represent the true single-photoelectron spectra from different photomultipliers with a variety of parameterized shapes, reflecting the variability in the design and in the individual parameters of the detectors. The new software tool is available for evaluation of the detectors' performance, response, and efficiency parameters that may be used in various applications including the ultra low background experiments such as the searches for Dark Matter and rare decays, underground neutrino studies, optimizing operations of the Cherenkov light detectors, help in the detector selection procedures, and in the experiment simulations.

  18. Fitness Consequences of Boldness in Juvenile and Adult Largemouth Bass.

    Science.gov (United States)

    Ballew, Nicholas G; Mittelbach, Gary G; Scribner, Kim T

    2017-04-01

    To date, most studies investigating the relationship between personality traits and fitness have focused on a single measure of fitness (such as survival) at a specific life stage. However, many personality traits likely have multiple effects on fitness, potentially operating across different functional contexts and stages of development. Here, we address the fitness consequences of boldness, under seminatural conditions, across life stages and functional contexts in largemouth bass (Micropterus salmoides). Specifically, we report the effect of boldness on (1) juvenile survivorship in an outdoor pond containing natural prey and predators and (2) adult reproductive success in three outdoor ponds across three reproductive seasons (years). Juvenile survival was negatively affected by boldness, with bolder juveniles having a lower probability of survival than shyer juveniles. In contrast, bolder adult male bass had greater reproductive success than their shyer male counterparts. Female reproductive success was not affected by boldness. These findings demonstrate that boldness can affect fitness differently across life stages. Further, boldness was highly consistent across years and significantly heritable, which suggests that boldness has a genetic component. Thus, our results support theory suggesting that fitness trade-offs across life stages may contribute to the maintenance of personality variation within populations.

  19. Spatiotemporal dynamics of the brain at rest--exploring EEG microstates as electrophysiological signatures of BOLD resting state networks.

    Science.gov (United States)

    Yuan, Han; Zotev, Vadim; Phillips, Raquel; Drevets, Wayne C; Bodurka, Jerzy

    2012-05-01

    Neuroimaging research suggests that the resting cerebral physiology is characterized by complex patterns of neuronal activity in widely distributed functional networks. As studied using functional magnetic resonance imaging (fMRI) of the blood-oxygenation-level dependent (BOLD) signal, the resting brain activity is associated with slowly fluctuating hemodynamic signals (~10s). More recently, multimodal functional imaging studies involving simultaneous acquisition of BOLD-fMRI and electroencephalography (EEG) data have suggested that the relatively slow hemodynamic fluctuations of some resting state networks (RSNs) evinced in the BOLD data are related to much faster (~100 ms) transient brain states reflected in EEG signals, that are referred to as "microstates". To further elucidate the relationship between microstates and RSNs, we developed a fully data-driven approach that combines information from simultaneously recorded, high-density EEG and BOLD-fMRI data. Using independent component analysis (ICA) of the combined EEG and fMRI data, we identified thirteen microstates and ten RSNs that are organized independently in their temporal and spatial characteristics, respectively. We hypothesized that the intrinsic brain networks that are active at rest would be reflected in both the EEG data and the fMRI data. To test this hypothesis, the rapid fluctuations associated with each microstate were correlated with the BOLD-fMRI signal associated with each RSN. We found that each RSN was characterized further by a specific electrophysiological signature involving from one to a combination of several microstates. Moreover, by comparing the time course of EEG microstates to that of the whole-brain BOLD signal, on a multi-subject group level, we unraveled for the first time a set of microstate-associated networks that correspond to a range of previously described RSNs, including visual, sensorimotor, auditory, attention, frontal, visceromotor and default mode networks. These

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

    Lifescience Database Archive (English)

    Full Text Available 16332394 ITAM-based signaling beyond the adaptive immune response. Fodor S, Jakus Z..., Mocsai A. Immunol Lett. 2006 Apr 15;104(1-2):29-37. Epub 2005 Nov 28. (.png) (.svg) (.html) (.csml) Show ITAM-based sign...aling beyond the adaptive immune response. PubmedID 16332394 Title ITAM-based signaling beyond

  1. Spatial Mnemonic Encoding: Theta Power Decreases and Medial Temporal Lobe BOLD Increases Co-Occur during the Usage of the Method of Loci.

    Science.gov (United States)

    Fellner, Marie-Christin; Volberg, Gregor; Wimber, Maria; Goldhacker, Markus; Greenlee, Mark W; Hanslmayr, Simon

    2016-01-01

    The method of loci is one, if not the most, efficient mnemonic encoding strategy. This spatial mnemonic combines the core cognitive processes commonly linked to medial temporal lobe (MTL) activity: spatial and associative memory processes. During such processes, fMRI studies consistently demonstrate MTL activity, while electrophysiological studies have emphasized the important role of theta oscillations (3-8 Hz) in the MTL. However, it is still unknown whether increases or decreases in theta power co-occur with increased BOLD signal in the MTL during memory encoding. To investigate this question, we recorded EEG and fMRI separately, while human participants used the spatial method of loci or the pegword method, a similarly associative but nonspatial mnemonic. The more effective spatial mnemonic induced a pronounced theta power decrease source localized to the left MTL compared with the nonspatial associative mnemonic strategy. This effect was mirrored by BOLD signal increases in the MTL. Successful encoding, irrespective of the strategy used, elicited decreases in left temporal theta power and increases in MTL BOLD activity. This pattern of results suggests a negative relationship between theta power and BOLD signal changes in the MTL during memory encoding and spatial processing. The findings extend the well known negative relation of alpha/beta oscillations and BOLD signals in the cortex to theta oscillations in the MTL.

  2. Comparative gel-based phosphoproteomics in response to signaling molecules

    KAUST Repository

    Marondedze, Claudius

    2013-09-03

    The gel-based proteomics approach is a valuable technique for studying the characteristics of proteins. This technique has diverse applications ranging from analysis of a single protein to the study of the total cellular proteins. Further, protein quality and to some extent distribution can be first assessed by means of one-dimensional gel electrophoresis and then more informatively, for comparative analysis, using the two-dimensional gel electrophoresis technique. Here, we describe how to take advantage of the availability of fluorescent dyes to stain for a selective class of proteins on the same gel for the detection of both phospho- and total proteomes. This enables the co-detection of phosphoproteins as well as total proteins from the same gel and is accomplished by utilizing two different fluorescent stains, the ProQ-Diamond, which stains only phosphorylated proteins, and Sypro Ruby, which stains the entire subset of proteins. This workflow can be applied to gain insights into the regulatory mechanisms induced by signaling molecules such as cyclic nucleotides through the quantification and subsequent identification of responsive phospho- and total proteins. © Springer Science+Business Media New York 2013.

  3. Improving OCD time to solution using Signal Response Metrology

    Science.gov (United States)

    Fang, Fang; Zhang, Xiaoxiao; Vaid, Alok; Pandev, Stilian; Sanko, Dimitry; Ramanathan, Vidya; Venkataraman, Kartik; Haupt, Ronny

    2016-03-01

    In recent technology nodes, advanced process and novel integration scheme have challenged the precision limits of conventional metrology; with critical dimensions (CD) of device reduce to sub-nanometer region. Optical metrology has proved its capability to precisely detect intricate details on the complex structures, however, conventional RCWA-based (rigorous coupled wave analysis) scatterometry has the limitations of long time-to-results and lack of flexibility to adapt to wide process variations. Signal Response Metrology (SRM) is a new metrology technique targeted to alleviate the consumption of engineering and computation resources by eliminating geometric/dispersion modeling and spectral simulation from the workflow. This is achieved by directly correlating the spectra acquired from a set of wafers with known process variations encoded. In SPIE 2015, we presented the results of SRM application in lithography metrology and control [1], accomplished the mission of setting up a new measurement recipe of focus/dose monitoring in hours. This work will demonstrate our recent field exploration of SRM implementation in 20nm technology and beyond, including focus metrology for scanner control; post etch geometric profile measurement, and actual device profile metrology.

  4. The effect of dissolved oxygen on the relaxation rates of blood plasma: Implications for hyperoxia calibrated BOLD.

    Science.gov (United States)

    Ma, Yuhan; Berman, Avery J L; Pike, G Bruce

    2016-12-01

    To determine the contribution of paramagnetic dissolved oxygen in blood plasma to blood-oxygenation-level-dependent (BOLD) signal changes in hyperoxic calibrated BOLD studies. Bovine blood plasma samples were prepared with partial pressures of oxygen (pO 2 ) ranging from 110 to 600 mmHg. R 1 , R 2 , and R 2 * of the plasma with dissolved oxygen were measured using quantitative MRI sequences at 3 Tesla. Simulations were performed to predict the relative effects of dissolved oxygen and deoxyhemoglobin changes in hyperoxia calibrated BOLD. The relaxivities of dissolved oxygen in plasma were found to be r 1, O2 =1.97 ± 0.09 ×10 -4 s -1 mmHg -1 , r 2, O2 =2.3 ± 0.7 ×10 -4 s -1 mmHg -1 , and r 2, O2 * = 2.3 ± 0.7 ×10 -4 s -1 mmHg -1 . Simulations predict that neither the transverse nor longitudinal relaxation rates of dissolved oxygen contribute significantly to the BOLD signal during hyperoxia. During hyperoxia, the increases in R 2 and R 2 * of blood from dissolved oxygen in plasma are considerably less than the decreases in R 2 and R 2 * from venous deoxyhemoglobin. R 1 effects due to dissolved oxygen are also predicted to be negligible. As a result, dissolved oxygen in arteries should not contribute significantly to the hyperoxic calibrated BOLD signal. Magn Reson Med 76:1905-1911, 2016. © 2015 International Society for Magnetic Resonance in Medicine. © 2015 International Society for Magnetic Resonance in Medicine.

  5. 17 CFR 232.307 - Bold face type.

    Science.gov (United States)

    2010-04-01

    ... an electronic format document by presenting such information in capital letters. (b) Paragraph (a) of this section does not apply to HTML documents. ...-GENERAL RULES AND REGULATIONS FOR ELECTRONIC FILINGS Preparation of Electronic Submissions § 232.307 Bold...

  6. Reversible vesicle restraint in response to spatiotemporally controlled electrical signals: a bridge between electrical and chemical signaling modes.

    Science.gov (United States)

    Zhu, Chao; Wu, Li-Qun; Wang, Xiang; Lee, Jae-Ho; English, Douglas S; Ghodssi, Reza; Raghavan, Srinivasa R; Payne, Gregory F

    2007-01-02

    Microelectronic devices employ electrons for signaling whereas the nervous system signals using ions and chemicals. Bridging these signaling differences would benefit applications that range from biosensing to neuroprosthetics. Here, we report the use of localized electrical signals to perform an operation common to chemical signaling in the nervous system. Specifically, we employ electrical signals to restrain vesicles reversibly. We perform this operation using the stimuli-responsive aminopolysaccharide chitosan that is able to electrodeposit onto cathode surfaces in response to localized electrical stimuli. We show that surfactant-vesicles and liposomes can be co-deposited with chitosan and are entrapped (i.e., restrained) within the deposited film's matrix. Vesicle co-deposition could be controlled spatially and temporally using microfabricated wafers with independent electrode addresses. Finally, we show that vesicles restrained within the deposited chitosan matrix can be mobilized under mildly acidic conditions (pH chitosan. Potentially, the ability to restrain and mobilize chemical signals that are segregated within vesicles may allow microfluidic systems to access the rich diversity offered by chemical signaling.

  7. Chemosensory responses of Acanthamoeba castellanii: visual analysis of random movement and responses to chemical signals.

    Science.gov (United States)

    Schuster, F L; Levandowsky, M

    1996-01-01

    A visual assay slide chamber was used in conjunction with time-lapse videomicroscopy to analyze chemotactic behavior of axenically grown Acanthamoeba castellanii. Data were collected and analyzed as vector scatter diagrams and cell tracks. Amebas responded to a variety of bacterial products or potential bacterial products by moving actively toward the attractant. Responses to the chemotactic peptide formyl-methionyl-leucyl-phenylalanine (fMLP), lipopolysaccharide, and lipid A were statistically significant (P 0.05). There was no single optimal concentration for response to any of the attractants tested, and amebas responded equally over the range of concentrations tested. Pretreatment of amebas with chemotactic peptides, bacterial products, and bacteria reduced the directional response to attractants. Amebas that had been grown in the presence of bacteria appeared more responsive to chemotactic peptides. Treatment of amebas with trypsin reduced the response of cells to chemotactic peptides, though sensitivity was restored within a couple of hours. This suggests the ameba membrane may have receptors, sensitive to these bacterial substances, which are different from the mannose receptors involved in binding bacteria to the membrane during phagocytosis. The rate of movement was relatively constant (ca. 0.40 microns/s), indicating that the locomotor response to these signals is a taxis, or possibly a klinokinesis, but not an orthokinesis. Studies of the population diffusion rate in the absence of signals indicate that the basic population motility follows the pattern of a Levy walk, rather than the more familiar Gaussian diffusion. This suggests that the usual mathematical models of ameboid dispersion may need to be modified.

  8. Compartmentalization of GPCR signalling controls unique cellular responses.

    Science.gov (United States)

    Ellisdon, Andrew M; Halls, Michelle L

    2016-04-15

    With >800 members, G protein-coupled receptors (GPCRs) are the largest class of cell-surface signalling proteins, and their activation mediates diverse physiological processes. GPCRs are ubiquitously distributed across all cell types, involved in many diseases and are major drug targets. However, GPCR drug discovery is still characterized by very high attrition rates. New avenues for GPCR drug discovery may be provided by a recent shift away from the traditional view of signal transduction as a simple chain of events initiated from the plasma membrane. It is now apparent that GPCR signalling is restricted to highly organized compartments within the cell, and that GPCRs activate distinct signalling pathways once internalized. A high-resolution understanding of how compartmentalized signalling is controlled will probably provide unique opportunities to selectively and therapeutically target GPCRs. © 2016 Authors; published by Portland Press Limited.

  9. G protein coupled receptors signaling pathways implicate in inflammatory and immune response of rheumatoid arthritis.

    Science.gov (United States)

    Shu, Jinling; Zhang, Feng; Zhang, Lingling; Wei, Wei

    2017-05-01

    G protein-coupled receptors (GPCRs) are transmembrane receptor proteins, which allow the transfer of signals across the membrane. Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovitis and accompanied with inflammatory and abnormal immune response. GPCRs signaling pathways play a significant role in inflammatory and immune response processes including RA. In this review, we have focused on the advances in GPCRs signaling pathway implicating the inflammatory and immune response of RA. The signaling pathways of GPCRs-adenylyl cyclase (AC)-cyclic adenosine 3', 5'-monophosphate (cAMP) include β 2 adrenergic receptors (β 2 -ARs)-AC-cAMP signaling pathways, E-prostanoid2/4 (EP2/4)-AC-cAMP signaling pathways and so on. Regulatory proteins, such as G protein-coupled receptor kinases (GRKs) and β-arrestins, play important modulatory roles in GPCRs signaling pathway. GPCRs signaling pathway and regulatory proteins implicate the pathogenesis process of inflammatory and immune response. GPCRs-AC-cAMP signal pathways involve in the inflammatory and immune response of RA. Different signaling pathways are mediated by different receptors, such as β 2 -AR, PGE2 receptor, chemokines receptor, and adenosine receptor. GRKs and β-arrestins are crucial proteins in the regulation of GPCRs signaling pathways. The potential therapeutic targets as well as strategies to modulate GPCRs signaling pathway are new development trends.

  10. Effects of percutaneous transluminal angioplasty on muscle BOLD-MRI in patients with peripheral arterial occlusive disease: preliminary results

    Energy Technology Data Exchange (ETDEWEB)

    Huegli, Rolf W. [University Hospital Basel, Department of Radiology, Division of Interventional Radiology, Basel (Switzerland)]|[Kantonsspital Bruderholz, Department of Radiology, Bruderholz (Switzerland); Schulte, Anja-Carina [University of Basel, Biocenter, Basel (Switzerland); Aschwanden, Markus; Thalhammer, Christoph [University Hospital Basel, Department of Angiology, Basel (Switzerland); Kos, Sebastian; Jacob, Augustinus L.; Bilecen, Deniz [University Hospital Basel, Department of Radiology, Division of Interventional Radiology, Basel (Switzerland)

    2009-02-15

    The purpose was to evaluate the effect of percutaneous transluminal angioplasty (PTA) of the superficial femoral artery (SFA) on the blood oxygenation level-dependent (BOLD) signal change in the calf musculature of patients with intermittent claudication. Ten patients (mean age, 63.4 {+-} 11.6 years) with symptomatic peripheral arterial occlusive disease (PAOD) caused by SFA stenoses were investigated before and after PTA. Patients underwent BOLD-MRI 1 day before and 6 weeks after PTA. A T2*-weighted single-shot multi-echo echo-planar MR-imaging technique was applied. The BOLD measurements were acquired at mid-calf level during reactive hyperaemia at 1.5 T. This transient hyperperfusion of the muscle tissue was provoked by suprasystolic cuff compression. Key parameters describing the BOLD signal curve included maximum T2*(T2*{sub max}), time-to-peak to reach T2*{sub max} (TTP) and T2* end value (EV) after 600 s of hyperemia. Paired t-tests were applied for statistic comparison. Between baseline and post-PTA, T2*{sub max} increased from 11.1{+-}3.6% to 12.3{+-}3.8% (p=0.51), TTP decreased from 48.5{+-}20.8 s to 35.3{+-}11.6 s (p=0.11) and EV decreased from 6.1{+-}6.4% to 5.0{+-}4.2% (p=0.69). In conclusion, BOLD-MRI reveals changes of the key parameters T2*{sub max}, TTP, and EV after successful PTA of the calf muscles during reactive hyperaemia. (orig.)

  11. Enhancement of temporal resolution and BOLD sensitivity in real-time fMRI using multi-slab echo-volumar imaging.

    Science.gov (United States)

    Posse, Stefan; Ackley, Elena; Mutihac, Radu; Rick, Jochen; Shane, Matthew; Murray-Krezan, Cristina; Zaitsev, Maxim; Speck, Oliver

    2012-05-15

    In this study, a new approach to high-speed fMRI using multi-slab echo-volumar imaging (EVI) is developed that minimizes geometrical image distortion and spatial blurring, and enables nonaliased sampling of physiological signal fluctuation to increase BOLD sensitivity compared to conventional echo-planar imaging (EPI). Real-time fMRI using whole brain 4-slab EVI with 286 ms temporal resolution (4mm isotropic voxel size) and partial brain 2-slab EVI with 136 ms temporal resolution (4×4×6 mm(3) voxel size) was performed on a clinical 3 Tesla MRI scanner equipped with 12-channel head coil. Four-slab EVI of visual and motor tasks significantly increased mean (visual: 96%, motor: 66%) and maximum t-score (visual: 263%, motor: 124%) and mean (visual: 59%, motor: 131%) and maximum (visual: 29%, motor: 67%) BOLD signal amplitude compared with EPI. Time domain moving average filtering (2s width) to suppress physiological noise from cardiac and respiratory fluctuations further improved mean (visual: 196%, motor: 140%) and maximum (visual: 384%, motor: 200%) t-scores and increased extents of activation (visual: 73%, motor: 70%) compared to EPI. Similar sensitivity enhancement, which is attributed to high sampling rate at only moderately reduced temporal signal-to-noise ratio (mean: -52%) and longer sampling of the BOLD effect in the echo-time domain compared to EPI, was measured in auditory cortex. Two-slab EVI further improved temporal resolution for measuring task-related activation and enabled mapping of five major resting state networks (RSNs) in individual subjects in 5 min scans. The bilateral sensorimotor, the default mode and the occipital RSNs were detectable in time frames as short as 75 s. In conclusion, the high sampling rate of real-time multi-slab EVI significantly improves sensitivity for studying the temporal dynamics of hemodynamic responses and for characterizing functional networks at high field strength in short measurement times. Copyright © 2012

  12. Adult wheel access interaction with activity and boldness personality in Siberian dwarf hamsters (Phodopus sungorus).

    Science.gov (United States)

    Kanda, L Leann; Abdulhay, Amir; Erickson, Caitlin

    2017-05-01

    Individual animal personalities interact with environmental conditions to generate differences in behavior, a phenomenon of growing interest for understanding the effects of environmental enrichment on captive animals. Wheels are common environmental enrichment for laboratory rodents, but studies conflict on how this influences behavior, and interaction of wheels with individual personalities has rarely been examined. We examined whether wheel access altered personality profiles in adult Siberian dwarf hamsters. We assayed animals in a tunnel maze twice for baseline personality, then again at two and at seven weeks after the experimental group was provisioned with wheels in their home cages. Linear mixed model selection was used to assess changes in behavior over time and across environmental gradient of wheel exposure. While animals showed consistent inter-individual differences in activity, activity personality did not change upon exposure to a wheel. Boldness also varies among individuals, and there is evidence for female boldness scores converging after wheel exposure, that is, opposite shifts in behavior by high and low boldness individuals, although sample size is too small for the mixed model results to be robust. In general, Siberian dwarf hamsters appear to show low behavioral plasticity, particularly in general activity, in response to running wheels. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Neuronal ERK signaling in response to graphene oxide in nematode Caenorhabditis elegans.

    Science.gov (United States)

    Qu, Man; Li, Yunhui; Wu, Qiuli; Xia, Yankai; Wang, Dayong

    2017-05-01

    ERK signaling is one of the important mitogen-activated protein kinases (MAPKs). However, the role of ERK signaling in the regulation of response to engineered nanomaterial exposure is still largely unclear. In this study, using in vivo assay system of Caenorhabditis elegans, we investigated the function of ERK signaling in response to graphene oxide (GO) exposure and the underlying molecular mechanism. GO exposure increased the expression of MEK-2/MEK and MPK-1/ERK in the ERK signaling pathway. Mutation of mek-2 or mpk-1 resulted in a susceptibility to GO toxicity. Both the MEK-2 and the MPK-1 acted in neurons to regulate the response to GO exposure, and the neuronal expression of MEK-2 or MPK-1 caused a resistance to GO toxicity. In the neurons, SKN-1b/Nrf acted downstream of the MPK-1, and AEX-3, a guanine exchange factor for GTPase, further acted downstream of the SKN-1b to regulate the response to GO exposure. Therefore, a signaling cascade of MEK-2-MPK-1-SKN-1b/-AEX-3 was identified in the neurons required for the regulation of response to GO exposure. Moreover, genetic interaction assay demonstrated that the neuronal ERK signaling-mediated signaling pathway and the intestinal p38 MAPK-mediated signaling pathway functioned synergistically in the regulation of response to GO exposure. Our results highlight the crucial function of the neuronal ERK signaling in the regulation of response to nanomaterial exposure in organisms.

  14. Recent Advances in Plant Early Signaling in Response to Herbivory

    Directory of Open Access Journals (Sweden)

    Gen-Ichiro Arimura

    2011-06-01

    Full Text Available Plants are frequently attacked by herbivores and pathogens and therefore have acquired constitutive and induced defenses during the course of their evolution. Here we review recent progress in the study of the early signal transduction pathways in host plants in response to herbivory. The sophisticated signaling network for plant defense responses is elicited and driven by both herbivore-induced factors (e.g., elicitors, effectors, and wounding and plant signaling (e.g., phytohormone and plant volatiles in response to arthropod factors. We describe significant findings, illuminating the scenario by providing broad insights into plant signaling involved in several arthropod-host interactions.

  15. Graph Theoretical Analysis of BOLD Functional Connectivity during Human Sleep without EEG Monitoring.

    Directory of Open Access Journals (Sweden)

    Jun Lv

    Full Text Available Functional brain networks of human have been revealed to have small-world properties by both analyzing electroencephalogram (EEG and functional magnetic resonance imaging (fMRI time series.In our study, by using graph theoretical analysis, we attempted to investigate the changes of paralimbic-limbic cortex between wake and sleep states. Ten healthy young people were recruited to our experiment. Data from 2 subjects were excluded for the reason that they had not fallen asleep during the experiment. For each subject, blood oxygen level dependency (BOLD images were acquired to analyze brain network, and peripheral pulse signals were obtained continuously to identify if the subject was in sleep periods. Results of fMRI showed that brain networks exhibited stronger small-world characteristics during sleep state as compared to wake state, which was in consistent with previous studies using EEG synchronization. Moreover, we observed that compared with wake state, paralimbic-limbic cortex had less connectivity with neocortical system and centrencephalic structure in sleep.In conclusion, this is the first study, to our knowledge, has observed that small-world properties of brain functional networks altered when human sleeps without EEG synchronization. Moreover, we speculate that paralimbic-limbic cortex organization owns an efficient defense mechanism responsible for suppressing the external environment interference when humans sleep, which is consistent with the hypothesis that the paralimbic-limbic cortex may be functionally disconnected from brain regions which directly mediate their interactions with the external environment. Our findings also provide a reasonable explanation why stable sleep exhibits homeostasis which is far less susceptible to outside world.

  16. Graph Theoretical Analysis of BOLD Functional Connectivity during Human Sleep without EEG Monitoring.

    Science.gov (United States)

    Lv, Jun; Liu, Dongdong; Ma, Jing; Wang, Xiaoying; Zhang, Jue

    2015-01-01

    Functional brain networks of human have been revealed to have small-world properties by both analyzing electroencephalogram (EEG) and functional magnetic resonance imaging (fMRI) time series. In our study, by using graph theoretical analysis, we attempted to investigate the changes of paralimbic-limbic cortex between wake and sleep states. Ten healthy young people were recruited to our experiment. Data from 2 subjects were excluded for the reason that they had not fallen asleep during the experiment. For each subject, blood oxygen level dependency (BOLD) images were acquired to analyze brain network, and peripheral pulse signals were obtained continuously to identify if the subject was in sleep periods. Results of fMRI showed that brain networks exhibited stronger small-world characteristics during sleep state as compared to wake state, which was in consistent with previous studies using EEG synchronization. Moreover, we observed that compared with wake state, paralimbic-limbic cortex had less connectivity with neocortical system and centrencephalic structure in sleep. In conclusion, this is the first study, to our knowledge, has observed that small-world properties of brain functional networks altered when human sleeps without EEG synchronization. Moreover, we speculate that paralimbic-limbic cortex organization owns an efficient defense mechanism responsible for suppressing the external environment interference when humans sleep, which is consistent with the hypothesis that the paralimbic-limbic cortex may be functionally disconnected from brain regions which directly mediate their interactions with the external environment. Our findings also provide a reasonable explanation why stable sleep exhibits homeostasis which is far less susceptible to outside world.

  17. Multi-regional investigation of the relationship between functional MRI blood oxygenation level dependent (BOLD activation and GABA concentration.

    Directory of Open Access Journals (Sweden)

    Ashley D Harris

    Full Text Available Several recent studies have reported an inter-individual correlation between regional GABA concentration, as measured by MRS, and the amplitude of the functional blood oxygenation level dependent (BOLD response in the same region. In this study, we set out to investigate whether this coupling generalizes across cortex. In 18 healthy participants, we performed edited MRS measurements of GABA and BOLD-fMRI experiments using regionally related activation paradigms. Regions and tasks were the: occipital cortex with a visual grating stimulus; auditory cortex with a white noise stimulus; sensorimotor cortex with a finger-tapping task; frontal eye field with a saccade task; and dorsolateral prefrontal cortex with a working memory task. In contrast to the prior literature, no correlation between GABA concentration and BOLD activation was detected in any region. The origin of this discrepancy is not clear. Subtle differences in study design or insufficient power may cause differing results; these and other potential reasons for the discrepant results are discussed. This negative result, although it should be interpreted with caution, has a larger sample size than prior positive results, and suggests that the relationship between GABA and the BOLD response may be more complex than previously thought.

  18. Interleaved quantitative BOLD: Combining extravascular R2' - and intravascular R2-measurements for estimation of deoxygenated blood volume and hemoglobin oxygen saturation.

    Science.gov (United States)

    Lee, Hyunyeol; Englund, Erin K; Wehrli, Felix W

    2018-03-23

    Quantitative BOLD (qBOLD), a non-invasive MRI method for assessment of hemodynamic and metabolic properties of the brain in the baseline state, provides spatial maps of deoxygenated blood volume fraction (DBV) and hemoglobin oxygen saturation (HbO 2 ) by means of an analytical model for the temporal evolution of free-induction-decay signals in the extravascular compartment. However, mutual coupling between DBV and HbO 2 in the signal model results in considerable estimation uncertainty precluding achievement of a unique set of solutions. To address this problem, we developed an interleaved qBOLD method (iqBOLD) that combines extravascular R 2 ' and intravascular R 2 mapping techniques so as to obtain prior knowledge for the two unknown parameters. To achieve these goals, asymmetric spin echo and velocity-selective spin-labeling (VSSL) modules were interleaved in a single pulse sequence. Prior to VSSL, arterial blood and CSF signals were suppressed to produce reliable estimates for cerebral venous blood volume fraction (CBV v ) as well as venous blood R 2 (to yield HbO 2 ). Parameter maps derived from the VSSL module were employed to initialize DBV and HbO 2 in the qBOLD processing. Numerical simulations and in vivo experiments at 3 T were performed to evaluate the performance of iqBOLD in comparison to the parent qBOLD method. Data obtained in eight healthy subjects yielded plausible values averaging 60.1 ± 3.3% for HbO 2 and 3.1 ± 0.5 and 2.0 ± 0.4% for DBV in gray and white matter, respectively. Furthermore, the results show that prior estimates of CBV v and HbO 2 from the VSSL component enhance the solution stability in the qBOLD processing, and thus suggest the feasibility of iqBOLD as a promising alternative to the conventional technique for quantifying neurometabolic parameters. Copyright © 2018. Published by Elsevier Inc.

  19. Advances in High-Field BOLD fMRI

    Directory of Open Access Journals (Sweden)

    Markus Barth

    2011-11-01

    Full Text Available This review article examines the current state of BOLD fMRI at a high magnetic field strength of 7 Tesla. The following aspects are covered: a short description of the BOLD contrast, spatial and temporal resolution, BOLD sensitivity, localization and spatial specificity, technical challenges as well as an outlook on future developments are given. It is shown that the main technical challenges of performing BOLD fMRI at high magnetic field strengths—namely development of array coils, imaging sequences and parallel imaging reconstruction—have been solved successfully. The combination of these developments has lead to the availability of high-resolution BOLD fMRI protocols that are able to cover the whole brain with a repetition time (TR shorter than 3 s. The structural information available from these high-resolution fMRI images itself is already very detailed, which helps to co-localize structure and function. Potential future applications include whole-brain connectivity analysis on a laminar resolution and single subject examinations.

  20. Probing Chromatin Modifications in Response to ERK Signaling.

    Science.gov (United States)

    Oksuz, Ozgur; Tee, Wee-Wei

    2017-01-01

    Chromatin immunoprecipitation (ChIP) is a technique used to determine the association of proteins or histone modifications with chromatin regions in living cells or tissues, and is used extensively in the chromatin biology field to study transcriptional and epigenetic mechanisms. Increasing evidence points to an epigenetic coordination of signaling cascades, such as ERK, that regulate key processes in development and disease, revealing novel principles of gene regulation. Here we describe a detailed protocol for performing chromatin immunoprecipitation followed by qPCR (ChIP-qPCR) for probing histone modifications regulated by ERK signaling in mouse ESCs.

  1. Wavelet entropy of BOLD time series: An application to Rolandic epilepsy.

    Science.gov (United States)

    Gupta, Lalit; Jansen, Jacobus F A; Hofman, Paul A M; Besseling, René M H; de Louw, Anton J A; Aldenkamp, Albert P; Backes, Walter H

    2017-12-01

    To assess the wavelet entropy for the characterization of intrinsic aberrant temporal irregularities in the time series of resting-state blood-oxygen-level-dependent (BOLD) signal fluctuations. Further, to evaluate the temporal irregularities (disorder/order) on a voxel-by-voxel basis in the brains of children with Rolandic epilepsy. The BOLD time series was decomposed using the discrete wavelet transform and the wavelet entropy was calculated. Using a model time series consisting of multiple harmonics and nonstationary components, the wavelet entropy was compared with Shannon and spectral (Fourier-based) entropy. As an application, the wavelet entropy in 22 children with Rolandic epilepsy was compared to 22 age-matched healthy controls. The images were obtained by performing resting-state functional magnetic resonance imaging (fMRI) using a 3T system, an 8-element receive-only head coil, and an echo planar imaging pulse sequence ( T2*-weighted). The wavelet entropy was also compared to spectral entropy, regional homogeneity, and Shannon entropy. Wavelet entropy was found to identify the nonstationary components of the model time series. In Rolandic epilepsy patients, a significantly elevated wavelet entropy was observed relative to controls for the whole cerebrum (P = 0.03). Spectral entropy (P = 0.41), regional homogeneity (P = 0.52), and Shannon entropy (P = 0.32) did not reveal significant differences. The wavelet entropy measure appeared more sensitive to detect abnormalities in cerebral fluctuations represented by nonstationary effects in the BOLD time series than more conventional measures. This effect was observed in the model time series as well as in Rolandic epilepsy. These observations suggest that the brains of children with Rolandic epilepsy exhibit stronger nonstationary temporal signal fluctuations than controls. 2 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2017;46:1728-1737. © 2017 International Society for Magnetic

  2. Heterogenous migraine aura symptoms correlate with visual cortex functional magnetic resonance imaging responses.

    Science.gov (United States)

    Arngrim, Nanna; Hougaard, Anders; Ahmadi, Khazar; Vestergaard, Mark Bitsch; Schytz, Henrik Winther; Amin, Faisal Mohammad; Larsson, Henrik Bo Wiberg; Olesen, Jes; Hoffmann, Michael B; Ashina, Messoud

    2017-12-01

    Migraine aura is sparsely studied due to the highly challenging task of capturing patients during aura. Cortical spreading depression (CSD) is likely the underlying phenomenon of aura. The possible correlation between the multifaceted phenomenology of aura symptoms and the effects of CSD on the brain has not been ascertained. Five migraine patients were studied during various forms of aura symptoms induced by hypoxia, sham hypoxia, or physical exercise with concurrent photostimulation. The blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) signal response to visual stimulation was measured in retinotopic mapping-defined visual cortex areas V1 to V4. We found reduced BOLD response in patients reporting scotoma and increased response in patients who only experienced positive symptoms. Furthermore, patients with bilateral visual symptoms had corresponding bihemispherical changes in BOLD response. These findings suggest that different aura symptoms reflect different types of cerebral dysfunction, which correspond to specific changes in BOLD signal reactivity. Furthermore, we provide evidence of bilateral CSD recorded by fMRI during bilateral aura symptoms. Ann Neurol 2017;82:925-939. © 2017 American Neurological Association.

  3. Brain activation by short-term nicotine exposure in anesthetized wild-type and beta2-nicotinic receptors knockout mice: a BOLD fMRI study

    Energy Technology Data Exchange (ETDEWEB)

    Suarez, S.V.; Changeux, J.P.; Granon, S. [Unite de Neurobiologie Integrative du Systeme Cholinergique, URA CNRS 2182, Institut Pasteur, Departement de Neuroscience, 25 rue du Dr Roux, 75015 Paris (France); Amadon, A.; Giacomini, E.; Le Bihan, D. [Service Hospitalier Frederic Joliot, 4 place du general Leclerc, 91400 Orsay (France); Wiklund, A. [Section of Anaesthesiology and Intensive Care Medicine, Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm (Sweden)

    2009-07-01

    Rationale: The behavioral effects of nicotine and the role of the beta2-containing nicotinic receptors in these behaviors are well documented. However, the behaviors altered by nicotine rely on the functioning on multiple brain circuits where the high-affinity {beta}2-containing nicotinic receptors ({beta}2*nAChRs) are located. Objectives We intend to see which brain circuits are activated when nicotine is given in animals naive for nicotine and whether the {beta}2*nAChRs are needed for its activation of the blood oxygen level dependent (BOLD) signal in all brain areas. Materials and methods: We used functional magnetic resonance imaging (fMRI) to measure the brain activation evoked by nicotine (1 mg/kg delivered at a slow rate for 45 min) in anesthetized C57BL/6J mice and {beta}2 knockout (KO) mice. Results: Acute nicotine injection results in a significant increased activation in anterior frontal, motor, and somatosensory cortices and in the ventral tegmental area and the substantia nigra. Anesthetized mice receiving no nicotine injection exhibited a major decreased activation in all cortical and subcortical structures, likely due to prolonged anesthesia. At a global level, {beta}2 KO mice were not rescued from the globally declining BOLD signal. However, nicotine still activated regions of a meso-cortico-limbic circuit likely via {alpha}7 nicotinic receptors. Conclusions: Acute nicotine exposure compensates for the drop in brain activation due to anesthesia through the meso-cortico-limbic network via the action of nicotine on {beta}2*nAChRs. The developed fMRI method is suitable for comparing responses in wild-type and mutant mice. (authors)

  4. Brain activation by short-term nicotine exposure in anesthetized wild-type and beta2-nicotinic receptors knockout mice: a BOLD fMRI study

    International Nuclear Information System (INIS)

    Suarez, S.V.; Changeux, J.P.; Granon, S.; Amadon, A.; Giacomini, E.; Le Bihan, D.; Wiklund, A.

    2009-01-01

    Rationale: The behavioral effects of nicotine and the role of the beta2-containing nicotinic receptors in these behaviors are well documented. However, the behaviors altered by nicotine rely on the functioning on multiple brain circuits where the high-affinity β2-containing nicotinic receptors (β2*nAChRs) are located. Objectives We intend to see which brain circuits are activated when nicotine is given in animals naive for nicotine and whether the β2*nAChRs are needed for its activation of the blood oxygen level dependent (BOLD) signal in all brain areas. Materials and methods: We used functional magnetic resonance imaging (fMRI) to measure the brain activation evoked by nicotine (1 mg/kg delivered at a slow rate for 45 min) in anesthetized C57BL/6J mice and β2 knockout (KO) mice. Results: Acute nicotine injection results in a significant increased activation in anterior frontal, motor, and somatosensory cortices and in the ventral tegmental area and the substantia nigra. Anesthetized mice receiving no nicotine injection exhibited a major decreased activation in all cortical and subcortical structures, likely due to prolonged anesthesia. At a global level, β2 KO mice were not rescued from the globally declining BOLD signal. However, nicotine still activated regions of a meso-cortico-limbic circuit likely via α7 nicotinic receptors. Conclusions: Acute nicotine exposure compensates for the drop in brain activation due to anesthesia through the meso-cortico-limbic network via the action of nicotine on β2*nAChRs. The developed fMRI method is suitable for comparing responses in wild-type and mutant mice. (authors)

  5. Perceptual distortions and delusional thinking following ketamine administration are related to increased pharmacological MRI signal changes in the parietal lobe.

    Science.gov (United States)

    Stone, James; Kotoula, Vasileia; Dietrich, Craige; De Simoni, Sara; Krystal, John H; Mehta, Mitul A

    2015-09-01

    Ketamine produces effects in healthy humans that resemble the positive, negative and cognitive symptoms of schizophrenia. We investigated the effect of ketamine administration on brain activity as indexed by blood-oxygen-level-dependent (BOLD) signal change response, and its relationship to ketamine-induced subjective changes, including perceptual distortion. Thirteen healthy participants volunteered for the study. All underwent a 15-min functional MRI acquisition with a ketamine infusion commencing after 5 min (approx 0.26 mg/kg over 20s followed by an infusion of approx. 0.42 mg/kg/h). Following the scan, participants self-rated ketamine-induced effects using the Psychotomimetic States Inventory. Ketamine led to widespread cortical and subcortical increases in BOLD response (FWE-corrected p distortions and delusional thoughts correlated with increased BOLD response in the paracentral lobule (FWE-corrected p < 0.01). The findings suggest that BOLD increases in parietal cortices reflect ketamine effects on circuits that contribute to its capacity to produce perceptual alterations and delusional interpretations. © The Author(s) 2015.

  6. Responses of domestic horses (Equus caballus) to human emotional signals

    OpenAIRE

    Smith, Amy Victoria

    2017-01-01

    The communication of emotion is fundamental for social cohesion and information sharing in social species. It may be highly beneficial for domestic animals to recognise human emotional signals, as this would allow them to make informed decisions about their interactions with humans, and about events in human-dominated environments. To date, the literature in this area has largely focused on domestic dogs’ (Canis familiaris) abilities. The present thesis extends this field of research to inclu...

  7. Integration of danger peptide signals with herbivore-associated molecular pattern signaling amplifies anti-herbivore defense responses in rice.

    Science.gov (United States)

    Shinya, Tomonori; Yasuda, Shigetaka; Hyodo, Kiwamu; Tani, Rena; Hojo, Yuko; Fujiwara, Yuka; Hiruma, Kei; Ishizaki, Takuma; Fujita, Yasunari; Saijo, Yusuke; Galis, Ivan

    2018-03-07

    Plant defense against herbivores is modulated by herbivore-associated molecular patterns (HAMPs) from oral secretions (OS) and/or saliva of insects. Furthermore, feeding wounds initiate plant self-damage responses modulated by danger-associated molecular patterns (DAMPs) such as immune defense-promoting plant elicitor peptides (Peps). While temporal and spatial co-existence of both patterns during herbivory implies a possibility of their close interaction, the molecular mechanisms remain undetermined. Here we report that exogenous application of rice (Oryza sativa) peptides (OsPeps) can elicit multiple defense responses in rice cell cultures. Specific activation of OsPROPEP3 gene transcripts in rice leaves by wounding and OS treatments further suggests a possible involvement of the OsPep3 peptide in rice-herbivore interactions. Correspondingly, we found that simultaneous application of OsPep3 and Mythimna loreyi OS significantly amplifies an array of defense responses in rice cells, including mitogen-activated protein kinase activation, and generation of defense-related hormones and metabolites. The induction of OsPROPEP3/4 by OsPep3 points to a positive auto-feedback loop in OsPep signaling which may contribute to additional enhancement of defense signal(s). Finally, the overexpression of the OsPep receptor OsPEPR1 increases the sensitivity of rice plants not only to the cognate OsPeps but also to OS signals. Our findings collectively suggest that HAMP-DAMP signal integration provides a critical step in the amplification of defense signaling in plants. © 2018 The Authors The Plant Journal © 2018 John Wiley & Sons Ltd.

  8. Somatosensory BOLD fMRI reveals close link between salient blood pressure changes and the murine neuromatrix.

    Science.gov (United States)

    Reimann, Henning Matthias; Todiras, Mihail; Hodge, Russ; Huelnhagen, Till; Millward, Jason Michael; Turner, Robert; Seeliger, Erdmann; Bader, Michael; Pohlmann, Andreas; Niendorf, Thoralf

    2018-05-15

    The neuromatrix, or "pain matrix", is a network of cortical brain areas which is activated by noxious as well as salient somatosensory stimulation. This has been studied in mice and humans using blood oxygenation level-dependent (BOLD) fMRI. Here we demonstrate that BOLD effects observed in the murine neuromatrix in response to salient somatosensory stimuli are prone to reflect mean arterial blood pressure (MABP) changes, rather than neural activity. We show that a standard electrostimulus typically used in murine somatosensory fMRI can induce substantial elevations in MABP. Equivalent drug-induced MABP changes - without somatosensory stimulation - evoked BOLD patterns in the neuromatrix strikingly similar to those evoked by electrostimulation. This constitutes a serious caveat for murine fMRI. The regional specificity of these BOLD patterns can be attributed to the co-localization of the neuromatrix with large draining veins. Based on these findings we propose a cardiovascular support mechanism whereby abrupt elevations in MABP provide additional energy supply to the neuromatrix and other essential brain areas in fight-or-flight situations. Copyright © 2018 Elsevier Inc. All rights reserved.

  9. Male responses to conspecific advertisement signals in the field cricket Gryllus rubens (Orthoptera: Gryllidae).

    Science.gov (United States)

    Jang, Yikweon

    2011-01-20

    In many species males aggregate and produce long-range advertisement signals to attract conspecific females. The majority of the receivers of these signals are probably other males most of the time, and male responses to competitors' signals can structure the spatial and temporal organization of the breeding aggregation and affect male mating tactics. I quantified male responses to a conspecific advertisement stimulus repeatedly over three age classes in Gryllus rubens (Orthoptera: Gryllidae) in order to estimate the type and frequency of male responses to the broadcast stimulus and to determine the factors affecting them. Factors tested included body size, wing dimorphism, age, and intensity of the broadcast stimulus. Overall, males employed acoustic response more often than positive phonotactic response. As males aged, the frequency of positive phonotactic response decreased but that of the acoustic response increased. That is, males may use positive phonotaxis in the early stages of their adult lives, possibly to find suitable calling sites or parasitize calling males, and then later in life switch to acoustic responses in response to conspecific advertisement signals. Males with smaller body size more frequently exhibited acoustic responses. This study suggests that individual variation, more than any factors measured, is critical for age-dependent male responses to conspecific advertisement signals.

  10. Physiological responses to taste signals of functional food components.

    Science.gov (United States)

    Narukawa, Masataka

    2018-02-01

    The functions of food have three categories: nutrition, palatability, and bioregulation. As the onset of lifestyle-related diseases has increased, many people have shown interest in functional foods that are beneficial to bioregulation. We believe that functional foods should be highly palatable for increased acceptance from consumers. In order to design functional foods with a high palatability, we have investigated about the palatability, especially in relation to the taste of food. In this review, we discuss (1) the identification of taste receptors that respond to functional food components; (2) an analysis of the peripheral taste transduction system; and (3) the investigation of the relationship between physiological functions and taste signals.

  11. Brushless DC motor control system responsive to control signals generated by a computer or the like

    Science.gov (United States)

    Packard, D. T.

    1985-04-01

    A control system for a brushless DC motor responsive to digital control signals is disclosed. The motor includes a multiphase wound stator and a permanent magnet rotor. The motor is arranged so that each phase winding, when energized from a DC source, will drive the rotor through a predetermined angular position or step. A commutation signal generator responsive to the shaft position provides a commutation signal for each winding. A programmable control signal generator such as a computer or microprocessor produces individual digital control signals for each phase winding. The control signals and commutation signals associated with each winding are applied to an AND gate for that phase winding. Each gate controls a switch connected in series with the associated phase winding and the DC source so that each phase winding is energized only when the commutation signal and the control signal associated with that phase winding are present. The motor shaft may be advanced one step at a time to a desired position by applying a predetermined number of control signals in the proper sequence to the AND gates and the torque generated by the motor be regulated by applying a separate control signal and each AND gate which is pulse width modulated to control the total time that each switch connects its associated winding to the DC source during each commutation period.

  12. Brushless DC motor control system responsive to control signals generated by a computer or the like

    Science.gov (United States)

    Packard, Douglas T. (Inventor); Schmitt, Donald E. (Inventor)

    1987-01-01

    A control system for a brushless DC motor responsive to digital control signals is disclosed. The motor includes a multiphase wound stator and a permanent magnet rotor. The rotor is arranged so that each phase winding, when energized from a DC source, will drive the rotor through a predetermined angular position or step. A commutation signal generator responsive to the shaft position provides a commutation signal for each winding. A programmable control signal generator such as a computer or microprocessor produces individual digital control signals for each phase winding. The control signals and commutation signals associated with each winding are applied to an AND gate for that phase winding. Each gate controls a switch connected in series with the associated phase winding and the DC source so that each phase winding is energized only when the commutation signal and the control signal associated with that phase winding are present. The motor shaft may be advanced one step at a time to a desired position by applying a predetermined number of control signals in the proper sequence to the AND gates and the torque generated by the motor may be regulated by applying a separate control signal to each AND gate which is pulse width modulated to control the total time that each switch connects its associated winding to the DC source during each commutation period.

  13. Defining treatment response in trichotillomania: a signal detection analysis.

    Science.gov (United States)

    Houghton, David C; Capriotti, Matthew R; De Nadai, Alessandro S; Compton, Scott N; Twohig, Michael P; Neal-Barnett, Angela M; Saunders, Stephen M; Franklin, Martin E; Woods, Douglas W

    2015-12-01

    The Massachusetts General Hospital Hairpulling Scale (MGH-HPS) and the NIMH Trichotillomania Severity Scale (NIMH-TSS) are two widely used measures of trichotillomania severity. Despite their popular use, currently no empirically-supported guidelines exist to determine the degrees of change on these scales that best indicate treatment response. Determination of such criteria could aid in clinical decision-making by defining clinically significant treatment response/recovery and producing accurate power analyses for use in clinical trials research. Adults with trichotillomania (N=69) participated in a randomized controlled trial of psychotherapy and were assessed before and after treatment. Response status was measured via the Clinical Global Impressions-Improvement Scale, and remission status was measured via the Clinical Global Impressions-Severity Scale. For treatment response, a 45% reduction or 7-point raw score change on the MGH-HPS was the best indicator of clinically significant treatment response, and on the NIMH-TSS, a 30-40% reduction or 6-point raw score difference was most effective cutoff. For disorder remission, a 55-60% reduction or 7-point raw score change on the MGH-HPS was the best predictor, and on the NIMH-TSS, a 65% reduction or 6-point raw score change was the best indicator of disorder remission. Implications of these findings are discussed. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Inter-donor variation in cell subset specific immune signaling responses in healthy individuals.

    Science.gov (United States)

    Longo, Diane M; Louie, Brent; Wang, Ena; Pos, Zoltan; Marincola, Francesco M; Hawtin, Rachael E; Cesano, Alessandra

    2012-01-01

    Single cell network profiling (SCNP) is a multi-parameter flow cytometry based approach that allows for the simultaneous interrogation of intracellular signaling pathways in multiple cell subpopulations within heterogeneous tissues, without the need for individual cell subset isolation. Thus, the technology is extremely well-suited for characterizing the multitude of interconnected signaling pathways and immune cell subpopulations that regulate the function of the immune system. Recently, SCNP was applied to generate a functional map of the healthy human immune cell signaling network by profiling immune signaling pathways downstream of 12 immunomodulators in 7 distinct immune cell subsets within peripheral blood mononuclear cells (PBMCs) from 60 healthy donors. In the study reported here, the degree of inter-donor variation in the magnitude of the immune signaling responses was analyzed. The highest inter-donor differences in immune signaling pathway activity occurred following perturbation of the immune signaling network, rather than in basal signaling. When examining the full panel of immune signaling responses, as one may expect, the overall degree of inter-donor variation was positively correlated (r = 0.727) with the magnitude of node response (i.e. a larger median signaling response was associated with greater inter-donor variation). However, when examining the degree of heterogeneity across cell subpopulations for individual signaling nodes, cell subset specificity in the degree of inter-donor variation was observed for several nodes. For such nodes, relatively weak correlations between inter-donor variation and the magnitude of the response were observed. Further, within the phenotypically distinct subpopulations, a fraction of the immune signaling responses had bimodal response profiles in which (a) only a portion of the cells had elevated phospho-protein levels following modulation and (b) the proportion of responsive cells varied by donor. These data

  15. Study on wing fanning as a signal of sexual response and courtship ...

    African Journals Online (AJOL)

    A series of experiments was carried out at the Institute of Biological Sciences, University of Malaya to identify wing fanning as an attraction or signal of sexual response and courtship behavior of Bactrocera papayae. Sexual natures such as signal or attraction and courtship behavior were determined through males and ...

  16. An Improved Response Surface Methodology Algorithm with an Application to Traffic Signal Optimization for Urban Networks

    Science.gov (United States)

    1995-01-01

    Prepared ca. 1995. This paper illustrates the use of the simulation-optimization technique of response surface methodology (RSM) in traffic signal optimization of urban networks. It also quantifies the gains of using the common random number (CRN) va...

  17. On the correct side of performance: Processing of internal and external signals in response speed evaluation.

    Science.gov (United States)

    Valt, Christian; Stürmer, Birgit

    2017-07-01

    Response appropriateness is not exclusively limited to accuracy. Nevertheless, the processing of parameters other than accuracy for response monitoring has been mostly neglected. The present experiment explored how the cognitive system processes response speed based on internal and external signals. Participants performed a response-choice task where correct responses were classified as fast, average, or slow. External signals informative about performance quality were presented after the response in most of the trials; in some trials, instead, participants had to judge their own performance. Event-related brain potentials (ERPs) of response and feedback processing were analysed to investigate how the cognitive system monitors correct responses. Response quality affected the processing of internal signals. That is, both the response-related negativity (correct-related negativity, CRN) and positivity (correct positivity, Pc) showed modulations related to speed: with the largest and the smallest amplitudes associated with fast and slow responses, respectively. We ascribe these modulations to positive arousal associated with the optimal nature of correct fast responses. Response quality, also affected feedback processing. Here, response speed significantly modulated the feedback-related negativity (FRN) and had an effect on the latency and the magnitude of the preceding positive peak. These effects in feedback processing seem related to feedback expectation in a context where awareness of feedback quality is vague and average performance, although more difficult to detected, is generally expected. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Group VII Ethylene Response Factors Coordinate Oxygen and Nitric Oxide Signal Transduction and Stress Responses in Plants1

    Science.gov (United States)

    Gibbs, Daniel J.; Conde, Jorge Vicente; Berckhan, Sophie; Prasad, Geeta; Mendiondo, Guillermina M.; Holdsworth, Michael J.

    2015-01-01

    The group VII ethylene response factors (ERFVIIs) are plant-specific transcription factors that have emerged as important regulators of abiotic and biotic stress responses, in particular, low-oxygen stress. A defining feature of ERFVIIs is their conserved N-terminal domain, which renders them oxygen- and nitric oxide (NO)-dependent substrates of the N-end rule pathway of targeted proteolysis. In the presence of these gases, ERFVIIs are destabilized, whereas an absence of either permits their accumulation; ERFVIIs therefore coordinate plant homeostatic responses to oxygen availability and control a wide range of NO-mediated processes. ERFVIIs have a variety of context-specific protein and gene interaction partners, and also modulate gibberellin and abscisic acid signaling to regulate diverse developmental processes and stress responses. This update discusses recent advances in our understanding of ERFVII regulation and function, highlighting their role as central regulators of gaseous signal transduction at the interface of ethylene, oxygen, and NO signaling. PMID:25944828

  19. Enhanced Toll-like receptor responses in the absence of signaling adaptor DAP12.

    OpenAIRE

    Hamerman, Jessica A; Tchao, Nadia K; Lowell, Clifford A; Lanier, Lewis L

    2005-01-01

    DAP12 is a signaling adaptor containing an immunoreceptor tyrosine-based activation motif (ITAM) that pairs with receptors on myeloid cells and natural killer cells. We examine here the responses of mice lacking DAP12 to stimulation through Toll-like receptors (TLRs). Unexpectedly, DAP12-deficient macrophages produced higher concentrations of inflammatory cytokines in response to a variety of pathogenic stimuli. Additionally, macrophages deficient in spleen tyrosine kinase (Syk), which signal...

  20. Estimating Response to Price Signals in Residential Electricity Consumption

    OpenAIRE

    Huang, Yizhang

    2013-01-01

    Based on a previous empirical study of the effect of a residential demand response program in Sala, Sweden, this project  investigated the economic consequences of consumer behaviour change after a demand-based time of use distribution tariff was employed. The economic consequences of consumers were proven to be disadvantageous in terms of unit electricity price. Consumers could achieve more electricity bill saving through stabilising their electricity consumption during peak hours, and this ...

  1. PRMT5 modulates the metabolic response to fasting signals.

    Science.gov (United States)

    Tsai, Wen-Wei; Niessen, Sherry; Goebel, Naomi; Yates, John R; Guccione, Ernesto; Montminy, Marc

    2013-05-28

    Under fasting conditions, increases in circulating glucagon maintain glucose balance by promoting hepatic gluconeogenesis. Triggering of the cAMP pathway stimulates gluconeogenic gene expression through the PKA-mediated phosphorylation of the cAMP response element binding (CREB) protein and via the dephosphorylation of the latent cytoplasmic CREB regulated transcriptional coactivator 2 (CRTC2). CREB and CRTC2 activities are increased in insulin resistance, in which they promote hyperglycemia because of constitutive induction of the gluconeogenic program. The extent to which CREB and CRTC2 are coordinately up-regulated in response to glucagon, however, remains unclear. Here we show that, following its activation, CRTC2 enhances CREB phosphorylation through an association with the protein arginine methyltransferase 5 (PRMT5). In turn, PRMT5 was found to stimulate CREB phosphorylation via increases in histone H3 Arg2 methylation that enhanced chromatin accessibility at gluconeogenic promoters. Because depletion of PRMT5 lowers hepatic glucose production and gluconeogenic gene expression, these results demonstrate how a chromatin-modifying enzyme regulates a metabolic program through epigenetic changes that impact the phosphorylation of a transcription factor in response to hormonal stimuli.

  2. Plant perception and response to the signal in gravity resistance

    Science.gov (United States)

    Hoson, Takayuki; Soga, Kouichi; Wakabayashi, Kazuyuki; Kamisaka, Seiichiro; Zhang, Yan; Otomi, Yasuhiro; Hashimoto, Takashi; Iida, Hidetoshi

    2012-07-01

    Gravity resistance, mechanical resistance to the gravitational force, is a principal graviresponse in plants, distinct from gravitropism. Plants increase the rigidity of their cell walls in the final step of gravity resistance. We studied cellular events leading to or related to the cell wall changes under hypergravity conditions produced by centrifugation and under microgravity conditions in space. The involvement of mechanosensitive ion channels (mechanoreceptors) in signal perception in gravity resistance has been suggested by experiments with inhibitors. As a candidate for the mechanoreceptor, we identified MCA1 and MCA2 in Arabidopsis. mca-null and MCA-overexpressing seedlings were normal in growth in the dark at 1 g. However, suppression by hypergravity of elongation growth was reduced in hypocotyls of mca-null seedlings. On the contrary, MCA-overexpressing seedlings were hypersensitive to hypergravity. These results suggest that MCAs act as the mechanoreceptor in signal perception of gravity resistance. Cortical microtubules play an essential role in maintenance of normal growth phenotype under hypergravity conditions. In Space Seed experiment in the Kibo Module (PI: S. Kamisaka), we examined the effects of microgravity on growth phenotypes of Arabidopsis tubulin mutant, tua6. Inflorescences of the mutant emerged earlier and elongated rapidly under microgravity conditions than under on-orbit or ground 1 g conditions. Also, the inflorescences grown under microgravity conditions showed higher cell wall extensibilities than the controls. The tubulin mutant thus grew and developed more or less normally under microgravity conditions, supporting the principal role of microtubules also in plant resistance to 1 g gravity. On the other hand, the cellular osmotic properties, as well as the cell wall properties, are important factors determining the rigidity of plant body. Azuki bean epicotyls were capable of maintaining osmoregulation even under hypergravity

  3. The time-course of cortico-limbic neural responses to air hunger.

    Science.gov (United States)

    Binks, Andrew P; Evans, Karleyton C; Reed, Jeffrey D; Moosavi, Shakeeb H; Banzett, Robert B

    2014-12-01

    Several studies have mapped brain regions associated with acute dyspnea perception. However, the time-course of brain activity during sustained dyspnea is unknown. Our objective was to determine the time-course of neural activity when dyspnea is sustained. Eight healthy subjects underwent brain blood oxygen level dependent functional magnetic imaging (BOLD-fMRI) during mechanical ventilation with constant mild hypercapnia (∼ 45 mm Hg). Subjects rated dyspnea (air hunger) via visual analog scale (VAS). Tidal volume (V(T)) was alternated every 90 s between high VT (0.96 ± 0.23 L) that provided respiratory comfort (12 ± 6% full scale) and low V(T) (0.48 ± 0.08 L) which evoked air hunger (56 ± 11% full scale). BOLD signal was extracted from a priori brain regions and combined with VAS data to determine air hunger related neural time-course. Air hunger onset was associated with BOLD signal increases that followed two distinct temporal profiles within sub-regions of the anterior insula, anterior cingulate and prefrontal cortices (cortico-limbic circuitry): (1) fast, BOLD signal peak 40s. BOLD signal during air hunger offset followed fast and slow temporal profiles symmetrical, but inverse (signal decreases) to the time-courses of air hunger onset. We conclude that differential cortico-limbic circuit elements have unique contributions to dyspnea sensation over time. We suggest that previously unidentified sub-regions are responsible for either the acute awareness or maintenance of dyspnea. These data enhance interpretation of previous studies and inform hypotheses for future dyspnea research. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. The primary nitrate response: a multifaceted signalling pathway.

    Science.gov (United States)

    Medici, Anna; Krouk, Gabriel

    2014-10-01

    Nitrate (NO3(-)) application strongly affects gene expression in plants. This regulation is thought to be crucial for their adaptation in response to a changing nutritional environment. Depending on the conditions preceding or concomitant with nitrate provision, the treatment can affect up to a 10th of genome expression in Arabidopsis thaliana. The early events occurring after NO3(-) provision are often called the Primary Nitrate Response (PNR). Despite this simple definition, PNR is a complex process that is difficult to properly delineate. Here we report the different concepts related to PNR, review the different molecular components known to control it, and show, using meta-analysis, that this concept/pathway is not monolithic. We especially bring our attention to the genome-wide effects of LBD37 and LBD38 overexpression, NLP7, and CHL1/NRT1.1 mutations. © The Author 2014. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  5. Heat-Responsive Photosynthetic and Signaling Pathways in Plants: Insight from Proteomics

    Directory of Open Access Journals (Sweden)

    Xiaoli Wang

    2017-10-01

    Full Text Available Heat stress is a major abiotic stress posing a serious threat to plants. Heat-responsive mechanisms in plants are complicated and fine-tuned. Heat signaling transduction and photosynthesis are highly sensitive. Therefore, a thorough understanding of the molecular mechanism in heat stressed-signaling transduction and photosynthesis is necessary to protect crop yield. Current high-throughput proteomics investigations provide more useful information for underlying heat-responsive signaling pathways and photosynthesis modulation in plants. Several signaling components, such as guanosine triphosphate (GTP-binding protein, nucleoside diphosphate kinase, annexin, and brassinosteroid-insensitive I-kinase domain interacting protein 114, were proposed to be important in heat signaling transduction. Moreover, diverse protein patterns of photosynthetic proteins imply that the modulations of stomatal CO2 exchange, photosystem II, Calvin cycle, ATP synthesis, and chlorophyll biosynthesis are crucial for plant heat tolerance.

  6. Changes in BOLD and ADC weighted imaging in acute hypoxia during sea-level and altitude adapted states

    DEFF Research Database (Denmark)

    Rostrup, Egill; Larsson, Henrik B.W.; Born, Alfred P.

    2005-01-01

    possible structural changes as measured by diffusion weighted imaging. Eleven healthy sea-level residents were studied after 5 weeks of adaptation to high altitude conditions at Chacaltaya, Bolivia (5260 m). The subjects were studied immediately after return to sea-level in hypoxic and normoxic conditions......, and the examinations repeated 6 months later after re-adaptation to sea-level conditions. The BOLD response, measured at 1.5 T, was severely reduced during acute hypoxia both in the altitude and sea-level adapted states (50% reduction during an average S(a)O(2) of 75%). On average, the BOLD response magnitude was 23......% lower in altitude than sea-level adaptation in the normoxic condition, but in the hypoxic condition, no significant differences were found. A small but statistically significant decrease in the apparent diffusion coefficient (ADC) was seen in some brain regions during acute hypoxia, whereas ADC...

  7. Neural responses to multimodal ostensive signals in 5-month-old infants.

    Directory of Open Access Journals (Sweden)

    Eugenio Parise

    Full Text Available Infants' sensitivity to ostensive signals, such as direct eye contact and infant-directed speech, is well documented in the literature. We investigated how infants interpret such signals by assessing common processing mechanisms devoted to them and by measuring neural responses to their compounds. In Experiment 1, we found that ostensive signals from different modalities display overlapping electrophysiological activity in 5-month-old infants, suggesting that these signals share neural processing mechanisms independently of their modality. In Experiment 2, we found that the activation to ostensive signals from different modalities is not additive to each other, but rather reflects the presence of ostension in either stimulus stream. These data support the thesis that ostensive signals obligatorily indicate to young infants that communication is directed to them.

  8. Bidirectional coupling of splicing and ATM signaling in response to transcription-blocking DNA damage

    NARCIS (Netherlands)

    M. Tresini (Maria); J.A. Marteijn (Jurgen); W. Vermeulen (Wim)

    2016-01-01

    textabstractIn response to DNA damage cells activate intricate protein networks to ensure genomic fidelity and tissue homeostasis. DNA damage response signaling pathways coordinate these networks and determine cellular fates, in part, by modulating RNA metabolism. Here we discuss a

  9. Connectivity Reveals Sources of Predictive Coding Signals in Early Visual Cortex During Processing of Visual Optic Flow.

    Science.gov (United States)

    Schindler, Andreas; Bartels, Andreas

    2017-05-01

    Superimposed on the visual feed-forward pathway, feedback connections convey higher level information to cortical areas lower in the hierarchy. A prominent framework for these connections is the theory of predictive coding where high-level areas send stimulus interpretations to lower level areas that compare them with sensory input. Along these lines, a growing body of neuroimaging studies shows that predictable stimuli lead to reduced blood oxygen level-dependent (BOLD) responses compared with matched nonpredictable counterparts, especially in early visual cortex (EVC) including areas V1-V3. The sources of these modulatory feedback signals are largely unknown. Here, we re-examined the robust finding of relative BOLD suppression in EVC evident during processing of coherent compared with random motion. Using functional connectivity analysis, we show an optic flow-dependent increase of functional connectivity between BOLD suppressed EVC and a network of visual motion areas including MST, V3A, V6, the cingulate sulcus visual area (CSv), and precuneus (Pc). Connectivity decreased between EVC and 2 areas known to encode heading direction: entorhinal cortex (EC) and retrosplenial cortex (RSC). Our results provide first evidence that BOLD suppression in EVC for predictable stimuli is indeed mediated by specific high-level areas, in accord with the theory of predictive coding. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  10. Vascular Reactivity Maps in Patients with Gliomas Using Breath-Holding BOLD fMRI.

    Science.gov (United States)

    Iranmahboob, Amir; Peck, Kyung K; Brennan, Nicole P; Karimi, Sasan; Fisicaro, Ryan; Hou, Bob; Holodny, Andrei I

    2016-01-01

    To evaluate whether breath-holding (BH) blood oxygenation level-dependent (BOLD) fMRI can quantify differences in vascular reactivity (VR), as there is a need for improved contrast mechanisms in gliomas. 16 patients (gliomas, grade II = 5, III = 2, IV = 9) were evaluated using the BH paradigm: 4-second single deep breath followed by 16 seconds of BH and 40 seconds of regular breathing for five cycles. VR was defined as the difference in BOLD signal between the minimal signal seen at the end of the deep breath and maximal signal seen at the end of BH (peak-to-trough). VR was measured for every voxel and compared for gray versus white matter and tumor versus normal contralateral brain. VR maps were compared to the areas of enhancement and FLAIR/T2 abnormality. VR was significantly lower in normal white matter than gray matter (P < .05) and in tumors compared to the normal, contralateral brain (P < 0.002). The area of abnormal VR (1103 ± 659 mm²) was significantly greater (P = .019) than the enhancement (543 ± 530 mm²), but significantly smaller (P = .0011) than the FLAIR abnormality (2363 ± 1232 mm²). However, the variability in the areas of gadolinium contrast enhancement versus VR abnormality indicates that the contrast mechanism elicited by BH (caused by abnormal arteriolar smooth muscles) appears to be fundamentally different from the contrast mechanism of gadolinium enhancement (caused by the presence of "leaky" gap junctions). BH maps based on peak-to-trough can be used to characterize VR in brain tumors. VR maps in brain tumor patients appear to be caused by a different mechanism than gadolinium enhancement.

  11. Brain signal variability is modulated as a function of internal and external demand in younger and older adults.

    Science.gov (United States)

    Grady, Cheryl L; Garrett, Douglas D

    2018-04-01

    Variability in the Blood Oxygen-Level Dependent (BOLD) signal from fMRI is often associated with better cognitive performance and younger age. It has been proposed that neural variability enables flexible responding to uncertainty in a changing environment. However, signal variability reflecting environmental uncertainty may reduce to the extent that a task depends on internally-directed attention and is supported by neural "solutions" that are schematic and relatively stable within each individual. Accordingly, we examined the hypothesis that BOLD variability will be low at rest, higher during internally-directed tasks, and higher still during externally-directed tasks, and that this effect will be reduced with aging. Modulation of BOLD variability across conditions was consistent with these hypotheses, and was associated with faster and more stable behavioral performance in both young and older adults. These data support the idea that brain signal variability may modulate in response to environmental uncertainty, which is presumed to be greater in the external environment than in the internal milieu. Reduced flexibility of signal variability with age may indicate less ability to switch between internal and external brain states. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Smart, Bold Reform for Powerful Schools

    Science.gov (United States)

    Cahill, Michelle

    2009-01-01

    Over the past 10 years, the author has spent time in hundreds of high schools reviewing data; observing classes; learning about interventions and whole-school reforms; and speaking with principals, teachers, counselors, and students. She has also been a district leader in New York City responsible for high school reform that has achieved promising…

  13. A predation cost to bold fish in the wild

    DEFF Research Database (Denmark)

    Hulthén, Kaj; Chapman, Ben; Nilsson, Anders P.

    2017-01-01

    Studies of predator-mediated selection on behaviour are critical for our understanding of the evolution and maintenance of behavioural diversity in natural populations. Consistent individual differences in prey behaviour, especially in the propensity to take risks ("boldness"), are widespread...... in the animal kingdom. Theory predicts that individual behavioural types differ in a cost-benefit trade-off where bolder individuals benefit from greater access to resources while paying higher predation-risk costs. However, explicitly linking predation events to individual behaviour under natural conditions...... evidence of behavioural type-dependent predation vulnerability in the wild, i.e. that there is a predation cost to boldness, which is critical for our understanding of the evolution and maintenance of behavioural diversity in natural populations....

  14. The Yeast Retrograde Response as a Model of Intracellular Signaling of Mitochondrial Dysfunction

    Directory of Open Access Journals (Sweden)

    S. Michal eJazwinski

    2012-05-01

    Full Text Available Mitochondrial dysfunction activates intracellular signaling pathways that impact yeast longevity, and the best known of these pathways is the retrograde response. More recently, similar responses have been discerned in other systems, from invertebrates to human cells. However, the identity of the signal transducers is either unknown or apparently diverse, contrasting with the well-established signaling module of the yeast retrograde response. On the other hand, it has become equally clear that several other pathways and processes interact with the retrograde response, embedding it in a network responsive to a variety of cellular states. An examination of this network supports the notion that the master regulator NFkB aggregated a variety of mitochondria-related cellular responses at some point in evolution and has become the retrograde transcription factor. This has significant consequences for how we view some of the deficits associated with aging, such as inflammation. The support for NFkB as the retrograde response transcription factor is not only based on functional analyses. It is bolstered by the fact that NFkB can regulate Myc-Max, which is activated in human cells with dysfunctional mitochondria and impacts cellular metabolism. Myc-Max is homologous to the yeast retrograde response transcription factor Rtg1-Rtg3. Further research will be needed to disentangle the pro-aging from the anti-aging effects of NFkB. Interestingly, this is also a challenge for the complete understanding of the yeast retrograde response.

  15. MAPK ERK signaling regulates the TGF-beta1-dependent mosquito response to Plasmodium falciparum.

    OpenAIRE

    Win Surachetpong; Naresh Singh; Kong Wai Cheung; Shirley Luckhart

    2009-01-01

    Malaria is caused by infection with intraerythrocytic protozoa of the genus Plasmodium that are transmitted by Anopheles mosquitoes. Although a variety of anti-parasite effector genes have been identified in anopheline mosquitoes, little is known about the signaling pathways that regulate these responses during parasite development. Here we demonstrate that the MEK-ERK signaling pathway in Anopheles is controlled by ingested human TGF-beta1 and finely tunes mosquito innate immunity to parasit...

  16. The internal state of medium spiny neurons varies in response to different input signals

    Directory of Open Access Journals (Sweden)

    Miller Gary W

    2010-03-01

    Full Text Available Abstract Background Parkinson's disease, schizophrenia, Huntington's chorea and drug addiction are manifestations of malfunctioning neurons within the striatum region at the base of the human forebrain. A key component of these neurons is the protein DARPP-32, which receives and processes various types of dopamine and glutamate inputs and translates them into specific biochemical, cellular, physiological, and behavioral responses. DARPP-32's unique capacity of faithfully converting distinct neurotransmitter signals into appropriate responses is achieved through a complex phosphorylation-dephosphorylation system that evades intuition and predictability. Results To gain deeper insights into the functioning of the DARPP-32 signal transduction system, we developed a dynamic model that is robust and consistent with available clinical, pharmacological, and biological observations. Upon validation, the model was first used to explore how different input signal scenarios are processed by DARPP-32 and translated into distinct static and dynamic responses. Secondly, a comprehensive perturbation analysis identified the specific role of each component on the system's signal transduction ability. Conclusions Our study investigated the effects of various patterns of neurotransmission on signal integration and interpretation by DARPP-32 and showed that the DARPP-32 system has the capability of discerning surprisingly many neurotransmission scenarios. We also screened out potential mechanisms underlying this capability of the DARPP-32 system. This type of insight deepens our understanding of neuronal signal transduction in normal medium spiny neurons, sheds light on neurological disorders associated with the striatum, and might aid the search for intervention targets in neurological diseases and drug addiction.

  17. ETHYLENE RESPONSE FACTOR1 Integrates Signals from Ethylene and Jasmonate Pathways in Plant DefenseW⃞

    Science.gov (United States)

    Lorenzo, Oscar; Piqueras, Raquel; Sánchez-Serrano, Jose J.; Solano, Roberto

    2003-01-01

    Cross-talk between ethylene and jasmonate signaling pathways determines the activation of a set of defense responses against pathogens and herbivores. However, the molecular mechanisms that underlie this cross-talk are poorly understood. Here, we show that ethylene and jasmonate pathways converge in the transcriptional activation of ETHYLENE RESPONSE FACTOR1 (ERF1), which encodes a transcription factor that regulates the expression of pathogen response genes that prevent disease progression. The expression of ERF1 can be activated rapidly by ethylene or jasmonate and can be activated synergistically by both hormones. In addition, both signaling pathways are required simultaneously to activate ERF1, because mutations that block any of them prevent ERF1 induction by any of these hormones either alone or in combination. Furthermore, 35S:ERF1 expression can rescue the defense response defects of coi1 (coronative insensitive1) and ein2 (ethylene insensitive2); therefore, it is a likely downstream component of both ethylene and jasmonate signaling pathways. Transcriptome analysis in Col;35S:ERF1 transgenic plants and ethylene/jasmonate-treated wild-type plants further supports the notion that ERF1 regulates in vivo the expression of a large number of genes responsive to both ethylene and jasmonate. These results suggest that ERF1 acts downstream of the intersection between ethylene and jasmonate pathways and suggest that this transcription factor is a key element in the integration of both signals for the regulation of defense response genes. PMID:12509529

  18. Hormone response element binding proteins: novel regulators of vitamin D and estrogen signaling.

    Science.gov (United States)

    Lisse, Thomas S; Hewison, Martin; Adams, John S

    2011-03-01

    Insights from vitamin D-resistant New World primates and their human homologues as models of natural and pathological insensitivity to sterol/steroid action have uncovered a family of novel intracellular vitamin D and estrogen regulatory proteins involved in hormone action. The proteins, known as "vitamin D or estrogen response element-binding proteins", behave as potent cis-acting, transdominant regulators to inhibit steroid receptor binding to DNA response elements and is responsible for vitamin D and estrogen resistances. This set of interactors belongs to the heterogeneous nuclear ribonucleoprotein (hnRNP) family of previously known pre-mRNA-interacting proteins. This review provides new insights into the mechanism by which these novel regulators of signaling and metabolism can act to regulate responses to vitamin D and estrogen. In addition the review also describes other molecules that are known to influence nuclear receptor signaling through interaction with hormone response elements. Copyright © 2011 Elsevier Inc. All rights reserved.

  19. Impaired cerebral vasoreactivity to CO2 in Alzheimer's disease using BOLD fMRI.

    Science.gov (United States)

    Cantin, S; Villien, M; Moreaud, O; Tropres, I; Keignart, S; Chipon, E; Le Bas, J-F; Warnking, J; Krainik, A

    2011-09-15

    To evaluate the cerebral vasoreactivity using blood oxygenation level dependent functional MRI during carbogen inhalation with 7% CO(2) in Alzheimer's disease and amnestic mild cognitive impairment. Thirty nine subjects were included to be investigated using blood oxygenation level dependent (BOLD) functional MRI at 1.5T during a block-design carbogen inhalation paradigm, with a high concentration face-mask under physiological monitoring. Basal cerebral perfusion was measured using pulsed arterial spin labeling. Image analyses were conducted using Matlab® and SPM5 with physiological regressors and corrected for partial volume effect. Among selected participants, 12 subjects were excluded because of incomplete protocol, leaving for analysis 27 subjects without significant microangiopathy diagnosed for Alzheimer's disease (n=9), amnestic mild cognitive impairment (n=7), and matched controls (n=11). No adverse reaction related to the CO(2) challenge was reported. Carbogen inhalation induced a whole-brain signal increase, predominant in the gray matter. In patients, signal changes corrected for gray matter partial volume were decreased (0.36±0.13% BOLD/mmHg in Alzheimer's disease, 0.36±0.12 in patients with mild cognitive impairment, 0.62±0.20 in controls). Cerebral vasoreactivity impairments were diffuse but seemed predominant in posterior areas. The basal hypoperfusion in Alzheimer's disease was not significantly different from patients with mild cognitive impairment and controls. Among clinical and biological parameters, no effect of apoE4 genotype was detected. Cerebral vasoreactivity values were correlated with cognitive performances and hippocampal volumes. Among age and hippocampal atrophy, mean CVR was the best predictor of the mini-mental status examination. This BOLD functional MRI study on CO(2) challenge shows impaired cerebral vasoreactivity in patients with Alzheimer's disease and amnestic mild cognitive impairment at the individual level. These

  20. Population response characteristics of intrinsic signals in the cat somatosensory cortex following canine mechanical stimulation.

    Science.gov (United States)

    Tao, Jianxiang; Wang, Jian; Li, Zhong; Meng, Jianjun; Yu, Hongbo

    2016-08-04

    Intrinsic signal optical imaging has been widely used to measure functional maps in various sensory cortices due to better spatial resolution and sensitivity for detecting cortical neuroplasticity. However, application of this technique in dentistry has not been reported. In this study, intrinsic signal optical imaging was used to investigate mechanically driven responses in the cat somatosensory cortex, when punctate mechanical stimuli were applied to maxillary canines. The global signal and its spatial organization pattern were obtained. Global signal strength gradually increased with stimulus strength. There was no significant difference in response strength between contralateral and ipsilateral mechanical stimulation. A slightly greater response was recorded in the sigmoidal gyrus than in the coronal gyrus. The cat somatosensory cortex activated by sensory inputs from mechanical stimulation of canines lacks both topographical and functional organization. It is not organized into columns that represent sensory input from each tooth or direction of stimulation. These results demonstrate that intrinsic signal optical imaging is a valid tool for investigating neural responses and neuroplasticity in the somatosensory cortex that represents teeth. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  1. PI3K Signaling and Stat92E Converge to Modulate Glial Responsiveness to Axonal Injury

    Science.gov (United States)

    Doherty, Johnna; Sheehan, Amy E.; Bradshaw, Rachel; Fox, A. Nicole; Lu, Tsai-Yi; Freeman, Marc R.

    2014-01-01

    Glial cells are exquisitely sensitive to neuronal injury but mechanisms by which glia establish competence to respond to injury, continuously gauge neuronal health, and rapidly activate reactive responses remain poorly defined. Here, we show glial PI3K signaling in the uninjured brain regulates baseline levels of Draper, a receptor essential for Drosophila glia to sense and respond to axonal injury. After injury, Draper levels are up-regulated through a Stat92E-modulated, injury-responsive enhancer element within the draper gene. Surprisingly, canonical JAK/STAT signaling does not regulate draper expression. Rather, we find injury-induced draper activation is downstream of the Draper/Src42a/Shark/Rac1 engulfment signaling pathway. Thus, PI3K signaling and Stat92E are critical in vivo regulators of glial responsiveness to axonal injury. We provide evidence for a positive auto-regulatory mechanism whereby signaling through the injury-responsive Draper receptor leads to Stat92E-dependent, transcriptional activation of the draper gene. We propose that Drosophila glia use this auto-regulatory loop as a mechanism to adjust their reactive state following injury. PMID:25369313

  2. Model-Based Synthesis of Locally Contingent Responses to Global Market Signals

    Directory of Open Access Journals (Sweden)

    Nicholas R. Magliocca

    2015-09-01

    Full Text Available Rural livelihoods and the land systems on which they depend are increasingly influenced by distant markets through economic globalization. Place-based analyses of land and livelihood system sustainability must then consider both proximate and distant influences on local decision-making. Thus, advancing land change theory in the context of economic globalization calls for a systematic understanding of the general processes as well as local contingencies shaping local responses to global signals. Synthesis of insights from place-based case studies is a path forward for developing such systematic knowledge. This paper introduces a generalized agent-based modeling framework for model-based synthesis to investigate the relative importance of structural versus agent-level factors in driving land-use and livelihood responses to changing global market signals. Six case-study sites that differed in environmental conditions, market access and influence, and livelihood settings were analyzed. Stronger market signals generally led to intensification and/or expansion of agriculture or increased non-farm labor, while changes in agents’ risk attitudes prompted heterogeneous local responses to global market signals. These results demonstrate model-based synthesis as a promising approach to overcome many of the challenges of current synthesis methods in land change science and identify generalized as well as locally contingent responses to global market signals.

  3. Satiation attenuates BOLD activity in brain regions involved in reward and increases activity in dorsolateral prefrontal cortex: an fMRI study in healthy volunteers.

    Science.gov (United States)

    Thomas, Jason M; Higgs, Suzanne; Dourish, Colin T; Hansen, Peter C; Harmer, Catherine J; McCabe, Ciara

    2015-04-01

    Neural responses to rewarding food cues are significantly different in the fed vs. fasted (>8 h food-deprived) state. However, the effect of eating to satiety after a shorter (more natural) intermeal interval on neural responses to both rewarding and aversive cues has not been examined. With the use of a novel functional magnetic resonance imaging (fMRI) task, we investigated the effect of satiation on neural responses to both rewarding and aversive food tastes and pictures. Sixteen healthy participants (8 men, 8 women) were scanned on 2 separate test days, before and after eating a meal to satiation or after not eating for 4 h (satiated vs. premeal). fMRI blood oxygen level-dependent (BOLD) signals to the sight and/or taste of the stimuli were recorded. A whole-brain cluster-corrected analysis (P analysis showed that the vmPFC was more highly connected to the dlPFC when individuals were exposed to food stimuli when satiated than when not satiated. These results suggest that natural satiation attenuates activity in reward-related brain regions and increases activity in the dlPFC, which may reflect a "top down" cognitive influence on satiation. This trial was registered at clinicaltrials.gov as NCT02298049. © 2015 American Society for Nutrition.

  4. Astrocyte-to-neuron signaling in response to photostimulation with a femtosecond laser

    Science.gov (United States)

    Zhao, Yuan; Liu, Xiuli; Zhou, Wei; Zeng, Shaoqun

    2010-08-01

    Conventional stimulation techniques used in studies of astrocyte-to-neuron signaling are invasive or dependent on additional electrical devices or chemicals. Here, we applied photostimulation with a femtosecond laser to selectively stimulate astrocytes in the hippocampal neural network, and the neuronal responses were examined. The results showed that, after photostimulation, cell-specific astrocyte-to-neuron signaling was triggered; sometimes the neuronal responses were even synchronous. Since photostimulation with a femtosecond laser is noninvasive, agent-free, and highly precise, this method has been proved to be efficient in activating astrocytes for investigations of astrocytic functions in neural networks.

  5. GA(3) enhances root responsiveness to exogenous IAA by modulating auxin transport and signalling in Arabidopsis.

    Science.gov (United States)

    Li, Guijun; Zhu, Changhua; Gan, Lijun; Ng, Denny; Xia, Kai

    2015-03-01

    We used auxin-signalling mutants, auxin transport mutants, and auxin-related marker lines to show that exogenously applied GA enhances auxin-induced root inhibition by affecting auxin signalling and transport. Variation in root elongation is valuable when studying the interactions of phytohormones. Auxins influence the biosynthesis and signalling of gibberellins (GAs), but the influence of GAs on auxins in root elongation is poorly understood. This study was conducted to investigate the effect of GA3 on Arabidopsis root elongation in the presence of auxin. Root elongation was inhibited in roots treated with both IAA and GA3, compared to IAA alone, and the effect was dose dependent. Further experiments showed that GA3 could modulate auxin signalling based on root elongation in auxin-signalling mutants and the expression of auxin-responsive reporters. The GA3-enhanced inhibition of root elongation observed in the wild type was not found in the auxin-signalling mutants tir1-1 and axr1-3. GA3 increased DR5::GUS expression in the root meristem and elongation zones, and IAA2::GUS in the columella. The DR5rev::GFP signal was enhanced in columella cells of the root caps and in the elongation zone in GA3-treated seedling roots. A reduction was observed in the stele of PAC-treated roots. We also examined the effect of GA3 on auxin transport. The enhanced responsiveness caused by GA3 was not observed in the auxin influx mutant aux1-7 or the efflux mutant eir1-1. Additional molecular data demonstrated that GA3 could promote auxin transport via AUX1 and PIN proteins. However, GA3-induced PIN gene expression did not fully explain GA-enhanced PIN protein accumulation. These results suggest that GA3 is involved in auxin-mediated primary root elongation by modulating auxin signalling and transport, and thus enhances root responsiveness to exogenous IAA.

  6. Sphingosine-1-Phosphate Signaling Regulates Myogenic Responsiveness in Human Resistance Arteries.

    Directory of Open Access Journals (Sweden)

    Sonya Hui

    Full Text Available We recently identified sphingosine-1-phosphate (S1P signaling and the cystic fibrosis transmembrane conductance regulator (CFTR as prominent regulators of myogenic responsiveness in rodent resistance arteries. However, since rodent models frequently exhibit limitations with respect to human applicability, translation is necessary to validate the relevance of this signaling network for clinical application. We therefore investigated the significance of these regulatory elements in human mesenteric and skeletal muscle resistance arteries. Mesenteric and skeletal muscle resistance arteries were isolated from patient tissue specimens collected during colonic or cardiac bypass surgery. Pressure myography assessments confirmed endothelial integrity, as well as stable phenylephrine and myogenic responses. Both human mesenteric and skeletal muscle resistance arteries (i express critical S1P signaling elements, (ii constrict in response to S1P and (iii lose myogenic responsiveness following S1P receptor antagonism (JTE013. However, while human mesenteric arteries express CFTR, human skeletal muscle resistance arteries do not express detectable levels of CFTR protein. Consequently, modulating CFTR activity enhances myogenic responsiveness only in human mesenteric resistance arteries. We conclude that human mesenteric and skeletal muscle resistance arteries are a reliable and consistent model for translational studies. We demonstrate that the core elements of an S1P-dependent signaling network translate to human mesenteric resistance arteries. Clear species and vascular bed variations are evident, reinforcing the critical need for further translational study.

  7. Toward a mechanistic understanding of vulnerability to hook-and-line fishing: Boldness as the basic target of angling-induced selection.

    Science.gov (United States)

    Klefoth, Thomas; Skov, Christian; Kuparinen, Anna; Arlinghaus, Robert

    2017-12-01

    In passively operated fishing gear, boldness-related behaviors should fundamentally affect the vulnerability of individual fish and thus be under fisheries selection. To test this hypothesis, we used juvenile common-garden reared carp ( Cyprinus carpio ) within a narrow size range to investigate the mechanistic basis of behavioral selection caused by angling. We focused on one key personality trait (i.e., boldness), measured in groups within ponds, two morphological traits (body shape and head shape), and one life-history trait (juvenile growth capacity) and studied mean standardized selection gradients caused by angling. Carp behavior was highly repeatable within ponds. In the short term, over seven days of fishing, total length, not boldness, was the main predictor of angling vulnerability. However, after 20 days of fishing, boldness turned out to be the main trait under selection, followed by juvenile growth rate, while morphological traits were only weakly related to angling vulnerability. In addition, we found juvenile growth rate to be moderately correlated with boldness. Hence, direct selection on boldness will also induce indirect selection on juvenile growth and vice versa, but given that the two traits are not perfectly correlated, independent evolution of both traits is also possible. Our study is among the first to mechanistically reveal that energy-acquisition-related behaviors, and not growth rate per se, are key factors determining the probability of capture, and hence, behavioral traits appear to be the prime targets of angling selection. We predict an evolutionary response toward increased shyness in intensively angling-exploited fish stocks, possibly causing the emergence of a timidity syndrome.

  8. [Analysis of the factors influencing the response of the skin to audio signals].

    Science.gov (United States)

    Cao, Lijia; Li, Jianwen

    2011-06-01

    Skin-hearing aid is a new type of electronic product, which can improve hearing for deaf patients. It is different from audiphones and cochlear implant. The instrument makes use of the effect of the skin response to audio signals. The working process of the instrument is as following. Firstly, the sound signal is converted to audio signal by microphone, then through the power amplifier and booster. Then the signal is transmitted to the brain via skin by electrodes. And finally the hearing is formed. As skin-hearing aid transmits signals through the skin by the electrodes, the intensity of the skin resistance becomes the main factor influencing the response of the skin to audio signal. Skin resistance depends mainly upon the stratum corneum. This article aims to discuss the factors affecting the skin resistance, such as the thickness of the stratum corneum, hydration level of stratum corneum, the relation of audio frequency and skin resistance, and the skin resistance of acupuncture points.

  9. From Chaos to Harmony: Responses and Signaling upon Microbial Pattern Recognition.

    Science.gov (United States)

    Yu, Xiao; Feng, Baomin; He, Ping; Shan, Libo

    2017-08-04

    Pathogen- or microbe-associated molecular patterns (PAMPs/MAMPs) are detected as nonself by host pattern recognition receptors (PRRs) and activate pattern-triggered immunity (PTI). Microbial invasions often trigger the production of host-derived endogenous signals referred to as danger- or damage-associated molecular patterns (DAMPs), which are also perceived by PRRs to modulate PTI responses. Collectively, PTI contributes to host defense against infections by a broad range of pathogens. Remarkable progress has been made toward demonstrating the cellular and physiological responses upon pattern recognition, elucidating the molecular, biochemical, and genetic mechanisms of PRR activation, and dissecting the complex signaling networks that orchestrate PTI responses. In this review, we present an update on the current understanding of how plants recognize and respond to nonself patterns, a process from which the seemingly chaotic responses form into a harmonic defense.

  10. Arabidopsis mutants affecting oxylipin signaling in photo-oxidative stress responses.

    Science.gov (United States)

    Satoh, Masanori; Tokaji, Yoshihito; Nagano, Atsushi J; Hara-Nishimura, Ikuko; Hayashi, Makoto; Nishimura, Mikio; Ohta, Hiroyuki; Masuda, Shinji

    2014-08-01

    Plant oxylipins derive from oxygenation of polyunsaturated fatty acids in thylakoid membranes and oxylipins such as jasmonic acid (JA) and 12-oxo-phytodienoic acid (OPDA) play important roles in adaptation to photo-oxidative stress. OPDA functions both as a JA precursor and as a biologically active signaling molecule that induces expression of a specific set of genes. These genes can be induced by OPDA in the JA-insensitive coronatine insensitive1 (coi1) mutant, suggesting that there is an alternative pathway for OPDA signaling, independent of COI1-dependent JA signaling. However, little is known about OPDA signaling in photo-oxidative stress responses. In this study, we isolated Arabidopsis mutants with constitutively enhanced expression from the OPDA-responsive HsfA2 promoter. We used deletion mapping and complementation analysis to identify one responsible gene as CATALASE2. Our results thus indicate that ROS-producing cellular metabolism links to OPDA signaling. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  11. Arsenic Alters ATP-Dependent Ca2+ Signaling in Human Airway Epithelial Cell Wound Response

    Science.gov (United States)

    Sherwood, Cara L.; Lantz, R. Clark; Burgess, Jefferey L.; Boitano, Scott

    2011-01-01

    Arsenic is a natural metalloid toxicant that is associated with occupational inhalation injury and contaminates drinking water worldwide. Both inhalation of arsenic and consumption of arsenic-tainted water are correlated with malignant and nonmalignant lung diseases. Despite strong links between arsenic and respiratory illness, underlying cell responses to arsenic remain unclear. We hypothesized that arsenic may elicit some of its detrimental effects on the airway through limitation of innate immune function and, specifically, through alteration of paracrine ATP (purinergic) Ca2+ signaling in the airway epithelium. We examined the effects of acute (24 h) exposure with environmentally relevant levels of arsenic (i.e., arsenic reduces purinergic Ca2+ signaling in a dose-dependent manner and results in a reshaping of the Ca2+ signaling response to localized wounds. We next examined arsenic effects on two purinergic receptor types: the metabotropic P2Y and ionotropic P2X receptors. Arsenic inhibited both P2Y- and P2X-mediated Ca2+ signaling responses to ATP. Both inhaled and ingested arsenic can rapidly reach the airway epithelium where purinergic signaling is essential in innate immune functions (e.g., ciliary beat, salt and water transport, bactericide production, and wound repair). Arsenic-induced compromise of such airway defense mechanisms may be an underlying contributor to chronic lung disease. PMID:21357385

  12. Evoked responses of the superior olive to amplitude-modulated signals.

    Science.gov (United States)

    Andreeva, N G; Lang, T T

    1977-01-01

    Evoked potentials of some auditory centers of Rhinolophidae bats to amplitude-modulated signals were studied. A synchronization response was found in the cochlear nuclei (with respect to the fast component of the response) and in the superior olivary complex (with respect to both fast and slow components of the response) within the range of frequency modulation from 50 to 2000 Hz. In the inferior colliculus a synchronized response was recorded at modulation frequencies below 150 Hz, but in the medial geniculate bodies no such response was found. Evoked responses of the superior olivary complex were investigated in detail. The lowest frequencies of synchronization were recorded within the carrier frequency range of 15-30 and 80-86 kHz. The amplitude of the synchronized response is a function of the frequency and coefficient of modulation and also of the angle of stimulus presentation.

  13. Visual cortex and auditory cortex activation in early binocularly blind macaques: A BOLD-fMRI study using auditory stimuli.

    Science.gov (United States)

    Wang, Rong; Wu, Lingjie; Tang, Zuohua; Sun, Xinghuai; Feng, Xiaoyuan; Tang, Weijun; Qian, Wen; Wang, Jie; Jin, Lixin; Zhong, Yufeng; Xiao, Zebin

    2017-04-15

    Cross-modal plasticity within the visual and auditory cortices of early binocularly blind macaques is not well studied. In this study, four healthy neonatal macaques were assigned to group A (control group) or group B (binocularly blind group). Sixteen months later, blood oxygenation level-dependent functional imaging (BOLD-fMRI) was conducted to examine the activation in the visual and auditory cortices of each macaque while being tested using pure tones as auditory stimuli. The changes in the BOLD response in the visual and auditory cortices of all macaques were compared with immunofluorescence staining findings. Compared with group A, greater BOLD activity was observed in the bilateral visual cortices of group B, and this effect was particularly obvious in the right visual cortex. In addition, more activated volumes were found in the bilateral auditory cortices of group B than of group A, especially in the right auditory cortex. These findings were consistent with the fact that there were more c-Fos-positive cells in the bilateral visual and auditory cortices of group B compared with group A (p visual cortices of binocularly blind macaques can be reorganized to process auditory stimuli after visual deprivation, and this effect is more obvious in the right than the left visual cortex. These results indicate the establishment of cross-modal plasticity within the visual and auditory cortices. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  14. SU-D-207A-03: Potential Role of BOLD MRI in Discrimination of Aggressive Tumor Habitat in Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Ford, J; Lopez, C; Tschudi, Y; Breto, A; Padgett, K; Pollack, A; Stoyanova, R [University of Miami Miller School of Medicine, Miami, FL (United States)

    2016-06-15

    Purpose: To determine whether blood oxygenation level dependent (BOLD) MRI signal measured in prostate cancer patients, in addition to quantitative diffusion and perfusion parameters from multiparametric (mp)MRI exams, can help discriminate aggressive and/or radioresistant lesions. Methods: Several ongoing clinical trials in our institution require mpMRI exam to determine eligibility (presence of identifiable tumor lesion on mpMRI) and prostate volumes for dose escalation. Upon consent, patients undergo fiducial markers placement and a T2*-weighted imaging at the time of CT sim to facilitate the fusion. In a retrospective analysis eleven clinical trial patients were identified who had undergone mpMRI on GE 3T magnet, followed by T2*-weighted imaging (time-period mean±SD = 48±20 days) using a consistent protocol (gradient echo, TR/TE=30/11.8ms, flip angle=12, matrix=256×256×75, voxel size=1.25×1.25×2.5mm). ROIs for prostate tumor lesions were automatically determined using ADC threshold ≤1200 µm2/s. Although the MR protocol was not intended for BOLD analysis, we utilized the T2*-weighted signal normalized to that in nearby muscle; likewise, T2-weighted lesion signal was normalized to muscle, following rigid registration of the T2 to T2* images. The ratio of these normalized signals, T2*/T2, is a measure of BOLD effect in the prostate tumors. Perfusion parameters (Ktrans, ve, kep) were also calculated. Results: T2*/T2 (mean±SE) was found to be substantially lower for Gleason score (GS) 8&9 (0.82±0.04) compared to GS 7 (1.08±0.07). A k-means cluster analysis of T2*/T2 versus kep = Ktrans/ve revealed two distinct clusters, one with higher T2*/T2 and lower kep, containing only GS 7 lesions, and another with lower T2*/T2 and higher kep, associated with tumor aggressiveness. This latter cluster contained all GS 8&9 lesions, as well as some GS 7. Conclusion: BOLD MRI, in addition to ADC and kep, may play a role (perhaps orthogonal to Gleason score) in

  15. Dopamine reward prediction-error signalling: a two-component response

    Science.gov (United States)

    Schultz, Wolfram

    2017-01-01

    Environmental stimuli and objects, including rewards, are often processed sequentially in the brain. Recent work suggests that the phasic dopamine reward prediction-error response follows a similar sequential pattern. An initial brief, unselective and highly sensitive increase in activity unspecifically detects a wide range of environmental stimuli, then quickly evolves into the main response component, which reflects subjective reward value and utility. This temporal evolution allows the dopamine reward prediction-error signal to optimally combine speed and accuracy. PMID:26865020

  16. Electrical signaling, stomatal conductance, ABA and Ethylene content in avocado trees in response to root hypoxia

    OpenAIRE

    Gil, Pilar M; Gurovich, Luis; Schaffer, Bruce; García, Nicolás; Iturriaga, Rodrigo

    2009-01-01

    Avocado (Persea americana Mill.) trees are among the most sensitive of fruit tree species to root hypoxia as a result of flooded or poorly drained soil. Similar to drought stress, an early physiological response to root hypoxia in avocado is a reduction of stomatal conductance. It has been previously determined in avocado trees that an extracellular electrical signal between the base of stem and leaves is produced and related to reductions in stomatal conductance in response to drought stress...

  17. Host plant defense signaling in response to a coevolved herbivore combats introduced herbivore attack

    OpenAIRE

    Woodard, Anastasia M; Ervin, Gary N; Marsico, Travis D

    2012-01-01

    Defense-free space resulting from coevolutionarily naïve host plants recently has been implicated as a factor facilitating invasion success of some insect species. Host plants, however, may not be entirely defenseless against novel herbivore threats. Volatile chemical-mediated defense signaling, which allows plants to mount specific, rapid, and intense responses, may play a role in systems experiencing novel threats. Here we investigate defense responses of host plants to a native and exotic ...

  18. Emergency Spatiotemporal Shift: The Response of Protein Kinase D to Stress Signals in the Cardiovascular System.

    Science.gov (United States)

    Wood, Brent M; Bossuyt, Julie

    2017-01-01

    Protein Kinase D isoforms (PKD 1-3) are key mediators of neurohormonal, oxidative, and metabolic stress signals. PKDs impact a wide variety of signaling pathways and cellular functions including actin dynamics, vesicle trafficking, cell motility, survival, contractility, energy substrate utilization, and gene transcription. PKD activity is also increasingly linked to cancer, immune regulation, pain modulation, memory, angiogenesis, and cardiovascular disease. This increasing complexity and diversity of PKD function, highlights the importance of tight spatiotemporal control of the kinase via protein-protein interactions, post-translational modifications or targeting via scaffolding proteins. In this review, we focus on the spatiotemporal regulation and effects of PKD signaling in response to neurohormonal, oxidant and metabolic signals that have implications for myocardial disease. Precise targeting of these mechanisms will be crucial in the design of PKD-based therapeutic strategies.

  19. Group VII Ethylene Response Factors Coordinate Oxygen and Nitric Oxide Signal Transduction and Stress Responses in Plants.

    Science.gov (United States)

    Gibbs, Daniel J; Conde, Jorge Vicente; Berckhan, Sophie; Prasad, Geeta; Mendiondo, Guillermina M; Holdsworth, Michael J

    2015-09-01

    The group VII ethylene response factors (ERFVIIs) are plant-specific transcription factors that have emerged as important regulators of abiotic and biotic stress responses, in particular, low-oxygen stress. A defining feature of ERFVIIs is their conserved N-terminal domain, which renders them oxygen- and nitric oxide (NO)-dependent substrates of the N-end rule pathway of targeted proteolysis. In the presence of these gases, ERFVIIs are destabilized, whereas an absence of either permits their accumulation; ERFVIIs therefore coordinate plant homeostatic responses to oxygen availability and control a wide range of NO-mediated processes. ERFVIIs have a variety of context-specific protein and gene interaction partners, and also modulate gibberellin and abscisic acid signaling to regulate diverse developmental processes and stress responses. This update discusses recent advances in our understanding of ERFVII regulation and function, highlighting their role as central regulators of gaseous signal transduction at the interface of ethylene, oxygen, and NO signaling. © 2015 American Society of Plant Biologists. All Rights Reserved.

  20. Unique responsiveness of angiosperm stomata to elevated CO2 explained by calcium signalling.

    Science.gov (United States)

    Brodribb, Timothy J; McAdam, Scott A M

    2013-01-01

    Angiosperm and conifer tree species respond differently when exposed to elevated CO2, with angiosperms found to dynamically reduce water loss while conifers appear insensitive. Such distinct responses are likely to affect competition between these tree groups as atmospheric CO2 concentration rises. Seeking the mechanism behind this globally important phenomenon we targeted the Ca(2+)-dependent signalling pathway, a mediator of stomatal closure in response to elevated CO2, as a possible explanation for the differentiation of stomatal behaviours. Sampling across the diversity of vascular plants including lycophytes, ferns, gymnosperms and angiosperms we show that only angiosperms possess the stomatal behaviour and prerequisite genetic coding, linked to Ca(2+)-dependent stomatal signalling. We conclude that the evolution of Ca(2+)-dependent stomatal signalling gives angiosperms adaptive benefits in terms of highly efficient water use, but that stomatal sensitivity to high CO2 may penalise angiosperm productivity relative to other plant groups in the current era of soaring atmospheric CO2.

  1. Molecular signal networks and regulating mechanisms of the unfolded protein response.

    Science.gov (United States)

    Gong, Jing; Wang, Xing-Zhi; Wang, Tao; Chen, Jiao-Jiao; Xie, Xiao-Yuan; Hu, Hui; Yu, Fang; Liu, Hui-Lin; Jiang, Xing-Yan; Fan, Han-Dong

    Within the cell, several mechanisms exist to maintain homeostasis of the endoplasmic reticulum (ER). One of the primary mechanisms is the unfolded protein response (UPR). In this review, we primarily focus on the latest signal webs and regulation mechanisms of the UPR. The relationships among ER stress, apoptosis, and cancer are also discussed. Under the normal state, binding immunoglobulin protein (BiP) interacts with the three sensors (protein kinase RNA-like ER kinase (PERK), activating transcription factor 6 (ATF6), and inositol-requiring enzyme 1α (IRE1α)). Under ER stress, misfolded proteins interact with BiP, resulting in the release of BiP from the sensors. Subsequently, the three sensors dimerize and autophosphorylate to promote the signal cascades of ER stress. ER stress includes a series of positive and negative feedback signals, such as those regulating the stabilization of the sensors/BiP complex, activating and inactivating the sensors by autophosphorylation and dephosphorylation, activating specific transcription factors to enable selective transcription, and augmenting the ability to refold and export. Apart from the three basic pathways, vascular endothelial growth factor (VEGF)-VEGF receptor (VEGFR)-phospholipase C-γ (PLCγ)-mammalian target of rapamycin complex 1 (mTORC1) pathway, induced only in solid tumors, can also activate ATF6 and PERK signal cascades, and IRE1α also can be activated by activated RAC-alpha serine/threonine-protein kinase (AKT). A moderate UPR functions as a pro-survival signal to return the cell to its state of homeostasis. However, persistent ER stress will induce cells to undergo apoptosis in response to increasing reactive oxygen species (ROS), Ca 2+ in the cytoplasmic matrix, and other apoptosis signal cascades, such as c-Jun N-terminal kinase (JNK), signal transducer and activator of transcription 3 (STAT3), and P38, when cellular damage exceeds the capacity of this adaptive response.

  2. Artificial Neural Network-Based Early-Age Concrete Strength Monitoring Using Dynamic Response Signals

    Directory of Open Access Journals (Sweden)

    Junkyeong Kim

    2017-06-01

    Full Text Available Concrete is one of the most common materials used to construct a variety of civil infrastructures. However, since concrete might be susceptible to brittle fracture, it is essential to confirm the strength of concrete at the early-age stage of the curing process to prevent unexpected collapse. To address this issue, this study proposes a novel method to estimate the early-age strength of concrete, by integrating an artificial neural network algorithm with a dynamic response measurement of the concrete material. The dynamic response signals of the concrete, including both electromechanical impedances and guided ultrasonic waves, are obtained from an embedded piezoelectric sensor module. The cross-correlation coefficient of the electromechanical impedance signals and the amplitude of the guided ultrasonic wave signals are selected to quantify the variation in dynamic responses according to the strength of the concrete. Furthermore, an artificial neural network algorithm is used to verify a relationship between the variation in dynamic response signals and concrete strength. The results of an experimental study confirm that the proposed approach can be effectively applied to estimate the strength of concrete material from the early-age stage of the curing process.

  3. An ancestral role for CONSTITUTIVE TRIPLE RESPONSE1 proteins in both ethylene and abscisic acid signaling

    NARCIS (Netherlands)

    Yasumura, Yuki; Pierik, Ronald; Kelly, Steven; Sakuta, Masaaki; Voesenek, Laurentius A C J; Harberd, Nicholas P.

    2015-01-01

    Land plants have evolved adaptive regulatory mechanisms enabling the survival of environmental stresses associated with terrestrial life. Here, we focus on the evolution of the regulatory CONSTITUTIVE TRIPLE RESPONSE1 (CTR1) component of the ethylene signaling pathway that modulates stress-related

  4. Mechanisms Underlying the Antidepressant Response of Acupuncture via PKA/CREB Signaling Pathway.

    Science.gov (United States)

    Jiang, Huili; Zhang, Xuhui; Wang, Yu; Zhang, Huimin; Li, Jing; Yang, Xinjing; Zhao, Bingcong; Zhang, Chuntao; Yu, Miao; Xu, Mingmin; Yu, Qiuyun; Liang, Xingchen; Li, Xiang; Shi, Peng; Bao, Tuya

    2017-01-01

    Protein kinase A (PKA)/cAMP response element-binding (CREB) protein signaling pathway, contributing to impaired neurogenesis parallel to depressive-like behaviors, has been identified as the crucial factor involved in the antidepressant response of acupuncture. However, the molecular mechanisms associated with antidepressant response of acupuncture, neurogenesis, and depressive-like behaviors ameliorating remain unexplored. The objective was to identify the mechanisms underlying the antidepressant response of acupuncture through PKA signaling pathway in depression rats by employing the PKA signaling pathway inhibitor H89 in in vivo experiments. Our results indicated that the expression of hippocampal PKA- α and p-CREB was significantly downregulated by chronic unpredicted mild stress (CUMS) procedures. Importantly, acupuncture reversed the downregulation of PKA- α and p-CREB. The expression of PKA- α was upregulated by fluoxetine, but not p-CREB. No significant difference was found between Acu and FLX groups on the expression of PKA- α and p-CREB. Interestingly, H89 inhibited the effects of acupuncture or fluoxetine on upregulating the expression of p-CREB, but not PKA- α . There was no significant difference in expression of CREB among the groups. Conclusively, our findings further support the hypothesis that acupuncture could ameliorate depressive-like behaviors by regulating PKA/CREB signaling pathway, which might be mainly mediated by regulating the phosphorylation level of CREB.

  5. Artificial Neural Network-Based Early-Age Concrete Strength Monitoring Using Dynamic Response Signals.

    Science.gov (United States)

    Kim, Junkyeong; Lee, Chaggil; Park, Seunghee

    2017-06-07

    Concrete is one of the most common materials used to construct a variety of civil infrastructures. However, since concrete might be susceptible to brittle fracture, it is essential to confirm the strength of concrete at the early-age stage of the curing process to prevent unexpected collapse. To address this issue, this study proposes a novel method to estimate the early-age strength of concrete, by integrating an artificial neural network algorithm with a dynamic response measurement of the concrete material. The dynamic response signals of the concrete, including both electromechanical impedances and guided ultrasonic waves, are obtained from an embedded piezoelectric sensor module. The cross-correlation coefficient of the electromechanical impedance signals and the amplitude of the guided ultrasonic wave signals are selected to quantify the variation in dynamic responses according to the strength of the concrete. Furthermore, an artificial neural network algorithm is used to verify a relationship between the variation in dynamic response signals and concrete strength. The results of an experimental study confirm that the proposed approach can be effectively applied to estimate the strength of concrete material from the early-age stage of the curing process.

  6. A transfer function approach to the small-signal response of saturated semiconductor optical amplifiers

    DEFF Research Database (Denmark)

    Nielsen, Mads Lønstrup; Blumenthal, D. J.; Mørk, Jesper

    2000-01-01

    response. The limitations to the magnitude of the spectral overshoot are also accounted for. Operating with the data and CW signals in a co-propagating configuration, we End that the resonance only exists for a finite waveguide loss. In a counter-propagating scheme, a resonance can exist regardless...

  7. Eating responses to external food cues and internal satiety signals in weight discordant siblings

    Science.gov (United States)

    Background: Compared to normal-weight children, over-weight children are more responsive to external food cues and less sensitive to internal satiety signals, either of which may facilitate greater energy intake. The ability to compensate for prior kcal intake may decrease with age, with children sh...

  8. Gamma rays induced bold seeded high yielding mutant in chickpea

    International Nuclear Information System (INIS)

    Wani, A.A.; Anis, M.

    2001-01-01

    In pulses especially in chickpea (Cicer arietinum L.), genetic variability has been exhausted due to natural selection and hence conventional breeding methods are not very fruitful. Mutation techniques are the best methods to enlarge the genetically conditioned variability of a species within a short time and have played a significant role in the development of many crop varieties. Investigations on the effects of ionizing radiations and chemical mutagens in induction of macro-mutations have received much attention owing to their utmost importance in plant breeding. The present study reports a bold seeded mutant in chickpea, the most dominating pulse crop on the Indian subcontinent. Fresh seeds of chickpea variety 'Pusa-212' were procured from IARI, New Delhi and treated with different doses/concentrations of gamma rays ( 60 Co source at NBRI, Lucknow) and ethyl methanesulphonate (EMS), individually as well as in combination, to raise the M1 generation. Seeds of M 1 plants were sown to raise M2 plant progenies. A bold seeded mutant was isolated from 400 Gy gamma ray treatments. The mutant was confirmed as true bred, all the mutant seeds gave rise to morphologically similar plants in M 3 , which were quite distinct from the control. The bold seeded mutant showed 'gigas' characteristics and vigorous growth. The plant remained initially straight but later on attained a trailing habit due to heavy secondary branching. The leaves, petioles, flowers, pods and seeds were almost double that of the parent variety, in size. The flowering occurred 10 days later than the parent and maturity was also delayed accordingly. Observations were recorded on various quantitative traits. Plant height and number of primary branches showed a significant improvement over the parent. It is interesting to note that the number of pods and number of seeds per pod significantly decreased. However, the hundred seed weight (31.73±0.59g) in the mutant plants was more than double in the parent

  9. Attenuated responses to emotional expressions in women with generalized anxiety disorder.

    Science.gov (United States)

    Palm, M E; Elliott, R; McKie, S; Deakin, J F W; Anderson, I M

    2011-05-01

    Generalized anxiety disorder (GAD) is under-researched despite its high prevalence and large impact on the healthcare system. There is a paucity of functional magnetic resonance imaging (fMRI) studies that explore the neural correlates of emotional processing in GAD. The present study investigated the blood oxygen level dependent (BOLD) response to processing positive and negative facial emotions in patients with GAD. A total of 15 female GAD patients and 16 female controls undertook an implicit face emotion task during fMRI scanning. They also performed a face emotion recognition task outside the scanner. The only behavioural difference observed in GAD patients was less accurate detection of sad facial expressions compared with control participants. However, GAD patients showed an attenuated BOLD signal in the prefrontal cortex to fearful, sad, angry and happy facial expressions and an attenuated signal in the anterior cingulate cortex to happy and fearful facial expressions. No differences were found in amygdala response. In contrast with previous research, this study found BOLD signal attenuation in the ventrolateral and medial prefrontal cortex and the anterior cingulate cortex during face emotion processing, consistent with a hypothesis of hypo-responsivity to external emotional stimuli in GAD. These decreases were in areas that have been implicated in emotion and cognition and may reflect an altered balance between internally and externally directed attentional processes.

  10. Phospholipid Encapsulated AuNR@Ag/Au Nanosphere SERS Tags with Environmental Stimulus Responsive Signal Property.

    Science.gov (United States)

    Su, Xueming; Wang, Yunqing; Wang, Wenhai; Sun, Kaoxiang; Chen, Lingxin

    2016-04-27

    Surface-enhanced Raman scattering (SERS) tags draw much attention due to the ultrasensitivity and multiplex labeling capability. Recently, a new kind of SERS tags was rationally designed by encapsulating metal nanoparticles with phospholipid bilayers, showing great potential in theranostics. The lipid bilayer coating confers biocompatibility and versatility to changing surface chemistry of the tag; however, its "soft" feature may influence SERS signal stability, which is rarely investigated. Herein, we prepared phospholipid-coated AuNR@Ag/Au nanosphere SERS tags by using three different kinds of Raman reporters, i.e., thio-containing 4-nitrothiophenol (NT), nitrogen-containing hydrophobic chromophore cyanine 7 monoacid (Cy7), and alkyl chain-chromophore conjugate 1,1'-dioctadecyl-3,3,3',3'-tetramethylindodicarbocyanine (DiD). It was found that signal responses were different upon additional stimulation which the tags may encounter in theranostic applications including the presence of detergent Triton X-100, lipid membrane, and photothermal treatment. Living-cell imaging also showed signal changing distinction. The different SERS signal performances were attributed to the different Raman reporter releasing behaviors from the tags. This work revealed that Raman reporter structure determined signal stability of lipid-coated SERS tags, providing guidance for the design of stimulus responsive tags. Moreover, it also implied the potential of SERS technique for real time drug release study of lipid based nanomedicine.

  11. Metabolic regulation of leaf senescence: interactions of sugar signalling with biotic and abiotic stress responses.

    Science.gov (United States)

    Wingler, A; Roitsch, T

    2008-09-01

    Sugars are important signals in the regulation of plant metabolism and development. During stress and in senescing leaves, sugars often accumulate. In addition, both sugar accumulation and stress can induce leaf senescence. Infection by bacterial and fungal pathogens and attack by herbivores and gall-forming insects may influence leaf senescence via modulation of the sugar status, either by directly affecting primary carbon metabolism or by regulating steady state levels of plant hormones. Many types of biotic interactions involve the induction of extracellular invertase as the key enzyme of an apoplasmic phloem unloading pathway, resulting in a source-sink transition and an increased hexose/sucrose ratio. Induction of the levels of the phytohormones ethylene and jasmonate in biotic interactions results in accelerated senescence, whereas an increase in plant- or pathogen-derived cytokinins delays senescence and results in the formation of green islands within senescing leaves. Interactions between sugar and hormone signalling also play a role in response to abiotic stress. For example, interactions between sugar and abscisic acid (ABA) signalling may be responsible for the induction of senescence during drought stress. Cold treatment, on the other hand, can result in delayed senescence, despite sugar and ABA accumulation. Moreover, natural variation can be found in senescence regulation by sugars and in response to stress: in response to drought stress, both drought escape and dehydration avoidance strategies have been described in different Arabidopsis accessions. The regulation of senescence by sugars may be key to these different strategies in response to stress.

  12. The Arabidopsis GAI gene defines a signaling pathway that negatively regulates gibberellin responses.

    Science.gov (United States)

    Peng, J; Carol, P; Richards, D E; King, K E; Cowling, R J; Murphy, G P; Harberd, N P

    1997-12-01

    The Arabidopsis gai mutant allele confers a reduction in gibberellin (GA) responsiveness. Here we report the molecular cloning of GAI and a closely related gene GRS. The predicted GAI (wild-type) and gai (mutant) proteins differ only by the deletion of a 17-amino-acid segment from within the amino-terminal region. GAI and GRS contain nuclear localization signals, a region of homology to a putative transcription factor, and motifs characteristic of transcriptional coactivators. Genetic analysis indicates that GAI is a repressor of GA responses, that GA can release this repression, and that gai is a mutant repressor that is relatively resistant to the effects of GA. Mutations at SPY and GAR2 suppress the gai phenotype, indicating the involvement of GAI, SPY, and GAR2 in a signaling pathway that regulates GA responses negatively. The existence of this pathway suggests that GA modulates plant growth through derepression rather than through simple stimulation.

  13. Toll-like receptor 2 signaling in response to brain injury

    DEFF Research Database (Denmark)

    Babcock, Alicia A; Wirenfeldt, Martin; Holm, Thomas

    2006-01-01

    , may have pathogen-independent roles. We show that TLR2 was selectively upregulated by microglia in the denervated zones of the hippocampus in response to stereotactic transection of axons in the entorhinal cortex. In mice lacking TLR2, there were transient, selective reductions in lesion......-mutant mice. Consistent with the fact that responses in knock-out mice had all returned to wild-type levels by 8 d, there was no evidence for effects on neuronal plasticity at 20 d. These results identify a role for TLR2 signaling in the early glial response to brain injury, acting as an innate bridge...

  14. Insulin-like signalling to the maternal germline controls progeny response to osmotic stress.

    Science.gov (United States)

    Burton, Nicholas O; Furuta, Tokiko; Webster, Amy K; Kaplan, Rebecca E W; Baugh, L Ryan; Arur, Swathi; Horvitz, H Robert

    2017-03-01

    In 1893 August Weismann proposed that information about the environment could not pass from somatic cells to germ cells, a hypothesis now known as the Weismann barrier. However, recent studies have indicated that parental exposure to environmental stress can modify progeny physiology and that parental stress can contribute to progeny disorders. The mechanisms regulating these phenomena are poorly understood. We report that the nematode Caenorhabditis elegans can protect itself from osmotic stress by entering a state of arrested development and can protect its progeny from osmotic stress by increasing the expression of the glycerol biosynthetic enzyme GPDH-2 in progeny. Both of these protective mechanisms are regulated by insulin-like signalling: insulin-like signalling to the intestine regulates developmental arrest, while insulin-like signalling to the maternal germline regulates glycerol metabolism in progeny. Thus, there is a heritable link between insulin-like signalling to the maternal germline and progeny metabolism and gene expression. We speculate that analogous modulation of insulin-like signalling to the germline is responsible for effects of the maternal environment on human diseases that involve insulin signalling, such as obesity and type-2 diabetes.

  15. Target of Rapamycin (TOR) Regulates Growth in Response to Nutritional Signals.

    Science.gov (United States)

    Weisman, Ronit

    2016-10-01

    All organisms can respond to the availability of nutrients by regulating their metabolism, growth, and cell division. Central to the regulation of growth in response to nutrient availability is the target of rapamycin (TOR) signaling that is composed of two structurally distinct complexes: TOR complex 1 (TORC1) and TOR complex 2 (TORC2). The TOR genes were first identified in yeast as target of rapamycin, a natural product of a soil bacterium, which proved beneficial as an immunosuppressive and anticancer drug and is currently being tested for a handful of other pathological conditions including diabetes, neurodegeneration, and age-related diseases. Studies of the TOR pathway unraveled a complex growth-regulating network. TOR regulates nutrient uptake, transcription, protein synthesis and degradation, as well as metabolic pathways, in a coordinated manner that ensures that cells grow or cease growth in response to nutrient availability. The identification of specific signals and mechanisms that stimulate TOR signaling is an active and exciting field of research that has already identified nitrogen and amino acids as key regulators of TORC1 activity. The signals, as well as the cellular functions of TORC2, are far less well understood. Additional open questions in the field concern the relationships between TORC1 and TORC2, as well as the links with other nutrient-responsive pathways. Here I review the main features of TORC1 and TORC2, with a particular focus on yeasts as model organisms.

  16. Interneuronal systems of the cervical spinal cord assessed with BOLD imaging at 1.5 T

    Energy Technology Data Exchange (ETDEWEB)

    Stracke, C.P.; Schoth, F.; Moeller-Hartmann, W.; Krings, T. [University Hospital of the University of Technology, Departments of Neuroradiology and Diagnostic Radiology, Aachen (Germany); Pettersson, L.G. [University of Goeteborg, Department of Physiology, Goeteborg (Sweden)

    2005-02-01

    The purpose of this study was to investigate if functional activity with spinal cord somatosensory stimulation can be visualized using BOLD fMRI. We investigated nine healthy volunteers using a somatosensory stimulus generator. The stimuli were applied in three different runs at the first, third, and fifth finger tip of the right hand, respectively, corresponding to dermatomes c6, c7, and c8. The stimuli gave an increase of BOLD signal (activation) in three different locations of the spinal cord and brain stem. First, activations could be seen in the spinal segment corresponding to the stimulated dermatome in seven out of nine volunteers for c6 stimulation, two out of eight for c7, and three out of eight for c8. These activations were located close to the posterior margin of the spinal cord, presumably reflecting synaptic transmission to dorsal horn interneurons. Second, activation in the medulla oblongata was evident in four subjects, most likely corresponding to the location of the nucleus cuneatus. The third location of activation, which was the strongest and most reliable observed was inside the spinal cord in the c3 and c4 segments. Activation at these spinal levels was almost invariably observed independently of the dermatome stimulated (9/9 for c6, 8/8 for c7, and 7/8 for c8 stimulation). These activations may pertain to an interneuronal system at this spinal level. The results are discussed in relation to neurophysiological studies on cervical spinal interneuronal pathways in animals and humans. (orig.)

  17. Negative BOLD in sensory cortices during verbal memory: a component in generating internal representations?

    Science.gov (United States)

    Azulay, Haim; Striem, Ella; Amedi, Amir

    2009-05-01

    People tend to close their eyes when trying to retrieve an event or a visual image from memory. However the brain mechanisms behind this phenomenon remain poorly understood. Recently, we showed that during visual mental imagery, auditory areas show a much more robust deactivation than during visual perception. Here we ask whether this is a special case of a more general phenomenon involving retrieval of intrinsic, internally stored information, which would result in crossmodal deactivations in other sensory cortices which are irrelevant to the task at hand. To test this hypothesis, a group of 9 sighted individuals were scanned while performing a memory retrieval task for highly abstract words (i.e., with low imaginability scores). We also scanned a group of 10 congenitally blind, which by definition do not have any visual imagery per se. In sighted subjects, both auditory and visual areas were robustly deactivated during memory retrieval, whereas in the blind the auditory cortex was deactivated while visual areas, shown previously to be relevant for this task, presented a positive BOLD signal. These results suggest that deactivation may be most prominent in task-irrelevant sensory cortices whenever there is a need for retrieval or manipulation of internally stored representations. Thus, there is a task-dependent balance of activation and deactivation that might allow maximization of resources and filtering out of non relevant information to enable allocation of attention to the required task. Furthermore, these results suggest that the balance between positive and negative BOLD might be crucial to our understanding of a large variety of intrinsic and extrinsic tasks including high-level cognitive functions, sensory processing and multisensory integration.

  18. Interneuronal systems of the cervical spinal cord assessed with BOLD imaging at 1.5 T

    International Nuclear Information System (INIS)

    Stracke, C.P.; Schoth, F.; Moeller-Hartmann, W.; Krings, T.; Pettersson, L.G.

    2005-01-01

    The purpose of this study was to investigate if functional activity with spinal cord somatosensory stimulation can be visualized using BOLD fMRI. We investigated nine healthy volunteers using a somatosensory stimulus generator. The stimuli were applied in three different runs at the first, third, and fifth finger tip of the right hand, respectively, corresponding to dermatomes c6, c7, and c8. The stimuli gave an increase of BOLD signal (activation) in three different locations of the spinal cord and brain stem. First, activations could be seen in the spinal segment corresponding to the stimulated dermatome in seven out of nine volunteers for c6 stimulation, two out of eight for c7, and three out of eight for c8. These activations were located close to the posterior margin of the spinal cord, presumably reflecting synaptic transmission to dorsal horn interneurons. Second, activation in the medulla oblongata was evident in four subjects, most likely corresponding to the location of the nucleus cuneatus. The third location of activation, which was the strongest and most reliable observed was inside the spinal cord in the c3 and c4 segments. Activation at these spinal levels was almost invariably observed independently of the dermatome stimulated (9/9 for c6, 8/8 for c7, and 7/8 for c8 stimulation). These activations may pertain to an interneuronal system at this spinal level. The results are discussed in relation to neurophysiological studies on cervical spinal interneuronal pathways in animals and humans. (orig.)

  19. Balancing past and present: how experience influences boldness over time in Eurasian perch.

    Science.gov (United States)

    Hellström, Gustav; Magnhagen, Carin

    2017-04-01

    Adapting to fluctuating predation conditions is a challenge for prey. By learning through experience, animals may adjust their anti-predator behavior to better reflect current predation risk. Although many studies show experience of predation to alter prey behavior, little is known about how prey rely on such experience over time. By comparing boldness over different temporal scales between individuals of Eurasian perch, either experienced or naïve of predators, we examine how risk is traded based on past and present experience. Differences in predator exposure during the first year of life were found to lead to differences in risk-taking behavior, even after the perch been kept in a predator-free environment for 9 months. However, the response to a potential predator was quickly readjusted after increased experience of current conditions. The results highlight how prey have to balance past experiences of predators against current threat levels.

  20. The Role of Phospholipase C Signaling in Macrophage-Mediated Inflammatory Response

    Directory of Open Access Journals (Sweden)

    Liqian Zhu

    2018-01-01

    Full Text Available Macrophages are crucial members of the mononuclear phagocyte system essential to protect the host from invading pathogens and are central to the inflammatory response with their ability to acquire specialized phenotypes of inflammatory (M1 and anti-inflammatory (M2 and to produce a pool of inflammatory mediators. Equipped with a broad range of receptors, such as Toll-like receptor 4 (TLR4, CD14, and Fc gamma receptors (FcγRs, macrophages can efficiently recognize and phagocytize invading pathogens and secrete cytokines by triggering various secondary signaling pathways. Phospholipase C (PLC is a family of enzymes that hydrolyze phospholipids, the most significant of which is phosphatidylinositol 4,5-bisphosphate [PI(4,5P2]. Cleavage at the internal phosphate ester generates two second messengers, inositol 1,4,5-trisphosphate (IP3 and diacylglycerol (DAG, both of which mediate in diverse cellular functions including the inflammatory response. Recent studies have shown that some PLC isoforms are involved in multiple stages in TLR4-, CD14-, and FcγRs-mediated activation of nuclear factor kappa B (NF-κB, mitogen-activated protein kinase (MAPK, and interferon regulatory factors (IRFs, all of which are associated with the regulation of the inflammatory response. Therefore, secondary signaling by PLC is implicated in the pathogenesis of numerous inflammatory diseases. This review provides an overview of our current knowledge on how PLC signaling regulates the macrophage-mediated inflammatory response.

  1. Perturbations in carotenoid and porphyrin status result in differential photooxidative stress signaling and antioxidant responses.

    Science.gov (United States)

    Park, Joon-Heum; Jung, Sunyo

    2018-02-12

    We examined differential photooxidative stress signaling and antioxidant responses in rice plants treated with norflurazon (NF) and oxyfluorfen (OF), which are inhibitors of carotenoid and porphyrin biosynthesis, respectively. Plants treated with OF markedly increased levels of cellular leakage and malondialdehyde, compared with NF-treated plants, showing that OF plants suffered greater oxidative damage with respect to membrane integrity. The enhanced production of H 2 O 2 in response to OF, but not NF, indicates the important role of H 2 O 2 in activation of photooxidative stress signaling in OF plants. In response to NF and OF, the increased levels of free salicylic acid as well as maintenance of the redox ratio of ascorbate and glutathione pools to a certain level are considered to be crucial factors in the protection against photooxidation. Plants treated with OF greatly up-regulated catalase (CAT) activity and Cat transcript levels, compared with NF-treated plants. Interestingly, NF plants showed no noticeable increase in oxidative metabolism, although they did show considerable increases in ascorbate peroxidase (APX) and peroxidase activities and transcript levels of APX, as in OF plants. Our results suggest that perturbations in carotenoid and porphyrin status by NF and OF can be sensed by differential photooxidative stress signaling, such as that involving H 2 O 2 , redox state of ascorbate and glutathione, and salicylic acid, which may be responsible for at least part of the induction of ROS-scavenging enzymes. Copyright © 2018 Elsevier Inc. All rights reserved.

  2. Estrogen signalling and the DNA damage response in hormone dependent breast cancers

    Directory of Open Access Journals (Sweden)

    C Elizabeth Caldon

    2014-05-01

    Full Text Available Estrogen is necessary for the normal growth and development of breast tissue, but high levels of estrogen are a major risk factor for breast cancer. One mechanism by which estrogen could contribute to breast cancer is via the induction of DNA damage. This perspective discusses the mechanisms by which estrogen alters the DNA damage response (DDR and DNA repair through the regulation of key effector proteins including ATM, ATR, CHK1, BRCA1 and p53 and the feedback on estrogen receptor signalling from these proteins. We put forward the hypothesis that estrogen receptor signalling converges to suppress effective DNA repair and apoptosis in favour of proliferation. This is important in hormone-dependent breast cancer as it will affect processing of estrogen-induced DNA damage, as well as other genotoxic insults. DDR and DNA repair proteins are frequently mutated or altered in estrogen responsive breast cancer which will further change the processing of DNA damage. Finally the action of estrogen signalling on DNA damage is also relevant to the therapeutic setting as the suppression of a DNA damage response by estrogen has the potential to alter the response of cancers to anti-hormone treatment or chemotherapy that induces DNA damage.

  3. Neuronal inhibition and excitation, and the dichotomic control of brain hemodynamic and oxygen responses

    DEFF Research Database (Denmark)

    Lauritzen, Martin; Mathiesen, Claus; Schaefer, Katharina

    2012-01-01

    Brain's electrical activity correlates strongly to changes in cerebral blood flow (CBF) and the cerebral metabolic rate of oxygen (CMRO(2)). Subthreshold synaptic processes correlate better than the spike rates of principal neurons to CBF, CMRO(2) and positive BOLD signals. Stimulation-induced ri......Brain's electrical activity correlates strongly to changes in cerebral blood flow (CBF) and the cerebral metabolic rate of oxygen (CMRO(2)). Subthreshold synaptic processes correlate better than the spike rates of principal neurons to CBF, CMRO(2) and positive BOLD signals. Stimulation......-induced rises in CMRO(2) are controlled by the ATP turnover, which depends on the energy used to fuel the Na,K-ATPase to reestablish ionic gradients, while stimulation-induced CBF responses to a large extent are controlled by mechanisms that depend on Ca(2+) rises in neurons and astrocytes. This dichotomy...

  4. Model-based synthesis of locally contingent responses to global market signals

    Science.gov (United States)

    Magliocca, N. R.

    2015-12-01

    Rural livelihoods and the land systems on which they depend are increasingly influenced by distant markets through economic globalization. Place-based analyses of land and livelihood system sustainability must then consider both proximate and distant influences on local decision-making. Thus, advancing land change theory in the context of economic globalization calls for a systematic understanding of the general processes as well as local contingencies shaping local responses to global signals. Synthesis of insights from place-based case studies of land and livelihood change is a path forward for developing such systematic knowledge. This paper introduces a model-based synthesis approach to investigating the influence of local socio-environmental and agent-level factors in mediating land-use and livelihood responses to changing global market signals. A generalized agent-based modeling framework is applied to six case-study sites that differ in environmental conditions, market access and influence, and livelihood settings. The largest modeled land conversions and livelihood transitions to market-oriented production occurred in sties with relatively productive agricultural land and/or with limited livelihood options. Experimental shifts in the distributions of agents' risk tolerances generally acted to attenuate or amplify responses to changes in global market signals. Importantly, however, responses of agents at different points in the risk tolerance distribution varied widely, with the wealth gap growing wider between agents with higher or lower risk tolerance. These results demonstrate model-based synthesis is a promising approach to overcome many of the challenges of current synthesis methods in land change science, and to identify generalized as well as locally contingent responses to global market signals.

  5. A signal detection-item response theory model for evaluating neuropsychological measures.

    Science.gov (United States)

    Thomas, Michael L; Brown, Gregory G; Gur, Ruben C; Moore, Tyler M; Patt, Virginie M; Risbrough, Victoria B; Baker, Dewleen G

    2018-02-05

    Models from signal detection theory are commonly used to score neuropsychological test data, especially tests of recognition memory. Here we show that certain item response theory models can be formulated as signal detection theory models, thus linking two complementary but distinct methodologies. We then use the approach to evaluate the validity (construct representation) of commonly used research measures, demonstrate the impact of conditional error on neuropsychological outcomes, and evaluate measurement bias. Signal detection-item response theory (SD-IRT) models were fitted to recognition memory data for words, faces, and objects. The sample consisted of U.S. Infantry Marines and Navy Corpsmen participating in the Marine Resiliency Study. Data comprised item responses to the Penn Face Memory Test (PFMT; N = 1,338), Penn Word Memory Test (PWMT; N = 1,331), and Visual Object Learning Test (VOLT; N = 1,249), and self-report of past head injury with loss of consciousness. SD-IRT models adequately fitted recognition memory item data across all modalities. Error varied systematically with ability estimates, and distributions of residuals from the regression of memory discrimination onto self-report of past head injury were positively skewed towards regions of larger measurement error. Analyses of differential item functioning revealed little evidence of systematic bias by level of education. SD-IRT models benefit from the measurement rigor of item response theory-which permits the modeling of item difficulty and examinee ability-and from signal detection theory-which provides an interpretive framework encompassing the experimentally validated constructs of memory discrimination and response bias. We used this approach to validate the construct representation of commonly used research measures and to demonstrate how nonoptimized item parameters can lead to erroneous conclusions when interpreting neuropsychological test data. Future work might include the

  6. The UVR8 UV-B Photoreceptor: Perception, Signaling and Response

    Science.gov (United States)

    Tilbrook, Kimberley; Arongaus, Adriana B.; Binkert, Melanie; Heijde, Marc; Yin, Ruohe; Ulm, Roman

    2013-01-01

    Ultraviolet-B radiation (UV-B) is an intrinsic part of sunlight that is accompanied by significant biological effects. Plants are able to perceive UV-B using the UV-B photoreceptor UVR8 which is linked to a specific molecular signaling pathway and leads to UV-B acclimation. Herein we review the biological process in plants from initial UV-B perception and signal transduction through to the known UV-B responses that promote survival in sunlight. The UVR8 UV-B photoreceptor exists as a homodimer that instantly monomerises upon UV-B absorption via specific intrinsic tryptophans which act as UV-B chromophores. The UVR8 monomer interacts with COP1, an E3 ubiquitin ligase, initiating a molecular signaling pathway that leads to gene expression changes. This signaling output leads to UVR8-dependent responses including UV-B-induced photomorphogenesis and the accumulation of UV-B-absorbing flavonols. Negative feedback regulation of the pathway is provided by the WD40-repeat proteins RUP1 and RUP2, which facilitate UVR8 redimerization, disrupting the UVR8-COP1 interaction. Despite rapid advancements in the field of recent years, further components of UVR8 UV-B signaling are constantly emerging, and the precise interplay of these and the established players UVR8, COP1, RUP1, RUP2 and HY5 needs to be defined. UVR8 UV-B signaling represents our further understanding of how plants are able to sense their light environment and adjust their growth accordingly. PMID:23864838

  7. Unfolded protein response (UPR) signaling regulates arsenic trioxide-mediated macrophage innate immune function disruption

    Energy Technology Data Exchange (ETDEWEB)

    Srivastava, Ritesh K.; Li, Changzhao; Chaudhary, Sandeep C. [Department of Dermatology and Skin Diseases Research Center, University of Alabama at Birmingham, Birmingham, AL (United States); Ballestas, Mary E. [Department of Pediatrics Infectious Disease, Children' s of Alabama, School of Medicine, University of Alabama at Birmingham, AL (United States); Elmets, Craig A. [Department of Dermatology and Skin Diseases Research Center, University of Alabama at Birmingham, Birmingham, AL (United States); Robbins, David J. [Department of Surgery, Molecular Oncology Program, Miller School of Medicine, University of Miami, Miami (United States); Matalon, Sadis [Department of Anesthesiology, University of Alabama at Birmingham, Birmingham, AL (United States); Deshane, Jessy S. [Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, AL (United States); Afaq, Farrukh [Department of Dermatology and Skin Diseases Research Center, University of Alabama at Birmingham, Birmingham, AL (United States); Bickers, David R. [Department of Dermatology, Columbia University Medical Center, New York (United States); Athar, Mohammad, E-mail: mathar@uab.edu [Department of Dermatology and Skin Diseases Research Center, University of Alabama at Birmingham, Birmingham, AL (United States)

    2013-11-01

    Arsenic exposure is known to disrupt innate immune functions in humans and in experimental animals. In this study, we provide a mechanism by which arsenic trioxide (ATO) disrupts macrophage functions. ATO treatment of murine macrophage cells diminished internalization of FITC-labeled latex beads, impaired clearance of phagocytosed fluorescent bacteria and reduced secretion of pro-inflammatory cytokines. These impairments in macrophage functions are associated with ATO-induced unfolded protein response (UPR) signaling pathway characterized by the enhancement in proteins such as GRP78, p-PERK, p-eIF2α, ATF4 and CHOP. The expression of these proteins is altered both at transcriptional and translational levels. Pretreatment with chemical chaperon, 4-phenylbutyric acid (PBA) attenuated the ATO-induced activation in UPR signaling and afforded protection against ATO-induced disruption of macrophage functions. This treatment also reduced ATO-mediated reactive oxygen species (ROS) generation. Interestingly, treatment with antioxidant N-acetylcysteine (NAC) prior to ATO exposure, not only reduced ROS production and UPR signaling but also improved macrophage functions. These data demonstrate that UPR signaling and ROS generation are interdependent and are involved in the arsenic-induced pathobiology of macrophage. These data also provide a novel strategy to block the ATO-dependent impairment in innate immune responses. - Highlights: • Inorganic arsenic to humans and experimental animals disrupt innate immune responses. • The mechanism underlying arsenic impaired macrophage functions involves UPR signaling. • Chemical chaperon attenuates arsenic-mediated macrophage function impairment. • Antioxidant, NAC blocks impairment in arsenic-treated macrophage functions.

  8. Unfolded protein response (UPR) signaling regulates arsenic trioxide-mediated macrophage innate immune function disruption

    International Nuclear Information System (INIS)

    Srivastava, Ritesh K.; Li, Changzhao; Chaudhary, Sandeep C.; Ballestas, Mary E.; Elmets, Craig A.; Robbins, David J.; Matalon, Sadis; Deshane, Jessy S.; Afaq, Farrukh; Bickers, David R.; Athar, Mohammad

    2013-01-01

    Arsenic exposure is known to disrupt innate immune functions in humans and in experimental animals. In this study, we provide a mechanism by which arsenic trioxide (ATO) disrupts macrophage functions. ATO treatment of murine macrophage cells diminished internalization of FITC-labeled latex beads, impaired clearance of phagocytosed fluorescent bacteria and reduced secretion of pro-inflammatory cytokines. These impairments in macrophage functions are associated with ATO-induced unfolded protein response (UPR) signaling pathway characterized by the enhancement in proteins such as GRP78, p-PERK, p-eIF2α, ATF4 and CHOP. The expression of these proteins is altered both at transcriptional and translational levels. Pretreatment with chemical chaperon, 4-phenylbutyric acid (PBA) attenuated the ATO-induced activation in UPR signaling and afforded protection against ATO-induced disruption of macrophage functions. This treatment also reduced ATO-mediated reactive oxygen species (ROS) generation. Interestingly, treatment with antioxidant N-acetylcysteine (NAC) prior to ATO exposure, not only reduced ROS production and UPR signaling but also improved macrophage functions. These data demonstrate that UPR signaling and ROS generation are interdependent and are involved in the arsenic-induced pathobiology of macrophage. These data also provide a novel strategy to block the ATO-dependent impairment in innate immune responses. - Highlights: • Inorganic arsenic to humans and experimental animals disrupt innate immune responses. • The mechanism underlying arsenic impaired macrophage functions involves UPR signaling. • Chemical chaperon attenuates arsenic-mediated macrophage function impairment. • Antioxidant, NAC blocks impairment in arsenic-treated macrophage functions

  9. MAPK ERK signaling regulates the TGF-beta1-dependent mosquito response to Plasmodium falciparum.

    Science.gov (United States)

    Surachetpong, Win; Singh, Naresh; Cheung, Kong Wai; Luckhart, Shirley

    2009-04-01

    Malaria is caused by infection with intraerythrocytic protozoa of the genus Plasmodium that are transmitted by Anopheles mosquitoes. Although a variety of anti-parasite effector genes have been identified in anopheline mosquitoes, little is known about the signaling pathways that regulate these responses during parasite development. Here we demonstrate that the MEK-ERK signaling pathway in Anopheles is controlled by ingested human TGF-beta1 and finely tunes mosquito innate immunity to parasite infection. Specifically, MEK-ERK signaling was dose-dependently induced in response to TGF-beta1 in immortalized cells in vitro and in the A. stephensi midgut epithelium in vivo. At the highest treatment dose of TGF-beta1, inhibition of ERK phosphorylation increased TGF-beta1-induced expression of the anti-parasite effector gene nitric oxide synthase (NOS), suggesting that increasing levels of ERK activation negatively feed back on induced NOS expression. At infection levels similar to those found in nature, inhibition of ERK activation reduced P. falciparum oocyst loads and infection prevalence in A. stephensi and enhanced TGF-beta1-mediated control of P. falciparum development. Taken together, our data demonstrate that malaria parasite development in the mosquito is regulated by a conserved MAPK signaling pathway that mediates the effects of an ingested cytokine.

  10. MAPK ERK Signaling Regulates the TGF-β1-Dependent Mosquito Response to Plasmodium falciparum

    Science.gov (United States)

    Surachetpong, Win; Singh, Naresh; Cheung, Kong Wai; Luckhart, Shirley

    2009-01-01

    Malaria is caused by infection with intraerythrocytic protozoa of the genus Plasmodium that are transmitted by Anopheles mosquitoes. Although a variety of anti-parasite effector genes have been identified in anopheline mosquitoes, little is known about the signaling pathways that regulate these responses during parasite development. Here we demonstrate that the MEK-ERK signaling pathway in Anopheles is controlled by ingested human TGF-β1 and finely tunes mosquito innate immunity to parasite infection. Specifically, MEK-ERK signaling was dose-dependently induced in response to TGF-β1 in immortalized cells in vitro and in the A. stephensi midgut epithelium in vivo. At the highest treatment dose of TGF-β1, inhibition of ERK phosphorylation increased TGF-β1-induced expression of the anti-parasite effector gene nitric oxide synthase (NOS), suggesting that increasing levels of ERK activation negatively feed back on induced NOS expression. At infection levels similar to those found in nature, inhibition of ERK activation reduced P. falciparum oocyst loads and infection prevalence in A. stephensi and enhanced TGF-β1-mediated control of P. falciparum development. Taken together, our data demonstrate that malaria parasite development in the mosquito is regulated by a conserved MAPK signaling pathway that mediates the effects of an ingested cytokine. PMID:19343212

  11. [Response of arbuscular mycorrhizal fungal lipid metabolism to symbiotic signals in mycorrhiza].

    Science.gov (United States)

    Tian, Lei; Li, Yuanjing; Tian, Chunjie

    2016-01-04

    Arbuscular mycorrhizal (AM) fungi play an important role in energy flow and nutrient cycling, besides their wide distribution in the cosystem. With a long co-evolution, AM fungi and host plant have formed a symbiotic relationship, and fungal lipid metabolism may be the key point to find the symbiotic mechanism in arbusculart mycorrhiza. Here, we reviewed the most recent progress on the interaction between AM fungal lipid metabolism and symbiotic signaling networks, especially the response of AM fungal lipid metabolism to symbiotic signals. Furthermore, we discussed the response of AM fungal lipid storage and release to symbiotic or non-symbiotic status, and the correlation between fungal lipid metabolism and nutrient transfer in mycorrhiza. In addition, we explored the feedback of the lipolysis process to molecular signals during the establishment of symbiosis, and the corresponding material conversion and energy metabolism besides the crosstalk of fungal lipid metabolism and signaling networks. This review will help understand symbiotic mechanism of arbuscular mycorrhiza fungi and further application in ecosystem.

  12. Time-dependent regulation of muscle caveolin activation and insulin signalling in response to high-fat diet.

    Science.gov (United States)

    Gómez-Ruiz, Ana; de Miguel, Carlos; Campión, Javier; Martínez, J Alfredo; Milagro, Fermín I

    2009-10-06

    We studied the effect of high-fat diet on the expression and activation of the three caveolins in rat skeletal muscle and their association with the insulin signalling cascade. Initial response was characterized by increased signalling through Cav-1 and Cav-3 phosphorylation, suggesting that both participate in an initial acute response to the calorie surplus. Afterwards, Cav-1 signalling was slightly reduced, whereas Cav-3 remained active. Late chronic phase signalling through both proteins was impaired inducing a prediabetic state. Summarizing, caveolins seem to mediate a time-dependent regulation of insulin cascade in response to high-fat diet in muscle.

  13. Efficient responses to host and bacterial signals during Vibrio cholerae colonization

    Science.gov (United States)

    Rothenbacher, Francesca P; Zhu, Jun

    2014-01-01

    Vibrio cholerae, the microorganism responsible for the diarrheal disease cholera, is able to sense and respond to a variety of changing stimuli in both its aquatic and human gastrointestinal environments. Here we present a review of research efforts aimed toward understanding the signals this organism senses in the human host. V. cholerae’s ability to sense and respond to temperature and pH, bile, osmolarity, oxygen and catabolite levels, nitric oxide, and mucus, as well as the quorum sensing signals produced in response to these factors will be discussed. We also review the known quorum sensing regulatory pathways and discuss their importance with regard to the regulation of virulence and colonization during infection. PMID:24256715

  14. ZAP-70 and p72syk are signaling response elements through MHC class II molecules

    DEFF Research Database (Denmark)

    Kanner, S B; Grosmaire, L S; Blake, J

    1995-01-01

    Ligation of major histocompatibility complex (MHC) class II antigens expressed on antigen-activated human CD4+ T-lymphocytes induces early signal transduction events including the activation of tyrosine kinases, the tyrosine phosphorylation of phospholipase-C gamma 1 and the mobilization...... of intracellular calcium. Similar responses have been observed in B-cells following stimulation of MHC class II molecules, including the increased production of intracellular cAMP. In this report, we demonstrate that the ZAP-70 tyrosine kinase is a responsive signaling element following cross-linking of HLA...... by herbimycin A. MHC class II ligation on B-lymphocytes resulted in cell death, which was both qualitatively distinct from Fas-induced apoptosis and partially protected by herbimycin A pretreatment. Thus, ligation of MHC class II molecules expressed on human lymphocytes stimulates the ZAP-70/p72syk family...

  15. A cell-cell communication signal integrates quorum sensing and stress response.

    Science.gov (United States)

    Lee, Jasmine; Wu, Jien; Deng, Yinyue; Wang, Jing; Wang, Chao; Wang, Jianhe; Chang, Changqing; Dong, Yihu; Williams, Paul; Zhang, Lian-Hui

    2013-05-01

    Pseudomonas aeruginosa uses a hierarchical quorum sensing (QS) network consisting of las, pqs and rhl regulatory elements to coordinate the expression of bacterial virulence genes. However, clinical isolates frequently contain loss-of-function mutations in the central las system. This motivated us to search for a mechanism that may functionally substitute las. Here we report identification of a new QS signal, IQS. Disruption of IQS biosynthesis paralyzes the pqs and rhl QS systems and attenuates bacterial virulence. Production of IQS is tightly controlled by las under normal culture conditions but is also activated by phosphate limitation, a common stressor that bacteria encounter during infections. Thus, these results have established an integrated QS system that connects the central las system and phosphate-stress response mechanism to the downstream pqs and rhl regulatory systems. Our discovery highlights the complexity of QS signaling systems and extends the gamut of QS and stress-response mechanisms.

  16. Quorum-Sensing Signal-Response Systems in Gram-Negative Bacteria

    Science.gov (United States)

    Papenfort, Kai; Bassler, Bonnie

    2016-01-01

    Abstract / Preface Bacteria use quorum sensing to orchestrate gene expression programmes that underlie collective behaviours. Quorum sensing relies on the production, release, detection and group-level response to extracellular signalling molecules, which are called autoinducers. Recent work has discovered new autoinducers in Gram-negative bacteria, shown how these molecules are recognized by cognate receptors, revealed new regulatory components that are embedded in canonical signalling circuits and identified novel regulatory network designs. In this Review we examine how, together, these features of quorum sensing signal–response systems combine to control collective behaviours in Gram-negative bacteria and we discuss the implications for host–microbial associations and antibacterial therapy. PMID:27510864

  17. Frequency response testing at Experimental Breeder Reactor II using discrete-level periodic signals

    International Nuclear Information System (INIS)

    Rhodes, W.D.; Larson, H.A.

    1990-01-01

    The Experimental Breeder Reactor 2 (EBR-2) reactivity-to-power frequency-response function was measured with pseudo-random, discrete-level, periodic signals. The reactor power deviation was small with insignificant perturbation of normal operation and in-place irradiation experiments. Comparison of results with measured rod oscillator data and with theoretical predictions show good agreement. Moreover, measures of input signal quality (autocorrelation function and energy spectra) confirm the ability to enable this type of frequency response determination at EBR-2. Measurements were made with the pseudo-random binary sequence, quadratic residue binary sequence, pseudo-random ternary sequence, and the multifrequency binary sequence. 10 refs., 7 figs., 3 tabs

  18. Mutant p53 shapes the enhancer landscape of cancer cells in response to chronic immune signaling.

    Science.gov (United States)

    Rahnamoun, Homa; Lu, Hanbin; Duttke, Sascha H; Benner, Christopher; Glass, Christopher K; Lauberth, Shannon M

    2017-09-29

    Inflammation influences cancer development, progression, and the efficacy of cancer treatments, yet the mechanisms by which immune signaling drives alterations in the cancer cell transcriptome remain unclear. Using ChIP-seq, RNA-seq, and GRO-seq, here we demonstrate a global overlap in the binding of tumor-promoting p53 mutants and the master proinflammatory regulator NFκB that drives alterations in enhancer and gene activation in response to chronic TNF-α signaling. We show that p53 mutants interact directly with NFκB and that both factors impact the other's binding at diverse sets of active enhancers. In turn, the simultaneous and cooperative binding of these factors is required to regulate RNAPII recruitment, the synthesis of enhancer RNAs, and the activation of tumor-promoting genes. Collectively, these findings establish a mechanism by which chronic TNF-α signaling orchestrates a functional interplay between mutant p53 and NFκB that underlies altered patterns of cancer-promoting gene expression.Inflammation is known to affect cancer development, yet the mechanisms by which immune signaling drives transformation remain unclear. Here, the authors provide evidence that chronic TNF-α signaling promotes the enhancer binding and transcriptional interplay between mutant p53 and NFκB.

  19. Brassinosteroid signaling-dependent root responses to prolonged elevated ambient temperature.

    Science.gov (United States)

    Martins, Sara; Montiel-Jorda, Alvaro; Cayrel, Anne; Huguet, Stéphanie; Roux, Christine Paysant-Le; Ljung, Karin; Vert, Grégory

    2017-08-21

    Due to their sessile nature, plants have to cope with and adjust to their fluctuating environment. Temperature elevation stimulates the growth of Arabidopsis aerial parts. This process is mediated by increased biosynthesis of the growth-promoting hormone auxin. How plant roots respond to elevated ambient temperature is however still elusive. Here we present strong evidence that temperature elevation impinges on brassinosteroid hormone signaling to alter root growth. We show that elevated temperature leads to increased root elongation, independently of auxin or factors known to drive temperature-mediated shoot growth. We further demonstrate that brassinosteroid signaling regulates root responses to elevated ambient temperature. Increased growth temperature specifically impacts on the level of the brassinosteroid receptor BRI1 to downregulate brassinosteroid signaling and mediate root elongation. Our results establish that BRI1 integrates temperature and brassinosteroid signaling to regulate root growth upon long-term changes in environmental conditions associated with global warming.Moderate heat stimulates the growth of Arabidopsis shoots in an auxin-dependent manner. Here, Martins et al. show that elevated ambient temperature modifies root growth by reducing the BRI1 brassinosteroid-receptor protein level and downregulating brassinosteroid signaling.

  20. Combining in silico evolution and nonlinear dimensionality reduction to redesign responses of signaling networks.

    Science.gov (United States)

    Prescott, Aaron M; Abel, Steven M

    2017-01-13

    The rational design of network behavior is a central goal of synthetic biology. Here, we combine in silico evolution with nonlinear dimensionality reduction to redesign the responses of fixed-topology signaling networks and to characterize sets of kinetic parameters that underlie various input-output relations. We first consider the earliest part of the T cell receptor (TCR) signaling network and demonstrate that it can produce a variety of input-output relations (quantified as the level of TCR phosphorylation as a function of the characteristic TCR binding time). We utilize an evolutionary algorithm (EA) to identify sets of kinetic parameters that give rise to: (i) sigmoidal responses with the activation threshold varied over 6 orders of magnitude, (ii) a graded response, and (iii) an inverted response in which short TCR binding times lead to activation. We also consider a network with both positive and negative feedback and use the EA to evolve oscillatory responses with different periods in response to a change in input. For each targeted input-output relation, we conduct many independent runs of the EA and use nonlinear dimensionality reduction to embed the resulting data for each network in two dimensions. We then partition the results into groups and characterize constraints placed on the parameters by the different targeted response curves. Our approach provides a way (i) to guide the design of kinetic parameters of fixed-topology networks to generate novel input-output relations and (ii) to constrain ranges of biological parameters using experimental data. In the cases considered, the network topologies exhibit significant flexibility in generating alternative responses, with distinct patterns of kinetic rates emerging for different targeted responses.

  1. Combining in silico evolution and nonlinear dimensionality reduction to redesign responses of signaling networks

    Science.gov (United States)

    Prescott, Aaron M.; Abel, Steven M.

    2016-12-01

    The rational design of network behavior is a central goal of synthetic biology. Here, we combine in silico evolution with nonlinear dimensionality reduction to redesign the responses of fixed-topology signaling networks and to characterize sets of kinetic parameters that underlie various input-output relations. We first consider the earliest part of the T cell receptor (TCR) signaling network and demonstrate that it can produce a variety of input-output relations (quantified as the level of TCR phosphorylation as a function of the characteristic TCR binding time). We utilize an evolutionary algorithm (EA) to identify sets of kinetic parameters that give rise to: (i) sigmoidal responses with the activation threshold varied over 6 orders of magnitude, (ii) a graded response, and (iii) an inverted response in which short TCR binding times lead to activation. We also consider a network with both positive and negative feedback and use the EA to evolve oscillatory responses with different periods in response to a change in input. For each targeted input-output relation, we conduct many independent runs of the EA and use nonlinear dimensionality reduction to embed the resulting data for each network in two dimensions. We then partition the results into groups and characterize constraints placed on the parameters by the different targeted response curves. Our approach provides a way (i) to guide the design of kinetic parameters of fixed-topology networks to generate novel input-output relations and (ii) to constrain ranges of biological parameters using experimental data. In the cases considered, the network topologies exhibit significant flexibility in generating alternative responses, with distinct patterns of kinetic rates emerging for different targeted responses.

  2. The effect of letter-stroke boldness on reading speed in central and peripheral vision.

    Science.gov (United States)

    Bernard, Jean-Baptiste; Kumar, Girish; Junge, Jasmine; Chung, Susana T L

    2013-05-24

    People with central vision loss often prefer boldface print over normal print for reading. However, little is known about how reading speed is influenced by the letter-stroke boldness of font. In this study, we examined the reliance of reading speed on stroke boldness, and determined whether this reliance differs between the normal central and peripheral vision. Reading speed was measured using the rapid serial visual presentation paradigm, where observers with normal vision read aloud short single sentences presented on a computer monitor, one word at a time. Text was rendered in Courier at six levels of boldness, defined as the stroke-width normalized to that of the standard Courier font: 0.27, 0.72, 1, 1.48, 1.89 and 3.04× the standard. Testings were conducted at the fovea and 10° in the inferior visual field. Print sizes used were 0.8× and 1.4× the critical print size (smallest print size that can be read at the maximum reading speed). At the fovea, reading speed was invariant for the middle four levels of boldness, but dropped by 23.3% for the least and the most bold text. At 10° eccentricity, reading speed was virtually the same for all boldness reading speed does not benefit from bold text in the normal fovea and periphery. Excessive increase in stroke boldness may even impair reading speed, especially in the periphery. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. Small Signal Stability Improvement of Power Systems Using Optimal Load Responses in Competitive Electricity Markets

    DEFF Research Database (Denmark)

    Hu, Weihao; Su, Chi; Chen, Zhe

    2011-01-01

    Since the hourly spot market price is available one day ahead in Denmark, the price could be transferred to the consumers and they may shift some of their loads from high price periods to the low price periods in order to save their energy costs. The optimal load response to an electricity price...... price is proposed. A 17-bus power system with high wind power penetrations, which resembles the Eastern Danish power system, is chosen as the study case. Simulation results show that the optimal load response to electricity prices is an effective measure to improve the small signal stability of power...

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

    DEFF Research Database (Denmark)

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

    2006-01-01

    In this article, we have described studies that have demonstrated that mast cells can be activated as a consequence of adaptive and innate immune reactions and that these responses can be modified by ligands for other receptors expressed on the surface of mast cells. These various stimuli...... differentially activate multiple signaling pathways within the mast cells required for the generation and/or release of inflammatory mediators. Thus, the composition of the suite of mediators released and the physiologic ramifications of these responses are dependent on the stimuli and the microenvironment...

  5. Activation of Brain Somatostatin Signaling Suppresses CRF Receptor-Mediated Stress Response

    Directory of Open Access Journals (Sweden)

    Andreas Stengel

    2017-04-01

    Full Text Available Corticotropin-releasing factor (CRF is the hallmark brain peptide triggering the response to stress and mediates—in addition to the stimulation of the hypothalamus-pituitary-adrenal (HPA axis—other hormonal, behavioral, autonomic and visceral components. Earlier reports indicate that somatostatin-28 injected intracerebroventricularly counteracts the acute stress-induced ACTH and catecholamine release. Mounting evidence now supports that activation of brain somatostatin signaling exerts a broader anti-stress effect by blunting the endocrine, autonomic, behavioral (with a focus on food intake and visceral gastrointestinal motor responses through the involvement of distinct somatostatin receptor subtypes.

  6. Assessing signal-driven mechanism in neonates: brain responses to temporally and spectrally different sounds

    Directory of Open Access Journals (Sweden)

    Yasuyo eMinagawa-Kawai

    2011-06-01

    Full Text Available Past studies have found that in adults that acoustic properties of sound signals (such as fast vs. slow temporal features differentially activate the left and right hemispheres, and some have hypothesized that left-lateralization for speech processing may follow from left-lateralization to rapidly changing signals. Here, we tested whether newborns’ brains show some evidence of signal-specific lateralization responses using near-infrared spectroscopy (NIRS and auditory stimuli that elicits lateralized responses in adults, composed of segments that vary in duration and spectral diversity. We found significantly greater bilateral responses of oxygenated hemoglobin (oxy-Hb in the temporal areas for stimuli with a minimum segment duration of 21 ms, than stimuli with a minimum segment duration of 667 ms. However, we found no evidence for hemispheric asymmetries dependent on the stimulus characteristics. We hypothesize that acoustic-based functional brain asymmetries may develop throughout early infancy, and discuss their possible relationship with brain asymmetries for language.

  7. Chemo- and thermosensory responsiveness of Grueneberg ganglion neurons relies on cyclic guanosine monophosphate signaling elements.

    Science.gov (United States)

    Mamasuew, Katharina; Hofmann, Nina; Kretzschmann, Verena; Biel, Martin; Yang, Ruey-Bing; Breer, Heinz; Fleischer, Joerg

    2011-01-01

    Neurons of the Grueneberg ganglion (GG) in the anterior nasal region of mouse pups respond to cool temperatures and to a small set of odorants. While the thermosensory reactivity appears to be mediated by elements of a cyclic guanosine monophosphate (cGMP) cascade, the molecular mechanisms underlying the odor-induced responses are unclear. Since odor-responsive GG cells are endowed with elements of a cGMP pathway, specifically the transmembrane guanylyl cyclase subtype GC-G and the cyclic nucleotide-gated ion channel CNGA3, the possibility was explored whether these cGMP signaling elements may also be involved in chemosensory GG responses. Experiments with transgenic mice deficient for GC-G or CNGA3 revealed that GG responsiveness to given odorants was significantly diminished in these knockout animals. These findings suggest that a cGMP cascade may be important for both olfactory and thermosensory signaling in the GG. However, in contrast to the thermosensory reactivity, which did not decline over time, the chemosensory response underwent adaptation upon extended stimulation, suggesting that the two transduction processes only partially overlap. Copyright © 2011 S. Karger AG, Basel.

  8. The role of gender differences in response to emotional music: a comprehensive analysis of autonomic signal characteristics

    Directory of Open Access Journals (Sweden)

    Atefeh Goshvarpour

    2016-10-01

    Full Text Available Abstract Background: Individual differences, especially gender, have an important role on individuals responds to the emotions. In cognitive science investigations, the analysis of biological signals has been introduced as a confident way to evaluate such responses. In this paper, by adopting a comprehensive approach on biomedical signal processing techniques, a precise examination on women and men differences in affective responses has been provided into different emotional stimuli, including fear, sadness, happiness, and peacefulness. Materials and Methods: Accordingly, signal processing methods were divided into three general categories, linear, wavelet, and non-linear based techniques. In the proposed method, different features from each of three categories and from three autonomic signals, including electrocardiogram (ECG, finger pulse, and galvanic skin response (GSR, were extracted. To induce emotions in participants, validated emotional pieces of music were broadcast in four affective classes. Results: The results indicate the different patterns of responses into affective incentives in women and men. The differences were more noticeable in the features of pulse signal than those of the other signals. Among emotional classes, fear resulted in the highest rate of distinction between men and women emotional responses. Conclusion: By the comprehensive evaluation of autonomic signals and different signal processing techniques, this study has tried to offer a new insight for better understanding of gender differences in emotional responses. In addition, it will help the researchers to adopt appropriate decisions in identifying efficient processing approach to deal with large amount of information achieved from signal analysis.

  9. BOLD data representing activation and connectivity for rare no-go versus frequent go cues

    Directory of Open Access Journals (Sweden)

    Harma Meffert

    2016-06-01

    Full Text Available The neural circuitry underlying response control is often studied using go/no-go tasks, in which participants are required to respond as fast as possible to go cues and withhold from responding to no-go stimuli. In the current task, response control was studied using a fully counterbalanced design in which blocks with a low frequency of no-go cues (75% go, 25% no-go were alternated with blocks with a low frequency of go cues (25% go, 75% no-go; see also “Segregating attention from response control when performing a motor inhibition task: Segregating attention from response control” [1]. We applied a whole brain corrected, paired t-test to the data assessing for regions differentially activated by low frequency no-go cues relative to high frequency go cues. In addition, we conducted a generalized psychophysiological interaction analysis on the data using a right inferior frontal gyrus seed region. This region was identified through the BOLD response t-test and was chosen because right inferior gyrus is highly implicated in response inhibition.

  10. Localization of cortical primary motor area of the hand using navigated transcranial magnetic stimulation, BOLD and arterial spin labeling fMRI.

    Science.gov (United States)

    Kallioniemi, Elisa; Pitkänen, Minna; Könönen, Mervi; Vanninen, Ritva; Julkunen, Petro

    2016-11-01

    Although the relationship between neuronavigated transcranial magnetic stimulation (nTMS) and functional magnetic resonance imaging (fMRI) has been widely studied in motor mapping, it is unknown how the motor response type or the choice of motor task affect this relationship. Centers of gravity (CoGs) and response maxima were measured with blood-oxygen-level dependent (BOLD) and arterial spin labeling (ASL) fMRI during motor tasks against nTMS CoGs and response maxima, which were mapped with motor evoked potentials (MEPs) and silent periods (SPs). No differences in motor representations (CoGs and response maxima) were observed in lateral-medial direction (p=0.265). fMRI methods localized the motor representation more posterior than nTMS (pmotor task (p>0.999) nor nTMS response type (p>0.999). ASL fMRI maxima did not differ from the nTMS nor BOLD fMRI CoGs (p≥0.070), but the ASL CoG was deeper in comparison to other methods (p≤0.042). The BOLD fMRI motor task did not influence the depth of the motor representation (p≥0.745). The median Euclidean distances between the nTMS and fMRI motor representations varied between 7.7mm and 14.5mm and did not differ between the methods (F≤1.23, p≥0.318). The relationship between fMRI and nTMS mapped excitatory (MEP) and inhibitory (SP) responses, and whether the choice of motor task affects this relationship, have not been studied before. The congruence between fMRI and nTMS is good. The choice of nTMS motor response type nor BOLD fMRI motor task had no effect on this relationship. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Transcriptome profiling of the cold response and signaling pathways in Lilium lancifolium.

    Science.gov (United States)

    Wang, Jingmao; Yang, Yang; Liu, Xiaohua; Huang, Jie; Wang, Qing; Gu, Jiahui; Lu, Yingmin

    2014-03-17

    Lilium lancifolium, a very important cold-resistant wild flower for lily cold resistance breeding, is widely distributed in southwestern and northeastern China. To gain a better understanding of the cold signaling pathway and the molecular metabolic reactions involved in the cold response, we performed a genome-wide transcriptional analysis using RNA-Seq. Approximately 104,703 million clean 90- bp paired-end reads were obtained from three libraries (CK 0 h, Cold-treated 2 h and 16 h at 4 °C); 18,736 unigenes showed similarity to known proteins in the Swiss-Prot protein database, and 15,898, 13,705 and 1849 unigenes aligned to existing sequences in the KEGG and COG databases (comprising 25 COG categories) and formed 12 SOM clusters, respectively. Based on qRT-PCR results, we studied three signal regulation pathways--the Ca(2+) and ABA independent/dependent pathways--that conduct cold signals to signal transduction genes such as LlICE and LlCDPK and transcription factor genes such as LlDREB1/CBF, LlAP2/EREBP, LlNAC1, LlR2R3-MYB and LlBZIP, which were expressed highly in bulb. LlFAD3, Llβ-amylase, LlP5CS and LlCLS responded to cold and enhanced adaptation processes that involve changes in the expression of transcripts related to cellular osmoprotectants and carbohydrate metabolism during cold stress. Our study of differentially expressed genes involved in cold-related metabolic pathways and transcription factors facilitated the discovery of cold-resistance genes and the cold signal transcriptional networks, and identified potential key components in the regulation of the cold response in L lancifolium, which will be most beneficial for further research and in-depth exploration of cold-resistance breeding candidate genes in lily.

  12. PKA catalytic subunit compartmentation regulates contractile and hypertrophic responses to β-adrenergic signaling

    Science.gov (United States)

    Yang, Jason H.; Polanowska-Grabowska, Renata K.; Smith, Jeffrey S.; Shields, Charles W.; Saucerman, Jeffrey J.

    2014-01-01

    β-adrenergic signaling is spatiotemporally heterogeneous in the cardiac myocyte, conferring exquisite control to sympathetic stimulation. Such heterogeneity drives the formation of protein kinase A (PKA) signaling microdomains, which regulate Ca2+ handling and contractility. Here, we test the hypothesis that the nucleus independently comprises a PKA signaling microdomain regulating myocyte hypertrophy. Spatially-targeted FRET reporters for PKA activity identified slower PKA activation and lower isoproterenol sensitivity in the nucleus (t50 = 10.60±0.68 min; EC50 = 89.00 nmol/L) than in the cytosol (t50 = 3.71±0.25 min; EC50 = 1.22 nmol/L). These differences were not explained by cAMP or AKAP-based compartmentation. A computational model of cytosolic and nuclear PKA activity was developed and predicted that differences in nuclear PKA dynamics and magnitude are regulated by slow PKA catalytic subunit diffusion, while differences in isoproterenol sensitivity are regulated by nuclear expression of protein kinase inhibitor (PKI). These were validated by FRET and immunofluorescence. The model also predicted differential phosphorylation of PKA substrates regulating cell contractility and hypertrophy. Ca2+ and cell hypertrophy measurements validated these predictions and identified higher isoproterenol sensitivity for contractile enhancements (EC50 = 1.84 nmol/L) over cell hypertrophy (EC50 = 85.88 nmol/L). Over-expression of spatially targeted PKA catalytic subunit to the cytosol or nucleus enhanced contractile and hypertrophic responses, respectively. We conclude that restricted PKA catalytic subunit diffusion is an important PKA compartmentation mechanism and the nucleus comprises a novel PKA signaling microdomain, insulating hypertrophic from contractile β-adrenergic signaling responses. PMID:24225179

  13. Starvation signals in yeast are integrated to coordinate metabolic reprogramming and stress response to ensure longevity.

    Science.gov (United States)

    Zhang, Nianshu; Cao, Lu

    2017-10-01

    Studies on replicative and chronological aging in Saccharomyces cerevisiae have greatly advanced our understanding of how longevity is regulated in all eukaryotes. Chronological lifespan (CLS) of yeast is defined as the age-dependent viability of non-dividing cell populations. A number of nutrient sensing and signal transduction pathways (mainly TOR and PKA) have been shown to regulate CLS, yet it is poorly understood how the starvation signals transduced via these pathways lead to CLS extension. Using reporters whose expressions are induced by glucose starvation, we have screened the majority of the 'signaling' mutants in the yeast genome and identified many genes that are necessary for stress response. Subsequent analyses of the 'signaling' mutants not only revealed novel regulators of CLS, such as the GSK-3 ortholog Mck1, but also demonstrated that starvation signals transmitted by SNF1/AMPK, PKC1 and those negatively regulated by TOR/PKA, including Rim15, Yak1 and Mck1 kinases, are integrated to enable metabolic reprogramming and the acquisition of stress resistance. Coordinated metabolic reprogramming ensures the accumulation of storage carbohydrates for quiescent cells to maintain viability. We provide new evidence that Yak1, Rim15 and Mck1 kinases cooperate to activate H 2 O 2 -scanvenging activities, thus limiting the levels of ROS in cells entering quiescence. These findings support the recent advances in higher organisms that the flexibility of metabolic reprogramming and the balance between energetics and stress resistance are the unifying principles of lifespan extension. Future work to reveal how the metabolic switch and stress response is coordinated will help delineate the molecular mechanisms of aging in yeast and shed novel insight into aging/anti-aging principles in higher organisms.

  14. Projecting boreal bird responses to climate change: the signal exceeds the noise.

    Science.gov (United States)

    Stralberg, D; Matsuoka, S M; Hamann, A; Bayne, E M; Sólymos, P; Schmiegelow, F K A; Wang, X; Cumming, S G; Song, S J

    2015-01-01

    For climate change projections to be useful, the magnitude of change must be understood relative to the magnitude of uncertainty in model predictions. We quantified the signal-to-noise ratio in projected distributional responses of boreal birds to climate change, and compared sources of uncertainty. Boosted regression tree models of abundance were generated for 80 boreal-breeding bird species using a comprehensive data set of standardized avian point counts (349,629 surveys at 122,202 unique locations) and 4-km climate, land use, and topographic data. For projected changes in abundance, we calculated signal-to-noise ratios and examined variance components related to choice of global climate model (GCM) and two sources of species distribution model (SDM) uncertainty: sampling error and variable selection. We also evaluated spatial, temporal, and interspecific variation in these sources of uncertainty. The mean signal-to-noise ratio across species increased over time to 2.87 by the end of the 21st century, with the signal greater than the noise for 88% of species. Across species, climate change represented the largest component (0.44) of variance in projected abundance change. Among sources of uncertainty evaluated, choice of GCM (mean variance component = 0.17) was most important for 66% of species, sampling error (mean= 0.12) for 29% of species, and variable selection (mean =0.05) for 5% of species. Increasing the number of GCMs from four to 19 had minor effects on these results. The range of projected changes and uncertainty characteristics across species differed markedly, reinforcing the individuality of species' responses to climate change and the challenges of one-size-fits-all approaches to climate change adaptation. We discuss the usefulness of different conservation approaches depending on the strength of the climate change signal relative to the noise, as well as the dominant source of prediction uncertainty.

  15. BOLD-MRI of breast invasive ductal carcinoma: correlation of R2* value and the expression of HIF-1{alpha}

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Min; Guo, Xiaojuan; Wang, Shuangkun [Capital Medical University, Department of Radiology, Beijing Chao Yang Hospital, Beijing (China); Jin, Mulan; Wang, Ying [Capital Medical University Beijing, Department of Pathology, Beijing Chaoyang Hospital, Beijing (China); Li, Jie; Liu, Jun [Capital Medical University Beijing, Department of Breast Surgery, Beijing Chaoyang Hospital, Beijing (China)

    2013-12-15

    To explore the reliability and feasibility of blood oxygenation level-dependent-based functional magnetic resonance imaging (BOLD-fMRI) to depict hypoxia in breast invasive ductal carcinoma. A total of 103 women with 104 invasive ductal carcinomas (IDCs) underwent breast BOLD-fMRI at 3.0 T. Histological specimens were analysed for tumour size, grade, axillary lymph nodes and expression of oestrogen receptors, progesterone receptors, human epidermal growth factor receptor 2, p53, Ki-67 and hypoxia inducible factor 1{alpha} (HIF-1{alpha}). The distribution and reliability of R2* were analysed. Correlations of the R2* value with the prognostic factors and HIF-1{alpha} were respectively analysed. The R2* map of IDC demonstrated a relatively heterogeneous signal. The mean R2* value was (53.4 {+-} 18.2) Hz. The Shapiro-Wilk test (W = 0.971, P = 0.020) suggested that the sample did not follow a normal distribution. The inter-rater and intrarater correlation coefficient was 0.967 and 0.959, respectively. The R2* values of IDCs were significantly lower in patients without axillary lymph nodes metastasis. The R2* value had a weak correlation with Ki67 expression (r = 0.208, P = 0.038). The mean R2* value correlated moderately with the level of HIF-1{alpha} (r = 0.516, P = 0.000). BOLD-fMRI is a simple and non-invasive technique that yields hypoxia information on breast invasive ductal carcinomas. (orig.)

  16. Regulation of fruit and seed response to heat and drought by sugars as nutrients and signals

    Directory of Open Access Journals (Sweden)

    Yong-Hua eLiu

    2013-08-01

    Full Text Available A large body of evidence shows that sugars function both as nutrients and signals to regulate fruit and seed set under normal and stress conditions including heat and drought. Inadequate sucrose import to, and its degradation within, reproductive organs cause fruit and seed abortion under heat and drought. As nutrients, sucrose-derived hexoses provide carbon skeletons and energy for growth and development of fruits and seeds. Sugar metabolism can also alleviate the impact of stress on fruit and seed through facilitating biosynthesis of heat shock proteins (Hsps and non-enzymic antioxidants (e.g. glutathione, ascorbic acid, which collectively maintain the integrity of membranes and prevent programmed cell death (PCD through protecting proteins and scavenging reactive oxygen species (ROS. In parallel, sugars (sucrose, glucose and fructose, also exert signalling roles through cross-talk with hormone and ROS signalling pathways and by mediating cell division and PCD. At the same time, emerging data indicate that sugar-derived signalling systems, including trehalose-6 phosphate (T6P, sucrose non-fermenting related kinase-1 (SnRK and the target of rapamycin (TOR kinase complex also play important roles in regulating plant development through modulating nutrient and energy signalling and metabolic processes, especially under abiotic stresses where sugar availability is low. This review aims to evaluate recent progress of research on abiotic stress responses of reproductive organs focusing on roles of sugar metabolism and signalling and addressing the possible biochemical and molecular mechanism by which sugars regulate fruit and seed set under heat and drought.

  17. microRNA-124 negatively regulates TLR signaling in alveolar macrophages in response to mycobacterial infection.

    Science.gov (United States)

    Ma, Chunyan; Li, Yong; Li, Min; Deng, Guangcun; Wu, Xiaoling; Zeng, Jin; Hao, Xiujing; Wang, Xiaoping; Liu, Jing; Cho, William C S; Liu, Xiaoming; Wang, Yujiong

    2014-11-01

    The emerging roles of microRNAs (miRNAs) in regulating immune responses have attracted increasing attention in recent years; and the alveolar macrophages (AMs) are the main targets of mycobacterial infection, which play a pivotal role in the pathogenesis of Mycobacterium tuberculosis infection. However, the immunoregulatory role of miRNAs in AMs has not been fully demonstrated. In this study, we find that miR-124 is up-regulated in the peripheral leukocytes of patients with pulmonary tuberculosis; furthermore, the expression miR-124 can be induced upon Mycobacterium bovis Bacillus Calmette-Guerin (BCG) infection in both RAW264.7 AM cells in vitro and murine AMs in vivo. Mechanistically, miR-124 is able to modulate toll-like receptor (TLR) signaling activity in RAW264.7 cells in response to BCG infection. In this regard, multiple components of TLR signaling cascade, including the TLR6, myeloid differentiation factor 88 (MyD88), TNFR-associated factor 6 and tumor necrosis factor-α are directly targeted by miR-124. In addition, both overexpression of TLR signaling adaptor MyD88 and BCG infection are able to augment miR-124 transcription, while MyD88 expression silenced by small interfering RNA dramatically suppresses miR-124 expression in AMs in vitro. Moreover, the abundance of miR-124 transcript in murine AMs of MyD88 deficient mice is significantly less than that of their wild-type or heterozygous littermates; and the BCG infection fails to induce miR-124 expression in the lung of MyD88 deficient mouse. These results indicate a negative regulatory role of miR-124 in fine-tuning inflammatory response in AMs upon mycobacterial infection, in part through a mechanism by directly targeting TLR signaling. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. BOLD fMRI in infants under sedation: Comparing the impact of pentobarbital and propofol on auditory and language activation.

    Science.gov (United States)

    DiFrancesco, Mark W; Robertson, Sara A; Karunanayaka, Prasanna; Holland, Scott K

    2013-11-01

    To elucidate differences in the disruption of language network function, as measured by blood oxygenation level-dependent (BOLD) contrast functional MRI (fMRI), attributable to two common sedative agents administered to infants under clinical imaging protocols. The sedatives pentobarbital (Nembutal) and Propofol, administered clinically to infants at 1 year of age, were compared with respect to BOLD activation profiles in response to passive story-listening stimulation. An intermittent event-related imaging protocol was used with which the temporal evolution of language processing resulting from this stimulation was explored. Propofol and Nembutal were found to have distinct and complementary responses to story-listening. Propofol exhibited more activation in higher processing networks with increasing response toward the end of narrative stimulus. Nembutal, in contrast, had much more robust activation of primary and secondary sensory cortices but a decreasing response over time in fronto-parietal default-mode regions. This may suggest a breakdown of top-down feedback for Propofol versus the lack of bottom-up feed-forward processing for Nembutal. Two popular sedative agents for use in children for clinical fMRI were found to induce distinct alteration of activation patterns from a language stimulus. This has ramifications for clinical fMRI of sedated infants and encourages further study to build a framework for more confident interpretation. Copyright © 2013 Wiley Periodicals, Inc.

  19. Systems approach to characterizing cell signaling in host-pathogen response to staphylococcus toxin.

    Energy Technology Data Exchange (ETDEWEB)

    Ambrosiano, J. J. (John J.); Gupta, G. (Goutam); Gray, P. C. (Perry C.); Hush, D. R. (Donald R.); Fugate, M. L. (Michael L.); Cleland, T. J. (Timothy J.); Roberts, R. M. (Randy M.); Hlavacek, W. S. (William S.); Smith, J. L. (Jessica L.)

    2002-01-01

    The mammalian immune system is capable of highly sensitive and specific responses when challenged by pathogens. It is believed that the human immune repertoire - the total number of distinct antigens that can be recognized - is between 10{sup 9} and 10{sup 11}. The most specific responses are cell mediated and involve complex and subtle communications among the immune cells via small proteins known as cytokines. The details of host-pathogen response are exceedingly complex, involving both intracellular and extracellular mechanisms. These include the presentation of antigen by B cells to helper T cells and subsequent stimulation of signal transduction pathways and gene expression within both B and T-cell populations. These in turn lead to the secretion of cytokines and receptor expression. Intercellular cytokine signaling can trigger a host of immune responses including the proliferation and specialization of naive immune cells and the marshaling of effector cells to combat infection. In the ever-evolving game of threat and countermeasure played out by pathogens and their intended hosts, there are direct assaults aimed at subverting the immune system's ability to recognize antigens and respond effectively to challenge by pathogens. Staphylococcus is one of these. Staph bacteria secrete a variety of toxins known generically as superantigens. Superantigen molecules bind simultaneously to the MHC receptors of antigen presenting cells and the TCR receptors of helper T cells, locking them in place and leading to overstimulation. This strategy can effectively burn out the immune system in a matter of days.

  20. Hypothalamic response to the chemo-signal androstadienone in gender dysphoric children and adolescents

    Directory of Open Access Journals (Sweden)

    Sarah M Burke

    2014-05-01

    Full Text Available The odorous steroid androstadienone, a putative male chemo-signal, was previously reported to evoke sex differences in hypothalamic activation in adult heterosexual men and women. In order to investigate whether puberty modulated this sex difference in response to androstadienone we measured the hypothalamic responsiveness to this chemo-signal in 39 prepubertal and 41 adolescent boys and girls by means of functional magnetic resonance imaging. We then investigated whether 36 prepubertal children and 38 adolescents diagnosed with Gender Dysphoria (GD; DSM-5 exhibited sex-atypical (in accordance with their experienced gender, rather than sex-typical (in accordance with their natal sex hypothalamic activations during olfactory stimulation with androstadienone. We found that the sex difference in responsiveness to androstadienone was already present in prepubertal control children and thus likely developed during early perinatal development instead of during sexual maturation. Adolescent girls and boys with GD both responded remarkably like their experienced gender, thus sex-atypical. In contrast, prepubertal girls with GD showed neither a typically male nor female hypothalamic activation pattern and prepubertal boys with GD had hypothalamic activations in response to androstadienone that were similar to control boys, thus sex-typical. We present here a unique data set of boys and girls diagnosed with GD at two different developmental stages, showing that these children possess certain sex-atypical functional brain characteristics and may have undergone atypical sexual differentiation of the brain.

  1. Hypothalamic Response to the Chemo-Signal Androstadienone in Gender Dysphoric Children and Adolescents

    Science.gov (United States)

    Burke, Sarah M.; Cohen-Kettenis, Peggy T.; Veltman, Dick J.; Klink, Daniel T.; Bakker, Julie

    2014-01-01

    The odorous steroid androstadienone, a putative male chemo-signal, was previously reported to evoke sex differences in hypothalamic activation in adult heterosexual men and women. In order to investigate whether puberty modulated this sex difference in response to androstadienone, we measured the hypothalamic responsiveness to this chemo-signal in 39 pre-pubertal and 41 adolescent boys and girls by means of functional magnetic resonance imaging. We then investigated whether 36 pre-pubertal children and 38 adolescents diagnosed with gender dysphoria (GD; DSM-5) exhibited sex-atypical (in accordance with their experienced gender), rather than sex-typical (in accordance with their natal sex) hypothalamic activations during olfactory stimulation with androstadienone. We found that the sex difference in responsiveness to androstadienone was already present in pre-pubertal control children and thus likely developed during early perinatal development instead of during sexual maturation. Adolescent girls and boys with GD both responded remarkably like their experienced gender, thus sex-atypical. In contrast, pre-pubertal girls with GD showed neither a typically male nor female hypothalamic activation pattern and pre-pubertal boys with GD had hypothalamic activations in response to androstadienone that were similar to control boys, thus sex-typical. We present here a unique data set of boys and girls diagnosed with GD at two different developmental stages, showing that these children possess certain sex-atypical functional brain characteristics and may have undergone atypical sexual differentiation of the brain. PMID:24904525

  2. How Do Parameters of Motor Response Influence Selective Inhibition? Evidence from the Stop-Signal Paradigm

    Directory of Open Access Journals (Sweden)

    Chien Hui Tang

    2011-05-01

    Full Text Available The ability to selectively inhibit the execution of an action while performing other ones is crucial in humans' multitasking daily life. The current study aims to compare selective inhibition for choice reaction involving two effectors or response directions. We adopted a variation of the stop-signal paradigm to examine how selective inhibition is modulated by the way potential motor responses are combined and inhibited. Experiment 1 investigated selective inhibition under different combinations of effectors, namely “index and middle fingers” versus “hand and foot”. The results showed SSRT of the index finger was longer when the other response option was the foot than the middle finger. Experiment 2 examined how selective inhibition differs between selective stopping of effectors and movement directions, and that for most of the situations SSRT is longer for stopping a response based on its direction than effector. After equating complexity of response mapping between direction and effector conditions in Experiment 2, Experiment 3 still showed that SSRT differs between selecting direction or effectors. To summarize, SSRT varies depending on the way response effectors are paired and selectively stopped. Selective inhibition is thus likely not amodal and may involve different inhibitory mechanisms depending on parameters specifying the motor response.

  3. Electrical signalling along the phloem and its physiological responses in the maize leaf

    Directory of Open Access Journals (Sweden)

    Joerg eFromm

    2013-07-01

    Full Text Available To elucidate the role of electrical signalling in the phloem of maize the tips of attached leaves were stimulated by chilling and wounding. Two different signals were detected in the phloem at the middle of the leaf using the aphid stylet technique: (i action potentials (AP arose in the phloem after chilling; and (ii variation potentials (VP were evoked after wounding the leaf tip. Combined electric potential and gas exchange measurements showed that while the wound-induced VP moved rapidly towards the middle of the leaf to induce a reduction in both the net-CO2 uptake rate and the stomatal conductance, there was no response in the gas exchange to the cold-induced AP. To determine if electrical signalling had any impact on assimilate transport the middle of the leaf was exposed to 14CO2. Autoradiography of labelled assimilates provided evidence that phloem and intercellular transport of assimilates from mesophyll to bundle sheath cells was strongly reduced while the cold-induced AP moved through. In contrast, wound-induced VP did not inhibit assimilate translocation but did reduce the amount of the labelled assimilate in phloem and bundle sheath cells. Biochemical analysis revealed that callose content increased significantly in chilled leaves while starch increased in chilled but decreased in wounded leaves. The results led to the conclusion that different stimulation types incite characteristic phloem-transmitted electrical signals, each with a specific influence on gas exchange and assimilate transport.

  4. Insulin secretion and signaling in response to dietary restriction and subsequent re-alimentation in cattle.

    Science.gov (United States)

    Keogh, Kate; Kenny, David A; Kelly, Alan K; Waters, Sinéad M

    2015-08-01

    The objectives of this study were to examine systemic insulin response to a glucose tolerance test (GTT) and transcript abundance of genes of the insulin signaling pathway in skeletal muscle, during both dietary restriction and re-alimentation-induced compensatory growth. Holstein Friesian bulls were blocked to one of two groups: 1) restricted feed allowance for 125 days (period 1) (RES, n = 15) followed by ad libitum feeding for 55 days (period 2) or 2) ad libitum access to feed throughout (periods 1 and 2) (ADLIB, n = 15). On days 90 and 36 of periods 1 and 2, respectively, a GTT was performed. M. longissimus dorsi biopsies were harvested from all bulls on days 120 and 15 of periods 1 and 2, respectively, and RNA-Seq analysis was performed. RES displayed a lower growth rate during period 1 (RES: 0.6 kg/day, ADLIB: 1.9 kg/day; P alimentation (RES: 2.5 kg/day, ADLIB: 1.4 kg/day; P alimentation (P > 0.05). Genes differentially expressed in the insulin signaling pathway suggested a greater sensitivity to insulin in skeletal muscle, with pleiotropic effects of insulin signaling interrupted during dietary restriction. Collectively, these results indicate increased sensitivity to glucose clearance and skeletal muscle insulin signaling during dietary restriction; however, no overall role for insulin was apparent in expressing compensatory growth. Copyright © 2015 the American Physiological Society.

  5. Molecular hydrogen is involved in phytohormone signaling and stress responses in plants.

    Directory of Open Access Journals (Sweden)

    Jiqing Zeng

    Full Text Available Molecular hydrogen (H2 metabolism in bacteria and algae has been well studied from an industrial perspective because H2 is viewed as a potential future energy source. A number of clinical trials have recently reported that H2 is a therapeutic antioxidant and signaling molecule. Although H2 metabolism in higher plants was reported in some early studies, its biological effects remain unclear. In this report, the biological effects of H2 and its involvement in plant hormone signaling pathways and stress responses were determined. Antioxidant enzyme activity was found to be increased and the transcription of corresponding genes altered when the effects of H2 on the germination of mung bean seeds treated with phytohormones was investigated. In addition, upregulation of several phytohormone receptor genes and genes that encode a few key factors involved in plant signaling pathways was detected in rice seedlings treated with HW. The transcription of putative rice hydrogenase genes, hydrogenase activity, and endogenous H2 production were also determined. H2 production was found to be induced by abscisic acid, ethylene, and jasmonate acid, salt, and drought stress and was consistent with hydrogenase activity and the expression of putative hydrogenase genes in rice seedlings. Together, these results suggest that H2 may have an effect on rice stress tolerance by modulating the output of hormone signaling pathways.

  6. Protein degradation mechanisms modulate abscisic acid signaling and responses during abiotic stress.

    Science.gov (United States)

    Jurkiewicz, Pawel; Batoko, Henri

    2018-02-01

    Abiotic stresses such as salinity, drought, high temperature or freezing can be perceived, in part, as a transient or permanent hyperosmotic stress by the plant cell. As sessile organisms, the detrimental effects of these environmental insults limit plants productivity but also their geographical distribution. Sensing and signaling events that detect the hyperosmotic (or simply osmotic) stress involve the cellular increase of active abscisic acid (ABA). The stress phytohormone ABA regulates fundamental growth and developmental processes in the plant by marshalling metabolic and gene-expression reprogramming. Among the ABA-responsive genes, some are strictly ABA-dependent in that their expression is almost undetectable in absence of elevated levels of cellular ABA, thus their physiological role may be required only transiently. In addition, ABA-dependent modulation of some of the signaling effectors can be irreversible. In this review, without any pretention to being exhaustive, we use specific examples to illustrate how mechanistically conserved eukaryotic cell proteolytic pathways affect ABA-dependent signaling. We describe how defined proteolysis mechanisms in the plant cell, including Regulated Intramembrane Proteolysis (RIP), the Ubiquitin 26S Proteasomal System (UPS), the endocytic and autophagy pathways, contribute to regulate the spatiotemporal level and activity of PP2Cs (protein phosphatases 2C), and how an intriguing ABA-induced protein, the plant Translocator protein (TSPO), is targeted for degradation. Degradation of regulatory or effector molecules modulates or desensitizes ABA-dependent signaling and reestablishes cellular homeostasis. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. ZAP-70 and p72syk are signaling response elements through MHC class II molecules

    DEFF Research Database (Denmark)

    Kanner, S B; Grosmaire, L S; Blake, J

    1995-01-01

    Ligation of major histocompatibility complex (MHC) class II antigens expressed on antigen-activated human CD4+ T-lymphocytes induces early signal transduction events including the activation of tyrosine kinases, the tyrosine phosphorylation of phospholipase-C gamma 1 and the mobilization of intra......Ligation of major histocompatibility complex (MHC) class II antigens expressed on antigen-activated human CD4+ T-lymphocytes induces early signal transduction events including the activation of tyrosine kinases, the tyrosine phosphorylation of phospholipase-C gamma 1 and the mobilization...... of intracellular calcium. Similar responses have been observed in B-cells following stimulation of MHC class II molecules, including the increased production of intracellular cAMP. In this report, we demonstrate that the ZAP-70 tyrosine kinase is a responsive signaling element following cross-linking of HLA...... by herbimycin A. MHC class II ligation on B-lymphocytes resulted in cell death, which was both qualitatively distinct from Fas-induced apoptosis and partially protected by herbimycin A pretreatment. Thus, ligation of MHC class II molecules expressed on human lymphocytes stimulates the ZAP-70/p72syk family...

  8. Unique responsiveness of angiosperm stomata to elevated CO2 explained by calcium signalling.

    Directory of Open Access Journals (Sweden)

    Timothy J Brodribb

    Full Text Available Angiosperm and conifer tree species respond differently when exposed to elevated CO2, with angiosperms found to dynamically reduce water loss while conifers appear insensitive. Such distinct responses are likely to affect competition between these tree groups as atmospheric CO2 concentration rises. Seeking the mechanism behind this globally important phenomenon we targeted the Ca(2+-dependent signalling pathway, a mediator of stomatal closure in response to elevated CO2, as a possible explanation for the differentiation of stomatal behaviours. Sampling across the diversity of vascular plants including lycophytes, ferns, gymnosperms and angiosperms we show that only angiosperms possess the stomatal behaviour and prerequisite genetic coding, linked to Ca(2+-dependent stomatal signalling. We conclude that the evolution of Ca(2+-dependent stomatal signalling gives angiosperms adaptive benefits in terms of highly efficient water use, but that stomatal sensitivity to high CO2 may penalise angiosperm productivity relative to other plant groups in the current era of soaring atmospheric CO2.

  9. Evc regulates a symmetrical response to Shh signaling in molar development.

    Science.gov (United States)

    Nakatomi, M; Hovorakova, M; Gritli-Linde, A; Blair, H J; MacArthur, K; Peterka, M; Lesot, H; Peterkova, R; Ruiz-Perez, V L; Goodship, J A; Peters, H

    2013-03-01

    Tooth morphogenesis involves patterning through the activity of epithelial signaling centers that, among other molecules, secrete Sonic hedgehog (Shh). While it is known that Shh responding cells need intact primary cilia for signal transduction, the roles of individual cilia components for tooth morphogenesis are poorly understood. The clinical features of individuals with Ellis-van Creveld syndrome include various dental anomalies, and we show here that absence of the cilial protein Evc in mice causes various hypo- and hyperplasia defects during molar development. During first molar development, the response to Shh signaling is progressively lost in Evc-deficient embryos and, unexpectedly, the response consistently disappears in a buccal to lingual direction. The important role of Evc for establishing the buccal-lingual axis of the developing first molar is also supported by a displaced activity of the Wnt pathway in Evc mutants. The observed growth abnormalities eventually manifest in first molar microdontia, disruption of molar segmentation and symmetry, root fusions, and delayed differentiation. Analysis of our data indicates that both spatially and temporally disrupted activities of the Shh pathway are the primary cause for the variable dental anomalies seen in patients with Ellis-van Creveld syndrome or Weyers acrodental dysostosis.

  10. Leptin signal transduction underlies the differential metabolic response of LEW and WKY rats to cafeteria diet.

    Science.gov (United States)

    Martínez-Micaelo, N; González-Abuín, N; Ardévol, A; Pinent, M; Petretto, E; Behmoaras, J; Blay, M

    2016-01-01

    Although the effect of genetic background on obesity-related phenotypes is well established, the main objective of this study is to determine the phenotypic responses to cafeteria diet (CAF) of two genetically distinct inbred rat strains and give insight into the molecular mechanisms that might be underlying. Lewis (LEW) and Wistar-Kyoto (WKY) rats were fed with either a standard or a CAF diet. The effects of the diet and the strain in the body weight gain, food intake, respiratory quotient, biochemical parameters in plasma as well as in the expression of genes that regulate leptin signalling were determined. Whereas CAF diet promoted weight gain in LEW and WKY rats, as consequence of increased energy intake, metabolic management of this energy surplus was significantly affected by genetic background. LEW and WKY showed a different metabolic profile, LEW rats showed hyperglycaemia, hypertriglyceridemia and high FFA levels, ketogenesis, high adiposity index and inflammation, but WKY did not. Leptin signalling, and specifically the LepRb-mediated regulation of STAT3 activation and Socs3 gene expression in the hypothalamus were inversely modulated by the CAF diet in LEW (upregulated) and WKY rats (downregulated). In the present study, we show evidence of gene-environment interactions in obesity exerted by differential phenotypic responses to CAF diet between LEW and WKY rats. Specifically, we found the leptin-signalling pathway as a divergent point between the strain-specific adaptations to diet. © 2016 Society for Endocrinology.

  11. Mechanical signaling and the cellular response to extracellular matrix in angiogenesis and cardiovascular physiology

    Science.gov (United States)

    Ingber, Donald E.

    2002-01-01

    Great advances have been made in the identification of the soluble angiogenic factors, insoluble extracellular matrix (ECM) molecules, and receptor signaling pathways that mediate control of angiogenesis--the growth of blood capillaries. This review focuses on work that explores how endothelial cells integrate these chemical signals with mechanical cues from their local tissue microenvironment so as to produce functional capillary networks that exhibit specialized form as well as function. These studies have revealed that ECM governs whether an endothelial cell will switch between growth, differentiation, motility, or apoptosis programs in response to a soluble stimulus based on its ability to mechanically resist cell tractional forces and thereby produce cell and cytoskeletal distortion. Transmembrane integrin receptors play a key role in this mechanochemical transduction process because they both organize a cytoskeletal signaling complex within the focal adhesion and preferentially focus mechanical forces on this site. Molecular filaments within the internal cytoskeleton--microfilaments, microtubules, and intermediate filaments--also contribute to the cell's structural and functional response to mechanical stress through their role as discrete support elements within a tensegrity-stabilized cytoskeletal array. Importantly, a similar form of mechanical control also has been shown to be involved in the regulation of contractility in vascular smooth muscle cells and cardiac myocytes. Thus, the mechanism by which cells perform mechanochemical transduction and the implications of these findings for morphogenetic control are discussed in the wider context of vascular development and cardiovascular physiology.

  12. Chronic hypoxia attenuates VEGF signaling and angiogenic responses by downregulation of KDR in human endothelial cells.

    Science.gov (United States)

    Olszewska-Pazdrak, Barbara; Hein, Travis W; Olszewska, Paulina; Carney, Darrell H

    2009-05-01

    Coronary artery disease results in progressive vascular stenosis associated with chronic myocardial ischemia. Vascular endothelial growth factor (VEGF) stimulates endothelial cell angiogenic responses to revascularize ischemic tissues; however, the effect of chronic hypoxia on the responsiveness of endothelial cells to VEGF remains unclear. We, therefore, investigated whether hypoxia alters VEGF-stimulated signaling and angiogenic responses in primary human coronary artery endothelial (HCAE) cells. Exposure of HCAE cells to hypoxia (1% O(2)) for 24 h decreased VEGF-stimulated endothelial cell migration ( approximately 82%), proliferation ( approximately 30%), and tube formation. Hypoxia attenuated VEGF-stimulated activation of endothelial nitric oxide (NO) synthase (eNOS) ( approximately 72%) and reduced NO production in VEGF-stimulated cells from 237 +/- 38.8 to 61.3 +/- 28.4 nmol/l. Moreover, hypoxia also decreased the ratio of phosphorylated eNOS to total eNOS in VEGF-stimulated cells by approximately 50%. This effect was not observed in thrombin-stimulated cells, suggesting that hypoxia specifically inhibited VEGF signaling upstream of eNOS phosphorylation. VEGF-induced activation of Akt, ERK1/2, p38, p70S6 kinases, and S6 ribosomal protein was also attenuated in hypoxic cells. Moreover, VEGF-stimulated phosphorylation of VEGF receptor-2 (KDR) at Y996 and Y1175 was decreased by hypoxia. This decrease correlated with a 70 +/- 12% decrease in KDR protein expression. Analysis of mRNA from these cells showed that hypoxia reduced steady-state levels of KDR mRNA by 52 +/- 16% and decreased mRNA stability relative to normoxic cells. Our findings demonstrate that chronic hypoxia attenuates VEGF-stimulated signaling in HCAE cells by specific downregulation of KDR expression. These data provide a novel explanation for the impaired angiogenic responses to VEGF in endothelial cells exposed to chronic hypoxia.

  13. Early Flood Detection for Rapid Humanitarian Response: Harnessing Near Real-Time Satellite and Twitter Signals

    Directory of Open Access Journals (Sweden)

    Brenden Jongman

    2015-10-01

    Full Text Available Humanitarian organizations have a crucial role in response and relief efforts after floods. The effectiveness of disaster response is contingent on accurate and timely information regarding the location, timing and impacts of the event. Here we show how two near-real-time data sources, satellite observations of water coverage and flood-related social media activity from Twitter, can be used to support rapid disaster response, using case-studies in the Philippines and Pakistan. For these countries we analyze information from disaster response organizations, the Global Flood Detection System (GFDS satellite flood signal, and flood-related Twitter activity analysis. The results demonstrate that these sources of near-real-time information can be used to gain a quicker understanding of the location, the timing, as well as the causes and impacts of floods. In terms of location, we produce daily impact maps based on both satellite information and social media, which can dynamically and rapidly outline the affected area during a disaster. In terms of timing, the results show that GFDS and/or Twitter signals flagging ongoing or upcoming flooding are regularly available one to several days before the event was reported to humanitarian organizations. In terms of event understanding, we show that both GFDS and social media can be used to detect and understand unexpected or controversial flood events, for example due to the sudden opening of hydropower dams or the breaching of flood protection. The performance of the GFDS and Twitter data for early detection and location mapping is mixed, depending on specific hydrological circumstances (GFDS and social media penetration (Twitter. Further research is needed to improve the interpretation of the GFDS signal in different situations, and to improve the pre-processing of social media data for operational use.

  14. Investigation on the role of IGF-1 signal transduction in the biological radiation responses

    International Nuclear Information System (INIS)

    Jung, U Hee; Jo, Sung Kee; Park, Hae Ran; Oh, Soo Jin; Cho, Eun Hee; Eom, Hyun Soo; Ju, Eun Jin

    2009-05-01

    Effects of γ-irradiation on the IGF-1 related gene expressions and activations in various cell lines - Various expression patterns of IGF-1 and IGF-1R following γ-irradiation were observed according to the cell lines - The increased expressions of IGF-1 and IGF-1R were observed in Balb/3T3 and NIH/3T3 cells - Among the IGF-1 downstream signaling molecules, the phosphorylated ERK5 were not changed by γ-irradiation in all three examined cell lines, whereas the phosphorylated p65 were increased by γ -irradiation in all cell lines. The role of IGF-1 and p38 signaling in γ-irradiated mouse embryonic fibroblast (MEF) cells - In MEF cells, IGF-1 signaling molecules were decreased and p21/phosphorylated p38 were increased by γ-irradiation - The experiments with IGF-1R inhibitor (AG1024) and p38 inhibitor (SB203580) revealed that IGF-1 signaling is involved but not essential in radiation-induced cell growth arrest and senescence and that p38 MAP kinase play a important role in this cellular radiation response. The role of IGF-1 and p38 signaling in γ-irradiated mouse fibroblast (NIH/3T3) cell - In NIH/3T3 cells, IGF-1 signaling molecules and p21/phosphorylated p38 were increased by γ -irradiation. - However, the experiments with IGF-1R inhibitor (AG1024) and p38 inhibitor (SB203580) revealed that IGF-1 and p38 signaling do not play a crucial role in radiation-induced cell growth arrest and senescence in NIH/3T3 cells. Effects of γ-irradiation on the expressions and activations on the genes related to the IGF-1 signaling in mouse tissues - In γ-irradiated mice, the increased expressions of IGF-1 and IGF-1R were observed in the lung and kidney at 2 months after irradiation, and in all the tissues examined (lung, liver and kidney) at 6 months after irradiation. - In the lung of γ-irradiated mice at 6 months after irradiation, the increases of IGF-1R, phosphorylated FOXO3a, p65, p38, p21 were observed. - The patterns of altered expressions showed significant

  15. SU-E-J-223: A BOLD Contrast Imaging Sequence to Evaluate Oxygenation Changes Due to Breath Holding for Breast Radiotherapy: A Pilot Study

    International Nuclear Information System (INIS)

    Adamson, J; Chang, Z; Cai, J; Palta, M; Horton, J; Yin, F; Blitzblau, R

    2015-01-01

    Purpose: To develop a robust MRI sequence to measure BOLD breath hold induced contrast in context of breast radiotherapy. Methods: Two sequences were selected from prior studies as candidates to measure BOLD contrast attributable to breath holding within the breast: (1) T2* based Gradient Echo EPI (TR/TE = 500/41ms, flip angle = 60°), and (2) T2 based Single Shot Fast Spin Echo (SSFSE) (TR/TE = 3000/60ms). We enrolled ten women post-lumpectomy for breast cancer who were undergoing treatment planning for whole breast radiotherapy. Each session utilized a 1.5T GE MRI and 4 channel breast coil with the subject immobilized prone on a custom board. For each sequence, 1–3 planes of the lumpectomy breast were imaged continuously during a background measurement (1min) and intermittent breath holds (20–40s per breath hold, 3–5 holds per sequence). BOLD contrast was quantified as correlation of changes in per-pixel intensity with the breath hold schedule convolved with a hemodynamic response function. Subtle motion was corrected using a deformable registration algorithm. Correlation with breath-holding was considered significant if p<0.001. Results: The percentage of the breast ROI with positive BOLD contrast measured by the two sequences were in agreement with a correlation coefficient of R=0.72 (p=0.02). While both sequences demonstrated areas with strong BOLD response, the response was more systematic throughout the breast for the SSFSE (T2) sequence (% breast with response in the same direction: 51.2%±0.7% for T2* vs. 68.1%±16% for T2). In addition, the T2 sequence was less prone to magnetic susceptibility artifacts, especially in presence of seroma, and provided a more robust image with little distortion or artifacts. Conclusion: A T2 SSFSE sequence shows promise for measuring BOLD contrast in the context of breast radiotherapy utilizing a breath hold technique. Further study in a larger patient cohort is warranted to better refine this novel technique

  16. SU-E-J-223: A BOLD Contrast Imaging Sequence to Evaluate Oxygenation Changes Due to Breath Holding for Breast Radiotherapy: A Pilot Study

    Energy Technology Data Exchange (ETDEWEB)

    Adamson, J; Chang, Z; Cai, J; Palta, M; Horton, J; Yin, F; Blitzblau, R [Duke University Medical Center, Durham, NC (United States)

    2015-06-15

    Purpose: To develop a robust MRI sequence to measure BOLD breath hold induced contrast in context of breast radiotherapy. Methods: Two sequences were selected from prior studies as candidates to measure BOLD contrast attributable to breath holding within the breast: (1) T2* based Gradient Echo EPI (TR/TE = 500/41ms, flip angle = 60°), and (2) T2 based Single Shot Fast Spin Echo (SSFSE) (TR/TE = 3000/60ms). We enrolled ten women post-lumpectomy for breast cancer who were undergoing treatment planning for whole breast radiotherapy. Each session utilized a 1.5T GE MRI and 4 channel breast coil with the subject immobilized prone on a custom board. For each sequence, 1–3 planes of the lumpectomy breast were imaged continuously during a background measurement (1min) and intermittent breath holds (20–40s per breath hold, 3–5 holds per sequence). BOLD contrast was quantified as correlation of changes in per-pixel intensity with the breath hold schedule convolved with a hemodynamic response function. Subtle motion was corrected using a deformable registration algorithm. Correlation with breath-holding was considered significant if p<0.001. Results: The percentage of the breast ROI with positive BOLD contrast measured by the two sequences were in agreement with a correlation coefficient of R=0.72 (p=0.02). While both sequences demonstrated areas with strong BOLD response, the response was more systematic throughout the breast for the SSFSE (T2) sequence (% breast with response in the same direction: 51.2%±0.7% for T2* vs. 68.1%±16% for T2). In addition, the T2 sequence was less prone to magnetic susceptibility artifacts, especially in presence of seroma, and provided a more robust image with little distortion or artifacts. Conclusion: A T2 SSFSE sequence shows promise for measuring BOLD contrast in the context of breast radiotherapy utilizing a breath hold technique. Further study in a larger patient cohort is warranted to better refine this novel technique.

  17. Cocaine-associated odor cue re-exposure increases blood oxygenation level dependent signal in memory and reward regions of the maternal rat brain.

    Science.gov (United States)

    Caffrey, Martha K; Febo, Marcelo

    2014-01-01

    Cue triggered relapse during the postpartum period can negatively impact maternal care. Given the high reward value of pups in maternal rats, we designed an fMRI experiment to test whether offspring presence reduces the neural response to a cocaine associated olfactory cue. Cocaine conditioned place preference was carried out before pregnancy in the presence of two distinct odors that were paired with cocaine or saline (+Cue and -Cue). The BOLD response to +Cue and -Cue was measured in dams on postpartum days 2-4. Odor cues were delivered to dams in the absence and then the presence of pups. Our data indicate that several limbic and cognitive regions of the maternal rat brain show a greater BOLD signal response to a +Cue versus -Cue. These include dorsal striatum, prelimbic cortex, parietal cortex, habenula, bed nucleus of stria terminalis, lateral septum and the mediodorsal and the anterior thalamic nucleus. Of the aforementioned brain regions, only the parietal cortex of cocaine treated dams showed a significant modulatory effect of pup presence. In this area of the cortex, cocaine exposed maternal rats showed a greater BOLD activation in response to the +Cue in the presence than in the absence of pups. Specific regions of the cocaine exposed maternal rat brain are strongly reactive to drug associated cues. The regions implicated in cue reactivity have been previously reported in clinical imaging work, and previous work supports their role in various motivational and cognitive functions. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  18. Phosphoinositide-signaling is one component of a robust plant defense response.

    Directory of Open Access Journals (Sweden)

    Imara Yasmin Perera

    2014-06-01

    Full Text Available The phosphoinositide pathway and inositol-1,4,5-triphosphate (InsP3 have been implicated in plant responses to many abiotic stresses; however, their role in response to biotic stress is not well characterized. In the current study, we show that both basal defense and systemic acquired resistance responses are affected in transgenic plants constitutively expressing the human type I inositol polyphosphate 5-phosphatase (InsP 5-ptase which have greatly reduced InsP3 levels. Flagellin induced Ca2+-release as well as the expressions of some flg22 responsive genes were attenuated in the InsP 5-ptase plants. Furthermore, the InsP 5-ptase plants were more susceptible to virulent and avirulent strains of Pseudomonas syringae pv. tomato (PstDC3000. The InsP 5-ptase plants had lower basal salicylic acid (SA levels and the induction of SAR in systemic leaves was reduced and delayed. Reciprocal exudate experiments showed that although the InsP 5-ptase plants produced equally effective molecules that could trigger PR-1 gene expression in wild type plants, exudates collected from either wild type or InsP 5-ptase plants triggered less PR-1 gene expression in InsP 5-ptase plants. Additionally, expression profiles indicated that several defense genes including PR-1, PR-2, PR-5 and AIG1 were basally down regulated in the InsP 5-ptase plants compared with wild type. Upon pathogen attack, expression of these genes was either not induced or showed delayed induction in systemic leaves. Our study shows that phosphoinositide signaling is one component of the plant defense network and is involved in both basal and systemic responses. The dampening of InsP3-mediated signaling affects Ca2+ release, modulates defense gene expression and compromises plant defense responses.

  19. PARP-1 modulation of mTOR signaling in response to a DNA alkylating agent.

    Directory of Open Access Journals (Sweden)

    Chantal Ethier

    Full Text Available Poly(ADP-ribose polymerase-1 (PARP-1 is widely involved in cell death responses. Depending on the degree of injury and on cell type, PARP activation may lead to autophagy, apoptosis or necrosis. In HEK293 cells exposed to the alkylating agent N-methyl-N'-nitro-N'-nitrosoguanine (MNNG, we show that PARP-1 activation triggers a necrotic cell death response. The massive poly(ADP-ribose (PAR synthesis following PARP-1 activation leads to the modulation of mTORC1 pathway. Shortly after MNNG exposure, NAD⁺ and ATP levels decrease, while AMP levels drastically increase. We characterized at the molecular level the consequences of these altered nucleotide levels. First, AMP-activated protein kinase (AMPK is activated and the mTORC1 pathway is inhibited by the phosphorylation of Raptor, in an attempt to preserve cellular energy. Phosphorylation of the mTORC1 target S6 is decreased as well as the phosphorylation of the mTORC2 component Rictor on Thr1135. Finally, Akt phosphorylation on Ser473 is lost and then, cell death by necrosis occurs. Inhibition of PARP-1 with the potent PARP inhibitor AG14361 prevents all of these events. Moreover, the antioxidant N-acetyl-L-cysteine (NAC can also abrogate all the signaling events caused by MNNG exposure suggesting that reactive oxygen species (ROS production is involved in PARP-1 activation and modulation of mTOR signaling. In this study, we show that PARP-1 activation and PAR synthesis affect the energetic status of cells, inhibit the mTORC1 signaling pathway and possibly modulate the mTORC2 complex affecting cell fate. These results provide new evidence that cell death by necrosis is orchestrated by the balance between several signaling pathways, and that PARP-1 and PAR take part in these events.

  20. Prospective MR image alignment between breath-holds: Application to renal BOLD MRI.

    Science.gov (United States)

    Kalis, Inge M; Pilutti, David; Krafft, Axel J; Hennig, Jürgen; Bock, Michael

    2017-04-01

    To present an image registration method for renal blood oxygen level-dependent (BOLD) measurements that enables semiautomatic assessment of parenchymal and medullary R2* changes under a functional challenge. In a series of breath-hold acquisitions, three-dimensional data were acquired initially for prospective image registration of subsequent BOLD measurements. An algorithm for kidney alignment for BOLD renal imaging (KALIBRI) was implemented to detect the positions of the left and right kidney so that the kidneys were acquired in the subsequent BOLD measurement at consistent anatomical locations. Residual in-plane distortions were corrected retrospectively so that semiautomatic dynamic R2* measurements of the renal cortex and medulla become feasible. KALIBRI was tested in six healthy volunteers during a series of BOLD experiments, which included a 600- to 1000-mL water challenge. Prospective image registration and BOLD imaging of each kidney was achieved within a total measurement time of about 17 s, enabling its execution within a single breath-hold. KALIBRI improved the registration by up to 35% as found with mutual information measures. In four volunteers, a medullary R2* decrease of up to 40% was observed after water ingestion. KALIBRI improves the quality of two-dimensional time-resolved renal BOLD MRI by aligning local renal anatomy, which allows for consistent R2* measurements over many breath-holds. Magn Reson Med 77:1573-1582, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

  1. Oxidative Stressors Modify the Response of Streptococcus mutans to Its Competence Signal Peptides.

    Science.gov (United States)

    De Furio, Matthew; Ahn, Sang Joon; Burne, Robert A; Hagen, Stephen J

    2017-11-15

    The dental caries pathogen Streptococcus mutans is continually exposed to several types of stress in the oral biofilm environment. Oxidative stress generated by reactive oxygen species has a major impact on the establishment, persistence, and virulence of S. mutans Here, we combined fluorescent reporter-promoter fusions with single-cell imaging to study the effects of reactive oxygen species on activation of genetic competence in S. mutans Exposure to paraquat, which generates superoxide anion, produced a qualitatively different effect on activation of expression of the gene for the master competence regulator, ComX, than did treatment with hydrogen peroxide (H 2 O 2 ), which can yield hydroxyl radical. Paraquat suppressed peptide-mediated induction of comX in a progressive and cumulative fashion, whereas the response to H 2 O 2 displayed a strong threshold behavior. Low concentrations of H 2 O 2 had little effect on induction of comX or the bacteriocin gene cipB , but expression of these genes declined sharply if extracellular H 2 O 2 exceeded a threshold concentration. These effects were not due to decreased reporter gene fluorescence. Two different threshold concentrations were observed in the response to H 2 O 2 , depending on the gene promoter that was analyzed and the pathway by which the competence regulon was stimulated. The results show that paraquat and H 2 O 2 affect the S. mutans competence signaling pathway differently, and that some portions of the competence signaling pathway are more sensitive to oxidative stress than others. IMPORTANCE Streptococcus mutans inhabits the oral biofilm, where it plays an important role in the development of dental caries. Environmental stresses such as oxidative stress influence the growth of S. mutans and its important virulence-associated behaviors, such as genetic competence. S. mutans competence development is a complex behavior that involves two different signaling peptides and can exhibit cell

  2. Arabidopsis PYL8 Plays an Important Role for ABA Signaling and Drought Stress Responses

    Directory of Open Access Journals (Sweden)

    Chae Woo Lim

    2013-12-01

    Full Text Available Plants are frequently exposed to numerous environmental stresses such as dehydration and high salinity, and have developed elaborate mechanisms to counteract the deleterious effects of stress. The phytohormone abscisic acid (ABA plays a critical role as an integrator of plant responses to water-limited condition to activate ABA signal transduction pathway. Although perception of ABA has been suggested to be important, the function of each ABA receptor remains elusive in dehydration condition. Here, we show that ABA receptor, pyrabactin resistance-like protein 8 (PYL8, functions in dehydration conditions. Transgenic plants overexpressing PYL8 exhibited hypersensitive phenotype to ABA in seed germination, seedling growth and establishment. We found that hypersensitivity to ABA of transgenic plants results in high degrees of stomatal closure in response to ABA leading to low transpiration rates and ultimately more vulnerable to drought than the wild-type plants. In addition, high expression of ABA maker genes also contributes to altered drought tolerance phenotype. Overall, this work emphasizes the importance of ABA signaling by ABA receptor in stomata during defense response to drought stress.

  3. Relating climate change signals and physiographic catchment properties to clustered hydrological response types

    Directory of Open Access Journals (Sweden)

    N. Köplin

    2012-07-01

    Full Text Available We propose an approach to reduce a comprehensive set of 186 mesoscale catchments in Switzerland to fewer response types to climate change and to name sensitive regions as well as catchment characteristics that govern hydrological change. We classified the hydrological responses of our study catchments through an agglomerative-hierarchical cluster analysis, and we related the dominant explanatory variables, i.e. the determining catchment properties and climate change signals, to the catchments' hydrological responses by means of redundancy analysis. All clusters except for one exhibit clearly decreasing summer runoff and increasing winter runoff. This seasonal shift was observed for the near future period (2025–2046 but is particularly obvious in the far future period (2074–2095. Within a certain elevation range (between 1000 and 2500 m a.s.l., the hydrological change is basically a function of elevation, because the latter governs the dominant hydro-climatological processes associated with temperature, e.g. the ratio of liquid to solid precipitation and snow melt processes. For catchments below the stated range, hydrological change is mainly a function of precipitation change, which is not as pronounced as the temperature signal is. Future impact studies in Switzerland can be conducted on a reduced sample of catchments representing the sensitive regions or covering a range of altitudes.

  4. Drug-induced death signaling strategy rapidly predicts cancer response to chemotherapy.

    Science.gov (United States)

    Montero, Joan; Sarosiek, Kristopher A; DeAngelo, Joseph D; Maertens, Ophélia; Ryan, Jeremy; Ercan, Dalia; Piao, Huiying; Horowitz, Neil S; Berkowitz, Ross S; Matulonis, Ursula; Jänne, Pasi A; Amrein, Philip C; Cichowski, Karen; Drapkin, Ronny; Letai, Anthony

    2015-02-26

    There is a lack of effective predictive biomarkers to precisely assign optimal therapy to cancer patients. While most efforts are directed at inferring drug response phenotype based on genotype, there is very focused and useful phenotypic information to be gained from directly perturbing the patient's living cancer cell with the drug(s) in question. To satisfy this unmet need, we developed the Dynamic BH3 Profiling technique to measure early changes in net pro-apoptotic signaling at the mitochondrion ("priming") induced by chemotherapeutic agents in cancer cells, not requiring prolonged ex vivo culture. We find in cell line and clinical experiments that early drug-induced death signaling measured by Dynamic BH3 Profiling predicts chemotherapy response across many cancer types and many agents, including combinations of chemotherapies. We propose that Dynamic BH3 Profiling can be used as a broadly applicable predictive biomarker to predict cytotoxic response of cancers to chemotherapeutics in vivo. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. The Neural Feedback Response to Error As a Teaching Signal for the Motor Learning System

    Science.gov (United States)

    Shadmehr, Reza

    2016-01-01

    When we experience an error during a movement, we update our motor commands to partially correct for this error on the next trial. How does experience of error produce the improvement in the subsequent motor commands? During the course of an erroneous reaching movement, proprioceptive and visual sensory pathways not only sense the error, but also engage feedback mechanisms, resulting in corrective motor responses that continue until the hand arrives at its goal. One possibility is that this feedback response is co-opted by the learning system and used as a template to improve performance on the next attempt. Here we used electromyography (EMG) to compare neural correlates of learning and feedback to test the hypothesis that the feedback response to error acts as a template for learning. We designed a task in which mixtures of error-clamp and force-field perturbation trials were used to deconstruct EMG time courses into error-feedback and learning components. We observed that the error-feedback response was composed of excitation of some muscles, and inhibition of others, producing a complex activation/deactivation pattern during the reach. Despite this complexity, across muscles the learning response was consistently a scaled version of the error-feedback response, but shifted 125 ms earlier in time. Across people, individuals who produced a greater feedback response to error, also learned more from error. This suggests that the feedback response to error serves as a teaching signal for the brain. Individuals who learn faster have a better teacher in their feedback control system. SIGNIFICANCE STATEMENT Our sensory organs transduce errors in behavior. To improve performance, we must generate better motor commands. How does the nervous system transform an error in sensory coordinates into better motor commands in muscle coordinates? Here we show that when an error occurs during a movement, the reflexes transform the sensory representation of error into motor

  6. Tilt-shift eddy current probe impact on information value of response signal

    Directory of Open Access Journals (Sweden)

    Chudacik Vladimir

    2016-03-01

    Full Text Available This article deals with the possibility for increasing of the informational value of a response signal using tilt-shift eddy current probe. Numerical simulations based on the FEM method using the OPERA 3D software as well as gained experimental results are presented. The simulated cracks are evaluated at the selected eddy current probe tilts and shifts with respect to conductive plate to obtain additional data needed for its evaluation and localization. Obtained simulation results are compared and discussed with the experimental results.

  7. Context Matters: Multiple Novelty Tests Reveal Different Aspects of Shyness-Boldness in Farmed American Mink (Neovison vison).

    Science.gov (United States)

    Noer, Christina Lehmkuhl; Needham, Esther Kjær; Wiese, Ann-Sophie; Balsby, Thorsten Johannes Skovbjerg; Dabelsteen, Torben

    2015-01-01

    Animal personality research is receiving increasing interest from related fields, such as evolutionary personality psychology. By merging the conceptual understanding of personality, the contributions to both fields of research may be enhanced. In this study, we investigate animal personality based on the definition of personality traits as underlying dispositional factors, which are not directly measurable, but which predispose individuals to react through different behavioural patterns. We investigated the shyness-boldness continuum reflected in the consistency of inter-individual variation in behavioural responses towards novelty in 47 farmed American mink (Neovison vison), which were raised in identical housing conditions. Different stages of approach behaviour towards novelty, and how these related within and across contexts, were explored. Our experimental design contained four tests: two novel object tests (non-social contexts) and two novel animated stimuli tests (social contexts). Our results showed consistency in shyness measures across multiple tests, indicating the existence of personality in farmed American mink. It was found that consistency in shyness measures differs across non-social and social contexts, as well as across the various stages in the approach towards novel objects, revealing that different aspects of shyness exist in the farmed American mink. To our knowledge this is the first study to reveal aspects of the shyness-boldness continuum in the American mink. Since the mink were raised in identical housing conditions, inherited factors may have been important in shaping the consistent inter-individual variation. Body weight and sex had no effect on the personality of the mink. Altogether, our results suggest that the shyness-boldness continuum cannot be explained by a simple underlying dispositional factor, but instead encompasses a broader term of hesitating behaviour that might comprise several different personality traits.

  8. Context Matters: Multiple Novelty Tests Reveal Different Aspects of Shyness-Boldness in Farmed American Mink (Neovison vison.

    Directory of Open Access Journals (Sweden)

    Christina Lehmkuhl Noer

    Full Text Available Animal personality research is receiving increasing interest from related fields, such as evolutionary personality psychology. By merging the conceptual understanding of personality, the contributions to both fields of research may be enhanced. In this study, we investigate animal personality based on the definition of personality traits as underlying dispositional factors, which are not directly measurable, but which predispose individuals to react through different behavioural patterns. We investigated the shyness-boldness continuum reflected in the consistency of inter-individual variation in behavioural responses towards novelty in 47 farmed American mink (Neovison vison, which were raised in identical housing conditions. Different stages of approach behaviour towards novelty, and how these related within and across contexts, were explored. Our experimental design contained four tests: two novel object tests (non-social contexts and two novel animated stimuli tests (social contexts. Our results showed consistency in shyness measures across multiple tests, indicating the existence of personality in farmed American mink. It was found that consistency in shyness measures differs across non-social and social contexts, as well as across the various stages in the approach towards novel objects, revealing that different aspects of shyness exist in the farmed American mink. To our knowledge this is the first study to reveal aspects of the shyness-boldness continuum in the American mink. Since the mink were raised in identical housing conditions, inherited factors may have been important in shaping the consistent inter-individual variation. Body weight and sex had no effect on the personality of the mink. Altogether, our results suggest that the shyness-boldness continuum cannot be explained by a simple underlying dispositional factor, but instead encompasses a broader term of hesitating behaviour that might comprise several different personality

  9. Response Analysis on Electrical Pulses under Severe Nuclear Accident Temperature Conditions Using an Abnormal Signal Simulation Analysis Module

    Directory of Open Access Journals (Sweden)

    Kil-Mo Koo

    2012-01-01

    Full Text Available Unlike design basis accidents, some inherent uncertainties of the reliability of instrumentations are expected while subjected to harsh environments (e.g., high temperature and pressure, high humidity, and high radioactivity occurring in severe nuclear accident conditions. Even under such conditions, an electrical signal should be within its expected range so that some mitigating actions can be taken based on the signal in the control room. For example, an industrial process control standard requires that the normal signal level for pressure, flow, and resistance temperature detector sensors be in the range of 4~20 mA for most instruments. Whereas, in the case that an abnormal signal is expected from an instrument, such a signal should be refined through a signal validation process so that the refined signal could be available in the control room. For some abnormal signals expected under severe accident conditions, to date, diagnostics and response analysis have been evaluated with an equivalent circuit model of real instruments, which is regarded as the best method. The main objective of this paper is to introduce a program designed to implement a diagnostic and response analysis for equivalent circuit modeling. The program links signal analysis tool code to abnormal signal simulation engine code not only as a one body order system, but also as a part of functions of a PC-based ASSA (abnormal signal simulation analysis module developed to obtain a varying range of the R-C circuit elements in high temperature conditions. As a result, a special function for abnormal pulse signal patterns can be obtained through the program, which in turn makes it possible to analyze the abnormal output pulse signals through a response characteristic of a 4~20 mA circuit model and a range of the elements changing with temperature under an accident condition.

  10. Signaling Product Quality Information in Supply Chains via Corporate Social Responsibility Choices

    Directory of Open Access Journals (Sweden)

    Yuhui Li

    2017-11-01

    Full Text Available This study focuses on how an upstream supplier signals the private information of its product quality with corporate social responsibility (CSR choices to a downstream retailer and uninformed consumers in the final market. We build a signaling model to: capture the strategic interactions among the supplier, the retailer, and the final consumers in the supply chain; characterize completely the set of all separating perfect Bayesian equilibriums (PBEs; and finally, select a unique equilibrium that satisfies the intuitive criterion for exploring some comparative statics. The equilibrium results show that under some technical conditions: (1 a set of moderate levels of CSR conduct signal the upstream supplier’s high quality in the sense of separating PBEs; (2 the unique separating PBE satisfying the intuitive criterion is the one with the lowest CSR level that separates a high-quality supplier from a low-quality supplier; (3 the lowest CSR level decreases in the proportion of informed consumers and the low-quality supplier’s marginal CSR cost, but is independent of the high-quality supplier’s marginal CSR cost; (4 the profits of the high-quality supplier increase in proportion to the number of informed consumers and the low-quality supplier’s marginal cost CSR, but decrease in proportion to the high-quality supplier’s marginal CSR cost. Managerial insights are also discussed.

  11. How do shared-representations and emotional processes cooperate in response to social threat signals?

    Science.gov (United States)

    Grèzes, Julie; Dezecache, Guillaume

    2014-03-01

    Research in social cognition has mainly focused on the detection and comprehension of others' mental and emotional states. Doing so, past studies have adopted a "contemplative" view of the role of the observer engaged in a social interaction. However, the adaptive problem posed by the social environment is first and foremost that of coordination, which demands more of social cognition beyond mere detection and comprehension of others' hidden states. Offering a theoretical framework that takes into account the dynamical aspect of social interaction - notably by accounting for constant interplay between emotional appraisal and motor processes in socially engaged human brain - thus constitutes an important challenge for the field of social cognition. Here, we propose that our social environment can be seen as presenting opportunities for actions regarding others. Within such a framework, non-verbal social signals such as emotional displays are considered to have evolved to influence the observer in consistent ways. Consequently, social signals can modulate motor responses in observers. In line with this theoretical framework we provide evidence that emotional and motor processes are actually tightly linked during the perception of threat signals. This is ultimately reflected in the human brain by constant interplay between limbic and motor areas. © 2013 Elsevier Ltd. All rights reserved.

  12. Validated Models for Radiation Response and Signal Generation in Scintillators: Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Kerisit, Sebastien N.; Gao, Fei; Xie, YuLong; Campbell, Luke W.; Van Ginhoven, Renee M.; Wang, Zhiguo; Prange, Micah P.; Wu, Dangxin

    2014-12-01

    This Final Report presents work carried out at Pacific Northwest National Laboratory (PNNL) under the project entitled “Validated Models for Radiation Response and Signal Generation in Scintillators” (Project number: PL10-Scin-theor-PD2Jf) and led by Drs. Fei Gao and Sebastien N. Kerisit. This project was divided into four tasks: 1) Electronic response functions (ab initio data model) 2) Electron-hole yield, variance, and spatial distribution 3) Ab initio calculations of information carrier properties 4) Transport of electron-hole pairs and scintillation efficiency Detailed information on the results obtained in each of the four tasks is provided in this Final Report. Furthermore, published peer-reviewed articles based on the work carried under this project are included in Appendix. This work was supported by the National Nuclear Security Administration, Office of Nuclear Nonproliferation Research and Development (DNN R&D/NA-22), of the U.S. Department of Energy (DOE).

  13. Flexible and wearable 3D graphene sensor with 141 KHz frequency signal response capability

    Science.gov (United States)

    Xu, R.; Zhang, H.; Cai, Y.; Ruan, J.; Qu, K.; Liu, E.; Ni, X.; Lu, M.; Dong, X.

    2017-09-01

    We developed a flexible force sensor consisting of 3D graphene foam (GF) encapsulated in flexible polydimethylsiloxane (PDMS). Because the 3D GF/PDMS sensor is based on the transformation of an electronic band structure aroused by static mechanical strain or KHz vibration, it can detect frequency signals by both tuning fork tests and piezoelectric ceramic transducer tests, which showed a clear linear response from audio frequencies, including frequencies up to 141 KHz in the ultrasound range. Because of their excellent response with a wide bandwidth, the 3D GF/PDMS sensors are attractive for interactive wearable devices or artificial prosthetics capable of perceiving seismic waves, ultrasonic waves, shock waves, and transient pressures.

  14. Cauliflower mosaic virus protein P6 inhibits signaling responses to salicylic acid and regulates innate immunity.

    Directory of Open Access Journals (Sweden)

    Andrew J Love

    Full Text Available Cauliflower mosaic virus (CaMV encodes a multifunctional protein P6 that is required for translation of the 35S RNA and also acts as a suppressor of RNA silencing. Here we demonstrate that P6 additionally acts as a pathogenicity effector of an unique and novel type, modifying NPR1 (a key regulator of salicylic acid (SA- and jasmonic acid (JA-dependent signaling and inhibiting SA-dependent defence responses We find that that transgene-mediated expression of P6 in Arabidopsis and transient expression in Nicotiana benthamiana has profound effects on defence signaling, suppressing expression of representative SA-responsive genes and increasing expression of representative JA-responsive genes. Relative to wild-type Arabidopsis P6-expressing transgenics had greatly reduced expression of PR-1 following SA-treatment, infection by CaMV or inoculation with an avirulent bacterial pathogen Pseudomonas syringae pv tomato (Pst. Similarly transient expression in Nicotiana benthamiana of P6 (including a mutant form defective in translational transactivation activity suppressed PR-1a transcript accumulation in response to Agrobacterium infiltration and following SA-treatment. As well as suppressing the expression of representative SA-regulated genes, P6-transgenic Arabidopsis showed greatly enhanced susceptibility to both virulent and avirulent Pst (titres elevated 10 to 30-fold compared to non-transgenic controls but reduced susceptibility to the necrotrophic fungus Botrytis cinerea. Necrosis following SA-treatment or inoculation with avirulent Pst was reduced and delayed in P6-transgenics. NPR1 an important regulator of SA/JA crosstalk, was more highly expressed in the presence of P6 and introduction of the P6 transgene into a transgenic line expressing an NPR1:GFP fusion resulted in greatly increased fluorescence in nuclei even in the absence of SA. Thus in the presence of P6 an inactive form of NPR1 is mislocalized in the nucleus even in uninduced plants

  15. Neural Responses to Injury: Prevention, Protection and Repair; Volume 7: Role Growth Factors and Cell Signaling in the Response of Brain and Retina to Injury

    National Research Council Canada - National Science Library

    Bazan, Nicolas

    1996-01-01

    ...: Prevention, Protection, and Repair, Subproject: Role of Growth Factors and Cell Signaling in the Response of Brain and Retina to Injury, are as follows: Species Rat(Albino Wistar), Number Allowed...

  16. Estimation of demand response to energy price signals in energy consumption behaviour in Beijing, China

    International Nuclear Information System (INIS)

    He, Y.X.; Liu, Y.Y.; Xia, T.; Zhou, B.

    2014-01-01

    Highlights: • Demand response to energy price signals in energy consumption in Beijing is studied. • The electricity price is of great importance to Beijing’s energy market stability. • Industrial sectors have a large electricity self-elasticity and cross-elasticity. • When consuming electricity, customers pay more attention to natural gas price. • Analysis of demand response to energy price can provide guidance to energy policies. - Abstract: The energy price system in Beijing has not fully exploited customers’ price elasticity, and has a negative impact on achieving the goals of energy saving. This paper analyses the response behaviours of different customers to typical energy prices. As for electricity self-elasticity, the range of the primary, secondary, tertiary industry and residents are −0.026 to −0.033, −0.045 to −0.059, −0.035 to −0.047 and −0.024 to −0.032, respectively. As regards self-elasticity on coal, the range of the primary, secondary, tertiary industry and residents are −0.030 to −0.037, −0.066 to −0.093, −0.055 to −0.072 and −0.034 to −0.051, respectively. The self-elasticities on oil and natural gas are very weak. As for cross-elasticity, when consuming electricity and oil, customers mainly focus on the prices of natural gas, which are 0.185 and 0.112. When consuming coal and natural gas, customers are concerned about the electricity prices, and their cross-elasticities are 0.03 and 0.36, respectively. The estimation of demand response to energy price signals in energy consumption behaviours can provide a decision support for formulating rational energy price policies

  17. The Timing of Stimulation and IL-2 Signaling Regulate Secondary CD8 T Cell Responses

    Science.gov (United States)

    Khan, Shaniya H.; Martin, Matthew D.; Starbeck-Miller, Gabriel R.; Xue, Hai-Hui; Harty, John T.; Badovinac, Vladimir P.

    2015-01-01

    Abstract Memory CD8 T cells provide protection to immune hosts by eliminating pathogen-infected cells during re-infection. While parameters influencing the generation of primary (1°) CD8 T cells are well established, the factors controlling the development of secondary (2°) CD8 T cell responses remain largely unknown. Here, we address the mechanisms involved in the generation and development of 2° memory (M) CD8 T cells. We observed that the time at which 1° M CD8 T cells enter into immune response impacts their fate and differentiation into 2° M CD8 T cells. Late-entry of 1° M CD8 T cells into an immune response (relative to the onset of infection) not only facilitated the expression of transcription factors associated with memory formation in 2° effector CD8 T cells, but also influenced the ability of 2° M CD8 T cells to localize within the lymph nodes, produce IL-2, and undergo Ag-driven proliferation. The timing of stimulation of 1° M CD8 T cells also impacted the duration of expression of the high-affinity IL-2 receptor (CD25) on 2° effector CD8 T cells and their sensitivity to IL-2 signaling. Importantly, by blocking or enhancing IL-2 signaling in developing 2° CD8 T cells, we provide direct evidence for the role of IL-2 in controlling the differentiation of Ag-driven 2° CD8 T cell responses. Thus, our data suggest that the process of 1° M to 2° M CD8 T cell differentiation is not fixed and can be manipulated, a notion with relevance for the design of future prime-boost vaccination approaches. PMID:26431533

  18. Electric signalling in fruit trees in response to water applications and light-darkness conditions.

    Science.gov (United States)

    Gurovich, Luis A; Hermosilla, Paulo

    2009-02-15

    A fundamental property of all living organisms is the generation and conduction of electrochemical impulses throughout their different tissues and organs, resulting from abiotic and biotic changes in environmental conditions. In plants and animals, signal transmission can occur over long and short distances, and it can correspond to intra- and inter-cellular communication mechanisms that determine the physiological behaviour of the organism. Rapid plant and animal responses to environmental changes are associated with electrical excitability and signalling. The same molecules and pathways are used to drive physiological responses, which are characterized by movement (physical displacement) in animals and by continuous growth in plants. In the field of environmental plant electrophysiology, automatic and continuous measurements of electrical potential differences (DeltaEP) between plant tissues can be effectively used to study information transport mechanisms and physiological responses that result from external stimuli on plants. A critical mass of data on electrical behaviour in higher plants has accumulated in the last 5 years, establishing plant neurobiology as the most recent discipline of plant science. In this work, electrical potential differences were monitored continuously using Ag/AgCl microelectrodes, which were inserted 15mm deep into sapwood at various positions in the trunks of several fruit-bearing trees. Electrodes were referenced to an unpolarisable Ag/AgCl microelectrode, which was installed 5cm deep in the soil. Systematic patterns of DeltaEP during day-night cycles and at different conditions of soil water availability are discussed as alternative tools to assess early plant stress conditions. This research relates to the adaptive response of trees to soil water availability and light-darkness cycles.

  19. Signaling network of dendritic cells in response to pathogens: a community-input supported knowledgebase

    Directory of Open Access Journals (Sweden)

    Nudelman Irina

    2010-10-01

    Full Text Available Abstract Background Dendritic cells are antigen-presenting cells that play an essential role in linking the innate and adaptive immune systems. Much research has focused on the signaling pathways triggered upon infection of dendritic cells by various pathogens. The high level of activity in the field makes it desirable to have a pathway-based resource to access the information in the literature. Current pathway diagrams lack either comprehensiveness, or an open-access editorial interface. Hence, there is a need for a dependable, expertly curated knowledgebase that integrates this information into a map of signaling networks. Description We have built a detailed diagram of the dendritic cell signaling network, with the goal of providing researchers with a valuable resource and a facile method for community input. Network construction has relied on comprehensive review of the literature and regular updates. The diagram includes detailed depictions of pathways activated downstream of different pathogen recognition receptors such as Toll-like receptors, retinoic acid-inducible gene-I-like receptors, C-type lectin receptors and nucleotide-binding oligomerization domain-like receptors. Initially assembled using CellDesigner software, it provides an annotated graphical representation of interactions stored in Systems Biology Mark-up Language. The network, which comprises 249 nodes and 213 edges, has been web-published through the Biological Pathway Publisher software suite. Nodes are annotated with PubMed references and gene-related information, and linked to a public wiki, providing a discussion forum for updates and corrections. To gain more insight into regulatory patterns of dendritic cell signaling, we analyzed the network using graph-theory methods: bifan, feedforward and multi-input convergence motifs were enriched. This emphasis on activating control mechanisms is consonant with a network that subserves persistent and coordinated responses to

  20. Effect of nicotine on exocytotic pancreatic secretory response: role of calcium signaling

    Directory of Open Access Journals (Sweden)

    Chowdhury Parimal

    2013-01-01

    Full Text Available Abstract Background Nicotine is a risk factor for pancreatitis resulting in loss of pancreatic enzyme secretion. The aim of this study was to evaluate the mechanisms of nicotine-induced secretory response measured in primary pancreatic acinar cells isolated from Male Sprague Dawley rats. The study examines the role of calcium signaling in the mechanism of the enhanced secretory response observed with nicotine exposure. Methods Isolated and purified pancreatic acinar cells were subjected to a nicotine exposure at a dose of 100 μM for 6 minutes and then stimulated with cholecystokinin (CCK for 30 min. The cell’s secretory response was measured by the percent of amylase released from the cells in the incubation medium Calcium receptor antagonists, inositol trisphosphate (IP3 receptor blockers, mitogen activated protein kinase inhibitors and specific nicotinic receptor antagonists were used to confirm the involvement of calcium in this process. Results Nicotine exposure induced enhanced secretory response in primary cells. These responses remained unaffected by mitogen activated protein kinases (MAPK’s inhibitors. The effects, however, have been completely abolished by nicotinic receptor antagonist, calcium channel receptor antagonists and inositol trisphosphate (IP3 receptor blockers. Conclusions The data suggest that calcium activated events regulating the exocytotic secretion are affected by nicotine as shown by enhanced functional response which is inhibited by specific antagonists… The results implicate the role of nicotine in the mobilization of both intra- and extracellular calcium in the regulation of stimulus-secretory response of enzyme secretion in this cell system. We conclude that nicotine plays an important role in promoting enhanced calcium levels inside the acinar cell.

  1. Response of decadal climatic variations to solar signals in the coastal region of the Barents Sea

    Science.gov (United States)

    Raspopov, O. M.; Dergachev, V. A.; Shumilov, O. I.; Nevanlinna, H.

    2003-04-01

    Variations in annual temperatures in the coastal region of the Barents sea in Murmansk (69 N, 33 E) for the period of instrumental records since 1878 have been analyzed. Annual temperature variations have been found to exhibit a pronounced decadal periodicity of the order of 1-1.8 degrees Celsius. Comparison of temperature variations with variations in solar activity (Wolf numbers W) point to the synchronism between decadal temperature variations and the 11-year Schwabe solar cycle. Spectral analysis of the tree ring growth (Pinus Sylvestris L.) in Tuloma Valley near Murmansk for the last 350 years has revealed variations in the tree ring growth with a period of 11-12 years. Thus, decadal climatic variations with the period of the Schwabe solar cycle are typical of the coastal region of the Barents sea. The amplitudes of the observed temperature variations (1-1.8 degrees Celsius) cannot be interpreted as resulting from changes in solar irradiation during the 11-year cycle. These changes are of the order of 0.15%, which can lead to the global temperature response of the order of 0.1-0.3 degrees Celsius. Therefore, a 5-6-fold enhancement of the solar signals takes place in the coastal region of the Barents sea. A similar solar signal enhancement was revealed earlier in variations in the Sea Surface Temperature (SST) in the Pacific Ocean. Possible reasons for enhancement of solar signals in variations in SST in the Pacific Ocean were considered by White et al.(2000) on the basis of the model of the delayed action oscillator in the ocean-atmosphere-terrestrial system. It is probable that in the Northern Atlantic region a similar solar signal enhancement occurs in the ocean-atmosphere-terrestrial system. This work was supported by INTAS, Grant 97-31008; PFBR, Grant 00-05-64921 and NorFa.

  2. Depression and treatment response: dynamic interplay of signaling pathways and altered neural processes

    Science.gov (United States)

    Duric, Vanja

    2014-01-01

    Since the 1960s, when the first tricyclic and monoamine oxidase inhibitor antidepressant drugs were introduced, most of the ensuing agents were designed to target similar brain pathways that elevate serotonin and/or norepinephrine signaling. Fifty years later, the main goal of the current depression research is to develop faster-acting, more effective therapeutic agents with fewer side effects, as currently available antidepressants are plagued by delayed therapeutic onset and low response rates. Clinical and basic science research studies have made significant progress towards deciphering the pathophysiological events within the brain involved in development, maintenance, and treatment of major depressive disorder. Imaging and postmortem brain studies in depressed human subjects, in combination with animal behavioral models of depression, have identified a number of different cellular events, intracellular signaling pathways, proteins, and target genes that are modulated by stress and are potentially vital mediators of antidepressant action. In this review, we focus on several neural mechanisms, primarily within the hippocampus and prefrontal cortex, which have recently been implicated in depression and treatment response. PMID:22585060

  3. Signaling beyond Punching Holes: Modulation of Cellular Responses by Vibrio cholerae Cytolysin

    Directory of Open Access Journals (Sweden)

    Barkha Khilwani

    2015-08-01

    Full Text Available Pore-forming toxins (PFTs are a distinct class of membrane-damaging cytolytic proteins that contribute significantly towards the virulence processes employed by various pathogenic bacteria. Vibrio cholerae cytolysin (VCC is a prominent member of the beta-barrel PFT (beta-PFT family. It is secreted by most of the pathogenic strains of the intestinal pathogen V. cholerae. Owing to its potent membrane-damaging cell-killing activity, VCC is believed to play critical roles in V. cholerae pathogenesis, particularly in those strains that lack the cholera toxin. Large numbers of studies have explored the mechanistic basis of the cell-killing activity of VCC. Consistent with the beta-PFT mode of action, VCC has been shown to act on the target cells by forming transmembrane oligomeric beta-barrel pores, thereby leading to permeabilization of the target cell membranes. Apart from the pore-formation-induced direct cell-killing action, VCC exhibits the potential to initiate a plethora of signal transduction pathways that may lead to apoptosis, or may act to enhance the cell survival/activation responses, depending on the type of target cells. In this review, we will present a concise view of our current understanding regarding the multiple aspects of these cellular responses, and their underlying signaling mechanisms, evoked by VCC.

  4. Analysis of the Human Mucosal Response to Cholera Reveals Sustained Activation of Innate Immune Signaling Pathways.

    Science.gov (United States)

    Bourque, Daniel L; Bhuiyan, Taufiqur Rahman; Genereux, Diane P; Rashu, Rasheduzzaman; Ellis, Crystal N; Chowdhury, Fahima; Khan, Ashraful I; Alam, Nur Haq; Paul, Anik; Hossain, Lazina; Mayo-Smith, Leslie M; Charles, Richelle C; Weil, Ana A; LaRocque, Regina C; Calderwood, Stephen B; Ryan, Edward T; Karlsson, Elinor K; Qadri, Firdausi; Harris, Jason B

    2018-02-01

    To better understand the innate immune response to Vibrio cholerae infection, we tracked gene expression in the duodenal mucosa of 11 Bangladeshi adults with cholera, using biopsy specimens obtained immediately after rehydration and 30 and 180 days later. We identified differentially expressed genes and performed an analysis to predict differentially regulated pathways and upstream regulators. During acute cholera, there was a broad increase in the expression of genes associated with innate immunity, including activation of the NF-κB, mitogen-activated protein kinase (MAPK), and Toll-like receptor (TLR)-mediated signaling pathways, which, unexpectedly, persisted even 30 days after infection. Focusing on early differences in gene expression, we identified 37 genes that were differentially expressed on days 2 and 30 across the 11 participants. These genes included the endosomal Toll-like receptor gene TLR8 , which was expressed in lamina propria cells. Underscoring a potential role for endosomal TLR-mediated signaling in vivo , our pathway analysis found that interferon regulatory factor 7 and beta 1 and alpha 2 interferons were among the top upstream regulators activated during cholera. Among the innate immune effectors, we found that the gene for DUOX2, an NADPH oxidase involved in the maintenance of intestinal homeostasis, was upregulated in intestinal epithelial cells during cholera. Notably, the observed increases in DUOX2 and TLR8 expression were also modeled in vitro when Caco-2 or THP-1 cells, respectively, were stimulated with live V. cholerae but not with heat-killed organisms or cholera toxin alone. These previously unidentified features of the innate immune response to V. cholerae extend our understanding of the mucosal immune signaling pathways and effectors activated in vivo following cholera. Copyright © 2018 American Society for Microbiology.

  5. Regulatory roles of cytokinins and cytokinin signaling in response to potassium deficiency in Arabidopsis.

    Directory of Open Access Journals (Sweden)

    Youn-Jeong Nam

    Full Text Available Potassium (K is an important plant macronutrient that has various functions throughout the whole plant over its entire life span. Cytokinins (CKs are known to regulate macronutrient homeostasis by controlling the expression of nitrate, phosphate and sulfate transporters. Although several studies have described how CKs signal deficiencies for some macronutrients, the roles of CKs in K signaling are poorly understood. CK content has been shown to decrease under K-starved conditions. Specifically, a CK-deficient mutant was more tolerant to low K than wild-type; however, a plant with an overaccumulation of CKs was more sensitive to low K. These results suggest that K deprivation alters CK metabolism, leading to a decrease in CK content. To investigate this phenomenon further, several Arabidopsis lines, including a CK-deficient mutant and CK receptor mutants, were analyzed in low K conditions using molecular, genetic and biochemical approaches. ROS accumulation and root hair growth in low K were also influenced by CKs. CK receptor mutants lost the responsiveness to K-deficient signaling, including ROS accumulation and root hair growth, but the CK-deficient mutant accumulated more ROS and exhibited up-regulated expression of HAK5, which is a high-affinity K uptake transporter gene that is rapidly induced by low K stress in ROS- and ethylene-dependent manner in response to low K. From these results, we conclude that a reduction in CK levels subsequently allows fast and effective stimulation of low K-induced ROS accumulation, root hair growth and HAK5 expression, leading to plant adaptation to low K conditions.

  6. Mapping hypercapnia-induced cerebrovascular reactivity using BOLD MRI

    International Nuclear Information System (INIS)

    Zande, F.H.R. van der; Hofman, P.A.M.; Backes, W.H.

    2005-01-01

    Severe carotid artery stenosis or occlusion may put patients at risk for ischaemic stroke. Reduced cerebrovascular reserve capacity is a possible indicator of an imminent ischaemic event and can be determined by assessment of cerebrovascular reactivity to a vasodilative stimulus. However, little is known about the distribution of cerebrovascular reactivity in healthy individuals. In 13 healthy volunteers, dynamic T 2 * MR images, acquired at alternating inspiratory pCO 2 levels, showed a high percentage of signal change in grey matter, with a strong linear correlation with end-tidal pCO 2 . The mean percentages of signal change for grey and white matter were 5.9±1.2% and 1.9±0.5%, respectively. The mean time lag between CO 2 stimulus and haemodynamic response was 15±4 s for grey matter and 180±12 s for white matter. Parameter mapping revealed a hemispherically symmetrical and homogeneous distribution of cerebrovascular reactivity over the entire grey matter. These findings indicate that it may be feasible to detect exhausted cerebrovascular autoregulation in patients with a compromised cerebral vasculature. (orig.)

  7. From signal to form: Nod factor as a morhogenetic signal molecule to induce symbiotic responses in legume root hairs

    NARCIS (Netherlands)

    Esseling, J.J.

    2004-01-01

    In this thesis, research is presented which contributes to a better understanding of nod factor (NF) induced signalling in Iegume root hairs, leading to a successful symbiosis. We mainly use root hairs of the model Iegume Medicago truncatula ('barrel medic') as an experimental system. In the

  8. Plasticity of the MAPK signaling network in response to mechanical stress.

    Directory of Open Access Journals (Sweden)

    Andrea M Pereira

    Full Text Available Cells display versatile responses to mechanical inputs and recent studies have identified the mitogen-activated protein kinase (MAPK cascades mediating the biological effects observed upon mechanical stimulation. Although, MAPK pathways can act insulated from each other, several mechanisms facilitate the crosstalk between the components of these cascades. Yet, the combinatorial complexity of potential molecular interactions between these elements have prevented the understanding of their concerted functions. To analyze the plasticity of the MAPK signaling network in response to mechanical stress we performed a non-saturating epistatic screen in resting and stretched conditions employing as readout a JNK responsive dJun-FRET biosensor. By knocking down MAPKs, and JNK pathway regulators, singly or in pairs in Drosophila S2R+ cells, we have uncovered unexpected regulatory links between JNK cascade kinases, Rho GTPases, MAPKs and the JNK phosphatase Puc. These relationships have been integrated in a system network model at equilibrium accounting for all experimentally validated interactions. This model allows predicting the global reaction of the network to its modulation in response to mechanical stress. It also highlights its context-dependent sensitivity.

  9. A Fasting-Responsive Signaling Pathway that Extends Life Span in C. elegans

    Directory of Open Access Journals (Sweden)

    Masaharu Uno

    2013-01-01

    Full Text Available Intermittent fasting is one of the most effective dietary restriction regimens that extend life span in C. elegans and mammals. Fasting-stimulus responses are key to the longevity response; however, the mechanisms that sense and transduce the fasting stimulus remain largely unknown. Through a comprehensive transcriptome analysis in C. elegans, we find that along with the FOXO transcription factor DAF-16, AP-1 (JUN-1/FOS-1 plays a central role in fasting-induced transcriptional changes. KGB-1, one of the C. elegans JNKs, acts as an activator of AP-1 and is activated in response to fasting. KGB-1 and AP-1 are involved in intermittent fasting-induced longevity. Fasting-induced upregulation of the components of the SCF E3 ubiquitin ligase complex via AP-1 and DAF-16 enhances protein ubiquitination and reduces protein carbonylation. Our results thus identify a fasting-responsive KGB-1/AP-1 signaling pathway, which, together with DAF-16, causes transcriptional changes that mediate longevity, partly through regulating proteostasis.

  10. Inhibition of TGFbeta1 Signaling Attenutates ATM Activity inResponse to Genotoxic Stress

    Energy Technology Data Exchange (ETDEWEB)

    Kirshner, Julia; Jobling, Michael F.; Pajares, Maria Jose; Ravani, Shraddha A.; Glick, Adam B.; Lavin, Martin J.; Koslov, Sergei; Shiloh, Yosef; Barcellos-Hoff, Mary Helen

    2006-09-15

    Ionizing radiation causes DNA damage that elicits a cellular program of damage control coordinated by the kinase activity of ataxia telangiectasia mutated protein (ATM). Transforming growth factor {beta}1 (TGF{beta}), which is activated by radiation, is a potent and pleiotropic mediator of physiological and pathological processes. Here we show that TGF{beta} inhibition impedes the canonical cellular DNA damage stress response. Irradiated Tgf{beta}1 null murine epithelial cells or human epithelial cells treated with a small molecule inhibitor of TGF{beta} type I receptor kinase exhibit decreased phosphorylation of Chk2, Rad17 and p53, reduced {gamma}H2AX radiation-induced foci, and increased radiosensitivity compared to TGF{beta} competent cells. We determined that loss of TGF{beta} signaling in epithelial cells truncated ATM autophosphorylation and significantly reduced its kinase activity, without affecting protein abundance. Addition of TGF{beta} restored functional ATM and downstream DNA damage responses. These data reveal a heretofore undetected critical link between the microenvironment and ATM that directs epithelial cell stress responses, cell fate and tissue integrity. Thus, TGF{beta}1, in addition to its role in homoeostatic growth control, plays a complex role in regulating responses to genotoxic stress, the failure of which would contribute to the development of cancer; conversely, inhibiting TGF{beta} may be used to advantage in cancer therapy.

  11. Primate fetal hepatic responses to maternal obesity: epigenetic signalling pathways and lipid accumulation.

    Science.gov (United States)

    Puppala, Sobha; Li, Cun; Glenn, Jeremy P; Saxena, Romil; Gawrieh, Samer; Quinn, Amy; Palarczyk, Jennifer; Dick, Edward J; Nathanielsz, Peter W; Cox, Laura A

    2018-03-07

    Maternal obesity (MO) increases offspring cardiometabolic disease risk. Altered fetal liver development in response to the challenge of MO has metabolic consequences underlying adverse offspring life-course health outcomes. Little is known about molecular pathways and potential epigenetic changes regulating primate fetal liver responses to MO. We hypothesized that MO would induce fetal baboon liver epigenetic changes resulting in dysregulation of key metabolic pathways that impact lipid metabolism. MO was induced prior to pregnancy by a high fat, high sucrose diet. Unbiased gene and microRNA (miRNA; small RNA Seq) abundance analyses were performed on fetal baboon livers at 0.9 gestation (G) and subjected to pathway analyses to identify fetal liver molecular responses to MO. Fetal baboon liver lipid and glycogen content were quantified by Computer Assisted Stereology Toolbox. In response to MO, fetal livers revealed dysregulation of TCA cycle, proteasome, oxidative phosphorylation, glycolysis and Wnt/β-catenin signalling pathways together with marked lipid accumulation supporting our hypothesis that multiple pathway dysregulation detrimentally impacts lipid management. This is the first study of MO programming of the nonhuman primate fetal liver using unbiased transcriptome analysis to detect changes in hepatic gene expression levels and identify potential miRNA epigenetic regulators of metabolic disruption. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  12. Role of Adrenal Glucocorticoid Signaling in Prefrontal Cortex Gene Expression and Acute Behavioral Responses to Ethanol

    Science.gov (United States)

    Costin, Blair N.; Wolen, Aaron R.; Fitting, Sylvia; Shelton, Keith L.; Miles, Michael F.

    2012-01-01

    Background Glucocorticoid hormones modulate acute and chronic behavioral and molecular responses to drugs of abuse including psychostimulants and opioids. There is growing evidence that glucocorticoids might also modulate behavioral responses to ethanol. Acute ethanol activates the HPA axis, causing release of adrenal glucocorticoid hormones. Our prior genomic studies suggest glucocorticoids play a role in regulating gene expression in the prefrontal cortex (PFC) of DBA2/J (D2) mice following acute ethanol administration. However, few studies have analyzed the role of glucocorticoid signaling in behavioral responses to acute ethanol. Such work could be significant, given the predictive value for level of response to acute ethanol in the risk for alcoholism. Methods We studied whether the glucocorticoid receptor (GR) antagonist, RU-486, or adrenalectomy (ADX) altered male D2 mouse behavioral responses to acute (locomotor activation, anxiolysis or loss-of-righting reflex (LORR)) or repeated (sensitization) ethanol treatment. Whole genome microarray analysis and bioinformatics approaches were used to identify PFC candidate genes possibly responsible for altered behavioral responses to ethanol following ADX. Results ADX and RU-486 both impaired acute ethanol (2 g/kg) induced locomotor activation in D2 mice without affecting basal locomotor activity. However, neither ADX nor RU-486 altered initiation of ethanol sensitization (locomotor activation or jump counts), ethanol-induced anxiolysis or LORR. ADX mice showed microarray gene expression changes in PFC that significantly overlapped with acute ethanol-responsive gene sets derived by our prior microarray studies. Q-rtPCR analysis verified that ADX decreased PFC expression of Fkbp5 while significantly increasing Gpr6 expression. In addition, high dose RU-486 pre-treatment blunted ethanol-induced Fkbp5 expression. Conclusions Our studies suggest that ethanol’s activation of adrenal glucocorticoid release and subsequent

  13. Feline mediastinal lymphoma: a retrospective study of signalment, retroviral status, response to chemotherapy and prognostic indicators.

    Science.gov (United States)

    Fabrizio, Francesca; Calam, Amy E; Dobson, Jane M; Middleton, Stephanie A; Murphy, Sue; Taylor, Samantha S; Schwartz, Anita; Stell, Anneliese J

    2014-08-01

    Historically, feline mediastinal lymphoma has been associated with young age, positive feline leukaemia virus (FeLV) status, Siamese breed and short survival times. Recent studies following widespread FeLV vaccination in the UK are lacking. The aim of this retrospective multi-institutional study was to re-evaluate the signalment, retroviral status, response to chemotherapy, survival and prognostic indicators in feline mediastinal lymphoma cases in the post-vaccination era. Records of cats with clinical signs associated with a mediastinal mass and cytologically/histologically confirmed lymphoma were reviewed from five UK referral centres (1998-2010). Treatment response, survival and prognostic indicators were assessed in treated cats with follow-up data. Fifty-five cases were reviewed. The median age was 3 years (range, 0.5-12 years); 12 cats (21.8%) were Siamese; and the male to female ratio was 3.2:1.0. Five cats were FeLV-positive and two were feline immunodeficiency-positive. Chemotherapy response and survival was evaluated in 38 cats. Overall response was 94.7%; complete (CR) and partial response (PR) rates did not differ significantly between protocols: COP (cyclophosphamide, vincristine, prednisone) (n = 26, CR 61.5%, PR 34.0%); Madison-Wisconsin (MW) (n = 12, CR 66.7%, PR 25.0%). Overall median survival was 373 days (range, 20-2015 days) (COP 484 days [range, 20-980 days]; MW 211 days [range, 24-2015 days] [P = 0.892]). Cats achieving CR survived longer (980 days vs 42 days for PR; P = 0.032). Age, breed, sex, location (mediastinal vs mediastinal plus other sites), retroviral status and glucocorticoid pretreatment did not affect response or survival. Feline mediastinal lymphoma cases frequently responded to chemotherapy with durable survival times, particularly in cats achieving CR. The prevalence of FeLV-antigenaemic cats was low; males and young Siamese cats appeared to be over-represented. © ISFM and AAFP 2013.

  14. Adrenergic Signaling: A Targetable Checkpoint Limiting Development of the Antitumor Immune Response.

    Science.gov (United States)

    Qiao, Guanxi; Chen, Minhui; Bucsek, Mark J; Repasky, Elizabeth A; Hylander, Bonnie L

    2018-01-01

    An immune response must be tightly controlled so that it will be commensurate with the level of response needed to protect the organism without damaging normal tissue. The roles of cytokines and chemokines in orchestrating these processes are well known, but although stress has long been thought to also affect immune responses, the underlying mechanisms were not as well understood. Recently, the role of nerves and, specifically, the sympathetic nervous system, in regulating immune responses is being revealed. Generally, an acute stress response is beneficial but chronic stress is detrimental because it suppresses the activities of effector immune cells while increasing the activities of immunosuppressive cells. In this review, we first discuss the underlying biology of adrenergic signaling in cells of both the innate and adaptive immune system. We then focus on the effects of chronic adrenergic stress in promoting tumor growth, giving examples of effects on tumor cells and immune cells, explaining the methods commonly used to induce stress in preclinical mouse models. We highlight how this relates to our observations that mandated housing conditions impose baseline chronic stress on mouse models, which is sufficient to cause chronic immunosuppression. This problem is not commonly recognized, but it has been shown to impact conclusions of several studies of mouse physiology and mouse models of disease. Moreover, the fact that preclinical mouse models are chronically immunosuppressed has critical ramifications for analysis of any experiments with an immune component. Our group has found that reducing adrenergic stress by housing mice at thermoneutrality or treating mice housed at cooler temperatures with β-blockers reverses immunosuppression and significantly improves responses to checkpoint inhibitor immunotherapy. These observations are clinically relevant because there are numerous retrospective epidemiological studies concluding that cancer patients who were

  15. Modeling the response of small myelinated axons in a compound nerve to kilohertz frequency signals

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    Pelot, N. A.; Behrend, C. E.; Grill, W. M.

    2017-08-01

    Objective. There is growing interest in electrical neuromodulation of peripheral nerves, particularly autonomic nerves, to treat various diseases. Electrical signals in the kilohertz frequency (KHF) range can produce different responses, including conduction block. For example, EnteroMedics’ vBloc® therapy for obesity delivers 5 kHz stimulation to block the abdominal vagus nerves, but the mechanisms of action are unclear. Approach. We developed a two-part computational model, coupling a 3D finite element model of a cuff electrode around the human abdominal vagus nerve with biophysically-realistic electrical circuit equivalent (cable) model axons (1, 2, and 5.7 µm in diameter). We developed an automated algorithm to classify conduction responses as subthreshold (transmission), KHF-evoked activity (excitation), or block. We quantified neural responses across kilohertz frequencies (5-20 kHz), amplitudes (1-8 mA), and electrode designs. Main results. We found heterogeneous conduction responses across the modeled nerve trunk, both for a given parameter set and across parameter sets, although most suprathreshold responses were excitation, rather than block. The firing patterns were irregular near transmission and block boundaries, but otherwise regular, and mean firing rates varied with electrode-fibre distance. Further, we identified excitation responses at amplitudes above block threshold, termed ‘re-excitation’, arising from action potentials initiated at virtual cathodes. Excitation and block thresholds decreased with smaller electrode-fibre distances, larger fibre diameters, and lower kilohertz frequencies. A point source model predicted a larger fraction of blocked fibres and greater change of threshold with distance as compared to the realistic cuff and nerve model. Significance. Our findings of widespread asynchronous KHF-evoked activity suggest that conduction block in the abdominal vagus nerves is unlikely with current clinical parameters. Our

  16. The Not-So-Global Blood Oxygen Level-Dependent Signal.

    Science.gov (United States)

    Billings, Jacob; Keilholz, Shella

    2018-04-01

    Global signal regression is a controversial processing step for resting-state functional magnetic resonance imaging, partly because the source of the global blood oxygen level-dependent (BOLD) signal remains unclear. On the one hand, nuisance factors such as motion can readily introduce coherent BOLD changes across the whole brain. On the other hand, the global signal has been linked to neural activity and vigilance levels, suggesting that it contains important neurophysiological information and should not be discarded. Any widespread pattern of coordinated activity is likely to contribute appreciably to the global signal. Such patterns may include large-scale quasiperiodic spatiotemporal patterns, known also to be tied to performance on vigilance tasks. This uncertainty surrounding the separability of the global BOLD signal from concurrent neurological processes motivated an examination of the global BOLD signal's spatial distribution. The results clarify that although the global signal collects information from all tissue classes, a diverse subset of the BOLD signal's independent components contribute the most to the global signal. Further, the timing of each network's contribution to the global signal is not consistent across volunteers, confirming the independence of a constituent process that comprises the global signal.

  17. TGF-β1 accelerates the DNA damage response in epithelial cells via Smad signaling

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jeeyong; Kim, Mi-Ra; Kim, Hyun-Ji; An, You Sun; Yi, Jae Youn, E-mail: yjy_71@kcch.re.kr

    2016-08-05

    The evidence suggests that transforming growth factor-beta (TGF-β) regulates the DNA-damage response (DDR) upon irradiation, and we previously reported that TGF-β1 induced DNA ligase IV (Lig4) expression and enhanced the nonhomologous end-joining repair pathway in irradiated cells. In the present study, we investigated the effects of TGF-β1 on the irradiation-induced DDRs of A431 and HaCaT cells. Cells were pretreated with or without TGF-β1 and irradiated. At 30 min post-irradiation, DDRs were detected by immunoblotting of phospho-ATM, phospho-Chk2, and the presence of histone foci (γH2AX). The levels of all three factors were similar right after irradiation regardless of TGF-β1 pretreatment. However, they soon thereafter exhibited downregulation in TGF-β1-pretreated cells, indicating the acceleration of the DDR. Treatment with a TGF-β type I receptor inhibitor (SB431542) or transfections with siRNAs against Smad2/3 or DNA ligase IV (Lig4) reversed this acceleration of the DDR. Furthermore, the frequency of irradiation-induced apoptosis was decreased by TGF-β1 pretreatment in vivo, but this effect was abrogated by SB431542. These results collectively suggest that TGF-β1 could enhance cell survival by accelerating the DDR via Smad signaling and Lig4 expression. -- Highlights: •TGF-β1 pretreatment accelerates γ-radiation-induced DNA damage response. •TGF-β1-accelerated DNA damage response is dependent on Smad signaling and DNA Ligase IV. •TGF-β1 pretreatment protects epithelial cells from γ-radiation in vivo.

  18. Non-invasive multiparametric qBOLD approach for robust mapping of the oxygen extraction fraction.

    Science.gov (United States)

    Domsch, Sebastian; Mie, Moritz B; Wenz, Frederik; Schad, Lothar R

    2014-09-01

    The quantitative blood oxygenation level-dependent (qBOLD) method has not become clinically established yet because long acquisition times are necessary to achieve an acceptable certainty of the parameter estimates. In this work, a non-invasive multiparametric (nimp) qBOLD approach based on a simple analytical model is proposed to facilitate robust oxygen extraction fraction (OEF) mapping within clinically acceptable acquisition times by using separate measurements. The protocol consisted of a gradient-echo sampled spin-echo sequence (GESSE), a T2-weighted Carr-Purcell-Meiboom-Gill (CPMG) sequence, and a T2(*)-weighted multi-slice multi-echo gradient echo (MMGE) sequence. The GESSE acquisition time was less than 5 minutes and the extra measurement time for CPMG/MMGE was below 2 minutes each. The proposed nimp-qBOLD approach was validated in healthy subjects (N = 5) and one patient. The proposed nimp-qBOLD approach facilitated more robust OEF mapping with significantly reduced inter- and intra-subject variability compared to the standard qBOLD method. Thereby, an average OEF in all subjects of 27±2% in white matter (WM) and 29±2% in gray matter (GM) using the nimp-qBOLD method was more stable compared to 41±10% (WM) and 46±10% (GM) with standard qBOLD. Moreover, the spatial variance in the image slice (i.e. standard deviation divided by mean) was on average reduced from 35% to 25%. In addition, the preliminary results of the patient are encouraging. The proposed nimp-qBOLD technique provides a promising tool for robust OEF mapping within clinically acceptable acquisition times and could therefore provide an important contribution for analyzing tumors or monitoring the success of radio and chemo therapies. Copyright © 2014. Published by Elsevier GmbH.

  19. Gamma-ray-induced bold seeded early maturing groundnut selections

    International Nuclear Information System (INIS)

    Manoharan, V.; Thangavelu, S.

    1990-01-01

    Full text: ''Chico'' is an early maturing (85-90 days) erect groundnut (Arachis hypogaea L.) genotype utilised in groundnut improvement to incorporate earliness in high yielding varieties. Though it has high shelling out-turn, its yield potential is low since it has small seeds. Mutation breeding was started with the objective of improving the seed size. In a preliminary experiment, dry seeds were treated with 20, 30, 40 or 50 kR of gamma rays. The M 1 generation was grown during the post rainy season of 1988-1989. The M 2 generation was planted as individual plant progeny rows during the rainy season of 1989. 105 progeny rows were studied, the total number of M 2 plants being 1,730. All the M 2 plants were harvested 90 days after sowing. Seven mutants with bold seed size were obtained. The mutants had 100 kernel weight ranging from 22.2 to 40.4 g compared to 21.1 g of control. The study is in progress. (author)

  20. Predictors of dyspnea prevalence: Results from the BOLD study

    Science.gov (United States)

    Grønseth, Rune; Vollmer, William M.; Hardie, Jon A.; Ólafsdóttir, Inga Sif; Lamprecht, Bernd; Buist, A. Sonia; Gnatiuc, Louisa; Gulsvik, Amund; Johannessen, Ane; Enright, Paul

    2014-01-01

    Dyspnea is a cardinal symptom for cardiorespiratory diseases. No study has assessed worldwide variation in dyspnea prevalence or predictors of dyspnea. We used cross-sectional data from population-based samples in 15 countries of the BOLD study to estimate prevalence of dyspnea in the full sample as well as in an a priori defined low-risk group (few risk factors or dyspnea-associated diseases). Dyspnea was defined by the modified Medical Research Council questions. We used ordered logistic regression analysis to study the association of dyspnea with site, sex, age, education, smoking habits, low/high BMI, self-reported disease, and spirometry results. Of the 9,484 participants, 27% reported any dyspnea. In the low-risk subsample (N=4,329), 16% reported some dyspnea. In multivariate analyses, all covariates were correlated to dyspnea, but only 13% of dyspnea variation was explained. Women reported more dyspnea than men (odds ratio ≈ 2.1). When forced vital capacity (FVC) fell below 60% of predicted, dyspnea was much more likely. There was considerable geographical variation in dyspnea, even when we adjusted for known risk factors and spirometry results. We were only able to explain 13% of dyspnea variation. PMID:24176991

  1. The quantitative genetic architecture of the bold-shy continuum in zebrafish, Danio rerio.

    Directory of Open Access Journals (Sweden)

    Mary E Oswald

    Full Text Available In studies of consistent individual differences (personality along the bold-shy continuum, a pattern of behavioral correlations frequently emerges: individuals towards the bold end of the continuum are more likely to utilize risky habitat, approach potential predators, and feed under risky conditions. Here, we address the hypothesis that observed phenotypic correlations among component behaviors of the bold-shy continuum are a result of underlying genetic correlations (quantitative genetic architecture. We used a replicated three-generation pedigree of zebrafish (Danio rerio to study three putative components of the bold-shy continuum: horizontal position, swim level, and feeding latency. We detected significant narrow-sense heritabilities as well as significant genetic and phenotypic correlations among all three behaviors, such that fish selected for swimming at the front of the tank swam closer to the observer, swam higher in the water column, and fed more quickly than fish selected for swimming at the back of the tank. Further, the lines varied in their initial open field behavior (swim level and activity level. The quantitative genetic architecture of the bold-shy continuum indicates that the multivariate behavioral phenotype characteristic of a "bold" personality type may be a result of correlated evolution via underlying genetic correlations.

  2. Impact of abnormal cerebrovascular reactivity on BOLD fMRI: a preliminary investigation of moyamoya disease.

    Science.gov (United States)

    Mazerolle, Erin L; Ma, Yuhan; Sinclair, David; Pike, G Bruce

    2018-01-01

    Blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) studies of patients with cerebrovascular disease have largely ignored the confounds associated with abnormal cerebral blood flow, vascular reactivity and neurovascular coupling. We studied BOLD fMRI activation and cerebrovascular reactivity in moyamoya disease. To characterize the impact of remote vascular demands on BOLD fMRI measurements, we varied the vascular territories engaged by manipulating the experimental task performed by the participants. Vascular territories affected by disease were identified using BOLD cerebrovascular reactivity. Preliminary evidence from two patients pre- and postrevascularization surgery and four controls indicates that neurovascular coupling in affected brain regions can be modulated by the task-related vascular demands in unaffected regions. In one patient studied, we observed that brain regions with improved cerebrovascular reactivity after surgery demonstrated normalized neurovascular coupling, that is the degree to which neurovascular coupling was modulated by task-related vascular demands was decreased. We propose that variations in task-dependent neurovascular coupling in patients with moyamoya disease are likely related to vascular steal. While preliminary, our findings are a proof of concept of the limitations of BOLD fMRI in cerebrovascular disease and suggest a role for assessment of cerebrovascular reactivity to improve interpretation of task-related BOLD fMRI activation. © 2016 The Authors. Clinical Physiology and Functional Imaging published by John Wiley & Sons Ltd on behalf of Scandinavian Society of Clinical Physiology and Nuclear Medicine.

  3. Light and circadian regulation of clock components aids flexible responses to environmental signals

    Science.gov (United States)

    Dixon, Laura E; Hodge, Sarah K; van Ooijen, Gerben; Troein, Carl; Akman, Ozgur E; Millar, Andrew J

    2014-01-01

    The circadian clock measures time across a 24 h period, increasing fitness by phasing biological processes to the most appropriate time of day. The interlocking feedback loop mechanism of the clock is conserved across species; however, the number of loops varies. Mathematical and computational analyses have suggested that loop complexity affects the overall flexibility of the oscillator, including its responses to entrainment signals. We used a discriminating experimental assay, at the transition between different photoperiods, in order to test this proposal in a minimal circadian network (in Ostreococcus tauri) and a more complex network (in Arabidopsis thaliana). Transcriptional and translational reporters in O. tauri primarily tracked dawn or dusk, whereas in A. thaliana, a wider range of responses were observed, consistent with its more flexible clock. Model analysis supported the requirement for this diversity of responses among the components of the more complex network. However, these and earlier data showed that the O. tauri network retains surprising flexibility, despite its simple circuit. We found that models constructed from experimental data can show flexibility either from multiple loops and/or from multiple light inputs. Our results suggest that O. tauri has adopted the latter strategy, possibly as a consequence of genomic reduction. PMID:24842166

  4. Cytosolic acidification as a signal mediating hyperosmotic stress responses in Dictyostelium discoideum

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    Klein Gérard

    2001-06-01

    Full Text Available Abstract Background Dictyostelium cells exhibit an unusual response to hyperosmolarity that is distinct from the response in other organisms investigated: instead of accumulating compatible osmolytes as it has been described for a wide range of organisms, Dictyostelium cells rearrange their cytoskeleton and thereby build up a rigid network which is believed to constitute the major osmoprotective mechanism in this organism. To gain more insight into the osmoregulation of this amoeba, we investigated physiological processes affected under hyperosmotic conditions in Dictyostelium. Results We determined pH changes in response to hyperosmotic stress using FACS or 31P-NMR. Hyperosmolarity was found to acidify the cytosol from pH 7.5 to 6.8 within 5 minutes, whereas the pH of the endo-lysosomal compartment remained constant. Fluid-phase endocytosis was identified as a possible target of cytosolic acidification, as the inhibition of endocytosis observed under hypertonic conditions can be fully attributed to cytosolic acidification. In addition, a deceleration of vesicle mobility and a decrease in the NTP pool was observed. Conclusion Together, these results indicate that hyperosmotic stress triggers pleiotropic effects, which are partially mediated by a pH signal and which all contribute to the downregulation of cellular activity. The comparison of our results with the effect of hyperosmolarity and intracellular acidification on receptor-mediated endocytosis in mammalian cells reveals striking similarities, suggesting the hypothesis of the same mechanism of inhibition by low internal pH.

  5. HIF-mediated innate immune responses: cell signaling and therapeutic implications

    Directory of Open Access Journals (Sweden)

    Harris AJ

    2014-05-01

    Full Text Available Alison J Harris, AA Roger Thompson, Moira KB Whyte, Sarah R Walmsley Academic Unit of Respiratory Medicine, Department of Infection and Immunity, University of Sheffield, Sheffield, UK Abstract: Leukocytes recruited to infected, damaged, or inflamed tissues during an immune response must adapt to oxygen levels much lower than those in the circulation. Hypoxia inducible factors (HIFs are key mediators of cellular responses to hypoxia and, as in other cell types, HIFs are critical for the upregulation of glycolysis, which enables innate immune cells to produce adenosine triphosphate anaerobically. An increasing body of evidence demonstrates that hypoxia also regulates many other innate immunological functions, including cell migration, apoptosis, phagocytosis of pathogens, antigen presentation and production of cytokines, chemokines, and angiogenic and antimicrobial factors. Many of these functions are mediated by HIFs, which are not only stabilized posttranslationally by hypoxia, but also transcriptionally upregulated by inflammatory signals. Here, we review the role of HIFs in the responses of innate immune cells to hypoxia, both in vitro and in vivo, with a particular focus on myeloid cells, on which the majority of studies have so far been carried out. Keywords: hypoxia, neutrophils, monocytes, macrophages

  6. Contributions of AMPK and p53 dependent signaling to radiation response in the presence of metformin.

    Science.gov (United States)

    Muaddi, Hala; Chowdhury, Sanjana; Vellanki, Ravi; Zamiara, Paul; Koritzinsky, Marianne

    2013-09-01

    Metformin is commonly prescribed to treat type 2 diabetes, and has additional potential as a cancer prophylactic and therapeutic. Metformin activates AMPK that in turn can launch a p53-dependent metabolic checkpoint. Possible interactions between metformin and radiation are poorly understood. Since radiation-induced signaling also involves AMPK and p53, we investigated their importance in mediating responses to metformin and radiation. A549 cells, HCT116 cells wildtype or knockout for p53 or MEFs wildtype or double knockout for AMPKα1 and α2 were irradiated in the presence or absence of metformin. The impact of metformin on oxygen consumption and proliferation rates was determined, as well as clonogenic radiation survival. Metformin resulted in moderate radiation protection in all cell lines, irrespective of AMPK and p53. Loss of AMPK sensitized cells to the anti-proliferative effects of metformin, while loss of p53 promoted both the growth inhibitory and toxic effects of metformin. Consequently, overall cell death after radiation was similar with and without metformin irrespective of AMPK or p53 genotype. The anti-proliferative activity of metformin may confer benefit in combination with radiotherapy, and this benefit is intensified upon loss of AMPK or p53 signaling. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  7. Best response game of traffic on road network of non-signalized intersections

    Science.gov (United States)

    Yao, Wang; Jia, Ning; Zhong, Shiquan; Li, Liying

    2018-01-01

    This paper studies the traffic flow in a grid road network with non-signalized intersections. The nature of the drivers in the network is simulated such that they play an iterative snowdrift game with other drivers. A cellular automata model is applied to study the characteristics of the traffic flow and the evolution of the behaviour of the drivers during the game. The drivers use best-response as their strategy to update rules. Three major findings are revealed. First, the cooperation rate in simulation experiences staircase-shaped drop as cost to benefit ratio r increases, and cooperation rate can be derived analytically as a function of cost to benefit ratio r. Second, we find that higher cooperation rate corresponds to higher average speed, lower density and higher flow. This reveals that defectors deteriorate the efficiency of traffic on non-signalized intersections. Third, the system experiences more randomness when the density is low because the drivers will not have much opportunity to update strategy when the density is low. These findings help to show how the strategy of drivers in a traffic network evolves and how their interactions influence the overall performance of the traffic system.

  8. Metal-organic semiconductor interfacial barrier height determination from internal photoemission signal in spectral response measurements

    Science.gov (United States)

    Kumar, Sandeep; Iyer, S. Sundar Kumar

    2017-04-01

    Accurate and convenient evaluation methods of the interfacial barrier ϕb for charge carriers in metal semiconductor (MS) junctions are important for designing and building better opto-electronic devices. This becomes more critical for organic semiconductor devices where a plethora of molecules are in use and standardised models applicable to myriads of material combinations for the different devices may have limited applicability. In this paper, internal photoemission (IPE) from spectral response (SR) in the ultra-violet to near infra-red range of different MS junctions of metal-organic semiconductor-metal (MSM) test structures is used to determine more realistic MS ϕb values. The representative organic semiconductor considered is [6, 6]-phenyl C61 butyric acid methyl ester, and the metals considered are Al and Au. The IPE signals in the SR measurement of the MSM device are identified and separated before it is analysed to estimate ϕb for the MS junction. The analysis of IPE signals under different bias conditions allows the evaluation of ϕb for both the front and back junctions, as well as for symmetric MSM devices.

  9. Cross Talk between H2O2 and Interacting Signal Molecules under Plant Stress Response

    Science.gov (United States)

    Saxena, Ina; Srikanth, Sandhya; Chen, Zhong

    2016-01-01

    It is well established that oxidative stress is an important cause of cellular damage. During stress conditions, plants have evolved regulatory mechanisms to adapt to various environmental stresses. One of the consequences of stress is an increase in the cellular concentration of reactive oxygen species, which is subsequently converted to H2O2. H2O2 is continuously produced as the byproduct of oxidative plant aerobic metabolism. Organelles with a high oxidizing metabolic activity or with an intense rate of electron flow, such as chloroplasts, mitochondria, or peroxisomes are major sources of H2O2 production. H2O2 acts as a versatile molecule because of its dual role in cells. Under normal conditions, H2O2 immerges as an important factor during many biological processes. It has been established that it acts as a secondary messenger in signal transduction networks. In this review, we discuss potential roles of H2O2 and other signaling molecules during various stress responses. PMID:27200043

  10. Yeast as a Tool to Study Signaling Pathways in Mitochondrial Stress Response and Cytoprotection

    Directory of Open Access Journals (Sweden)

    Maša Ždralević

    2012-01-01

    Full Text Available Cell homeostasis results from the balance between cell capability to adapt or succumb to environmental stress. Mitochondria, in addition to supplying cellular energy, are involved in a range of processes deciding about cellular life or death. The crucial role of mitochondria in cell death is well recognized. Mitochondrial dysfunction has been associated with the death process and the onset of numerous diseases. Yet, mitochondrial involvement in cellular adaptation to stress is still largely unexplored. Strong interest exists in pharmacological manipulation of mitochondrial metabolism and signaling. The yeast Saccharomyces cerevisiae has proven a valuable model organism in which several intracellular processes have been characterized in great detail, including the retrograde response to mitochondrial dysfunction and, more recently, programmed cell death. In this paper we review experimental evidences of mitochondrial involvement in cytoprotection and propose yeast as a model system to investigate the role of mitochondria in the cross-talk between prosurvival and prodeath pathways.

  11. Alcohol affects neuronal substrates of response inhibition but not of perceptual processing of stimuli signalling a stop response.

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    Kyriaki Nikolaou

    Full Text Available Alcohol impairs inhibitory control, including the ability to terminate an initiated action. While there is increasing knowledge about neural mechanisms involved in response inhibition, the level at which alcohol impairs such mechanisms remains poorly understood. Thirty-nine healthy social drinkers received either 0.4 g/kg or 0.8 g/kg of alcohol, or placebo, and performed two variants of a Visual Stop-signal task during acquisition of functional magnetic resonance imaging (fMRI data. The two task variants differed only in their instructions: in the classic variant (VSST, participants inhibited their response to a "Go-stimulus" when it was followed by a "Stop-stimulus". In the control variant (VSST_C, participants responded to the "Go-stimulus" even if it was followed by a "Stop-stimulus". Comparison of successful Stop-trials (Sstop>Go, and unsuccessful Stop-trials (Ustop>Sstop between the three beverage groups enabled the identification of alcohol effects on functional neural circuits supporting inhibitory behaviour and error processing. Alcohol impaired inhibitory control as measured by the Stop-signal reaction time, but did not affect other aspects of VSST performance, nor performance on the VSST_C. The low alcohol dose evoked changes in neural activity within prefrontal, temporal, occipital and motor cortices. The high alcohol dose evoked changes in activity in areas affected by the low dose but importantly induced changes in activity within subcortical centres including the globus pallidus and thalamus. Alcohol did not affect neural correlates of perceptual processing of infrequent cues, as revealed by conjunction analyses of VSST and VSST_C tasks. Alcohol ingestion compromises the inhibitory control of action by modulating cortical regions supporting attentional, sensorimotor and action-planning processes. At higher doses the impact of alcohol also extends to affect subcortical nodes of fronto-basal ganglia- thalamo-cortical motor circuits

  12. Jasmonate and Phytochrome A Signaling in Arabidopsis Wound and Shade Responses Are Integrated through JAZ1 Stability[C][W

    Science.gov (United States)

    Robson, Frances; Okamoto, Haruko; Patrick, Elaine; Harris, Sue-Ré; Wasternack, Claus; Brearley, Charles; Turner, John G.

    2010-01-01

    Jasmonate (JA) activates plant defense, promotes pollen maturation, and suppresses plant growth. An emerging theme in JA biology is its involvement in light responses; here, we examine the interdependence of the JA- and light-signaling pathways in Arabidopsis thaliana. We demonstrate that mutants deficient in JA biosynthesis and signaling are deficient in a subset of high irradiance responses in far-red (FR) light. These mutants display exaggerated shade responses to low, but not high, R/FR ratio light, suggesting a role for JA in phytochrome A (phyA) signaling. Additionally, we demonstrate that the FR light–induced expression of transcription factor genes is dependent on CORONATINE INSENSITIVE1 (COI1), a central component of JA signaling, and is suppressed by JA. phyA mutants had reduced JA-regulated growth inhibition and VSP expression and increased content of cis-(+)-12-oxophytodienoic acid, an intermediate in JA biosynthesis. Significantly, COI1-mediated degradation of JASMONATE ZIM DOMAIN1-β-glucuronidase (JAZ1-GUS) in response to mechanical wounding and JA treatment required phyA, and ectopic expression of JAZ1-GUS resulted in exaggerated shade responses. Together, these results indicate that JA and phyA signaling are integrated through degradation of the JAZ1 protein, and both are required for plant responses to light and stress. PMID:20435902

  13. Increased Sucrose Accumulation Regulates Iron-Deficiency Responses by Promoting Auxin Signaling in Arabidopsis Plants.

    Science.gov (United States)

    Lin, Xian Yong; Ye, Yi Quan; Fan, Shi Kai; Jin, Chong Wei; Zheng, Shao Jian

    2016-02-01

    Previous studies have identified that auxins acts upstream of nitric oxide in regulating iron deficiency responses in roots, but the upstream signaling molecule of auxins remains unknown. In this study, we showed that Fe deficiency increased sucrose (Suc) level in roots of Arabidopsis (Arabidopsis thaliana). Exogenous application of Suc further stimulated Fe deficiency-induced ferric-chelate-reductase (FCR) activity and expression of Fe acquisition-related genes FRO2, IRT1, and FIT in roots. The opposite patterns were observed in the dark treatment. In addition, FCR activity and expression of Fe acquisition-related genes were higher in the Suc high-accumulating transgenic plant 35S::SUC2 but were lower in the Suc low-accumulating mutant suc2-5 compared with wild-type plants under Fe-deficient conditions. Consequently, Fe deficiency tolerance was enhanced in 35S::SUC2 but was compromised in suc2-5. Exogenous Suc also increased root β-glucuronidase (GUS) activity in auxin-inducible reporter DR5-GUS transgenic plants under Fe deficiency. However, exogenous Suc failed to increase FCR activity and expression of Fe acquisition-related genes in the auxin transport-impaired mutants aux1-7 and pin1-1 as well as in the wild-type plants treated with an auxin transport inhibitor under Fe deficiency. In summary, we found that increased Suc accumulation is required for regulating Fe deficiency responses in plants, with auxins acting downstream in transmitting the Fe deficiency signal. © 2016 American Society of Plant Biologists. All Rights Reserved.

  14. Equivalent dose determination in foraminifera: analytical description of the CO{sub 2}{sup -}-signal dose-response curve

    Energy Technology Data Exchange (ETDEWEB)

    Hoffmann, D. E-mail: dirk.hoffmann@iup.uni-heidelberg.de; Woda, C.; Mangini, A

    2003-02-01

    The dose-response of the CO{sub 2}{sup -}signal (g=2.0006) in foraminifera with ages between 19 and 300 ka is investigated. The sum of two exponential saturation functions is an adequate function to describe the dose-response curve up to an additional dose of 8000 Gy. It yields excellent dating results but requires an artificial doses of at least 5000 Gy. For small additional doses of about 500 Gy the single exponential saturation function can be used to calculate a reliable equivalent dose D{sub E}, although it does not describ the dose-response for higher doses. The CO{sub 2}{sup -}-signal dose-response indicates that the signal has two components of which one is less stable than the other.

  15. Morphogen and community effects determine cell fates in response to BMP4 signaling in human embryonic stem cells.

    Science.gov (United States)

    Nemashkalo, Anastasiia; Ruzo, Albert; Heemskerk, Idse; Warmflash, Aryeh

    2017-09-01

    Paracrine signals maintain developmental states and create cell fate patterns in vivo and influence differentiation outcomes in human embryonic stem cells (hESCs) in vitro Systematic investigation of morphogen signaling is hampered by the difficulty of disentangling endogenous signaling from experimentally applied ligands. Here, we grow hESCs in micropatterned colonies of 1-8 cells ('µColonies') to quantitatively investigate paracrine signaling and the response to external stimuli. We examine BMP4-mediated differentiation in µColonies and standard culture conditions and find that in µColonies, above a threshold concentration, BMP4 gives rise to only a single cell fate, contrary to its role as a morphogen in other developmental systems. Under standard culture conditions BMP4 acts as a morphogen but this requires secondary signals and particular cell densities. We find that a 'community effect' enforces a common fate within µColonies, both in the state of pluripotency and when cells are differentiated, and that this effect allows a more precise response to external signals. Using live cell imaging to correlate signaling histories with cell fates, we demonstrate that interactions between neighbors result in sustained, homogenous signaling necessary for differentiation. © 2017. Published by The Company of Biologists Ltd.

  16. Global brain blood-oxygen level responses to autonomic challenges in obstructive sleep apnea.

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    Paul M Macey

    Full Text Available Obstructive sleep apnea (OSA is accompanied by brain injury, perhaps resulting from apnea-related hypoxia or periods of impaired cerebral perfusion. Perfusion changes can be determined indirectly by evaluation of cerebral blood volume and oxygenation alterations, which can be measured rapidly and non-invasively with the global blood oxygen level dependent (BOLD signal, a magnetic resonance imaging procedure. We assessed acute BOLD responses in OSA subjects to pressor challenges that elicit cerebral blood flow changes, using a two-group comparative design with healthy subjects as a reference. We separately assessed female and male patterns, since OSA characteristics and brain injury differ between sexes. We studied 94 subjects, 37 with newly-diagnosed, untreated OSA (6 female (age mean ± std: 52.1±8.1 yrs; apnea/hypopnea index [AHI]: 27.7±15.6 events/hr and 31 male 54.3±8.4 yrs; AHI: 37.4±19.6 events/hr, and 20 female (age 50.5±8.1 yrs and 37 male (age 45.6±9.2 yrs healthy control subjects. We measured brain BOLD responses every 2 s while subjects underwent cold pressor, hand grip, and Valsalva maneuver challenges. The global BOLD signal rapidly changed after the first 2 s of each challenge, and differed in magnitude between groups to two challenges (cold pressor, hand grip, but not to the Valsalva maneuver (repeated measures ANOVA, p<0.05. OSA females showed greater differences from males in response magnitude and pattern, relative to healthy counterparts. Cold pressor BOLD signal increases (mean ± adjusted standard error at the 8 s peak were: OSA 0.14±0.08% vs. Control 0.31±0.06%, and hand grip at 6 s were: OSA 0.08±0.03% vs. Control at 0.30±0.02%. These findings, indicative of reduced cerebral blood flow changes to autonomic challenges in OSA, complement earlier reports of altered resting blood flow and reduced cerebral artery responsiveness. Females are more affected than males, an outcome which may contribute to the sex

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

    Science.gov (United States)

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

    2011-01-01

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

  18. Grapevine immune signaling network in response to drought stress as revealed by transcriptomic analysis.

    Science.gov (United States)

    Haider, Muhammad S; Kurjogi, Mahantesh M; Khalil-Ur-Rehman, M; Fiaz, Muhammad; Pervaiz, Tariq; Jiu, Songtao; Haifeng, Jia; Chen, Wang; Fang, Jinggui

    2017-12-01

    Drought is a ubiquitous abiotic factor that severely impedes growth and development of horticulture crops. The challenge postured by global climate change is the evolution of drought-tolerant cultivars that could cope with concurrent stress. Hence, in this study, biochemical, physiological and transcriptome analysis were investigated in drought-treated grapevine leaves. The results revealed that photosynthetic activity and reducing sugars were significantly diminished which were positively correlated with low stomatal conductance and CO 2 exchange in drought-stressed leaves. Further, the activities of superoxide dismutase, peroxidase, and catalase were significantly actuated in the drought-responsive grapevine leaves. Similarly, the levels of abscisic acid and jasmonic acid were also significantly increased in the drought-stressed leaves. In transcriptome analysis, 12,451 differentially-expressed genes (DEGs) were annotated, out of which 8021 DEGs were up-regulated and 4430 DEGs were down-regulated in response to drought stress. In addition, the genes encoding pathogen-associated molecular pattern (PAMP) triggered immunity (PTI), including calcium signals, protein phosphatase 2C, calcineurin B-like proteins, MAPKs, and phosphorylation (FLS2 and MEKK1) cascades were up-regulated in response to drought stress. Several genes related to plant-pathogen interaction pathway (RPM1, PBS1, RPS5, RIN4, MIN7, PR1, and WRKYs) were also found up-regulated in response to drought stress. Overall the results of present study showed the dynamic interaction of DEG in grapevine physiology which provides the premise for selection of defense-related genes against drought stress for subsequent grapevine breeding programs. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  19. Ring modulator small-signal response analysis based on pole-zero representation.

    Science.gov (United States)

    Karimelahi, Samira; Sheikholeslami, Ali

    2016-04-04

    We present a closed-form expression for the small-signal response of a depletion-mode ring modulator and verify it by measurement results. Both electrical and optical behavior of micro-ring modulator as well as the loss variation due to the index modulation is considered in the derivation. This expression suggests that a ring modulator is a third-order system with one real pole, one zero and a pair of complex-conjugate poles. The exact positions of the poles/zero are given and shown to be dependent upon parameters such as electrical bandwidth, coupling condition, optical loss, and sign/value of laser detunings. We show that the location of zero is different for positive and negative detuning, and therefore, the ring modulator frequency response is asymmetric. We use the gain-bandwidth product as a figure of merit and calculate it for various pole/zero locations. We show that gain-bandwidth for the over-coupled ring modulator is superior compared to other coupling conditions. Also, we show that the gain-bandwidth product can be increased to a limit by increasing the electrical bandwidth.

  20. Molecular signal for induction of the adaptive response to alkylating agents in E. coli

    Energy Technology Data Exchange (ETDEWEB)

    Lindahl, T.; Sedgwick, B.; Teo, I.; Kilpatrick, M.; McCarthy, T.; Hughes, S.

    1986-05-01

    Exposure of E. coli to simple alkylating agents such as methylnitrosourea causes the induction of at least three DNA repair functions, which are under the control of the ada gene. The intracellular signal for switching on the response has been identified as one of the two stereoisomers of methyl phosphotriesters generated in DNA by alkylation. The methyl group is transferred from the phosphotriester moiety to a specific cysteine residue within the regulatory Ada protein in a self-methylation reaction. This protein also corrects the mutagenic lesion O/sup 6/-methylguanine by transfer of its methyl group to a separate cysteine residue in the Ada protein. Methylation of the protein from repair of a DNA phosphotriester residue, but not from O/sup 6/-methylguanine, converts it to an activator of transcription of genes involved in the adaptive response. The activated form of the Ada protein enhances transcription by binding specifically to a sequence d(AAA--AAAGCGCA), located immediately upstream of the RNA polymerase binding site in relevant promoter regions.

  1. Fractional modeling of the AC large-signal frequency response in magnetoresistive current sensors.

    Science.gov (United States)

    Ravelo Arias, Sergio Iván; Ramírez Muñoz, Diego; Moreno, Jaime Sánchez; Cardoso, Susana; Ferreira, Ricardo; de Freitas, Paulo Jorge Peixeiro

    2013-12-17

    Fractional calculus is considered when derivatives and integrals of non-integer order are applied over a specific function. In the electrical and electronic domain, the transfer function dependence of a fractional filter not only by the filter order n, but additionally, of the fractional order α is an example of a great number of systems where its input-output behavior could be more exactly modeled by a fractional behavior. Following this aim, the present work shows the experimental ac large-signal frequency response of a family of electrical current sensors based in different spintronic conduction mechanisms. Using an ac characterization set-up the sensor transimpedance function Z(t)(JF) is obtained considering it as the relationship between sensor output voltage and input sensing current, Z(t)(jf)= V(o, sensor)(jf)/I(sensor)(jf). The study has been extended to various magnetoresistance sensors based in different technologies like anisotropic magnetoresistance (AMR), giant magnetoresistance (GMR), spin-valve (GMR-SV) and tunnel magnetoresistance (TMR). The resulting modeling shows two predominant behaviors, the low-pass and the inverse low-pass with fractional index different from the classical integer response. The TMR technology with internal magnetization offers the best dynamic and sensitivity properties opening the way to develop actual industrial applications.

  2. Reactive Transformation and Increased BDNF Signaling by Hippocampal Astrocytes in Response to MK-801.

    Directory of Open Access Journals (Sweden)

    Wenjuan Yu

    Full Text Available MK-801, also known as dizocilpine, is a noncompetitive N-methyl-D-aspartic acid (NMDA receptor antagonist that induces schizophrenia-like symptoms. While astrocytes have been implicated in the pathophysiology of psychiatric disorders, including schizophrenia, astrocytic responses to MK-801 and their significance to schizotypic symptoms are unclear. Changes in the expression levels of glial fibrillary acid protein (GFAP, a marker of astrocyte activation in response to a variety of pathogenic stimuli, were examined in the hippocampus of rats treated with the repeated MK-801 injection (0.5 mg/10 ml/kg body weight for 6 days and in primary cultured hippocampal astrocytes incubated with MK-801 (5 or 20 μM for 24 h. Moreover, the expression levels of BDNF and its receptors TrkB and p75 were examined in MK-801-treated astrocyte cultures. MK-801 treatment enhanced GFAP expression in the rat hippocampus and also increased the levels of GFAP protein and mRNA in hippocampal astrocytes in vitro. Treatment of cultured hippocampal astrocytes with MK-801 enhanced protein and mRNA levels of BDNF, TrkB, and p75. Collectively, our results suggest that hippocampal astrocytes may contribute to the pathophysiology of schizophrenia symptoms associated with NMDA receptor hypofunction by reactive transformation and altered BDNF signaling.

  3. Fractional Modeling of the AC Large-Signal Frequency Response in Magnetoresistive Current Sensors

    Directory of Open Access Journals (Sweden)

    Sergio Iván Ravelo Arias

    2013-12-01

    Full Text Available Fractional calculus is considered when derivatives and integrals of non-integer order are applied over a specific function. In the electrical and electronic domain, the transfer function dependence of a fractional filter not only by the filter order n, but additionally, of the fractional order α is an example of a great number of systems where its input-output behavior could be more exactly modeled by a fractional behavior. Following this aim, the present work shows the experimental ac large-signal frequency response of a family of electrical current sensors based in different spintronic conduction mechanisms. Using an ac characterization set-up the sensor transimpedance function  is obtained considering it as the relationship between sensor output voltage and input sensing current,[PLEASE CHECK FORMULA IN THE PDF]. The study has been extended to various magnetoresistance sensors based in different technologies like anisotropic magnetoresistance (AMR, giant magnetoresistance (GMR, spin-valve (GMR-SV and tunnel magnetoresistance (TMR. The resulting modeling shows two predominant behaviors, the low-pass and the inverse low-pass with fractional index different from the classical integer response. The TMR technology with internal magnetization offers the best dynamic and sensitivity properties opening the way to develop actual industrial applications.

  4. Reactive Transformation and Increased BDNF Signaling by Hippocampal Astrocytes in Response to MK-801.

    Science.gov (United States)

    Yu, Wenjuan; Zhu, Hao; Wang, Yueming; Li, Guanjun; Wang, Lihua; Li, Huafang

    2015-01-01

    MK-801, also known as dizocilpine, is a noncompetitive N-methyl-D-aspartic acid (NMDA) receptor antagonist that induces schizophrenia-like symptoms. While astrocytes have been implicated in the pathophysiology of psychiatric disorders, including schizophrenia, astrocytic responses to MK-801 and their significance to schizotypic symptoms are unclear. Changes in the expression levels of glial fibrillary acid protein (GFAP), a marker of astrocyte activation in response to a variety of pathogenic stimuli, were examined in the hippocampus of rats treated with the repeated MK-801 injection (0.5 mg/10 ml/kg body weight for 6 days) and in primary cultured hippocampal astrocytes incubated with MK-801 (5 or 20 μM for 24 h). Moreover, the expression levels of BDNF and its receptors TrkB and p75 were examined in MK-801-treated astrocyte cultures. MK-801 treatment enhanced GFAP expression in the rat hippocampus and also increased the levels of GFAP protein and mRNA in hippocampal astrocytes in vitro. Treatment of cultured hippocampal astrocytes with MK-801 enhanced protein and mRNA levels of BDNF, TrkB, and p75. Collectively, our results suggest that hippocampal astrocytes may contribute to the pathophysiology of schizophrenia symptoms associated with NMDA receptor hypofunction by reactive transformation and altered BDNF signaling.

  5. Functional dissociation of transient and sustained fMRI BOLD components in human auditory cortex revealed with a streaming paradigm based on interaural time differences.

    Science.gov (United States)

    Schadwinkel, Stefan; Gutschalk, Alexander

    2010-12-01

    A number of physiological studies suggest that feature-selective adaptation is relevant to the pre-processing for auditory streaming, the perceptual separation of overlapping sound sources. Most of these studies are focused on spectral differences between streams, which are considered most important for streaming. However, spatial cues also support streaming, alone or in combination with spectral cues, but physiological studies of spatial cues for streaming remain scarce. Here, we investigate whether the tuning of selective adaptation for interaural time differences (ITD) coincides with the range where streaming perception is observed. FMRI activation that has been shown to adapt depending on the repetition rate was studied with a streaming paradigm where two tones were differently lateralized by ITD. Listeners were presented with five different ΔITD conditions (62.5, 125, 187.5, 343.75, or 687.5 μs) out of an active baseline with no ΔITD during fMRI. The results showed reduced adaptation for conditions with ΔITD ≥ 125 μs, reflected by enhanced sustained BOLD activity. The percentage of streaming perception for these stimuli increased from approximately 20% for ΔITD = 62.5 μs to > 60% for ΔITD = 125 μs. No further sustained BOLD enhancement was observed when the ΔITD was increased beyond ΔITD = 125 μs, whereas the streaming probability continued to increase up to 90% for ΔITD = 687.5 μs. Conversely, the transient BOLD response, at the transition from baseline to ΔITD blocks, increased most prominently as ΔITD was increased from 187.5 to 343.75 μs. These results demonstrate a clear dissociation of transient and sustained components of the BOLD activity in auditory cortex. © 2010 The Authors. European Journal of Neuroscience © 2010 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  6. Promiscuous Diffusible Signal Factor Production and Responsiveness of the Xylella fastidiosa Rpf System.

    Science.gov (United States)

    Ionescu, Michael; Yokota, Kenji; Antonova, Elena; Garcia, Angelica; Beaulieu, Ellen; Hayes, Terry; Iavarone, Anthony T; Lindow, Steven E

    2016-07-19

    Cell density-dependent regulation of gene expression in Xylella fastidiosa that is crucial to its switching between plant hosts and insect vectors is dependent on RpfF and its production of 2-enoic acids known as diffusible signal factor (DSF). We show that X. fastidiosa produces a particularly large variety of similar, relatively long-chain-length 2-enoic acids that are active in modulating gene expression. Both X. fastidiosa itself and a Pantoea agglomerans surrogate host harboring X. fastidiosa RpfF (XfRpfF) is capable of producing a variety of both saturated and unsaturated free fatty acids. However, only 2-cis unsaturated acids were found to be biologically active in X. fastidiosa X. fastidiosa produces, and is particularly responsive to, a novel DSF species, 2-cis-hexadecanoic acid that we term XfDSF2. It is also responsive to other, even longer 2-enoic acids to which other taxa such as Xanthomonas campestris are unresponsive. The 2-enoic acids that are produced by X. fastidiosa are strongly affected by the cellular growth environment, with XfDSF2 not detected in culture media in which 2-tetradecenoic acid (XfDSF1) had previously been found. X. fastidiosa is responsive to much lower concentrations of XfDSF2 than XfDSF1. Apparently competitive interactions can occur between various saturated and unsaturated fatty acids that block the function of those agonistic 2-enoic fatty acids. By altering the particular 2-enoic acids produced and the relative balance of free enoic and saturated fatty acids, X. fastidiosa might modulate the extent of DSF-mediated quorum sensing. X. fastidiosa, having a complicated lifestyle in which it moves and multiplies within plants but also must be vectored by insects, utilizes DSF-based quorum sensing to partition the expression of traits needed for these two processes within different cells in this population based on local cellular density. The finding that it can produce a variety of DSF species in a strongly

  7. Wnt and β-Catenin Signaling and Skeletal Muscle Myogenesis in Response to Muscle Damage and Resistance Exercise and Training

    Directory of Open Access Journals (Sweden)

    Dan Newmire

    2015-10-01

    Full Text Available The factors that regulate skeletal muscle hypertrophy in human adults in response to resistance training (RT has largely focused on endogenous endocrine responses. However, the endocrine response to RT as having an obligatory role in muscle hypertrophy has come under scrutiny, as other mechanisms and pathways seem to also be involved in up-regulating muscle protein synthesis (MPS. Skeletal muscle myogenesis is a multifactorial process of tissue growth and repair in response to resistance training is regulated by many factors.  As a result, satellite cell-fused myogenesis is a possible factor in skeletal muscle regeneration and hypertrophy in response to RT.  The Wnt family ligands interact with various receptors and activate different downstream signaling pathways and have been classified as either canonical (β-catenin dependent or non-canonical (β-catenin independent.  Wnt is secreted from numerous tissues in a paracrine fashion. The Wnt/β-catenin signaling pathway is a highly-regulated and intricate pathway that is essential to skeletal muscle myogenesis.  The canonical Wnt/β-catenin pathway may influence satellite cells to myogenic commitment, differentiation, and fusion into muscle fibers in response to injury or trauma, self-renewal, and normal basal turnover.  The current literature has shown that, in response mechanical overload from acute resistance exercise and chronic resistance training, that the Wnt/β-catenin signaling pathway is stimulated which may actuate the process of muscle repair and hypertrophy in response to exercise-induced muscle damage. The purpose of this review is to elaborate on the Wnt/β-catenin signaling  pathway, the current literature investigating the relationship of the Wnt/β-catenin pathway and its effects on myogenesis is response to muscle damage and resistance exercise and training.      Keywords: skeletal muscle, hypertrophy, myogenesis, cell signaling, protein synthesis, resistance

  8. Iron is a signal for Stenotrophomonas maltophilia biofilm formation, oxidative stress response, OMPs expression and virulence

    Directory of Open Access Journals (Sweden)

    Carlos Adrian Garcia

    2015-09-01

    Full Text Available Stenotrophomonas maltophilia is an emerging nosocomial pathogen. In many bacteria iron availability regulates, trough the Fur system, not only iron homeostasis but also virulence. The aim of this work was to assess the role of iron on S. maltophilia biofilm formation, EPS production, oxidative stress response, OMPs regulation, quorum sensing (QS, and virulence. Studies were done on K279 and its isogenic fur mutant F60 cultured in the presence or absence of dipyridyl. This is the first report of spontaneous fur mutants obtained in S. maltophilia. F60 produced higher amounts of biofilms than K279a and CLSM analysis demonstrated improved adherence and biofilm organization. Under iron restricted conditions, K279a produced biofilms with more biomass and enhanced thickness. In addition, F60 produced higher amounts of EPS than K279a but with a similar composition, as revealed by ATR-FTIR spectroscopy. With respect to the oxidative stress response, MnSOD was the only SOD isoenzyme detected in K279a. F60 presented higher SOD activity than the wt strain in planktonic and biofilm cultures, and iron deprivation increased K279a SOD activity. Under iron starvation, SDS-PAGE profile from K279a presented two iron-repressed proteins. Mass spectrometry analysis revealed homology with FepA and another putative TonB-dependent siderophore receptor of K279a. In silico analysis allowed the detection of potential Fur boxes in the respective coding genes. K279a encodes the QS diffusible signal factor (DSF. Under iron restriction K279a produced higher amounts of DSF than under iron rich condition. Finally, F60 was more virulent than K279a in the Galleria mellonella killing assay. These results put in evidence that iron levels regulate, likely through the Fur system, S. maltophilia biofilm formation, oxidative stress response, OMPs expression, DSF production and virulence.

  9. Region-, Neuron-, and Signaling Pathway-Specific Increases in Prolactin Responsiveness in Reproductively Experienced Female Rats

    Science.gov (United States)

    Sjoeholm, Annika; Bridges, Robert S.; Grattan, David R.

    2011-01-01

    Pregnancy and lactation cause long-lasting enhancements in maternal behavior and other physiological functions, along with increased hypothalamic prolactin receptor expression. To directly test whether reproductive experience increases prolactin responsiveness in the arcuate, paraventricular, and supraoptic nuclei and the medial preoptic area, female rats experienced a full pregnancy and lactation or remained as age-matched virgin controls. At 5 wk after weaning, rats received 2.5, 100, or 4000 ng ovine prolactin or vehicle intracerebroventricularly. The brains underwent immunohistochemistry for the phosphorylated forms of signal transducer and activator of transcription 5 (pSTAT5) or ERK1/2 (pERK1/2). There was a marked increase in pSTAT5 and pERK1/2 in response to prolactin in the regions examined in both virgin and primiparous rats. Primiparous rats exhibited approximately double the number of prolactin-induced pSTAT5-immunoreactive cells as virgins, this effect being most apparent at the higher prolactin doses in the medial preoptic area and paraventricular and supraoptic nuclei and at the lowest prolactin dose in the arcuate nucleus. Dual-label immunohistochemistry showed that arcuate kisspeptin (but not oxytocin or dopamine) neurons displayed increased sensitivity to prolactin in reproductively experienced animals; these neurons may contribute to the reduction in prolactin concentration observed after reproductive experience. There was no effect of reproductive experience on prolactin-induced pERK1/2, indicating a selective effect on the STAT5 pathway. These data show that STAT5 responsiveness to prolactin is enhanced by reproductive experience in multiple hypothalamic regions. The findings may have significant implications for understanding postpartum disorders affecting maternal care and other prolactin-associated pathologies. PMID:21363933

  10. Promiscuous Diffusible Signal Factor Production and Responsiveness of the Xylella fastidiosa Rpf System

    Directory of Open Access Journals (Sweden)

    Michael Ionescu

    2016-07-01

    Full Text Available Cell density-dependent regulation of gene expression in Xylella fastidiosa that is crucial to its switching between plant hosts and insect vectors is dependent on RpfF and its production of 2-enoic acids known as diffusible signal factor (DSF. We show that X. fastidiosa produces a particularly large variety of similar, relatively long-chain-length 2-enoic acids that are active in modulating gene expression. Both X. fastidiosa itself and a Pantoea agglomerans surrogate host harboring X. fastidiosa RpfF (XfRpfF is capable of producing a variety of both saturated and unsaturated free fatty acids. However, only 2-cis unsaturated acids were found to be biologically active in X. fastidiosa. X. fastidiosa produces, and is particularly responsive to, a novel DSF species, 2-cis-hexadecanoic acid that we term XfDSF2. It is also responsive to other, even longer 2-enoic acids to which other taxa such as Xanthomonas campestris are unresponsive. The 2-enoic acids that are produced by X. fastidiosa are strongly affected by the cellular growth environment, with XfDSF2 not detected in culture media in which 2-tetradecenoic acid (XfDSF1 had previously been found. X. fastidiosa is responsive to much lower concentrations of XfDSF2 than XfDSF1. Apparently competitive interactions can occur between various saturated and unsaturated fatty acids that block the function of those agonistic 2-enoic fatty acids. By altering the particular 2-enoic acids produced and the relative balance of free enoic and saturated fatty acids, X. fastidiosa might modulate the extent of DSF-mediated quorum sensing.

  11. The cellular response to vascular endothelial growth factors requires co-ordinated signal transduction, trafficking and proteolysis.

    Science.gov (United States)

    Smith, Gina A; Fearnley, Gareth W; Tomlinson, Darren C; Harrison, Michael A; Ponnambalam, Sreenivasan

    2015-08-18

    VEGFs (vascular endothelial growth factors) are a family of conserved disulfide-linked soluble secretory glycoproteins found in higher eukaryotes. VEGFs mediate a wide range of responses in different tissues including metabolic homoeostasis, cell proliferation, migration and tubulogenesis. Such responses are initiated by VEGF binding to soluble and membrane-bound VEGFRs (VEGF receptor tyrosine kinases) and co-receptors. VEGF and receptor splice isoform diversity further enhances complexity of membrane protein assembly and function in signal transduction pathways that control multiple cellular responses. Different signal transduction pathways are simultaneously activated by VEGFR-VEGF complexes with membrane trafficking along the endosome-lysosome network further modulating signal output from multiple enzymatic events associated with such pathways. Balancing VEGFR-VEGF signal transduction with trafficking and proteolysis is essential in controlling the intensity and duration of different intracellular signalling events. Dysfunction in VEGF-regulated signal transduction is important in chronic disease states including cancer, atherosclerosis and blindness. This family of growth factors and receptors is an important model system for understanding human disease pathology and developing new therapeutics for treating such ailments. © 2015 Authors.

  12. Response of neural reward regions to food cues in autism spectrum disorders

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    Cascio Carissa J

    2012-05-01

    Full Text Available Abstract Background One hypothesis for the social deficits that characterize autism spectrum disorders (ASD is diminished neural reward response to social interaction and attachment. Prior research using established monetary reward paradigms as a test of non-social reward to compare with social reward may involve confounds in the ability of individuals with ASD to utilize symbolic representation of money and the abstraction required to interpret monetary gains. Thus, a useful addition to our understanding of neural reward circuitry in ASD includes a characterization of the neural response to primary rewards. Method We asked 17 children with ASD and 18 children without ASD to abstain from eating for at least four hours before an MRI scan in which they viewed images of high-calorie foods. We assessed the neural reward network for increases in the blood oxygenation level dependent (BOLD signal in response to the food images Results We found very similar patterns of increased BOLD signal to these images in the two groups; both groups showed increased BOLD signal in the bilateral amygdala, as well as in the nucleus accumbens, orbitofrontal cortex, and insula. Direct group comparisons revealed that the ASD group showed a stronger response to food cues in bilateral insula along the anterior-posterior gradient and in the anterior cingulate cortex than the control group, whereas there were no neural reward regions that showed higher activation for controls than for ASD. Conclusion These results suggest that neural response to primary rewards is not diminished but in fact shows an aberrant enhancement in children with ASD.

  13. Bacterial response to siderophore and quorum-sensing chemical signals in the seawater microbial community

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    Kamino Kei

    2001-10-01

    Full Text Available Abstract Background Oceans are iron-deficient and nutrient-poor environments. These conditions impart limitations on our understanding of and our ability to identify microorganisms from the marine environment. However, less of knowledge on the influence of siderophores and N-acyl homoserinelactone as interspecies communication signals on the bacterial diversity of seawater has been understood. Results In the presence of 0.1 nM of the commercial siderophore desferroixamine and the known quorum-sensing chemical signals, synthetic N-(3-oxo-hexanoylhomoserine lactone (0.1 nM or N-octanoylhomoserine lactone (0.1 nM, the total numbers of bacteria in S9905 seawater increased nearly three-fold, and nearly eight-fold in S0011 seawater as determined by DAPI staining and counting, and increased three-fold by counting colony forming units in S9905 seawater after 7 days of incubation. Similar bacterial changes in bacterial abundance were observed when high concentration of desferroixamine (1 μM and each of homoserine lactone compounds (1 μM were presented in seawater samples. The number of cultivable bacterial species observed was also found to increase from 3 (without addition to 8 (with additions including three unknown species which were identified by phylogenetic analysis of 16S rDNA sequences. The growth of unknown species was found to be related to their siderophore production with response to the addition of desferroixamine and N-acyl homoserine lactones under iron-limited conditions. Conclusion Artificial addition of siderophores and HSLs may be a possible method to aid in the identification and isolation of marine bacterial species which are thought to be unknown.

  14. Profile of select hepatic insulin signaling pathway genes in response to 2-aminoanthracene dietary ingestion.

    Science.gov (United States)

    Mattis, N D; Jay, J W; Barnett, G W; Rosaldo, J J; Howerth, E W; Means, J C; Gato, W E

    2014-01-01

    Some genes that regulate various processes such as insulin signaling, glucose metabolism, fatty acid, and lipid biosynthesis were profiled. The objective of the current investigation is to examine the mRNA expression of some genes that mediate insulin signaling due to 2AA toxicity. 2AA is a polycyclic aromatic hydrocarbon (PAH) that has been detected in broiled food and tobacco smoke. Twenty-four post-weaning 3-4-week-old F344 male rats were exposed to 0 mg/kg-diet, 50 mg/kg-diet, 75 mg/kg-diet, and 100 mg/kgdiet 2AA for 2 weeks and 4 weeks. The mRNA expression of AKT1, G6PC, GCK, GLUT4, INSR, IRS1, PP1R3C, PAMPK, SOCS 2, and SREBF1 was determined by qRTPCR followed by the quantification of G6PC and AMPK via ELISA. The results suggest that 2AA modulates these genes depending on the length of exposure. Up-regulation of AMPK and SOCS2 genes in animals treated with 100 mg/kg-diet and 50 mg/kg-diet, respectively, during 14 days of feeding was noted. G6PC expression was inhibited in the 2-week group while being dose-dependently increased in the 4-week group. Hepatic activity of G6PC was enhanced significantly in the livers of rats that ingested 2AA. It appears that 2AA intoxication leads to the activation of irs1 and akt1 genes in the liver. Quantified AMPK amounts increased significantly in the short-term treatment group. Dose-dependent rise of AMPK in animals treated to 2AA showed an increased production of hepatic AMPK in response to the toxicity of 2AA in order to maintain cellular homeostasis. In contrast, the reduction in AMPK concentration in treated animals within the 4-week set indicated an adaptive recovery.

  15. BOLD contrast fMRI of whole rodent tumour during air or carbogen breathing using echo-planar imaging at 1.5 T

    Energy Technology Data Exchange (ETDEWEB)

    Landuyt, W.; Bogaert, W. van den; Lambin, P. [Lab. of Experimental Radiobiology and Department of Radiotherapy/Oncology,Univ. Hospitals Leuven (Belgium); Hermans, R.; Bosmans, H.; Sunaert, S.; Beatse, E.; Farina, D.; Meijerink, M.; Zhang, H.; Marchal, G. [University Hospital, Leuven (Belgium). Dept. of Radiology

    2001-11-01

    The aim of this study was to evaluate the feasibility of functional MR imaging (fMRI) at 1.5 T, exploiting blood oxygenation level-dependent (BOLD) contrast, for detecting changes in whole-tumour oxygenation induced by carbogen (5% CO{sub 2}+95% O{sub 2}) inhalation of the host. Adult WAG/Rij rats with rhabdomyosarcomas growing subcutaneously in the lower flank were imaged when tumours reached sizes between 1 and 11 cm{sup 3} (n=12). Air and carbogen were alternatively supplied at 2 l/min using a snout mask. Imaging was done on a 1.5-T MR scanner using a T2*-weighted gradient-echo, echo-planar imaging (GE-EPI) sequence. Analysis of the whole-tumour EPI images was based on statistical parametric maps. Voxels with and without signal intensity changes (SIC) were recorded. Significance thresholds were set at p<0.05, corrected for multiple comparisons. In continuous air breathing condition, 3 of 12 tumours showed significant negative SIC and 1 tumour had a clear-cut positive SIC. The remaining tumours showed very little or no change. When switching to carbogen breathing, the SIC were significantly positive in 10 of 12 tumours. Negative SIC were present in 4 tumours, of which three were simultaneously characterised by positive SIC. The overall analysis indicated that 6 of the 12 tumours could be considered as strong positive responders to carbogen. Our research demonstrates the applicability of fMRI GE-EPI at 1.5 T to study whole-tumour oxygenation non-invasively. The observed negative SIC during air condition may reflect the presence of transient hypoxia during these measurements. Selection of tumours on the basis of their individual response to carbogen is possible, indicating a role of such non-invasive measurements for using tailor-made treatments. (orig.)

  16. Food restriction promotes signaling effort in response to social challenge in a short-lived electric fish.

    Science.gov (United States)

    Gavassa, Sat; Stoddard, Philip K

    2012-09-01

    Vertebrates exposed to stressful conditions release glucocorticoids to sustain energy expenditure. In most species elevated glucocorticoids inhibit reproduction. However individuals with limited remaining reproductive opportunities cannot afford to forgo reproduction and should resist glucocorticoid-mediated inhibition of reproductive behavior. The electric fish Brachyhypopomus gauderio has a single breeding season in its lifetime, thus we expect males to resist glucocorticoid-mediated inhibition of their sexual advertisement signals. We studied stress resistance in male B. gauderio (i) by examining the effect of exogenous cortisol administration on the signal waveform and (ii) by investigating the effect of food limitation on androgen and cortisol levels, the amplitude of the electric signal waveform, the responsiveness of the electric signal waveform to social challenge, and the amount of feeding activity. Exogenous cortisol administration did reduce signal amplitude and pulse duration, but endogenous cortisol levels did not rise with food limitation or social challenge. Despite food limitation, males responded to social challenges by further increasing androgen levels and enhancing the amplitude and duration of their electric signal waveforms. Food-restricted males increased androgen levels and signal pulse duration more than males fed ad libitum. Socially challenged fish increased food consumption, probably to compensate for their elevated energy expenditure. Previous studies showed that socially challenged males of this species simultaneously elevate testosterone and cortisol in proportion to signal amplitude. Thus, B. gauderio appears to protect its cortisol-sensitive electric advertisement signal by increasing food intake, limiting cortisol release, and offsetting signal reduction from cortisol with signal-enhancing androgens. Copyright © 2012 Elsevier Inc. All rights reserved.

  17. The Essential Function for Serum Response Factor in T-Cell Development Reflects Its Specific Couplin